bluuebunny/crossref_metadata_2025 huggingface dataset:
CD63-Snorkel tagging for isolation of tissue-specific small extracellular vesicles
Authors: Qin Gangjian , Han Chaoshan
Published: May 2023

Exosomes are important mediators of inter-tissue communications; however, no effective method is available to allow for isolating, thus characterizing, tissue-specific exosomes in vivo. Since CD63 is a reliable marker for exosomes, we have developed a tagging strategy, term “CD63-Snorkel (CD63-SNKL),” in which CD63 at its intracellular C-terminus was fused to a fragment of PDGFRB that contains the transmembrane domain tethered to multiple epitope tags (HA, His, and FLAG) in tandem on the surface. We found that the CD63-SNKL protein has similar subcellular localizations as endogenous CD63 and can be effectively sorted into small EV (sEV), primarily exosomes. Furthermore, sEV secreted from CD63-SNKL–transduced cells can be effectively captured on anti-HA magnetic beads and eluted with HA peptides. Thus, CD63-SNKL may be engineered for isolating and tracking endogenous tissue-specific sEV in vivo.

This work was supported by the American Heart Association (Grant# 19TPA34910227 to G.Q., 830472 to C.H., and 19IPLOI34760713 to J.Y.) and Southern University of Science and Technology (startup fund to G.Q.).

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Pancreatic islet cell reprogramming into insulin producers: a multi-omics approach
Authors: Monteiro Rodrigues Luis , Farrim Maria , Gomes Andreia , Milenkovic Dragan , Echaniz Regina
Published: May 2023

The loss of β-cell mass is a common pathological process of type 1 and type 2 diabetes and α- to β-cell-like transdifferentiation has gained attention as a potential strategy to increase insulin production.This study used powerful integrative multi-omics bioinformatic tools to scrutinize and perform integrated analyses of publicly available diabetes-associated “omics” data to unveil novel molecular targets associated with α- to β-cell-like transdifferentiation. To achieve this goal, a comprehensive search on PubMed for human studies on gene expression alterations associated with diabetes was conducted Ninety-eight entries were retrieved from which 8 studies reporting microarray data, RNAseq and single-cell RNAseq (scRNAseq) were selected for the in-dept bioinformatic analysis. Each dataset was analyzed individually to identify differently expressed genes (DEG) (p < 0.05). DEGs were obtained using GEO2R tool available at Gene Expression Omnibus (GEO) repository or the supplementary data of the respective studies. Pathway enrichment analyses of DEGs were conducted using GeneTrail as a platform to access KEGG and WIKI pathways databases. Potential transcription factors were identified with Enrichr as a platform to TRRUST and TRANSFAC. For non-coding differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), targets were identified using the MIENTURNET27 and LncRRIsearch28 tools, respectively. Comparison of genes among studies reporting microarray data showed 808 common genes (3 studies in total). Pathways enrichment analysis pointed out cell signaling, endocrine system (insulin resistance and insulin secretion) and metabolism as common to at least two studies. A similar analysis was conducted for 5 studies reporting diabetes-related alterations of mRNA levels in RNAseq/scRNAseq analyses, further supporting these data. The extracted transcriptomic data was then used to search for potential transcription factors modulating specific diabetes-related regulons, which revealed the transcription factors RXRA, ELK1, CTCF, and AR in common to two or more studies.Regarding the non-coding RNAs, we identified 101 miRNAs in 5 studies from which 22 were common between 2 or more studies, together with 10 common lncRNAs among 3 or more studies. Bioinformatic analyses are ongoing to pinpoint the targets and pathways of these regulatory molecules in particular targeting α- to β-cell-like transdifferentiation.

This research is funded by Fundação Ciência Tecnologia (FCT) by grant UIDB/04567/2020. R. Menezes is supported by the Science Employment Stimulus program from FCT.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Dietary pattern, body composition, metabolic markers, and skin physiology
Authors: Monteiro Rodrigues Luis , Menezes Regina , Andrade Sergio , Fontes Tatiana , Lopes Sofia , Ferreira-Pego Cintia
Published: May 2023

Dietary patterns have been linked to differences in cardiovascular physiology, metabolic markers, and ahealthy skin condition.. However, published evidence on these issues is still insufficient and often controversial. This study aimed to identify differences in total body composition, biochemical markers, and skin physiology among omnivorous (OM) and vegetarian (VG) individuals. Participants (n=176, both sexes, mean age 31yo) included 115 OM and 61 VG. Body composition was assessed by absorptiometry (DXA Lunar-GE Healthcare®) and metabolic markers measured from capillary blood sampling (LINX DUO, Menarini). Skin physiology, regarded as an indicator of health, was assessed by transepidermal water loss (TEWL, Tewameter® CK electronics), hydration (Moisturemeter® DTec), and biomechanics (Cutometer® CK electronics) in five anatomical sites (forehead, cheek, neck, hand, and leg). No significant differences were observed between groups for any body composition variables although VG participants showed higher levels of Visceral (VAT) and Subcutaneous Adipose Tissue (SAT). The OM group presented significantly higher levels of total cholesterol, LDL cholesterol, and non-HDL cholesterol, and VAT was positively correlated (p<0.05) with all the biomarkers evaluated. Meanwhile, in the VG group (a) higher levels of fat mass were statistically correlated with higher levels of Hemoglobin A1c, LDL-cholesterol, and Non-HDL-cholesterol; (b) VAT was positively correlated with triglycerides/HDL ratio, Non-HDL-cholesterol, and systolic blood pressure; and (c) SAT was negatively correlated with HDL-cholesterol, and positively correlated with LDL-cholesterol and non-HDL-cholesterol. Prospective (10 year) cardiovascular risk calculations were considerably higher in OM participants compared to VG (2.17 vs. 1.06 points). Noteworthy, the VG participants were more active physically than the OM, and reported diets of lower energetic density, protein, saturated fat, and cholesterol, with higher contents of fiber and complex carbohydrates and sugars. VG participants have shown a higher TEWL, hydration, elasticity, and skin carotenoid content. Correlation analysis regarding VAT, SAT, and skin parameters showed a significant positive correlation between TEWL, hydration, and skin elasticity, and a negative correlation with skin retraction (after creep). These results suggest that some composition features, cardiovascular risk, and skin physiology differ between VG and OM individuals and might be related to their dietary patterns.

