bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for the interplay between post‐translational modifications in regulating mycobacterial sirtuin activity
Authors: Yadav Ghanshyam Singh , Ravala Sandeep K , Malhotra Neha , Chakraborti Pradip K 
Published: November 2023

Regulation of cellular processes by post‐translational modification of proteins is well known throughout the phylogeny. Phosphorylation/dephosphorylation of a given protein in bacteria is often controlled by Eukaryotic‐type serine/threonine kinases and cognate phosphatases. Similarly bacterial proteins are also governed by acetylation/deacetylation events. In this context, we focussed on only sirtuin, the NAD+‐dependent deacetylase present in the Mycobacterium tuberculosis genome, involved in removal of acetyl group from Nɛ‐acetyl‐lysine of a protein. Sirtuin family of proteins are conserved throughout the phylogeny and in eukaryotes they are also regulated by different kinases affecting diverse cellular functions. This interplay of kinase(s) and sirtuins is not elucidated in prokaryotes. Utilizing in vitro and in vivo transphosphorylation assays we found PknA, an essential mycobacterial eukaryotic‐type serine/threonine kinase is able to phosphorylate only sirtuin (mDAC) of M. tuberculosis. Compared to unphosphorylated mDAC, phosphorylation of mDAC causes decrease in deacetylase activity. Utilizing mass spectrometry approach, we observed that different serine and threonine residues were phosphorylated. In vitro kinase assays with different phospho‐site mutants of mDAC identified Thr‐214 as the major phosphosite. Over‐expression of mDAC or T214A in Mycobacterium smegmatis, where endogenous kinases are present, yielded phosphorylated proteins. Expectedly, magnitude of phosphorylation, as assessed by monitoring band intensity in western blot using anti‐phosphothreonine antibody, was considerably low in T214A protein compared to that of the mDAC. We further noted that sirtuin knock‐out E. coli strain was compromised in its growth profile in nutrient deprived condition (acetate medium). This phenotype, however, was reversed upon mDAC expression. Interestingly, expression of PknA in the mDAC complemented E. coli strain exhibited growth inhibition in acetate medium, indicating phosphorylation mediated regulation of mycobacterial sirtuin. In consonance with this finding, a phosphomimic, T214E also exhibited growth compromised behaviour compared to that of the wild‐type. Our study therefore, draws its logical inspiration on the possibility of interactions of two distinct post‐translational events in successful pathogens like M. tuberculosis for their versatile metabolic adaptability.Support or Funding InformationThis study was supported by institutional (CSIR‐Institute of Microbial Technology, Chandigarh) research grants (OLP‐97) and also from Department of Science and Technology (JC Bose National Fellowship to PKC, No. SR/S2/JCB‐87/2012, Science and Engineering Research Board), New Delhi, India.
Quantitative Analysis of Cross‐Talk Between RET and Other Growth Factor Receptors
Authors: Huestis Mikayla Joy , Chow Jennifer 
Published: November 2023

RET (Rearranged During Transfection) is a receptor tyrosine kinase, involved in neuronal and kidney development, that activates multiple signaling cascades, including the Raf/MEK/ERK MAP Kinase and Akt pathways. We developed a luciferase reporter gene assay that is responsive to MAP Kinase pathway activation, and used it to investigate RET signaling dynamics from receptor activation to gene transcription and translation, and to quantitatively characterize crosstalk between RET and other receptor signaling pathways. The results showed that the first committed step in RET‐activated protein expression is gene transcription. Previous studies from the Hynes and Tufro laboratories have shown that crosstalk between RET and other receptors has biological importance. However, quantitative analysis of crosstalk between growth factor receptors has rarely been investigated. We used our luciferase assay, in conjunction with ELISAs measuring the amplitude and dynamics of ERK and Akt signaling, and assays measuring functional cellular outcomes, to screen for growth factors and corresponding receptors involved in cross‐talk with RET, and to achieve quantitative insights into the interaction between the pathways and its functional significance.Support or Funding InformationArnold and Mabel Beckman Foundation, National Institutes of Health, Biogen Idec
Involvement of Stromal Interaction Molecule‐1 in Angiotensin‐II‐Induced Expression of The Early Growth Response Protein‐1 in Vascular Smooth Muscle Cells
Authors: SIMO CHEYOU ESTELLE R , TAN JU JING , GRYGORCZYK RYSZARD , SRIVASTAVA ASHOK K 
Published: November 2023

