bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing the HYPE: Studies of the mammalian Fic protein
Authors: Woolery Andrew Ryan , Hao Yi-Heng , Luong Phi , Orth Kim 
Published: June 2021

ObjectiveTo characterize the mammalian Fic protein HYPE in terms of its subcellular localization, tissue specific expression, molecular function and potential substratesMethodsClick chemistry, qRT‐PCR, stable cell lines, protein expression and purificationResultsUsing a variety of tools developed in our lab, we have partially characterized the subcellular localization, glycosylation state and tissue specific expression of the mammalian Fic protein termed HYPE. Several forms of the human and mouse HYPE protein have been successfully expressed and purified for use in a variety of assays to determine its potential substrates, and stable cell lines containing HYPE shRNA knockdown and HYPE mutants are being generated in a variety of cell lines to attempt to determine its cellular function and substrates.ConclusionThe significance of the Fic domain activity of mammalian HYPE is not currently known, but our current knowledge, including its subcellular localization and tissues of relevance, combined with our ongoing research with tools like click chemistry, recombinant HYPE protein and stable mammalian cells lines should allow us to elucidate the substrates and functions of this enigmatic protein.
Structural biology of MAPK (p38/ERK) regulation by phosphatases and scaffolding proteins
Authors: Page Rebecca , Peti Wolfgang 
Published: June 2021

~70% of all eukaryotic cellular proteins are regulated by phosphorylation. While structural data for kinases and phosphatases are readily available, only a handful of protein:protein complex structures, which are necessary to understand the biological function of the underlying regulation, have been described. Here we report our efforts to close this gap by describing our novel, structural insights into the regulation of MAPKs (p38, ERK2) by the kinase interaction motif family KIM‐PTPs (HePTP, STEP, PTP‐SL). In order to obtain a molecular picture of these large MAPK protein:protein complexes, we are integrating high resolution techniques (NMR/X‐ray) for the analysis of basic components with lower resolution techniques (SAXS) for constraints on the higher order, dynamic, multi‐protein assemblies. This has allowed us to determine the first detailed structures of MAPK:MAPK regulatory protein complexes, which, in combination with a thorough ITC study, has enabled us to identify the molecular determinants that drive MAPK specificity and fidelity. Finally, we are also providing new structural insights into the MAPK spatial control by elucidating the structures of MAPK scaffolding complexes.Supported by RSG‐08‐067‐01‐LIB from the American Cancer Society.
Identification of Methylation‐Dependent Protein Phosphatase 2A Activity Correlated with Changes in Insulin Secretion and Glucose Tolerance in Mice with Hypomorphic Expression of the LCMT1 Protein Carboxyl Methyltransferase
Authors: MacKay Kennen Burke , Clarke Steven , Young Stephen 
Published: June 2021

Protein Phosphatase 2 A (PP2A) is a highly conserved, broad specificity, heterotrimeric serine/threonine phosphatase involved in nearly all cytosolic processes. PP2A control is manifested through subunit composition, small molecule and peptide inhibitors as well as post‐translational modifications. One such modification, methylation of the C‐terminal leucine by LCMT1, regulates PP2A subunit assembly, specifically Bα subunit binding, and thus substrate specificity. In this study we generate a mouse homozygous for an Lcmt1 gene‐trap cassette, yet expressing reduced Lcmt1 transcript and protein. Full length Lcmt1 transcript is achieved through alternative splicing around the genetrap cassette in a tissue specific manner. Reduced LCMT1 correlates with a concomitant reduction of PP2A methylation and an increase in PP2A demethylation confirming LCMT1 as the main PP2A methyltransferase. Lcmt1 homozygous gene‐trapped mice were born in a non‐mendelian ratio suggesting embryonic lethality. Adult Lcmt1 hypomorphic animals display decreased glucose tolerance and increased glucose‐stimulated insulin secretion suggesting an insulin resistance phenotype. Our results indicate that PP2A methylation has a role in propagation of the insulin‐signaling cascade, possibly through altered subunit composition of PP2A.This work was supported by the National Institutes of Health (GM026020)
Modeling receptor‐mediated uptake of polymer‐functionalized iron oxide nanoparticles by macrophages
Authors: Lunov Oleg , Zablotskii Vitalii , Syrovets Tatiana , Roecker Carlheinz , Tron Kyrylo , Nienhaus G. Ulrich , Simmet Thomas 
Published: June 2021

