bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversing glycocalyx degradation; identification of a pharmacological target to improve endothelial function in type II diabetes
Authors: Foote Christopher A , Castorena‐Gonzalez Jorge A , Padilla Jaume , Sowers James R , Martinez‐Lemus Luis A 
Published: November 2023

In diabetes, diminished production or reduced bioavailabilty of nitric oxide (NO) in the vasculature, referred to as endothelial dysfunction, is consistently observed and significantly increases the risk for the subsequent development of cardiovascular disease. We posit that, early in the pathogenesis of endothelial dysfunction, elevated levels of neuraminidase lead to the degradation of the glycocalyx and significantly impairs endothelial function as reflected by a reduction in the ability of arteries to dilate in response to sheer stress. In support of this hypothesis, we provide evidence that flow‐mediated dilation is reduced ex vivo in mouse mesenteric arteries exposed to neuraminidase, and that neuraminidase treatment reduces glycocalyx volume. Utilizing an animal model of diabetes (4‐week old male mice fed a western diet (WD) for 16 weeks) we demonstrate that serum neuraminidase activity is elevated compared to control fed animals and this is coincident with a reduced ability of femoral arteries from WD fed animals to dilate in response to Acetylcholine. We also report that both femoral and mesenteric arteries from WD fed animals have an increased modulus of elasticity, a measure of wall stiffness that is typically associated with reduced NO bioavailability in vascular beds. We propose that the inhibition of neuraminidase activity with an FDA approved viral neuraminidase inhibitor could potentially reverse endothelial dysfunction in animal models of diabetes as well as in patients with type II diabetes by reversing glycocalyx degradation and restoring the glycocalyx to its fully functional volume.Support or Funding InformationNIH‐HL‐088105 to LAM and NIH‐HL‐107910 to JRS
Neuromuscular regeneration following whole muscle transplantation
Authors: Pollock Natalie , Davis Carol S , Hassett Cheryl A , Staunton Caroline A , Vasilaki Aphrodite , Jackson Malcolm J , Brooks Susan V , McArdle Anne 
Published: November 2023

Age‐related loss of muscle mass and function has been attributed to failed adaptive responses to insults experienced by the neuromuscular system with evidence of smaller, weaker muscles and disrupted neuromuscular junctions (NMJs). It has been suggested that extrinsic factors such as the environment of the host organism is likely to influence these adaptations and also regenerative processes in nerve and muscle. Previous work has used whole muscle transplants between adult and old hosts to examine the role of the environment on neuromuscular regeneration. Subsequent morphological changes in the regenerating muscle have been well documented (eg. Carlson and Faulkner 1989). However, there is limited information relating to the role of the environment on neuronal morphology following degeneration and regeneration after transplantation.In the current work we investigated the regenerative progress of the nerve following whole muscle transplantation.Experiments were performed in old (22–24months) and adult (4–6months) C57Bl6 mice. The distal and proximal tendons of the extensor digitorum longus (EDL) muscle were cut to free the muscle and the nerve transected. Each mouse had both EDLs removed and cross or same age transplanted. The severed motor nerve was implanted into the donor muscle and both tendons sutured onto the tendon stumps of the hosts. Following 60 days recovery, contractile properties of the muscle were measured and the tissue fixed for examination of NMJ structure. Fluorescently labelled antibodies including s100 (Schwann cells) and synaptophysin (pre‐synapse) were used to visualise the neuronal components and acetyl choline receptors (AchRs) were labelled with bungarotoxin.In all samples a large proportion of the AchRs were localised in small dispersed loci running parallel along the skeletal muscle fibres which clearly overlapped with s100 positive cells. This pattern was especially evident in muscles from old mice transplanted into old mice. Intact AchR clusters displaying the normal “pretzel” formation were limited but were most apparent in adult to adult specimens. Although there was limited synaptic occupancy it has been suggested that even limited synaptic overlap is sufficient to cause muscle contraction.Neuronal contact is required to begin the process of AchR clustering in the formation of NMJs. The differences seen in AchR clustered versus that seen dispersed along the muscle fibres may be indicative of the effect of environment on the nerve regenerative progress.Support or Funding InformationSupported by the UK Biotechnology and Biological Sciences Research Council (BBSRC) and National Institutes of Health (NIH).
Studies on the Interaction of Human Phospholipid Scramblase 1 with C‐Terminal Domain of Topoisomerase IIα
Authors: Sivagnanam Ulaganathan , Gummadi Sathyanarayana Naidu 
Published: November 2023

