Publications by authors named "Keshari Thakali"

Introduction: Clustering of cardiometabolic risk factors in childhood significantly increases the risk of atherosclerotic cardiovascular disease later in life. Identification of modifiable parental factors that contribute to offspring cardiometabolic health is critical for the prevention of disease. The objective was to identify factors associated with child cardiometabolic risk factors at age 5 years.

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The correlation between obesity and cardiovascular disease has long been understood, yet scant investigations endeavored to determine the impact of an obesogenic diet on platelet activation or function. As platelets drive clot formation, the terminus of cardiovascular events, we aimed to elucidate the longitudinal effect of an obesogenic diet on platelet phenotype by assessing markers of platelet activation using flow cytometry. Male, weanling mice were fed either a Western diet (30% kcal sucrose, 40% kcal fat, 8.

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Objective: Bioprosthetic venous valves have yet to achieve long-term patency due to issues with calcification following implantation that is influenced by current xenograft fixation methods, most notably glutaraldehyde. The goal of this study was to investigate the effects of glutaraldehyde fixation on the functional properties of venous tissue to establish a benchmark for the evaluation of alternative fixation methods.

Methods: The degree of crosslinking was evaluated by determining shrink temperature and the stability of tissue with pronase and collagenase digestion.

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At present, the worldwide prevalence of obesity has become alarmingly high with estimates foreshadowing a continued escalation in the future. Furthermore, there is growing evidence attributing an individual's predisposition for developing obesity to maternal health during gestation. Currently, 60% of pregnancies in the US are to either overweight or obese mothers which in turn contributes to the persistent rise in obesity rates.

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The meat quality of different pig breeds is associated with their different muscle tissue physiological processes, which involves a large variety of genes related with muscle fat and energy metabolism. Understanding the differences of biological processes of muscle after slaughter is helpful to reveal the meat quality development of different breeds. Therefore, eight native Large Black pigs (BP), with high fat content in meat, and seven cross-bred commercial pigs (CP), which had a high feed efficiency with high lean meat, were used to investigate the differences in their meat quality and RNA transcriptomes.

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Introduction: Maternal obesity and poor quality diets are associated with greater risk of obesity in offspring. Maternal diet and obesity influence placental gene expression and nutrient transport, but the impact of diet and obesity on global epigenetic changes in the placenta are poorly understood. We hypothesized that placental DNA methylation patterns are associated with maternal body mass index (BMI) and/or maternal diet composition.

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Objective: This study investigated which antenatal and postnatal factors determine offspring adiposity during the first 2 years of life.

Methods: Participants were mother and child pairs (N = 224). Offspring percent fat mass (%FM) was obtained using quantitative nuclear magnetic resonance at 11 time points between ages 0.

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Background: Maternal obesity increases offspring's obesity risk. However, studies have not often considered maternal metabolic and exercise patterns as well as paternal adiposity as potential covariates.

Objective: To assess the relationship between parental and newborn adiposity.

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The contributions of maternal diet and obesity in shaping offspring microbiome remain unclear. Here we employed a mouse model of maternal diet-induced obesity via high-fat diet feeding (HFD, 45% fat calories) for 12 wk prior to conception on offspring gut microbial ecology. Male and female offspring were provided access to control or HFD from weaning until 17 wk of age.

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One mechanism by which the female sex may protect against elevated coronary vascular tone is inhibition of Ca entry into arterial smooth muscle cells (ASMCs). In vitro findings confirm that high estrogen concentrations directly inhibit voltage-dependent Ca 1.2 channels in coronary ASMCs.

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Introduction: Maternal obesity (OB) and excessive gestational weight gain (GWG) are strong independent contributors that augment obesity risk in offspring. However, direct evidence of epigenetic changes associated with maternal habitus remains sparse.

Methods: We utilized Bisulfite Amplicon Sequencing (BSAS) to conduct targeted DNA methylation association analysis of maternal obesity and excessive GWG with DNA methylation of select metabolism-related and imprinted genes.

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Objective: Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated.

Methods: Two independent studies were performed to examine whether maternal over-nutrition via exposure to high fat diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and methionine choline deficient (MCD) diets in the offspring.

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Nonshivering thermogenesis is the process of biological heat production in mammals and is primarily mediated by brown adipose tissue (BAT). Through ubiquitous expression of uncoupling protein 1 (Ucp1) on the mitochondrial inner membrane, BAT displays uncoupling of fuel combustion and ATP production in order to dissipate energy as heat. Because of its crucial role in regulating energy homeostasis, ongoing exploration of BAT has emphasized its therapeutic potential in addressing the global epidemics of obesity and diabetes.

