I want you to formulate FOUR simple Case Study Questions (with Answers) from this given Research paper that I can use in my Presentation. Topic of the Research Paper: Mechanism of Hypertension and it&...

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I want you to formulate FOUR simple Case Study Questions (with Answers) from this given Research paper that I can use in my Presentation. Topic of the Research Paper: Mechanism of Hypertension and it's therapy targets I am a Postgraduate Student. This is a Physiology Major Question. Please make use of this theoretical knowledge ONLY.  RESEARCH trasuuclion is nol clear. PIEnd PIE12 are rhanicayativat in chaels Lhat play crucial roles in several mechanotransduction p cesses (o), PIEZ01 is prominently expressed in the carciovascular syst , 12 and PICZO2 is &#1103;bundant in vanons populations of sensory neurons (13-15). NEUROSCIENCE PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex pression in nodose andpetrosal ganglia, where baroreceptor cell bodies are located (). These gli are uscd wilh ah lher and wilh lhe ngular ganglion in mie. Piea and Pien2 were highly expressed in the nodose-petrusal-jugular ganglion couplex (NTJc) (Fg. 1A) Similar mm- bers of cellsere identified that highly expressed either Pieor Pieno2 exclusively (123 and 124 cells with ach ranseripl, rspelivly, ig A sall popla f neurs expressed both (43 double Peso-positive cells, or 14.8% of all Piea-expressing cells, 6mice, Fig. IB) Wei-Zheng Zeng, Kara L. Marshall, Soohong Min2, Ihab Daou, Mark W. Chapleau, Trancois M. Abboud, Stephen D. Liberles2, Ardem Patapoutian Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for more than 80 years, the molecular identity of baroreceptor mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 and PIEZO2 are together required for baroreception. Genetic ablation of both PiezoI and Piezo2 in the nodose and petrosal sensory ganglia of mice abalished drug-induced baroreflex and aortic depressor nerve activity. Awake, To test whether PiczoI and Pico2 are ex behaving animals that lack Piezos had labile hypertension and increased blood pressure variability, consistent with phenotypes in baroreceptor-denervated animals and humans with baroreflex failure. Optogenetic activation of Piezo2-positive sensory afferents was sufficient to initiate baroreflex in mice. These findings suggest that PIEZ01 and PIEZO2 are the long-sought baroreceptor mechanosensors critical for acute blood pressure control. pressed in baroreceptors, we performed retr grade labellug &omicron;&#943; carulid sensory neuLuns. We into the carotid sinus beneath the serosal vessel covering. All CTE-positive neurons detected in the NPJc from eiglht mice were quautified for the presenc of Pie or Pin2 transcript (Fig., the initial increase in BP , 2). Compromised Cto F). Six aut of 95 retrogradely labeled cells lood pressure (BP) is tightly regulated to varied daily activity demands. Mechanisms premature death in humans with postmyocardial positive ig. B). Pieo-negative cells were likely chemoreceptors, which abundantly innervate term BP regulation. Within seconds andveral ion channels (s-9) hare been sug- the carotid sinus but do not require mecha- S that change blood volume control long-infarction and heart failure (3, 4). minutes, BP is initiated primrilyb rit to bareeeption. Howensitivity. No the 95 CTB-labeled c baroteceptors, a class ofstretch-sensitive neurons ever, substantial residual baroreflex is observed wilhin lhe nluluse and pelrusal ganglia with when tese than nels are ablaled ittlplicaLinx &#3618; ll. vs hru al rrs.iluri urusa u Dowrre peripheral projections in the walls of the aorta the involvement of other sensory systems. None and carotid