bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bbs1 gene is required for wound healing (216.5)
Authors: Guo Deng Fu , Starks Rachel , Sheffield Val , Rahmouni Kamal 
Published: June 2021

Bardet‐Biedl syndrome (BBS) is a pleiotropic autosomal recessive disorder associated with several features including obesity, polydactyly, retinal degeneration, hypogenitalism, leaning difficulty and renal dysfunction. Mice bearing an M390R mutation in Bbs1 gene (which a common mutation in human BBS) recapitulates many BBS phenotypes including obesity and hypogenitalism. However, the role and contribution of Bbs1 gene to cell migration and tissue repair remains unclear. Using wound healing assays, we found that cultured mouse embryonic fibroblasts (MEFs) derived from Bbs1M390R knock‐in mice have severely compromised migratory ability compared to the MEF derived from wild type mice. Activation of AKT by platelet‐derived growth factor‐AA (PDGF‐AA) was also markedly reduced in Bbs1M390R MEF, suggesting that decreased PDGFRα signaling contributes to the migratory defects. Immunofluorescence microscopy analysis with acetylated α‐tubulin showed that both wt and BBS1‐Ki MEFs form primary cilia. The primary cilia were oriented towards the leading edge of the wound in wt MEFs. In marked contrast, primary cilia of BBs‐KI MEFs appeared randomly positioned and lacked an axis of orientation towards the edge of the wound. Furthermore, in vivo wound healing assays showed defects in Bbs1M390R knock‐in mouse compared to control littermates. These findings demonstrate that the Bbs1 gene is required for migration and tissue repairs.Grant Funding Source: NIH and AHA
Drugs and the brain, the MOOC (221.2)
Authors: Lester Henry , Cohen Bruce 
Published: June 2021

How does a MOOC differ in value and impact from previous “distance‐learning” technologies? (1) A major additional possibility is the online community that springs up around the course. “Drugs and the Brain” brought some people with real‐life interest in drug mechanisms, and others with detailed scientific experience. Quantifying the letter group: of the students who finished the 2012‐2013 course and earned “statements of accomplishment”, ~ 10% of the students had PHD degrees and 7% had MD degrees, and ~ 7% had professional degrees in pharmacy. This online community requires detailed curation, moderation, and judgment. For the 2013‐2014 rendition, we plan to have two undergraduate TA's as curators. (2) A secondary possibility is the concept of instantaneous feedback on exams and quizzes. This can also be incorporated in previous technologies.What are limitations of the MOOC? (1) After all limitations in bandwidth and technology have been overcome, “internet time” will still be constrained by the fact that the world is round. The instructor will be asleep when some students want to communicate, and vice‐versa. (2) The course staff must invest formidable effort to optimize the learning experience. In this area, we include analyzing quiz responses, clicks, etc. We also include human evaluation of essays and other student responses. These are both wonderful problems, in the sense that we have too much data!
Selective autophagy in the cellular stress response (237.3)
Authors: Cuervo Ana Maria 
Published: June 2021

Our group is interested on a selective form of inducible autophagy, known as chaperone‐mediated autophagy (CMA) and its connections with aging and disease.Substrate proteins for CMA are delivered to the lysosomal lumen for degradation by directly crossing the lysosomal membrane. This process is mediated by a set of cytosolic and lysosomal chaperones and by a receptor protein at the lysosomal membrane, the lysosome‐associated membrane protein type 2A (LAMP‐2A). The limiting step of CMA is the binding of substrates to LAMP‐2A and levels and organization of LAMP‐2A at the lysosomal membrane underlie the molecular basis for the regulation of CMA. This pathway is active in most cell types in mammalians but its activity varies depending on cellular conditions. In recent years, to gain a better understanding of the physiological role of this pathway we have developed a transgenic mouse models with compromised CMA in different organs. These studies have provide unique insights on the consequences of CMA malfunctioning in the pathogenesis of detrimental human pathologies, such as cancer, neurodegenerative and metabolic diseases.In this talk, I will describe some of the recent findings on the molecular effectors and regulators of CMA, on the physiological relevance of CMA and the contribution of its malfunctioning to disease.This work is supported by grants from NIH/NIA and NIH/NIDDK
Burkinabe infants given small quantity lipid‐based nutrient supplements and illness treatment in infancy score higher in motor, language, and personal‐social development (251.1)
Authors: Prado Elizabeth , Abbeddou Souheila , Jimenez Elizabeth , Somé Jérôme , Ouédraogo Zinewendé , Vosti Stephen , Dewey Kathryn , Hess Sonja , Ouédraogo Jean‐Bosco , Brown Kenneth 
Published: June 2021

