bluuebunny/crossref_metadata_2025_split huggingface dataset:
XPLN is a novel regulator of mTORC2
Authors: Khanna Nidhi , Fang Yimin , Yoon MeeSup , Chen Jie 
Published: June 2021

mTORC2 (mammalian or mechanistic target of rapamycin complex 2) signaling controls a wide range of cellular and developmental processes, but the regulation of mTORC2 is incompletely understood. Here we report the identification of a novel regulator of mTORC2. In a yeast two‐hybrid screen using the C‐terminal 1188 amino acids of mTOR as bait, we identified XPLN (eXchange factor found in platelets and leukemic and neuronal tissues), a GEF (Guanine Exchange Factor) for RhoA and RhoB, as a positive hit. The physical interaction between XPLN and full‐length mTOR was validated by pulldown assays, and found to be dependent on rictor but not raptor suggesting that XPLN specifically interacts with mTORC2. Recombinant XPLN inhibited mTORC2 kinase activity toward Akt in vitro, and overexpression of XPLN suppressed Akt phosphorylation in both HEK293 cells and C2C12 myoblasts. Conversely, knockdown of XPLN increased AKT phosphorylation in those cells. Furthermore, we found that XPLN negatively regulated cell survival and myoblast differentiation through Akt. Surprisingly, these functions of XPLN were independent of its GEF activity. Taken together, our results reveal XPLN as a novel regulator of mTORC2 signaling to Akt in the regulation of cell survival and differentiation.This work was supported by NIH grants to JC (AR048914 & GM089771).
Interaction between RGS7 binding protein and receptor protein tyrosine kinases
Authors: Fatora Christopher , Witherow D. Scott 
Published: June 2021

The function of the dimer between the G protein beta subunit 5 and the regulator of G protein signaling 7 (Gβ5‐RGS7) in cell signaling is not well understood. However, it is known that the Gβ5‐RGS7 dimer reversibly binds the regulator of G protein signaling binding protein (R7BP). To determine potential binding partners that might be involved in regulation of Gβ5‐RGS7 and R7BP activity, we performed a yeast two‐hybrid screen with R7BP. Of numerous potential interacting proteins, we have studied the interaction of the two specific isoforms of protein receptor tyrosine phosphatases, delta and kappa. Using in vitro binding assays with recombinant proteins as well as cell‐based immunoprecipitation assays, the interaction of R7BP with the protein receptor tyrosine phosphatases was analyzed in the presence and absence of Gβ5‐RGS7. These data suggest new signaling pathways that might be regulated via the Gβ5‐RGS7 dimer.This work was supported by a University of Tampa David Delo Research Professor Grant (DSW), a University of Tampa Dana Foundation Grant (DSW), and the University of Tampa Honors Program (CMF).
Andrographolide activates the Wnt pathway and modulates the APP processing by direct inhibiton of GSK3β
Authors: Tapia Cheril Cecilia , Mejías Cristóbal , Bustamante Hianara , Burgos Patricia , Inestrosa Nibaldo C 
Published: June 2021

ObjectivesWe carry out a detailed analysis of the effect of Andrographolide (ANDRO), the major component of Andrographis paniculata, on the activation of Wnt signaling and APP processing.MethodsHuman H4 neuroglioma cells stably expressing APP695 and slices from wild‐type mice were incubated with ANDRO. The samples were used for biochemical analysis.ResultsANDRO modulates the Wnt/β‐catenin signaling components increasing the levels of the β‐catenin by inactivation of GSK‐3β and inducing the transcription of Wnt target genes. ANDRO acts downstream from the ligand‐receptor binding, by direct inhibition of GSK3β. Finally, ANDRO seems to stimulate non‐amyloidogenic proteolytic cleavage of APP, leading to a significant increase in C83 levels, a product of α‐secretase.ConclusionsWe conclude that ANDRO activated Wnt pathway modulating the non‐amyloidogenic APP processing pathway by a mechanism that target inhibition of GSK3β.
The mechanism by which the TfR2/HFE complex affects iron homeostasis
Authors: Worthen Christal Anna , Chloupková Maja , Noguchi Ken , Enns Caroline A 
Published: June 2021

