bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential mechanisms of cardiac hypertrophy in mice with a null deletion of MAFbx (1164.7)
Authors: Matern Philip , Gomes Aldrin , Bodine Sue 
Published: June 2021

The E3 ubiquitin ligase, MAFbx, has been shown to target specific proteins for degradation through poly‐ubiquitination and the ubiquitin proteasome system. A null deletion of MAFbx reveals no cardiac phenotype in young unchallenged knock out (KO) mice, but leads to the development of congestive heart failure and sudden death (at 18 months) in unchallenged aging mice. The aim of this study was to determine potential mechanisms underlying the development of congestive heart failure in MAFbx KO animals. Echocardiograms demonstrated functional changes (reduced fractional shortening and left ventricular ejection fraction) in KO animals beginning at 11 months and markers for multiple growth pathways were elevated in KO mice at 14 months of age. Calcineurin expression was elevated above wildtype (WT) at 14 months and remained elevated at 18 months. Phosphorylated Akt (S473) and GSK3β (S9) expression were also elevated at 14 months. Markers of the proteasome system demonstrated altered expression and activity relative to WT animals. Expression of 19 and 20S proteasome subunits (RPT1, α3, β5) were elevated in KO mice at 14 months, but only the 26S β1 subunit showed higher activity, with no change in β2 or β5 activity. The 14 month mice also had elevated total ubiquitinated proteins and reduced free ubiquitin. Together, these findings suggest that MAFbx deletion results in a progressive disruption of protein quality control (increased protein synthesis and limited increase in protein degradation) leading to activation of pathological signaling pathways and the development of cardiomyopathy.Grant Funding Source: Muscular Dystrophy Association
Assessment of student nutrition knowledge and self‐efficacy at Boston University School of Medicine (118.1)
Authors: Ireland Kathy , Robbins Jennifer , Manders Aaron , Lenders Carine 
Published: June 2021

Objective: To determine baseline nutrition knowledge and perceived self‐efficacy in BUSM students and identify associated demographic factors.Methods: We conducted a cross‐sectional survey of 1st to 4th year medical students (n=775) including 6 knowledge and 4 self‐efficacy nutrition questions. Students were encouraged to take the survey via email and Blackboard postings from February‐April 2013. Data included year in medical school, gender, and involvement in a student nutrition interest group (SNAAC). Outcomes included an average composite knowledge score (mean±sd) and self‐efficacy ratings related to confidence to provide dietary counseling, refer to Registered Dietitians (RDs), and refer to food programs (Likert scale ranging from “strongly disagree” to “strongly agree”). Descriptive and multivariate analyses were performed.Results: 166 (23%) students responded. Average knowledge score was 52±19%. Confidence to provide dietary counseling, refer to Registered Dietitians (RDs), and refer to food programs was 55%, 37% and 24%, respectively. After adjusting for all covariates, knowledge score increased with each education year (3.1 ±1.4%, p<0.05) and was lower in males (‐9.3±3.2%, p<0.05). Students were more likely to feel confident to counsel with each education year (AOR=1.41, 95% CI 1.03‐1.96) and with SNAAC involvement (AOR=2.74, 95% 1.39‐5.40). Confidence to refer to RDs was more likely with involvement in SNAAC (AOR=2.47, 95% CI 1.26‐4.83).Conclusions: Medical student knowledge and self‐efficacy in nutrition is low. More nutrition education and prospective evaluations are needed. Funded by the New Balance Foundation.
Investigating py‐STAT6 protein levels and mRNA expression of STAT6 regulated genes in renal epithelial cells (1180.8)
Authors: Boslett Brianna , Resnick Andrew 
Published: June 2021

