bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skeletal muscle HNE is related to insulin resistance in sedentary individuals
Authors: Ingram Katherine Heimburger , Brandon L. Jerome , Ingalls Christopher P. , Rupp Jeffrey C. , Penumetcha Meera , Garvey W. Timothy 
Published: June 2021

The relationships among skeletal muscle lipid peroxidation (HNE), intramyocellular lipid content (IMCL), and insulin sensitivity were studied in sedentary adults. We assessed IMCL, glucose uptake (GDR), homeostasis model assessment index (HOMA), BMI, body fat (DXA), waist girth (WAIST), and skeletal muscle HNE adducts in 9 insulin‐sensitive (IS), 13 insulin‐resistant (IR), and 10 adults with type 2 diabetes (DB).GDR and HOMA differed among IS, IR, and DB (GDR: 16.6 ±2.6, 9.3 ± 1.6, 6.6 ± 2.1, p < 0.01; HOMA: 2.0 ± 0.7, 5.2 ± 3.7, 7.0 ± 5.1, p < 0.05. HNE was higher in DB than IS (971 ± 436 vs. 609 ± 170; p < 0.05) and correlated with GDR (R = −0.43, p < 0.05), HOMA (R = 0.43, p < 0.05), and BMI (R = 0.42, p < 0.05), but not with IMCL, WAIST, or DXA. IMCL was higher in DB than in IS and IR (8.1 ± 3.8 vs. 2.0 ± 1.0 and 3.8 ± 2.8, p < 0.01) and correlated with GDR (R = −0.56, p < 0.01). IMCL was the primary predictor of GDR (R2 = 0.31, p < 0.01), while HNE was that of HOMA (R2 = 0.18, p < 0.05).Our data show that (1) skeletal muscle HNE and IMCL are both determinants of the severity of insulin resistance assessed by hyperinsulinemic clamp or HOMA in sedentary adults; (2) HNE and IMCL are not related and thus impact GDR independently. These results reveal, for the first time, a negative relationship between skeletal muscle HNE and insulin sensitivity in sedentary individuals and underscore the importance of lipid peroxidation in insulin resistance.Funded by NIH (DK‐038764, HL‐055782), Department of Veterans Affairs (Merit Review), and Gatorade Sport Science Institute's Student Grant Program.
Restoration of blood flow to hypoperfused contracting muscle is related to changes in vascular resistance
Authors: Casey Darren P. , Joyner Michael J. 
Published: June 2021

We examined the relationship between flow restoration and vascular resistance in the exercising forearm during hypoperfusion caused by balloon inflation in the brachial artery. 75 trials (with and without nitric oxide synthase (NOS) inhibition) were analyzed. Each included forearm exercise (10% or 20% of max), exercise with inflation, and exercise after deflation (3 min each). FBF (ultrasound), local (brachial artery; BAP), and systemic arterial pressure (SAP) were measured. FBF restoration during balloon inflation was calculated as (steady state inflation plus exercise value – nadir)/[steady state exercise (control) value‐nadir] and expressed as % recovery of FBF. Balloon resistance [(SAP‐BAP)/flow] and vascular resistance (BAP/flow) were expressed as the % change from onset of inflation to end inflation. The % recovery of FBF was strongly related to the drop in vascular resistance for all trials (r = 0.664, P <0.001). This relationship was unaffected by NOS inhibition (n= 27; r = 0.623, P < 0.001 vs. control n = 48; r = 0.685, P < 0.001). The relationship was also stronger with increasing exercise intensity (r = 0.57 vs. 0.704). The % recovery of FBF was unrelated to changes in balloon resistance under any condition. Thus, flow restoration is determined primarily by the fall in local vascular resistance during forearm exercise with hypoperfusion.Supported by NIH HL‐46493 (MJJ), AR‐55819 (DPC) and RR‐024150.
Domestic violence against women is associated with lower household food security in rural Bangladesh
Authors: Coates Jennifer , Rogers Beatrice Lorge , Brewer Nicole , Schoonmaker Lindsay 
Published: June 2021