This research is funded by Fundação Ciência Tecnologia (FCT) by grant UIDB/04567/2020. C.F.-P. and R.M. are supported by the Science Employment Stimulus program from FCT.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The potential role of matrix metalloproteinases on reducing small artery stiffness and improving vasodilation in old spontaneously hypertensive rats
Authors: Augenreich Marc , Jurrissen Thomas , Ramirez-Perez Francisco , Castorena-Gonzalez Jorge , Morales-Quinones Mariana , Foote Christopher , Nourian Zahra , Lateef Olubodun , Sun Luke , Hill Michael , Meininger Gerald , Padilla Jaume , Martinez-Lemus Luis
Published: May 2023

Arterial stiffening is a major risk factor for cardiovascular disease development and progression. Both hypertension and aging are associated with presence of microcirculation endothelial dysfunction, hypercontractility, and vascular stiffening. Reports suggest that while hypertension results in inward remodeling, aging is associated with either no changes in internal diameter or outward remodeling with or without increases in wall thickness. Herein, we hypothesized that small arteries from old spontaneously hypertensive rats (SHR) would be inwardly remodeled and stiffer than old normotensive Wistar Kyoto (WKY) rats due to aggravated endothelial dysfunction, hypercontractility, and an increased presence of vascular smooth muscle stress fibers and collagen to elastin ratios. We further hypothesized that these characteristics would be associated with reduced expression of matrix metalloproteinases (MMPs). These hypotheses were tested in mesenteric arteries isolated from 88-week-old SHR and WKY rats. All reported differences are significant at P<0.05. SHRs had increased mean arterial pressure (P), pulse P, and heart weight normalized to body weight vs WKY rats. No differences in small mesenteric artery responses to phenylephrine or acetylcholine were observed between the rat strains. However, responses to the sodium nitroprusside were greater in SHR than in WKY isolated arteries. SHR arteries also had increased wall thickness and wall to lumen ratios, in addition to reduced cross-sectional compliance at 5-40 mmHg intraluminal P and lesser incremental modulus of elasticity at 80-120 mmHg. No differences in content of the extracellular matrices, collagen or elastin, were observed between arteries from either strain, whereas smooth muscle F-actin stress fibers were more abundant in the SHR arteries and MMP-2 and -9 expression were increased in the SHR arteries. In conclusion, these data suggest the interaction of age and hypertension in SHRs is associated with hypertrophic remodeling and increased responsiveness to nitric oxide likely due to increased MMP activity and reduced arterial stiffness.

NIH HL-088105-02 to LAM-L

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Furosemide rescues hypercalciuria in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis model
Authors: Mutig Kerim , Kriuchkova Natalia , Breiderhoff Tilman , Müller Dominik , Yilmaz Duygu , Demirci Hasan , Drewell Hoora , Günzel Dorothee , Himmerkus Nina , Bleich Markus , Persson Pontus
Published: May 2023

Aim: Impaired calcium homeostasis limits life expectancy and quality in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC). This rare disease is caused by loss-of-function mutations in CLDN16 or CLDN19 genes leading to impaired paracellular reabsorption of divalent cations along the cortical thick ascending limb (cTAL). The ensuing late distal nephron and collecting duct system partially compensate for the defect in cTAL by increased transcellular Ca2+ reabsorption via the luminal transient receptor potential channel V5 (TRPV5), as well as basolateral plasma membrane calcium ATPase (PMCA) and sodium-potassium exchanger (NCX1). The loop diuretic furosemide induces compensatory activation in these distal segments due to blockade of NaCl and divalent cation reabsorption in the preceeding TAL. Although furosemide enhances urinary calcium excretion via inhibition of the aforementioned cTAL in general population, this effect is not expected in FHHNC patients with already severely impaired Ca2+ transport in the cTAL. The present study follows the hypothesis that furosemide may alleviate hypercalciuria in this disease by activation of the distal transcellular Ca2+ transport proteins. Methods: Cldn16-deficient mice (Cldn16-/- ) served as a FHHNC model. Wild-type (WT) and Cldn16-/- mice were treated with furosemide (7 days of 40 mg/kg bw) or vehicle. We assessed renal electrolyte handling (metabolic cages) and key divalent transport proteins. Results: Cldn16-/- mice show increased Ca2+ excretion than WT and compensatory stimulation of Cldn2 in the proximal tubule, as well as of TRPV5, and NCX1 in the distal nephron at baseline. Furosemide reduced hypercalciuria in Cldn16-/- mice and enhanced TRPV5 and PMCA levels in Cldn16-/- but not in WT mice. Conclusions: Furosemide alleviated hypercalciuria in a mouse FHHNC model, likely via stimulation of transcellular luminal and basolateral Ca2+ transport systems in the distal nephron and collecting duct. These results may have a clinical implication in FHHNC patients.