The current study will investigate the mechanosensory‐signaling pathway leading to STAT6 gene transcription in mouse cortical collecting duct epithelial cells. Many stimulants are capable of activating STAT6 in the kidney, but it is still unknown how STAT6 is directed to specific gene targets. In several cases, transcription co‐factors, such as a fragment of polycystin 1, have been found to enter the nucleus along with STAT6 dimers. Additionally, the mechanism by which STAT6 becomes activated by mechanosensation is currently unknown. A primary goal of this study is to determine the kinase involved in STAT6 phosphorylation (activation) in changing flow conditions.The STAT family has cell‐type specific promoter binding sites. Common STAT controlled cis‐regulatory modules (cSCCs) are cis‐regulatory modules (CRMs) that can be recognized by all STAT family members across cell types. 116 cSCCs have been identified and correspond to JAK/STAT signaling genes. I hypothesize that different stimulants (cytokines vs. fluid flow) will lead STAT6 to transcribe different genes. Therefore, STAT6 binding sites that do not correspond to cSCCs will be investigated for cell specific, or stimuli‐specific STAT6 gene transcription.These results will have implications for ADPKD, which is caused by genetic mutations leading to defects in polycystin 1 (PC1) and polycystin 2 (PC2) proteins.Grant Funding Source: Supported by the National Institute of Diabetes and Digestive and Kidney Diseases 1R15DK092716
Proteolytic activation of the human epithelial sodium channel by trypsin and trypsin IV involves distinct cleavage sites (1181.2)
Authors: Haerteis Silke , Krappitz Annabel , Krappitz Matteus , Murphy Jane , Knecht Wolfgang , Bunnett Nigel , Korbmacher Christoph 
Published: June 2021

Proteolytic channel activation is a unique feature of the epithelial sodium channel (ENaC) but is not yet fully understood. The serine protease trypsin is known to activate ENaC in vitro but may not be relevant in vivo. In this study, we wanted to investigate whether the trypsin‐like serine protease trypsin IV, known to be expressed in several epithelial tissues, can activate human ENaC. Moreover, using site‐directed mutagenesis we wanted to identify functionally relevant cleavage sites in the γ‐subunit of the channel. In the Xenopus laevis oocyte expression system, we monitored the proteolytic activation of ENaC currents and the appearance of γ‐ENaC cleavage products at the cell surface. We demonstrated that trypsin IV can stimulate ENaC and that this activation involves a critical cleavage site (K189) in the extracellular domain of the γ‐subunit. Moreover, we showed that channel activation by trypsin was prevented by mutating three putative trypsin cleavage sites (K168; K170; R172) in addition to mutating previously described prostasin (RKRK178), plasmin (K189), and neutrophil elastase (V182;V193) sites. In conclusion, we demonstrated for the first time that trypsin IV can activate ENaC and that trypsin and trypsin IV use specific cleavage sites to achieve channel activation. Preferential cleavage sites may provide a mechanism for differential ENaC regulation by tissue‐specific proteases.Grant Funding Source: Supported by grants of the Interdisziplinäres Zentrum für Klinische Forschung (IZKF) (S.H., M.K.)
Differential role of epithelial Na+ channel lysines in Nedd4‐2 regulation (1181.5)
Authors: Tomkovicz Vivian , Snyder Peter 
Published: June 2021

The epithelial sodium channel (ENaC) plays a critical role in blood pressure control. Defects in ENaC regulation by the E3 ubiquitin ligase Nedd4‐2 cause Liddle’s syndrome, an inherited form of hypertension. Nedd4‐2 catalyzes ubiquitination of ENaC lysines, which enhances ENaC endocytosis and degradation. To identify the lysines required for Nedd4‐2 regulation, we mutated them to arginine and tested the effect of Nedd4‐2 on ENaC cell surface expression. Mutation of all cytoplasmic lysines in ENaC reduced the ability of Nedd4‐2 to decrease ENaC surface expression (detected by biotinylation) and ENaC current. In contrast, mutation of all cytoplasmic lysines in ‐ and ENaC had no effect. By mutating ENaC lysines individually and in combination, we identified differential roles for each. K8, K10, and K26 were partially required for Nedd4‐2 regulation, whereas K6, K12, and K13 were not. Mutation of lysines in ‐ and ENaC also revealed differential roles. In ENaC, mutation of K22 and K25 to arginine reduced ENaC inhibition by Nedd4‐2. In contrast, mutation of K83 enhanced Nedd4‐2 inhibition. In ENaC, mutation of K16 and K23 produced a small decrease in Nedd4‐2 regulation, but mutation of other lysines did not. Combination of mutations in ‐, , and ENaC produced an additive reduction in Nedd4‐2 regulation, but did not abolish regulation. Thus, Nedd4‐2 regulates ENaC in part through a subset of ENaC lysines, as well as through a second mechanism that is independent of ENaC lysines.Grant Funding Source: supported by NIH HL072256 (PMS)
Association of parental emotional feeding with preschool child intake of sugar‐sweetened beverages (252.7)
Authors: Lora Karina , Wakefield Dorothy , Ferris Ann 
Published: June 2021

