bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting muscle sympathetic nerve activity and mean arterial blood pressure responses to mental stress
Authors: Wakeham Travis R , Fonkoue Ida A , Wang Min , Carter Jason R , Durocher John J 
Published: November 2023

Mental stress consistently increases mean arterial pressure (MAP), but changes in muscle sympathetic nerve activity (MSNA) during mental stress can vary widely between subjects. The MAP responsiveness to mental stress has been reported to be augmented in both prehypertensive and obese adults when compared to normotensive and normal weight adults, respectively. Cardiovascular reactivity to mental stress has been suggested as a predictor of hypertensive risk (i.e., cardiovascular reactivity hypothesis), yet the major contributing factors to the MSNA and MAP responses to mental stress remain unclear. Predictive independent variables include factors such as resting blood pressure, sex, and body mass index (BMI). Therefore, we used a regression selection method with an algorithm that employed both forward selection and backward elimination to determine the best explanatory variable for the changes in MSNA (ΔMSNA) and MAP (ΔMAP) during mental stress. Predictive independent variables included resting systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), mean arterial blood pressure (MAP), heart rate, sex, age, and BMI in 97 adults (67 males and 30 females). Heart rate, MSNA, and MAP were simultaneously and continuously recorded during a 5–10 min supine baseline and 5 min of mental stress (via mental arithmetic). The strongest predicting variable for ΔMSNA responses to mental stress was BMI (p<0.02), which explained 3.5% of the variance; BMI and ΔMSNA were significantly correlated (p<0.04). In contrast, the strongest predicting variable for ΔMAP responses to mental stress was resting SAP (p<0.02), which explained 5.6% of the variance; resting SAP and ΔMAP responses to mental stress were significantly correlated (p<0.01). We conclude that BMI is the predominant factor that contributes to the ΔMSNA response to mental stress, while resting SAP is the most important contributing factor to ΔMAP responses. Our findings reinforce the importance of both BMI and resting blood pressure in neural cardiovascular reactivity studies.Support or Funding InformationThis project was supported by a Michigan Technological University Research Excellence Fund Seed Grant to J. Durocher.
Central projections to medulla for autonomic adjustments to exercise in rats
Authors: Koba Satoshi , Kato Momone , Hanai Eri , Watanabe Tatsuo 
Published: November 2023

While research efforts have been made on determination of central regions responsible for autonomic adjustments to exercise, neurocircuitries between the regions are little known. Rostral ventrolateral medulla (RVLM), which contains sympathetic premotor neurons, is reportedly activated by exercise. In this study, we attempted to identify central efferent pathways which project to the RVLM and play a role in cardiovascular regulation during exercise. In the first set of experiments, immunofluorescence staining was performed on coronal brain sections of treadmill‐exercised rats which had preliminarily received microinjection of cholera toxin B subunit (CTb, a monosynaptic retrograde tracer) into the RVLM. A significant number of RVLM‐CTb‐labelled cells with immunoreactivity of Fos, a marker of activated neuronal cells, was found in paraventricular hypothalamic nucleus (PVN) and caudal periaqueductal gray (cPAG) of the exercised rats. These data suggest that PVN neurons sending efferent projections to the RVLM (PVN‐RVLM neurons) as well as cPAG neurons projecting to the RVLM are activated by voluntary exercise. In the second set of experiments, effects of selective stimulation of PVN‐RVLM neurons on blood pressure in anesthetized rats were investigated. Adeno‐associated virus (AAV) vector encoding channelrhodopsin2 had been ejected into the PVN of rats. Photostimulation of the RVLM of the AAV‐ejected rats caused a pressor response (N=4). These data suggest that activation of PVN‐RVLM neurons causes sympathoexcitation. Taken together, PVN‐RVLM neurons are considered a pathway which plays a role in evoking sympathoexcitatory response to exercise in rats.Support or Funding InformationSupported by JSPS KAKENHI Grant number 15H05367 (SK) and 26670112 (SK).
Exercise Training Increases Baroreflex Control of Heart Rate and Decreases Muscle Sympathetic Nerve Activity in Chronic Chagasic Cardiomyopathy Patients
Authors: Sarmento Adriana Oliveira , Antunes‐Correa Ligia Moraes , Lobo Denise Moreira Lima , Carvalho Bruna Elisa Piovezani , Trombetta Ivani Credidio , Alves Maria Janieire Nazaré Nunes , Rondon Maria Urbana Pinto Brandão , Rondon Eduardo , Vieira Marcelo Luiz Campos , Mady Charles , Negrao Carlos Eduardo , Ianni Barbara Maria 
Published: November 2023

