bluuebunny/crossref_metadata_2025_split huggingface dataset:
Daily eating frequency is associated with diet quality and weight status in US adults
Authors: Shin Dayeon , Krumhar Kim , Richardson Rhonda , Song Won O. 
Published: June 2021

Few studies have reported eating frequencies in relation to diet quality and weight status. Using 24h diet‐recall, anthropometric and socio‐demographic data of US adults (≥20y, n=4544 excluding pregnant/lactating women and diabetics) in NHANES 2007–8, we examined the association between daily eating frequencies (1–3, 4, 5, 6 and ≥7), diet quality (HEI 2005), and weight status (BMI ≥25). With SAS 9.3 (Cary, NC), we accounted for the complex survey design and sample weights in detecting the differences, trends and associations among the variables and/or subgroups by covariate‐adjusted logistic regressions and linear regression analyses. Mean eating frequencies were similar between men and women (5.0 and 5.3, respectively) with increasing frequencies from 20y to 65y (p<0.05). Eating frequencies were positively associated with diet quality in both genders, with some variations among age subgroups within a gender (p<0.05); and inversely associated with mean BMI and the prevalence of individuals with BMI ≥25 in women (p=0.06), but not in men. Findings from this cross‐sectional survey suggest that, although the degree of strength differs among age/gender groups, eating frequency is an indicator of diet quality and weight status in US adults.Grant Funding Source: Nestle USA
Weight change and the matching of energy consumption and expenditure
Authors: Hand Gregory A. , Hebert James R. , Hill James O. , Blair Steven N. 
Published: June 2021

We evaluated the balance of energy consumption and expenditure on body weight change over one year in 430 healthy young adults.METHODSOver a 14‐day measurement period activity was objectively measured (BodyMedia armband) and diet was measured by 3 random 24‐hr recalls. Change in weight was calculated as measured weight at baseline minus self‐reported weight 1 year earlier. Total daily physical activity (TDEE) was stratified as low/sedentary (LSA, <3METS) moderate/vigorous (MVPA, 3+METS). Correlational analyses were performed on weight change and TDEE, total daily energy intake (TDEI), and the two activity levels. Variables were determined per kg of weight. Analyses were adjusted for age and race.RESULTSWomen averages: 69.1±0.9 kgs, rTDEE=35.1±0.4 kcals/kg/day (KKD). Men averages: 81.3±0.9 kgs, rTDEE=39±0.4 KKD. Correlations (*significant, **very significant) with 1 year weight change were TDEE (−.231**), TDEI (−.122*), MVPA (−.187**), and LSA (−.076, NS). Correlations with TDEI were rTDEE (.444**), MVPA (.893**) and LSA (.164*).CONCLUSIONSRegulation of body weight is a complex interaction of physical, psychological and environmental factors. While absolute TDEE is dependent on body mass, rTDEE and rTDEI correlated most significantly with moderate and vigorous activity. These data suggest that how energy is expended is a critical component of energy balance.
The Hyaluronan Receptor RHAMM Promotes Constrictive Artery Wall Remodeling
Authors: Ma Xue , Pearce Jeffrey D , Li Jing , Wilson David B. , English William P. , Edwards Matthew S. , Geary Randolph L. 
Published: June 2021

