bluuebunny/crossref_metadata_2025_split huggingface dataset:
microRNAs in Cardiac Development and Function
Authors: Wang Da-Zhi 
Published: June 2021

MicroRNAs (miRNAs) negatively regulate gene expression at the post‐transcriptional level, primarily by base‐pairing with the 3’‐untranslated region (3’‐UTR) of their target mRNAs. Many miRNAs are expressed in a tissue/organ‐specific manner and are associated with an increasing number of cell proliferation, differentiation and tissue development events.Cardiac muscle expresses distinct genes encoding structural proteins and a subset of signal molecules that control tissue specification and differentiation. The transcriptional regulation of cardiac and skeletal muscle development has been well established, yet only until recently has it been uncovered that miRNAs participate in the regulatory networks.A subset of miRNAs are either specifically or highly expressed in cardiac and skeletal muscle, providing an opportunity to understand how gene expression is controlled by miRNAs at the post‐transcriptional level in this muscle type. miR‐1, miR‐133, miR‐206 and miR‐208 have been found to be muscle‐specific, and thus have been called myomiRs. Our studies, using a conditional knockout strategy, show that microRNAs are essential for proper development and function of the heart. We further demonstrated that miR‐1 and miR‐133 play a vital role in myocyte proliferation and differentiation. Gain‐ and loss‐of‐function studies identify miR‐208a an important regulator of cardiac remodeling in response to stress.The discovery of myomiRs as a previously unrecognized component in the regulation of gene expression adds an entirely new layer of complexity to our understanding of cardiac, skeletal muscle development and function. Investigating myomiRs will not only reveal novel molecular mechanisms of the miRNA‐mediated regulatory network in cardiac and skeletal muscle development, but also raise new opportunities for therapeutic intervention for cardiovascular diseases.
Metabolic engineering of Saccharomyces cerevisiae for alkaloid production
Authors: Smolke Christina Dawn 
Published: June 2021

Natural products or natural‐product inspired molecules comprise most successful drugs. However, these high‐value molecules are difficult to synthesize chemically and are often isolated through inefficient extractions from natural sources. As such, they are increasingly targeted for production by biosynthesis from engineered microorganisms. The budding yeast species Saccharomyces cerevisiae has proven to be a powerful microorganism for heterologous expression of biosynthetic pathways. Yet many challenges are currently faced in engineering yeast strains for the biosynthesis of complex secondary metabolite production. Synthetic biology is advancing the development of new tools for constructing, controlling, and optimizing complex metabolic pathways in yeast.I will describe recent work in engineering yeast as a production host for diverse alkaloid compounds, and in particular the benzylisoquinoline alkaloids (BIAs). Yeast strains engineered to express enzymes from diverse organisms, including plants, bacteria, and humans, have been demonstrated to synthesize numerous intermediates and end‐products in this biosynthetic pathway. In addition, I will describe the development of synthetic biology platforms that are providing new approaches to optimizing complex biosynthetic pathways.
Purified diets are obesigenic, promote insulin resistance and confer sensitivity to chemical colitogens
Authors: Aitken Jesse D , Vijay-Kumar Matam , Srinivasan Gayathri , Gewirtz Andrew 
Published: June 2021

The paradigm that an obesigenic metabolic profile results from excess caloric intake has come under question as a growing number of caveats, especially that predisposition to insulin resistance and obesity is heritable, through epigenetic and microbiotal mechanisms, and self‐perpetuating, as adipose tissue is both a source and sink for inflammatory actors, emerge. As obesity penetrance increases in developing countries on adoption of Western diet and food processing regimes, it seems logical to investigate the obesigenic potential of highly processed, although nominally chow‐equivalent, diets in mice. Naturally sourced chow and purified 10% saturated fat diets were given to 4 week old mice whose weights were followed for 12 weeks at which time metabolic and inflammatory parameters were assessed. Further, chow‐ and purified diet‐fed mice were subjected to chronic and acute models of DSS colitis. We report that purified diets induce weight gain and insulin resistance relative to isocaloric naturally‐sourced chow. Purified diet also induced mild splenomegaly and wasting of intestinal tissues accompanied by increases in neutrophil infiltration, proinflammatory cytokines and acute phase proteins, perhaps reflecting diet‐mediated degradation of barrier function. Purified diet‐fed mice were sensitive to DSS‐induced mortality and weight loss immediately following co‐administration of purified diets.Grant Funding Source : NIH
Adipocytes from obese subjects increase NF‐kB activation in invasive breast cancer cells
Authors: Siriwardhana Nalin , Karwandyar Ayub , Wimalasena Jay , Moustaid-Moussa Naima 
Published: June 2021

