bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recruitment Order of Diaphragm Motor Units During Different Respiratory Behaviors
Authors: Seven Yasin Baris , Zhan Wen‐Zhi , Sieck Dylan C. , Sieck Gary C. , Mantilla Carlos B. 
Published: June 2021

In skeletal muscles, force gradation depends on the level of motor unit (MU) activation. MU recruitment generally follows a specific order, with MUs comprising type I or type IIa fibers more active than type IIx and/or IIb. Direct evidence of MU recruitment across motor behaviors is limited to samples of relatively few MUs within a pool. The purpose of this study was to determine the extent of diaphragm MU recruitment across different motor behaviors. We hypothesized that in vivo labeling of individual neuromuscular junctions (NMJs) by FM4‐64 reflects the activation of MUs. Adult rats were exposed to eupneic (E), hypoxic/hypercarbic (H) conditions or supramaximal phrenic nerve stimulation (S). Individual diaphragm NMJs were type‐identified by myosin heavy chain expression. Average FM4‐64 labeling for NMJs at type I or IIa fibers vs. type IIx and/or IIb fibers increased progressively from E to H to S. The proportion of labeled NMJs of each type also increased significantly. At type I or IIa fibers, 40%, 59% and 90% of NMJs were labeled during E, H and S, respectively. At type IIx and/or IIb fibers, 21%, 32% and 82% of NMJs were labeled during E, H and S, respectively. Thus, using an in vivo labeling method there is direct evidence of progressive MU recruitment across different ventilatory and non‐ventilatory behaviors in the rat diaphragm.Supported by NIH grants HL37680 and AR51173, and the Mayo Clinic.
Bestrophin‐3‐associated Ca2+‐activated Cl− channel in vascular smooth muscle and endothelial cells
Authors: Matchkov Vladimir V. , Eriksen Tina Fransgaard , Larsen Per , Pedersen Finn Skou , Nilsson Holger , Aalkjaer Christian 
Published: June 2021

We have recently shown (1) that bestrophin‐3, a member of the Best family, is essential for the cGMP‐dependent Ca2+‐activated Cl− current (I(Ca, cGMP)Cl) (2) which has been shown in different types of smooth muscles (3). The I(Ca, cGMP)Cl has similar characteristics as the currents produced by heterologous expression of bestrophins and distributs similarly to Best‐3 expression. Furthermore, downregulation of Best‐3 with siRNA was associated with a significant reduction of the I(Ca, cGMP)Cl.To study the physiological significance of Best‐3 immunohistochemical (IHC) and siRNA approaches were used. Wistar rats were used in accordance with national guidelines for animal research.We characterized the Best‐3 specific antibody by expression of eGFP‐fusion‐protein with the epitope containing peptide. IHC showed a broad expression of Best‐3 (e.g. kidney, heart, brain and mesentery) primarily in the vasculature. Within the vascular wall Best‐3 was shown to be strongly expressed in both smooth muscle and endothelial cells. This was supported by PCR cloning. Specific siRNAs significantly suppressed Best‐3 expression and the I(Ca, cGMP)Cl.Our study demonstrates the functional significance of Best‐3 protein for the cGMP‐dependent Ca2+‐activated Cl− channel in vascular tissue.1. Matchkov et al., Circ Res 20082. Matchkov et al., J Gen Physiol 20043. Matchkov et al., Pflugers Arch 2005
Frequency response characteristics of whole body autoregulation of blood flow in rats
Authors: Stauss Harald Martin , Rarick Kevin R , Deklotz Richard J , Sheriff Don D 
Published: June 2021

