bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPARC‐Network‐Scale Interactions Among Simultaneously Recorded Brainstem Neurons In The Dorsal Medulla, Ventrolateral Medulla, And Pons: A Substrate For Central Autonomic Control And Processing Of Cardiovascular Afferent Feedback
Authors: Morris Kendall F. , Segers Lauren S. , Nuding Sarah C. , Lindsey Bruce G. , Pitts Teresa G. , Iceman Kimberly E. , Bolser Donald C. 
Published: April 2020

The central autonomic control system provides parasympathetic and sympathetic drive to peripheral ganglia that regulate a host of visceral functions. Detailed knowledge of the network scale organization of this central circuit is incomplete. We hypothesized that functional synaptic interactions between many simultaneously recorded neurons in and around the nucleus of the tractus solitarius (NTS), the retrotrapezoid nucleus (RTN), ventral respiratory column (VRC) and pons would yield information about the network‐scale strategy that is employed by this system to regulate autonomic drive. Experiments were conducted in 73 decerebrated, paralyzed, and artificially ventilated cats. Multi‐electrode arrays including up to 100 channels were placed in the areas of the NTS, RTN, and VRC. A total of 2,643 neurons were challenged with alterations in blood pressure (BP) and cardiac modulation was assessed in 3,531 neurons. The spike activity patterns of many simultaneously recorded single neurons were evaluated during breathing, the cardiac cycle, increased activation of baroreceptors by inflation of a balloon in the abdominal aorta and unloading of baroreceptors by inflation of a balloon in the vena cava. There was no apparent anatomical segregation of neurons in these areas with regard to cardiac or BP modulation based on stereotaxic coordinates. Cross correlation analysis revealed robust excitatory and inhibitory functional interactions between neurons in the areas of the NTS, VRC, RTN, and pons. Plots customized to reveal patterns of information transfer between neurons in different areas provided evidence that units in the RTN and VRC were predominantly exciting those in the NTS area, while these same NTS neurons were exciting and inhibiting different neurons in the RTN and VRC. Specific evidence was found for putative intermediate ventrolateral medulla (iVLM) neurons that were excited by BP and involved in inhibitory interactions with putative rostral ventrolateral medulla (RVLM) neurons that were inhibited by increased BP. However, this mechanism was a low frequency feature of the dataset. Evidence for synaptic inhibition between neurons that responded to increased BP was a predominant finding. Among neurons that responded to decreased BP, evidence for synaptic excitation was more common. These results support differential organization of brainstem networks that mediate autonomic responses to increased BP relative to those that mediate decreased BP. The brainstem network that mediates sympatho‐inhibition in response to increased blood pressure is sparsely excitatory and may depend on abundant inhibitory mechanisms to enhance signal/noise ratios in support of information transmission from baroreceptors.Support or Funding InformationSupported by 3OT2OD023854
Sex differences in salt‐responsive modulation of bile acids by microbiota regulates Hypertension
Authors: Chakraborty Saroj , Lulla Anju , Cheng Xi , McCarthy Cameron G. , Yeo Ji-Youn , Alimadadi Ahmad , Mandal Juthika , Saha Piu , Yeoh Beng San , Louis Evangelina F , Mell Blair , Jia Wei , Wenceslau Camilla F. , Kumar Matam Vijay , Meyer Katie 
Published: April 2020