Conception to age two years is a crucial period for brain growth and development of motor, cognitive, and socio‐emotional skills. Many children in developing countries fail to reach their developmental potential in these areas. Small‐quantity lipid‐based nutrient supplements (SQ‐LNS) during infancy may improve these aspects of development, which depend on adequate nutrition. Zinc is a key nutrient, which affects brain development through its role in DNA and RNA synthesis and macronutrient metabolism.In a partially masked, placebo‐controlled, randomized trial, communities in rural Burkina Faso were assigned to intervention (IC) or non‐intervention communities (NIC). 2469 eligible IC children were randomly assigned to receive 20g LNS/day with varying amounts of zinc, and treatment of malaria and diarrhea from 9‐18 months of age. Children in NIC (n=797) did not receive any intervention during the same period. Motor, language, and personal‐social development was assessed at 18 months in a subgroup (n=747 IC; n=376 NIC).Children in IC scored 0.33 SD higher in motor, 0.33 SD higher in language, and 0.30 SD higher in personal‐social development than children in NIC. Compared to NIC 52%, 45%, and 60% fewer children in IC were in the lowest decile of motor, language, and personal‐social scores, respectively. Children who received different amounts of zinc in LNS (0 or 10 mg) or a tablet (5 mg) did not differ significantly in 18‐month motor, language, or personal‐scores.Providing SQ‐LNS daily with or without zinc along with malaria and diarrhea treatment significantly improved motor, language, and personal‐social development in young Burkinabe children.Grant Funding Source: Bill & Melinda Gates Foundation
Socioeconomic influences moderate the relation between the size of food‐based activity spaces and body mass index (255.6)
Authors: Scully Jason , Moudon Anne , Hurvitz Phil , Cook Andrea , Aggarwal Anju , Drewnowski Adam 
Published: June 2021

Objective: To investigate socioeconomic influences on the association between food‐based activity spaces and body mass index.Background: Activity space (AS), comprising all the places that people visit in a given period of time, is one measure of exposure to the built environment. Decomposing AS by activity type allows researchers to examine agent‐environment interactions and their impacts on health. Food‐based activity space (FBAS), defined as the places where people purchase food, is a subset of AS.Methods: The Seattle Obesity Study II used address‐based sampling and survey methods to recruit a population‐based longitudinal cohort of 516 male and female King County adults. All participants completed behavioral, dietary and health questionnaires, maintained travel logs for 7 days and were issued GPS tracking devices for 7 days. Both AS and FBAS were represented by convex hulls generated from GPS points corresponding to times in travel logs when subjects recorded food shopping or visiting a supermarket.Results: AS was significantly linked to diverse socio‐demographic measures including education, income, employment, number of cars, commuting distance, and number of children in the household. A small correlation between average FBAS area and BMI (r=0.17, p<0.01) was found.Conclusions: This relation may be moderated by socio‐demographic variables affecting AS. Lower FBAS may limit access to healthier foods by lower‐income participants, whereas higher income participants have greater AS areas and therefore may have more options.Grant Funding Source: NIH grant R01 DK076608‐06
Antenatal care and counseling measures increase iron and folic acid receipt among pregnant women in Bihar, India (256.3)
Authors: Wendt Amanda , Young Melissa , Stephenson Robert , Webb Girard Amy , Ramakrishnan Usha , Martorell Reynaldo 
Published: June 2021