PurposeThis research was intended to examine whether there is a relationship between household food security and domestic violence among households in rural Bangladesh.MethodsThe study uses data collected from the USAID/FANTA funded 2001–2003 Bangladesh Food Insecurity Measurement and Validation Study conducted by Tufts University. The study measured both physical and psychological abuse of women by their husbands using scales developed from the data. Household food security was measured using the Household Food Insecurity Access Scale developed for Bangladesh. Logistic regression was performed, controlling for religion, food security status, age, decision‐making input of the female, women's status relative to their husbands, participation in microcredit or labor force, and number of sons in the household.ResultsThe large majority of female respondents experienced psychological abuse and about half of women reported physical abuse from their husbands in the past year. Older husbands were less likely to be abusive, and the number of sons was inversely related to the likelihood of abuse. Women's decision making power was positively associated with abuse. Both physical and psychological abuse were more likely to occur in households with lower food security status.
Lack of interaction between angiotensin II and angiotensin (1‐7) on lipid metabolism from isolated adipocytes
Authors: Oh Young‐bin , Yu Jiahua , Kim Jong Hun , Park Byung‐Hyun , Kim Suhn Hee 
Published: June 2021

The renin‐angiotensin system is an important link between cardiovascular diseases and obesity. It is well known that angiotensin II (Ang II) is consequently related with obesity and G‐protein coupled receptor Mas, an essential mediator of angiotensin‐(1‐7) [Ang‐(1‐7)], deficient mouse leads to dramatic change inducing metabolic syndrome. However, the role of Ang‐(1‐7) which counteracts Ang II functions is not thoroughly known. The aim of present study is to define the interaction between Ang II and Ang‐(1‐7) on the lipid metabolism using isolated adipocytes from rodent and human visceral adipose tissues. Isoproterenol (10−7, 10−6, 10−5 M) induced an increase in glycerol release in a dose‐dependent manner in the adipocytes isolated from rat epididymal and human visceral adipose tissues. Ang II (10−7, 10−6, 10−5 M) did not cause any change of lipolysis by itself However, the pretreatment with Ang II reduced glycerol release induced by with isoproterenol (10−6 M) in both types of isolated adipocytes. No differences in inhibition of isoproterenol‐induced lipolysis by Ang II was found between large and small size of human adipocytes Ang‐(1‐7) (10−8, 10−7, 10−6 M) did not show any change in lipolysis by itself. In addition, the pretreatment with Ang‐(1‐7) did not modify any effects of Ang II and isoproterenol on lipolysis. Ang II (10−8, 10−7, 10−6 M) induced preadipocyte differentiation in 3T3‐L1 cells, whereas Ang‐(1‐7) did not change growth and differentiation compared with control preadipocytes. These results suggest that Ang‐(1‐7) does not appear to have counterbalance with Ang II in the lipid metabolism of adipocytes isolated from rat and human adipose tissues.Supported by the KOSEF (R13‐2008‐005‐00000‐0).
Gender differences in the cardiac A1 adenosine receptor anti‐adrenergic effect
Authors: McIntosh Victoria J , Chandrasekera P. Charukeshi , Lasley Robert D 
Published: June 2021

There have been few reports on gender differences in cardiac adenosine receptors (AR). The A1AR modulation of the male and female cardiac β‐adrenergic response was studied in isolated perfused hearts (constant perfusion pressure, paced at 420 bpm) from C57BL/6 mice, monitoring left ventricular systolic pressure (LVSP), +dP/dT and –dP/dT (n≥4). To study the effects of estrogen withdrawal, a subset of females was studied 5–7 weeks post‐ovariectomy (OvX). No differences were seen between male (M), female (F) and OvX female (OvXF) hearts in baseline hemodynamic parameters, or in the β‐adrenergic response following isoproterenol (ISO) administration. In M, 2 nM ISO increased LVSP 86±8%, +dP/dT 131± 9% and –dP/dT 147±11%. 2 nM ISO responses were similar in F and OvXF. As shown in Table 1, pretreatment with 200 nM A1AR agonist CCPA produced an enhanced blunting of the 2 nM ISO response in F as compared to M and OvXF. These observations could be explained by differences in cardiac AR gene expression, with intact females showing 25% higher A1AR and 40% lower A2aAR expression than M and OvXF. These results suggest that ovarian hormones modulate AR gene expression, contributing to gender differences in AR function.
Percent change from pre‐ ISO baseline in CCPA‐Treated Hearts