Men and women are differently prone to cardiovascular diseases. Salt‐sensitive women are more likely to develop aggravated hypertension in response to an overloaded salt diet than men. Men and women also differ in gut microbiota, which regulates both bile acid composition and hypertension; however, whether sex may differentially influence the gut microbial production of bile acids, with attendant effects on hypertension, is not known. We hypothesized that reshaping of gut microbiota by dietary salt is sex‐dependent and adversely affects bile acids to promote hypertension. To test this hypothesis, groups of male and female salt‐sensitive hypertensive (Dahl S) and salt‐resistant normotensive (Dahl R) rats (n=6/gp) on low (0.3% NaCl) or high (2% NaCl) diets were profiled for fecal microbiota by 16S sequencing and serum bile acids by targeted GC‐TOF‐MS metabolomics. Hierarchical clustering analysis of bile acids with microbiotal profiles revealed that glycine‐ and taurine‐conjugated bile acids were prominently negatively correlated with blood pressure (BP) in female rats, while only taurine‐conjugated bile acids were negatively correlated with BP in male rats. These observations were corroborated by microbiotal and bile acid metabolomic profiling of human hypertensive samples from a population‐based cohort (CARDIA). Next, to test whether hypertension can be prevented by supplementing substrates for bile acid conjugation, high salt fed S rats were administered with either taurine (3% v/v in drinking water) or glycine (1% v/v in drinking water) in drinking water, monitored for BP by telemetry, and profiled for bile acid metabolites. Both taurine and glycine feeding prevented hypertension in females (Systolic BP: taurine:176±7*, glycine: 182±4*, control: 197±4 mmHg, n=6–9/gp, *p<0.05) likely by rescuing levels of levels of respective conjugated bile acids, whereas only taurine, but not glycine, prevented hypertension in males (Systolic BP: taurine: 166±2*, glycine:184±5, control: 184±8 mmHg, n= 5–6/gp, *p<0.05). Our results connect sex‐specific differences in salt‐sensitive hypertension to the gut‐liver axis and suggests that nutritional restoration of host taurine‐ or glycine‐conjugated bile acids for women and host taurine‐conjugated bile acids for men as potential therapeutics for salt‐sensitive hypertension.Support or Funding InformationNational Institutes of Health (R01HL143082)
Utilizing BASIL Consortium Modules to Characterize Putative Kinases of Unknown Function
Authors: Wheeler Baleigh , Memic Nejla , Dollen Julia , Duplan Amanda , Hall Bonnie L. 
Published: April 2020

The Protein Data Bank (PDB) contains 157,712 solved protein structures, with 4,465 of these listed as having an unknown function. We are interested in identifying novel kinases, and screened for them using modules from the BASIL Consortium’s curriculum. BLASTp was initially used to analyze almost 1,500 protein structures of unknown function, narrowing the list to 12 putative kinases. Next, in silico tools including Pfam, DALI, PANNZER, SANS, and ProMOL (a PyMOL plug‐in) were used to further characterize these putative kinases. Two structures were identified as likely kinases: 1ZBS and 3DNU. The 1ZBS protein is predicted to be an N‐acetyl‐glucosamine (NAG) kinase. The 3DNU protein appears to be a toxin‐antitoxin type 2 protein that functions as a serine‐threonine kinase. To further confirm these assignments, docking simulations were performed with the PyRx plug‐in for PyMOL. NAG plus ATP could be docked into the 1ZBS protein with a good calculated binding affinity, supporting its function as a NAG kinase. Similarly, ATP and the tri‐peptide RTV were stably docked with the 3DNU protein. In vitro confirmation of these in silico results is now underway for both 1ZBS and 3DNU. Protein over‐expression and purification are being optimized, and the purified proteins will be used to confirm the identification of NAG/ATP and RTV/ATP respectively as viable substrates for these enzymes.Support or Funding InformationThis project is supported by NSF IUSE 1709170
Essential Anatomy for Obstetrics and Gynecology in the Undergraduate Medical Curriculum
Authors: Harrell Kelly , Davies David , Topping Daniel , Keim Sarah , Marzban Hassan , Latacha Kimberly , Mork Amy , Wineski Lawrence , Lopez Lisa , Kirera Francis , McNary Thomas , McWhorter David , Zumwalt Ann , Carpenetti Tiffany , Downs Mary Beth , Sanky Charles , Laitman Jeffrey , Reidenberg Joy S , Pratt Rebecca , Lewis Steven , Farias Anna , Brooks William , Royer Danielle , Cotter Meghan , Martindale Jim , Harmon Derek , Hankin Mark 
Published: April 2020