sinus (,2). An increase in BP stretcheecandidate ion channels have been directlyDpar ment of Call Bolhgy, Harvd Medical Schcol. Bostan baroreceptor nerve endings to trigger atferent activated by mechanical stimuli in heterologousMA C2I15, USA. 8Atbeud Crdivscula Resh Cerit lla A9207. LSA anid Hiophyi,aver Collee edicine, Uriversity of system. The conseqs of baroeceptor actimolecules to form a mechanosensory complex. vation are&#23380;decrease in heart rate &#12308;HR), cardiac Furthermore, whether these channels are acting Cater, Iowa City, A 52242, USA output, and vascular resistance that counteract as sensos or play a role donstrean of mechan- Coesponding aurthor: Email: andemEscripps.edu .P1 & P2 (43 P1 only (123) . P2 only (124) All Piezo+ nodose cells . P1 only (8) -P2 only (8) All CTB+nodose cells 0.8 0.6 0.4 Carotid CTB 0. 0. 0.0 0.2 04 0.6 Piezo1 (fraction cell area) .0 0.2 0. 06 Piezo1 (fraction cell area) Piezo1 Fig. l. Expression of Pezol and Peza2 transcripts &#305;n NPJC. A prnecik I'l n parer! les es nd cal H nu.rbe : 1 cells. &#53412;&middot; ie/12; P2. PiH. tr. CI :) F Pk of NPJc tisse after fluorescent in situ hyrid zation with crobes targeting Piezol (ed) and PiezoZ (cyan). Nuc ei are laceled w tn &#34;,6- green] and Pezo transcript [(E) and (F), red and cyan]. Arrows indicate dian dino-2-phengi incloic DA7l, blue . Amo ws &#3634; ark do&#12375;ble &#1511; ozc-postivo a P ozo ocsit ve cell n(C) and (E and a Nizo positive cel in (D) cells. (B Quantification of trapt label ng a a as a fact on of to nkG) Quantification of Pieo trascript labeling area in CTB paitive cell area (n = 2SC ce ls, s x m ce). Eaen dat recesets one cell. &#44593;urr,bers cells (n-95 cells, eigt ce). Pezo-negative cells are not shown. oell codies back-abeled by carotid sins C B injections c) and D) Zeng et.. Siience 362. 404-407 018 26 Outober 2018 Fig. 2. Baroreflex is abolished in nodase and petrasal g n systol c BF (6), HR (C and ba oref ex)s afte intravenous njection of PE) knockout (KO) mice. Nu&#3634;1 be-of animals shown example before and after FE in ection. Expanded time sca e s &#3634;0wed bursts of ADN activ ty in onase with inclivicl al arterial pulses in W-Nc-mtograted ativ ty is ohse vedind0rice. *P005. *.0l,andn.s. isstatist cally ot signif cant by Lnpai ed Student's tteat: data are reaneSEM &#44564;ezo2 KO indicates F2cKn mice. Piezol Pie202 40 ndicates dKO mice RESEARCH I REPORT cibsuved a lauk drug-induced ADN activily in (IKO mice corrl[MLed 1&#3648;&#3623; wr mice (-131.9 1629 versus 5558 &plusmn; 1234 normalized area under curve ofintegrated ADN activity, P< 0.; Fig. 2, Eto G). The dkO mice had no appreciable responses during both phasic and tonic phases of PE induced ADN activity (g. S, D and E This is Sid Deviason observed comparable baroreceptor ending den sities within the aortic arch of dKO and WT mice Impaired baroreceptor iinetin leads t dys regulation of BP, including volatile hypertension and increased EP variability in humans (18-20) We examined daily BP variability in freely mov ing, conscious mice using a telemetric sensor (6). p-4 10 10 2-10 Doy ight Fig. 3. Increased BP variability in conscious nodose and petrosal gangtia-specitic dKO mice. A Continuous measurements of MAP and HRover 72 hours, binned by hour. The dliferences betman arterilpess (MAP)ng their c- groups were s gn ficant during the ight gray shading, to wa analys s of variance data are means tive time gry shading, 6 pm to am com pared with WT littermates &#12308;112 &plusmn; 0.4 versus 96 &plusmn; (&#1057; &#1103; 3R5 expressed as char e n FI rr pr r hangE &eta; SWstal c R3(TTHg), was san firant y red! ced 0.5 min Ig, Pc O001) (FL A and B, and figs. n doo mice {o = 17 mice) compared wim w mice n-15 mce {D equency distr but on histog am S3, A and B and S . The HR of dKO mice was slighlly increase during active ties ompared of the systolic BP over 72 hours, Rod ar-ows nd cate wider distribution of B in clKC mice. (E) 5? var ability recorted as standard devat on f om the 72-our oerod F) Maxmum and m imum BP va P alues a e ndicated &#3634; the bars. p:005 'npared Studenl'a r test was used Liless ind caled other&middot;se; dala a 'e ir Eart&#299; &plusmn; les l.