The study examined parental feeding practices with preschool children consumption of sugar‐sweetened beverages (SSB). Baseline data from a longitudinal study with low‐income multicultural caregivers of 3‐5 y old children (n=326). Participants provided demographics; two‐consecutive weekend food recalls for the child and responded to the Preschooler Feeding Questionnaire. Children’s height and weight were measured in triplicate. Food recalls were averaged over the two days. General linear models tested association of feeding practices with child intake (oz.) of SSB (juice drinks, soda) among children with SSB intake in their food recalls (consumers). Among consumers, median total child intake of SSB was 8.7 oz/day, while juice drinks and soda were 6.7 oz/day and 5.4 oz/day, respectively. Total SSB and juice drinks intakes were positively associated with caregiver’s “Use of Food to Calm the Child” in Latino and White children (p<.05). Use of Food to Calm the Child was positively associated with BMI percentile in White children only (p<.05). SSB and juice drinks intakes were not associated with child’s BMI percentile. No other feeding practice was associated with child’s intake of SSB. Caregivers’ use of SSB for emotional feeding seems to occur in the context of negative emotions in the child. Ethnic/racial differences exist in the use of foods for child’s emotional regulation.Grant Funding Source: USDA/NRI 2008‐55215‐19071
Health implications of adopting nutritious, low‐carbon diets in the U.K. (255.3)
Authors: Green Rosemary , Milner James , Dangour Alan , Haines Andy , Chalabi Zaid , Markandya Anil , Spadaro Joseph , Wilkinson Paul 
Published: June 2021

Objective: To design diets for the UK adult population that are plausible, conform to nutritional guidelines and reduce greenhouse gas emissions (GHGEs), and to quantify the health impacts associated with these diets.Methods: We used data from the National Diet and Nutrition Survey and a Life Cycle Analysis of GHGEs to calculate the emissions associated with current average diets in the UK. We then optimised these diets so that they conformed to World Health Organization (WHO) nutritional guidelines while minimising deviation from the current diet and reducing the GHGEs associated with the diet. We assessed the changes in Quality Adjusted Life Years (QALYs) from mortality and morbidity from coronary heart disease, stroke, cancer and type II diabetes if the optimised diets were adopted.Results: The current average diet among UK adults does not conform to WHO guidelines. If diets were optimised to comply with these guidelines, an incidental reduction of 15% in GHGEs would be achieved. Further reductions in GHGEs could be achieved by modifying diets so that they contain fewer animal products and more fruit, vegetables and cereals, but dietary changes that reduced GHGEs by more than 50% resulted in implausible changes to dietary patterns. Adopting healthy diets 50% lower in GHGEs than the current diet would result in a large saving in QALYs over a 20 year follow‐up period, half of which would be from coronary heart disease.Conclusions: There are large potential co‐benefits to health from adopting diets with lower associated GHGEs. However, the nutritional value and acceptability of these diets is likely to peak at a reduction in GHGEs of around 50% for a country like the UK, therefore in the absence of major changes in dietary preferences any additional reductions in emissions from food will have to come from other means such as waste reduction and increased production efficiency.
Prolonged enteral leucine supplementation improves lean growth in neonatal pigs fed a restricted protein diet (258.6)
Authors: Columbus Daniel , Steinhoff‐Wagner Julia , Suryawan Agus , Kao Michelle , Hernandez‐Garcia Adriana , Boutry Claire , Nguyen Hanh , Almonaci Rosemarie , Scull Brooks , Fiorotto Marta , Davis Teresa 
Published: June 2021

