bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying Longitudinal Network Geometry Alterations in Rat Skeletal Microvasculature Subject to Ischemia
Authors: Alimorad Gabrielle , Taing Melvin , Frisbee Jefferson C. , Goldman Daniel , Kharche Sanjay R. 
Published: May 2022

Study objectiveIntra‐vital video microscopy (IVVM) data of rat subcutaneous skeletal muscle microvasculature under ischemic conditions at two time points (0 hours, 3 hours) was obtained from our collaborator. The objectives of this study are to elicit network geometries from the IVVM data and quantify the alterations in the network statistics of the geometries due to ischemia.HypothesisWe hypothesize that ischemia causes blood vessel de‐recruitment.MethodsIVVM data from six experiments was obtained, where each experiment provided a video at the start (0 hours) and end (3 hours) of the experiment. Using consecutive still images from the videos, vessel centerlines were manually drawn using Procreate and the NIH software, ImageJ. The included vessels were chosen based on two features: (1) visible red blood cell flow and (2) clearly defined edges. The centerlines were used to guide thresholding by identifying appropriate vessels. This was followed by the generation of binarized representations of the microvascular networks. The network statistics were quantified by measuring vessel segment lengths and diameters, counting the number of bifurcations, and calculating vessel density in ImageJ.ResultsAt 3 hours, the average vessel length changed from 283.91 + 252.14 pixels to 316.75 + 292.37 pixels, the average diameter changed from 16.02 + 7.99 pixels to 15.42 + 7.50 pixels, the average number of bifurcations changed from 32.42 to 18.92 and the average vessel density changed from 0.0085 + 0.0017 to 0.0061 + 0.0024.ConclusionThere is a clear decrease in average diameter, vessel density and the number of bifurcations characterizing the microvascular networks. However, an increase in the average vessel length accompanies these findings. The data indicates that ischemia may cause de‐recruitment of blood vessels.
Pilot Study Using An Online Platform “EPrescribe” in the Training and Assessment of 4th Year Medical Students’ Competency in Prescribing
Authors: Soliman Youssef , Szarek John 
Published: May 2022

PURPOSEThe Association of American Medical Colleges has delineated 13 Entrustable Professional Activities (EPAs) that entering residents should be expected to perform on day 1 of residency without direct supervision. EPA4, Enter and discuss orders and prescriptions, describes an activity that all recent medical graduates (Interns) spend a great deal of time daily on.Additionally, with the ever‐increasing numbers of pharmaceuticals and biologics, there is a need for clinical pharmacology education in the curriculum to help students achieve EPA4. The Department of Medical Education at GCSOM partnered with the BPS to use their online platform in a two‐week clinical pharmacology elective for 4th year medical students. The hypothesis of this study was that completion of the program modules will enhance student learning and satisfaction with respect to prescribing.METHODSWe used the BPS Assessment platform which provides prescribing skills modules for learners, which they access through a cloud‐based, content‐rich online assessment environment, with real‐time feedback. The assessments were reconciled to the US context insuring they were relevant to our students. Mean scores before and after completing the modules were compared using a paired t‐test. Students also completed a satisfaction questionnaire.RESULTSTo date, 6 students have completed the program. The average scores (±SD) after completing the modules increased significantly (Before: 42%±14%; After: 74%±10%; p=0.001). This represented a normalized gain of 54%. Students tended to Agree/Strongly Agree to the 6 items related to the eLearning sessions, interface and assessment in the satisfaction questionnaire.CONCLUSIONSThe results indicate that students’ knowledge and skills in prescribing increased as a result of their study of the modules. Their high ratings of the program suggest that students found it useful. In conclusion, the BPS program facilitates students’ abilities in prescribing therapies or interventions beneficial to patients and will be helpful in meeting the expectations of EPA4 as students enter residency.
Anti‐platelet effect of prednisolone is regulated by ERK‐mediated thromboxane generation
Authors: Kim Sanggu , Chaudhary Preeti K. , Kim Soochong 
Published: May 2022