Iron homeostasis is tightly controlled. Since there is no regulated way of excreting excess iron, levels are finely tuned through dietary uptake. This is mostly accomplished by the peptide hormone, hepcidin, which is produced in the liver and regulated by the BMP‐signaling pathway. The hereditary hemochromatosis protein (HFE) and transferrin receptor 2 (TfR2) form a complex and regulate the BMP‐signaling pathway in response to blood transferrin‐bound iron levels. Mutations in either protein result in a reduction in BMP signaling and hepcidin expression, leading to iron overload. How the TfR2/HFE complex affects BMP signaling is unknown. The purpose of this study was to determine the mechanism by which TfR2 and HFE affect BMP‐signaling and iron homeostasis. We found that TfR2 and the BMP co‐receptor, hemojuvelin, interact through immunoprecipitation, and that HFE stabilizes this interaction. This establishes an important link between the iron‐sensing TfR2/HFE complex and BMP signaling. To further understand how this complex affects BMP signaling, we created mutant forms of TfR2 and HFE and studied them in vitro, using minicircle DNA technology in primary hepatocytes, and in vivo, using adeno‐associated virus under the control of a liver‐specific promoter.NIH RO1 DK054488T32 5T32GM071338–08
Using Chemical Genetics to Define Zipper‐Interacting Protein Kinase Signalling Events
Authors: Al‐Ghabkari Abdulhameed Saleh , Sutherland Cindy , Walsh Michael P , MacDonald Justin A 
Published: June 2021

Zipper‐interacting protein kinase (ZIPK) has emerged as an important regulator of apoptosis, cell motility and vascular smooth muscle (VSM) contraction. To identify the precise role of ZIPK in these processes, we set out to identify ZIPK substrates using a chemical‐genetic approach. Mutation of ZIPK at the conserved gatekeeper residue (L93G) within the ATP‐binding site was performed in order to develop cell‐based model systems for the analysis of ZIPK function. As proof of principle, kinetic analyses support the selectivity of analog‐sensitive kinase inhibitors (pyrazolo[3,5‐d]pyrimidine; PP1) for L93G‐ZIPK with minimal inhibitory potential observed for WT‐ZIPK or other VSM contractile kinases (ROK or MLCK). In this regard, the 1NM‐PP1 inhibitor (10 mM) provides maximal distinction of L93G‐ZIPK and WT‐ZIPK activities with essentially no off‐target effects. Moreover, the PP1 compounds have no effect on Ca2+‐dependent or Ca2+‐independent VSM contractions. These results are expected since the PP1 inhibitors have high specificity for the mutated kinase but minimal ‘off‐target’ effects on endogenous kinases. Although some novel off‐target effects of the analog‐sensitive kinase inhibitors were identified (i.e., able to inhibit ROK in vitro), we conclude that application of the chemical‐genetics approach with the L93G‐ZIPK and 1NM‐PP1 pairing will enable us to define the explicit actions of ZIPK.This submission is sponsored by Justin A. MacDonald, society affiliation member of ASBMB, jmacdo@ucalgary.caSupported by the Heart & Stroke Foundation of Canada
A picture is worth a thousand data points: An analysis of textbook visualizations in the molecular life sciences
Authors: Offerdahl Erika , Arneson Jessie 
Published: June 2021

Calls to transform science instruction underscore the need to develop students’ understanding of the disciplinary practices of scientists. Visual thinking – the ability to interpret and make sense of visualizations (e.g. graphs, diagrams, figures) – is one such practice that is seldom an explicit learning outcome of undergraduate curricula.Extracting meaning from visualizations requires translation across levels of organization (e.g. organismal level to the molecular) and levels of abstraction (e.g. from graphs to schematic models). The goal of this study was to determine the role of textbook figures in developing students’ visual thinking skills.Figures from biology and biochemistry textbooks and from five high‐profile scientific journals were analyzed for level of organization, level of abstraction, and the nature of transitions between levels (e.g. implicit vs. explicit). We found that textbook figures generally display only a single level of organization, represent relationships between levels implicitly, and show little progression in complexity from intro to upper‐level. Further, figures from upper‐level textbooks are less complex and seldom represent quantitative data when compared to scientific figures. Our results suggest that visualizations used in traditional instruction lack the complexity necessary to explicitly support the development of visual thinking skills.
Protective Effect of Peanut Sprout Extract on Glutamate‐induced Neuronal Toxicity and Kainic acid‐induced Memory Loss
Authors: Kim Jong‐Sang , Kim Seong Soon , Kim Hyo Jung , Seo Ji Yeon , Park In Sil , Kang Hye‐Ryung , Kim Bo Ram , Zakharova Alexsandra 
Published: June 2021