Many low birth weight infants experience growth failure due to feeding intolerance resulting in reduced nutrient intake. The branched‐chain amino acid, leucine, has been shown to have anabolic effects on skeletal muscle. The objective of the study was to determine if prolonged enteral leucine supplementation improves lean growth in neonatal pigs fed a restricted protein diet. Five‐day‐old pigs (N = 22; 1.9 ± 0.3 kg initial BW) were fed by gastric catheter either a control protein (CP; 22.5% protein, 0.98% leucine) or restricted protein (RP; 11.2% protein, 0.49% leucine) milk replacement diet or RP supplemented with leucine to the same level as in the CP diet (RP+L). Pigs were fed 40 ml/kg BW per meal every 4 h for 21 d. Body composition was determined by dual‐energy x‐ray absorptiometry on d 0 and 20. Feeding the CP diet resulted in greater total body weight and lean body mass after 21 d compared to RP fed pigs (P < 0.05). Mass of the longissimus dorsi muscle, heart, and kidney were also greater in the CP than RP fed pigs (P < 0.05). Body weight, lean body mass, and mass of the longissimus dorsi, heart, and kidney in pigs fed the RP+L diet were intermediate to the RP and CP fed pigs. Fat content and gain were similar for all groups. Prolonged leucine supplementation of a marginal protein diet has the potential to improve overall growth in neonatal pigs and infants with restricted protein intake through an increase in lean tissue growth.Grant Funding Source: Supported by NIH HD072891 and USDA/ARS 6250‐51000‐055
The more sugar and calories, the better? Children’s perspective on sugar‐sweetened beverages (262.7)
Authors: Kharmats Anna , Hopkins Laura , Anderson Steeves Elizabeth , Mui Yeeli , Gittelsohn Joel 
Published: June 2021

Caloric menu labeling is currently used as a strategy to promote healthier dietary choices. However, because caloric menu labels may be challenging to interpret, providing information about the amount of time it would take to burn off the calories consumed has been suggested. Unfortunately, children may interpret this information in an unintended way. Three focus groups were conducted with youth participants (n=17) ages 10 to 14 to investigate their understanding of promotional materials that depicted the high sugar and caloric content of sugar‐sweetened beverages (SSBs) and the amount of jogging time it would take to burn off the calories. Before viewing the promotional materials, children expressed positive opinions of water, and negative opinions of soda. Younger boys commented that soda makes them hyper. Surprisingly, when reviewing promotional materials, younger boys expressed positive views of sports drinks, because the sugar and calories in these beverages would give them more energy to exercise, even when the messaging portrayed added sugar negatively. Girls and older participants interpreted the promotional materials as intended by the researchers. These results indicate the need for additional research to find effective communication strategies to promote consumption of healthier beverages among younger children, and to counteract marketing campaigns that depict SSBs as healthy options.Grant Funding Source: NIH
Meetings Outside the Box: a program to build skills in science communication through networking of graduate level trainees and high school teens (29.1)
Authors: Evans Teresa , Blake Nicquet 
Published: June 2021

The vision of this project is to leverage an existing program for graduate level trainees (Trainee Meetings Outside the Box, TMOB) in the launch of a newly developed program for high school teens (Teen Meetings Outside the Box, TeenMOB). TMOB has been extremely well received amongst graduate students and postdoctoral fellows at the University of Texas Health and Science Center at San Antonio (UTHSCSA). The mission of TMOB is to provide a structured setting for the discussion and development of scientific communication skills for trainees, which will serve as the foundation for the continued effective communication of science and career development. Following this model, we will create an environment that allows TMOB trainees to work closely with teens interested in science to organize a sustainable teen science café (TeenMOB). The goals of TeenMOB are to: 1. Provide dynamic, engaging, and facilitated group discussions designed to promote scientific career building skills and mentoring relationships among UTHSCSA research trainees and San Antonio teens with a focus on underrepresented minority (URM); 2. Increase STEM education experiences for high school students who are underrepresented in STEM fields; 3. Provide experiences for graduate trainees to increase science communication and mentoring skills; and 4. Establish the first sustainable teen science café network within San Antonio.Grant Funding Source: Supported by ASBMB Science Outreach Seed Grant
The role of aggrecan in embryonic growth plate cytoarchitecture and differentiation: a rescue model (344.6)
Authors: Lauing Kristen , Cortes Mauricio , Domowicz Miriam , Henry Judith , Schwartz Nancy 
Published: June 2021