In Bihar, India maternal anemia is a public health problem. Using District Level Household Survey data (2007‐08), we used logistic regression to examine associations between ANC practice and counseling, and any IFA receipt, adjusting for covariates. We created two 3‐level variables to describe ANC quality using 9‐point scales assigning credit to activities that are part of routine ANC practice (e.g. measuring weight, height, blood pressure) and counseling (e.g. advice on nutrition, breastfeeding, cleanliness). The women (n=12,515) were 15‐49 years old (mean: 25.5 years), 38% received any IFA, 9% consumed any IFA for 90+ days, 22% received 5‐9 ANC practices, and 22% received 5‐9 ANC counseling topics.We found women reporting 5‐9 and 1‐4 ANC practices completed vs. none (AOR: 4.4, 95% CI: (3.8, 5.0); AOR: 2.7; 95% CI: (2.5, 3.0), respectively) were more likely to receive any IFA during their last pregnancy. The adjusted models also revealed that women who reported 5‐9 and 1‐4 vs. no ANC counseling topics addressed (AOR: 2.2, 95% CI: (1.9, 2.5); AOR: 1.7, 95% CI: (1.6, 1.9), respectively) were also more likely to receive IFA. Education, wealth index, and number of ANC visits were also positively associated (p<0.05) with IFA receipt. Our findings indicate that ANC quality measures are significantly associated with prenatal IFA receipt even after controlling for number of ANC visits and socio‐demographic characteristics.Grant Funding Source: Funding support provided by a BMGF grant through a subcontract with CARE‐India
Qualitative evaluation of interactive features in HOT (Healthy Outcomes for Teens) Project website (262.4)
Authors: Muzaffar Henna , Chapman‐Novakofski Karen , Castelli Darla 
Published: June 2021

The objective was to identify the adolescents’ perceived usefulness of incorporating different interactive features; and also to assess any gender differences for preference of interactive features on the intervention website. An iterative process developed the questions focused on internet use, ease of using the intervention site, general content/language, preference for interactive features and reading. Nine focus groups (19 boys, 18 girls) were conducted and the data was analyzed using content analysis, inductive development, and negative case analysis. Majority (81%) thought website was easy to use (wording, information and navigation); 19% thought some words were complex. Preference of the interactive features was videos (68%), games (62%), pictures (41%) and voiceovers (20%). Majority (70%) thought nothing was distracting. Four themes emerged: 1) ‘preference for computer over classical classroom’ with subcategories familiarity, fun, and learn at your own pace; 2) ‘reinforcements’; 3) ‘distractions’; 4) ‘gender evaluations’. Conclusion: Internet based interventions were perceived more favorably by the adolescent population than traditional classroom instruction. The majority of the interactive features were perceived as reinforcements except Google maps and seeing rating of friends. Future work should evaluate concepts learned more fully when interactive features included.Grant Funding Source: Funding: American Dietetic Association, National Soybean Laboratory, University of Illinois Extensio
Novel alkylresorcinol metabolites in human urine as potential exposure biomarkers for whole grain wheat and rye intake (270.6)
Authors: Sang Shengmin , Zhu Yingdong , Shurlknight Kelly 
Published: June 2021

Biomarkers of dietary intake are prominent tools in nutritional research. Alkylresorcinol (AR) metabolites, 3,5‐dihydroxybenzoic acid (3,5‐DHBA) and 3‐(3,5‐dihydroxyphenyl)propanoic acid (3,5‐DHPPA), have been proposed as exposure biomarkers of whole grain (WG) wheat and rye intake. However, the profile of AR metabolites is not fully understood. The aim of this study was to investigate the metabolism of ARs in mice and in humans, while further determining urinary pharmacokinetics of the novel AR metabolites to explore their potential as biomarkers of WG wheat intake. Utilization of LC‐MS approach resulted in ten AR metabolites (1‐10) identified in mice and in humans, including three phenolic acids and seven of their phase II conjugates. Among them, two novel metabolites were discovered, 5‐(3,5‐dihydroxyphenyl)pentanoic acid (3,5‐DHPPTA) and 2‐(3,5‐dihydroxybenzamido)acetic acid (3,5‐DHBA glycine). The structures of these two metabolites were confirmed by comparing with authentic standards synthesized in house. In the pharmacokinetic study, a group of twelve volunteers followed a polyphenolic restricted diet for 4 d before ingesting WG wheat bread containing 61mg ARs. Urine samples were collected for 32 h, and AR metabolites were quantified with HPLC‐CEAD. The mean urinary excretion rates and mean t1/2 of 3,5‐DHPPTA, 3,5‐DHBA glycine, 3,5‐DHBA and 3,5‐DHPPA at each time point were determined. Our results suggest that 3,5‐DHPPTA and 3,5‐DHBA glycine may be utilized in combination with 3,5‐DHBA and 3,5‐DHPPA as potential biomarkers to increase the accuracy of recording WG wheat and rye intake in epidemiologic studies. Further validation of 3,5‐DHPPTA and 3,5‐DHBA glycine as potential biomarkers is warranted.Grant Funding Source: 1This work was partially supported by funding from USDA‐NIFA grant 2012‐38821‐20012 to S. Sang.
Solving large and difficult structures with less experimental data (346.1)
Authors: Levitt Michael 
Published: June 2021