Asymptomatic or mild symptomatic chronic chagasic cardiomyopathy (CCC) patients even with preserved ventricular function already have autonomic dysfunction. It is well known that decreased baroreflex control of heart rate (HR) and increased muscle sympathetic nerve activity (MSNA) increases mortality of patients with ventricular dysfunction to mortality, and that exercise training (ET) improves cardiovascular autonomic function of these patients. However, the effects of ET on baroreflex control of HR and MSNA in CCC patients with preserved ventricular function are unknown. We hypothesized that ET would increase baroreflex control of HR and decrease MSNA of these patients. Twenty CCC patients with electrocardiographic alterations and ejection fraction (EF)>55% were randomly divided into 2 groups: exercise‐trained (n=8; 47.8±2.5 yrs) and untrained (n=12, 51.7±2.4 yrs). Baroreflex control of HR (ECG) was assessed by stepwise intravenous infusions of phenylephrine and sodium nitroprusside and analyzed by linear regression. MSNA was measured using microneurography. BP was monitored on a beat‐to‐beat basis. Peak VO2 was determined by cardiopulmonary exercise test and cardiac function by echocardiography. ET consisted of three 60‐minute exercise sessions per week on a cycle ergometer for four months. There were no significant differences in gender, age and body mass index among groups. Under baseline conditions (before training), HR, BP, Peak VO2, MSNA and baroreflex control of HR were similar among groups. ET decreased resting HR (67.8±3.6 vs 59.7±3.7 bpm, P=0.009) and increased peak VO2 (25.5±2.6 vs 29.6±1.5 ml/kg/min, P=0.04) whereas there was no change in BP. ET increased baroreflex control of HR in response to phenylephrine infusion (0.24±0.1 vs 0.46±0.1, P=0.01). Furthermore, ET also reduced MSNA (31.8±3.3 vs 22.4±2.8 bursts/min, P=0.04). In conclusion, ET enhanced cardiovascular autonomic function in CCC patients with electrocardiographic alterations and preserved ventricular function. These findings highlight importance of including ET in the treatment of these patients which may lead to a better prognosis of them.Support or Funding InformationThis study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP ‐ #2011/17533‐6d) and, in part, by Fundação Zerbini. Adriana O Sarmento was supported by Conselho Nacional de Pesquisa (CNPq, #142179/2013‐2). Ligia M Antunes‐Correa was supported by FAPESP (#2013/15651‐7). Denise ML Lobo was supported by Conselho Nacional de Pesquisa (CNPq #140265/2013‐9). Carlos E Negrao and Maria UPB Rondon were supported by CNPq (#301867/2010‐0 and #308068/2011‐4, respectively).
The Structural Recognition of G‐quadruplex DNA by PC4: How Does a ssDNA Binding Protein Decide?
Authors: Griffin Wezley C. , Gao Jun , Byrd Alicia K. , Chib Shubeena , Raney Kevin D. 
Published: November 2023

Over the past two decades, guanine‐rich nucleic acids have received considerable attention due to their potential to fold into a secondary DNA structure that has been termed a G‐quadruplex. G‐quadruplex sequences are distributed throughout the genome in distinct, non‐random locations such as the promoters of proto‐oncogenes and telomeric regions of chromosomes. Consequently, because of their non‐random location within the genome G‐quadruplex structures have been implicated in the regulation of genomic processes and their mis‐regulation can result in detrimental disease phenotypes such as cancer or neurodegenerative disorders. G‐quadruplexes are primarily formed by appropriately spaced di‐ or tri‐ guanine nucleotide repeats that self‐associate through Hoogsteen hydrogen bonding to form a planar G‐quartet. G‐quartets then stack onto one another, aided by the stabilization of monovalent cations, such as K+ or Na+ to form a complete G‐quadruplex. Utilizing the G‐quadruplex forming sequence from the c‐MYC gene promoter, we identified positive coactivator of transcription (PC4), a single‐stranded DNA (ssDNA) binding protein, as a novel G‐quadruplex interactor that binds with a low nano‐molar Kd value of ~2 nM, similar to that observed with ssDNA. Based on the structural differences between G‐quadruplex and ssDNA, we surmised that substantial differences might exist between the binding mode for each DNA form. Thus, we set out to investigate what differences exist between these two complexes. Equilibrium binding experiments with alternative G‐quadruplex structures did not influence the Kd value for the binding interaction. Fluorescence resonance energy transfer (FRET) stopped‐flow unwinding experiments revealed that formation of the PC4‐G‐quadruplex complex does not result in complete destabilization of the G‐quadruplex structure. Intrinsic protein fluorescence quenching experiments revealed the stoichiometry of the PC4‐G‐quadruplex complex to be a 1:1 ratio. Mutation of key amino acid residues involved in DNA binding revealed a difference in the requirement for the base‐stacking residues W89 and F77 in ssDNA and G‐quadruplex DNA binding. Taken together, these results provide a novel mode of binding by PC4 through the recognition of DNA secondary structure. The binding data indicates that PC4 can interact with G‐quadruplex DNA in a manner distinct from its binding to ssDNA, consistent with a potential role for this activity in vivo.Support or Funding InformationThis work was supported by NIH Grant R01 GM098922 and the Department of Biochemistry and Molecular Biology, UAMS.
Integrative Teaching of Breast Histology in Clinical Case‐Based Learning
Authors: Leo Joyce Mo‐Ting , Naus Gregory , Ionescu Diana , Hayes Malcolm , Kuo Kuo‐Hsing 
Published: November 2023