The homozygous cmd mouse harbors a mutation resulting in the complete absence of the proteoglycan aggrecan in the extracellular matrix of growth plate cartilage. In this study, we examine specifically how this proteoglycan influences the cytoarchitecture and differentiation of chondrocytes within growth plate zones. We utilize the cmd mouse (cmd/cmd) and a novel transgenic mouse expressing chick aggrecan driven by the Col2a1 promoter (tg/+) to elucidate the role of this proteoglycan on chondrocyte survival and proliferation, as well as growth factor production and chondrocyte transcription factor expression. E18.5 cmd embryos display a 55% decrease in limb length, aberrant spatial and temporal mRNA expression patterns of chondrocyte growth factors, and a significant increase in cell death levels in chondrocytes adjacent to the perichondrium compared to wild type controls. Expression of the novel transgene in “rescue” embryos (cmd/cmd::tg/+) results in a 20% increase in limb element length compared to cmd mutant embryos. In situ hybridization demonstrates a partial restoration of normal growth factor and transcription factor gene expression patterns for Indian hedgehog, Patched, Collagen X, FGFR3, and Sox9 compared to cmd growth plates. In addition, the growth plates of rescue embryos display improved chondrocyte morphology and matrix production, particularly within the proliferative and hypertrophic zones. Notably, rescue growth plates display significantly decreased cell death levels compared to cmd embryos in the perichondrial region while concomitantly increasing proliferation levels in the growth plate. The results of this study suggest that aggrecan influences the temporal and spatial patterns of growth factor production by chondrocytes in the embryonic growth plate, and is essential to chondrocyte organization, morphology, and survival during embryonic limb growth.Grant Funding Source: Supported by the National Institutes of Child Health and Human Development (R01 HD017332)
Iodized salt benefits infant mental development: preliminary results from a cluster randomized trial in Ethiopia (389.4)
Authors: Bougma Karim , Marquis Grace , Aboud Frances , Frongillo Edward , Melka Tizita , Samuel Aregash 
Published: June 2021

Iodine deficiency is thought to contribute to delayed mental development. The effectiveness of iodized salt programs to eliminate this delay has not been studied in children under 36 months. Using a cluster randomized design, 1880 infants 6 to 10 mo old were administered Bayley Scales of Infant and Toddler Development (BSID‐III) in 60 villages in Amhara, Ethiopia. Following salt iodization legislation, iodized salt was forced early into the markets of 30 villages (intervention group) before it became available in the 30 control villages. The two groups had similar socioeconomic, nutrition, and mental development scores at baseline. The same children (86% of the baseline sample) were re‐assessed with the BSID‐III when 20 to 29 mo of age. Analysis was done with a linear mixed model. The intervention group had significantly higher scores at reassessment on three of the four subscales: cognitive (std mean 6.4 vs 6.1, p<0.05), receptive language (std mean 7.2 vs 6.9, p<0.05), expressive language (std mean 6.4 vs 6.2, ns), and fine motor (std mean 7.94 vs 7.63, p<0.05). Effect sizes were small (d=0.11), possibly due to the low socioeconomic status, diet diversity, and stimulation as well as high prevalence of stunting and access to iodized salt in some control areas that may have hampered greater benefits that iodine alone could provide.Grant Funding Source: Supported by Micronutrient Initiative, Canada
Nanoparticles in lungs: a model of effects after infection (406.3)
Authors: Fotouhi Ariana , Fotouhi Anna , Boyer Daniella , Herndon Betty , Quinn Tim , Molteni Agostino 
Published: June 2021

Single wall nanoparticles (CN) are considered toxic with pulmonary effects that have been compared to asbestos. Our previous studies suggested only acute pulmonary toxicity by CN, but to evaluate synergistic effects this study compared acute (3 hr) intratracheal CN effects on rat lungs in animals with or without an ongoing “second hit” of an intraabdominal Staph. Aureus infection (1 week). Comparison groups: (1) CN only, (2) CN + infection, (3) infection only. Histopathology on 8 features of pulmonary tissue was scored. Lumen patency of pulmonary vessels was averaged. Macrophage (mφ) counts on CD68 stained sections and PMN counts on the three groups were made.Histopathology showed significant acute toxicity in lung septa (p=0.04), small bronchi (p=0.045) and pulmonary vessels (0.001). Lumen of lung vessels showed greater patency with nanoparticles (3 hr) than either group with infection, although the values had a p >0.05.Both macrophages (Mφ) and neutrophils (PMN) were elevated in lungs. The infection only group was highest, nanoparticles alone second highest, and nanoparticles plus infection had the lowest total cell counts, but group comparisons were below significance. We conclude that the initial steps to pulmonary toxicity by nanoparticle exposure are not exacerbated by the “second hit” of an ongoing distant infection in this model although acute toxicity was found histologically.Grant Funding Source: St Luke's Hospital foundation grant