Endogenous hypercortisolism is associated with increased risk of blood‐related diseases such as high blood pressure and hyperglycemia that result in fatal cardiovascular disorders. Platelet plays a major role in hemostasis and thrombosis. Although it is well known that glucocorticoids exert a significant effect on hemostasis, the effect of endogenous cortisol on platelet function is much less clear.We aimed to characterize the in vitro effect of prednisolone and its molecular basis on regulation of platelet function using murine platelets.We first evaluated the concentration‐dependent effect of prednisolone on 2‐MeSADP‐induced platelet function and found that 2‐MeSADP‐induced secondary wave of aggregation and dense granule secretion were completely inhibited from 500 nM prednisolone. Since 2‐MeSADP‐induced secretion and the resultant secondary wave of aggregation is mediated by thromboxane A2 (TxA2) generation, this result suggested a role of prednisolone on TxA2generation in platelets. Consistently, prednisolone did not affect the 2‐MeSADP‐induced aggregation in aspirin‐treated platelets, where the secondary wave of aggregation and secretion were blocked by eliminating the contribution of TxA2 generation by aspirin. In addition, AYPGKF‐ and thrombin‐induced platelet aggregation and secretion were inhibited in the presence of prednisolone by inhibiting the positive‐feedback effect of TxA2 generation on platelet function. Furthermore, prednisolone completely inhibited 2‐MeSADP‐induced TxA2 generation confirming the role of prednisolone on TxA2 generation. Finally, Western blot analysis revealed that prednisolone inhibited the 2‐MeSADP‐induced ERK phosphorylation.In conclusion, prednisolone affects platelet function by the inhibition of TxA2 generation through the regulation of ERK phosphorylation, thereby shedding light on the clinical characterization and its treatment efficacy in patients with cardiovascular disorders in the future.
Interdisciplinary Research in Physiology: Insights into the Physiological Society's (UK) Report on “The Future of Interdisciplinary Research beyond REF 2021”
Authors: Witchel Harry J. 
Published: May 2022

The role of interdisciplinary research (IDR) to address research questions posed by global social, economic, ecological and political changes is widely recognised (e.g. addressing Covid‐19). Physiology is by nature an interdisciplinary science – understanding how fundamental processes work and interact with other systems in the body in good health to then understand how to respond to ill health. In November 2021 the Physiological Society (UK) published a report that has since been presented to the UK Parliament on the specific challenges faced by bioscience researchers (including but not exclusively physiologists) whose work is interdisciplinary. These problems are experienced by both senior researchers and especially early career researchers. There are prominent issues relating to funding, peer review, bibliometrics, risk in career progression, and team research. Particularly with the UK's discipline‐based Research Excellence Framework (REF), there has been a perception that interdisciplinary researchers have been disadvantaged. The author, who was a member of the committee that oversaw the drafting of the report, will provide a personal view of the drives to present the report to Parliament, and its conclusions. The proposals include more research into the nature of interdisciplinary research, more flexibility in the assessment of research, and the use of narrative to contextualise the potential impacts of such research. The report in its entirety can be found here:https://www.physoc.org/policy/research‐landscape‐and‐funding/interdisciplinary‐research/
Lactic metabolism and swimming. Comparison between freestyle swimming and swimming with fins in french athletes
Authors: Duvallet Alain , Duvallet Emilie , Lhuissier François , Beaudry Michèle 
Published: May 2022