LVSP
+dP/dT
−dP/dT

Male
32± 5*
52±8*
67±11*

Female
6±1
12±2
16±3

OvX Female
43±7†
83±18†
71±15†

p<0.05 Female vs Male
p<0.05 Female vs. OvX Female
Intermittent Hypoxia in Rats Reduces Hydrogen Sulfide Dependent Dilation to Enhance Myogenic Tone in Mesenteric Arteries
Authors: Jackson‐Weaver Olan , Bosc Laura Gonzalez , Walker Benjimen , Kanagy Nancy 
Published: June 2021

Sleep apnea is an independent risk factor for hypertension and rats exposed to intermittent hypoxia (IH) develop hypertension. We have shown that exposing rats for 14 days to IH enhances myogenic tone (MT) in small mesenteric arteries (MA) compared to MA from control (Sham) rats. Endothelial disruption enhanced MT in Sham arteries but had no effect in IH arteries. H2S is an endogenous vasodilator produced by cystathionine‐γ‐lyase (CSE) in the vasculature. We hypothesized that H2S produced by CSE in the endothelium reduces MT in MA from Sham rats and that H2S production in MA is impaired after 14 days of IH. Vessel wall [Ca2+]i and inner diameter were recorded in pressurized, fura‐2 loaded MA from IH and Sham rats. The CSE inhibitor β cyano L‐alanine (BCA) enhanced MT in Sham arteries compared to vehicle (20.2 ± 6.5% vs. 8.6 ± 1.0) and had no effect in IH arteries (24.0 ± 5.2 vs. 23.6 ± 7.9%). The H2S scavenger Bi(III) subsalicylate enhanced MT in Sham arteries similarly to BCA (20.4 ± 3.4%). NaHS (H2S donor) dilated both Sham and IH endothelium disrupted arteries (42.7 ± 5.7 vs. 57.5 ± 14.4%) with MT. These results suggest that H2S produced by CSE reduces MT in small endothelium intact MA and IH abolishes this effect of H2S. Dilation to NaHS is unaffected in IH endothelium disrupted arteries suggesting that enhanced MT is due to lower levels of endogenous H2S in MA.This work was supported by NIH grants HL82799 (NLK) and HL07736 (OJW).
Modelling the negative regulation of muscle protein degradation by attachment complexes using C. elegans
Authors: Etheridge Timothy , Szewczyk Nathaniel J 
Published: June 2021

Focal adhesions are present in both human and C. elegans muscle, with many of the constituent proteins (~115 of at least 150) of these complexes having putative orthology between the two systems. In both worms and humans, components of focal adhesions have been suggested as regulators of (mal)adaptive changes in muscle size in response to a range of pathological/environmental conditions. We aimed to examine the involvement of a known subset of genes comprising the worm muscle focal adhesions (termed dense bodies) in regulating three sub‐cellular compartments: cytosol, mitochondria and myofibres. RNAi experiments were conducted acutely in adult C. elegans against these genes (25 in total) in order to assess the physiologic significance of acute loss of dense body constituents. Acute RNAi treatment of all 25 muscle attachment‐related genes resulted in degradation of reporter protein in muscle cytosol, and mitochondrial and myofibrillar dystrophies in 18 and 19 of the target genes, respectively. It thus appears that maintenance of this set of the dense body complex is crucial in maintaining muscle cell integrity in all sub‐cellular compartments tested. Uncovering the mechanism(s) regulating protein degradation and/or dystrophy may provide novel therapeutic targets for understanding, treating or preventing human diseases where muscle atrophy is characteristic.Support: MRC (G0801271)
Heat stress enhances fiber size increment in regenerating soleus fibers of rats via satellite cell activation
Authors: Oishi Yasuharu , Hayashida Mari , Nakamura Tomohiro , Roy Roland R , Ohira Yoshinobu 
Published: June 2021