IntroductionTo prepare medical students for clinical training and practice, it is critical to understand the anatomical knowledge considered most important for different clinical specialties.AimTo address this issue, a consortium of anatomists in the US and Canada is collecting data from clinical educators in Obstetrics and Gynecology (ObGyn) clerkships and electives to identify the anatomy they consider essential.MethodsAn IRB‐approved, online survey (Qualtrics, Seattle, WA) was used to assess the importance of 98 anatomical topics in seven body regions. The study first examined the percentage of ObGyn clinical educators (clerkship/elective directors and attending physicians) that considered each anatomical region important to their specialty. Second, the study examined the rank assigned to each anatomical topic using an ordinal scale from 1 (not important) to 4 (essential).ResultsAt the time of abstract submission, data had been collected from 71 ObGyn clinical educators at 22 medical schools. The percentage of ObGyn clinical educators that considered each anatomical region important to their specialty were (highest‐to‐lowest): Pelvis & Perineum (100%), Abdomen (96%), Lower Limb (47%), Back (34%), Thorax (26%), Head & Neck (18%), and Upper Limb (13%). Further data analysis has identified the highest ranked anatomical topics in each body region for the ObGyn clerkship/elective.Discussion and ConclusionThis database provides detailed information regarding the most clinically relevant anatomical topics as identified by ObGyn clinical educators. This information can aid in focusing preclinical learning to best prepare medical students for success in their undergraduate and graduate clinical experiences.
Cardiovascular Deconditioning Enhances Cardiovascular and Autonomic Response to Arterial Chemoreflex Stimulation
Authors: De Andrade Ozahyr , Kline David D. , Hasser Eileen M. 
Published: April 2020

Cardiovascular deconditioning (CVD) due to bedrest, inactivity or exposure to microgravity impairs cardiovascular regulation and circulatory homeostasis. Cardiovascular changes associated with CVD, including resting tachycardia, decreased exercise capacity and autonomic impairments are reproduced in an animal model of CVD, hindlimb unloaded (HU) rats. Autonomic dysfunction, including blunted baroreflex function, in CVD is associated with mechanisms involving the central nervous system. We hypothesized that CVD augments the arterial chemoreflex. Male Sprague‐Dawley rats were subjected to 2 weeks hindlimb unloading (HU) to simulate CVD, or maintained at normal postural position (cage control, CC). Under inactin anesthesia, baseline heart rate (HR) was elevated in HU vs CC (381±8 bpm vs 334±6 bpm). To examine the chemoreflex, HU and CC rats (n=5–6 each) were given bolus NaCN (25, 50, 75ug/kg, iv) or acute hypoxia (12% O2, 45 seconds). NaCN dose dependently increased HR and mean arterial pressure (MAP) in HU but not CC. At the highest NaCN concentration, HU increased MAP (22±4 mmHg) and HR (16±3 bpm) more than CC MAP (8±1 mmHg) and HR (6±2 bpm). NaCN also increased splanchnic sympathetic and phrenic nerve activity (SSNA and PhrNA) in both groups, and responses tended to be greater in HU rats. Likewise, the peak hypoxic response of SSNA and PhrNA were greater in HU than CC rats (SSNA, HU 143 ± 26% vs CC 111 ± 9%; PhrAmp%; HU 382 ± 208 vs CC 300 ± 103). Exposure to NaCN or hypoxia did not change PhrFreq in either group. These data suggest that HU enhances cardiovascular responses to chemoreflex activation.Support or Funding InformationFunding: HL132836
Environmental Chemicals Disrupted Lipid/Fatty Acid Contents of Rat Organs and Reversed by Treatment With Citrus Lime Nano‐particle
Authors: Gonnabathula Pavani Kumar , Yakubu Momoh A. 
Published: April 2020

