bluuebunny/crossref_metadata_2025_split huggingface dataset:
PDZ interactions between PHLPP phosphatases and the NHERF scaffold
Authors: Kunkel Maya , Garcia Erin L , Hall Randy A , Newton Alexandra C 
Published: June 2021

The PHLPP family of serine/threonine protein phosphatases plays a critical role in regulating the balance between cell survival and apoptosis. The PHLPP family consists of three members, the N‐terminal alternative splice variants, PHLPP1α and PHLPP1β, and PHLPP2, a separate gene product. All isozymes contain a type I PDZ‐binding motif at their C‐terminus: TPL for PHLPP1 and TAL for PHLPP2. We sought to identify potential PDZ domain‐containing proteins that scaffold these phosphatases in order to elucidate differences in PHLPP1 and PHLPP2 signaling at spatially restricted locations within the cell. Using a proteomic array containing 96 purified PDZ domains, we have identified domains that interact with the 25 C‐terminal residues of PHLPP1 and PHLPP2. Specifically, we have observed that the PDZ ligands of both PHLPP1 and PHLPP2 can interact with the scaffold proteins NHERF‐1 and NHERF‐2. In live cells, addition of the last 10 residues of PHLPP1 or PHLPP2 to cyan fluorescent protein (CFP) is sufficient to relocalize CFP to NHERF‐1 or NHERF‐2. However, NHERF‐dependent relocalization is only observed for full‐length PHLPP2; full‐length PHLPP1 is in a conformation in which the C‐terminus is not available to interact with the NHERF PDZ domains. These results suggest differential signaling by PHLPP2 versus PHLPP1 at the NHERF scaffold.This work was supported by NIH P01 DK54441
Glucagon‐like peptide‐1 signals to PKB and mTORC1 via the activation of the insulin‐like growth factor receptor (IGF1R) in islets of Langerhans
Authors: Mostafa Norhan Mohamed El-Sayed Badr El-Din , Moore Claire E , Herbert Terry P 
Published: June 2021

ObjectivesGlucagon‐like peptide‐1(GLP‐1) stimulates β‐cell proliferation and protects cells against cytokine induced apoptosis via activation of mTORC1 and PKB. However, it is not fully understood how GLP1 receptor activation leads to the activation of PKB/mTORC1 although it has been reported that this is mediated by EGFR transactivation. Therefore, study aims to investigate the transduction pathways by which GLP‐1 regulates PKB/mTORC1 activation.ResultsWe showed that that AG1478 (an EGFR inhibitor), at a dose that effectively blocks EGF‐stimulated Erk phosphorylation, does not affect GLP1‐stimulated PKB or mTORC1 activation. However, diazoxide, an inhibitor of exocytosis, significantly reduced GLP1‐induced PKB and mTORC1 activation. siRNA mediated knock‐down of insulin receptor expression was unable to inhibit GLP1‐stimulated PKB or mTORC1 activation. In contrast, siRNA mediated knockdown of the IGF1 receptor effectively blocked GLP1‐stimulated PKB and mTORC1 activation.ConclusionsAcute activation of PKB and mTORC1 by GLP1 is mediated via the activation of the IGF1 receptor, presumably through the autocrine effect of IGF.
Mechanisms of transformation by the MEK1 mutants K57N and D67N
Authors: Procaccia Shiri , Seger Rony 
Published: June 2021

The MAPK kinase MEK1 is a central component of the Extracellular signal‐Regulated Kinase (ERK) cascade. Its proper function is required for the regulation of a variety of cellular processes. Recently, activating mutations of MEK1 were found in different cancers and shown to be the driver of cellular transformation in these cases. These included mainly the substitutions of Lys57 to Asn (K57N) and Asp67 to Asn (D67N). In order to understand the mechanism of transformation by MEK1 mutants, we undertook to study their signaling properties. Overexpression of both mutants resulted in increased proliferation of cells. Western blot analysis revealed that K57N and to some extent D67N mutant had increased phosphorelation of both their activatory Ser (218 and 222) and also Ser298. Interestingly, the overexpressed mutants only marginally affected the activities of downstream targets, indicating a possible ERK1/2‐independent mechanism of transformation. Indeed, the D67N mutant exhibited different subcellular localization, and was much more abundant in the nucleus, regardless of stimulation. In addition, both mutants resulted in increased phosphorylation of Elongation Factor 2 (EF2). The aberrant cross‐talk with other signaling pathways, the increased phosphorylations and the nuclear localization, are likely to contribute carcinogenesis by these mutants.Supported by grant from the Israel Science Foundation.
PPP1CC2 levels are highly regulated in testis to ensure normal spermatogenesis and male fertility
Authors: Dasgupta Shuvalaxmi , Sinha Nilam , Vijayaraghavan Srinivasan 
Published: June 2021

