bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secretin Regulates the Expression of the Renin‐Angiotensin System in Rat Cardiac Fibroblasts
Authors: Afroze Syeda , Nizamutdinov Damir , Feng Hao , Gerilechaogetu Fnu , Jensen Kendal , Munshi MK , Golden Honey , Dostal David , Alpini Gianfranco , Glaser Shannon 
Published: June 2021

Secretin (SCT) is a peptide hormone produced mainly by the S cells of the duodenum that exerts its biological effects through the G‐protein coupled secretin receptor (SCTR). Studies have indicated that SCT stimulates cardiac adenylyl cyclase activity and exerts a positive inotropic action in the heart. The expression of SCT/SCTR or the effect of SCT on cardiac fibroblasts has not been fully explored. The AIM of our study was to determine the expression of SCT and SCTR in cardiac fibroblasts and to explore the effect of SCT on cardiac fibroblast expression of the renin‐angiotensin system (RAS).ResultsRat cardiac fibroblasts express SCT and SCTR by qPCR, IF and FACS. SCT (0.43 ± 0.21 ng/ml) is secreted into supernatants collected from fibroblasts after 6 h. SCT stimulates an increase in intracellular cAMP (but not IP3) and induces an increase in PCNA expression (an indicator of increased cell proliferation) at 6 h. SCT decreases gene expression of the profibrogenic RAS components, AT1a, AT1b and ACE and upregulates expression of AT2.ConclusionsThe findings suggest that SCT may have antifibrotic properties, which are protective during cardiac dysfunction.
In vivo screening of chromatin remodelers in zebrafish reveals proteins governing cardiac growth
Authors: Monte Emma , Mouillesseaux Kevin , Kimball Todd , Vondriska Thomas M , Chen Jau-Nian , Franklin Sarah 
Published: June 2021

Cardiac hypertrophy is a common precursor to heart failure. Hypertrophic cardiomyocytes undergo a global change in gene expression (conserved between humans and animal models of disease) that recapitulates aspects of early development. To investigate the role of chromatin reorganization in this phenotype, mass spectrometry was used to quantify changes in the chromatin proteome during heart disease in mice. Candidate chromatin remodelers, including nucleolin (Ncl), which exhibited a four‐fold increase in the hypertrophied mouse heart, were further tested in zebrafish.In situ hybridization for Ncl demonstrated expression in the developing heart. Morpholinos were used to knockdown (KD) Ncl in zebrafish embryos, resulting in a global increase in histone H3K9 trimethylation, indicative of a more heterochromatic genome. In situ hybridization revealed that the normal restriction of BMP4 to the atrial/ventricular boundary was lost in KD embryos, suggesting delayed ventricular differentiation. Microscopy of 48‐hour embryos showed defects in chamber development in 21% of fish, including delayed (15%) or reversed (5%) looping. Impaired contractility led to blood pooling and edema in a small (3%) population of fish. We conclude that alterations in Ncl expression and activity contribute to chromatin remodeling in the setting of mammalian heart hypertrophy and zebrafish development. Supported by NIH/NHLBI.
ZINC, IGF‐1, AND FOOD INTERVENTION IN MALNOURISHED PREGNANT WOMEN ON CHILDREN BODY HEIGHT AFTER 6 YEARS IN INDONESIA
Authors: Daud Nurpudji Astuti 
Published: June 2021