To investigate the effects of heat stress on skeletal muscle fiber‐regeneration, the soleus muscles of adult male Wistar rats were injected bilaterally with a single dose of bupivacaine. The rats were assigned to a normal control (Con), heat stress (Heat), bupivacaine‐injected (BPVC), or bupivacaine‐injected plus heat stress (BPVC+Heat) group. Heat stress was induced by immersion of the rats into hot water (42 ± 1°C) for 30 min 48 h after the injection of bupivacaine and every other day during the following 1 or 2 weeks. The fiber cross‐sectional area, myonuclear number, and the protein levels of heat shock protein 72 (Hsp72) and calcineurin (CaN) were lower in the BPVC than in the Con or Heat groups at both time points. In contrast, several of these parameters in the BPVC+Heat group were not different or higher than in the Con or Heat groups after 1‐ and/or 2‐week recovery. The number of total and activated satellite cells, estimated by analyses of Pax7‐, M‐cadherin‐, and MyoD‐positive‐nuclei, was greater in BPVC+Heat than all other groups. These results indicate that heat stress‐related activation of satellite cells and up‐regulation of Hsp72 and CaN played an important role in the regeneration of the soleus fibers after bupivacaine injection.This study was supported, in part, by Grant‐in‐Aid for Scientific Research C (18500511, Yasu Oishi) from the Japan Society for the Promotion of Science.
Characterization of sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA) expression and function in Zuckerfa/fa obese rat skeletal muscle
Authors: Vigna Chris , Holloway Graham , Bonen Arend , Tupling A. Russell 
Published: June 2021

The purpose of this study was to characterize SERCA expression and function in extensor digitorum longus (EDL) and soleus (SOL) muscles from Zuckerfa/fa obese (321±5 g) and lean (233±10 g) control rats (n=6/group). The rate of Ca2+‐uptake in EDL and SOL homogenates was measured spectrofluorometrically using Indo‐1. Maximal Ca2+‐ATPase activity (Vmax) was determined using a 96‐well spectrophotometric assay. When comparing Zucker to control rats, there were no differences (p>0.05) in Vmax in either EDL (592±40 vs. 536±31 μmol/g/min) or SOL (120±12 vs. 120±13). However, Ca2+‐uptake rates were higher (p<0.05) in the SOL from Zuckerfa/fa rats (4.10±0.30 μmol/g/min) when compared to control animals (2.92±0.61 μmol/g/min). In addition, the rate of Ca2+ leak from Ca2+ loaded SR vesicles in the SOL homogenate was lower (p<0.05) in Zuckerfa/fa rats compared to controls. These observations were not mirrored in the EDL. Furthermore, the SERCA1a and SERCA2a contents were not different between genotypes in either tissue. These data suggest that the reduced rate of Ca2+ leak in slow‐twitch skeletal muscle from Zuckerfa/fa rats improves Ca2+‐pumping efficiency and may result in a lower energy cost of Ca2+cycling.Research supported by NSERC Canada
Human brain activation associated with cough and cough suppression
Authors: Mazzone Stuart , Cole Leonie , Ando Ayaka , Farrell Michael 
Published: June 2021