Human phospholipid scramblase 1 (hPLSCR1) is a multifunctional protein that plays key roles in several cellular processes including apoptosis, tumorigenesis, anti‐viral defense, cell signalling and several protein‐protein interactions. It has been shown that hPLSCR1 interacts with the C‐terminal domain of topoisomerase IIα (topo IIα) and enhances its decatenation activity in vitro. The interacting region in topo IIα was identified but till date, no reports exist on the binding region in hPLSCR1. This study aims to identify the region of hPLSCR1 that interacts with topo IIα. To identify the topo IIα interacting sites in hPLSCR1, N‐terminal deletion constructs of hPLSCR1 viz Δ25‐hPLSCR1, Δ50‐hPLSCR1, Δ75‐hPLSCR1, Δ100‐hPLSCR1 and Δ160‐hPLSCR1 were generated by PCR, cloned, overexpressed and purified to homogeneity using Ni2+‐NTA purification. The C‐terminal domain (CTD) of topo IIα was cloned in pGEX6P‐1 and was expressed as a GST fusion protein. GST pull down assays will be performed with the deletion constructs of hPLSCR1 and the GST‐CTD‐topo IIα. The binding region in hPLSCR1 will be confirmed by peptide competition assays. Our initial results show that the decatenation activity of topo IIα was enhanced when topo II was pretreated with hPLSCR1. Δ100‐hPLSCR1 did not show any enhancement of the decatenation activity compared to full length hPLSCR1. Hence, the binding region could be in the 1–100 region of hPLSCR1. Further deletions were done in the 1–100 region of hPLSCR1 as described earlier. GST‐pull down assays and decatenation assays will be performed for the deletion constructs to narrow down the region of hPLSCR1 that binds to topo IIα. We conclude that hPLSCR1 interacts with and enhances the activity of topo IIα and the 1–100 region of hPLSCR1 is critical for enhancement of decatenation activity. Further work is under progress to identify the exact topo IIα binding region of hPLSCR1 and the physiological relevance of this interaction in the cell.Support or Funding InformationThis work was funded by Council of Scientific and Industrial Research (CSIR), Government of India. Authors thank Ministry of Human Resources and Development Govt. of India and Indian Institute of Technology Madras for fellowship.
Color Vision and Signal Color Evolution in Anolis lizards
Authors: Maximov Katherine Joy , Wadman Catherine 
Published: November 2023

Animals rely on different signaling patterns to communicate both within and between different species. Anolis is a diverse genus of small arboreal lizards that utilize a colorful expandable throat‐fan (or dewlap) for visual communication, in order to attract females and repel males. The environment the lizard lives in has influenced the coloring of these dewlaps in different species. Species that occupy shaded habitats tend to have yellow dewlaps while those that inhabit brighter, less shaded, habitats, tend to have red or orange dewlaps. Natural backgrounds are formed by green vegetation. Modelling these dewlap colors in a perceptual color space predicts that red is more visible against a green background than yellow, yet studies have shown that the majority of anoles have yellow dewlaps. However, quantal fluctuations under low lighting may result in a higher degree of receptor noise for some colors which can affect the discrimination of one color from another by changing the distance between them in perceptual color space. Modelling that takes receptor noise into account predicts that yellow colors, which reflect more photons, will be more visible than red in low light conditions, while red should be more visible in bright light where receptor noise is less.In this experiment, we used a color perception assay to test whether a red or yellow stimulus was more visible to the lizard under different light intensities against a green background, mimicking a dewlap appearing in a forested or open habitat. We flashed red, yellow, and green (control) stimuli against a green background. If the lizard detected a change, indicated by a swift head or eye movement towards the stimulus, a positive response was noted. We found that there was a significantly greater response to red stimuli in high light compared to low light. The visibility of yellow, however, did not change significantly with light intensity. In high light there was a greater response to red than to yellow, while in low light there was a greater response to yellow than to red. Our experiment confirmed the results predicted by the perceptual color space model when accounting for receptor noise. Since light intensity has a greater effect on the discriminability of red against green than yellow against green, this may account for the prevalence of yellow dewlaps in shaded habitats.
Influence of Spinal Neurotransmission on Renal Sympathetic Nerve Activity in Renovascular Hypertension
Authors: Campos Ruy R , Milanez Maycon I. O. , Nishi Erika E , Bergamaschi Cássia T 
Published: November 2023

