bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐fat diet exacerbates bone loss in mice implanted with low‐dose slow‐release lipopolysaccharide pellets
Authors: Cao Jay J , Shen Chwan‐Li 
Published: June 2021

Obesity is associated with chronic up‐regulation of inflammatory cytokines which stimulate osteoclast activity and bone resorption. Osteopenia or low bone mass is observed in a variety of physiological conditions with chronic inflammation including aging and post‐menopause with estrogen deficiency. This study investigated whether obesity induced by a high‐fat diet alters bone loss in an animal model of chronic inflammation with low‐dose, slow‐release of lipopolysaccharide (LPS). Forty‐eight 6‐wk‐old female C57BL/6 mice were randomly assigned to four treatment groups (n=12/group) in a 2×2 factorial design: control (placebo) or LPS treatment and fed either a normal‐fat (NF, 10% energy as fat) or a high‐fat (HF, 45% energy as fat) diet ad libitum for 3 mon. LPS (E‐coli serotype 0127:B8) was incorporated into time‐release pellets designed to provide a consistent dose (1.3μg/day) for 3 months The LPS and placebo (containing just biodegradable carrier binder) pellets were implanted subcutaneously in the dorsal region of the neck. Mice implanted with LPS had similar body weight, fat mass and lean mass to those in the placebo (NF + HF) groups. LPS treatment increased serum concentration of tartrate‐resistant acid phosphatase (TRAP, a bone resorption marker), expression of proinflammatory cytokines (TNF‐α and IL‐6) in abdominal adipose tissue, and bone marrow osteoclast differentiation, while decreasing tibial and vertebral trabecular bone volume, trabecular thickness, connectivity density, and bone mineral density (P < 0.05). Mice fed the HF diet had higher body weight (P < 0.05) mainly due to increased fat mass (P < 0.05) than animals fed the NF diet. Obesity induced by the HF diet increased serum TRAP concentration, bone marrow osteoclast differentiation, and expression of TNF‐α and IL‐6 in adipose tissue (P < 0.05). Compared to the NF groups, mice in the HF groups had decreased bone volume, connectivity density, trabecular number while had increased trabecular separation, and structure model index (P < 0.05). Mice implanted with LPS pellets and fed the high‐fat diet had the lowest bone mineral density compared to all other groups. These results show that obesity exacerbates bone loss in mice with chronic inflammation induced by low‐dose slow‐release LPS administration.Support or Funding Informationthe USDA Agricultural Research Service program “Bone Metabolism in Obesity,” Current Research Information System no. 5450‐51000‐046‐00D
Leucine ameliorates endotoxin‐induced alterations in protein‐protein interactions within mTORC1 complex in neonatal piglets
Authors: Hernandez‐Garcia Adriana D , Suryawan Agus , Nguyen Hanh , Columbus Daniel A , Manjarin Rodrigo , Orellana Renan A , Davis Teresa A 
Published: June 2021

Sepsis decreases protein synthesis in skeletalmuscle in part by limiting the phosphorylation of translation initiationregulatory factors, eukaryotic initiation factor (eIF) 4E‐binding protein (4EBP1)and S6 kinase (S6K1), that are downstream of the mammalian target of rapamycincomplex 1 (mTORC1). Previous work inmature rats suggests that decreased raptor binding activity to eIF3b mayunderline the sepsis‐induced reduction in protein synthesis in skeletal muscle. Raptor‐eIF3b interaction is crucial for thestimulation of protein translation and its alteration during endotoxemia inmature animals appears to block the anabolic response to the branched‐chainamino acid, leucine (Leu). We have shown in healthy neonatal pigs that Leu supplementation increases muscle protein synthesis by enhancing the activation of mTORC1 and its downstream targets, 4EBP1 and S6K1. To determine if supplemental Leu can stimulate raptor‐eIF3b binding and muscle protein synthesis in theneonate during endotoxemia, overnight fasted neonatal pigs (n=6–8/group) were infused for 8 h with LPS or saline while plasma amino acids, glucose, and insulin were maintained at fasting levels during pancreatic‐substrate clamps. Leu (400 μmol·kg−1·hr−1) or saline was infused during the last h. Phosphorylation of 4EBP1 and S6K1, eIF4E‐eIF4G complex formation, raptor‐eIF3b binding, protein synthesis rates, ribosomal translational capacity (Cs) and translational efficiency (KRNA) were determined in longissimus dorsi (LD), gastrocnemius (Gast) and soleus muscles. LPS decreased protein synthesis and KRNA in LD, Gast, and soleus muscles (P<0.05) while Cs did not change compared to controls. Leu infusion in the LPS group increased 4EBP1 and S6K1 phosphorylation, eIF4E‐eIF4G complex formation, KRNA, and the binding of raptor to eIF3b (by 2 to 3 fold) and protein synthesis (by over 80%) in LD, Gast, and soleus muscles compared to LPS infusion alone (P<0.05). Compared to saline, Leu infusion increased protein synthesis, KRNA, raptor‐eIF3b interaction, 4EBP1 and S6K1 phosphorylation and eIF4E·eIF4G complex formation in all muscles (P<0.05). Raptor‐eIF3b binding showed a linear correlation with 4EBP1 and S6K1 phosphorylation, eIF4E‐eIF4G formation, and protein synthesis in LD, Gast, and soleus muscles that was independent of treatment(P<0.01). These findings suggest that parenteral Leu supplementation attenuates the reduction in muscle protein synthesis induced by endotoxemia by stimulating the interaction of raptor with eIF3 within the mTORC1 complex in the neonate.Support or Funding InformationSupported by NIH AR444474, USDA/ARS 6250‐51000‐055, NIH HD072891, and USDA NIFA 2013‐67015‐20438
Intracerebroventricular Oxytocin Effects on mRNA Abundance Differ in Adipose Tissue of Chicks from Low and High Body Weight‐Selected Lines
Authors: Koskinen Anna , McConn Betty , Wang Guoqing , Siegel Paul B , Cline Mark A , Gilbert Elizabeth R 
Published: June 2021