PPP1CC2 is one of the four isoforms of type 1 serine/threonine protein phosphatase (PP1). PPP1CC1 and PPP1CC2 are two alternatively spliced isoforms of Ppp1cc gene. Targeted deletion of Ppp1cc gene causes male infertility; females are normal suggesting that PPP1CC isoforms are indispensable in testis.To determine the specific role of the two PPP1CC isoforms, we transgenically expressed PPP1CC2 driven by the testis specific Pgk2 promoter. The results show that fertility as determined by sperm number, morphology and motility is restored in Ppp1cc null mice in lines where transgene expression was relatively high.The goal of the present work was to determine if overexpression of PPP1CC2 in wildtype (+/+) testis affected spermatogenesis and sperm function. Wild type mice were crossed with Ppp1cc2 transgenic mice (+/−; Tg+) to derive lines with three copies of Ppp1cc2 gene (two endogenous and one transgenic copy; +/+, Tg+). Analysis of +/+;Tg+ adult mice show that they are phenotypically indistinguishable from +/+ and +/− control littermates in terms of sperm morphology, motility and number. Western blot analysis showed there was no increase in PPP1CC2 levels despite a dramatic increase in Ppp1cc2 mRNA levels in testis of +/+;Tg+ compared to +/+ mice. We suggest that homeostatic mechanisms operating post‐transcriptionlly limit the steady state amounts of testis PP1CC2 levels. (NIH ……..)
Characterization of Noni component damnacanthal in anti‐tumorigenic activity
Authors: Nualsanit Thararat , Rojanapanthu Pleumchitt , Gritsanapan Wandee , Baek Seung Joon 
Published: June 2021

Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases including cancer. In this report, we examined systematic approaches on the cancer suppressing capability of damnacanthal in colorectal tumorigenesis. Damnacanthal exhibits cell growth arrest as well as caspase activity induction in colorectal cancer cells. We also examined several potential target proteins and found that the pro‐apoptotic protein Nonsteroidal anti‐inflammatory activated gene‐1 (NAG‐1) is highly induced. Subsequently, we have found that damnacanthal also enhances transcription factor C/EBPβ, which controls NAG‐1 transcriptional activity. Blocking of C/EBPβ by shRNA results in the reduction of NAG‐1 expression as well as caspase activity in the presence of damnacanthal. Taken together, these results indicate that damnacanthal increases anti‐tumorigenic activity in human colorectal cancer cells, and C/EBPβ plays a role in damnacanthal‐induced NAG‐1 expression.This work was supported by NIH grant‐R01CA108975 and University of Tennessee Center of Excellence in Livestock Diseases and Human Health grant. Financial support for TN by the Royal Golden Jubilee PhD Program (PHD/0159/2546), Thailand.
Pretreatment with morin ameliorates lipid profiles in isoproterenol‐induced myocardial infarction in wistar rats
Authors: Govindasamy Chandramohan , Alnumair Khalid S , Alsaif Mohammed A 
Published: June 2021

ObjectiveLipids and lipoproteins play an important role in the pathology of myocardial infarction. In the present study evaluated the flavonoid‐morin on lipid profiles in isoproterenol (ISO) induced myocardial infarction in rats.MethodsMale albino Wistar rats were pretreated with morin at the optimum dose of 40 mg/kg daily for a period of 30 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected in rats at an interval of 24 h for 2 days.ResultsIsoproterenol caused a significant increase in the activity of total, ester, free cholesterol, triglycerides (TG), free fatty acids (FFA) and phospholipids (PL), low density lipoprotein‐cholesterol (LDL‐C) and very low density lipoprotein‐cholesterol (VLDL‐C) in serum and decreased activities in heart phospholipids, serum high density lipoprotein‐cholesterol (HDL‐C) levels. Pretreatment with morin at 40 mg/kg dose blocked these changes to normality which proved their antihyperlipidemic action. Histopathology of heart of ISO administered rat pretreated with morin showed normal myocardium.ConclusionThese findings provided evidence that morin was found to be protecting the myocardium against ischemic insult and the protective effect could attribute to its antihyperlipidemic activities.Source: The authors would like to express their gratitude to the National Nutrition Policy Chair, King Saud University, Riyadh, Saudi Arabia for their generous financial support.
Do mother's self‐reported reasons for introducing solid foods vary by age at introduction and socio‐demographic characteristics?
Authors: Clayton Heather Breeze , Scanlon Kelley , Perrine Cria , Li Ruowei 
Published: June 2021