This study is to investigate effects of zinc and food supplementation on malnourished pregnant women to child body height after 6 years old in Takalar district, Indonesia. Cohort retrospective as a design study (subjects was from double blind study 2003). Samples were children 6 years old, divided into three groups: (1) had zinc, food supplementation history (54 subject), (2) group had food supplementation (20 subject), (3) without zinc and food supplementation (50 subject). Child Growth status is calculated by Marshall and Schwan formula.The study showed, average of weight gain during 6 years period for boys in group one, two and three were 0.181, 0.181, and 0.177 respectively. For girls were 0.177, 0.169, and 0.168. Children born from mother with zinc and food supplementation had high zinc and IGF‐1 level compared without zinc or food supplement history. The average of height gain (cm/month) for boys in group 1, 2 and 3 were 0,786, 0,786 and 0,773 respectively. For girls were 0.791, 0.739 and 0,672. There were no significant differences of food intake for child growth (weight and height gain status). Rate of weight and height growth of children in group 1 and 2 were better and higher than children in group 3.Nutrition intervention for malnourished pregnant women continuously (zinc and food supplementation) to prevent growth retardation in children is needed.
Racial Differences in Blood Pressure after Exercise in Young Individuals
Authors: Yan Huimin , Ranadive Sushant M , Sun Peng , Lane Abbi D , Kappus Rebecca M , Fahs Chris A , Rossow Lindy , Fernhall Bo 
Published: June 2021

Hypertension prevalence is higher in Caucasians (CA) than in Chinese (CH), and high blood pressure (BP) is associated with greater cardiovascular disease risk. However, little is known about the response of BP to an acute bout of exercise.18 college age young CH (height: 170 ± 2 cm, weight: 63 ± 3 kg, BMI: 21.8 ± 0.6 kg/m2) and 19 CA (height: 171 ± 3 cm, weight: 73 ± 4 kg, BMI: 24.7 ± 0.8 kg/m2) underwent measures of BP and central (carotid‐femoral) and leg (carotid‐femoral) pulse‐wave velocity (PWV) before, 15 min, and 30 min after a graded maximal aerobic exercise test (EX) on a stationary bike by applanation tonometry.Diastolic BP was increased in CA but decreased in CH following exercise (CH: from 64 ± 2 to 61 ± 3 to 62 ± 2 mmHg; CA from 65 ± 2 to 67 ± 2 to 67 ± 2 mmHg, race by time interaction, p<0.05). Systolic BP changed with time (CH: from 112 ± 3 to 115 ± 4 to 111 ± 3 mmHg; CA from 118 ± 3 to 121 ± 3 to 116 ± 3 mmHg, p<0.05), but no racial differences. A significant time by race interaction was found in leg PWV (CH: from 8.5 ± 0.4 to 6.9 ± 0.4 to 7.3 ± 0.4 m/s; CA: from 8.6 ± 0.4 to 8.3 ± 0.3 to 8.0 ± 0.3m/s, p< 0.05). Central PWV was not statistically different between CA and CH. Statistically adjusting for BMI did not change these findings.This is the first study to note racial differences in the BP and peripheral arterial response to exercise, suggesting increased BP in young CA and differences in peripheral arterial stiffening following exercise compared to CH.
Acute aerobic exercise increases AdipoR1 and RAGE proteins and decreases HSP60 protein in skeletal muscle of physically inactive older adults
Authors: Markofski Melissa M , Timmerman Kyle L , Reidy Paul T , Dickinson Jared M , Walker Dillon K , Timmerman Jennifer Z , Rasmussen Blake B , Volpi Elena 
Published: June 2021

Aerobic exercise training reduces inflammation and improves insulin sensitivity. Less known are the acute effects of aerobic exercise on skeletal muscle in older, physically inactive adults. We present preliminary data from a study designed to determine the effects of acute aerobic exercise on skeletal muscle markers of inflammation in non‐obese (n=9; BMI: 26.4±1.9 kg·m−2) inactive (3822±1502 steps/day; VO2peak: 22.7±3.5 mL·kg−1·min−1) older adults (72.9±3.9 yrs). After collection of a basal, resting muscle biopsy from the vastus lateralis, subjects walked on a treadmill for 45 min at 70% heart rate reserve, and muscle biopsies were collected 1 and 3 hrs post‐exercise. Protein expression was determined by Western blot. 1 hr post‐exercise, AdipoR1 and receptor for advanced glycation end product (RAGE) were 40.1% and 24.7% higher (p<0.05) than basal. When compared to basal, 3 hrs post‐exercise AdipoR1 was 42.6% higher, heat shock protein 60 (HSP60) was 41.4% lower, and there was a trend for elevation of toll‐like receptor 4 (32.3%). In conclusion, an acute bout of aerobic exercise in physically inactive older adults affects receptors and a ligand (e.g. HSP60) associated with inflammation. These acute effects on inflammation may be necessary for aerobic exercise to initiate muscle adaptation to increased activity in previously sedentary older adults. Future studies are warranted.NIH R01 AG030070, P30 AG024832
Effect of hypohydration and altitude exposure on skin blood flow responses to local heating
Authors: Castellani John , Alinovi Martha , Charkoudian Nisha 
Published: June 2021