Glutamate, one of major excitatory neurotransmitter in central nervous system, has been known to induce oxidative stress such as reactive oxygen species (ROS) by overstimulation of neuron. In this context, we investigated the neuroprotective effect of peanut sprout extract (PSE) against glutamate/kainic acid‐induced oxidative stress in the mouse hippocampal HT22 cells and ICR mice. PSE significantly increased the cell viability and decreased the ROS generation under glutamate‐induced oxidative stress in HT22 cells. PSE induced heme oxygenase‐1(HO‐1) known as a phase 2 enzyme and, its protective effect was abolished by HO‐1 and PI3K inhibitors. Furthermore, to examine the effect of PSE on learning and memory abilities in mice, kainic acid was treated to induce learning and memory loss, an analogue of glutamate. Passive avoidance and Y‐maze tests were performed to examine abilities of learning memory and spatial cognition respectively. The results showed that PSE had protective effect on kainic acid‐induced memory loss in mice, suggesting that PSE protects neuronal cells from glutamate/kainic acid‐induced oxidative stress through induction of HO‐1.Grant Funding Source: ASN
B vitamin intake in early adulthood and cognition in late midlife: CARDIA
Authors: Qin Bo , Xun Pengcheng , Zhu Na , Jacobs David , Steffen Lyn , Daviglus Martha , Van Horn Linda , Reis Jared , Loria Catherine , Liu Kiang , He Ka 
Published: June 2021

Epidemiologic evidence regarding B vitamin intake in association with cognitive function in late midlife is limited. We hypothesized that higher intake of B vitamins predicted better cognition in late midlife. This study comprised a community‐based multicenter cohort of black and white men and women aged 18–30 years in 1985–1986 (Y0) from the Coronary Artery Risk Development in Young Adults (CARDIA) study. The CARDIA diet history at Y0 was used to assess nutrient intake, including dietary and supplemental B vitamins‐ thiamine, riboflavin, niacin and folic acid. Cognitive function was measured once at Y25 by Rey auditory‐verbal learning (RAVLT) for verbal memory, Digit symbol substitution test (DSST) for psychomotor speed, and modified Stroop interference test for executive function. After multivariate adjustment, the highest quintile (Q5) of riboflavin intake (median 5.4 mg/day) was significantly associated with 0.71 more words recalled in RAVLT (p=0.001 vs Q1, median 1.3 mg/day). 10 mg/day of niacin was associated with 0.3 more digits in DSST, the highest quintile of niacin intake predicted 3.6 more digits in DSST (p<0.001 vs Q1). We found a threshold association of folic acid intake with memory (0.6 word for Q5 vs Q1, p=0.001). In conclusion, higher intake of B vitamins in early adulthood was associated with better cognitive function in late midlife.Grant Funding Source: UNC Chapel Hill start‐up funding, Lineberger Cancer Center
Fish intake and cognitive function in Chinese older adults: the China Health and Nutrition Survey (CHNS)
Authors: Qin Bo , Mendez Michelle Ann 
Published: June 2021