The early growth response protein 1 (Egr‐1) is a zinc finger transcription factor that has been suggested to regulate the expression of genes linked with inflammation and cell cycle regulation. An up‐regulation of Egr‐1 expression has been reported in models of atherosclerosis and intimal hyperplasia. Various vasoactive peptides and growth promoting stimuli have been shown to induce the expression of Egr‐1 in vascular smooth muscle cells (VSMC). Angiotensin‐II (Ang‐II) is a critical vasoactive peptide implicated in the pathogenesis of vascular diseases. Ang‐II elevates the intracellular level of Ca2+ through activation of store‐operated Ca2+ entry involving inositol‐3‐phosphate receptor (IP3R)‐coupled depletion of endoplasmic reticular Ca2+ and stromal interaction molecule 1 (STIM‐1). However, an involvement of IP3R/STIM‐1‐induced Ca2+ signaling pathway in Ang‐II‐induced Egr‐1 expression remains unexplored. Therefore in the present studies we have examined the role of Ang‐II‐induced Ca2+ release in Egr‐1 expression in VSMC and investigated the contribution of STIM‐1 in this process. Ca2+ chelation with BAPTA‐AM as well as pharmacological blockade of IP3R with 2‐aminoethoxydiphenyl borate (2‐APB) reduced Ang‐II‐induced Ca2+ release in VSMC loaded with Fura‐2 AM. Consistent with this, both BAPTA‐AM and 2‐APB attenuated Ang‐II‐induced enhanced expression of Egr‐1 protein levels. In addition, pharmacological blockade of both the epidermal growth factor receptor and the insulin‐like growth factor‐1 receptor attenuated Ca2+ release and inhibited the Egr‐1 up‐regulation induced by Ang‐II. Furthermore, silencing of STIM‐1 via RNA interference significantly abrogated STIM‐1 protein and mRNA expression and resulted in an attenuation of Ang‐II‐induced Egr‐1 expression as well as ERK1/2 phosphorylation. In summary, our data demonstrate that Ang‐II‐induced Egr‐1 expression is mediated by STIM‐1 and Ca2+ release in A‐10 VSMC and suggest an implication of STIM‐1 in the pathogenesis of vascular proliferative diseases.Support or Funding InformationSupported by a grant from the Canadian Institutes of Health Research
Histopathology for the Influence of CMV Infection on Tomato Cellular Structures
Authors: Montasser Magdy S , Al‐Ajmy Afrah Moshare 
Published: November 2023

Cucumber mosaic virus (CMV) causes wide‐spread diseases that damage some crops worldwide. One strain of the virus was isolated from tomato plants grown in Kuwait designated CMV‐KU1. This isolate was found to be associated with a benign viral satellite RNA, causing mild symptoms on infected tomato plants. Another isolate, CMV‐16, a severe stunting strain and lacking viral satellite RNA was used in a comparative study with the isolated mild strain of the virus CMV‐KU1. Both CMV strains were used as antigens to prepare murine monoclonal and polyclonal antibodies for serological confirmation using enzyme linked immunosorbent assay (ELISA) to confirm the identity of viral strains in infected plant tissues. The objectives of this study were to investigate the effects of the viral infection on tissues, cells and cellular organelles in test plants using Transmission Electron Microscopy (TEM) to determine the extent of infection and host‐virus interactions and damage caused by virus isolates on tomato. Electron micrographs of ultra‐thin sections proved the presence of the viral particles, the formation of viral crystalline bodies, chloroplast damage and malformation due to the infection caused by the virus in infected plant tissues. The viral infection caused a reduction in chloroplast number and size. As the infection progressed, chloroplasts were completely destroyed and the grana were disorganized and scattered into the cytoplasm that causes reduction in chlorophyll contents in plant tissues.Support or Funding InformationThis work was supported and funded by Kuwait University Research Grant No. [SL 01/13 & YS 07/10]
Early Life Methyl Donor Supplementation Attenuates Obesity‐Risk
Authors: McKee Sarah E , Reyes Teresa M 
Published: November 2023

