bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo assessment of resting and catecholamine stimulated cardiac function in rat models of low and high aerobic running capacity
Authors: Morgan Eric E. , Ways Justin A. , Cicila George T. 
Published: June 2021

Our laboratory has previously identified inbred rat strains divergent for aerobic running capacity (ARC); low performing Buffalo (BUF) and high performing DA rats. Subsequent studies of isolated DA and BUF hearts showed a strong correlation between ARC and cardiac output (CO). In the present study, we tested the hypotheses that 1) there is increased in vivo basal LV function in DA compared with BUF rats and 2) the cardiac response to catecholamine stress is increased in DA vs. BUF rats. A high‐fidelity microtip pressure‐volume catheter was used to examine cardiac function in intact male BUF (n=13) and DA (n=12) rats at rest and during dobutamine infusion. Resting DA hearts outperformed BUF hearts as evidenced by a significantly higher cardiac output (39±2 vs 63±6 mL/min, P<0.05) and contractility index (136±4 vs 154±7 mmHg2/sec, P<0.05). Following dobutamine infusion (10μg/kg/min), CO was significantly greater in DA compared to BUF rats (50±2 vs 92±9 mL/min, P<0.05). DA rats showed a greater increase in stroke volume whereas BUF rats displayed a greater increase in heart rate following dobutamine infusion (Figure). We conclude that cardiac function is greater at rest in DA compared to BUF rats, and that DA and BUF hearts differ in their response to catecholamine stress.This work was supported by NIH grant HL67276 (GTC) and a Medical Student Research Fellowship from The University of Toledo College of Medicine (EEM).
Field trials of a new physiological data logger in active fishes
Authors: Clark Timothy Darren , Frappell Peter B , Taylor Brian , Farrell Anthony , Hinch Scott , Seymour Roger S 
Published: June 2021

We have designed and constructed implantable data loggers that measure heart rate (HR) and body temperature of free‐ranging animals. We present data from the first field trials of these loggers in penned southern bluefin tuna (Thunnus maccoyii) under aquacultural conditions, and in spawning sockeye salmon (Oncorhynchus nerka) under natural conditions. Bluefin tuna (~ 15.2kg) maintained visceral temperature (VT) between 0.4 – 2.6°C above ambient water temperature (18.5°C) during non‐digesting periods, while HR ranged from 33 – 74 beats/min. VT rose to 1.4 – 6.5°C above ambient at the peak of the digestive period, and the magnitude of this increase was dependent on ration size. HR followed a similar trend during the digestive period, reaching levels of 52 – 117 beats/min and implying that the postprandial increase in oxygen consumption is assisted largely by an increase in HR. The duration of digestion ranged from 10.7 to 30.9 h depending on ration size.Sockeye salmon were implanted with data loggers in October 2007 when they had migrated from the ocean to their natal stream to spawn and subsequently die. Data analyses are ongoing, but it has been confirmed that salmon carrying data loggers do not have a reduced lifetime on the spawning ground, implanted salmon display normal courting and mating behaviours, and implanted salmon completed their lifecycle normally by spawning before death.
MRI volumetry of the amygdala: an anatomic background
Authors: Brabec Jiri , Horinek Daniel , Krasensky Jan , Vaneckova Manuela , Seidl Zdenek , Petrovicky Pavel 
Published: June 2021

MRI volumetry of amygdala is much disputed in literature. The complexity of amygdalar structure and the small differences in the intensities of the magnetic resonance signals for the temporal lobe structures makes it difficult to elaborate the methodology that would accurately reflect its true anatomic relations.The goal of our study was to elaborate standard protocol for the MRI volumetry of the amygdala by means of classic neuroanatomic methods and MRI examinations in a sample of 70 healthy adults (18 – 99 years of age). On the basis of comparison of amygdalar cytoarchitecture and intensities of the MR signal, two methodological approaches emerged: classical approach and expanded approach.Neither volumetric differences between two sexes nor interhemispheric differences were significant for absolute volumes of amygdala in either of the two approaches. A significant correlation between the size and age of the amygdala was not found.In spite of the fact that it is not possible for clinicians to measure all necessary dimensions, another goal was to find a simplified measurement technique, which could serve as an indicator of the actual size of the amygdala. From a wide variety of approaches, a single measurement of the plane in the level of the most anterior tip of the hippocampus is very promising.Supported by grants IGA MZ 2006 NR8931‐4, and No. 0021620806 from the Ministry of Education of the Czech Republic
S100A1 expression in mouse embryos
Authors: Cheung Siu Yuen , Wang Xia , Bao Li Hua , Heizmann Claus W , Chan Wood Yee 
Published: June 2021