Neuropeptide oxytocin (OXT), an important anorexigenic factor in the central nervous system, has been shown to have effects on adipose tissue lipid metabolism in mammals. The purpose of this study was to determine the effect of intracerebroventricular (ICV) administration of OXT on subcutaneous adipose tissue mRNA abundance in chicks from lines selected for low (LWS) or high (HWS) juvenile body weight. These lines differ in adiposity. At 5 days post‐hatch, LWS and HWS chicks were fasted for 3 hours, injected ICV with 0 (vehicle), 0.039, 0.312, or 2.5 nmol OXT (n=10 per group).Their food intake was monitored, and subcutaneous adipose tissue was collected at 3 hours post‐injection. Total RNA was isolated, reverse transcribed and real time PCR performed to measure mRNA abundance of the following adipose metabolism‐associated factors: acyl‐CoA dehydrogenase, long chain, 1‐acylglycerol‐3‐phosphate O‐acyltransferase 9, CCAAT/enhancer‐binding protein alpha, CCAAT/enhancer‐binding protein beta, fatty acid binding protein 4 (FABP4), lipoprotein lipase (LPL), monoglyceride lipase (MGLL), OXT, peroxisome proliferator‐activated receptor gamma, and sterol regulatory element‐binding transcription factor 1. The relative quantity values were analyzed by ANOVA in JMP Pro 11 (SAS Inst.). The model included the main effects of genetic line, OXT treatment, and the interaction between them. Significant interactions prompted ANOVAs within each line, and means were separated by Tukey's test. Abundance of FABP4 (P = 0.02), MGLL (P = 0.0002), and OXT (P = 0.001) mRNA was greater in LWS than HWS chicks. There were no main effects of OXT treatment, however there were two‐way interactions of genetic line and OXT treatment on LPL (P = 0.003), MGLL (P = 0.02), and OXT (P = 0.02) mRNA. ANOVAs conducted within each line revealed an effect of treatment on LPL (P = 0.004), MGLL (P = 0.02), and OXT (P = 0.04) in LWS, but not HWS (P > 0.05 for all three genes). In LWS, LPL mRNA was greater in the fat of chicks treated with 0.312 nmol OXT than in those treated with 0.039 or 2.5 nmol (P < 0.05), whereas expression of MGLL was greater in chicks treated with 0.312 nmol OXT than in those injected with vehicle or 2.5 nmol OXT (P < 0.05). Oxytocin mRNA was greater in the fat of LWS injected with 0.312 nmol OXT than in those injected with 2.5 nmol OXT (P < 0.05). Results show that central administration of oxytocin to young chicks may have effects on adipose tissue physiology and that they are genetic line‐dependent.Support or Funding InformationFunding for this work was provided in part, by the Virginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture, U.S. Department of Agriculture
Redox Regulation of the M1/M2 Shift in Microglia: Programming the Deleterious Phenotype
Authors: Block Michelle L. 
Published: June 2021