Constrictive remodeling of the extracellular matrix (ECM) contributes significantly to restenosis after angioplasty. Hyaluronan (HA) accumulates at sites of injury where it facilitates collagen remodeling. SMCs interact with HA via specific receptor RHAMM for HA‐induced migration. We hypothesized that RHAMM may also mediate SMC‐ECM interactions that alter the extent of constrictive remodeling.We determined the role of RHAMM in HA‐induced SMC adhesion to collagen, migration, and collagen gel contraction by blocking cell‐surface RHAMM with antibodies or by employing SMC from RHAMM −/− (rKO) mice. We then studied the impact of RHAMM on constrictive remodeling by measuring changes in artery wall geometry 1 month after carotid ligation in rKO and RHAMM+/+ (rWT) mice.Attachment to collagen‐coated plates was enhanced by HA and inhibited by antibody blockade of RHAMM. RKO SMC also showed reduced adhesion. HA enhanced SMC contraction of collagen gels and RHAMM blockade or RHAMM gene deletion increased the extent of gel contraction even further. RHAMM also mediated constrictive artery wall remodeling in vivo, as carotid artery wall caliber was significantly greater in rKO mice after ligation. Neointimal thickening was similar but artery size (EEL area) was much larger in rKO mice. Thus, strategies to block RHAMM at sites of injury may prove useful in the prevention of clinical restenosis.
CONTRACEPTIVE AND ABORTIFACIENT EFFECTS OF LIME VAGINAL DOUCHE IN ALBINO WISTAR RATS
Authors: Bassey Rosemary Basiono , Bakare Airat Adeola , Edagha Innocent Asuquo , Peter Aniekan Imoh 
Published: June 2021

ObjectiveTo study the contraceptive and abortifacient effects of lime vaginal douche and its consequent histopathologies on reproductive organs of adult female albino Wistar rats.MethodologyThirty‐five adult female Wistar rats were used and five adult males kept for mating. The animals were randomly divided into groups of five animals per cage. Group 1: concentrated lime juice, group 2: 50% concentrated lime juice group 3: concentrated lime juice and mated, group 4: 50% concentrated lime juice and mated, group 5: mated then administered concentrated lime juice, group 6: mated then administered 50% lime juice and group 7: control. The lime juice was administered intra‐vaginally for 2 weeks. Vaginal smears were taken daily to study the estrous cycle. Groups 1, 2 and 7 were sacrificed after two weeks and uterus, ovary and vagina were prepared for histology; while groups 3 to 6 were sacrificed on the 21st day of gestation.ResultsLime juice showed some contraceptive but no abortifacient effects; however the fetus were not well‐developed. There were some irregularities in the estrous cycle. In the rats administered lime juice, the uterus showed areas of inflammation and vascular congestion; the ovaries showed cortical area with lining degenerated, marked cellular degeneration, follicular degeneration, atrophy and inflammation while the vagina showed marked areas of cellular degeneration, vascular degeneration and inflammation.ConclusionLime juice vaginal douche has teratogenic effects and adverse effects on female reproductive system.
Septic cardiomyopathy is improved by enhancing cardiomyocyte denitrosylation capacity
Authors: Sips Patrick Yves , Zou Lin , Irie Tomoya , Nguyen Rebecca , Chao Wei , Kaneki Masao , Ichinose Fumito 
Published: June 2021

Objectiveto test the hypothesis that reducing cardiomyocyte protein S‐nitrosylation can improve myocardial depression associated with sepsis.Methods and resultsWe generated novel transgenic mice overexpressing S‐nitrosoglutathione reductase (GSNOR), an enzyme promoting protein denitrosylation, specifically in cardiomyocytes (GSNOR‐CMTg mice). Echocardiographic measurements showed that GSNOR‐CMTg mice had a significantly improved cardiac function compared to wild‐type (WT) mice 6 hours after lipopolysaccharide (LPS) injection, while no difference was observed at baseline. Analysis of isolated heart function on a Langendorff setup confirmed a higher contractility in GSNOR‐CMTg hearts than in WT hearts after LPS. Isolated GSNOR‐CMTg cardiomyocytes showed increased cell shortening compared to WT cells after LPS, with no differences at baseline. However, we found a similar LPS‐induced depression in intracellular systolic Ca2+ transients in both genotypes. This suggests that GSNOR‐CMTg cardiomyocytes have an increased Ca2+ sensitivity after LPS. Finally, we confirmed that overexpression of GSNOR resulted in a decrease in total cardiac protein S‐nitrosylation after LPS.ConclusionOur results indicate that cardiomyocyte‐specific reduction of protein S‐nitrosylation protects against sepsis‐induced cardiac dysfunction, presumably by improving cardiomyocyte Ca2+ sensitivity.
The role of cGMP‐dependent nitric oxide signalling on cardiac repolarisation
Authors: Brack Kieran , Caves Rachel , Ng G. Andre , Mitcheson John 
Published: June 2021