Obesity in post‐menopausal women doubles the breast cancer risk and metastasis. Concomitantly, nuclear factor kappa B (NF‐κB) is known to play a significant role in breast cancer cell metastasis. We used a novel three dimensional (3D) co‐culture system with breast cells (non‐cancerous, MCF10A, cancerous, MCF7 and invasive, MDA231) and adipocytes from pre‐ and post‐menopausal women in lean and obese groups. Comparison of cytokine profiles of co‐cultures revealed two‐way interaction of adipocytes and breast cells. Highly significant cytokine changes were reported for post‐menopausal adipocytes and MDA MB 231 co‐culture. Therefore, we assayed the NF‐κB activation effects of lean and obese post‐menopausal adipocytes on MDA MB 231 cells. Media transfer from lean/obese post‐menopausal adipocyte cultures in to growing MDA MB 231 breast cells resulted significant changes in NF‐κB activation pathway genes. This further verified our previous data that obese conditioned media increased the levels of NF‐κB family members (P65, P50, P52, Rel B and Rel C) compared to the lean counterpart. Therefore, our data indicates that adipocytes from post‐menopausal obese women can increase the NF‐κB activation in MDA MB 231 cells. In conclusion, this study suggests that increased breast cancer risk in obese post‐menopausal women may be at least in part due to obesity mediated NF‐κB activation. Support: UTORC, AgResearch and UTGSM.Grant Funding Source : Internal
Effect of (−)‐epigallocatechin gallate on cyclin D1 down‐regulation at the post‐translational level
Authors: Zhang Xiaobo , Baek Seung Joon 
Published: June 2021

The potential anti‐carcinogenic effect of green tea catechins has been well documented, especially for one of the major components, (−)‐epigallocatechin gallate (EGCG). Cyclin D1, an oncogenic protein, has been shown to be up‐regulated in various cancer cells, including colorectal cancer. It has been reported that EGCG inhibited cyclin D1 at the transcriptional and translational levels; however, the detailed mechanisms by which EGCG suppresses cyclin D1 expression have not been elucidated. Our objective was to elucidate the molecular mechanism(s) and biological consequence of EGCG‐induced cyclin D1 down‐regulation in colorectal cancer cells. We examined the effect of EGCG on the expression of cell growth related proteins in colorectal cancer cells. As a result, we found that EGCG inhibited cell growth and induced cell cycle arrest and apoptosis. The expression of cylin D1 and D3, but not cyclin E was down‐regulated, while p21 was up‐regulated in the presence of EGCG. Moreover, the cyclin D1 down‐regulation by EGCG was mediated by the 26S proteasome pathway dependent of glycogen synthase kinase‐3 beta (GSK‐3β). Collectively, EGCG facilitates the proteasomal degradation of cyclin D1, which could, at least in part, be responsible for the anti‐cancer effect of EGCG in colorectal cancer.Supported by: NIH R01CA108975 and The University of Tennessee Center of Excellence in Livestock Diseases and Human Health grantGrant Funding Source: NIH R01CA108975
Change in eating behaviors in a 6 month pilot worksite weight loss intervention
Authors: Batra Payal J , Salinardi Taylor , Robinson Lisa , Saltzman Edward , Roberts Susan , Das Sai K 
Published: June 2021

The eating behavior constructs restraint, hunger and disinhibition may play an important role in successful weight control. However, the extent to which these constructs can be influenced to sustain weight loss during an intervention remains uncertain. The objective of this pilot study was to determine whether a weight loss intervention at worksites would cause significant changes in eating behaviors. A 6‐mo randomized controlled trial was conducted at 4 worksites [2 intervention (I), 2 control(C)] in the Boston metropolitan area. Measures included fasting body weight and eating behavior assessed using the Eating Inventory at baseline and 6‐months. Results were analyzed using an ANCOVA model with baseline scores as covariates. There were significant increases in restraint (I=5.43Â±4.25, C=0.29Â±3.80,p<0.001), decreases in disinhibition (I=−2.5Â±3.63, C=0.66Â±1.85, p<0.001) and hunger scores (I=−2.79Â±3.13, C=0.56Â±2.63, p<0.001) in the I compared to the C group. Within the I group, decrease in hunger is the strongest predictor of weight loss, the model contributing to 32% of the variance (p<0.001) after controlling for gender and site. This is in contrast to previous studies that have shown change in restraint to be the strongest predictor of weight loss. These findings identify reduction in hunger as an important predictor of successful weight loss.Grant Funding Source: HNRCA
High‐dose (4000 IU) vitamin D supplementation improves insulin resistance in obese adolescents
Authors: Belenchia Anthony M. , Tosh Aneesh K , Hillman Laura S , Peterson Catherine A. 
Published: June 2021