No conflict of interests

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Assessment of Functional Characteristics of Small Arterioles and Capillaries Using an Intact Dura Mater Preparation
Authors: Arnold Amanda , Sprouse-Blum Adam , Nelson Mark , Klug Nicholas
Published: May 2023

The dura mater, a protective layer surrounding the brain and spinal cord, plays a crucial role in maintaining homeostatic function of the central nervous system. The large arteries and veins of the dura mater are relatively sparse and have been extensively studied with respect to their contribution to pain sensation, with unclear and controversial contributions to headache and migraine pathology. Small arterioles and capillaries exhibit nearly ubiquitous coverage of the entire dura, yet their physiological and pathophysiological functions remain largely unexplored. Here, using ex vivo mouse dura, we examined the electrical (membrane potential recordings), Ca2+ signaling properties (GCaMP or Cal-520 AM imaging), and vasomotor behavior (pressurized dura vessels with diameter measurement) of these exquisitely small vessels. Furthermore, we show electrical and Ca2+ responses in smooth muscle and pericytes in response to calcitonin gene-related peptide (CGRP) receptor and transient receptor potential V1 (TRPV1) channel activation, which are two principal targets in headache and migraine pathology. Last, we highlight unique anatomical interactions between nerves and arterioles in the dura mater using immunostaining techniques. In conclusion, we hypothesize that microvessels consisting of arterioles and capillaries are a logical and unexplored region for studying homeostatic and pathological roles of the dura mater.

Funding Provided by the Totman Medical Trust

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Comparing amount of mechanical work and metabolic cost between two kettlebell swing protocols
Authors: Vencel Daniel , Crecelius Anne , Beerse Matthew
Published: May 2023

The kettlebell swing has been touted as having both cardiovascular-driven metabolic and strength benefits which several studies have investigated. However, to the authors’ knowledge, none have researched the work economy of the exercise by capturing both mechanical work and metabolic cost. Here, we implement a commonly studied kettlebell swing protocol consisting of short intervals of 20 reps and 30 seconds of rest and compare it to longer intervals of 60 reps followed by 90 seconds of rest. Work-rest ratio was 1:1 for both protocols based on a consistent cadence (short: 36.75 ± 2.12 vs. long: 37.08 ± 1.66 reps/min) total volume was the same. A group of 6 healthy young adults, familiar with the kettlebell swing, performed both protocols in a counterbalanced order and separated by 20 minutes of rest. To calculate total mechanical work performed (J/kg), we used the Noraxon motion capture system with inertial measurement units (IMUs) and conducted a segmental analysis of the feet, shanks, thigh, pelvis, trunk, upper arms, forearms, hands, and head. Oxygen consumption (VO2) and other metabolic variables were captured using a metabolic cart (Parvo). We hypothesized that longer intervals might challenge form due to muscle fatigue, thereby changing economy despite matched work-rest ratios and total volume. Contrary to our hypothesis, there is no statistical significance in total mechanical work (short: 1043 ± 261 J/kg vs long: 1159 ± 334 J/kg, paired t-test: p = 0.49) between the two protocols. Similarly, total VO2 (short: 121 ± 14 vs long: 126 ± 15 vs long: mL/kg; paired t-test: p = 0.62) was not significantly different and as a result the total work economy, total VO2 divided by total work, was also not significantly different (short: 0.122 ± 0.031 ml/J vs long: 0.118 ± 0.043 ml/J; paired t-test: p = 0.34). The present findings suggest that protocols of the same work-rest ratios for the kettlebell swing elicit similar work, metabolic responses and therefore economy, even with different duration intervals.

University of Dayton University Honors Program, Berry Summer Thesis Institute

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Exercise pressor response in healthy Hispanic Adults
Authors: Dalve Ashlesha , Perez Justo , Liu Randy , Nyarko Ruby , Appiah Crystal , Van Wagoner Tyler , Kaur Jasdeep
Published: May 2023