&#34;xxp <C 001, and s s statistically nt s gnificant with Lhal of w r mice (5831 3 ver 11 566 <C 3 bpm P-0.001), whereas the HR pena ned unchanged during inactive times ( a.m. to 6pm. 32 3 versus 536 3 bpn, not sigmificant) (Fig. 3B No diftecomor activity was observed between dKL) and WT mice (Gy. S3), ruli ou Lh posibilily lhal arlivily caused the increased BP and IIR in dKO mice. We scanned telemetry data for spontaneous changes in systolic BP and pulse interval (PI) consistent with baionship. Ths method sequence technique) is used to nonin vasivuly sess bareflex fui (21, 22). lhe spontaneous baroredlex sensitivity (sBRS) s de -M&middot;&ugrave;-j to 1/ rTI1LE. anglion Carotid Sinus Aortic Dcpressor Supcrior Larynpea Aortic Arch fined as the slope of changes in systolic BPversus 9 PI from 1 hour of recording, SBRS was severely 2 0.2 ms/mmHg for WT, P 0.001, FI 3). Sinaortic3 baritecepto denetvaled mice also show residual SBRS (22), and this may be due to compensation &#1042;&#1056; HR fiomother sesory systems. We compared the BP variability of WT and were distributed in a broader range than those of WT littermates (Fig. 3D). Variability was greatly enhanced in dKO mice (.903 versus i | 0.3 mm HK in WT. p 0.001, Fig. 3E), we [&#25187;an- tified the range of BP variability of mean, sys- Piezo2Cre 2 72-hour period. Xlaximum values of BP from dKO mice were significantly higher than those trom WI littemates, whereas miuimum values WT 1 2 3 150 bpm 40 mmH were significantly lower (Hig. 3F) Lastlyhm 30 sec vanillic acid concentrations in dKO mouse urine were significantly higher than those in WT utine Fig. 4. Piezo2-positive sensory neurons acutely control blood pressure. (A) Scnematic dep cti nof t70 ChA2-exress ng Pirs senso y neurons. Tme&#417;ztical fibe was paced on area 1. vagus nerve tri.nk; area 2, supe or aryngeal branch; and area 3, carotds nus. B) Iraces of cardiovascular eltects alle loal ausner .inag bl.a aest eliHd PC2 Y WT, black trace) and Piezo2Cr CnR2-eYFP m ce (Piezo2re, gray. blie, and p nk traces). Numbers on the eft (1 to 3) oores oond to areas in&#36877;). 3 ood pressure was measured by a oressure transducer cannulated in the cft carotd artery. BP. carotid ateral presse (C Lght-indueecl ogonetic strategy. To car t cl sinus and ya us orucs wcro i n inated to acti atc (13.9 &plusmn; o06 versus 121 &plusmn; &omicron; fig. SSD &mu;& suggesting an increase in hormone nonpneph- rine coucentration, as in human baroreflex failu: palicnLs (18). Ther r sigiia BP variability aud sBRS differences in PIO | (fig. S5) and P2&#34;K&#34;(fig. S6) single-knockout mice compared with WT littermates. T2mice and s. s statist cally not significant ty unpaired Student's teat: data are reang t SEM Zeng et.. Siience 362. 