The objective of integrative teaching of breast histology aims to improve learning efficiency for medical students in both content knowledge and clinical application.The traditional content structure of Histology is designed to assist students in acquiring in‐depth knowledge of cell and tissue in a systemic order. However, current trends in medical curriculum are headed towards clinical presentation‐based formats to better assist students’ in developing critical thinking abilities under clinical settings. The system‐based content structure of Histology has therefore required revision to focus on presenting content relevant to clinical applications. The topic of breast pathology was identified for a pilot project to develop an integrative model of histology teaching. In the traditional system‐based structure, the topic of breast histology was either delivered within the systems of reproduction or endocrine, which lacked correlation with clinical applications and negatively impacted the effect of learning. With the integration of breast pathology, the learning experience of breast histology is expected to be more meaningful.A team of histologists and breast pathologists developed an integrative module of breast histology and pathology, incorporating content knowledge from histology and pathology for a clinical approach.The delivery of the integrative module contains two stages: (1) on‐line self‐learning and (2) clinical‐case discussion, which are designed to fulfill the purpose of developing content knowledge, while further fostering critical thinking. The on‐line component feature the designs of outcome‐based learning with escalating levels of knowledge. The outcome‐based design aims to prepare students with competent levels of knowledge for case discussion and to further enhance learning experience during the clinical application. The design of escalating knowledge levels allows students to learn based on individuals’ learning pace as well as allowing for real‐time review of fundamental material. The integrative teaching model is currently undergoing the piloting phase.Support or Funding InformationThe Teaching and Learning Enhancement Fund/University of British Columbia
Effect of Smallanthus sonchifolius (Ss) leaf extract on glucose metabolism in mice fed a high fructose diet (HF)
Authors: de Melo Nunes Núbia Alexandre , Simoni Eduardo Bassi , Oliveira Michael Eder , Chagas Viviany Santos , Oliveira Letícia Fernandes , Santos Maria Emilia Soares Martins 
Published: November 2023

A high fructose diet (HF) might play a role in the onset of metabolic disorders and excess weight gain. Usually, the consumption of this diet can induce insulin resistance and increase intrahepatocellular lipids. Smallanthus sonchifolius (Ss) leaf have been studied for their hypoglycemic activity in diabetes type I models. It seems that effect could be related with the high content of phenolic compounds and their in vitro antioxidant activity. For most of the studies using Ss, the leaf extract was obtained using classic techniques of extraction such as maceration followed by organic extraction and evaporation. During this manipulation process, several active substances can be lost. In this study, our Ss extract was obtained using a spray drying encapsulation technique with the intuit to prevent as much as possible the bioactive loss. The aim of this work was evaluate the Ss extract capacity to prevent disorders in glucose metabolism (in a diabetes type II model). Male mice (n=6/group) were fed with a control (C) or high fructose (HF‐ 30%) diets for 8 weeks (C,HF). They also received regular water or a Ss enriched water for the same period (CS, HFS). Food (g) and water or tea intake (ml) were measured daily. Body weight (g) was evaluated weekly. After 8 weeks, non fasting blood glucose levels (GLU) (mg/dl) were measured using a commercial kit. Glucose tolerance test (GTT) was also performed. A basal blood sample was obtained after a 6 hours fasting. A bolus of glucose (2g/kg) was then ip administered. Blood samples were acquired at 30, 60, and 120 min following the glucose bolus for measurement of blood glucose using a glucometer. Results were expressed as mean ± SEM. Data were analyzed using T‐test. P<0.05 was considered significant for all data.No difference was observed in body weight, food and water or Ss water intake in any group. There was an increase of ~30% in HF(403.2) vs C (311.0) and a decrease ~13% in HFS (348.9) vs HF (403.2) at GLU. No difference in GTT was observed between HF and HFS at 0, 30 and 60 minutes. However, a decrease ~9 % HFS (285) vs HF (311) was observed at 120 minutes.In conclusion, we observed that Smallanthus sonchifolius was able to prevent glucose metabolism alterations also in a model of diabetes type II. We believe that more pronounced results could be achieved if we increase the dose and also the period of Ss enriched water administration.Support or Funding InformationCNPq, Labtest
Radiology: a Powerful Ally of Human Anatomy in Medical Education
Authors: Silva Vivian Alessandra , Vilela Daniel Mendonça , Ribeiro Fábio , Regacini Rodrigo , Curcio Daniella Franco 
Published: November 2023