Although nanosized materials are quickly taken up by macrophages, our understanding of the involved processes is still rather limited. Here we have analyzed the uptake of carboxydextran‐coated superparamagnetic iron oxide particles by human macrophages. In vitro knock‐down and pharmacological approaches revealed that the main uptake mechanism proceeds via clathrin‐dependent, scavenger receptor‐mediated endocytosis. We created a mathematical model of the uptake process that permits determination of key parameters of endocytosis, such as the uptake rate, the mean uptake time, the number of particles per cell, and the correlation between the number of internalized particles and the extracellular concentration. The calculated parameters correlate well with experimental data obtained by spinning disc confocal microscopy. The model also provides information on the individual and collective wrapping time of the nanoparticles and describes the relation between biophysical parameters such as cytoskeletal forces, membrane elasticity and the uptake time. Finally, we also gained information on the minimal linear spacing between simultaneously acting neighboring endocytotic pits that governs the collective uptake process. This model provides novel insight into the biophysical processes involved in endocytosis of nanoparticles.Supported by the DFG, SPP1313.
Detection and prevention of aggregate formation of cobinamide as an antidote for cyanide poisoning
Authors: Glasheen Megan Elizabeth , Chan Adriano , Boss Gerry , Ali Sameh S. 
Published: June 2021

Cobinamide, a vitamin B12 precursor, has a high affinity for cyanide and is an effective antidote for cyanide poisoning in animal models. However, when given as an intramuscular injection at high concentrations, the compound forms aggregates that both inhibit its absorption and damage the muscle tissue. The objective of this study is to investigate aggregate formation in terms of aggregate number and thermodynamics of formation as a means to prevent aggregate formation in the drug formulation. Cobinamide solutions ranging in concentrations from 5μM to 1mM were scanned from 400nm to 600nm at 25°C, 35°C, 45°C, and 65°C using a spectrophotometer. The spectrum within this range was representative of aggregate formation as visible changes were observed with increasing concentrations and temperatures. A variety of compounds were tested for their ability to prevent aggregate formation. We analyzed the effect of temperature on the stability of the aggregated compounds to determine the heat of formation of the complexes. Our results show that cobinamide forms very strong aggregates that can be largely prevented using carboxylic acids.Supported by the CounterACT Program, Office of Director, NIH and NINDS, Grant #U01NS058030.
Towards the glycoproteome of Mycobacterium tuberculosis
Authors: Hess Sonja , Bell Christina , Smith Geoffrey T , Sweredoski Michael J 
Published: June 2021

Tuberculosis continues to be a major threat to public health having one of the highest mortalities of any infectious disease despite the use of antibacterial therapy and a partially effective vaccine. Mycobacterium tuberculosis has a complex relationship with its host that is mediated in part by glycosylated proteins, but knowledge about the glycoproteome of tuberculosis is still lacking. In fact, the glycostructures are currently known only for two glycoproteins (alanine and proline rich secreted protein APA and superoxide dismutase SODC).To identify potentially glycosylated proteins in M. tuberculosis, we investigated mycobacterial subcellular fractions (cell wall, cell membrane and culture filtrate proteins) using the following lectins: Concanavalin A (ConA), Soybean Agglutinin (SBA), and Wheat Germ Agglutinin (WGA) followed by liquid chromatography‐mass spectrometry approaches and bioinformatic analyses.As expected, there was some overlap between the different lectins in their ability to bind potential glycoproteins. Interestingly, there was no general trend in that one lectin may be better than another. In fact, ConA identified the most glycoprotein candidates in CFP but the least in cell wall and membrane. SBA identified the most candidates in the cell wall whereas WGA identified the largest number of potential glycoproteins from the cell membrane..To validate the presence of glycoproteins, several strategies were pursued including collision induced dissociation and electron transfer dissociation techniques, novel bioinformatics analyses involving a novel virtual neutral loss algorithm and statistical analysis of enrichment in cell fractions with and without lectin treatment.
The feasibility of incorporating whole grains into the diet of older populations
Authors: Gorski Sara Ann , Rosen Renee , Arndt Elizabeth A. , Marquart Len 
Published: June 2021