Hispanic adults (HA) have the highest prevalence of type 2 diabetes and obesity compared to any other ethnic/racial group in the United States. Given that hypertension is a common comorbidity in diabetic patients, this further increases the cardiovascular risk in HA. In fact, recent data indicate an increased mortality attributable to hypertension in HA. Despite accumulating evidence of health disparities in the HA population, studies investigating the mechanism are lacking. Previous studies have demonstrated an exaggerated exercise pressor response in patients with hypertension and type 2 diabetes, two common risk factors highly prevalent in HA. In this study, we investigated whether young, healthy HA exhibit an augmented pressor response during exercise compared to the age-matched non-Hispanic White (NHW) adults. In 5 Hispanic (age 21±1 years; BMI 23±1 kg/m2; MVC= 76±5kg) and 6 NHW adults (age 22±2 years; BMI 24±1 kg/m2; MVC=75±5 kg), blood pressure (finger photoplethysmography) and heart rate (ECG) were measured at rest and during 2 min of static handgrip exercise performed at 30% and 40% of their maximal voluntary contraction (MVC). Muscle metaboreflex was isolated by post-exercise ischemia (PEI; supra-systolic cuff inflation of the exercising arm) for 2 min. A cold pressor test (CPT) was also performed as a generalized sympatho-excitatory stimulus. Resting mean arterial pressure was similar in both the groups (HA=77±2 mmHg vs. NHW=79±7 mmHg, p=0.79). The increase in blood pressure during exercise was not different between HA and NHW (ΔMAP: 40% MVC; HW=44±9 mmHg vs NHW=40±3 mmHg; p=0.74). Similarly, MAP during isolation of muscle metaboreflex did not reach statistical significance when compared between HA and NHW (ΔMAP: 40% MVC PEI, HW=42±7.3 vs NHW=34±1.6 mmHg; p=0.16). During CPT, HA had a significantly higher increase in blood pressure compared to NHW (ΔMAP: HW=30±6 mmHg vs NHW=20±2 mmHg; p=0.09). These preliminary data suggest that while exercise pressor reflex is not augmented in young, healthy HA, the heightened pressor response to a non-exercise stimulus potentially indicates exaggerated sympathetic reactivity in this population.

Supported by Kinesiology and Health Education UT Austin Start-up Account 19-2635-91

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The effects of fish oil supplementation on arterial stiffness and cognitive function in healthy adults: a pilot study
Authors: Pellinger Thomas , Gimblet Colin , Leaver Echo , Werner Timothy
Published: May 2023

Introduction: Elevated aortic and carotid artery stiffness are associated with subclinical brain damage and cognitive impairment. Fish oil (FO) is a popular dietary supplement that lowers blood pressure and aortic stiffness. However, the hypothesis that FO supplementation reduces carotid artery stiffness and improves cognitive function in healthy adults requires further investigation. Our objective was to determine the effects of FO supplementation on arterial stiffness and cognitive function in healthy adults. We hypothesized that 6-weeks of FO supplementation would lower arterial stiffness and improve cognitive function. Methods: 25 healthy adults were enrolled in a randomized, double-blind, placebo-controlled, parallel-arms intervention to investigate the effects of 6-week FO supplementation (4g/day) on vascular and cognitive function. Aortic stiffness was measured using applanation tonometry and quantified as carotid-femoral pulse wave velocity (cfPWV) and beta-stiffness index (bstiff), and carotid artery stiffness was determined using ultrasonography. Cognitive function was assessed using NIH toolbox cognitive battery. A two-way analysis of variance was used to test differences in treatment groups over time. Results: The mean (± SD) baseline age, body mass index, systolic, and diastolic blood pressure was 40.4 ± 20.6 years, 23.7 ± 2.4 kg/m2, 120.9 ± 14.7 mmHg, and 74.9 ± 12.4 mmHg in the fish oil group and 33.3 ± 14.5 years, 25.3 ± 3.9 kg/m2, 120.8 ± 6.4 mmHg, and 71.9 ± 7.8 mmHg in the placebo group, respectively. Compared to the national averages, our participants scored slightly above average (within one standard deviation) on all tests within the NIH cognitive battery. Within-group comparison revealed no differences in central or peripheral blood pressure, aortic or carotid stiffness, and cognitive function after fish oil supplementation (all p>0.05). Conclusion: Our preliminary data suggest that in healthy, cognitively normal adults, 6- weeks of FO supplementation does not impact indices of arterial stiffness or cognitive function. Further investigation with more participants and of longer duration is needed to confirm our findings regarding the effects of fish oil supplementation on carotid artery stiffness and cognitive function.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
TRPM8 channels do not regulate endothelium-dependent and -independent vascular reactivity in mice
Authors: Arishe Olufunke , Pontes Roberto , Kumar Ravi , Falayi Olufunke , Michael Olugbenga , Williams Jada , Adebiyi Adebowale
Published: May 2023

Foremost among the ion channels that control vascular tone is the transient receptor potential (TRP) cation channels. The TRPM subfamily of the TRP channels includes eight members, expressed in various excitable and non-excitable cells and involved in diverse functions, such as sensing membrane potential, cold, taste, redox, osmolarity, and cell survival. Previous analysis of TRPM gene expression showed the highest expression of TRPM8 in intact blood vessels compared with other isoforms (TRPM1-7). Studies have also revealed that activating TRPM8 by menthol and icilin modulates endothelium-dependent and independent vascular reactivity. However, the non-selectivity of pharmacological TRPM8 modulators constitutes a significant limitation in the prior studies aimed at delineating TRPM8-dependent vasoregulation. In this study, we demonstrate that acetylcholine (ACH)- and sodium nitroprusside (SNP)-induced reduction in arterial pressure was unaltered in mice lacking TRPM8. We generated endothelial-specific knockout (KO) of TRPM8 (ecTRPM8-/-) by breeding TRPM8 floxed (TRPM8fl/fl) with Cdh5-Cre (VE-Cadherin-Cre) mice. Unlike global TRPM8 KO, ecTRPM8-/- mice were not resistant to cold temperatures. Phenylephrine-induced contraction of renal and mesenteric arteries isolated from TRPM8fl/fl and ecTRPM8-/- mice were similar. Also, ACH- and SNP-induced relaxation of phenylephrine-precontracted renal and mesenteric arteries from TRPM8fl/fl and ecTRPM8-/- mice were comparable. These findings suggest that TRPM8 channels do not regulate endothelium-dependent and -independent vasorelaxation in mice.