The undergraduate medical curriculum is constantly changing to absorb the exponentially growing knowledge generated by advances in science and technology, particularly in medicine and associated health care fields. This increasing demand for adaption has pushed many educational settings worldwide to experiment and develop innovative pedagogic strategies, in order to add clinical perspective to the traditional knowledge of gross anatomy, and thus enhance student's learning experience. In countries where new teaching methods are replacing human cadaver dissections, the use of imaging exams has become a valuable resource for students to understand human body structures and functions. This study reports the perception of first‐year medical students regarding the inclusion of radiology modules in the Gross Anatomy course of a Brazilian medical school. One hundred students volunteered to answer a survey comprised by 30 questions, using a 5‐point Likert scale. The majority of the students reported a positive outcome of exploring radiology concepts in the anatomy classes (84%). The experience was considered fun (67%), stimulating and challenging (73%). The participants agreed that the use of imaging modules has facilitated learning (96%) and engagement in active search for further and complementary knowledge (69%). Most participants agreed that the strategy has stimulated the study of clinical applications of anatomical concepts, which made them feel more prepared to interact with patients in the future (78%), and helped them to understand the significance of human anatomy in medical clinical practice (93%). After the radiology modules, 71% of the students felt more capable of identifying structures and 69% reported increased interest in imaging diagnosis as a future practice and specialization (69%). The use of radiology images was perceived as a useful resource to learn human anatomy (87%), because it has raised students’ interest in anatomy (77%) and made them more open and prone to acquire new vocabulary, memorize facts and comprehend concepts (74%). Overall, 84% of participants consider that the radiology modules has facilitated learning and helped them to retain anatomical knowledge. An early overview and introduction to diagnostic imaging was perceived as an exciting experience, stimulating students to engage in proactive learning actions, both individually and in teams. The clinical knowledge from radiology was perceived as an excellent complement to the often arid area of Gross Anatomy, especially in the absence of dissection practice of human bodies in lab.Support or Funding InformationCNPq ‐ Brazilian National Counsel of Technological Development
FRET Cytometric Method for High Throughput Screening of Potential Metabolic Inhibitors in Trypanosoma brucei
Authors: Voyton Charles Michael , Morris Meredith T , Ackroyd P. Christine , Morris James C , Christensen Kenneth A 
Published: November 2023