Studies performed in our laboratory showed a higher glutamate and angiotensin II type 1 (AT1) receptors activation in the rostral ventrolateral medulla (RVLM) that may lead to sympathoexcitation in renovascular hypertensive rats. However, the role of the spinal cord neurons on the renal sympathoexcitation remains unclear in this model. Thus, we aimed to assess the influence of spinal glutamatergic (ionotropic receptors) and AT1 receptors on the renal sympathetic nerve activity (RSNA) and blood pressure (BP) in renovascular hypertension. Male Wistar (250–300g) rats were divided into two independent groups: CTL‐control rats (n=11) and 2K1C‐hypertensive rats (n=9). All experiments were approved by the Institutional Ethical Committee. Renovascular hypertension was induced by clipping the renal artery with a silver clip. After six weeks, a polyethylene catheter (PE‐10) was inserted into the subarachnoid space and advanced to the T10–11 vertebrae level in urethane‐anaesthetized rats (1,2 g/Kg, iv). The effects of intrathecal (i.t.) injection of kynurenic acid (KYN) (2 μl, 160 nmol) or losartan (Los) (2 μl, 2nmol) on BP and RSNA were analyzed for 2 consecutive hours. KYN i.t. injection induced a larger and significant fall on RSNA in the 2K1C compared with control group (CTL × 2K1C: −8 ± 3 × −52 ± 9* spikes/s after 120′). Los i.t. injection also evoked a larger and significant fall in RSNA in the 2K1C compared with control group from 80' after Los i.t. administration (CTL × 2K1C – 80 min: −10 ± 2 × −32 ± 6*; 100 min: −15 ± 4 × −37 ± 9*; 120 min: −12 ± 5 × −37 ± 8* spikes/s). KYN decreased BP similarly in CTL and 2K1C groups, however, Los significantly decreased BP in the 2K1C group only. Therefore, our data show that ionotropic spinal cord excitatory aminoacid and AT1 receptors play an important role in the control of RSNA in the 2K1C model that may contribute to the maintenance of hypertension. The origin of those projections remains unclear. *p<0,05.Support or Funding InformationCNPq, FAPESP (13/22522‐9), CAPES.
The Human Milk Oligosaccharide 3–Fucosyllactose Facilitates Preservation of Nitric Oxide‐Induced Vasodilation in Aortic Vessels In vitro
Authors: Varadharaj Saradhadevi , Helal Mustafa , Duska‐McEwen Geralyn O , Boslett Jim , Pereira Suzette L , Buck Rachael H , Ahmed Naseeruddin , Zweier Jay L 
Published: November 2023

BackgroundThe human milk oligosaccharides (HMOs) 2′‐Fucosyllactose (2′‐FL) and 3‐Fucosyllactose (3‐FL) structurally mimic human histo‐blood group antigens. It is estimated that ~1% of HMOs consumed are absorbed systemically. Although HMOs can reduce platelet‐neutrophil complex formation in vitro, direct effects on endothelial vascular reactivity and tone following an inflammatory stimulus are unknown. In vascular disease associated with intestinal ischemia, coronary ischemia, hypertension, diabetes and hyperlipidemia, vasodilation is impaired due to loss of endothelial nitric oxide synthase (eNOS) function with a pivotal switch from production of the vasodilator nitric oxide (NO) to vasoconstrictor superoxide (O2•−). Necrotizing enterocolitis (NEC) is a risk factor in premature infants with congenital heart disease and pulmonary hypertension due to altered vascular reactivity. We hypothesize that HMO facilitates NO‐mediated vascular smooth muscle cell relaxation leading to increased vasodilation. Therefore, we investigated the effect of HMO‐3‐FL on NO‐dependent aortic vessel relaxation.MethodsStudies were performed using rat thoracic aortic rings treated with or without 3‐FL and the vessel rings were grouped as Control, Lipopolysaccharide (LPS), LPS + 3‐FL. The rings were pre‐incubated with 3‐FL (250 μg/500 μl) followed by incubation with LPS for 4 hours in 5 μg/500 μl LPS/media. The rings were then assessed for endothelial‐dependent and independent relaxation by pre‐constricting vessels with phenylephrine (PHE) 1 μM and then progressive addition of acetylcholine (Ach) 0.001 to 100 uM or nitroprusside (SNP), 0.01 – 1000 nM. Vasorelaxation was calculated as a percentage of the PE‐induced maximal response.Results and DiscussionCumulative dosing of Ach or SNP to PHE‐pre‐constricted rings caused typical dose‐dependent relaxation in control aortic rings. However, after LPS treatment, this response was impaired with ~80% decrease. In rings that were pre‐incubated with 3‐FL, significant preservation of relaxation was seen with over 50% higher maximal relaxation compared to vehicle control LPS treatment. When pre‐incubated with 3‐FL (0.5mg/ml) the LPS stimulated aortic rings showed an increase in vasorelaxation (p<0.05) over the full dose range of NO donor (SNP). Thus, 3‐FL enhanced endothelial‐independent relaxation, which is based on the function of the smooth muscle in the vessel wall. These results suggest an approach to prevent or limit NEC by reversing vasoconstriction. Preservation of vasomotor activity and vasodilation by HMOs may provide a novel nutritional approach for the prevention of NEC‐associated vascular dysfunction.
Paleolithic Diet and Exercise Improve Metabolic and Cardiovascular Risk Factors
Authors: Baker Mark , Eason Alex , Miutz Lauren , Gyorkos Amy Morrison 
Published: November 2023