Disclosure of Funding: NHLBI: R01 HL151735-01 and R01HL151735-S

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Possible role of heme iron for mitochondrial homeostasis in the heart of Friedreich's ataxia at early stage
Authors: Kim Yuho , Dhorajia Varun , Cheng Ruiying , Kim Jonghan
Published: May 2023

Friedreich’s ataxia (FRDA) is a rare genetic disorder that progressively develops cardiac hypertrophy and dysfunction (i.e., cardiomyopathy) along with neurodegenerative problems. Although this disease is largely caused by mitochondrial dysfunction, the underlying mechanism is unclear particularly in the heart. Using FRDA mouse model (YG8s(GAA)>800; Jackson Laboratory; #030395), we have sought to characterize the phenotype and mitochondrial markers that may be important for the development of FRDA cardiac complication. Here, we observed cardiac hypertrophy at 2-3 months old, as evidenced by increased levels of both ANP (Atrial natriuretic peptide) and BNP (Brain natriuretic peptide) in the heart of FRDA mice as compared to control mice (FXN carrier), as well as increased ratio of heart weight to body weight ( p>0.05). However, mitochondrial oxidative markers (e.g., OXPHOS, aconitase activity) were shown to be similar between FRDA and control mice, suggesting that mitochondrial function is maintained in the heart of FRDA mice at early stage. Notably, we observed that heme oxygenase-1 (HO-1) protein levels are significantly upregulated in the FRDA heart. Although increased HO-1 activity is known to elevate free iron levels, non-heme iron levels were slightly lower in the FRDA heart. Therefore, it may be possible that mitochondria can sustain their functionality in the heart of FRDA at early stage, at least in part, through altering heme iron metabolism.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Plasma exosome derived MiR221 as a driver of long term hypoxia induced aberrations in pulmonary arterial phenotype in fetal sheep
Authors: Sierra Julio , Gheorghe Ciprian , Leslie Eric , Dasgupta Chiranjib , Brito Alex , Zhang Lubo , Newman John , La Frano Michael , Fiehn Oliver , Wilson Sean
Published: May 2023

Pregnancy at high altitude (> 2500 meters) reduces oxygenation to the fetus (i.e., gestational hypoxia). The low oxygenation causes abnormal fetal lung development, with pulmonary arteries becoming thicker and dysfunctional. Associated with these structural and functional aberrations there is an increased risk of pulmonary hypertension, an intractable disease that increases infant mortality. Our previous work using a gestational high-altitude sheep model shows that the fetus has pulmonary vascular remodeling, heart dysfunction, endoplasmic reticulum stress, metabolomic alterations and inflammatory responses. To better understand the relationships between inflammation, vascular remodeling, and the development of pulmonary arterial hypertension, we used a multi-omic approach examining pulmonary arteries and plasma exosomes in fetal sheep exposed to high altitude (3801 meters) for most of pregnancy (110+ days out of 138-141 days of pregnancy). We sought to understand the role of exosome derived microRNA as drivers of the malformations in fetal pulmonary vascular development using ingenuity pathway analysis of exosomal microRNA in combination with pulmonary arterial metabolites and proteins. Transcriptomic analysis showed that miR221 was upregulated in plasma exosomes. Pathway analysis identified a miR221 - AKT dependent signaling axis as a candidate pathway that downregulates pulmonary arterial expression of smooth muscle myosin heavy chain 11 and multiple collagen isoforms. Although the pathway analysis needs validation, the predictions show that changes in plasma exosomes are likely coordinated to discrete alterations in proteins coupled to smooth muscle phenotype and arterial wall structure. These effects are predicted to be linked to pulmonary arterial aberrations associated with the development of pulmonary hypertension in response to gestational hypoxia.

This work was supported by the National Institutes of Health Grants R03HD098477, a West Coast Metabolomics Center Pilot Project, NIH R01HL155295, R01HL149608, R03HD098477, P01HD083132, R01HL149608, and U24DK097154. Additional support was provided by the USDA to JWN [Intramural Projects 2032-51530-022-00D, 2032-51530-025-00D]. The content is solely the responsibility of the authors and does not represent the official views of the NIH or USDA. The USDA is an equal opportunity employer and provider.