Primary prevention to reduce cognitive decline is of great public health significance. Epidemiologic evidence on associations between fish intake and cognitive function in older adults is mixed, with limited data from China. We hypothesized that higher fish intake would predict better cognition in Chinese older adults. This study comprised a household‐based cohort of older adults (≥55y) who undertook cognitive function tests in 2000 and 2004 within the China Health and Nutrition Survey (CHNS). Three‐day 24‐ hour dietary recalls were used to assess fish intake in 2000. Outcomes were immediate and delayed memory measured by a 10 word verbal‐learning task, and working memory by the serial 7 subtraction test. After multivariate adjustment for age, gender, education, total energy intake, physical activity, alcohol drinking, smoking and respective cognitive scores in 2000, fish intakes ≥1 serving/wk was associated with 0.34 more words recalled in the delayed recall task in 2004 (p=0.023), and 0.34 higher serial 7 test scores (p=0.002), each compared with fish intake <1 serving/wk. In exploratory analysis, we found that hypertension modified the relation between fish intake and delayed memory. There was a stronger association of fish intake with delayed memory among subjects with hypertension (0.85 words, p=0.022). In conclusion, higher fish intakes predicted better cognition 4 years later in Chinese older adults.Grant Funding Source: UNC Chapel Hill start‐up funding, Lineberger Cancer Center
Characteristics and Barriers Associated with Participation in the Supplemental Nutrition Assistance Program (SNAP) Participants by Persons Living with HIV
Authors: Hatsu Irene , Campa Adriana , Baum Marianna K , Thomlison Barbara , Johnson Paulette , Huffman Fatma 
Published: June 2021

ObjectiveSNAP serves 50 million Americans. For HIV‐infected people in poverty, SNAP participation provides nutritional support for the management of HIV disease. The objective of this study was to characterize barriers for participation in SNAP in this population.MethodsAfter consenting 175 participants, questionnaires on sociodemographics and lifestyle were collected. SPSS was used for analyses.ResultsParticipants were 66% male, 74% African‐American and 70% received SNAP. Antiretroviral use (OR=15.2, 95%CI:4.3–52.7,p<0.001), income<$1000/month (OR=5.28,95%CI:1.6–17.0,p=0.006) and US‐born (OR=16.50,95%CI:3.6–75.5, p<0.001) were associated with SNAP participation; 27% of nonparticipants cited denial of application as the main reason for not participating in SNAP. Recent incarceration (17.4%) and being unaware of eligibility or living or living in a shelter (15.4%) were barriers to participation.ConclusionSNAP participation is high in this HIV‐infected cohort; however, recent incarceration and living in a shelter are barriers that are distinct to this population. Outreach programs targeting low income HIV‐infected persons should consider these barriers and develop strategies to overcome them.
Factors associated with not using antenatal iron/folic acid supplements in Indonesia: the 2002/2003 and 2007 Indonesia Demographic and Health Survey
Authors: Titaley Christiana Rialine , Dibley Michael J 
Published: June 2021

ObjectiveTo examine factors associated with non use of antenatal iron/folic acid (IFA) supplements in Indonesia.MethodsThis study used data from two most recent Indonesia Demographic and Health Survey (IDHS), the 2002/2003 and 2007 IDHS and providing survival information of 26,591 most recent deliveries over 5 years, prior to each survey. The outcome variable was non use of IFA supplements. Using logistic regression we examined the role of external environment, predisposing, enabling, need factors, and previous utilization of maternal care services in non use of antenatal IFA supplements.ResultsAmongst external environmental factors, mothers from outer Java‐Bali Region and rural areas had increased odds for not using antenatal IFA supplements. For the predisposing factors, the odds increased along with the reduction of household wealth index and parental education. Enabling factors associated with increased odds for non use of IFA supplements included mothers reporting money to pay health services (OR=1.28, p<0.001) and distance to health services (OR=1.20, p=0.03) was a major problem. Our study also demonstrated the importance of antenatal care as a distribution channel of IFA supplements.ConclusionEfforts to increase the use of antenatal IFA supplements should be conducted comprehensively by addressing the significant predictors of IFA utilization, as found in this study.Research Support:None
Your neighborhood is not my neighborhood: a mapped comparison of the neighborhoods of public housing developments with other neighborhoods in Boston
Authors: ElShourbagy Sanae Yu , Farmer Grant W , Bowen Deborah 
Published: June 2021

Components of a neighborhood provide insight into people's daily life and needs. Limited food access can subsequently adversely affect health status. Challenges to environmental accessibility to healthy foods and transportation are drivers of obesity. Therefore, the immediate environment of people who live in public housing developments may not be conducive for residents to purchase and eat healthy foods, and be physically active. Mapping Boston's public housing developments with ArcGIS (Geographic Information Systems) and defining key asset characteristics of the neighborhoods surrounding them is a powerful strategy to visually depict regions which are known as “food deserts” due to the limited accessibility to healthy foods. Food deserts proximal to public housing developments may then be major factors in the occurrence of obesity in urban at‐risk populations. We demonstrate the relevant differences between neighborhoods containing public housing developments and those which do not. We further use mapping to present an accessible picture of a complex urban public health issue: the interaction between type of neighborhood and differential access to healthy nutrition and activity options.CDCU48DP001922Grant Funding Source: CDCU48DP001922
Increased healthy food purchasing associated with exposure to carry‐out intervention in low‐income urban setting
Authors: Lee‐Kwan Seung Hee , Yong Rachel , Bleich Sara N , Gittelsohn Joel 
Published: June 2021