Less than five percent of adults meet the Dietary Guidelines recommendations of consuming at least half their grains as whole grains. The purpose of this research was to gain a better understanding of whole grain consumption among 40 older adults, mean age 78 years. Focus groups were conducted to examine current knowledge and practices of residents regarding whole grain products in assisted and free living facilities. Qualitative data analyses were used to generate themes. Residents perceived that whole grains provide benefits such as a healthy addition to the diet, good taste/texture and improvement in some medical conditions. Barriers related to whole grains included cost, availability, package size and hard/dry texture. Factors reported that influence whole grain consumption include family, medical professionals and the assisted living facility. Residents had difficulty identifying whole grain and fiber containing foods. Acceptance of five whole grain products was also determined based on survey questions regarding taste, texture, appearance and overall liking of each product. Preliminary taste test results of whole grain food samples indicated the muffin was the most accepted product and hot cereal the least. Older adults’ ability to identify, purchase, prepare and consume whole grains may be limited by a lack of knowledge and familiarity with whole grain products, cost of whole grains, persons of influence, and other facility‐related circumstances.Grant Funding Source : ConAgra Foods
Reelin signaling in the hippocampus and entorhinal cortex contributes to age‐related alterations in cognitive function
Authors: Stranahan Alexis M 
Published: June 2021

Reelin, a glycoprotein implicated in synaptic plasticity, is expressed by entorhinal cortical layer II neurons that project to the hippocampus. Here we report that an age‐related reduction in reelin expression in the entorhinal cortex is associated with cognitive decline. Using immunohistochemistry and in situ hybridization, we observed decreases in the number of Reelin‐immunoreactive cells and reelin mRNA expression in the lateral entorhinal cortex of aged rats that are cognitively impaired relative to young adults and aged rats with preserved cognitive abilities. By contrast, hippocampal reelin signaling decreased with age and was not correlated with cognitive status. The lateral entorhinal cortex of aged rats with cognitive impairment also exhibited changes in other molecular markers, including increased accumulation of phosphorylated tau and decreased synaptophysin immunoreactivity. Interference with reelin signaling in the lateral entorhinal cortex of young rats was sufficient to impair both cognition and synaptic marker expression. Taken together, these findings suggest that reduced reelin expression, emanating from layer II entorhinal neurons, may contribute to network dysfunction that occurs during memory loss in aging.Grant Funding Source: startup
Prevalence and Determinants of Overweight and Obesity in a National Sample of 5–12 Years Old Lebanese Children
Authors: Nasreddine Lara , Naja Farah , Akl Christelle , Adra Nada , Sibai Abla , Hwalla Nahla 
Published: June 2021

The objective of this study is to estimate the prevalence of overweight and obesity among Lebanese children, and to examine associated socio‐demographic, lifestyle and dietary covariates. Based on weight and height measurements obtained from a national cross‐sectional survey conducted in 2009 on 5 – 12 years old subjects (n=493), BMI was calculated. Overweight and obesity were defined according to WHO 2007 growth standards. The association between overweight (including obesity) and baseline socio‐demographic, lifestyle and dietary covariates was examined. Prevalence rates of overweight and obesity were higher among boys as compared to girls (40.0% vs. 34.7% and 20.8% vs. 11.4%, respectively). Saturated fatty acids intake was significantly greater among overweight and obese children compared to their normal weight counterparts (23.64 vs. 20.81 g/d, respectively). Odds of overweight were significantly lower among children living outside the capital Beirut (OR=0.33) and among those consuming daily breakfast (OR=0.29). Odds of overweight were significantly higher among sedentary children (OR=1.44) and among girls with higher maternal educational level (OR=2.24). Findings of this study underline high levels of childhood overweight and obesity in Lebanon and call for national intervention programs to control this epidemic.Study funded by CNRS‐Lebanon, TEPHINET (US) and WHO
School‐age children might be the best source of information for their digestive health
Authors: Kranz Sibylle , Brauchla Mary , Miller Kevin 
Published: June 2021