Excessive gestational weight gain is defined when women with a normal pre‐pregnancy body mass index gain more weight than recommended during pregnancy. Excessive gestational weight gain (GWG) has a prevalence rate of nearly 50% and it significantly increases the risk for the development of obesity in the offspring. Excessive GWG can be modeled in animals by feeding pregnant dams a high fat diet, leading to increased maternal weight gain and obesity‐promoting phenotypes in the offspring. Using a mouse model of excessive GWG, we have documented in the offspring an increased preference for sucrose and fat, increased expression of genes that underlie reward‐related behaviors, and both global and gene specific decreases in DNA methylation. These changes in reward‐related neural circuitry may contribute to the increased risk for the development of obesity in the offspring by altering the animal's response to highly palatable, energy dense foods. Methyl donor supplementation (MDS) during pregnancy can reverse some of these obesity‐promoting phenotypes in offspring, yet it is unknown whether postnatal MDS can reverse these phenotypes. To determine this, offspring from dams fed either a high fat diet (HFD) or control diet during gestation were fed a methyl donor supplemented diet during early life (3–6 weeks). We find that postnatal MDS significantly decreased body weight in both male and female adult HFD offspring, and does not alter body weights of control diet offspring. Further, postnatal MDS can rescue adult male fat preference and contributes to region specific normalization of global DNA hypomethylation. We also find that MDS can increase motivation to work for palatable reinforcer in adult female offspring. Continued assessment of obesity development, preference for palatable foods, metabolic phenotypes, and expression changes of genes underlying homeostatic and hedonic feeding will elucidate the mechanism by which early postnatal MDS offsets adult obesity risk.Support or Funding InformationNIH MH087978, MH100828, MH106330 to TMR and ES019851 to SEM
Weight Loss Success Among Obese Women of Mexican‐origin in Mexico and the US
Authors: Kaufer‐Horwitz Martha , Weintraub Miranda Ritterman , Guendelman Sylvia 
Published: November 2023

BackgroundWe assessed variations in and correlates of weight‐loss success among overweight/obese women in Mexico (WIMX) and Mexican‐American women (MA).MethodsWe used cross‐national data from 2006 ENSANUT (Mexico) and NHANES (2001–2008) to compare 5,061 WIMX with 550 MA's without known metabolic conditions. WLS was defined as losing ≥ 5% of body weight over one year.ResultsMA's were more likely to attain weight‐loss success (OR=1.31; 95%CI=1.01–1.70). Weight‐loss success among WIMX was higher in those with at least high school, a provider screen of overweight and a lower BMI. Among MA's, an incomplete high school versus primary education reduced the odds of weight‐loss success. Among women who lost ≥10lbs, weight‐loss strategies such as eating less were higher among MA's.DiscussionMA women were more likely than WIMX to attain weight loss success. Understanding these disparities can help design customized public health interventions that curb the obesity epidemic in these women in both countries.Support or Funding InformationPrograma de Investigación en Migración y Salud (PIMSA).
Child Dietary Patterns and Diversity in Rural and Semi‐Rural Ghanaian Communities
Authors: Gyenes Natalie , Agbemafle Isaac , Zotor Francis , Duggan Christopher , Fawzi Wafaie , Willett Walter , Ellahi Basma 
Published: November 2023