S100A1 protein is an EF‐hand type calcium‐binding protein with unique functions in adult tissues. However, its role in the embryonic development is largely unknown. To better understand its developmental role, we sought to determine the spatio‐temporal expression of S100A1 with reverse transcription‐PCR and specific immunohistochemical localization in normal and S100A1‐deficient mouse embryos which were generated previously by gene trap mutagenesis. The S100A1 mRNA started to express in normal embryos at E9.5 and was steadily increased until birth. At E15.5 and E17.5, S100A1 protein expression was observed in the heart, cartilages, bones, liver, lung and hindbrain. The expression was not detected in S100A1‐deficient embryos at all stages examined and S100A1‐deficient embryos did not exhibit any morphological anomalies. The S100B protein, which forms heterodimers with the S100A1 protein, was expressed in both normal and S100A1‐deficient embryos, indicating that the absence of the S100A1 protein did not influence S100B protein expression. Taken together, our results suggest that the widely expressed S100A1 protein in embryos may be a functionally redundant protein whose developmental functions can be supplemented by other proteins.Acknowledgements: The work was supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project no. CUHK4421/05M).
SYNTHESIS OF ESTROGENS AND ANDROGENS IN THE GONADS OF THE FETAL SHEEP
Authors: Gomez Yolanda , Infante Veronica Chavez , Ramirez Esther Bautista , Pardo Marta Romano 
Published: June 2021

In this work we investigated the secretion of 17B‐estradiol (E2) and testosterone (T) in the gonads of ovine fetuses of 3.6 and 12 inches in crown‐rump (C‐R) length. The fetus were obtained immediately after the slaughtering of animals and transferred to phosphate‐buffer in cold. The gonads were carefully dissected and cells were obtained by dissociation trypsin treatment, the cells isolated were incubated in Dulbecco's medium plus 0.1 BSA during one hour to 370C. The secretion of E2 and T were measured by radioimmunoassay in the incubation medium of the cells.The 17B‐ estradiol was the predominant estrogen produced by ovaries during the developing sheep gonad. The fetuses of 12 in showed the highest secretion of E2 58pg/mg protein whereas, the minimum secretion level of E2 were 10 pg/mg protein in the fetuses of 8 in. The amount of testosterone in these ovaries was not detectable in the previous fetuses until the 8 in fetuses an average of 15pg/mg protein and the secretion was maintain during all fetuses development.Testosterone was the principal androgens synthesized by the testes. The maximum level of T secretion 600pg/mg protein was found in the feto 6.4 in. By the other hand, the E2 secretion was low during the process.These results show that during the development of the ovine fetal gonads synthesizes estrogens and androgens, which strongly suggests the activity of P450‐aromatase and 17B‐HSD.CONACYT 41423 Q
Meiotic recombination hotspot ade6‐M26: Phosphorylation‐independent regulation of Atf1‐Pcr1 heterodimer by SAP/MAP kinase Spc1
Authors: Gao Jun , Davidson Mari K , Wahls Wayne P 
Published: June 2021

Homologous recombination occurs at a high frequency in meiosis, is clustered at hotspots, and aids chromosome segregation. In the fission yeast S. pombe, Atf1‐Pcr1 heterodimer (ATF/CREB proteins) binds to and activates a meiosis‐specific recombination hotspot, ade6‐M26. The stress‐activated protein kinase Spc1 (a homolog of human p38) phosphorylates Atf1 and is also essential for hotspot activity. We determined the roles of Atf1, Pcr1, and Spc1 in hotspot recombination. Deletion analyses revealed that only the bZIP (DNA binding/protein dimerization) domain of Pcr1 was required. In contrast, bZIP and non‐bZIP regions of Atf1 affected hotspot recombination. Remarkably, a mutant form of Atf1 that can not be phosphorylated by Spc1 kinase still activated the hotspot. Furthermore, artificial tethering of Atf1 to ade6 promoted recombination in the absence of its own bZIP domain, or Pcr1, or Spc1 kinase. Therefore: 1) An amino‐terminal “activation domain” of Atf1 is necessary and sufficient to promote hotspot recombination. 2) Pcr1 confers DNA binding site specificity to Atf1‐Pcr1 heterodimer in vivo, thus targeting the Atf1 activation domain to specific chromosomal sites. 3) Phosphorylation of Atf1 by Spc1 kinase is, unexpectedly, not required for hotspot activity. 4) The Spc1 kinase regulates hotspot recombination only at or prior to binding of Atf1‐Pcr1 to ade6‐M26 DNA.Research supported by NIH R01 GM062244
A model of Chlorella DNA ligase substrate discrimination and binding analysed by surface plasmon resonance
Authors: Brooke Clare , Odell Mark 
Published: June 2021