Supramedullary brain regions may contribute to control of cough by facilitating or inhibiting brainstem reflex pathways. Using functional brain imaging, we put this putative model to the test. Blood oxygen level‐dependent (BOLD) contrast images were acquired from 15 healthy subjects after inhaling saline, inhaling capsaicin without cough, inhaling capsaicin with cough, and voluntary cough after inhaling saline. BOLD signals were analysed to identify changes associated with cough, capsaicin stimulation and their interactions. Contrary to the hypothesised effect, the positive interaction of cough and capsaicin stimulation did not implicate brain activation uniquely associated with evoked cough. However, the negative interaction revealed brain activations that may be requisite for the initiation of voluntary cough and suppression of evoked cough (inferior frontal gyrus, SMA, cingulate cortex) as well as ongoing sensations associated with capsaicin in the airways (insula, orbitofrontal cortex)(P<0.05). These data show that voluntary cough and suppression of evoked cough are associated with brain activation in excess of that associated with evoked cough. This outcome suggests that evoked cough is a default motor pattern that does not require active facilitation by higher order centres, but is under higher order inhibitory influences.Funding: NHMRC Australia #454776, #566734
Characterization of novel kidney specific manganese superoxide dismutase knockout mice
Authors: Parajuli Nirmala , Saba Hamida , Mitchell Tanecia , MacMillan‐Crow Lee Ann 
Published: June 2021

Inactivation of manganese superoxide dismutase (MnSOD), the major mitochondrial antioxidant, is a key issue in renal failure following transplantation or ischemia/reperfusion (IR) injury. Homozygous MnSOD knock out (KO) mice die shortly after birth, and heterozygous MnSOD KO mice have decreased MnSOD activity in all tissues/organs. To address the role MnSOD inactivation has on renal injury, we generated bi‐transgenic kidney specific MnSOD KO (50% and 100%) mice by breeding KidneyCre mice1 and floxed MnSOD mice2. Characterization of these KOs revealed that phenotypically the mice are smaller in size compared to littermate controls, but show no survival differences. Immunohistochemistry data showed that the Cre‐recombinase mediated MnSOD deletion occurred specifically in the kidney and was located predominantly in the medullary region. The kidney specific KOs exhibited histologic evidence of mild renal damage, increased tyrosine nitration, and renal cell death. KO mice renal function was not altered; however, more renal damage was observed following IR injury compared to littermate controls. In summary, we have developed a novel kidney specific MnSOD KO mouse model that will help define the molecular pathways that occur downstream of MnSOD inactivation during renal injury.Supported by NIH grant 1RO1DK0789361.
Effects of chronic antioxidant treatment on AT‐1 receptor, NAD(P)H oxidase subunits and main antioxidant enzymes gene expression in the kidneys of 2K‐1C rats
Authors: Nishi Erika Emy , Oliveira‐Sales Elizabeth B , Bergamaschi Cassia T , Oliveira Thais G. C. , Boim Mirian A , Campos Ruy R 
Published: June 2021

Previous studies showed that chronic treatment with an antioxidant: vitamin C (vC) improves hypertension and sympathetic vasomotor hyperactivity in an Ang II‐dependent model of renovascular arterial hypertension. To test the hypothesis that oxidative stress is associated with NAD(P)H oxidase activation by Ang II, gene expressions of AT‐1 receptor (AT1R), NAD(P)H oxidase subunits (p47phox and gp91phox) and main antioxidant enzymes were evaluated in the renal cortex of 2 kidney‐1 clip model (2K1C, 6 weeks after clipping) rats before and after vC (150mg/kg/day). Gene expression of AT1R was elevated (51%) in the clipped kidney (CK) and reduced (47%) in the nonclipped kidney (NK) of 2K1C group. vC reduced AT1R expression only in the CK (31%). Elevated gene expression of p47phox and gp91phox was observed only in the CK of 2K‐1C group (184% and 132%, respectively) and vC produced no changes in these expressions. Gene expression of catalase was reduced in the CK (70%) and NK (83%) of 2K1C rats. vC increased gene expression of glutathione peroxidase (GPx) in the CK (185%) and NK (212%) of 2K1C. The present study suggests that renal oxidative stress may be related to elevated AT1R and NAD(P)H oxidase subunits gene expression in the CK of 2K1C rats and vitC treatment may produce beneficial effects by AT1R downregulation in the CK and increase in GPx gene expression in the kidneys of 2K1C rats.Supported by FAPESP (07/56925‐1)
Metabolic modeling of acetate metabolism in the human brain
Authors: Shestov Alexander A , Deelchand Dinesh , Henry Pierre‐Gilles 
Published: June 2021