Compare lactatemia after freestyle and swimming with fins competitions among French athletes specialized in these sports. Fifty two athletes participated in the study, 32 athletes in freestyle and 20 with fins, 28 male and 24 female athletes. Lactatemia was measured on samples (n=102) obtained by micro puncture from the earlobe at 5th minute recovery [LA].Comparisons are made based on the race distance. Speed for the same distance is always higher when swimming with fins versus freestyle swimming. We calculated the working power (distance/speed) and the power provided by lactic metabolism ((LA)/time, M/min) to analyze the lactatemia as a function of work.Mean lactatemia increased during both swimming exercices with maximal values after 100m race. The lactatemia after swimming with fins is always highter than after freestyle swimming. Significant differences were found only for the 800‐1500m races (p<0.001).The power provided by lactic metabolism was maximal for short races. For 50,100, 200 and 400m it was higher when swimming with fins. For 1500 m the values were identical. The differences were not significant.The increase of lactatemia indicates the sollicitation of energy source producing lactic acid. According to Margaria and Edward and Di Prampero et al., a lactic process, i.e., the ATP and CP splitting may be sufficient to provide all the energy necessary for 5 to 10 sec physical exercise. And during short exercices of 30 sec, the oxygen stores may play an important rôle in postponing lactate production.The results indicate that lactic metabolim condition is identical in both exercise. This metabolim in more important during short race. With the power of work more important when swimming with fins, the lactic power is always higher, but not‐significant. So the most determinant parameter for lactic metabolim is the work power and not the type of exercice.
Identification of Genes Essential for Sulfamate and Fluorine Incorporation During Nucleocidin Biosynthesis
Authors: Pasternak Ola , Zechel David 
Published: May 2022

Nucleocidin, a secondary metabolite of Streptomyces calvus(1), is a derivative of adenosine that contains 4’‐fluorine and 5’‐O‐sulfamate groups. Both substituents are rarely observed in natural products. A minimal biosynthetic gene cluster has yet to be defined for nucleocidin, and at least 24 genes appear to be involved. To date, only two functions have been assigned, neither of which are directly involved in sulfamate biosynthesis or fluorination (2, 3). In this presentation, we present biosynthetic studies on two newly discovered producers of nucleocidin, Streptomyces virens B‐24331 and Streptomyces aureorectusB‐24301 (4). Both strains are shown to be significantly (up to 30‐fold) better producers of nucleocidin than S. calvus. Gene disruption experiments in S. virens have identified, for the first time, genes differentially impacting sulfmate and 4’‐fluorine biosynthesis. These and additional results will be presented.References:(1) Zhu, X. M., et al., Biosynthesis of the Fluorinated Natural Product Nucleocidin in Streptomyces calvus Is Dependent on the bldA‐Specified Leu‐tRNA(UUA) Molecule. ChemBioChem 2015, 16, 2498–2506.(2) Feng, X., et al. Two 3’‐O‐b‐glucosylated nucleoside fluorometabolites related to nucleocidin in Streptomyces calvus.Chem. Sci. 2019, 10, 9501‐9505.(3) Ngivprom, U., et al. Characterization of NucPNP and NucV involved in theearly steps of nucleocidin biosynthesis in Streptomyces calvus. RSC Adv., 2021, 11, 3510‐3515.(4) Chen, Y., et al., Streptomyces aureorectus DSM 41692 and Streptomyces virens DSM 41465 are producers of the antibiotic nucleocidin and 4’‐fluoroadenosine is identified as a co‐product. Org. Biomol. Chem. 2021, DOI: 10.1039/d1ob01898a.
SRI 22136, A Novel Delta Opioid Receptor (DOR) Antagonist for the Treatment of Alzheimer’s Disease
Authors: Tanguturi Parthasaradhi R. , Ananthan Subramaniam A. , Pathak Vibha , Venukadasula Phanindra K. , Zhang Sixue , Chafiq Omar Moukha , Szafran Corinne E. A. , Streicher John M. 
Published: May 2022