The environment is rich with trace concentrations of toxicants, these toxicants in the living system can disrupt biological homeostasis. We had reported that trace concentrations of emerging contaminants dysregulate antioxidant systems. In the present study we investigated the effects of these cellular defense disrupting chemicals on organs’ fatty acids and lipids contents and evaluated effects of Citrus lime conjugated nano‐particles. Rats were treated with environmental chemicals (EC) consisting of mixture of atrazine, dieldrine, endrine, endosulfan, anthracene, 17‐alpha ethynyl estradiol, diethylstilbestrol, estradiol, estrone, testosterone and estriol at a concentration of 1–10 ug/L in drinking water for 6 weeks along with control. Another group was treated with synthesized 2 μM Citrus lime nano‐particle alone or in combination with EC. At the end of the treatment, rats were euthanized, and organs collected. Samples were extracted for determination of fatty acids and lipids using Agilent 7890B/5977B GC/MSD System with SQ detector with HP‐5 MS capillary column. Results shows treatment with environmental toxicants dysregulated fatty acid species in the heart, liver, lung, spleen, brain, and fat with changes that varied up to 7.0×108 % when compared to the control. Similarly, cholesterol contents were severely dysregulated with the range of changes varying from −68 to 2.0×1010 %. The highest dysregulation occurred in the fat tissues. All these changes were reversed in the group treated with synthesized Citrus lime nano‐particle. Our results indicate that environmental chemicals in trace concentrations disrupts fatty acids species and cholesterol contents of different organs. The disrupted fatty acids are Hexadexcanoic acid methyl ester; n‐Hexadecanoic acid, 10‐methyl‐, methyl ester; 9,12‐Octadecadienoic acid; Heptadecanoic acid; Eicosatetraenoic acid, methyl ester, Methyl stearate. These disruptions by environmental chemicals were reversed by nano‐particle conjugated to alkaloid from Citrus lime. These fatty acid species possess antioxidants, anti‐inflammatory, and other cellular defense and regulatory functions. Thus, our results suggest that low concentrations of environmental chemicals’ disruptions of these functions is the hallmark of slow and long‐term developing health altering conditions such as diabetes, Alzheimer’s, rheumatoid arthritis etc. possibly mediated by inflammatory processes and induced oxidative stress. Our results further suggest that nano‐particle conjugated alkaloid could serve as an antidote to long term effects of exposure to trace concentrations of environmental chemicals.Support or Funding InformationThis research is supported by Tittle III under the Award Number P031B090216;Title III, Part B, HBGI (CFDA No. 84.031B).
‐ Two Alternative Mechanisms Regulate the Onset of Chaperone‐mediated Assembly of the Proteasomal ATPases
Authors: Park Soyeon , Nahar Asrafun 
Published: April 2020

The proteasome holoenzyme is a molecular machine that degrades most proteins in eukaryotes. In the holoenzyme, its heterohexameric ATPase injects protein substrates into the proteolytic core particle, where degradation occurs. The heterohexameric ATPase, referred to as ‘Rpt ring’, assembles through six ATPase subunits (Rpt1‐Rpt6) individually binding to specific chaperones (Rpn14, Nas6, Nas2 and Hsm3). Here, our findings suggest that the onset of Rpt ring assembly can be regulated by two alternative mechanisms. Excess Rpt subunits relative to their chaperones are sequestered into multiple puncta specifically during early‐stage Rpt ring assembly. Sequestration occurs during stressed conditions, for example heat, which transcriptionally induce Rpt subunits. When the free Rpt pool is limited experimentally, Rpt subunits are competent for proteasome assembly even without their cognate chaperones. These data suggest that sequestration may regulate amounts of individual Rpt subunits relative to their chaperones, allowing for proper onset of Rpt ring assembly. Indeed, Rpt subunits in the puncta can later resume their assembly into the proteasome. Intriguingly, when proteasome assembly resumes in stressed cells or is ongoing in unstressed cells, excess Rpt subunits are recognized by an alternative mechanism—degradation by the proteasome holoenzyme itself. Rpt subunits undergo proteasome assembly until the holoenzyme complex is generated at a sufficient level. The fully‐formed holoenzyme can then degrade any remaining excess Rpt subunits, thereby regulating its own Rpt ring assembly. These two alternative mechanisms, degradation and sequestration of Rpt subunits, may help control the onset of chaperone‐mediated Rpt ring assembly, thereby promoting proper proteasome holoenzyme formation.Support or Funding InformationR01GM127688
Cardiac Neuroanatomy and Chronotropic Modulation of the Adult Giant Danio Heart
Authors: Nelson Emma , Koch Alyssa , Lafontant Pascal J. 
Published: April 2020