Complexes of protein and nucleic acid molecules are the major machines of living cells. Solving their structures is hard so we generate millions of models that are examined against data from cross‐linking mass spectrometry, cryo‐electron microscopy and X‐ray crystallography.Our methods are developed on Eukaryotic group II Chaperonin CCT, a 0.95 megaDalton (mD) complex. In eukaryotes, 8 different genes encode the subunits of this ATP‐powered nanomachine; sequence similarity made the 40,320 (8 factorial) possible arrangements indistinguishable in previous cryo‐electron microscopy and crystallographic analysis.We used cross‐linking, mass spectrometry (XL‐MS) and combinatorial homology modeling. After using mass spectrometry to identify 63 cross‐linked pairs, we construct all 40,320 homology models of the TRiC particle. By comparing each model with the cross‐link set, we discovered that one model is significantly more compatible than any other model.Next, we re‐examine the 3.8 Å resolution X‐ray data of yeast CCT. Our method of R‐Value Exploration tests all 2,580,460 possible models. This unbiased analysis singles out with overwhelming significance one model. This models refines to a lower R‐free than other models Our structure reveals details of the unique conformation of each subunit, and suggests a mechanism of action.For a new system, we combine our methods with cryo‐EM to determine the arrangement of subunits of a complete, 1.5 mD, 32‐protein, RNA polymerase II (pol II) transcription pre‐initiation complex (PIC). Promoter DNA associates with the general transcription factors (GTFs) suspended above the pol II active center cleft. DNA‐pol II interaction occurs only after promoter melting.
Metformin ameliorates diet‐induced hepatic steatosis and inflammation without altering adipose phenotype (37.1)
Authors: Woo Shih‐Lung , Xu Hang , Li Honggui , Guo Xin , Guo Ting , Qi Ting , Huo Yuqing , Wu Chaodong 
Published: June 2021

Non‐alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and inflammation, and is closely associated with obesity. We examined the effects of metformin on hepatic steatosis and inflammation to elucidate the possible protective mechanisms of metformin actions. Wild‐type C57BL/6J mice were fed a high‐fat diet (HFD) for 12 weeks and treated with metformin (150 mg/kg/d) orally for the last four weeks of HFD feeding. We found that metformin improved glucose tolerance and insulin sensitivity, and decreased liver weight and hepatic steatosis but not adiposity of HFD‐fed mice compared with controls. Additionally, metformin increased the phosphorylation of liver AMP‐activated protein kinase (AMP) and decreased the phosphorylation of liver c‐Jun N‐terminal kinase 1 (JNK1) and the mRNA levels of lipogenic enzymes and proinflammatory cytokines. These changes were not observed in adipose tissue. In cultured hepatocytes, metformin increased AMPK phosphorylation and decreased fat deposition and inflammatory responses. In cultured macrophages, metformin partially blunted the stimulatory effects of lipopolysaccharide on JNK1 and nuclear factor kappa B p65 phosphorylation and cytokine expression. Thus, metformin protects against NAFLD largely through direct effects on decreasing hepatocyte fat deposition and on inhibiting inflammatory responses in both hepatocytes and macrophages.Grant Funding Source: Supported by ADA, AHA, NIH
Effects of oat β‐glucan on bile salts absorption across porcine intestinal mucosa using Ussing chamber system (372.4)
Authors: Gunness Purnima , Michiels Joris , De Smet Stefaan , Vanhaecke Lynn , Gidley Mike 
Published: June 2021