For nearly 6 million years, the ability to store dietary energy for later times has served humans well during food scarce periods. In our current world of over‐consumption; overweight and obesity are linked to more deaths worldwide than underweight, with 1.9 billion adults classified as overweight and of these, 600 million obese (World Health Organization, 2014). This puts those individuals at an increased risk for chronic diseases, such as cardiovascular disease, metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease, Alzheimer dementia, and some cancers. This trend has had devastating effects on the loss of health, reductions in quality of life, and health system resources. One approach to slow the pandemic of obesity and chronic disease is to look to our evolutionary past for clues of the changing behaviors contributing to the emergence of ‘diseases of civilization’. One theory is that agricultural and technological advances have introduced pressures (i.e. diet and activity changes) quicker than our genetic ability to respond, causing a mismatch between our systems and the environment. Over the past 10,000 years, we have had profound changes in feeding and activity behavior which have left an imprint on the human genome.PURPOSEThe purpose of this study was to investigate the health effects of diet and exercise patterns that more closely resemble those of our evolutionary past in individuals characterized as having Metabolic Syndrome (MetS).METHODSSubjects (N=4) were instructed to consume a diet consisting of unprocessed lean meat, fish, eggs, leafy and cruciferous vegetables, root vegetables, fruit, and nuts and devoid of cereal grains, dairy, beans, legumes, refined fats, bakery items, soft drinks, beer, extra salt and sugar. Foods such as nuts, dried fruit, potatoes (<1 medium‐sized per day) and wine (<1 glass per day) were recommended in limited amounts. Carbohydrate restriction was set at <50gCHO with emphasis on fat intake for replacement. Subjects also participated in high intensity interval training (HIIT), which included a 3‐min warm‐up, 10 × 60 s cycling intervals interspersed with 60s of active recovery, and a 3‐min cool‐down for 4 total weeks.RESULTSCompared to baseline, the intervention led to improvements in MetS markers; including mean arterial pressure (124+6.2 vs. 82+4.1), waist adiposity (110+8.9 vs. 92.1+9.0), fasting glucose (114.2+6.9 vs. 83.3+5.4), high density lipoprotein (HDL; 34.8+7.4 vs. 54.2+6.9), and triglycerides (TG; 214.8+35.5 vs. 92.9+24.2). Improvements were also observed in peak oxygen uptake (VO2max; 20.5+3.2 vs. 25.1+2.2) and low grade inflammation (hsCRP; 7.2+0.6 vs. 4.4+1.3).CONCLUSIONThe combined intervention of paleolithic diet with exercise elicits favorable metabolic and cardiovascular profiles in those that characterize with MetS. The type 2 diabetes epidemic and associated risk factors may be improved from an evolutionary approach in diet and exercise as a preventable and reversible treatment.
Nutrition versus Functional Respiratory Capacity: A Cardinal Interplay
Authors: Chakrabarty Kaveri , Gautam Dinesh Kumar , Guha Satyakam , Arora Anubhuti , Das Anup , Aggarwal Deepak , Gulati Divya , Sharma Harshita , Yadav Nitin , Chakraborty Ranabir , Thapliyal Somesh , Rathi Utkarsha , Chaudhary Vikas 
Published: November 2023