It is unknown whether hypohydration (HYPO) or hypobaric hypoxia alter skin blood flow (SkBF) responses to local heating. We hypothesized that HYPO (4% of body weight) and acute altitude (ALT, 3,048 m) would decrease forearm SkBF responses to local heating and that ALT‐HYPO together would result in a further decline. Four healthy young men (23 ± 6 years, 175 ± 5 cm, 74 ± 5 kg) completed 4 trials each: a) sea‐level–euhydrated (SL‐ EUH); b) SL‐HYPO; c) ALT‐EUH; and d) ALT‐HYPO. Local thermal control of cutaneous vascular conductance (CVC) was assessed by local heating to 42°C for 30 min. CVC was calculated as laser‐Doppler flow/mean arterial pressure and analyzed for initial peak (~2–4 min after onset of warming), and plateau (last 3–5 min of warming). Initial peak CVC values were 1107 ± 593, 673 ± 273, 619 ± 241 and 784 ± 440 % of baseline for SL‐EUH, SL‐HYPO, ALT‐EUH, and ALT‐HYPO, respectively. Plateau CVC values were 1585 ± 797, 1340 ± 609, 962 ± 396 and 1082 ± 869 % of baseline. There were no significant influences of HYPO or ALT (P > 0.05 for all), although HYPO and ALT reduced initial peak SkBF by 29–44% and plateau SkBF by 15–39%. Based on these pilot data, 14–18 subjects would be required to give 80% power to detect statistical differences in initial peak and plateau SkBF responses during local heating as a result of hypohydration and altitude exposure.The opinions contained herein are not official and do not reflect Army/DOD views
Epinephrine opens intrapulmonary arteriovenous anastomoses in healthy humans at rest
Authors: Laurie Steven , Elliott Jonathan E. , Lovering Andrew T. 
Published: June 2021

During exercise or while breathing hypoxic gas mixtures large diameter intrapulmonary arteriovenous anastomoses (IPAVA) open and can be detected with saline contrast echocardiography (SCE). The mechanisms regulating these vessels remain unknown, but both of these conditions activate the sympathetic nervous system and increase plasma catecholamine concentrations. We hypothesized that exogenously increasing the plasma epinephrine concentration would open IPAVA. Using SCE, we studied 5 subjects at rest, before and after continuous infusions of epinephrine at 20, 40, 80, 160, and 320 ng/kg/min for 3 min each. Cardiac output (Q) and pulmonary artery systolic pressure (PASP) were measured using ultrasound. Bubble scores (0–5) increased in a dose‐dependent fashion in all subjects to a max score ranging from 2–4. Q and PASP doubled at the highest infusion rate. After a 30 min break, epinephrine infusions were repeated while subjects breathed 100% O2 and bubble scores did not increase despite similar increases in cardiac output and PASP. These data demonstrate that during exercise or when breathing hypoxic gas mixtures the sympathetically‐mediated release of epinephrine may directly open IPAVA independent of changes in cardiac output or PASP. Mechanisms responsible for hyperoxia‐mediated closure remain elusive.Support: Eugene Evonuk Graduate Fellowship in Exercise & Environmental Physiology
Methionine Adenosyltransferase 2A Positively Regulates Bcl‐2 Expression in a Ubiquitin‐Conjugating Enzyme 9‐Dependent Manner
Authors: Tomasi Maria Lauda , Lu Shelly C. 
Published: June 2021