BackgroundPoor child feeding practices contribute to childhood malnutrition and have long‐term consequences for non‐communicable diseases (NCDs) in later life, but little is known about these patterns in rural Ghana. This study assessed dietary patterns and diversity among children under five years in rural and semi‐rural areas in Ghana.MethodsA cross‐sectional survey was undertaken among 1185 households in Eastern, Volta and Brong Ahafo regions of Ghana. Households with children under age 5 years were sampled. Children from the households were randomly selected and information on liquid/medicine, supplement use, breast feeding history and special foods consumed were obtained from their caregivers using a pretested semi‐structured questionnaire. Dietary intake patterns and dietary diversity of the children were assessed using a 24‐hour recall. Pearson's chi‐square was used to determine associations between region and dietary patterns and diversity.Results873 children were recruited of whom 52% were females. Breastfeeding frequency (at least 6 times) was highest within each of the three geographical regions. Multivitamins and oral rehydration solutions were the commonly reported medications. In increasing order of consumption, the main liquids consumed were soup, porridge and plain water. The main ingredients used for porridge were maize flour, water and sugar. Food items used to enrich the porridge varied by region. Groundnut paste and milk were commonly used to enrich porridge in all the three regions. Special foods such as commercially prepared fortified cereal‐legume blends and locally prepared wheat/corn‐soy blend were reported to be eaten occasionally. The commonly consumed food groups were cereals (14.9%), vegetables (14.9%), fish and sea foods (12.2%) and roots and tubers (10.4%) and these differed significantly by region (p<0.0001). Dietary diversity was low for 91% of the children and this trend was similar in all the three regions. There were significant differences in dietary diversity across the three regions (p=0.001).ConclusionChild feeding practices in rural and semi‐rural communities in Ghana show low dietary diversity. This has implications for childhood malnutrition and non communicable diseases in adult life, highlighting the importance of prioritizing nutrition interventions in order to address childhood malnutrition.Support or Funding InformationThis Research was supported in part by a grant from the Department of Global Health and Population, Harvard T.H. Chan School of Public Health, as well as the Department of Nutrition, Harvard T.H.Chan School of Public Health.
Normal Plasma Volume Expansion and Micronutrient Status in Pregnancy
Authors: Aguree Sixtus , Roy Aditi , Gernand Alison D. 
Published: November 2023

Plasma volume expansion is widely known as an important physiologic change in pregnancy, yet normal expansion in healthy pregnancies has not been well described. This expansion influences plasma micronutrient concentrations and may impact interpretation of biomarkers. Our objective was to review studies that measured plasma volume longitudinally across gestation to describe normal plasma volume expansion; secondarily, we examined the impact of plasma volume expansion on micronutrient biomarkers. We systematically searched PubMed for original articles that directly measured plasma volume in pregnant women at more than one time across gestation. We also searched reference lists from these publications for additional papers. We found 15 studies published from 1963 to 2006 that directly measured plasma volume in pregnancy more than one time. We excluded 3 studies because the measurements were not longitudinal and one study because it used an unconventional measurement technique (iron dextran) and some values appeared extreme. Of the 11 longitudinal studies included, 8 studies were conducted in the UK and one each was conducted in India, Chile, and Nigeria. All studies used the Evans blue dye (T‐1824) indicator dilution method to measure the plasma volume. The total number of women in all studies was 524; study size ranged from 11 to 95. Plasma volume was measured 3 to 7 times in women across the studies. Two studies measured plasma volume before conception and 5 studies measured postpartum values (6–8 weeks after birth) as a proxy for pre‐conception. Plasma volume increases varied across the studies. Plasma volume increased by 8% between preconception and 12 weeks, 18% by 16 weeks, 27% by 20 weeks and 36% by 25 weeks gestation. The maximum mean plasma volume increase was 52% (1267 ± 38 ml) at 33–34 weeks gestation. This peak mean expansion ranged from 48% to 59% (1218 to 1323 ml) across studies, while reports of expansion for individual women ranged from 25% to 80%. Plasma volume slightly declined from late third trimester to term. Only one plasma volume study measured micronutrient status. In that study, plasma zinc concentrations declined across gestation to 30 weeks but intravascular zinc mass (the product of zinc concentration and plasma volume) increased across pregnancy. Plasma copper concentration increased up to gestational week 35 but intravascular copper mass was not reported. Few studies have measured plasma volume longitudinally in pregnancy. Studies of healthy pregnancies similarly show plasma volume increases progressively to approximately 52% above the non‐pregnant state in the third trimester with a slight decline to term. Plasma zinc concentration changes in pregnancy did not reflect actual changes in zinc status. Future studies in pregnancy should measure plasma volume to have a valid estimation of micronutrient status and to understand underlying physiologic changes that may be related to adverse outcomes.Support or Funding InformationNIH BIRCWH 12HD055882 (Dr. Gernand)
Metformin to Augment Low Milk Supply: A Protocol Summary
Authors: Nommsen‐Rivers Laurie A , Riddle Sarah W , Thompson Amy A , Ward Laura P , Wagner Erin A 
Published: November 2023