Early solid food introduction may shorten breastfeeding duration and increase risk of adverse health outcomes. We analyzed data from 1,117 women who participated in the Infant Feeding Practice Study II, a longitudinal study of mothers and their infants, to describe mothers’ reasons for introducing solid foods. From a 12‐ item list of reasons, we calculated the percentage of women who indicated a reason for introducing solid food as “important” and used multiple logistic regression to assess whether reasons varied by socio‐demographic characteristics and infant age at introduction.The four most common reasons for introducing solid foods were: (1)“my baby was old enough to begin eating solid food” (91%), (2)“my baby wanted the food I ate or in other ways showed an interest in solid food” (71%), (3)“I wanted to feed my baby something in addition to breast milk or formula” (65%), and (4)“a doctor or other health care professional said my baby should begin eating solid food” (62%). In multivariable models, age at introduction to solid foods varied significantly for reasons 1,2 & 4 while socio‐demographic characteristics varied significantly for reasons 2,3 & 4. Women's reasons for introducing solid foods varied significantly by age at introduction, and by socio‐demographic characteristics.
Workplace accommodations to support breastfeeding in New Jersey
Authors: Gaits Susan , Bai Yeon , Wunderlich Shahla M. 
Published: June 2021

Returning to an unsupportive work environment has been identified as a major reason for avoidance or early abandonment of breastfeeding among working mothers. The purpose of this study was to examine the nature and extent of accommodations offered to breastfeeding employees among New Jersey employers (hospitals, education, and retail) since the Federal Reasonable Break Time for Nursing Mothers law enactment. Respondents (N=51) completed a 22‐item online questionnaire during Fall 2011. Level of support was measured by the amenities of the lactation room (furnishings, proximity to running water, and breast pump), then transformed to a composite “amenity score” ranging from 0 to 3 (superior). The support level was compared by type of organization: hospital (n=34) vs. non‐hospital (n=17). The amenity score of hospitals, although moderate, was higher than non‐hospitals (1.44 vs. 0.45, p=0.002). Hospitals were more likely to have separate lactation room, (62 vs. 40%, p=0.06), and higher awareness of the federal law (55 vs. 14%, p=0.06) and their own breastfeeding policy (62 vs. 21%, p=0.003). All employers need to improve the level of lactation support regardless of the type of organization.Grant Funding Source : Montclair State University
Prevalence of Folate deficiency and Folate Deficiency Anemia in REGARDS 2003–2007
Authors: odewole oluwaseun , Zakai Neil , Judd Susan , Berry Robert , Qi Yan Ping , McClellan William , Williamson Rebecca , Demilade Adedinsewo , Oakley Godfrey 
Published: June 2021

ObjectiveWe aim to determine the prevalence of folate deficiency and folate deficiency anemia within the REGARDS cohort post flour fortification.MethodsThe Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a prospective population‐based cohort that is comprised of half African‐American and half white participants aged ≥50. We measured serum folate levels of 1547 REGARDS participants, we defined serum folate concentrations <3 ng/mL as deficient, anemia by WHO and age, sex, race specific criteria; Folate deficiency anemia as the presence of folate deficiency and anemia as previously defined.ResultsWe found a mean hemoglobin level of 13.6g/dL; prevalence of anemia was 15.9%; mean serum folate of 14.6ng/mL and two (0.13%) participants were folate deficient. Both participants are African American females with markedly elevated C reactive protein levels, but normal serum B12 levels. The prevalence of folate deficiency anemia in the sample was 0.06%.ConclusionThere is negligible folate deficiency anemia in the post fortification era. Thus, in addition to being instrumental in the decline of neural tube defects, folic acid fortification has also resulted in diminishing the prevalence of folate deficiency anemia in the US.Grant Funding Source: none
Choline metabolism biomarkers predict the risk of metabolic unfitness among young men
Authors: Yan Jian , Winter Lilia B. , Burns-Whitmore Bonny , Vermeylen Francoise , Caudill Marie A. 
Published: June 2021