The infectious form of Trypanosoma brucei survives in the mammalian host by converting blood glucose into ATP in a specialized peroxisome‐like organelle called the glycosome. Compartmentalization of glycolysis and the requirement of glucose as the sole carbon source for parasite survival make glucose metabolism and hexose transport in T. brucei an important area of investigation and a promising pathway for targeted anti‐parasite therapy. Here we describe the application of a genetically encoded fluorescent biosensor (FLII12Pglu‐600u) which we endogenously expressed in the cytosol of the infectious bloodstream form (BSF) and in the glycosome of the insect intermediate procyclic form (PCF) allowing for quantification of cytosolic and glycosomal glucose concentration. This methods utilizes flow cytometry for high throughput analysis, as opposed lower throughput microscopy methods typically used with fluorescent protein sensors. Using this method we have measured glucose flux in live BSF and PCF cells showing that under normal growth conditions glycosomal glucose is nearly ten times that of the cytosol. Cellular glucose concentrations were monitored in the presence of candidate glycolytic and hexose transporter inhibitors allowing for inhibition efficacy to be scored. Using this methodology we have now developed high throughput screening (HTS) assays for inhibitors of glucose metabolism and hexose transport in PCF and BSF parasites. The screen allows scoring of 250 test compounds per hour and a robust Z’‐values of 0.56 and 0.74 for BSF and PCF assays respectively. We have demonstrated that flow cytometric analysis of FRET biosensors can serve as a potent platform for analysis of metabolite flux in live T. brucei as well as implementing this strategy in a high throughput screen for molecules that inhibit glucose metabolism and transport in live T. brucei.Support or Funding InformationR21AI105656 from NIH and Brigham Young University
Thermogenic adipocytes regulate axonal growth, innervation, and thermogenic remodeling of white adipose tissue via retinoic acid‐ephrin A5‐dependent pathway
Authors: Ziouzenkova Ouliana , Shen Qiwen , Rumana Yasmeen , Popovich Phillip 
Published: November 2023

Innervation regulates lipolysis, thermogenesis, and vascularization in white adipose tissue (WAT) and undergoes pathological changes in obesity. It is widely believed that mechanisms responsible for innervation during WAT remodeling depend on the central nervous system or neural precursor cells.ObjectiveWe test thermogenic adipocytes in WAT regulate neuronal growth.MethodsWe examined this hypothesis using gene expression analysis, neronal and adipose co‐cultures in vitro. We also used diet induced obesity models including a xenograft model inducing thermogenesis in WAT in obese mice.ResultsWe showed that thermogenic adipocytes in WAT efficiently stimulate neurite outgrowth in vitro and innervation in vivo. We identified their axon guiding secretome that includes ephrin A5 and A4, semaphorins and adamtS9 protease. Diet‐induced and genetically obese mice have decreased expression of these axon guiding molecules in WAT. However, engraftment of encapsulated Aldh1a1−/− adipocytes in intra‐abdominal WAT rescues diminished innervation in obese WT mice. The gain of function studies identified ephrin A5 as an inducer of innervation. Ephrin A5 and A4 are under the control of aldehyde dehydrogenase 1a1 (Aldh1a1) and retinoic acid which represses expression of ephrins and axon growth.ConclusionsOur data support a neuroregulatory role of thermogenic adipocytes and a mechanism for WAT innervation via bidirectional communication between thermogenic adipocytes and the nervous system.Support or Funding InformationThis research was supported by the American Egg Board (20020728), from Novo Nordisk Pharmaceuticals (10040042), and the Ray W. Poppleton Endowment (P.G.P., J.M.), and NSF Center funding (EEC‐0914790). The project was supported by NIH grants R21OD017244 and R01NS047175 (P.G.P., J.M.), and by the National Center for Research Resources UL1RR025755, UL1TR001070, and NCI P30CA16058 (OSUCCC), and supported by the NIH Roadmap for Medical Research.
Reactive Sulphydryl Groups present in Horse (Equus Ferus Caballus) Carbonmonoxyhaemoglobin by Titrating with 5, 5′‐Dithiobis‐2‐Nitrobenzoate (DTNB)
Authors: Iheagwam Franklyn Nonso , OMOTOSHO Omolola Elizabeth , Oloruntola Ayobami , Edobor‐Osor Abiola , Omotosho Temidayo Victor , Chinedu Shalom N 
Published: November 2023

This research was carried out to determine the number of reactive sulphydryl groups in horse (Equus ferus caballus) haemoglobin. Haemolysate was prepared from the horse blood. The haemoglobin was separated into major and minor fractions using carboxymethyl cellulose (CMC‐52). Each haemoglobin fraction, in phosphate buffer pH 7.6, was accurately measured into several clean, dry test tubes. Increasing volumes of stock 5,5′‐dithiobis‐2‐nitrobenzoate (DTNB) were added to the different test tubes and left to equilibrate for 3 hours. Absorbance of each solution in each test tube was read at 412 nm. A graph of change in absorbance against the volume of DTNB was plotted; maximum change in absorbance was obtained at the point where the graph levels off. The ratios of 5‐thio‐2‐nitrobenzoate (TNB) concentration to the concentration of haemoglobin tetramer (Hb4) were calculated and plotted against the volume of DTNB. The number of sulphydryl groups reacting with DTNB was found to be two in both the major and minor haemoglobin.Support or Funding InformationCovenant University, Ota.