Alzheimer’s disease (AD) is the most common form of dementia, which affects 47 million people worldwide. There are over five million AD patients over the age of 65 in the U.S. which is predicted to increase to 16 million by 2050. There are currently no approved disease‐modifying therapies for AD and attempts to prevent or slow the progression of the formation of beta‐amyloid plaques by targeting both the beta‐secretase 1 (BACE1) and gamma‐secretase enzymes have not yet achieved clinical success.Studies suggest that indirect modulation of the function of these enzymes via G‐protein coupled receptors (GPCRs) may provide a novel strategy to reduce A‐beta peptide production with potentially less side effects. Among GPCRs that influence amyloidogenesis, the delta opioid receptor (DOR), in particular, has been shown to play an important role in the trafficking and function of BACE1 and gamma‐secretase and in the production of A‐beta peptide. DOR activation increases BACE1 and gamma‐secretase activity in vitro and in a mouse model of AD, and antagonism of DOR specifically blocks the amyloidogenic pathway and efficaciously prevents AD progression in mice. These effects were demonstrated using a known DOR antagonist, naltrindole. However, the potential of DOR antagonists as therapeutic agents for AD has yet to be explored.The aim of this project is to create novel DOR antagonists via medicinal chemistry and identify the most promising lead compound based on binding, selectivity, and functional profile in vitro. Further, select a small set of the most promising compounds and evaluate the compound’s ability to mitigate AD‐like pathology in vivo using APP/PS double‐transgenic mice. We report here the identification of several selective DOR antagonists with low nanomolar affinity/potency that have been shown to block BACE1 activity in vitro. Lead compound SRI‐22136, showed systemic stability and blood brain barrier penetration using the in vivo tail flick assay in CD‐1 mice. SRI‐22136 also showed efficacy in Novel Object Recognition (NOR) behavioral studies and in brain histological analysis studies we observed greater reduction in the AD pathological markers at a dose of 1mg/kg twice daily for 90 days continuous treatment in vivo using the APP/PS AD model double‐transgenic mice. Also, in our brain histological analysis the compound exhibited greater efficacy in reduction of the AD pathology markers such as Aβ signal, and secondary inflammation and activated glia detected by GFAP (astrocytes) and CD11b (microglia) in APP/PS AD model double‐transgenic mice. We further report our progress in testing this compound’s effect on biochemical marker evaluation using the cortex and hippocampus regions of the APP/PS AD model double‐transgenic mice.
Lower‐limb venous function in hypoxia and hyperoxia: effect of healthy ageing
Authors: Fan Jui‐Lin , Sayegh Ana L. C. , Kaur Manpreet , Dawes Mathew , Paton Julian F. R. , Fisher James P. 
Published: May 2022

Oxygen is an important modulator of vascular function, but its influence on the veins is incompletely understood. While age‐related impairments on arterial function have been well‐established, the effects of ageing on the venous circulation have not been examined. The purpose of this study was to determine the effects of hypoxia and hyperoxia on lower limb venous function in healthy young and older humans. We tested the hypothesis that the venomotor response to hypoxia and hyperoxia is attenuated with ageing.In fifteen young (29±8 years, mean±SD) and seven older (age: 66±6 years) healthy individuals, we assessed peripheral oxygen saturation (SpO2) and the cross‐sectional area (CSA) of the great saphenous vein (GSV; Doppler ultrasound) during a standard thigh cuff inflation‐deflation protocol (11 min) while breathing room air, hypoxia (fraction in inspired oxygen [FIO2]: 0.10) or hyperoxia (FIO2: 0.50), in a single‐blinded, randomized manner. The pressure‐CSA relationship was modelled using an established quadratic regression equation and GSV compliance derived.Resting SpO2 was decreased by hypoxia (80.9±5.6%) and increased by hyperoxia (98.8±0.7%) compared to room air (96.3±1.1%, p<0.001) in both young and older groups. In the young group, hypoxia selectively decreased GSV CSA (index of capacity) (13.4±5.7 mm2, p<0.001) compared to room air (17.0±7.9 mm2), while GSV compliance was unchanged (p=1.000). In contrast, hyperoxia did not alter GSV CSA (17.1±8.7 mm2, p=0.883) in the young group, but GSV compliance was increased by 2‐3 fold compared to room air and hypoxia (p=0.007). In room air, GSV capacity was almost double in older participants (+19.6m2, p=0.016), but GSV compliance was not different from the younger group (p=0.423). Neither hypoxia nor hyperoxia affected GSV CSA and compliance in the older group (p>0.05 vs. room air).These preliminary data suggest that in young healthy individuals, hypoxia reduces GSV capacity and hyperoxia increases GSV compliance. However, such manipulations in blood oxygenation do not alter venous function in older healthy individuals. Further investigations are required to determine whether local and/or chemoreflex‐mediated sympathetic mechanisms underpin such alterations in venous function.
Comparison of del Nido and Histidine‐tryptophan‐ketoglutarate cardioplegic solutions on cardiac and endothelial function
Authors: Xue Hong‐Mei , Hou Hai‐Tao , Sun Wen‐Tao , Wang Shi‐Fu , Guo Shan , Yang Qin , He* Guo‐Wei 
Published: May 2022