To test the hypothesis that plasma choline metabolism biomarkers, alone and together with genetic determinants of one carbon (1‐C) metabolism, predict metabolic unfitness associated with a lipid overload (i.e. obesity), a cross‐sectional analysis was conducted involving 249 Mexican American men with a median age of 22 y. Circulating concentrations of choline, betaine, folate, metabolic unfitness indicators (i.e. lipid panel and liver enzymes), and polymorphisms of 1‐C metabolizing genes (i.e. MTHFD1 G1958A) were assessed. Bivariate partial correlation tests and multivariate regression models were performed in data analysis. Plasma choline positively and plasma betaine negatively associated with body mass index (BMI) with lower plasma betaine observed in men whose BMI > 25.8 kg/m2 (cohort median). In age‐ and BMI‐adjusted regression models, plasma betaine associated positively with serum HDL‐cholesterol. Further, plasma betaine associated negatively with serum alanine aminotransferase (ALT) among men with serum folate < 14.5 ng/mL (cohort median) or among men with at least one copy of MTHFD1 1958A allele. In sum, these data demonstrate that choline metabolism markers predict the risk of metabolic unfitness and support the need to investigate the potential therapeutic benefits of choline/betaine on metabolic fitness.Grant Funding Source : NIH Grant #S06GM053933 and California Agriculture Research Initiative
Hepatoprotective Activities of Black Soybean in High Cholesterol Diet‐induced Non‐alcoholic fatty liver disease
Authors: jung ji-hye , cho hyun-sook , liu yanan , kim hyun-sook 
Published: June 2021

Non‐alcoholic Fatty Liver Disease(NAFLD) is characterized by an increase in intra‐hepatocellular triglycerides, which is not due to alcohol. This study investigated the effect of black soybean supplementation on high cholesterol diet induced NAFLD. Mice were divided into five groups: normal control(NCD), high cholesterol control(HCD), and the high cholesterol diet supplemented with black soybean powder(1B‐HCD:1%, 2BHCD: 2%, 4B‐HCD:4%). Blood glucose, insulin, lipid profiles, adiponectin, and malondialdehyde(MDA) were determined. Blood glucose and insulin in HCD(163.2mg/dl, 3.07μIU/ml) were higher than in NCD(100.0mg/dl, 1.62μIU/ml), reducing in all experimental groups(129.2mg/dl, 1.76μIU/ml; 98.6mg/dl, 2.30μIU/ml; 113.7mg/dl, 2.29μIU/ml). Total cholesterol and triglyceride were only decreased in 4B‐HCD compared to HCD. Adiponectin was significantly decreased in HCD(6.68ng/ml), while increased in experimental groups(8.13ng/ml; 8.89ng/ml; 9.12ng/ml). MDA was dropped in all experimental groups(20.04μM; 33.89μM; 15.89μM), compared to HCD(35.96μM). The results indicate that supplementation of black soybean may improve lipid profiles and oxidative damage in NAFLD. This work was supported by SRC and BK 21.Grant Funding Source: Brain Korea 21
Adipose tissue gene expression in adult rats fed with highfructose diet. Effects of EPA supplementation
Authors: Leray Véronique , Jonchère Camille , Zaman Muhammad-Quaid , Nguyen Patrick 
Published: June 2021

The study of the expression of genes involved in obesity‐related disorders has been promising for a better understanding of the links between components of the metabolic syndrome.Our aim was to measure the effects of a high‐fructose diet on metabolic status and on the mRNA expression of several genes involved in insulin‐signaling pathway, and glucido‐lipid metabolism in rats, and to assess the effects of EPA supplementation.Rats were given for 10 wk either a control or a high‐fructose diet (65% fructose cal), supplemented or not with EPA (120 mg/d). At the end of the 10‐wk period, body composition and IS were assessed, lipid plasma were assayed, and mRNA expression of insulin receptor, IRS1, perilipin, leptin, ACC, FAS, HSL, LPL, GLUT, TNFα, SREBP‐1c, PPARγ was semi‐quantified from adipose tissue biopsies.In high‐fructose rats, IS tended to be lower, plasma triglyceride level tended to be higher, and Glut4 expression was lower than in control rats. In rats fed with high‐fructose diet plus EPA, plasma NEFA concentration was lower, and PPARγ and FAS mRNA levels were higher than in rats fed with unsupplemented high fructose diet.Our results show change in Glut4 expression in rats fed highfructose diet that could reflect an alteration of glucose uptake, and impair systemic IS. They also show that EPA could stimulate transcription of PPARγ and its target gene FAS that could account for its beneficial effect on lipidemia.
Comparison of a higher protein yogurt vs. other commonly consumed afternoon snacks on time to meal request
Authors: Ortinau Laura C , Culp Julie M , Hoertel Heather A , Douglas Steve M , Leidy Heather J 
Published: June 2021