Obese adolescents with vitamin D (vit D) deficiency have been observed to have greater body weights and exhibit early signs of insulin sensitivity and higher risk of developing type 2 diabetes. Our objective was to determine the effect of high‐dose vit D supplementation on insulin resistance in this population. Forty‐four male and female patients (age=13.9±2.5 years; BMI Z‐score= 2.52±0.25) were recruited from the University of Missouri‐ Adolescent Diabetes and Obesity clinic and were randomized to receive either placebo or vit D3 (4000 IU/day) as part of their standard treatment for 6 months. At the start, all but three patients were vit D deficient (<20ng/ml) or insufficient (20–29 ng/ml). Within 3 months of supplementation, none of the subjects taking vit D were “deficient”, and by 6 months, 93% had 25‐ hydroxyvitaminD levels considered “sufficient”. Likewise, adolescents receiving vit D had significant improvements in both homeostasis model assessment‐estimated insulin resistance (HOMA‐IR, −1.86 vs +0.22 for placebo; P=0.037); and quantitative Insulin Sensitivity Check Index (QUICKI, +0.017 vs −0.003; P=.036). Correcting the poor vit D status associated with obesity may be an effective and inexpensive adjuvant to treatment of obesity‐related metabolic complications.Grant Funding Source : Support: J.R. Albert Foundation, Inc.
Vitamin D Status in Relation to Metabolic Risk Factors in Older Puerto Ricans
Authors: Jamal-Allial Aziza , Homsi Yamen , Tucker Katherine L 
Published: June 2021

Vitamin D deficiency is a global problem. Several reports suggest an association between plasma 25‐hydroxy vitamin D concentration (25(OH)D) and metabolic risk factors. We examined, corss‐sectionally, the relation between serum 25(OH)D concentration and adiposity and glucose metabolism among 1505 Puerto Rican adults, 484 men and 1058 women aged 45–75 years. Among all participants, body mass index (BMI), glycosylated hemoglobin (HbA1c), insulin resistance (HOMA‐IR), waist circumference (WC) and waist‐to‐hip‐ratio (WHR) showed significant inverse association with plasma 25(OH)D (P<0.05); but diabetes status and insulin concentration did not. After stratification by sex, 25(OH)D was significantly associated with BMI, HbA1c, HOMA‐IR, WC, and insulin concentration (P<0.05) in women. Among men, only HbA1c and WHR showed constant inverse association with plasma 25(OH)D (P<0.05). Women with BMI ≥ 35 or BMI 30–35, respectively, had lower serum 25(OH)D concentrations than women with BMI <25 (P<0.01 and P<0.001 respectively and p‐trend=0.001). In conclusion, lower serum 25(OH)D concentration was significantly associated with adiposity measurements and metabolic risk factors in this population of older Puerto Rican adults living in the Boston area. Longitudinal studies are needed to clarify causal pathways.This study was supported by the National Institutes of Health grants P01 AG023394 and P50 HL105185.Grant Funding Source: NIH
Iron biomarkers identify similar risk factors for iron deficiency but provide different estimates of the national prevalence of iron deficiency and iron‐deficiency anemia in Cameroon
Authors: Engle-Stone Reina , Nankap Martin , Ndjebayi Alex O. , Erhardt Juergen G. , Brown Kenneth H. 
Published: June 2021