Microglia, the resident innate immune cells in the brain, are implicated in the progressive nature of diverse neurodegenerative diseases associated with aging, including Parkinson's disease. Our recent findings point to the loss of NF‐κB p50 function due to reactive oxygen species as a key mechanism driving microglial failure to resolve the M1 (pro‐inflammatory) response and impaired M2 (alternative) activation, where loss of NF‐κB p50 function leads to a CNS‐specific vulnerability to chronic inflammation. Moreover, our current work indicates that aging synergistically augments the brain M1 activation response in NF‐κB p50−/− mice, implicating a role for loss of NF‐κB p50 function in age‐associated microglial priming (heightened sensitivity to pro‐inflammatory stimuli) and dopaminergic neurotoxicity. Together, these findings implicate NF‐κB p50 as pivotal redox signaling mechanism regulating the M1/M2 activation balance in microglia, where loss of function tips this balance to favor a M1 polarized and neurotoxic phenotype. These findings support that loss of NF‐κB p50 function and aging may interact to excessively augment microglial priming and point to a novel pro‐inflammatory signaling mechanism independent the NF‐κB p50/p65 transcription factor in this process.Support or Funding InformationNIEHS/NIH ONES Award R01ES016951; DOD GW120068
Response of Skeletal Muscle Arterioles In Vivo to Modulation of Endothelial Glycocalyx (EG) by Resuscitation Fluids after Hemorrhagic Shock (HS)
Authors: Torres Luciana , Salgado Christi , Sondeen Jill , Dubick Michael , Filho Ivo Torres 
Published: June 2021

EG shedding may be associated with deleterious endothelial function, leading to edema, inflammation, poor vasomotor control and tissue hypoxia. Previous studies reported that fluid shear stress may stimulate glycocalyxsynthesis and modulate arteriolar diameter. Administration of resuscitation fluids in severely hemorrhaged patients may result in hemodilution, edema and impairment of microvascular perfusion. Therefore this study aims to elucidate the effects of such fluids on arteriolar glycocalyx and the overall hemodynamic response after HS followed by hypotensive resuscitation. Anesthetized rats (n=30) subjected to HS for 1h (25mL/kg blood loss) were resuscitated with fresh frozen plasma (FFP), fresh whole blood (FWB), 5% Albumin (ALB), lactated Ringer's (LR) or normal saline (NS). The volume infused was 15 mL/kg (FFP, FWB and ALB) or 45 mL/kg (LRor NS). In addition of systemic parameters, EG thickness, red cell velocity, blood flow, wall shear rate (WSR) and wall shear stress (WSS), as well as permeability were studied on over 30 arterioles using intravital microscopy. Post‐resuscitation arterial pressure was 20% lower than baseline in alltreated‐rats. Also post‐resuscitation hematocrit decreased equally to 24±1 % in all groups, except in FWB group (33±1 %). Arteriolar blood flow was significantly lower on rats treated with LR and NS compared to FFP, FWB and ALB treatments. After resuscitation, arteriolar WSR returned to baseline levels in all groups, however WSS was significantly lower in LR and NS compared to FFP, FWB and ALB. Arteriolar EG thickness was lower in LR and NS, whereas it recovered in FFP, FWB and ALB, compared to baseline (p<0.05). A linear correlation between changes in arteriolar diameter (relative to baseline) and changes in EG thickness (R=0.56, p<0.05) as well as changes in WSS (R=0.60, p<0.05)were observed. To conclude, as previously shown in venules, shedding/recovery of the EG occurs also within arterioles of the rat cremaster network. In addition, fluid resuscitation after HS may improve arteriolar EG recovery, endothelium function and microhemodynamics, possibly due to higher viscosity fluids that modulates shear stress and its effect on the endothelium, without volume overload.Support or Funding InformationSupported by US Army Medical Research & Materiel Command
Maternal High Fat Diet Induces the Expression of an Inhibitory Glycinergic Current in Rat Dorsal Motor Nucleus of the Vagus Neurons Regulating Gastric Functions
Authors: McMenamin Caitlin A , Browning Kirsteen N 
Published: June 2021