BACKGROUND & AIMSUbiquitin‐conjugating enzyme 9 (Ubc9) is required for sumoylation and inhibits apoptosis via Bcl‐2 expression by unknown mechanism. Ubc9 and Bcl‐2 expression is up‐regulated in several malignancies. S‐adenosylmethionine (SAMe) is the methyl donor synthesized by methionine adenosyltransferase (MAT). MATII, encoded by MAT2A, is overexpressed in liver and colon cancers. SAMe decreases MAT2A expression and is pro‐apoptotic in cancer cells. Here we investigated whether MAT2A's effect on apoptosis may involve Bcl‐2 and Ubc9.METHODSOur studies used human colon and liver cancer cell lines RKO and Huh‐7, respectively. Gene and protein expression, Bcl2 promoter activity and protein binding were measured.RESULTSSAMe and its metabolite methylthioadenosine (MTA) treatment lowered Bcl‐2 expression at mRNA and protein levels by 55–80%. Knockdown of Ubc9 lowered MAT2A protein (but not mRNA) levels by 25%. Knockdown of MAT2A reduced Bcl‐2 mRNA level and Bcl‐2 promoter activity by 50–65%, while MAT2A overexpression doubled Bcl2 promoter activity in both cell types. Chip assay showed that MATII could physically interact with Bcl‐2 promoter in an Ubc9‐dependent manner.CONCLUSIONSMATII binds to the Bcl‐2 promoter region and this requires Ubc9. Ubc9's protective effect on apoptosis may be mediated at least in part by enhancing MATII expression, which in turn positively maintains Bcl‐2 expression.This work was supported by NIH grants R01DK51719, R01AT1576 and R01AT004896 (SC Lu), and F32AA020150 (ML Tomasi). Huh‐7 and RKO cells were provided by the Cell Culture Core of the USC Research Center for Liver Diseases (P30DK48522).
Mesenchymal stem cell niches in tooth growth and repair
Authors: Sharpe Paul 
Published: June 2021

When teeth are damaged to the extent that the pulp tissue is exposed, a natural repair process is activated to prevent infection. Mesenchymal stem cells (MSCs) located in the pulp are mobilised to proliferate, migrate to the site and damage and differentiate into specialised cells (odontoblasts) that repair the dentine.In rodent incisor teeth, a specialised MSC niche is located at the cervical end of the tooth to provide a source of cells to replace those lost during the continuous growth of these specialised teeth. These cells are also mobilised following damage and can be observed migrating towards the site of damage. In addition damage also induces a pericyte‐MSC response where pericytes are stimulated to proliferate and can be seen differentiating into odontoblasts at the site of damage (Feng et al 2011). During feeding, the pulp at the tips of the incisors becomes exposed and a third MSC niche can be identified that acts to rapidly mineralise the pulp to prevent blood loss and infection. Interestingly this same niche can also been found at the tips of molar teeth that do not grow continuously in rodents or humans. The continuously‐growing rodent incisor thus has three separate MSC niches, involved in homeostasis and repair. Non‐growing teeth (as found in humans) have two MSC niches involved only in repair.The ease with which MSCs can be obtained from teeth makes them a highly attractive source for all therapeutic applications requiring MSCs and numerous dental pulp cell banks are in operation. The multiple niches in the rodent incisor make this organ an attractive model system to study the molecular and structural properties of MSCs and their niches and the molecules involved in the processes of mobilisation during tissue repair.
Combining Ultrasound and Gross Anatomic Dissection in Teaching 3‐D anatomy: Effectiveness in a first year medical course curriculum
Authors: Yee Alyssa Mae , Hwang Jiye , Pagano Anthony S , Marquez Samuel 
Published: June 2021