Previous studies from our laboratory suggested that myogenic vascular function contributes to VLF BPV. Here we tested the hypothesis that the dynamic properties of whole body autoregulation of blood flow is consistent with the frequency range of VLF BPV (0.02‐0.2 Hz) in rats.In anesthetized rats (n=11) BPV (0.016‐0.5 Hz) was induced by computer‐regulated cardiac pacing while blood pressure and cardiac output (CO) were recorded during control conditions (NaCl, 1mL/h i.v.) and α1‐adrenergic receptor stimulation (phenylephrine, 1mg/mL/h i.v.) that has been reported to facilitate myogenic vascular function.During control conditions, transfer function analyses between mean arterial pressure (MAP) and CO and between MAP and total vascular conductance (CO/MAP) indicated autoregulation of blood flow at 0.016 Hz, passive vascular responses between 0.033 Hz and 0.2 Hz, and baroreflex‐like responses at 0.333 Hz and 0.5 Hz. Stimulation of α1‐adrenergic receptors extended the frequency range of autoregulation of blood flow to frequencies up to 0.033 Hz.Depending on sympathetic vascular tone, whole body autoregulation of blood flow most effectively operates at frequencies below 0.05 Hz. This frequency range is consistent with VLF BPV in rats. Baroreceptor reflex‐like mechanisms contribute to LF (0.2‐0.6 Hz) but not VLF BPV‐induced vascular responses.Supported by the American Heart Association (0630329N)
Nitric Oxide mediating L‐glutamate cardiovascular responses in the paraventricular nucleus in unanesthetized rats
Authors: Busnardo Cristiane , Tavares Rodrigo Fiacadori , Resstel Leonardo , Crestani Carlos Cesar , Correa Fernando Morgan Aguiar 
Published: June 2021

ObjectiveIn a previous study we have reported pressor and tachycardiac responses after L‐glutamate (L‐glu) microinjection in the hypothalamic paraventricular nucleus (PVN) in unanesthetized rats. In a present study we evaluated the possible involvement of local nitric oxide (NO) mediating cardiovascular effects evoked by L‐glu injection in the PVN.MethodsMale Wistar rats were used (250‐270g). Guide cannulas were implanted into the PVN. A catheter was introduced into the right femoral artery for blood pressure and heart rate recording.ResultsMicroinjection of L‐glu in 10nmol/100 nL in the PVN caused pressor and tachycardiac responses in unanesthetized rats. Microinjections of artificial cerebrospinal fluid (ACF) in the PVN did not affect the pressor and tachycardiac responses to L‐glu microinjected in the PVN. The cardiovascular responses to L‐glu in the PVN was blocked by local pretreatment with the selective neuronal NO‐synthase (nNOS) inhibitor Nω‐Propyl‐L‐arginine (N‐Propyl, 0.04 nmol/100nL) or with the NO scavenger carboxi‐PTIO (C‐PTIO, 1nmol/100nL).ConclusionThe present results support the idea of an involvement of PVN glutamatergic neurotransmission in cardiovascular modulation through the NO pathway.Financial SupportFAPESP (06/52446‐9) and FAEPA.
Cell‐protective mechanisms of alpha 1 antitrypsin (A1AT) in the lung endothelium
Authors: Lockett Angelia Denise , Garrison Jana , Kamocki Krzysztof , Schweitzer Kelly , Petrache Irina 
Published: June 2021

Recent studies uncovered non‐cannonical functions of A1AT that lead to cellular protection from apoptosis and inflammation, including suppression of cigarette smoke (CS)‐induced increases in TNFα. We set out to investigate the mechanisms by which A1AT antagonizes TNFα?in vivo and in primary lung endothelial cell cultures. Mice were exposed to CS for up to 6 months and total lung RNA or protein was analyzed by real‐time PCR or Western blot, respectively. Primary rat lung microvascular cells were pretreated with A1AT, followed by studies of signaling and inflammatory responses in response to TNFα. Despite a decrease in the total lung TNFα message level (21 % at 16 weeks), both IκBα and MCP1 levels increased in CS‐exposed mice (1.7 fold + sem=.075; p=.05 and 1.4 fold +sem=.029; p<0.01, respectively). A1AT treatment increased basal IκBα?and delayed the IκBα?degradation induced by TNFα (10 ng/ml) in endothelial cells by 15 min. In conclusion, although TNFα message levels are not increased in smoked animals, the increased IκBα and MCP1 expression suggest that TNFα protein is activated by cigarette smoke. At the endothelial cell level, A1AT may alter TNFα signaling by regulating IκBα degradation. Understanding the anti‐inflammatory mechanisms of A1AT is important for developing therapeutic strategies against CS‐induced emphysema.Funded by: 1P50 HL084945
Elevated levels of von Hippel‐Lindau protein in human and mouse fibrotic lungs
Authors: Zhou Guofei , Pardo Annie , Koenigshoff Melanie , Dada Laura A , Eickelberg Oliver , Varga John , Selman Moises , Sznajder Jacob I 
Published: June 2021