The perinatal period is critically important in the development of autonomic neurocircuits and maternal overnutrition during this period has been shown to predispose offspring to obesity and associated comorbidities. Previous studies suggest there is an increased inhibition of gastric projecting dorsal motor nucleus of the vagus nerve (DMV) neurons in rats fed a high fat diet (HFD) during the perinatal period, but the underlying neural mechanisms and the effects on gastric motility have yet to be determined. This aim of this study was to assess the effects of perinatal HFD on (i) inhibitory synaptic inputs to gastric‐projecting DMV neurons and (ii) gastric tone and motility.Whole cell patch clamp recordings were made from gastric projecting DMV neurons in thin brainstem slices from Sprague‐Dawley rats (4–6 weeks of age) fed either a control or HFD (14 or 60%kcal from fat, respectively) from embryonic day 13. Gastric motility and tone was measured via miniature strain gauges attached to the antrum of anesthetized rats.In the present study, perinatal HFD rats were not significantly heavier than age‐matched control rats (6 weeks; 232±17g vs 209±5g). The glycine receptor antagonist, strychnine (1μM), induced a larger inward current in perinatal HFD vs control DMV neurons (23±2pA vs 3±1pA, n=8, P<0.05), suggesting that glycine is a tonically released neurotransmitter in perinatal HFD, but not control, rats. Strychnine also increased the rise time (5.0±0.3ms vs 3.5±0.2ms), decay time (9.5±0.8ms vs 5.3±0.6ms), and half width (8.8±0.9ms vs 5.0±0.5ms) of miniature inhibitory postsynaptic currents (mIPSCs) in perinatal HFD (n=5, P<0.05 vs baseline for each parameter) but had no effect in control neurons rise time (3.45±0.2ms vs 3.7±0.2ms), decay time (4.5±0.3ms vs 4.9±0.5ms), or half‐width (4.3±0.3ms vs 4.8±0.5ms) of miniature postsynaptic currents (n=5, P>0.05 for each). Microinjection of strychnine (300pmoles/60nl) into the DMV increased gastric tone and motility in the antrum in perinatal HFD rats (82–101mg, 20–25% of baseline, respectively, n=2) but not in control rats (11–21mg, 2–10% of baseline, n=2, P<0.05 vs perinatal HFD for each), suggesting the tonic glycinergic inputs onto DMV neurons decreased vagal efferent outflow and reduced basal gastric motility and tone.The studies suggest that perinatal overnutrition induces the expression of a novel tonic glycinergic input onto gastric projecting DMV neurons, increasing the inhibitory drive to the stomach. Such alterations in brainstem neurocircuit development as a consequence of maternal over‐nutrition may induce gastric dysmotility and dysregulated gastointestinal reflexes, hence influencing offspring to develop obesity.Support or Funding InformationFunded by NIH 078364 and NSF IOS1148978
An update on arsenic in rice, impact on dietary arsenic intakes and U.S. Department of Agriculture efforts at mitigation
Authors: Finley John W 
Published: June 2021

Dietary arsenic from rice came to the attention of the public in 2012 following the release of analyses by Consumer Reports and Dr. Ozshowing levels of concern. Subsequently the U.S. Food and Drug Administration (USFDA) conducted their own analyses as well as a risk analysis for consumption of arsenic‐containing rice and rice foods (unreleased). Potentially high inorganic arsenic (iAs) levels previously have been reported in drinking water and apple juice. To understand the impact that rice consumption has on arsenic intake relative to other sources, an analysis was conducted using NHANES consumption data and USFDA data from analyses of arsenic in rice. These data show that water intake and arsenic levels in water are the primary determinants of iAs intake; however rice can be a significant source, especially among consumers of brown rice in areas where arsenic levels in wate rare low. The U.S. Department of Agriculture is committed to maintaining a safe and nutritious food supply and has put efforts into mitigating these problems. Agricultural Research Service projects include development of varieties of rice that take up less arsenic, agronomic techniques such as water management that reduce arsenic accumulation and methods of analysis that are quicker and cheaper and allow identification of arsenic content of harvested rice before mixing at grain elevators.Support or Funding InformationThis work was conducted by the U.S> Department of Agriculture, Agricultural Research Service
Does Attenuated Skin Blood Flow Lower Sweat Rate and Thereby the Critical Environmental Limit for Heat Balance?
Authors: Jay Ollie , Cramer Matthew N , Gagnon Daniel , Crandall Craig G 
Published: June 2021