Right from the very beginning of life on earth, organisms have always been in search for sources of energy. From the most primitive of organisms to where biodiversity stands today, the demand of energy has always been met by the supply of food. Nutrition plays a crucial role in normal functioning of all the organs of our body. Any form of imbalance in the dietary intake becomes evident in the concerned physiology. This study was undertaken to explore the variations of Functional Respiratory Capacities (FRCs) associated with diet and the underpinned lifestyle habits in a sample of 70 (36 male/34 female) college going students in Delhi within the age group of 19–21.Balanced diet is a pre‐requisite for a healthy lifestyle. But one of the major problems faced by developing countries is malnourishment, wherein the nutrient intake is either insufficient or over‐sufficient. As dyspnea and poor lung volumes are theoretically expected in people with the global phenomenon of obesity, this study aimed at correlating the data of three major functional respiratory parameters, Forced Vital Capacity (FVC), Forced Expiratory Volume in the first second of expiration (FEV) and FEV % {(FEV /FVC) × 100} obtained using a MiniSpir spirometer and the answers in the questionnaire concerning dietary and lifestyle habits filled by the volunteers themselves. An additional insight into the analysis was made by calculating the Body Mass Index (BMI) of the volunteers using a Tanita InnerScanV Body Composition Analyser.The pulmonary function results obtained was typically a spectrum of restrictions and obstructions flanked by normal spirometry. Volunteers who indulged themselves in cigarettes and alcohol showed mild to severe obstructions, and those feeding on excessive calories showed mild to severe restrictions. High calorie intake (prolonged obesity) and cigarette smoking could increase the severity of the results (which were mild given the age group of volunteers) in due course of time, possibly deteriorating their pulmonary health further down the line.Support or Funding InformationResearch Council, University of Delhi
Buccal rhythm generation in metamorphic bullfrogs is dependent on glycine
Authors: Reed Mitchell , Iceman Kimberly , Varier Thorne , Harris Michael , Taylor Barbara 
Published: November 2023

Fish and early developmental amphibians use gill structures to exchange gases in water. In jawless fish, the neural circuit responsible for generating gill ventilation (buccal) rhythm is adjacent to the trigeminal nerve (CN V). In amphibians, a homologous rhythm generating site has been identified just caudal to the vagus nerve (CN X). The amphibian buccal oscillator is reported to be driven by Cl− mediated mechanisms, and subsequent inhibition of either GABA or glycinergic receptors abolishes this rhythm. This study investigates the effects of Cl− mediated antagonism of buccal rhythm generation and the distribution of buccal rhythm generating circuits.We isolated brainstems from bullfrog tadpoles, placed them in a recording chamber, and allowed them to recover for 1 hour perfused with artificial cerebral spinal fluid (aCSF) equilibrated with 98.5% O2 and 1.5% CO2 (pH 7.8). During this time, neural activity from the facial (CN VII) and hypoglossal (CN XII) cranial nerves was recorded. Following recovery, brainstems were either transected at the level of the glossopharyngeal nerve (CN IX), removing the caudal medulla (rostral to the amphibian “buccal oscillator”) or left intact. Activity from the trigeminal (CN V), facial (CN VII), or hypoglossal (CN XII) nerves were recorded. A cocktail containing bicuculline methochloride (5 μM) and strychnine (5 μM) or bicuculline or strychnine alone was subsequently bath applied for 30 minutes.Small amplitude rhythms were observed following transection, similar to buccal rhythms of intact isolated brainstems. These were accompanied by large amplitude rhythms, which we consider putative lung rhythms. Upon application of bicuculline, putative buccal rhythms in transected and intact brainstems remained and lung activity increased. Application of strychnine alone or in the presence of bicuculline abolished the small amplitude rhythm, and still enhanced lung activity. These results suggest that buccal‐like rhythms are glycine dependent, and may be produced by a diffuse medullary network.Support or Funding InformationResearch reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Numbers UL1GM118991, TL4GM118992, or RL5GM118990. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.