ObjectiveFibronectin (FN) deposition and fibroproliferation contribute to pulmonary fibrosis. von Hippel‐Lindau protein (pVHL) regulates assembly of fibronectin matrix. We sought to determine whether pVHL participates in pulmonary fibrosis.Methods and ResultsWe found that lungs from idiopathic pulmonary fibrosis (IPF) patients expressed higher levels of pVHL mRNA and protein as measured by quantitative real time RT‐PCR (qRT‐PCR) and Western blot analysis. We also discovered that lungs from IPF patients displayed strong staining of pVHL in fibrotic foci upon immunohistochemistry analysis. In the bleomycin‐induced mouse model, fibrotic lungs exhibited increased levels of pVHL mRNA and protein as determined by qRT‐PCR and immunofluorescence staining. Overexpression of exogenous pVHL stimulated proliferation of primary rat and human lung fibroblasts and increased FN expression, assembly and phosphorylation of focal adhesion kinase (FAK).ConclusionsOur results suggest that fibrotic lungs have increased pVHL expression and overexpression of pVHL increases FN/integrin/FAK signaling, resulting in fibroproliferation and fibrosis.This study is supported by NIH HL‐071643, AR‐042309 and Parker B. Francis foundation.
Calcium Handling in Postganglionic Sympathetic Neurons is enhanced in Prehypertensive Spontaneously Hypertensive rat
Authors: LI DAN , LEE CHEE‐WAN , BUCKLER KEITH , PATERSON DAVID J 
Published: June 2021

Noradrenergic hyperactivity is associated with hypertension that may precede the developing of hypertension itself. We hypothesized that Ca2+ signalling in sympathetic neurons is enhanced in young pre‐hypertensive spontaneously hypertensive rats (SHR). We measured depolarisation (high [K+]0) evoked Ca2+ transient ([Ca2+]i) with fluorescence imaging using fura‐2 in superior cervical ganglia from age and gender matched hypertensive and normotensive Wistar‐Kyoto (WKY) rats. In 4‐7 day old rats, no difference was observed in [Ca2+]i between the SHR and WKY. In contrast, among young pre‐hypertensive (4‐5 weeks old) rats, [Ca2+]i were higher in the SHR (male: 1.39±0.11 μM; female: 1.21±0.05 μM) compared with the gender matched WKY (male: 1.08±0.13 μM, p<0.05; female: 1.07±0.05 μM, p<0.05). In adult (16‐18 weeks old) rats the [Ca2+]i were also increased in the SHR (male: 1.82±0.06 μM; female: 1.58±0.07 μM) compared with the gender matched WKY (male: 1.59±0.09 μM, p<0.01; female: 1.12±0.06 µM, p<0.001). Interestingly, in the adult SHR and WKY, [Ca2+]i was significantly higher in male. The overall responses are consistent with the hypothesis that enhanced Ca2+ signalling may contribute to the noradrenergic hyperactivity that is seen before the onset of hypertension itself.This work was supported by British Heart Foundation and Welcome Trust.
Differential intracellular localization of Sry proteins expressed in Rattus norvegicus
Authors: Underwood Adam C , Turner Monte E. , Ely Daniel L. , Milsted Amy 
Published: June 2021