Studies in non‐mammalian models species have contributed significantly to our understanding of the biology and the nature of innervation in the heart. The giant danio (D. malabaricus) is a teleost fish species closely related to zebrafish, that is also capable of heart regeneration. We previously described the development and maturation of the giant danio (GD) heart. However, little is known about its innervation. We hypothesized that the pattern of innervation in the GD heart is anatomically and physiologically complex, and that the heart is responsive to physiological modulation similar to that seen in cyprinid fish and mammals. Using various neuronal markers and electron microcopy, we described the presence, distribution, and nature of nerves in the GD heart. Our study shows first that fine intrinsic cardiac nerve fibers are present throughout the heart chambers. Second, nerve soma and ganglia are highly concentrated at nerve plexuses located near the sinoatrial (SA) and atrioventricular (AV) junctions. However, the volume density of axonal processes_ projecting from ganglia located over the ventral aorta_ is highest over the corpus of the bulbus arteriosus. Third, using an ex vivo GD heart preparation, we found that the GD heart responded to both adrenergic and cholinergic agonists, in a manner that mirrors mammalian and teleost hearts. Taken together, our studies show that the GD heart displays complex patterns of innervation, and conserved cardiac physiological responses, and strongly suggest that the GD could be used as a viable model for investigating cardiac biology.Support or Funding Information• NIH R15 HD084262‐01, Martha C. Rieth Faculty Fellowship, Buehler Family Foundation
Employment of Different Waveform Shapes for Electrical Stimulation of the Vagus Nerve in Rats
Authors: Gomes Amanda Rodrigues Correa Frota , Subar Leonardo Guimarães , Ribeiro Raianne Stefane Dias , Brognara-Dias Fernanda , Dias Daniel Penteado Martins 
Published: April 2020

The electrical stimulation of neural pathways has gained therapeutic relevance over the past decades. A wide range of clinical conditions benefits from vagus nerve stimulation (VNS), such as depression, epilepsy, heart failure, rheumatoid arthritis, cluster headache, traumatic brain injury, among others. Considering the relevance of experimental protocols aimed at a better understanding of mechanisms underlying the effects of VNS, proper adjustment of stimulation parameters such as frequency, pulse width, electric tension and waveform shape is crucial. The current study was intended to evaluate the effects of VNS on bradycardic response using three different waveform shapes. Wistar male rats were anesthetized with a ketamine/xylazine mixture and implanted with an electrode for electrocardiogram (ECG) recording and a bipolar stainless‐steel electrode into the cervical portion of the vagus nerve for VNS. Anesthetized animals had the ECG recorded and heart rate (HR) calculated on a beat‐to‐beat basis. Baseline HR was obtained during 5 minutes, followed by sessions of electrical stimulation of the vagus nerve. Taking into consideration the shape of the waveform used into VNS, rats were assigned into three groups: monopolar pulse (MP), depolarizing prepulse (DPP) and bipolar pulse (BP). Stimulation parameters were similar for all groups (frequency: 5 Hz; pulse width: 100 microseconds; electric tension: 1 V). Each VNS session lasted 30 seconds and sessions were 3 minutes apart. HR response during VNS was calculated to ensure the reliability of the preparation and was taken as the difference between average HR preceding VNS onset and maximum bradycardic response during the 30 seconds session. The magnitude of bradycardic response following the first VNS session was higher among DPP rats (Δ115 ± 23 bpm) when compared to MP (Δ37 ± 9 bpm) and BP (Δ83 ± 14 bpm) groups. Also, since our experimental setting contributes for better establishment of neural pathway longevity following exposure to electrical stimulation, the averaged bradycardic response among the three successive sessions of VNS was assessed. In a similar fashion to the findings regarding one single VNS session, it was observed a trend towards higher bradycardic response in DPP rats (Δ90 ± 32 bpm), when compared to MP (Δ56 ± 24 bpm) and BP (Δ70 ± 5 bpm) groups. From our findings, we can conclude that depolarizing prepulse waveform elicits a higher bradycardic response when VNS is conducted using parameters that match other waveform shapes. It is noteworthy to mention that the employment of VNS using techniques gentle (i.e. diminished damage) to neural pathways could contribute to nerve longevity.Support or Funding InformationBarao de Maua University Center: 344/18; FAPESP: 2017/05163‐6