Recently, roles for nitric oxide (NO) signalling pathways have been linked with regulation of cardiac repolarisation and protection from arrhythmias. In this study, cGMP‐dependent regulation of repolarisation was investigated using BAY 60–2770, a novel NO and haem‐independent soluble guanylyl cyclase (sGC) activator. Action potentials (AP) were recorded from isolated guinea‐pig ventricular myocytes using the perforated‐patch clamp technique. Cellular cGMP was quantified by radioimmunoassay. 1 μM BAY 60–2770 increased cellular cGMP by 2.1 ± 0.2 (n=5) fold on its own, by 7.9 ± 0.7 (n=4) fold in the presence of 100 μM IBMX a non‐selective phosphodiesterase (PDE) inhibitor, and by 38.7 ± 0.2 (n=2) fold in the presence of ODQ (which strongly potentiates the action of BAY 60–2770 on sGC). Despite substantial increases in cellular cGMP, changes in AP duration were modest. BAY 60–2770 shortened AP duration from 223.3 ± 8.1 ms in basal conditions to 213.0 ± 7.4 ms (n=6, P<0.001) ms and ODQ + BAY 60–2770 caused no further shortening. Importantly, when cGMP hydrolysis was blocked by IBMX, BAY 60–2770 prolonged APs by 19.5 ± 5.6 ms (p < 0.01, n = 8). Overall, these findings demonstrate the complex interplay between cGMP and cAMP mediated effects on cardiac repolarisation. Our results further demonstrate that PDEs limit cGMP accumulation close to ion channels in the sarcolemma, thus compartmentalising cGMP signalling.KEB is supported by a British Heart Foundation Fellowship and REC by a University of Leicester PhD studentship
Moving through Barriers: Unlocking the Mysteries of How Enzymes Really Work
Authors: Klinman Judith 
Published: June 2021

Delineating the physical principles that underlie enzyme catalysis remains a major challenge at the biology/chemistry interface. Recent investigations in enzymology have moved beyond the historical focus on “transition state stabilization”, toward an understanding of the important interplay between protein motions and the generation of highly precise active site interactions. The almost universal contribution of nuclear tunneling to enzymatic C‐H activation reactions offers an especially powerful tool to quantify the role of reduced barrier width in catalysis and its inherent link to enzyme flexibility. The ability to detect positionally specific networks of protein motions implicates an evolutionary tuning of large regions of the protein that extend beyond the active site. These studies are beginning to uncover design principles for the generation of de novo catalysts.(Supported by funding from the NIH, GM025765)
Neurochemical Phenotype of Afferent Neurons of the Nucleus Tractus Solitarius in Response to Esophageal Distension in the Rat
Authors: Ambler Jason , Babic Tanja , Travagli R.Alberto 
Published: June 2021