Sry is a transcription factor with a conserved HMG domain that facilitates DNA interactions and nuclear localization, through amino (n) and carboxy (c) terminal nuclear localization sequences (NLS). There are seven Sry loci on the SHR/Akr Y chromosome. Amino acid (aa) differences among Sry proteins are in the nNLS at aa 21 (His vs. Arg), cNLS at aa 76 (Pro vs. Thr), and in the presence/absence of 13 aa in a c‐ terminal activation motif. The objective of this study was to determine if these aa differences between proteins alter nuclear localization. Native, chimeric, mutated and truncated Sry sequences were transfected into CHO cells followed by immunocytochemistry and Western blot analysis of nuclear and cytoplasmic CHO cell fractions. Results showed that Sry2 exhibits both cytoplasmic and nuclear accumulation, while Sry1 and 3 localize only to the nucleus. Sry1 and 3 sequences containing the truncated or deleted activation region exhibit no reduction in nuclear localization, while mutations to the NLS result in cytoplasmic accumulation. Changing His to Arg at aa 21 of Sry1 or Sry3 results in nuclear localization patterns equivalent to native Sry2. Results demonstrate that aa variability in Sry proteins leads to different intracellular localization in vivo and may account for the different phenotypes observed in rats after delivery of exogenous Sry1, Sry2 or Sry3.Support from NIH HL71579 and the University of Akron.
Diet‐induced obesity impairs the T cell memory response to influenza virus infection
Authors: Karlsson Erik A , Beck Melinda A 
Published: June 2021

The global obesity epidemic combined with yearly influenza outbreaks and potential for a pandemic makes it crucial to determine how protection from influenza differs in an obese host. In contrast to a vaccine antibody response which recognizes surface proteins, memory T cells generated during a primary infection target internal viral proteins and are protective against heterologous strains. As our prior work demonstrated that obese mice have an impaired primary response to influenza virus infection, we hypothesized that obese mice would also have an impaired memory response to a secondary influenza infection. To test this hypothesis, obese and lean mice were infected with influenza X‐31. At 31 days post infection, mice were challenged with a lethal dose of a different strain, influenza A/PR/8. While lean mice were protected from lethal infection, obese mice had 25% mortality, increased lung pathology and virus titers, reduced antiviral cytokine expression, and decreased and delayed adaptive immune cytokine expression following secondary challenge. These results indicate that memory response to influenza in obese mice is significantly altered and ineffective and obesity may hinder the generation or function of these protective cells. These results suggest obese populations are at risk for impaired immune memory response, which has significant public health implications for current vaccination protocols.Grant Funding SourceDK56350
Wilms Tumor 1 (WT1) and Foxc2 are required for podocyte development in Xenopus
Authors: White Jeffrey Thomas , Wessely Oliver 
Published: June 2021

Single‐gene knockout studies have shown that Foxc2, Lmx1b, MafB, Tcf21 and WT1 are the necessary transcriptional regulators of podocyte development. It is still unclear, however, whether these five transcription factors (TFs) can explain all aspects of podocyte development. To this end, we have used the Xenopus pronephros as a tool to study podocyte development.To test the roles of these five TFs in podocyte development, each was individually knocked down with antisense morpholino oligomer technology. In situ hybridization for podocyte TFs (Foxc2, Lmx1b, MafB, Tcf21 and WT1) and markers of terminal differentiation (Nephrin, Neph1, Glepp1 and Podocin) was used to analyze the resultant phenotype. These data were compiled to construct a gene regulatory network for podocyte development (PGRN). The PGRN displayed classical characteristics of a gene regulatory network, including master regulators, multi‐gene loops and a high degree of redundancy. Based on the network, we hypothesized that WT1 and Foxc2 are the master regulators of podocyte development. Simultaneous depletion of WT1 and Foxc2 resulted in loss of expression of downstream podocyte TFs (Lmx1b, MafB and Tcf21) and markers of terminal differentiation (Nephrin, Neph1, Glepp1 and Podocin); moreover, these embryos were characterized by a complete loss of the glomus structure. This work was supported by F30DK082121.Grant Funding SourceNIDDK
Milk consumption after resistance exercise increases fat loss and increases muscle mass and strength gains in young women
Authors: Josse Andrea R , Tang Jason E , Wilkinson Sarah B , Tarnopolsky Mark A , Phillips Stuart M 
Published: June 2021

