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La verità sul vino, dal punto di vista salutistico e nutrizionale. 15 Novembre 2013 ore 09:00 - RICCAGIOIA S.C.p.A. – TORRAZZA COSTE (PV) Il vino e la genetica del gusto nell’uomo Roberto Barale – Dipartimento di Biologia , Università di Pisa
Transcript
Page 1: Barale b

La veritagrave sul vino dal punto di vista salutistico e nutrizionale 15 Novembre 2013 ore 0900 - RICCAGIOIA SCpA ndash TORRAZZA COSTE (PV)

Il vino e la genetica del gusto nellrsquouomo ndash

Roberto Barale ndash Dipartimento di Biologia Universitagrave di Pisa

User
Timbro

Gli umani possono distinguere 5 classi di sapori

1) dolce

2) acido

3) amaro

4) salato e

5) umami (glutammato)

taste perception

Taste

sour and salty mediated by ion channels

umami sweet and bitter mediated by GPCR

TAS1R1 + 3 TAS1R2 + 3 25 TAS2Rs

Figures by Chandrashekar et al 2006 The felids lack of this gene Panda lacks this gene

bitter

sweet

Umami

TAS2Rs genes are clustered in chromosome 7 and 12

close to the olfactive gene clusters

Cluster opsine Olfactory receptors fam 6

Olfactory receptors fam 2

Cluster taste genes

Cluster taste genes

bitter taste perception and the genetic background

25 TAS2Rs

2-Acetylpyrazine

Saccharin

Caffeine

Absinthin

Strychnine

Phenylthio-carbamide (PTC)

Epicatechin

Theobromine

Amygdalin

deorphanized hTAS2Rsligand pairs

Humulone

[Li et al patent application US 20080038739 Bufe et al 2005 Behrens et al 2004 Brockhoff et al 2007 Ley 2008]

Valpolicella Classico

Pinot Noir LEpayrie

INTENSITA DEL SAPORE AMARO

LAMARO DEL PTC (TAS2R38) CORRELA CON LAMARO DEL

VINO

Individual variability in wine perception

La ricerca Possono le varianti dei geni del gusto influenzare la percezione di alcune caratteristiche del vino Possono le caratteristiche culturali di due popolazioni diverse influenzare la valutazione di un vino

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 2: Barale b

Gli umani possono distinguere 5 classi di sapori

1) dolce

2) acido

3) amaro

4) salato e

5) umami (glutammato)

taste perception

Taste

sour and salty mediated by ion channels

umami sweet and bitter mediated by GPCR

TAS1R1 + 3 TAS1R2 + 3 25 TAS2Rs

Figures by Chandrashekar et al 2006 The felids lack of this gene Panda lacks this gene

bitter

sweet

Umami

TAS2Rs genes are clustered in chromosome 7 and 12

close to the olfactive gene clusters

Cluster opsine Olfactory receptors fam 6

Olfactory receptors fam 2

Cluster taste genes

Cluster taste genes

bitter taste perception and the genetic background

25 TAS2Rs

2-Acetylpyrazine

Saccharin

Caffeine

Absinthin

Strychnine

Phenylthio-carbamide (PTC)

Epicatechin

Theobromine

Amygdalin

deorphanized hTAS2Rsligand pairs

Humulone

[Li et al patent application US 20080038739 Bufe et al 2005 Behrens et al 2004 Brockhoff et al 2007 Ley 2008]

Valpolicella Classico

Pinot Noir LEpayrie

INTENSITA DEL SAPORE AMARO

LAMARO DEL PTC (TAS2R38) CORRELA CON LAMARO DEL

VINO

Individual variability in wine perception

La ricerca Possono le varianti dei geni del gusto influenzare la percezione di alcune caratteristiche del vino Possono le caratteristiche culturali di due popolazioni diverse influenzare la valutazione di un vino

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 3: Barale b

taste perception

Taste

sour and salty mediated by ion channels

umami sweet and bitter mediated by GPCR

TAS1R1 + 3 TAS1R2 + 3 25 TAS2Rs

Figures by Chandrashekar et al 2006 The felids lack of this gene Panda lacks this gene

bitter

sweet

Umami

TAS2Rs genes are clustered in chromosome 7 and 12

close to the olfactive gene clusters

Cluster opsine Olfactory receptors fam 6

Olfactory receptors fam 2

Cluster taste genes

Cluster taste genes

bitter taste perception and the genetic background

25 TAS2Rs

2-Acetylpyrazine

Saccharin

Caffeine

Absinthin

Strychnine

Phenylthio-carbamide (PTC)

Epicatechin

Theobromine

Amygdalin

deorphanized hTAS2Rsligand pairs

Humulone

[Li et al patent application US 20080038739 Bufe et al 2005 Behrens et al 2004 Brockhoff et al 2007 Ley 2008]

Valpolicella Classico

Pinot Noir LEpayrie

INTENSITA DEL SAPORE AMARO

LAMARO DEL PTC (TAS2R38) CORRELA CON LAMARO DEL

VINO

Individual variability in wine perception

La ricerca Possono le varianti dei geni del gusto influenzare la percezione di alcune caratteristiche del vino Possono le caratteristiche culturali di due popolazioni diverse influenzare la valutazione di un vino