The nucleus tractus solitarius (NTS) receives visceral information from the gastrointestinal, cardiovascular and respiratory systems via type‐A and type‐C fibers. NTS nucleus centralis (cNTS) receives afferent inputs from the esophagus and previous studies have shown that esophageal afferents display diverse properties. It has also been shown that gastro‐esophageal vagal fibers are under modulatory control of group III metabotropic glutamate receptors (mGluRs). The aim of this study was to determine whether esophageal distention activates cNTS neurons that express group III mGluRs.Rats were anesthetized and an esophageal balloon was placed 5 mm from the lower esophageal sphincter. The esophagus was extended for 1s every 10s for 30min. 90min following esophageal distention, rats were perfused with saline, followed by 4% paraformaldehyde. Brainstem sections were reacted for c‐fos and mGluR8 immunoreactivity (IR). In five control rats, 8±1.8 NTS neurons/section were c‐Fos IR and 9±2.3% were also mGluR8 IR. In cNTS, 0.2±0.05 neurons/section were labelled for c‐fos, 5.7±2% of these neurons were also labelled for mGluR8. Following esophageal distension, 17±3.1 NTS neurons/section were c‐Fos IR and 22±1.5% were also mGluR8 IR (p<0.05 vs. control for both). In cNTS, 2.9±0.5 neurons/section were labelled for c‐fos, i.e. 27±1.9 % of these neurons were also labelled for mGluR8 (p<0.05 vs. control for both).These data show that esophageal distension activates mGluR8‐ir neurons in cNTS, suggesting that integration of sensory inputs from the esophagus may be modulated by group III mGluRs.Supported by NIH grant DK‐55530 and a “Frontiers in Physiology Research Teacher Professional Development Fellowship Award” from APS
High‐fat Diet Causes Loss of Nitric Oxide Motor Neurons and Impairs Inhibitory Neuromuscular Communication in the Mouse Distal Colon
Authors: Bhattarai Yogesh , Fried David , Gulbransen Brian , Galligan James 
Published: June 2021

High‐fat (HF) diet increases the risks of gastrointestinal (GI) motility complications, however, the mechanisms that underlie these complications are still not entirely understood. We tested the hypothesis that HF diet causes oxidative stress, loss of nitric oxide (NO) motor neurons in the myenteric plexus, disrupted inhibitory neuromuscular communication and impaired GI motility.MethodsDistal colon segments from mice fed a control (10 Kcal%) or HF diet (60 Kcal%) were used in vitro. Alexa fluor 546 and 680 conjugated maleimides were used to assess the oxidized/reduced glutathione ratio in myenteric NO neurons. NO neuronal density was assessed using nNOS immunohistochemistry. Basal NO availability was measured using NO induced fluorescence of DAF‐FM diacetate. Electrical field stimulation was applied across varying voltages (60‐120V) and train (200‐1000ms) durations to evoke inhibitory junction potentials (IJPs) in colonic circular smooth muscle cells. Amplitude and area of IJP were examined to assess fast and slow IJPs respectively.ResultsWe observed an increase (17%, p<0.01) in oxidized/reduced glutathione fluorescence ratio in nNOS neurons of HF mice. HF mice had lower (28%, p<0.01) nNOS neurons per ganglionic area than controls. Fluorescence intensity of DAF‐FM diacetate was also lower (20%, p<0.01) in HF mice. HF mice showed a significant loss (52%, p<0.05) in IJP area, when stimulated at higher train duration (800‐1000ms).ConclusionWe conclude that HF diet causes oxidative stress, leading to loss of inhibitory NO neurons, lower NO availability, and disrupted neuromuscular transmission in the mouse distal colon. Supported by NIH (DK094932).
Effects of PCB126 on the Development of Non Alcoholic Fatty Liver Disease
Authors: Boucher Marie‐Pier , Chapados Natalie 
Published: June 2021