Bowel movement frequency and stool consistency are important components of children's well‐being, activity, and academic performance. We conducted a pilot study on obtaining these data from school‐age children using a “Regularity Assessment Questionnaire” (RA) in 22 child/parent dyads (41% boys, 7–11 years) who completed a child‐ and a parent‐version of the RA: 8 questions and a picture‐based tool to help classify stool consistency. The RAs were completed weekly for 4 weeks and parents completed a questionnaire summarizing their experience with the RA, their children's understanding of the questions, and the ease of completing the RA. 91% of parents reported that the RA was easy to complete and children understood each of the questions. Interestingly, 50% of parents estimated that children answered “very accurately” and 50% thought the child responded “accurately”. However, more than 60% of the parents reported not to have seen their child's bowel movement in the past week. The matching of responses between the child and the parent increased weekly, ranging 15% – 95%, depending on the question. 5–22% of parents helped their child, 80% only did so the first time. Overall, children in this sample were comfortable reporting on their bowel movements and other questions related to digestive function; studies focusing on digestive health in children should use the child, not the parents, as source of this information.Grant Funding Source : The Kellogg Company
The effect of weight loss on quality of life in obese adults: A study using physical activity and dietary intervention
Authors: Lee Yi Yi , Manan WM Wan Abdul , Rohana A.J. , Mohamad W.B. Wan , Ruhani H. , Ooi G.S. , Rubiah O. , Suzuki M. 
Published: June 2021

This study was carried out to evaluate the maintenance of weight after completing a 12‐week weight reduction program and to record the compliance in continuing the dietary regiment and physical activity during a follow‐up study. This is a repeated measure design to identify the changes in quality of life among participants through three levels of time (pre, post and follow‐up periods). Respondents were assigned into 4 groups using a quasi‐experimental approach which fulfilled the following criteria: BMI>28.0 kg/m2, adults and volunteers. All the four groups (N=60) went through a basic intervention and had performed different packages for 12 weeks as follows: Group 1: Package I (Basic Intervention + Music Therapy + Aerobic Exercise), Package II (Basic Intervention + Aerobic Exercise + Record Keeping), Group 3: Package III (Basic Intervention + Music Therapy + Dumbbell Exercise + Record Keeping), Group 4: Package IV (Basic Intervention + Aerobic Exercise + Dumbbell Exercise + Record Keeping). Quality of life of participants was evaluated by using the SF‐36 questionnaire. The results showed that there was a significant difference of means (p<0.05) for anthropometric variables and quality of life scores. There was an improvement in quality of life among respondents after their weight loss and weight maintenance through compliance of nutritional intake and physical activity.Grant Funding Source: Prof Masashige Suzuki
Adiposity is Associated with Menstrual Cycle Irregularity in Young Women
Authors: Natarajan Radhika , Bertone-Johnson Elizabeth , Zagarins Sofija , Gehlbach Stephen H , Ronnenberg Alayne G 
Published: June 2021

Abnormal menstrual cycles are associated with reduced fecundity and increased risk of miscarriage, possibly due to altered endocrine function. Obesity influences sex steroid levels and has been adversely associated with menstrual cycle length and pattern. However, existing studies lack accurate measures of adiposity and include older women, whose cycles may be affected by other factors. This study examined the association between adiposity and menstrual cycle regularity in young women.METHODSThe UMass Vitamin D Status Study is a cross‐sectional study of 18‐ to 30‐year‐old women. This analysis includes 164 women who did not use oral contraceptives. Women were weighed and measured during the late luteal phase of their menstrual cycle, and percent body fat was assessed using dual energy x‐ray absorptiometry (DXA).RESULTSMean (SD) age, body mass index (BMI) and percent body fat were 21.5 y (3.1), 23.1 kg/m2 (3.3), and 32% (7.8), respectively; 52% of women attained menarche at or before age 12. After adjusting for age and physical activity, women with 32% body fat or less were nearly four‐times more likely to have irregular cycles than women with higher body fat (OR: 3.7; 95% CI:1.1–11.9). BMI was not associated with menstrual cycle characteristics. DXA estimates of percent body fat—but not BMI—suggest that low adiposity is associated with menstrual cycle irregularity. This research is supported by University of MA.
Changes in dietary protein intake differentially affect glucose tolerance and lipid profile in adults with impaired versus normal glucose tolerance
Authors: Janle Elsa M , Conley Travis B , DePalma Glen R , Weinheimer Eileen M , Sands Laura P , Campbell Wayne W 
Published: June 2021