PurposeTo determine whether an afternoon snack of higher‐protein yogurt, (14 g protein, HPY) delays the onset of eating vs. other commonly consumed eucaloric snacks varying in macronutrient content, including Pretzels (P), Crackers (Cr), Chocolate (Ch), and No Snack (NS).MethodsUsing a randomized crossover design, 23 women (age 27 ± 1y; BMI 23.4 ± 0.6) were acclimated to each snack for 3 consecutive days. On day 4, the participants consumed a standard breakfast, at home, and came to our facility 1 hr prior to their habitual lunch time. A standard lunch was provided followed by their respective snack (160 kcal) consumed 3 h post‐lunch. Subjective appetite was assessed by VAS completed every 30 min throughout the afternoon until dinner was voluntarily requested.ResultsNS led to an earlier dinner request time (2:09 ± 0:37 h) vs. HPY (2:43 ± 0:39 h; p<0.001), P (2:40 ± 0:31 h, p<0.001), and Cr (2:24 ± 0:38 h p=0.08), but not Ch (2:18 ± 0:39 h post‐snack). Between snacks, HPY and P had a greater delay in eating vs. Ch (p<0.05, both); HPY also led to a greater delay vs. Cr (p=0.09).ConclusionsA higher‐protein afternoon yogurt snack delayed subsequent eating vs. crackers and chocolate while a pretzel snack delayed subsequent eating longer than chocolate, suggesting that macronutrient content and sensory characteristics of snacks influence energy intake regulation. Funded by: General Mills, Inc.
Effects of protein quantity and source (animal versus plant) on appetite and plasma amino acid responses in energy‐restricted subjects
Authors: Wilson Hailey Kay , Armstrong Cheryl LH , Hogan Jacqueline A , Campbell Wayne W 
Published: June 2021

This study was designed to assess appetitive and plasma amino acid (AA) responses to protein (P) intakes that span the acceptable macronutrient distribution range and predominantly from meat vs. plant sources. Thirty‐four overweight/obese subjects (53±12 y, BMI 30.8±2.6 kg/m2 mean ± SD) were randomly assigned to consume diets with 750 kcal/d below energy need and beef/pork (5M:12F) or soy/pulses (6M:11F). All subjects randomly completed 3, 28d trials with the diets containing 10, 20 or 30% energy from P. On day 28 of each trial, subjects consumed a trial‐specific test meal and rated hunger and fullness before and 25, 60, 120, 180 and 240 min after eating. AAs were measured in 5 subjects each from the two P source groups. Postprandial (PP) branched chain, essential, and large neutral AA and leucine (weighted averages) were higher for beef/pork vs. soy/pulses (p<0.05) and progressively higher with increasing P intake (p<0.01). PP hunger was lower and fullness was higher than fasting (p<0.001). The hunger response was greater for 30 vs. 20 and 10 % P, whereas P quantity did not affect fullness. Protein source did not affect hunger or fullness. PP hunger and fullness responses were not related to PP AA responses. Higher protein intake from meat or plant sources promotes reduced hunger, unrelated to differential plasma amino acid responses to feeding.Support: The Beef Checkoff, National Pork Board, and NIH RR025761Grant Funding Source: The Beef Checkoff, National Pork Board, and NIH RR025761
The Impact of Dietary Glycemic Load and Physical Activity on Weight status of Healthy College‐Aged Female Students in Oman
Authors: Waly Mostafa , Ali Amanat , Al-Nassri Amira , Kilani Hashem A. 
Published: June 2021

BackgroundThe dietary glycemic load (GL) score for an entire day is calculated as the sum of the GL for all consumed food servings.ObjectiveThe following study was conducted to correlate the GL of all meals served for female students and physical activity, with their weight gain/loss status for an entire period of 3 months.Methods200 female students with the same age (18–25 years) living in campus at Sultan Qaboos University (SQU), were randomly recruited for this study. They were all healthy and free of any chronic diseases, as confirmed by biochemical analysis and medical history. The dietary food intake data was measured using semiquantitative food frequency questionnaires through a personal interview with the investigators. Anthropometric measurements (weight, height and waist, hip circumferences) and physical activity level were also evaluated.ResultsOur results show that the study subjects are consuming low glycemic load foods and maintain a normal body mass index (BMI) (<25). Waist to hip ratios values were <1. They were having a comparable moderate level of physical activity.ConclusionOur study indicates that the meals served inside the SQU campus are of low GL and it was a major determinate of the weight status for the female students attending SQU independent of their dietary habits, physical activity and cultural differences.