The recent structure of Paramecium bursaria Chlorella virus 1 (PBCV‐1) DNA ligase complexed with DNA highlights differences in the substrate engagement of this minimal ligase when compared with the multi‐domain human DNA ligase 1 (huLig1). HuLig1 consists of a catalytic core, equivalent to the Chlorella enzyme, with additional structural domains including a DNA‐binding domain (DBD). Chlorella ligase lacks a DBD but possesses a ‘latch’ region that stabilises DNA interaction.We have studied binding of a number of Chlorella and huLig1 mutants with various synthetic DNA substrates; a double‐strand (ds) nick (5′PO4 juxtaposed to 3′OH), an intact ds duplex and a duplex containing a one‐nucleotide gap. Chlorella ligase has been shown by gel shift analysis to discriminate between nicked dsDNA and an intact duplex. We observe similar on rates for all DNA species however the ligase remains more tightly bound to nicked DNA. A polypeptide derived from huLig1 equivalent to the Chlorella ligase, shows poor substrate discrimination and a ∼15‐fold lower affinity for dsDNA compared to the Chlorella enzyme.Alanine replacement of two conserved phenylalanine residues in the Chlorella enzyme significantly alters the DNA interaction profile. We surmise that following stabilisation of DNA by the latch the two phe residues interdigitate into the DNA sequentially, phe286 inserting first (closest to the 5′PO4) followed by phe75.
Involvement of eukaryotic translation initiation factor 5A (eIF5A) in skeletal muscle stem cell differentiation
Authors: Luchessi Augusto Ducati , Hirabara Sandro Massao , Lambertucci Rafael Herling , Cambiaghi Tavane David , Neto Claudio Miguel Costa , Curi Rui 
Published: June 2021

The protein eIF5A is involved in different steps of mRNA metabolism. This factor contains a special amino acid residue named hypusine. Hypusine is required for the eIF5A activity being produced by a post‐translational modification involving spermidine as substrate. Stem cells (satellite cells) from skeletal muscle rats were submitted to differentiation and an increase of eIF5A gene expression was observed. An increased content of eIF5A protein was observed in satellite cells on differentiation in comparison to non‐differentiated satellite cells and muscle tissue. The treatment with GC7, a hypusination inhibitor, abolished the differentiation process. In association with the differentiation blockage, an increase in glucose consumption and lactate production and a decrease in glucose and palmitate decarboxylation were observed. Also, there was a reduction in cell proliferation and protein synthesis. L‐arginine, a partial suppressor of muscle dystrophic phenotype and spermidine precursor, partially abolished the GC7 effects. Our results reveal a new physiological role for eIF5A and contribute to elucidate the molecular mechanisms involved in muscle differentiation.Supported by: FAPESP, CNPq and CAPES.
Techniques in microfluidics: creation of microspheres for cellular encapsulation
Authors: Tesche Leora Jeanne , Gavigan Thomas , Samuelson Lisa , Gerber David 
Published: June 2021

BackgroundWith new innovations in stem cell research, cell therapy as a treatment modality has broad potential. Current pursuits range from treatment of diabetes and cardiovascular disorders to wound healing and aesthetic medicine. For stem cell therapy to be realized, a reliable method for transplanting cells is critical. Currently, technical difficulties including mechanical shearing and failure of a cell to engraft limit the long‐term survival of transplanted cells. Microencapsulation of cells within a protective biosphere allows cells to be safely injected into the host where they can proliferate and engraft providing therapeutic benefit.Research ProposalThis abstract describes a novel technique of creating a two layered microsphere. In this model, cells suspended within a nutrient rich collagen matrix are encapsulated by a protective alginate coating.MethodsSpecially patterned microfluidic molds are created using lithography. T‐junction geometry within the mold creates 200μ spheres which contain select cell populations. Phase contrast imaging is used to track cell growth within the microspheres.ResultsHepatic cells survive and proliferate within this microenvironment for extended periods in culture, up to 2 weeks.DiscussionPerfecting this technique has implications in studying 3‐dimesional cell culture as well as cellular transplantation.
Changes in neuropeptide expression in hypothalamic neurons of rats with chronic heart failure
Authors: Llewellyn‐Smith Ida J , Smith Cameron M 
Published: June 2021