The effects of changes in total protein intake (PRO) on oral glucose tolerance (GT) and lipid‐lipoprotein profile (LLP) were studied in 136 overweight/obese 35–65y, free feeding adults who consumed supplements with 400 kcal/d and 0, 20, 40 or 60 g/d whey protein and exercised 3d/week for 9 months. Retrospectively, subjects were divided into impaired GT (baseline 2‐h glucose > 140 mg/dL) and normal GT groups. Insulin sensitivity was assessed by the Homeostatic Model Assessment (HOMA: 405/(glucosef (mg/dL) • insulinf (U/L)). A multiple regression model assessed the moderating effects of impaired GT on the impact of change in PRO on the GT, HOMA and LLP parameters (adjusted for weight change and gender). A change in PRO was positively associated with changes in HOMA, fasting triacylglycerol (p<0.05) and fasting insulin (p=0.060) in the GT impaired group only (group by PRO, p < 0.05, < 0.05 and 0.061). Change in PRO was not associated with changes in glucose and insulin responses to a 75‐g oral glucose tolerance challenge, or changes in total cholesterol and HDL. In summary, while most research has focused on the effects of total protein intake on health‐related outcomes, these results indicate that the change in protein intake is also important to consider when helping overweight/obese adults with impaired glucose tolerance improve their health.Support: US Whey Protein Res Consort; NIH T32AG025671 and UL1 RR025761
Relationships between features of metabolic syndrome and fatty acid composition of the diet, plasma, and adipose tissue in older adults
Authors: Rose Angela Marie , Asp Michelle , Collene Angela , Belury Martha A 
Published: June 2021

The metabolic syndrome (MetS) is a cluster of conditions including central adiposity, dyslipidemia, hypertension, and hyperglycemia. We conducted a study of 142 healthy older adults aged 60–88, examining fat quality as measured by diet history questionnaire, and plasma and adipose fatty acid composition as predictors for components of MetS.Plasma 16:0, 16:3n4, 18:1n9, and 20:1n9 and dietary saturated fat, monounsaturated fat, and cholesterol predict for having MetS. Dietary monounsaturated fat increases, while adipose 16:1n7 and 18:4n3 decrease, in subjects with increasing numbers of MetS features.Adipose 16:0 is correlated with each feature of MetS. Plasma saturated and monounsaturated fatty acids were positively correlated, while plasma polyunsaturated fatty acid composition was negatively correlated, with triglyceride levels.This study demonstrates several important relationships between the features of metabolic syndrome and fatty acid quality in the diet, plasma, and adipose tissue. Further research should be conducted to determine if these relationships are the result of differences in dietary intake or fatty acid metabolism.
Is the serum level of 25‐hydroxyvitamin D (25[OH]D) inversely associated with obesity and metabolic syndrome in Korean children and adolescents?
Authors: Kim Myung-Hee , Kim Eun-Kyung 
Published: June 2021

To evaluate the association of vitamin D status with metabolic risk factors, fasting blood glucose, insulin, lipid profiles and 25[OH]D were assessed by using venous blood, and body composition was determined by the bioelectrical impedance in 74 subjects aged 7–17 years (42 boys, 32 girls; BMI range 14.8–31.8 kg/m2). Vitamin D status were categorized according to serum 25[OH]D concentration as insufficiency (< 50 nmol/L) and sufficiency (¡Ã 50 nmol/L). Vitamin D insufficiency was present 85.1% of the subjects. BMI, body fat, serum triglyceride (TG), total cholesterol, LDL‐cholesterol, and atherogenic index were significantly higher in vitamin D‐insufficient group (22.7 kg/m2, 29.0%, 70.8 mg/dl, 167.6 mg/dl, 98.9 mg/dl, and 2.23) than in vitamin D‐sufficient group (19.5 kg/m2, 21.2%, 43.4 mg/dl, 144.3 mg/dl, 76.1 mg/dl, and 1.53). And serum 25[OH]D was negatively correlated with age(r=−0.369, p<0.01), weight(r=−0.235, p<0.05), tricep skinfold thickness(r=−0.386, p<0.001), and serum TG (r=−0.274, r<0.05). These results show that a low level of serum 25[OH]D is related with the risk of obesity and hyperlipidemia, not with blood pressure and glucose intolerance, in Korean young people.This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Science and Technology(2010‐0004472).