Persistent organic pollutants (POPs), are chemicals that were mostly used historically as pesticides, solvents, flame retardants, and other applications. Among POPs, polychlorinated biphenyls (PCB) have been recognized to be of environmental and potential toxicologic concerns. Specifically, PCB126 could act as endocrine disruptors and have recently been associated with hepatic fat accumulation. Fatty liver results from alteration in lipid synthesis and elimination mechanisms such as very low density lipoprotein (VLDL) production and de novo lipogenesis. The purpose of the study was to investigate the effects of PCB126 on the molecular development of non‐alcoholic fatty liver disease (NAFLD) in animals. Male sprague‐Dawley (275‐300g) were injected with a single dose of PCB126 (1 ug/kg) or Corn Oil (control group). Seven days later, liver triglyceride (TAG) content was measured along with protein quantification of microsomal triglyceride transfer protein (MTP) and sterol regulatory element binding protein 1c (SREBP1c).ResultsExposure to PCB126 resulted in significant increases of hepatic TAG concentrations (64%, P <0.001) in rats compared to respective control groups. Rats with fatty livers depicted lower MTP (40%, P <0.02) and higher SREBP1c (27%, P < 0.05) protein content levels compared to Placebo group in rats.ConclusionIt seems that exposure to PCB126 has an important emerging role in the pathophysiology of NAFLD by 1) altering elimination mechanisms such as VLDL synthesis and secretion, mainly through MTP; and 2) increasing hepatic TAG synthesis mechanisms through SREBP1c.
Glycomacropeptide Shows Prebiotic and Immune Modulating Properties in Phenylketonuria and Wild Type Mice
Authors: Sawin Emily , Aktas Busra , DeWolfe Travis , Stroup Bridget , Murali Sangita , Steele James , Ney Denise 
Published: June 2021

BackgroundGlycomacropeptide (GMP) is a 64 amino acid (AA) glycophosphopeptide with application to the nutritional management of phenylketonuria (PKU), obesity and intestinal disorders. GMP is a putative prebiotic based on its carbohydrate content including sialic acid.ObjectiveTo determine the prebiotic properties of GMP by characterizing cecal and fecal microbiota populations and immune responses in C57Bl/6 mice.MethodsWeanling PKU (Pahenu2) and wild type (WT) mice were fed isoenergetic AA, GMP or casein diets for 8 weeks. The cecum content and feces were collected for microbial DNA extraction to perform 16S microbiota analysis by Ion Torrent PGM sequencing. Plasma cytokines were determined using a Bio‐Plex Pro assay and splenocyte T cell populations were assessed using flow cytometry.ResultsPairwise comparison suggests that changes in cecal microbiota are primarily diet dependent. The GMP diet resulted in a significant reduction in Proteobacteria, genera Desulfovibrio, in both WT and PKU mice with genotype‐dependent changes in Bacteroides or Firmicutes. The percentage of stimulated spleen cells producing interferon‐gamma (IF‐γ) was significantly reduced in mice fed GMP compared to casein. Plasma concentrations of IF‐γ and tumor necrosis factor‐α were lowest in mice fed GMP.ConclusionsGMP is a prebiotic based on modulation of the intestinal microbiota compared with casein and AA diets in mice. The shift in microbial populations with GMP appears to be beneficial based on lower indices of inflammation with GMP.
Oscillatory Pattern of Breathing in Healthy Humans at Exercise: Effects of Hypoxia, Hyperoxia and Hypercapnia
Authors: Hermand Eric , Pichon Aurélien , Lhuissier François , Richalet Jean‐Paul 
Published: June 2021

Periodic breathing has been rarely studied in wakefulness during exercise in healthy humans.Spectral analyses of 82 healthy subjects breath‐by‐breath ventilation (VE) signals, from hypoxia exercise tests, evidenced a periodic pattern with a period from 11.1 to 12.0 seconds. VE Peak power was higher in the group 'high ventilatory response to hypoxia at exercise' (HVRe) group (vs low HVRe, P<0.001). A prospective study (25 subjects) was performed to evaluate the influence of cardiorespiratory factors on the amplitude and period of ventilation oscillations in various conditions of exercise (20 to 40% maximal aerobic power) and hypoxia (0 to 4,000m altitude). VE period was shorter during exercise (vs rest) and during hypoxia (vs normoxia) (P<0.001). VE peak power was higher at exercise (P<0.001) and hypoxia (P<0.001). It was also positively related in hypoxia with the ventilatory response to CO2 (HCVR). We assessed respective contributions of central and peripheral chemoreceptors in hypoxia under acetazolamide (ACZ), in hyperoxia and in hypercapnic hyperoxia. ACZ reduced VE peak power (P<0.001), for an unchanged period. VE Peak power remained unchanged in hyperoxia (vs normoxia), but increased in hypercapnic hyperoxia (P<0.001). This novel observation suggests that healthy subjects demonstrate a spontaneous periodic breathing, triggered by hypoxic exercise, enhanced in subjects with high HVRe, high HCVR and hypercapnic conditions, suggesting that hypoxia and CO2 play a synergistic role in the modulation of these oscillations.
Mitochondria Homeostasis Plays a Key Role in the Age‐related Susceptibility to Lung Epithelial Injury and Fibrosis
Authors: Bueno Marta , Lai Yen‐Chu , Romero Yair , Brands Judith , St. Croix Claudette , Rojas Mauricio , Shiva Sruti , Chu Charleen , Mora Ana 
Published: June 2021