Post‐resistance exercise consumption of fat free milk in men promoted greater lean mass accretion and fat mass loss than soy or carbohydrate. It is unknown if similar body compositional changes and strength gains occur in women. Twenty young women were randomized to drink 500ml of fat‐free milk (MILK: n=10; BMI=26.2±2.0kg/m2; mean±SE) or carbohydrate (CON: n=10; BMI=25.6±1kg/m2) on 2 occasions; immediately post and 1h post‐exercise. Subjects underwent resistance training 5d/wk for 12‐wk. Body compositional changes were measured by DXA, and subjects' strength was measured by 1RM pre‐ and post‐training. Baseline body mass did not differ between groups and only CON gained weight after training (CON: 68.3±4.1kg to 69.1±4.0kg, P=0.05; MILK: 72.0±4.1kg to 72.5±3.8kg, P=0.24). Lean mass increased with training in both groups (P< 0.01), with a greater net change in MILK vs CON (1.9±0.2kg vs 1.1±0.2kg, respectively; P<0.01). Fat mass decreased with training in MILK only (‐1.64±0.4kg, P<0.01) with no change in CON (‐0.27±0.3kg, P=0.47). Bench press and tricep push‐down strength increased more in MILK than CON (P<0.05). Thus, post‐exercise consumption of milk vs isoenergetic carbohydrate resulted in greater muscle mass accretion, fat mass loss and strength gains in women after 12‐wk of resistance training. Our results parallel those shown previously in men.Sponsored by NSERC, CIHR and The Dairy Farmers of CanadaGrant Funding SourceCIHR
Effects of zinc supplementation on growth of children under 5 years of age: A meta‐analysis of randomized controlled trials
Authors: Nguyen Phuong , Ramakrishnan Usha , Martorell Reynaldo 
Published: June 2021

BackgroundZinc interventions have received much attention as a cost‐effective and promising strategy to improve child health, but their roles in preventing growth retardation in early childhood remain unclear.ObjectiveMeta‐analyses of randomized controlled trials were conducted to evaluate the effect of zinc interventions on the growth of children < 5 y old.DesignEligible studies were identified by PubMed database search and other methods. Weighted mean effect sizes and 95% CI were calculated for changes in height, weight and weight‐for‐ height Z‐scores (WHZ) using random effect models. Tests for homogeneity and stratified analyses by predefined characteristics were conducted using meta‐regression techniques. Tests for publication bias were done using funnel plots.ResultsForty‐three trials (56 datasets) had relevant information. There was no evidence of publication bias. Zinc interventions had a small positive effect on change in WHZ (effect size: 0.06; 95% CI: 0.006, 0.11) but no effect on height or weight gain (effect size: 0.07; 95% CI: ‐0.03, 0.17 and 0.06; 95% CI: ‐0.10, 0.23, respectively). The results were similar across categories of age, duration of intervention, and baseline anthropometric status.ConclusionsContrary to the earlier findings, we failed to detect any benefits of zinc supplementation in improving early childhood growth. Other strategies are needed to prevent stunting.
CD11d expression is dramatically increased in white adipose tissue of obese rodents
Authors: Thomas Anthony , Oort Pieter J. , Newman John W. , Dunn Tamara N. , Knotts Trina A. , Stern Judith S. , Stanhope Kimber L. , Havel Peter J. , Adams Sean H. 
Published: June 2021