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 4: Barale b

TAS2Rs genes are clustered in chromosome 7 and 12

close to the olfactive gene clusters

Cluster opsine Olfactory receptors fam 6

Olfactory receptors fam 2

Cluster taste genes

Cluster taste genes

bitter taste perception and the genetic background

25 TAS2Rs

2-Acetylpyrazine

Saccharin

Caffeine

Absinthin

Strychnine

Phenylthio-carbamide (PTC)

Epicatechin

Theobromine

Amygdalin

deorphanized hTAS2Rsligand pairs

Humulone

[Li et al patent application US 20080038739 Bufe et al 2005 Behrens et al 2004 Brockhoff et al 2007 Ley 2008]

Valpolicella Classico

Pinot Noir LEpayrie

INTENSITA DEL SAPORE AMARO

LAMARO DEL PTC (TAS2R38) CORRELA CON LAMARO DEL

VINO

Individual variability in wine perception

La ricerca Possono le varianti dei geni del gusto influenzare la percezione di alcune caratteristiche del vino Possono le caratteristiche culturali di due popolazioni diverse influenzare la valutazione di un vino

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 5: Barale b

bitter taste perception and the genetic background

25 TAS2Rs

2-Acetylpyrazine

Saccharin

Caffeine

Absinthin

Strychnine

Phenylthio-carbamide (PTC)

Epicatechin

Theobromine

Amygdalin

deorphanized hTAS2Rsligand pairs

Humulone

[Li et al patent application US 20080038739 Bufe et al 2005 Behrens et al 2004 Brockhoff et al 2007 Ley 2008]

Valpolicella Classico

Pinot Noir LEpayrie

INTENSITA DEL SAPORE AMARO

LAMARO DEL PTC (TAS2R38) CORRELA CON LAMARO DEL

VINO

Individual variability in wine perception

La ricerca Possono le varianti dei geni del gusto influenzare la percezione di alcune caratteristiche del vino Possono le caratteristiche culturali di due popolazioni diverse influenzare la valutazione di un vino

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 6: Barale b

Valpolicella Classico

Pinot Noir LEpayrie

INTENSITA DEL SAPORE AMARO

LAMARO DEL PTC (TAS2R38) CORRELA CON LAMARO DEL

VINO

Individual variability in wine perception

La ricerca Possono le varianti dei geni del gusto influenzare la percezione di alcune caratteristiche del vino Possono le caratteristiche culturali di due popolazioni diverse influenzare la valutazione di un vino

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 7: Barale b

Individual variability in wine perception

La ricerca Possono le varianti dei geni del gusto influenzare la percezione di alcune caratteristiche del vino Possono le caratteristiche culturali di due popolazioni diverse influenzare la valutazione di un vino

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 8: Barale b

La ricerca Possono le varianti dei geni del gusto influenzare la percezione di alcune caratteristiche del vino Possono le caratteristiche culturali di due popolazioni diverse influenzare la valutazione di un vino

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 9: Barale b

00

20

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60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

panel non esperti

Primitivo

igt toscana

Il Vino scelto Il Raboso

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

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3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 10: Barale b

00

20

40

60

80

100aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezzaglobale

panel esperti

primitivo

igt toscana

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 11: Barale b

0

1

2

3

4

5

6

7

8

9

10

aciditagrave

morbidezza

astringenza

amaro

struttura

volumeretrogusto

equilibrio

persistenza

stato evolutivo

gradevolezza globale

Panel completo (esperti + non esperti)

grifone primitivo

toscana igt

raboso del piave cecchetto

monte antico toscana igt (BIB)