ObjectivesThis study was designed to compare cardiac and endothelial protection of three clinically used cardioplegias del Nido (DNC), Histidine‐tryptophan‐ketoglutarate (HTK), and cold blood (BC) cardioplegia followed by HTK (BC+HTK) in ischemia/reperfusion(I/R)rat model.MethodsSixty male Wistar rats were subjected to either 120‐min global ischemia at 4°C followed by 90‐min reperfusion at 37°C or no I/R (Control) in Langendorff apparatus and were randomly allocated into five groups: Control, I/R, DNC, HTK, and BC+HTK. Hemodynamic parameters were continuously recorded. The endothelium‐dependent relaxation to acetylcholine (ACh) was measured in the left anterior descending artery thereafter in myograph. The protein expression of cardiac Troponin T (cTnT) and creatine Kinase MB (CKMB) were measured by western blotting.ResultsDuring reperfusion, HTK had higher LVSP whereas DNC had lower LVEDP, better LVDP, and best +dp/dtmax and ‐dp/dtmax than other two groups but the differences disappeared at the end of the reperfusion. HTK or BC+HTK preserves the ACh‐induced endothelium‐dependent relaxation better than DNC (Emax=48.2±8.0% in DNC vs. 75.0±8.0% in HTK, p<0.05; vs. 96.9±3.5% in BC+HTK, p<0.001). The protein level of cTnT and CKMB was downregulated in the three groups.ConclusionsDNC shows a better recovery in diastolic function, whereas HTK or BC+HTK exerts better protection in coronary endothelial function. All these three cardioplegias could ameliorate the myocardium injury at the protein level. These findings may suggest that searching for “perfect” cardioplegia is warranted.
SIRT1‐mediated Lysine Crotonylation is Involved in the Regulation of CaMKII Activity in Myocardium
Authors: Wang Xiang‐Chong , Chen Huan‐Xin , Hou Hai‐Tao , Xue Hong‐Mei , Sun Wen‐Tao , Yang Qin , He Guo‐Wei 
Published: May 2022

ObjectivesPost‐translational modifications (PTMs) can modify proteins and regulate their functions. Lysine crotonylation is a novel protein PTM that can be regulated by silent mating type information regulation 2 homolog 1 (SIRT1). Ca2+/calmodulin‐dependent protein kinase II (CaMKII) plays a significant role in mediating cellular responses to external signaling molecules. Little is known regarding the effect of SIRT1 on CaMKII crotonylation and the impact of crotonylation on the activity of this enzyme.MethodsCre‐Loxp technology was used to generate conditional cardiac‐specific SIRT1 knockout mice (SIRT1 KO). Protein crotonylation modification was studied by PTMomics. CaMKII activity was determined by ELISA. Western blot and co‐immunoprecipitation (CO‐IP) were performed to examine the expression and crotonylation of CaMKIIResultsPTMomics showed changes in protein crotonylation profiles in the myocardium of cardiac‐specific SIRT1 knockout mice. Crotonylation of CaMKII was significantly increased at lysine 301 and the enhanced CaMKII crotonylation was further confirmed by CO‐IP (2.37±0.25 in SIRT1 KO vs. 0.96±0.10 in wild‐type and 1.04±0.10 in SIRT1fl/fl mice, p<0.01). Cardiac‐specific knockout of SIRT1 did not affect the protein expression of CaMKII whereas significantly increased CaMKII activity (2.75±0.17 m units/μL in SIRT1 KO vs. 2.10±0.13 m units/μL in wild‐type and 1.98±0.17 m units/μL in SIRT1fl/fl mice, p<0.05). CO‐IP showed no physical interaction between SIRT1 and CaMKII.ConclusionsSIRT1 deficiency increases CaMKII activity in myocardium at least partially through enhancing lysine crotonylation of CaMKII, which advances our understanding of the role played by PTM in the regulation of CaMKII.