Macrophages (MΦ) infiltrate white adipose tissue (WAT) with increasing adiposity and are primarily localized to necrotic adipocytes. Mechanisms underlying WAT MΦ recruitment, tissue migration/retention, and function in obese animals is unclear. Integrins are cell adhesion proteins critical for leukocyte extravasation, migration, and phagocytosis. CD11d encodes the α‐subunit of the integrin αDβ2 and is expressed predominantly on monocytes/MΦ; however, its role in systemic and WAT inflammation is poorly understood. We have demonstrated for the first time that CD11d expression in retroperitoneal (RP) WAT is increased dramatically (by >200 fold) in obese female Zucker rats (n=7) compared to lean controls (n=9), further confirmed in a polygenic obese SD male rat model (~70 fold). To assess whether this upregulation in WAT is the result of obesity‐induced inflammation or generalized inflammation outside the context of obesity, we measured CD11d expression in RP WAT of non‐obese mice administered lipopolysaccharide (LPS) at 0.5 mg/kg (5 day; n=5) vs. vehicle‐treated controls. CD11d expression was increased by LPS treatment, but the fold increase (~3.6 fold) was far less than observed in obesity. Our results are consistent with the hypothesis that CD11d plays a critical role in WAT MΦ migration, tissue retention, and or phagocytosis of cellular debris and lipid from necrotic adipocytes in obesity.Grant Funding SourceWestern Human Nutrition Research Center
Web‐based dietary assessment software for 24‐hour recall interview
Authors: Park Eunyoung , Shin Sangah , Hwang Soochan , Lee Kyo‐Joon , Lee Myung‐Joo , Joung Hyojee 
Published: June 2021

The purpose of this study was to develop computerized dietary assessment software for 24 hr recall interview and evaluate its applicability. Subject management system, standardized interview protocol, food composition table, and recipe databases were established for this program. The client software, developed using Microsoft's ClickOnce technology, can be distributed over the internet and automatically installed on user's PC. The client software communicates with the database system via http server to insert or retrieve its data. The steps of operation consist of subject and researcher tracking, input, calculating, output, and evaluation system. To evaluate the feasibility, 191 adults aged between 24 and 68 participated 24 hr recall interview with software and regular 24 hr recall interview using a questionnaire. On‐line interview took 9.7±4.5 min for one day recall and regular interview did 7.5±3.2 min. There were no significant differences in preferences, satisfaction, and ease of response between two methods. The results indicate that the web‐based software was well accepted tothe subjects and can reduce time‐consuming and error‐causing coding work significantly. Further validation studies for the program could prove usefulness of the software. (This study was supported by a grant of the Korea Centers for Disease Control and Prevention (2007‐E00034‐00) and by the Brain Korea 21 Project in 2008.)
Adolescent' ability to correctly identify foods up to fourteen hours postprandial when prompted with an image of a meal
Authors: Schap TusaRebecca E. , Six Bethany L. , Kerr Deborah A. , Delp Edward J. , Ebert David S. , Boushey Carol J. 
Published: June 2021

Mobile telephones are widely used throughout the world and can provide a unique mechanism for collecting dietary information that reduces burden on record keepers. Our belief is that allowing the user to interact with the mobile phone Food Record (mpFR) after the eating occasion removes one layer of burden while maintaining accuracy for nutrient analysis. The purpose of this study is to investigate adolescents' ability to correctly identify foods up to fourteen hours postprandial when prompted with an image of their meals. Fifteen adolescents (ages 11‐18 y) were provided lunch and dinner meals. The participants were asked to identify each food (fifteen foods total) in the image up to fourteen hours after the respective meal. One hundred percent of participants exactly identified five of the fifteen foods, i.e., milk, spaghetti, peaches, ketchup, and french fries. The other foods were identified within their same respective major food groups. For example, 80% of participants identified lettuce as salad and 33% labeled Coke as soda, pop, or cola. Further probing programmed into the mpFR would lead to an accurate identification of these food items. The results provide evidence that it is feasible to delay user interaction with the mpFR and still obtain accurate food identification.Grant Funding SourceNIH‐NIDDK & NCI