Soluble dietary fibres (SDFs) such as oat β‐glucan decrease blood triglycerides and cholesterol. The current lead hypothesis is that this is caused by slowing the re‐absorption of bile salts (BS), possibly by SDF causing an increase in the barrier properties of the unstirred water layer lining the epithelium of the small intestine (SI) by adhering and/or penetrating between the microvilli, thus hindering the uptake of BS. Pigs used as a human model were fed on a control diet (n=6) and a diet containing 10% oat βG (n=6) for 27‐29 d. The SI was sectioned into proximal, mid jejunum and terminal ileum. Each section was prepared and mounted in triplicate into 18 Ussing chambers. Glycodeoxycholate (GDC) and fluorescein isothiocyanate‐labelled dextran (FITC‐dextran (4kDa), to check for tissue integrity) with or without oat βG were added to the mucosal side of the chambers and samples for GDC and FITC‐dextran analyses taken from the serosal side, every 20 min for 80 min. Fresh tissue and tissues after diffusion experiment in the Ussing chambers were fixed for microscopic comparison. The preliminary GDC results show that (1) there is a decrease in the amount of GDC diffusing across the epithelium with the βG diet compared to the control diet, (2) ileal passage is different to passage across the jejunum, and (3) added βG to the mucosal side causes a reduction in the absorption of GDC in the terminal ileum of pigs from the control diet and a reduction in both the proximal jejunum and terminal ileum for tissues from the βG diet. The Ussing chamber seems to be a useful system to test hypotheses on how SDF reduces the diffusion of BS across the epithelium of the SI and thereby helps to understand the mechanisms and properties of SDF required for lipid management and consequent reduction in risk for cardiovascular disease.Grant Funding Source: Supported by ARC Centre of Excellence in Plant Cell Walls
Genistein promotes a gene expression profile characteristic of brown rather than white adipocytes and increases Sirt1 expression in mouse NIH3T3‐L1 cells (372.7)
Authors: Aziz Sadat , Wakeling Luisa , Hesketh John , Ford Dianne 
Published: June 2021

Various possible benefits have been attributed to the dietary isoflavone genistein. In common with resveratrol, which may act via sirtuin 1 (Sirt1), these benefits include protection from diet‐induced obesity. We thus aimed to determine if genistein affected adipogenesis and/or Sirt1 expression using a cell culture model.NIH3T3‐L1 cells were differentiated into adipocytes (from 48 h post‐confluence, taken as day 0) in the presence or absence of genistein. Gene expression was measured by RT‐qPCR.A low concentration of genistein (10 µM) and/or shorter exposure (days 0‐12) promoted differentiation to white adipocytes, indicated by large fat droplets and increased expression of adipocyte marker genes (Acaca (acetyl Co‐A carboxylase‐α), Fasn (fatty acid synthase), Fabp4 (fatty acid binding protein 4), Lipe (hormone sensitive lipase), Retn (resistin), Rarres2 (chemerin)). However, at higher concentrations of genistein (50‐100 µM) and/or after longer exposure (days 0‐12) cells had smaller fat droplets and lower expression of these genes, coupled with increased expression of Sirt1 and of genes characteristic of brown adipocytes (Ucp1 (uncoupling protein 1) and Cebpb (CCAAT/enhancer binding protein‐β)).Dietary genistein may thus protect against obesity by encouraging the development of brown, rather than white, adipose tissue, possibly through a mechanism involving Sirt1.Grant Funding Source: Kurdistan Regional Government
Differential impacts of high fat and high Se diets on tissue lipid profiles of young adult and old wild‐type and GPX1‐/‐ mice (374.5)
Authors: Zhao Zeping , Kim Jonggun , Lei Xin Gen 
Published: June 2021

Our previous research has demonstrated hyperinsulinemia and elevated lipogenesis by feeding pigs and rats with Se at 3.0 mg/kg of diet. This study was to determine the impacts of a moderately high Se (1.0 vs. 0.3 mg/kg as selenite) and(or) high fat (60 vs. 16% energy from fat) on lipid profiles in plasma, adipose and liver tissues of young adult (2‐4 mo of age) and old (6‐10 mo of age) wild‐type (WT) and GPX1‐/‐ (KO) male mice. A total of 80 mice were divided into 4 parallel (genotype by age) experiments (n = 5/group) and fed one of 4 diets for 6 wk. Body weight was elevated (P < 0.05) by the high fat diet in old WT and young KO mice, but decreased by high Se diet (P < 0.05) in young WT mice. Both high fat and Se intakes enhanced (P < 0.05) plasma glucose concentrations in old WT mice. High Se intake decreased plasma non‐esterified fatty acids (NEFA) concentrations in young WT mice. There was little effect of high fat or Se intake on plasma lipid profiles of KO mice. Adipose tissue concentrations of triglycerides, cholesterol, and NEFA were consistently elevated by high fat and Se in both young WT and KO mice. In comparison, such effects of the dietary treatments on adipose tissue of old WT and KO mice or on liver of all 4 groups of mice were less obvious or consistent. In conclusion, our results revealed a uniquely high response of adipose tissue lipid profile to dietary intakes of high fat and Se and a strong interaction of age by GPX1 knockout on the response (NIH DK 53018).Grant Funding Source: (NIH DK 53018).