404-407 018 26 Outober 2018 RESEARCH I REPORT 8. C, Rotertson et a,N. Engi J. iked 329, 449 155 channetrhodopsin-2 (Cht2) reporter mice toelimination of baroreceptor function (e sino recorded the cardiovascular respose o activatereases n BP and HR (23, 24). Over time, the 21. J. Oostng, H. A. Sta ker Bcudier,B. J. arssen. Hpsitens. enhanced yellow duorescent protein gene. Wand persists (I8-20, 21, 25). We observed a sig lon (ptn genetic stimulation (5-mes pulse, 50 Hz, the peso d KO mice that falls Jilstunder the 10 s)of the vagal nerve trunk (arealin Fig44: BPdesignation for hypertension (26), and dKO 25. C. S. I, A. M. Scher, Cinc. Res. 48, 576-59 1921 Pig. 4,A to C). Next, we focused on speciflcallyvariability. These data show that losing PIEZO1 ACKNOWLEDGMENTS nerve brah, which arris afferent innts fi as with barrfex tailun: (TR-20. HowEwr the ADN (area 2 in Fig. 4A) For carotid baro we cannot exclude the possibility that sensory grants DEC22358 and R25 N$136087 to .P.ZZ. a Hwtt Fc.tr frr Aica . SD.. uppartd b NIH EraTS CP. AT03497 and OT2 UD023848YC and S.UL. ae ir estigators t the Howand ges edical irsttu:e. Author contributons: Z.Z.. KLA., and A.P -50.5 -32.8 2.0%; area 3: BP,-37.5 3.5%, and HR, | 8.7%; P e0.001) compared with the un- -. X-2.2. performed drug-ind&#12301;29d tereflex assessTnt. performed ADN &icirc;ctrw:, recordngs tta S.C.L. labratory. Competing Interests: The a thors decare ne cometing interests Data and terials availability: A data tion of the B-adrenergic receptor-blocker pro- was imecdiated prmarily by inhibitin of caurlia: sympathetie nerve activity (fig. ST. Piezo2Cre ClueYPmice(WTj did nol show any chagea. S. .h, .E. Dion, A. Perapou: a si M &#12375;3. K.Nesmra et a!.. Aatire 541, 176-181 (2317). 4. 3. H. at Neuosc 18 173 1762 20.5)  RESEARCH trasuuclion is nol clear. PIEnd PIE12 are rhanicayativat in chaels Lhat play crucial roles in several mechanotransduction p cesses (o), PIEZ01 is prominently expressed in the carciovascular syst , 12 and PICZO2 is &#1103;bundant in vanons populations of sensory neurons (13-15). NEUROSCIENCE PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex pression in nodose andpetrosal ganglia, where baroreceptor cell bodies are located (). These gli are uscd wilh ah lher and wilh lhe ngular ganglion in mie. Piea and Pien2 were highly expressed in the nodose-petrusal-jugular ganglion couplex (NTJc) (Fg. 1A) Similar mm- bers of cellsere identified that highly expressed either Pieor Pieno2 exclusively (123 and 124 cells with ach ranseripl, rspelivly, ig A sall popla f neurs expressed both (43 double Peso-positive cells, or 14.8% of all Piea-expressing cells, 6mice, Fig. IB) Wei-Zheng Zeng, Kara L. Marshall, Soohong Min2, Ihab Daou, Mark W. Chapleau, Trancois M. Abboud, Stephen D. Liberles2, Ardem Patapoutian Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for more than 80 years, the molecular identity of baroreceptor mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 and PIEZO2 are together required for baroreception. Genetic ablation of both PiezoI and Piezo2 in the nodose and petrosal sensory ganglia of mice abalished drug-induced baroreflex and aortic depressor nerve activity. Awake, To test whether PiczoI and Pico2 are ex behaving animals that lack Piezos had labile hypertension and increased blood pressure variability, consistent with phenotypes in baroreceptor-denervated animals and humans with baroreflex failure. Optogenetic activation of Piezo2-positive sensory afferents was sufficient to initiate baroreflex in mice. These findings suggest that PIEZ01 and PIEZO2 are the long-sought baroreceptor mechanosensors critical for acute blood pressure control. pressed in baroreceptors, we performed retr grade labellug &omicron;&#943; carulid sensory neuLuns. We into the carotid sinus beneath the serosal vessel covering. All CTE-positive neurons detected in the NPJc from eiglht mice were quautified for the presenc of Pie or Pin2 transcript (Fig., the initial increase in BP , 2). Compromised Cto F). Six aut of 95 retrogradely labeled cells lood pressure (BP) is tightly regulated to varied daily activity demands. Mechanisms premature death in humans with postmyocardial positive ig. B). Pieo-negative