Iron status indicators reflect different aspects of iron metabolism. We compared the prevalence and distribution of iron deficiency (ID) and iron‐deficiency anemia (IDA) in a national survey of Cameroonian women and children using plasma ferritin (F), soluble transferrin receptor (sTfR), body iron stores (BIS), and hemoglobin (Hb), with and without adjustments for inflammation. We randomly selected 30 clusters in each of 3 zones (North, South, and Large Cities) and 10 households (HH) per cluster, each with a woman 15–49 y and a child 12–59 mo (n=904 HH). Plasma F and BIS were adjusted for inflammation using C‐reactive protein and α1‐acid glycoprotein. Inflammation was present in 21% of women and 48% of children; 39% of women and 58% of children were anemic. The prevalence of ID ranged from 12–32% among women and 14–68% among children, depending on the iron status indicator, and IDA ranged from 9–19% among women and 12–47% among children. The proportion of anemia associated with ID ranged from 26–50% among women and 21–82% among children. However, the indicators identified similar groups at highest risk of ID and IDA: HH in the North and rural areas and younger children and pregnant women. SES was less consistently related to ID. Research is needed to clarify relationships among iron indicators, particularly during infection, to harmonize global data on ID and IDA.Grant Funding Source : Michael and Susan Dell Foundation, UNICEF
Paraoxonase 1 (PON1) as a marker of short term death in breast cancer recurrence
Authors: Bard Jean-Marie , Jaffré Isabelle , Joalland Marie-Pierre , Classe Jean-Marc , Campone Mario , Bobin-Dubigeon Christine 
Published: June 2021

ObjectiveTo relate paraoxonase (PON1) activity to survival time and short term death in breast cancer recurrence.Design and methodsPON1 activity was measured by its rate of hydrolysis of two different substrates, paraoxon (PON) and phenylacetate (ARE) in 50 patients who experienced disease recurrence for breast cancer. Results were compared between patients surviving more than one year after the analysis (n=22) and those who died within one year (n=28).ResultsIn a logistic regression analysis, ARE was significantly and negatively associated with early death (OR = 0.10 [0.02–0.58], p=0.0109). PON did not reach significance (OR = 0.43 [0.17–1.11], p=0.0826). As assessed by the Kaplan‐Meier method, the survival distributions across quartiles of ARE was significantly different (Log rang test, p=0.0393). The Cox proportional hazards model indicated that quartile 1 of ARE was significantly different from quartile 4 (HR= 5.48 [1.48–20.36], p=0.0110. In a multiple logistic regression analysis model, ARE was independently associated with early death (OR = 0.12 [0.02–0.98], p=0.0476), besides interval time between diagnosis and recurrence (OR = 0.54 [0.27–1.07], p=0.0781) and undernutrition (OR = 3.95 [0.81–19.19], p=0.0883).ConclusionParaoxonase activity may predict survival in patients with breast cancer recurrence.
Formative Research Supports a Change Agent Approach to Prevent Obesity in American Indian Households
Authors: Gadhoke Preety , Christiansen Karina , Rowan Megan , Anliker Jean , Frick Kevin , Gittelsohn Joel 
Published: June 2021

High obesity rates among Americans Indians are associated with environmental factors that influence food and physical activity‐related behaviors. Formative research in Michigan consisted of 98 interviews (workshops, in‐depth, focus groups, and household groups). The AI household is a key influential environment upon health behaviors. Children as change agents can impact household diets and physical activity by “sharing” their learned knowledge from school, and by “encouraging,” “reminding,” and “asking” for healthier foods and to be physically active with them. Adults “listen” to and are “inspired” by children's “energy.” Intervention trials for AI communities will use a novel child as change agent approach for improving health behaviors among adult household members. USDA/NIFA/NRI, Grant #2010‐85215‐20666.Grant Funding Source : USDA/NIFA/NRI, Grant #2010‐85215‐20666
LINEAR GROWTH IN VERY PREMATURE INFANTS IS SIGNIFICANTLY RELATED TO PROTEIN INTAKE
Authors: Berseth Carol Lynn , Harris Cheryl , Mitmesser Susan Hazels 
Published: June 2021