Pre‐autonomic and neuroendocrine neurons in the hypothalamic paraventricular nucleus (PVN) are important for regulating blood pressure and fluid balance. In chronic heart failure (CHF), changes occur in the anatomy and physiology of the PVN to compensate for reduced heart function. We investigated the effect of CHF on hypothalamic neurons immunoreactive for corticotropin releasing factor (CRF), vasopressin (VP), enkephalin (ENK), pro‐ENK or nitric oxide synthase (NOS). To induce myocardial infarctions that occupied >40% of the left ventricle, we ligated left coronary arteries in male rats and perfused them 6‐8 weeks later. Hypothalamic sections from CHF rats and control rats without ligations were stained with immunoperoxidase and immunoreactive neurons were counted. We found more CRF‐ and VP‐immunoreactive neurons in the PVN of CHF than control rats (p<0.05, n=5‐6 rats/group). There was also a trend towards a decreased number of NOS‐immunoreactive neurons in the PVN in CHF rats (p=0.07, n=5/group). ENK neurons were not found in the PVN itself but in the anterior hypothalamic area. The number of ENK‐ (p=0.34, n=4/group) and pro‐ENK‐immunoreactive (p=0.57, n=3/group) neurons did not differ between CHF and control rats. These results suggest that CHF causes widespread changes in the neurochemistry of hypothalamic neurons involved in the regulation of autonomic function.Support: NH&MRC of Australia
The sympathetic chemoreflex response to hypoxia in humans is sensitised by prior exposure to 8 h of isocapnic hypoxia
Authors: Croft Quentin , Sander Mikael , MacDonald Ian , Simpson Liz , Dorrington Keith , Robbins Peter 
Published: June 2021

In healthy humans the ventilatory sensitivity to acute hypoxia is increased by prior exposure to hypoxia for 8 h. Here we test the hypothesis that the sympathetic chemoreflex is similarly sensitised by a prior short‐term exposure to hypoxia. Healthy humans (n=9) were exposed to eucapnic hypoxia (controlled end‐expiratory PO2 = 45 mmHg) for 10 minutes before and after 8 h in an hypoxic chamber (controlled end‐expiratory PO2 = 50 mmHg). Muscle sympathetic nervous activity (MSNA) was determined by peroneal microneurography (morning recording in one leg and evening recording from the contralateral leg). Acute hypoxic exposure before vs after the chamber resulted in oxygen desaturation (arterial saturations 82±1 vs 81±1 %) and increases in heart rate (+15±2 vs +20±1 b·min‐1), ventilation (+8±1 vs +20±1 l·min‐1), and MSNA (+61±14 vs +154±34 % total activity), all p<0.05. These results demonstrate robust sensitization of sympathetic as well as ventilatory chemoreflexes in healthy humans following an 8‐h exposure to mild hypoxia.This work was supported by The Wellcome Trust and University College, Oxford.
Increased vasopressin transmission from the hypothalamic paraventricular nucleus (PVN) to the rostroventrolateral medulla (RVLM) augments cardiorespiratory outflow in CIH‐conditioned rats
Authors: Kc Prabha , Balan Kannan V , Tjoe Steven S , Martin Richard J , LaManna Joseph C , Dick Thomas E 
Published: June 2021

Conditioning with chronic intermittent hypoxia (CIH) causes hypertension associated with elevated sympathetic nerve activity and increased cardiorespiratory sensitivity to hypoxia. Hypoxia sensed by the carotid bodies drives cardiorespiratory regulating sites, including the PVN via the nucleus tractus solitarius. Our hypothesis is that CIH‐conditioning alters the balance of excitatory and inhibitory influences on CR control via the PVN. Male SD rats were exposed to CIH for 8 h/day for 10 days. Blood pressure (BP), heart rate (HR), diaphragm (DEMG) and genioglossus (GGEMG) activity were recorded in anesthetized, ventilated and vagotomized rats. The PVN was disinhibited by injecting bicuculline (BIC, a GABAA receptor antagonist, 100 pmol) before and after blocking AVP receptors in the RVLM with SR49059 (200 pmol/side, bilateral). In control rats, BIC increased BP, HR, minute DEMG and GGEMG. Following RVLM blockade, these variables were significantly decreased (p < 0.05). Although more pronounced, similar responses were observed in CIH‐conditioned rats; however, it required a higher dose of blocker (400 pmol/side, bilateral) to blunt the effect (p < 0.05). These finding suggests that AVP modulates cardiorespiratory output via the RVLM and CIH‐conditioned rats show augmented AVP transmission, suggesting AVP as a candidate neuropeptide that controls sympathetic tone and respiratory output during CIH.Supported by: HL 87620.
Effects of high salt diet on NF‐KB and CREB DNA binding activity in heart, kidney and hypothalamus of SHR
Authors: Shang Qianhui , Wang HongWei , Stewart Alexandre FR , Leenen Frans H. H. 
Published: June 2021