The practice of exposing medical students to different imaging modalities has been advanced by the wave of curriculum reform sweeping the nation. Cross‐sectional imaging has taken up a central role in diagnostic medicine, particularly with CT imaging and now, more recently, Ultrasound (US) technology. Exposing students to US imaging lectures without careful coordination of in‐lab serial dissection has, however, been met with mixed reviews. This study reports on the use of serial dissection activities on three donor bodies combined with US technology on live subjects (n=3). Six distinct diarthrodal joints were targeted: 1) shoulder, elbow, wrist, hip, knee, and ankle. Each joint was approached from different perspectives, each noting tissue depths. The shoulder was dissected in the anterior, posterior, lateral and superior orientation. Measures on US and dissections were from epidermis to: dermis, superficial fascia, muscle, deep fascia, superficial joint surface and joint capsule. Results showed no statistically significant (p<0.05) differences between the two approaches, confirming the accuracy of US. One notable qualitative result was the impression felt by students that combining traditional dissection activities with US improved understanding of contiguous structures in 3‐D space. Many felt that their learning experience was greatly enriched by the use of a new imaging modality tool.Grant Funding Source: none
Oligosaccharides as Recognition Molecules – A coming of age
Authors: Kornfeld Stuart 
Published: June 2021

Most membrane and secreted proteins as well as lysosomal acid hydrolases contain covalently‐linked oligosaccharides that exhibit a vast array of structures. We now recognize that these oligosaccharides participate in numerous biologic processes ranging from folding of nascent glycoproteins to trafficking of lymphocytes in the circulation. The requirement for proper glycosylation is underscored by the growing list of human diseases that result from defects in glycan assembly.Our early work focused on the structural analysis of Asn‐linked glycans and their biosynthesis. We then turned to the study of a specific glycosylation event that serves to target acid hydrolases to lysosomes, i.e. the formation of mannose 6‐ phosphate residues on the Asn‐linked glycans of these enzymes. We have investigated the unique two‐step pathway for the biosynthesis of this marker and explored how the first enzyme in this process distinguishes acid hydrolases from non‐lysosomal glycoproteins, a critical step in the sorting process. This led to studies of the two Man‐6‐P receptors that bind the Man‐6‐P determinant and deliver the hydrolases to lysosomes. This pathway serves as a valuable model for studies of intracellular protein trafficking. Analysis of mouse models of lysosomal storage disorders caused by the failure to synthesize the Man‐6‐P recognition marker is providing insight into the pathophysiology of these disorders.
Relation of Whole Grain Intake to Risk of Type 2 Diabetes, Cardiovascular Disease and Weight Gain: A Systematic Review and Meta‐Analysis
Authors: Chacko Sara , Ye Eva Qing , Chou Elizabeth L , Kugizaki Matthew , Liu Simin 
Published: June 2021

BackgroundWhole grain intake is routinely recommended for prevention of vascular disease, however current literature lacks a comprehensive and quantitative review of potential benefits.PurposeSystematically examine longitudinal studies investigating whole‐grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors.Study Selection45 prospective cohort studies and 17 randomized‐controlled trials were identified between 1966‐December 2010 in CINAHL, EMBASE and PUBMED using a standardized protocol.Data SynthesisCompared to never/rare consumers, those who consumed an average of 3 servings/day of whole grains had a ~26% lower risk of T2D [RR=0.74 (0.70, 0.79)], ~14% lower risk of CVD [RR=0.86 (0.83, 0.89)] and ~49% lower risk of weight gain [RR=0.51 (0.39, 0.67)]. In randomized settings, mean differences of fasting glucose [−0.28 mmol/L(−0.48, −0.09)], total cholesterol [−0.99 mmol/L (−1.49, −0.49)], low‐density lipoprotein cholesterol [−1.10 mmol/L (−1.68, −0.51)], and systolic blood pressure [−0.34, ( −0.57, −0.11)] were significantly lower after whole grain interventions than after control diets.ConclusionWhole‐grain intake may have beneficial effects for vascular disease prevention. Potential mechanisms require further investigation in large intervention trials.
Rescue of Stalled Replication Forks by the DNA Translocase FANCM
Authors: Constantinou Angelos , Basbous Jihane , Luke-Glaser Sarah , Gari Kerstin 
Published: June 2021