This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Are parental physical activity and social support associated with adolescents’ meeting physical activity recommendations?
Authors: Camargo Edina Maria de , López-Gil José Francisco , Piola Thiago Silva , Mota Jorge , Campos Wagner de
Published: May 2023

OBJETIVE: To verify whether parental physical activity and social support are associated with adolescents meeting physical activity recommendations. METHODS: This is a cross-sectional study which selected 1,390 adolescents (59.6% girls) from Curitiba, Paraná, Brazil. The IPAQ (International Physical Activity Questionnaire), QAFA (Physical Activity Questionnaire for Adolescents), and ASAFA (Social Support for Physical Activity Practice in Adolescents) questionnaires were applied. Binary logistic regression was used to test the relationship among the study variables. RESULTS: For boys, having parents who “always offer assistance” (OR = 1.96; 95%CI: 1.16–3.32) and having parents or legal guardians who meet the PA recommendations (OR = 2.78; 95%CI: 1.76–4.38) were associated with meeting the PA recommendations. Odds were greater after adjusting for socioeconomic status (OR = 3.47; 95%CI: 1.73–6.96) and schooling level (OR = 4.20; 95%CI: 1.96–9.02). For girls, those with parents or legal guardians who “sometimes encourage them” (OR = 0.61; 95%CI: 0.37–0.98) had lower odds of meeting PA recommendations. These odds were higher after adjusting for socioeconomic status (OR = 2.11; 95%CI: 1.36–3.29) and schooling level (OR = 4.30; 95%CI: 2.41–7.69). CONCLUSIONS: Boys and girls were more likely to meet PA recommendations daily by having parents met PA recommendations than by receiving parental social support. These results could help establish future interventions aimed at modifying behaviors related to PA in adolescents.
Clinicopathologic Analysis of COVID‐19 Associated Thrombi in the Setting of Large Vessel Occlusion: A Prospective Case–Control Study
Authors: Sheriff Faheem , Lavezo Jonathan , Floresca Ryan , Chaudhury Mohammad Rauf , Colina Gabriela , Regenhardt Robert , Gupta Vikas , Rodriguez Gustavo , Maud Alberto
Published: May 2023

Background

Acute ischemic stroke secondary to large vessel occlusion is among the most serious complications associated with COVID‐19 infection resulting in worse morbidity and mortality. We sought to study the association between COVID‐19 infection and large vessel occlusion thrombus pathology to better define the etiopathogenesis of this atypical cause of stroke.

Methods

Thrombi were collected during mechanical thrombectomy and stained using hematoxylin and eosin. Blinded analysis of pathology was prospectively performed by a board‐certified neuropathologist. Red blood cell, fibrin, and white blood cell predominance was ascertained. Concomitant peripheral blood counts and clinical and imaging data were collected and analyzed. All samples underwent performance of reverse transcription polymerase chain reaction for SARS‐CoV2.

Results

Between January 2020 and February 2022, a total of 952 acute ischemic stroke admissions were seen at the University Medical Center of El Paso, TX. Of these, 195 patients (20.5%) had large vessel occlusions and underwent mechanical thrombectomy and 53 patients had thrombus collected and analyzed. Seven patients (3.6%) tested positive for SARS‐CoV2. COVID‐19 positive patients were more likely to be younger (mean 57.4 years;
P
=0.07), male (85.7%;
P
=0.03), and have red blood cell predominant thrombi (85.7%;
P
=0.03). There was a statistically significant association between peripheral neutrophil count and white blood cell lysis in the overall cohort (
P
=0.015), who did not differ according to COVID‐19 status.

Conclusion

Thrombi retrieved from patients who were COVID‐19 positive and had stroke demonstrated red blood cell predominance. This finding requires further investigation using appropriate immunohistochemical techniques in a larger cohort of patients.
Rediscovery, range extension, phylogenetic relationships and updated diagnosis of the Ornate Long-tailed Lizard Latastia ornata Monard, 1940 (Squamata: Lacertidae)
Authors: PAUWELS OLIVIER S. G. , DAS SUNANDAN , CAMARA LEWEI BOYO , CHIRIO LAURENT , DOUMBIA JOSEPH , D’ACOZ CÉDRIC D’UDEKEM , DUFOUR SYLVAIN , MARGRAF NICOLAS , SONET GONTRAN
Published: May 2023

The lacertid Latastia ornata was known to date only by its holotype collected in 1938 in Bafatá, central Guinea-Bissau. We report new specimens and localities from Guinea-Conakry, a new country record and major range extension of 700 km SE of the type-locality. We provide an updated diagnosis of the species, including the first genetic and osteological data, and confirm that Latastia ornata is closely related to, but distinct from, L. longicaudata based on external morphology, cranial osteology, DNA data and zoogeography.
A new species of the genus Clypeuspinus Balkenohl, 2021 (Coleoptera: Carabidae: Scaritinae) from India
Authors: NEETHU V.P. , SABU K. THOMAS
Published: May 2023

The description of a new carabid species from Indian mainland belonging to the genus Clypeuspinus Balkenohl, 2021 which was formerly known in Sri Lanka. Revised generic characteristics of Clypeuspinus, and a key to species are provided.
Replacement names for three preoccupied genus-group names of Cetoniinae (Coleoptera: Scarabaeidae)
Authors: ALLSOPP PETER G. , JÁKL STANISLAV , REY ANTONIO
Published: May 2023