Maternal obesity is associated with shortened breastfeeding duration, but the mechanism remains unclear. A progression of research is pointing to waning insulin secretion in the context of insulin resistance as a strong contributor to low milk supply in mothers attempting to exclusively breastfeed. Metformin enhances insulin action, but it is not known if it improves milk production. Our primary aim is to enact a phase I/II double‐masked randomized placebo‐controlled trial (RCT) of metformin versus placebo to treat low milk supply in women with signs of insulin resistance. At baseline, all referred women receive standard guidance for increasing milk supply with breast expression, record 24‐hours of milk production, and are evaluated for RCT eligibility. If eligible, participants are randomly assigned to metformin or placebo. Specimen collection includes milk fat RNA at baseline and post‐treatment. Baseline measurements are ongoing until N=30 RCT‐eligible participants complete the trial. The study is powered to demonstrate feasibility, obtain variance estimates, and test for a trend in the primary hypothesis that the metformin group will experience a greater increase in milk output as compared to the placebo group. Trial completion expected July, 2016.Support or Funding InformationNIH 5 K12 HD051953 (Tsevat, PI), Bridging Interdisciplinary Research Careers in Women's Health (BIRCWH award to LN‐R)
The Relationship between Neighborhood Walkability and Adiposity in the WHI Cohort
Authors: Sriram Urshila , LaCroix Andrea , Barrington Wendy , Corbie‐Smith Giselle , Garcia Lorena , Going Scott , LaMonte Michael , Manson JoAnn , Sealy‐Jefferson Shawnita , Stefanick Marcia , Waring Molly , Seguin Rebecca 
Published: November 2023

The aim of the present study was to explore associations of Walk Score, a validated measure of neighborhood walkability, with body mass index (BMI) and waist circumference in a large, diverse sample of older women. We linked cross‐sectional data on 6,164 older postmenopausal women from the Women's Health Initiative Long Life Study to Walk Scores for each participant's address in 2012. Linear and logistic regression models were used to estimate associations of BMI and waist circumference with continuous and categorical Walk Score measures. Secondary analyses examined whether these relationships could be explained by walking expenditure or total physical activity. Higher Walk Score was associated with lower waist circumference but not BMI, after adjustment for sociodemographic and lifestyle factors. Participants in highly walkable areas had lower odds of abdominal obesity as compared to those in less walkable locations. Observed associations between walkability and waist circumference were partly explained by walking expenditure. Findings suggest that neighborhood walkability is linked to waist circumference but not BMI among older women and provide support for future longitudinal research on associations between Walk Score and adiposity in this population.Support or Funding InformationFunded by NIH, NHLBI, HHS grants/contracts HL60712, K01HL10880705, HHSN268201100‐046C/‐001C/‐002C/‐003C/‐004C