Fanconi anemia (FA) is a chromosomal instability syndrome that manifests with congenital abnormalities, bone marrow failure and cancer predisposition. To date, fourteen FA genes have been identified and implicated in a ubiquitin signaling pathway, in S phase checkpoint activation, in lesion bypass and in DNA double‐strand break (DSB) repair by homologous recombination.FANCM is a DNA translocase that acts as a molecular scaffold involved in multiple DNA damage signaling and processing reactions. FANCM interacts with : 1) the checkpoint protein HCLK2 to facilitate DNA damage signaling; 2) with the Bloom's complex at stalled forks; 3) and with the FA ubiquitin ligase complex, promoting its recruitment to chromatin and the monoubiquitination of FANCD2 and FANCI.Our biochemical studies revealed that FANCM binds and translocates the branch point of DNA structures that mimic replication and repair intermediates, suggesting that FANCM may remodel replication intermediates to promote recovery. Using a molecular combing approach, we have observed that FANCM facilitates the restart of replication forks stalled by DNA topoisomerase I inhibitors. Our recent efforts have focused on studying the role new DNA damage response proteins that interact with FANCM.Research support: ARC Association pour la Recherche sur le Cancer, ANR Agence Nationale de la Recherche, SNSF Swiss National Science Foundation.
Development of a simple in vitro digestion model suitable for multi‐nutrient food systems
Authors: Garcia-Campayo Vicenta M , Ross Keri , Ayeni Philip , Bonnema Angela , Berger Alvin 
Published: June 2021

In vitro digestion models screen kinetics of digestion of nutrients, as alternatives to in vivo testing. Most models digest only one type of macronutrient. We developed a batch in vitro digestion model for ranking digestion of all macronutrients alone, mixed, or as whole food. Ingredients are sequentially agitated with saliva, gastric, and duodenal/bile solutions at 37°C for up to 72 h. Ingredients are characterized by: primary structure (PS), physical form (PF), and controlled architecture (CA). We selected ingredients of known digestibility and predicted their rate (slow/fast) and extent (complete/incomplete) of digestion.
Selected rate examples

Nutrient: Concept
Digestibility

PS
CHO: High Amylose (Amy) slows digestion  Proteins: Native structure
Waxy corn starch (CS) > common CS>50%Amy CS  Casein≈Whey≈Soy>Pea>Rice

PF
CHO:Gelatinization increases digestion  Proteins: Processing  Lipids: Higher melting point (MP) slows digestion
Gelatinized CS >Native 50% Amy CS  Native Soy>Freeze dried soy  Olive oil >high MP solid fats

CA
Whole food: Processing
Bread Whole wheat (WW) flour >Raw WW flour

The model is suitable for digestion of mixed macronutrients and appropriately ranks their rate/extent of digestion on basis of PS, PF, and CA. Applications include slowed digestion as a satiety marker, and enhanced digestibility for clinical/animal husbandry use. Comparative studies in pigs are ongoing. Funded by Cargill Inc.
A novel student‐centered nutrition medicine education model
Authors: Lenders Carine M , Gorman Kathy , Peace Kaitlin 
Published: June 2021

BackgroundFor more than a decade, national surveys have reported that most common deaths in the United States are preventable and related to nutrition. As a result, physicians have been urged to counsel their patients but with minimal improvement in nutrition medicine education in US medical schools.ObjectiveTo partner with various BU communities and enhance medical students’ knowledge, attitudes, and counseling skills in nutrition medicine.InterventionWe developed a novel student–centered model of nutrition medicine education that focuses on student mentored extra‐curricular activities to develop, evaluate, and sustain nutrition medicine. Using the NAA nutrition objectives from NIH and AAMC CurrMit software to evaluate nutrition content in the curriculum, we found that three‐quarter of pre‐clerkship objectives were met.ConclusionsThese findings are encouraging. We further plan to conduct program evaluations, administer surveys to students and faculty, and partner with national groups to improve population wellness and services. Support from the New Balance Foundation.