Most 13C metabolic modeling studies have been performed using 13C‐glucose as the infused substrate. Acetate, a glial‐specific substrate, is an attractive alternative to glucose to study neuronal‐glial interactions [1,2]. The goals of the present study were to determine kinetic parameters for acetate transport and utilization and to perform dynamic metabolic modeling of glutamate and glutamine 13C turnover curves obtained during [2–13C]acetate infusion in the human brain with a two‐compartment neuronal‐glial model.ResultsFitted values for acetate transport and uptake kinetics were: Vtrmax=0.30&#61617;0.07 μmol/g/min and Vutmax=0.17&#61617;0.03 μmol/g/min [3]. Metabolic fluxes determined from metabolic modeling of the glutamate and glutamine positional 13C time courses were (in μmol/g/min): VTCA(n)=0.68&#61617;0.20, VTCA(g)=0.09&#61617;0.02, VPC=0.00&#61617;0.01, VX=0.83&#61617;0.20 and VNT=0.14&#61617;0.03. These values are in agreement with rates reported in previous studies [2,4].ConclusionDynamic metabolic modeling of glutamate and glutamine 13C turnover curves measured during [2–13C]acetate infusion with a two‐compartment neuronal‐glial model is feasible and allows determination of compartmentalized metabolic rates in human brain.
Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal and prostate cancer cells
Authors: Clarke John , Yu Zhen , Ho Emily 
Published: June 2021

Epidemiological data indicate that a diet high in cruciferous vegetables may lower the overall risk of prostate cancer. The ability of sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, to inhibit histone deacetylases (HDAC) may be one mechanism by which it acts as a chemoprevention agent. Interestingly, the antiproliferative effects of pharmacological HDAC inhibitors are specific to cancer cells. The objective of this study was to compare the effects of SFN on HDAC inhibition and downstream molecular targets in both normal (PrEC) and cancerous (PC3) prostate epithelial cells. We hypothesize that SFN will act similar to pharmacological HDAC inhibitors and selectively target cancer cells. In PC3, SFN decreased HDAC activity, decreased HDACs 3, 6, and 8, increased acetylated histone H3 at the promoter for p21, induced p21 expression and increased tubulin acetylation. These data suggest that SFN targets both Class I and II HDACs in prostate cancer cells. In PrEC, SFN caused only a transient reduction in HDAC activity with no change in any other endpoints tested. SFN also induced selective cell cycle arrest and apoptosis in PC3 but not PrEC. We conclude that SFN exerts differential effects on HDAC activity and downstream targets in normal and cancer cells. Together, these data highlight the potential of SFN, a dietary HDAC inhibitor as an effective chemoprevention agent. Funded by NIHCA122906.Grant Funding Source: NIHCA122906
All climate change is local: using physiology and biophysics to explore a changing world
Authors: Helmuth Brian 
Published: June 2021

Understanding the mechanisms by which organisms respond to their physical environment is a powerful tool for forecasting the impacts of climate change on ecosystems. Despite the pervasive effects of climate change on a global scale, organisms respond physiologically and behaviorally only to the very local characteristics of their immediate environment. Predicting where, when and with what magnitude the likelihood of changes in community structure are likely to occur requires that we understand how large‐scale processes (“environmental signals”) are downscaled to the level of the organism.Biophysical models (models that track heat inputs and outputs) provide a key tool for analyzing how environmental signals drive organism and ecosystem processes. Importantly, such approaches show that predictions cannot always be made through correlations with large‐scale signals, such as those measured by buoy or satellite. While such measurements are a vital tool for measuring environmental parameters over large spatial and long temporal scales, they are not sufficient for predicting organism responses. By understanding how factors such as body temperature interact with stressors such as nutrient load, fishing pressure and sedimentation, we can triage specific locations by modifying these latter stressors through effective management.