RationaleAging is associated with increased susceptibility to lung pathologies. The prevalence of idiopathic pulmonary fibrosis (IPF) has been found to increase with age. While familial disease has been related to disordered telomerase activity and mutations of SPC, the effects of advancing age and lung epithelium dysfunction and fibrosis remains unclear.MethodsLung fibrosis and mitochondria function, morphology and dynamics were analyzed in alveolar epithelial cell type II (AECII) of patients with IPF, aging mice and mice deficient in PINK1 (PTEN‐induced putative kinase 1).ResultsWe found that AECII in IPF lung have marked accumulation of dysmorphic and dysfunctional mitochondria. These mitochondrial abnormalities were recapitulated in normal mice with advancing age and ER stress stimulation. We found that impaired mitochondria in IPF and aging lungs were associated with low expression of the PINK1. Knockdown of PINK1 expression in lung epithelial cells resulted in mitochondria depolarization, and expression of pro‐fibrotic factors. Moreover, young mice deficient in PINK1 develop similar dysmorphic dysfunctional mitochondria in the AECII and are highly vulnerable to apoptosis and development of lung fibrosis.ConclusionOur data indicates that PINK1 deficiency and the subsequent swollen mitochondria dysfunction in the presence of ER stress causes defective mitophagy and promotion of fibrosis in the aging lung.
Akt‐Mediated Mitochondrial Oxidative Stress Induces Mitophagy and Development of Pulmonary Fibrosis
Authors: Casey Jennifer , Ryan Alan , Murthy Shubha , Carter A Brent 
Published: June 2021

Macrophage mitochondrial oxidative stress is directly linked to pulmonary fibrosis. Mitophagy is the selective engulfment of dysfunctional mitochondria by autophagasomes and can be induced by mitochondrial oxidative stress. Oxidative stress can trigger the PINK1/Parkin pathway, which target mitochondria for mitophagy. Mitophagy is important for quality control for cell homeostasis. In this study we show Akt induces macrophage mitochondrial ROS and is associated with an increase in PTEN‐induced kinase 1 (PINK1) and Parkin. Mitochondrial recruitment of PINK1 was determined to be Akt‐dependent, as knockdown of Akt reduced PINK1 mitochondrial localization. Akt did not modulate mitochondrial dysfunction by altering membrane depolarization; however, macrophages exposed to chrysotile asbestos had a decrease in mitochondrial membrane potential in a time‐dependent manner. Akt enhanced macrophage survival and induced autophagosome formation by an induction of LC3 expression. Biological evidence to support this shows that Akt deficient mice have reduced mitochondrial localized PINK1 and Parkin expression, decreased macrophage survival, and are protected from pulmonary fibrosis compared to WT mice. Moreover, alveolar macrophages obtained from asbestosis and idiopathic pulmonary fibrosis patients had increased cell survival and increased mitochondrial localization of PINK1 and Parkin. These observations suggest a direct link between Akt activation, mitophagy, and pulmonary fibrosis by regulating mitochondrial dynamics.2R01ES015981‐07 & BX001135‐01