In Dahl S or SHR on high salt diet, activation of NF‐κB contributes to cardiac hypertrophy and renal damage, which may be offset by activation of CREB. The brain RAAS mediates the salt‐induced hypertension, possibly by NF‐κB in the PVN. We assessed effects of high salt diet on DNA‐binding activity of NF‐κB and CREB in the heart, kidney and PVN of WKY rats and SHR on high (8%) or reg (0.6%) salt diet for 2 or 4 weeks (n=6). NF‐κB and CREB DNA binding activity were studied by electrophoretic mobility shift assay.In WKY, high salt only increased CREB DNA binding activity in the LV and NFκB in the PVN. In SHR, high salt increased NF‐κB DNA‐binding activity in the heart and kidney, but decreased CREB binding activity in the heart, kidney, and the PVN.ConclusionHigh salt causes an inverse relationship between NF‐κB and CREB in the LV, kidney and PVN which may contribute to salt induced sympathetic hyperactivity, LV and renal hypertrophy in SHR.
Hemolysis‐induced pulmonary hypertension and treatment with infused or inhaled nitrite, or inhaled NO in the newborn lamb
Authors: Vrancken K , Schroeder H , Terry M H , Merrill‐Henry J , Power G G , Blood A B 
Published: June 2021

BackgroundNO is a tonic vasodilator in the lung. Plasma‐free hemoglobin scavenges NO, resulting in pulmonary vasoconstriction. Oxidized hemoglobin, produced by the reaction of NO with oxyhemoglobin, does not scavenge NO. We hypothesized that NO, administered as a gas (iNO) or as nitrite that is endogeneously converted to NO, would attenuate pulmonary hypertension caused by hemolysis.MethodsIntravenous hemolyzed blood was administered to newborn lambs for 180 min while measuring pulmonary arterial pressure and flow. Changes in pulmonary and systemic pressures and resistances were measured. During the final 90 min of hemoglobin infusion, intravenous nitrite, nebulized nitrite, or iNO (20ppm) were administered.ResultsHemolyzed blood resulted in a significant increase in pulmonary (p<0.01) but not systemic vascular resistance that was sustained throughout the first 90 min of hemolysate infusion. iNO resulted in a rapid return of pulmonary vascular resistance to baseline levels, associated with nearly complete oxidation of plasma hemoglobin (p<0.01). Inhaled nitrite resulted in a significant increase in exhaled NO gas, and a significant decrease in pulmonary vascular resistance. Intravenous nitrite did not alter pulmonary vascular resistance significantly.ConclusionsHemolyzed blood causes selective pulmonary hypertension. Inhaled nitrite produces vasoactive amounts of NO. The benefits of iNO therapy for treatment of hemolysis‐induced pulmonary hypertension may result from both direct vasodilation as well as oxidation of the plasma free hemoglobin to methemoglobin, which does not scavenge NO.
Manipulation of lipid bioaccessibility influences postprandial vitamin E concentrations in healthy human subjects: implications for inflammation, oxidative stress and vascular responses.
Authors: Berry Sarah E , Lapsley Karen , Tydeman Elizabeth A , Lewis Hannah B , Phalora Ravneet , Rosborough Jennifer , Picout David R , Ellis Peter R 
Published: June 2021

Postprandial lipemia is associated with an acute elevation in oxidative stress, inflammation and impaired vascular function, which is attenuated by the presence of antioxidant vitamins. We previously reported that slow release (low bioaccessibility) of lipid from whole almonds (WA) during digestion, compared with free oil from almond (AO) or sunflower (SO) seeds, reduced postprandial lipemia (over 8h), but no effects on oxidative stress and vascular function were found1. Subjects (n=20, aged 18‐40y) were fed test meals containing 50g fat provided as WA, AO or SO in a randomised cross‐over design, with 1‐wk washout. Additional analysis to investigate the effects of differences in lipid bioaccessibility on changes in plasma vitamin E and interleukin 6 (IL‐6; inflammatory marker) concentrations are presented. Plasma vitamin E concentrations were lower (mean incremental area under curve with 95% CI) following the WA meal (69 (25, 113)) vs. the AO (150 (211, 88)) and CO (137 (190, 84)) meals; P=0.003. IL‐6 concentrations increased significantly from fasting following the test meals (P=0.023), but did not differ between meals. The concomitant increase in plasma vitamin E with postprandial lipemia from the free oils may counterbalance the deleterious effects of exaggerated lipemia on oxidative stress, inflammation and vascular function.1Berry et al. Am J Clin Nutr 2008;88:922‐9