Americans are eating out more frequently. This is particularly true in low‐income urban settings where residents commonly purchase foods at carry‐outs (non‐franchised food establishments selling ready to‐eat food and beverages for off‐premise consumption). Baltimore Healthy Carry‐outs, a three phase multi‐component environmental intervention, was conducted in four carry‐outs, with another four as matching comparisons (Feb – Sept 2011). To assess impact, intervention exposure assessment was conducted (n=186) and exposure scores were created to reflect the 24 intervention strategies. Linear and logistic regression analyses using cluster robust variance were used. Intervention carry‐out customers purchased 4.5 varieties of promoted healthy items while comparison customers purchased less than 1 item (p<0.001). There was a strong dose response relationship between the combined intervention exposure score (range 0–24) and the frequency of healthy food purchased (beta 0.38, CI 0.26–0.49). Among customers exposed to the intervention, there were increased odds of purchasing specific healthy food items, such as a turkey club sandwich (OR 1.54, p<0.0001), fruit cup (OR 1.37, p<0.0001), or cooked greens (OR 1.30, p<0.0001). An environmental intervention at carry‐outs was shown to effectively increase healthy food purchasing frequency among consumers.Grant Funding Source: Johns Hopkins Center for a Livable Future and Diabetes Research & Training Center
Children's response to food price and warning interventions when purchasing snack foods
Authors: Cash Sean B , Adamowicz Wiktor L. , Allen Shannon , McAlister Anna R. 
Published: June 2021

ObjectiveThe process by which children make food purchasing decisions is not well understood, despite some evidence that children have considerable autonomous purchasing power, and that much of it is directed toward food. Of particular interest is the extent to which proposed “fat taxes” and inclusion of additional information may influence children's food purchases and consumption, and what developmental measures best predict responsiveness to such interventions.MethodsIncentive‐compatible purchase experiments involving snack foods conducted with 10–12 year olds in after‐school problems in Edmonton, Alberta, accompanied by 6 measures of child development.ResultsParticipating children show responsiveness to price of snack food items in the experimental setting.Conclusion and commentThe ability to influence children's food purchasing choices depends on their attending to price differences and point‐of‐purchase information. The role of children's autonomous purchasing decisions has largely been ignored by practitioners and researchers to date, but is key to understanding the complete picture of modern children's diets. Research support was provided by the Agriculture and Agri‐Food Canada Research Network on Consumer and Market Demand.
Identifying healthy foods for promotion in an urban corner store intervention
Authors: Liu Debra , Budd Nadine , Cuccia Alison , Jock Brittany , Jeffries Jayne , Katz Fred , Gittelsohn Joel 
Published: June 2021

In Baltimore City, 33% and 35% of adults are either overweight or obese, respectively. Interventions aimed at improving the food environment, particularly in corner stores, have been shown to increase access to healthier foods in low‐income settings. It is important to identify healthy foods for such programs through formative research, which helps interventionists understand the target population's food needs in order to develop culturally appropriate strategies. Both structured and unstructured pile sorts with healthier foods and beverages were conducted with 33 (15 females, 18 males) low‐income African American adult residents of Baltimore City, in order to better understand how individuals categorize these items and their likelihood to purchase them at corner stores. Multi‐dimensional scaling and average‐link cluster analysis (stress=0.141) using Visual Anthropac identified 3 groups: (1) drinks, (2) dairy products and (3) fruits, vegetables, and fiber foods. Reduced‐fat cheese, 1% milk and baked chips were ranked low in likelihood to buy across all rankings, while fruits such as grapes and bananas were ranked high. These results were used to create the phases for a corner store intervention.Funded by National Heart, Lung & Blood Institute (Grant #1R21HL102812–01A1).