The names of three genus-level taxa of Cetoniinae from Southeast Asia are reviewed. Aurelia Thomson, 1880, currently a subgenus of Ixorida Thomson, 1880, is preoccupied by Aurelia Lamarck, 1816, and Emas Allsopp, Jákl & Rey, new replacement name, is proposed. This results in Ixorida (Emas) decorata Antoine, 1986, Ixorida (Emas) gloriosa Jákl, 2014, Ixorida (Emas) kaorui Jákl, 2019, Ixorida (Emas) philippei Sakai & Nagai, 1998, and Ixorida (Emas) thoracica (Wallace, 1867). Legrandia Jákl, 2019, currently a subgenus of Ruteraetia Krikken, 1980, is preoccupied by Legrandia Beddome, 1883, and Legrandetia Allsopp, Jákl & Rey, new replacement name is proposed, resulting in Ruteraetia (Legrandetia) pahangensis Jákl, 2019. Sternoplus Wallace, 1867 is preoccupied by Sternoplus Mulsant & Rey, 1864, and Walsternoplus Allsopp, Jákl & Rey, new replacement name is proposed, resulting in Walsternoplus schaumii (White, 1856), new combination, and Walsternoplus chicheryi (Antoine, 1999), new combination.
“Early Post-operative Mechanical Small Bowel Obstruction Induced by Unidirectional Barbed Suture”
Authors: Gee Kaylan N. , Many Heath R. , Foulke Evan , Smith Lou M.
Published: May 2023

Unidirectional barbed suture is widely used in minimally invasive procedures as a secure alternative to traditional knot tying. In this report, a 44-year-old female with endometriosis and complex gynecological history presented to our emergency department 2 weeks after undergoing minimally invasive gynecological surgery. She had persistent, progressive signs and symptoms typical of intermittent partial small bowel obstruction. On her third admission within 7 days for this pattern, laparoscopic abdominal exploration was performed. She was noted to have small bowel obstruction secondary to ingrowth of the tail of a unidirectional barbed suture kinking the terminal ileum during this procedure. We discuss small bowel obstruction due to unidirectional barbed suture and make recommendations on how to avoid this complication.
Outcome of Endoscopic Repair of Nasal Septal Perforation
Authors: Tumlin Parker , Assi Sahar , Armeni Mark , Ramadan Hassan H. , Reyes Camilo , Makary Chadi A.
Published: May 2023

Introduction:

The anterior ethmoidal artery (AEA) flap has been demonstrated to be a reliable option for endoscopic repair of symptomatic nasal septal perforations. The purpose of this study is to study the outcome of this technique.

Methods:

A retrospective case series of all consecutive patients who underwent repair of nasal septal perforation utilizing the AEA flap among 2 institutions from August 2020 to July of 2022 was conducted. Demographics and comorbidities were collected preoperatively and postoperatively. The main outcome of this study was to identify the risk factors for surgical failure.

Results:

Forty-one patients were included. Mean perforation size was 2.2 cm (range 0.5-4.5 cm). Mean age was 42.5 years (range 14-65 years), 53.6% were female, 39% were active smokers, mean body-mass-index (BMI) was 31.9 (range 19.1-45.5), 20% with history of CRS and 31.7% had diabetes mellitus (DM). Etiologies of the perforation included idiopathic (n = 12), iatrogenic (n = 13), intranasal drug use (n = 7), trauma (n = 6), and secondary to tumor resection (n = 3). Overall success rate for complete closure was 73.2%. Active smoking, history of intranasal drug use, and DM were significantly associated with surgical failure (72.7%vs 26.7%, P = .007; 36.4%vs 10%, P = .047; and 63.6%vs 20%, P = .008 respectively).

Conclusion:

The endoscopic AEA flap is a reliable technique for closure of nasal septal perforation. It may not work when the etiology is intranasal drug use. Close attention to diabetes and smoking status is also needed.
Sugarbeet Seed Germination Prediction Using Hyperspectral Imaging Information Fusion
Authors: Wang Jiaying , Sun Laijun , Xing Wang , Feng Guojun , Yang Jun , Li Jiajia , Li Wangsheng
Published: May 2023

Germination rate is important for seed selection and planting and quality. In this study, hyperspectral image technology integrated with germination tests was applied for feature association analysis and germination performance prediction of sugarbeet seeds. In this study, we proposed a nondestructive prediction method for sugarbeet seed germination. Sugarbeet seed was studied, and hyperspectral imaging (HIS) performed by binarization, morphology, and contour extraction was applied as a nondestructive and accurate technique to achieve single seed image segmentation. Comparative analysis of nine spectral pretreatment methods, SNV + 1D was used to process the average spectrum of sugarbeet seeds. Fourteen characteristic wavelengths were obtained by the Kullback–Leibler (KL) divergence, as the spectral characteristics of sugarbeet seeds. Principal component analysis (PCA) and material properties verified the validity of the extracted characteristic wavelengths. It was extracted of six image features of the hyperspectral image of a single seed obtained based on the gray-level co-occurrence matrix (GLCM). The spectral features, image features, and fusion features were used to establish partial least squares discriminant analysis (PLS-DA), CatBoost, and support vector machine radial-basis function (SVM-RBF) models respectively to predict the germination. The results showed that the prediction effect of fusion features was better than spectral features and image features. By comparing other models, the prediction results of the CatBoost model accuracy were up to 93.52%. The results indicated that, based on HSI and fusion features, the prediction of germinating sugarbeet seeds was more accurate and nondestructive.
Peacekeepers Without Helmets: How Violence Shapes Local Peacebuilding by Civilian Peacekeepers
Authors: Duursma Allard , Smidt Hannah
Published: May 2023