BackgroundWe have previously shown that preterm infants fed human milk fortified with a liquid human milk fortifier (LHMF), which provides approximately 20% more protein than current powder fortifier (Control), have significantly greater linear growth. Previous studies have shown that preterm growth is a function of parenteral protein intake; however, this relationship for enteral protein has not been confirmed.ObjectiveTo assess linear growth as a function of protein intake.MethodsFifty‐six preterm infants (BW ≤1,250 g) fed expressed and/or donor breast milk were randomized to receive Control or LHMF for 28 days. Length and total protein intake (parenteral and enteral) were recorded.ResultsOn study day 28, LHMF fed infants were significantly longer than Control (42.4±0.28 cm vs. 41.2±0.24 cm, p=0.003). There was no difference between groups for total calorie intake (116.0±1.5 kcal/kg/d vs. 119.3±1.3 kcal/kg/d, p=0.113). The change in length in all infants was significantly related to total protein intake (p=0.0077) (see Figure); a similar relationship was not present for nonprotein calorie intake (p=0.12). This relationship was also dependent upon the fortifier consumed (p=0.0327).ConclusionLinear growth in preterm infants reflects protein intake regardless of route of delivery. The better length growth seen in LHMF infants appears to be due to the higher enteral protein it provides.
Exposure to Simulated Microgravity Affects Development of the Skull in Danio rerio
Authors: Franz-Odendaal Tamara Anne , Edsall Sara 
Published: June 2021

To determine how exposure to simulated microgravity (SMG) affects development of the skull, zebrafish embryos were exposed to SMG starting at one of three developmental stages: 10, 12 or 14 hours post‐fertilization. Juvenile and adult fish were analyzed after exposure to SMG using whole‐mount staining and geometric morphometrics. Fish were examined for changes in melanophore surface area and number, in addition to changes in skull morphology. Analyses reveal an overall decrease in the surface area of melanophores and an increase in melanophore number over the period of a week in experimental and control groups; with significant differences in the number of melanophores on the first day after exposure. These effects are short‐term and do not persist in adults. Gross morphological analyses of whole‐mount stained adults, however, identified buckling in several (but not all) craniofacial bones. In conclusion, exposure to SMG affects both skeletal tissues and pigmentation in the head. These results will be discussed in context of germ layer origin. This is the first study examining the long‐term effects of exposure to SMG on zebrafish and provides valuable insight into phenotypic variation.Grant Funding Source : NSERC, Canada; and CSA, Canada
The Trapezius Complex in Mammalia
Authors: Voegele Georgina McKusick 
Published: June 2021

Within Mammalia, the five portions of the trapezius complex ‐ sternomastoideus, cleidomastoideus, clavotrapezius, acromiotrapezius, and spinotrapezius ‐ have been adapted for specializations relating to arboreal, aquatic, fossorial, cursorial, and flying locomotor patterns. Yet despite the diversity of forms, features persist which may give us clues about evolutionary history. This is especially important for the controversial clade Afrotheria, which is based on genetic data but has no unifying skeletal or dental characters and a scanty fossil record. My research indicates that there are several characters of the trapezius complex which unite some members of the Afrotheria. For example, the sternomastoideus originates from the mandible, the clavotrapezius inserts on the sternum rather than the clavicle and has a slip to the pinna, and the acromiotrapezius fuses with the scapular head of deltoideus. There are also several characters of the trapezius complex which some members of Afrotheria share with other mammals. For example, some members of Eulipotyphla also have a bifid acromiotrapezius and a lumbar origin of the spinotrapezius, and the aclavicular Afrotherians share with Artiodactyla the fusion of clavotrapezius and cleidomastoideus with the clavicular head of deltoideus.Grant Funding Source: none
Francisella enters host cells by Clathrin‐mediated endocytosis at a cholesterol rich domain
Authors: Lin Ann E , Kim Youra , Law HT , Nano Francis E , Guttman Julian A 
Published: June 2021

Francisella tularensis are highly infectious bacterial pathogens that cause a type of acute debilitating febrile illness called tularemia. While Francisella reportedly colonize and establish infection in multiple organs, the liver remains as the primary site of infections. Although these infections are responsible for the mortality of 35% of infected individuals if left untreated, the strategies these pathogens use to invade non‐phagocytic cells remain elusive. Therefore, our objective is to examine the subcellular mechanisms these bacteria utilize to infect their hosts. We generated the hypothesis that Francisella co‐opt normal human endocytic machinery to internalize into host epithelial cells. To test this, we developed two in vitro Francisella‐based infection models using murine hepatocyte epithelial cells. By using a combination of pharmacological inhibitors, RNA interference‐mediated protein knock down and protein immunolocalization, we showed that Francisella exploit clathrin and cholesterol dependent mechanisms to gain entry into hepatocytes. We conclude that this is the first study demonstrating the importance and significance of clathrin‐mediated endocytosis to facilitate efficient Francisella invasion into non‐phagocytic cells.Grant Funding Source: CIHR