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 12: Barale b

Sourness

Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Astringency

0-25 3-55 6-10

Sourness

0-25

3-55

6-10

Astringency Bitterness

0-25 3-55 6-10

0-25

3-55

6-10

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 13: Barale b

Chromosome12 1084410011231900

1201bp

7857bp

126866bp

2451bp

1641bp

45610bp

169bp

1592bp

9796bp

644bp 30005bp

715bp

31656bp

885bp 67bp

71876bp

52869bp

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 14: Barale b

390bp

1370bp

876bp

18826637bp

15771bp

266bp

11664bp

182366bp

101bp

640bp 220241bp

1208195bp

38191bp

1503bp 33679bp

191bp

Chromosome7

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 15: Barale b

Mosaic Chart for Astringency Integer_1 3 by TAS1R2_rs4920566_GA

1

2

3

TAS1R2_rs4920566_GA

AA

GA

GG Test Statistic Df P-Value

Chi-Squared 9552 4 00487

Tests of Independence

Mosaic Chart for Astringency Integer_1 3 by TAS2R7_rs2588350_GA

1

2

3

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 5911 4 02059

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 16: Barale b

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 12177 4 00161

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R30_rs2599404_TG

1

2

3

TAS2R30_rs2599404_TG

GG

TG

TT

Test Statistic Df P-Value

Chi-Squared 13129 4 00107

Tests of Independence

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 17: Barale b

Mosaic Chart for Sourness Integer_1 3 by TAS2R16_rs6466849_AG

1

2

3

TAS2R16_rs6466849_AG

AA

AG

GG

Test Statistic Df P-Value

Chi-Squared 13118 4 00107

Tests of Independence

Warning some cell counts lt

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 18: Barale b

Mosaic Chart for N_Group by TAS2R38_rs10246939_CT

1

2

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 7670 2 00216

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 19: Barale b

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 9379 4 00523

Tests of Independence

Mosaic Chart for B itterness_1 by TAS2R38_rs10246939_CT

1

2

3

TAS2R38_rs10246939_CT

CC

CT

TT

Test Statistic Df P-Value

Chi-Squared 5110 4 02762

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 20: Barale b

Mosaic Chart for N_group by W ineglass_die_3class

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 21538 3 00001

Tests of Independence

0

4

8

12

16

20

perc

en

tage

N_group

Barchart for N_group by B itterness_3class

1 2

Bitterness_3class

0

1

2

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 21: Barale b

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Astringency_3class

1 2

Astringency_3class

0

1

2

Mosaic Chart for Astringency_3class by Wineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 10116 6 01198

Tests of Independence

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 22: Barale b

0

30

60

90

120

150

180fr

equ

en

cy

N_Group

Barchart for N_Group by Sourness_3class

1 2

Sourness_3class

0

1

2

Test Statistic Df P-Value

Chi-Squared 28229 2 00000

Tests of Independence

Mosaic Chart for Sourness_3class by W ineglass_die_3class

0

1

2

W ineglass_die_3class

0

1

2

3

Test Statistic Df P-Value

Chi-Squared 4427 6 06191

Tests of Independence

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 23: Barale b

Mosaic Chart for Balsamicvinegar3classes by TAS2R9_rs3741845_TC

0

1

2

TAS2R9_rs3741845_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 17231 4 00017

Mosaic Chart for A rtichoke3classes by TAS2R7_rs2588350_GA

0

1

2

TAS2R7_rs2588350_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 13080 4 00109

Tests of Independence

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 24: Barale b

Mosaic Chart for A rtichoke3classes by CA6_rs2274333_GA

0

1

2

CA6_rs2274333_GA

AA

GA

GG

Test Statistic Df P-Value

Chi-Squared 12886 4 00118

Tests of Independence

Mosaic Chart for Onion3classes by TAS2R42_rs5020531_TC

0

1

2

TAS2R42_rs5020531_TC

CC

TC

TT

Test Statistic Df P-Value

Chi-Squared 16351 4 00026

Tests of Independence

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 25: Barale b

Mosaic Chart for Cabbage3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 10862 4 00282

Tests of Independence

Warning some cell counts

Mosaic Chart for B itterchocolate3classes by TAS2R31_rs10845296_TC_N

0

1

2

TAS2R31_rs10845296_TC_N

0

1

2

Test Statistic Df P-Value

Chi-Squared 16632 4 00023

Tests of Independence

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 26: Barale b

Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving

CCK

Jeon TI et al Biochem J 2011 Aug 15438(1)33-7

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 27: Barale b

Bitter taste receptors on airway smooth muscle bronchodilate by

localized calcium signaling and reverse obstruction

Deshpande DA et al Nat Med 2010 Nov16(11)

T2R38 taste receptor polymorphisms underlie

susceptibility to upper respiratory infection

Lee RJ et all J Clin Invest

2012 Nov 1122(11)4145-59

Receptor activation regulates calcium-dependent NO production resulting in stimulation of mucociliary clearance

and direct antibacterial effects polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory

cells to clear and kill bacteria Lastly TAS2R38 genotype correlated with human sinonasal gram-negative bacterial

infection These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation

contributes to individual differences in susceptibility to respiratory infection

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 28: Barale b

Figure 2 QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte osteocyte

and chondrocyte lineages n = 3 donors with 3 technical replicates each

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 29: Barale b

Figure 6 Human vascular smooth muscle cells express hTAS2R46 and are stimulated by

denatonium

Lund TC Kobs AJ Kramer A Nyquist M et al (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have

Chemosensory Capacity via Bitter Taste Receptor Expression PLoS ONE 8(3) e58945 doi101371journalpone0058945

httpwwwplosoneorgarticleinfodoi101371journalpone0058945

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 30: Barale b

Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male germ cells traces of calcium responses from acrosome (A) midpiece (M) and principal piece (P) of a spermatid (left) and epididymal sperm (right) to 200 microM bitter-tastant mixture (BTM) or

individual bitter tastants procainamide denatonium PTC PROP and cycloheximide

Xu J et al Mol Hum Reprod 20131917-28

copy The Author 2012 Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology All rights reserved For Permissions please email journalspermissionsoupcom

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 31: Barale b

C Human testis

1-3 TAS2R14

4-6 TAS2R16

7-9 TAS2R38

Page 32: Barale b

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