Attenuated skin blood flow (SkBF) is often assumed to critically impair core temperature (Tc) regulation. Recent evidence has shown that a profound pharmacologically‐induced attenuation of SkBF leads to a reduction in local sweat rate. Whether attenuated SkBF to a level more commonly observed in aged or diseased populations leads to decrements in sweat rate, and consequently, a reduction in heat loss potential is presently unknown. Therefore, the purpose of the present study was to test the hypothesis that attenuated SkBF would lead to lower sweat rate and heat loss potential, defined as the critical ambient vapour pressure (Pcrit) at which core temperature (Tc) inflected, while maintenance of a high SkBF would preserve sweat rate and heat loss potential. Seven healthy males (28±4 y) completed the protocol, which consisted of non‐encapsulated passive heat exposure (41°C), while ambient vapour pressure increased by 0.17 kPa (~2% RH) from 2.57 to a maximum of 5.95 kPa every 6 min until an upward inflection in Tc occurred. Three separate treatments elicited changes in plasma volume (ΔPV) with the goal of achieving three distinct levels of SkBF: control (CON), diuretic‐induced iso‐osmotic dehydration to lower SkBF (DEH), and continuous saline infusion to maintain SkBF (SAL). Tc, mean skin temperature (Tsk), heart rate (HR), mean laser‐Doppler flux (forearm, thigh; LDFmean), mean local sweat rate (LSRmean), and metabolic rate were measured. In DEH, a −14.2 ± 5.7% ΔPV resulted in a ~20% lower LDFmean (DEH: 139 ± 23, CON: 176 ± 22, SAL: 186 ± 22 PU; P = 0.034). However, LSRmean and whole‐body sweat losses were unaffected by treatment (P > 0.482). Pcrit for Tc was similar between treatments (CON: 5.05 ± 0.30, DEH: 4.93 ± 0.16, SAL: 5.12 ± 0.10 kPa; P = 0.166). Further, no differences were observed in the Tsk‐Ta gradient, metabolic rate, and changes in Tc (P > 0.197). In conclusion, a physiological reduction in SkBF consistent with those reported in the elderly and diseased populations alters neither local and whole‐body sweating nor heat loss potential during non‐encapsulated passive heat stress.Support or Funding InformationFunded by National Institutes of Health GM068865 and Department of Defense W81XWH‐12‐1‐0152 (CGC), and a Natural Sciences and Engineering Research Council Discovery Grant #386143‐2010 (OJ).
Van‐Gogh‐Like 2, Frizzled, and Knypek Control Distinct Aspects of Polarized Cellular Migration During Neural Convergence
Authors: Singh Karndeep , Brown Sharlene , Werner Jonathan , Vital Eudorah , Sanchez Stephanie , McFarland Rebecca , Brewster Rachel 
Published: June 2021

The planar cell polarity (PCP) pathway plays a significant role in facilitating neural convergence (NC) – the narrowing of the neural plate before the formation of the neural tube. Evidence from the literature and our laboratory suggests that NC in zebrafish requires elongation and midline‐directed polarized migration of neural plate cells. Failure of NC or delayed stages of neural tube morphogenesis can result in severe neural tube defects (NTDs) which have been observed in all vertebrates studied. Although perturbation of the PCP pathway is associated with NTDs in model organisms and humans, the underlying neural cell behaviors remain elusive.In order to investigate the cellular effects of the PCP pathway, we used Knypek (Knyfr6), Van gogh‐like 2 (Vangl2vu67), and Frizzled 7a−/7b− (Fzd7ae3−; Fzd7bhu3495), three zebrafish lines carrying null mutations. We confirmed the published result that mutations in the PCP pathway delayed NC. We analyzed the width of the neural plate in 4–5 somite stage embryos to confirm NC by performing in situ hybridization using probes against the hindbrain and neural crest mRNAs Krox20 and Dlx3, respectively. Next, our comparative cellular analysis revealed how cell elongation, membrane dynamics, and trajectory are affected in homozygotes. We show that wild type (WT) neural plate cells elongate and medially restrict membrane protrusions, thus narrowing the neural tube. Our preliminary data show that cells in all mutants failed to elongate initially, specifically Vangl2 and Fzd7a/b mutant cells extend randomized protrusions while Kny mutant cells show temporally restricted protrusive activity. Furthermore, cell behavioral analysis revealed that neural plate cells in PCP mutant embryos are unable to polarize or migrate toward the midline effectively. Live cell behaviors were assessed by confocal fluorescence microscopy of embryos neural convergence extension movements.Evidence from the literature revealed that Kny is a Fzd co‐receptor thought to present Fzd with various Wnt ligands in the PCP pathway. Differences between Kny and Fzd7a/b cellular phenotypes could suggest a ligand‐independent aspect of PCP signaling during NC. While current literature understands that PCP genes regulate cell polarity and migration, the mechanisms of these genes in neural tissue and how they contribute to NTDs is poorly understood. By studying cell behaviors in the neural plate, our laboratory aims to further reveal how the PCP pathway promotes NC and identify additional genes affecting NTDs.Support or Funding InformationU.S. DOD W81XWH‐15‐RTR‐IDA NIH R01‐GM085290 NIH R03‐3HD076615 NSF DBI‐0722569 Meyerhoff Graduate Fellowship U.S. Department of Education GAANN Fellowship NIH/NIGMS MARC U*STAR T3408663 National Research Service Award to UMBC