cells were likely chemoreceptors, which abundantly innervate term BP regulation. Within seconds andveral ion channels (s-9) hare been sug- the carotid sinus but do not require mecha- S that change blood volume control long-infarction and heart failure (3, 4). minutes, BP is initiated primrilyb rit to bareeeption. Howensitivity. No the 95 CTB-labeled c baroteceptors, a class ofstretch-sensitive neurons ever, substantial residual baroreflex is observed wilhin lhe nluluse and pelrusal ganglia with when tese than nels are ablaled ittlplicaLinx &#3618; ll. vs hru al rrs.iluri urusa u Dowrre peripheral projections in the walls of the aorta the involvement of other sensory systems. None and carotid sinus (,2). An increase in BP stretcheecandidate ion channels have been directlyDpar ment of Call Bolhgy, Harvd Medical Schcol. Bostan baroreceptor nerve endings to trigger atferent activated by mechanical stimuli in heterologousMA C2I15, USA. 8Atbeud Crdivscula Resh Cerit lla A9207. LSA anid Hiophyi,aver Collee edicine, Uriversity of system. The conseqs of baroeceptor actimolecules to form a mechanosensory complex. vation are&#23380;decrease in heart rate &#12308;HR), cardiac Furthermore, whether these channels are acting Cater, Iowa City, A 52242, USA output, and vascular resistance that counteract as sensos or play a role donstrean of mechan- Coesponding aurthor: Email: andemEscripps.edu .P1 & P2 (43 P1 only (123) . P2 only (124) All Piezo+ nodose cells . P1 only (8) -P2 only (8) All CTB+nodose cells 0.8 0.6 0.4 Carotid CTB 0. 0. 0.0 0.2 04 0.6 Piezo1 (fraction cell area) .0 0.2 0. 06 Piezo1 (fraction cell area) Piezo1 Fig. l. Expression of Pezol and Peza2 transcripts &#305;n NPJC. A prnecik I'l n parer! les es nd cal H nu.rbe : 1 cells. &#53412;&middot; ie/12; P2. PiH. tr. CI :) F Pk of NPJc tisse after fluorescent in situ hyrid zation with crobes targeting Piezol (ed) and PiezoZ (cyan). Nuc ei are laceled w tn &#34;,6- green] and Pezo transcript [(E) and (F), red and cyan]. Arrows indicate dian dino-2-phengi incloic DA7l, blue . Amo ws &#3634; ark do&#12375;ble &#1511; ozc-postivo a P ozo ocsit ve cell n(C) and (E and a Nizo positive cel in (D) cells. (B Quantification of trapt label ng a a as a fact on of to nkG) Quantification of Pieo trascript labeling area in CTB paitive cell area (n = 2SC ce ls, s x m ce). Eaen dat recesets one cell. &#44593;urr,bers cells (n-95 cells, eigt ce). Pezo-negative cells are not shown. oell codies back-abeled by carotid sins C B injections c) and D) Zeng et.. Siience 362. 404-407 018 26 Outober 2018  Fig. 2. Baroreflex is abolished in nodase and petrasal g n systol c BF (6), HR (C and ba oref ex)s afte intravenous njection of PE) knockout (KO) mice. Nu&#3634;1 be-of animals shown example before and after FE in ection. Expanded time sca e s &#3634;0wed bursts of ADN activ ty in onase with inclivicl al arterial pulses in W-Nc-mtograted ativ ty is ohse vedind0rice. *P005. *.0l,andn.s. isstatist cally ot signif cant by Lnpai ed Student's tteat: data are reaneSEM &#44564;ezo2 KO indicates F2cKn mice. Piezol Pie202 40 ndicates dKO mice  RESEARCH I REPORT cibsuved a lauk drug-induced ADN activily in (IKO mice corrl[MLed 1&#3648;&#3623; wr mice (-131.9 1629 versus 5558 &plusmn; 1234 normalized area under curve ofintegrated ADN activity, P

 · Answer

1. What are the distributions of Peizo 1 and 2 in the body

2. Which Peizo 1 or 2 is associated with BP regulations

3. What are methods can be used to confirm the hypothesis in the study

4. What are the pitfalls in the current study

.

I want you to formulate FOUR simple Case Study Questions (with Answers) from this given Research paper that I can

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