While United Nations (UN) peacekeeping operations are increasingly deployed during ongoing violent conflict, they are also increasingly staffed with civilian personnel tasked with peacebuilding at the local level. How does violent conflict affect civilian peacekeepers’ peacebuilding efforts locally? Shifting the research focus from military to civilian peacekeepers, we argue that the latter have various incentives and the capacity to concentrate their local-level peacebuilding efforts in violence-affected areas. We test our argument using novel, georeferenced data on peacebuilding by “Civil Affairs” personnel of the peacekeeping operation in the Central African Republic. Consistent with our expectation, violence positively correlates with civilian peacekeepers’ peacebuilding interventions both within and across localities. Furthermore, mediation analyses suggest that this correlation is not merely due to greater UN military deployments in violence-affected areas. Instrumental variable regression supports a causal interpretation: violence leads to more efforts by civilian peacekeepers. These findings inform expectations and assessments of peacekeeping effectiveness.
Capture the Fort: Explaining the Timing of Rebel Assaults on Cities During Wartime
Authors: Uzonyi Gary , Reeder Bryce W.
Published: May 2023

Rebels that fight near or capture cities gain more concessions from the government than those that remain in the periphery. Yet, not all groups challenge urban centers. Previous scholarship expects rebel strength to explain this strategic decision. However, weak rebel groups challenge cities, too. Our approach focuses on the conflict process more broadly. We argue that as the network of rebels challenging the government increases, opposition groups become more likely to attack cities as either they become emboldened, given the government’s disadvantage in multi-front wars, or they are propelled to strategic and resource centers in competition with the other groups. Statistical analysis of all African conflicts from 1989-2009 strongly supports this logic, while an exploration of most typical cases highlights each of these mechanisms in practice. This project thus links literature on civil war tactics and conflict contagion.
Cuspal Shape Alterations by Bmp4 Directing Cell Proliferation and Apoptosis
Authors: Kim E.-J. , Kim H.-Y. , Li L. , Tang Q. , Kim K.-H. , Ohshima H. , Jung H.-S.
Published: May 2023

The enamel knot (EK), located at the center of cap stage tooth germs, is a transitory cluster of nondividing epithelial cells. The EK acts as a signaling center that provides positional information for tooth morphogenesis and regulates the growth of tooth cusps. To identify species-specific cuspal patterns, this study analyzed the cellular mechanisms in the EK that were related to bone morphogenetic protein (Bmp), which plays a crucial role in cell proliferation and apoptosis. To understand the cellular mechanisms in the EK, the differences between 2 species showing different cuspal patterning, mouse (pointy bunodont cusp) and gerbil (flat lophodont cusp), were analyzed with quantitative reverse transcriptase polymerase chain reaction and immunofluorescent staining. Based on these, we performed protein-soaked bead implantation on tooth germs of the 2 different EK regions and compared the cellular behavior in the EKs of the 2 species. Many genes related with cell cycle, cell apoptosis, and cell proliferation were involved in BMP signaling in the EK during tooth development. A comparison of the cell proliferation and apoptosis associated with Bmp revealed distinctive patterns of the cellular mechanisms. Our findings indicate that the cellular mechanisms, such as cell proliferation and apoptosis, in the EK are related to Bmp4 and play an important role in tooth morphogenesis.
Police officer Perspectives on a Pre-booking Diversion Program for People who use Drugs in Philadelphia
Authors: Shefner Ruth T. , Johnson Josephine , Shofer Francis S. , Anderson Evan D.
Published: May 2023

Pre-booking diversion enables police officers to divert individuals to supportive services in lieu of prosecution for minor crimes related to substance use. We surveyed 204 Philadelphia Police Department officers authorized to initiate pre-booking diversions. We used bivariate x2 tests and multivariate logistic regression to examine differences in respondent perspectives. 78% agreed that pre-booking diversion provides important services to people who use drugs, 69% wanted to expand the geographic score of programming, and 52% wanted to expand eligibility. Yet 59% questioned whether diversion is “what police should be doing”, and only 27% believed that it will improve public safety. In logistic regression, the perceived value that the police department places on referrals correlated with agreement that PAD improves safety, provides important services for people who use drugs, and fits within officers’ role. Tension between beliefs that the program provides important services but may not improve safety reflects both potential value and inherent challenges of pre-booking diversion models.
Preventing the Development of Dyslexia: A Reply to Mather
Authors: Fischer Jean-Paul
Published: May 2023

Because reading/writing is a fundamental tool for children’s development, the main failure in its learning—developmental dyslexia—gives rise to many attempts to remediate. A recent remedy proposed by Mather (2022), published in Perceptual and Motor Skills [129(3), p. 468], is impressive through its radical nature and the extent of its consequences. It consists of delaying the teaching of writing to the age of 7–8 years, whereas, at present, most children in Western or comparable cultures learn to write even before compulsory school (generally at age six). In this article, I present a set of arguments whose addition and possible interaction lead, if not to reject, at least to restrict Mather’s proposal. My arguments show both the inefficiency of Mather’s proposal through two observational studies, its practical inapplicability in contemporary society, the importance of learning to write at least in the first year of elementary school, and the stinging past failure of a math reform of similar scope (i.e., learning to count). I also question the neurological theory underlying Mather’s proposal, and, finally, I point out that, even if delaying learning to write were limited to students who Mather expects (at age six) to experience future dyslexia, this remedy would be inapplicable and probably ineffective.