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The consequences of excessive maternal weight and adiposity at conception for the offspring are now well recognized. Maternal obesity increases the risk of overweight and obesity even in children born with appropriate-for-gestational age (AGA) birth weights. Studies in animal models have employed both caloric excess and manipulation of macronutrients (especially high-fat) to mimic hypercaloric intake present in obesity.

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Introduction: Syncytialization is a process essential to the genesis and vitality of the decisive maternal-fetal interface, the syncytiotrophoblast. While the role of specific genes important in syncytial fusion is appreciated, an integrated global analysis of syncytialization is absent.

Methods: We leveraged a variety of approaches (RNA-seq, genome-scale DNA methylation and ChIP-seq) to assemble a genome-wide transcriptomic and epigenomic view of syncytialization in BeWo cells.

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Objective: To study potential effects of maternal body composition on central nervous system (CNS) development of newborn infants.

Methods: Diffusion tensor imaging (DTI) was used to evaluate brain white matter development in 2-week-old, full-term, appropriate for gestational age (AGA) infants from uncomplicated pregnancies of normal-weight (BMI < 25 at conception) or obese ( BMI = 30 at conception) and otherwise healthy mothers. Tract-based spatial statistics (TBSS) analyses were used for voxel-wise group comparison of fractional anisotropy (FA), a sensitive measure of white matter integrity.

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Highbush (cultivated) and lowbush (wild) are the two major blueberry species in the US market. Eight phenolic acids were detected and quantified from these two species by HPLC-MS. Chlorogenic acid was found to be the predominant phenolic acid in both species, with 0.

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The umbilical cord (UC) matrix is a source of multipotent mesenchymal stem cells (MSCs) that have adipogenic potential and thus can be a model to study adipogenesis. However, existing variability in adipocytic differentiation outcomes may be due to discrepancies in methods utilized for adipogenic differentiation. Additionally, functional characterization of UCMSCs as adipocytes has not been described.

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Background: Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC).

Methods: UCs from 12 lean (pregravid BMI < 24.9) and 10 overweight/obese (pregravid BMI ≥ 25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays.

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Obesity is associated with low-grade chronic inflammation, which contributes to cellular dysfunction promoting metabolic disease. Obesity during pregnancy leads to a proinflammatory milieu in the placenta; however, the underlying causes for obesity-induced placental inflammation remain unclear. Here, we examine the mechanisms by which saturated fatty acids and inflammatory cytokines induce inflammation in placental trophoblasts.

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Ion channels are multimeric, transmembrane proteins that selectively mediate ion flux across the plasma membrane in a variety of cells including vascular smooth muscle cells (VSMCs). The dynamic interplay of Ca(2+) and K(+) channels on the plasma membrane of VSMCs plays a pivotal role in modulating the vascular tone of small arteries and arterioles. The abnormally-elevated arterial tone observed in hypertension thus points to an aberrant expression and function of Ca(2+) and K(+) channels in the VSMCs.

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Voltage-gated L-type Ca(2+) (Ca(v)1.2) channels in vascular smooth muscle cells are a predominant Ca(2+) influx pathway that mediates arterial tone. Channel biogenesis is accomplished when the pore-forming α(1C) subunit coassembles with regulatory Ca(v)β subunits intracellularly, and the multiprotein Ca(v)1.

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Postsynaptic density-95 (PSD95) is a 95 kDa scaffolding molecule in the brain that clusters postsynaptic proteins including ion channels, receptors, enzymes and other signalling partners required for normal cognition. The voltage-gated, Shaker-type K(+) (K(V)1) channel is one key binding partner of PSD95 scaffolds in neurons. However, K(V)1 channels composed of α1.

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Sepsis is a leading cause of acute kidney injury (AKI) and mortality in children. Understanding the development of pediatric sepsis and its effects on the kidney are critical in uncovering new therapies. The goal of this study was to characterize the development of sepsis-induced AKI in the clinically relevant cecal ligation and puncture (CLP) model of peritonitis in rat pups 17-18 days old.

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Rationale: Calcium channel blockers (CCBs) exert their antihypertensive effect by reducing cardiac afterload but not preload, suggesting that Ca(2+) influx through L-type Ca(2+) channels (LTCC) mediates arterial but not venous tone.

Objective: The object of this study was to resolve the mechanism of venous resistance to CCBs.

Methods And Results: We compared the sensitivity of depolarization (KCl)-induced constriction of rat small mesenteric arteries (MAs) and veins (MVs) to the dilator effect of CCBs.

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