bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF LIFE‐LONG ENDURANCE EXERCISE ON COLLAGEN CROSS‐LINKING OF THE HUMAN PATELLAR TENDON
Authors: Couppé Christian , Svensson René Brüggebusch , Grosset Jean‐Francois , Kovanen Vuokko , Karlsen Anders , Nielsen Rie Harboe , Skovgaard Dorthe , Kjaer Michael , Magnusson S. Peter 
Published: June 2021

IntroductionIt remains unknown if life‐long habitual endurance exercise influences the accumulation of Advanced Glycation Endproducts (AGE) cross‐links that are closely associated with aging and disease in connective tissue.PurposeTo examine the effect of aging and life‐long habitual endurance exercise on the collagen cross‐linking of the human patellar tendon.MethodsWe investigated 13 healthy injury free master athletes (old trained men, OT; age 59–75 years, running distance of 49±3 km/wk over 29±3 yrs (mean±SEM)), 12 old untrained controls (OC; matched to OT for BMI and age) and 10 young men matched for current running distance (young trained,YT; age 21–34, 48±4 km/week) and 12 young untrained controls (YC; matched to YT for BMI and age). Percutaneous tendon biopsies were obtained and analyzed for enzymatic (HP&LP) cross‐links, pentosidine, and collagen concent from the patellar tendon. A 2‐way ANOVA was used for statistical analysis.ResultsPentosidine increased with age (P<0.001)(Pentosidine: OT, 39±4; OC, 48±3; YT, 11±2 and YC, 9±1 mmol/mol collagen). There was an interaction between age and training (P=0.019), such that master athletes (OT) had a lower tendon pentosidine than OC (P = 0.006).ConclusionThese are the first data to demonstrate AGE cross‐links in tendon in male master athletes are lower compared to old untrained controls. The results suggest that life‐long habitual endurance exercise can counteract the aging process in tendon and thereby possibly reducing the risk of injury. Research support: Danish Association of Rheumatism.
Expression of Calbindin‐D9k and Vitamin D Receptors in the External Genitalia of She‐Camels (Camelus dromedarius)
Authors: Inpanbutr Nongnuch , Emam Mahmoud A. , El‐Zoghby Ihab , Bolon Brod 
Published: June 2021

To investigate the possible role of calcium metabolism in modulating external genitalia function of she‐camels, the localization and distribution of calbindin‐D9k (CaBP9k) and vitamin D3 receptors (VDR) were examined immunohistochemically in samples of vestibule, vulva, and clitoris acquired during breeding and non‐breeding seasons. Animals (n=6 per season) were healthy adults (5 to 10 years) with no history of reproductive tract or systemic disease. CaBP9k was expressed in the cytoplasm of epithelia, but not the stroma or muscles of all three regions examined. Moreover, CaBP9k was expressed in the superficial squamous cell layer of the vulva, and in the basal and parabasal layers of the vestibule. VDR was expressed in the nuclei of epithelia of all three regions, vestibule, vulva, and clitoris. The chondrocytes of the clitoris also expressed VDR. The expression of CaBP9k and VDR was higher during the breeding season than the non‐breeding season, suggesting that external genitalia function may be dependant in part on elevated calcium metabolism during this season.This paper was supported by grant from the government of Egypt (MAE and EME) and OSU Research Fund (NI).
Evolution of the colon in paddlefish, Polyodon
Authors: Wechter Todd , Theodosiou Nicole 
Published: June 2021

Evolution of the colon in paddlefish, PolyodonDuring the vertebrate transition from water to land, the colon played a vital role in water retention, thus allowing for survival in new terrestrial environments. While the colon was previously thought to have evolved following the vertebrate transition onto land, research showing that cartilaginous fish contain a colon‐like organ suggests pre‐adaptation to the terrestrial movement. To determine if the rudimentary colon is unique to cartilaginous fish or was retained throughout the vertebrate lineage, I am examining the paddlefish for a rudimentary colon. The paddlefish, Polyodon is a basal ray‐finned fish, and can provide insight into the evolution of the colon in the vertebrate lineage. Polyodon digestive tracts were examined for the presence of acid mucins, a histological marker for water absorption in the colon. In addition, I will report isolation and expression of the colon patterning genes Hoxd13 and Hoxa13. The possible existence of a region in the paddlefish digestive tract containing acid mucins and Hoxd13 and Hoxa13 expression would suggest that vertebrates were pre‐adapted to transition to land. Furthermore, this data would imply that the colon‐like organ found in cartilaginous fish was not the result of convergent evolution, but was rather a homologous organ.
Creation of a Physical 3D Homo sapiens Single‐cell Model using Confocal Microscopy Data via Rapid Prototyping
Authors: Paliwal Vipin , Hausch Paul , Padmanabhan Vakeel , Ramachandran Ramani 
Published: June 2021

Physical three‐dimensional (3D) cells models are used to enhance understanding of cellular processes. Previously 3D models were artist's renditions of how cells were thought to look like and were not exact. The purpose of this study was to develop a novel process of converting a z‐axis stack of two‐dimensional confocal microscopy images into physical three‐dimensional cell models. Confocal microscope images of a single Homo sapiens endothelial cell were captured depicting the various cell stages of mitosis/cytokinesis or cell division. The high resolution of these images allowed for a single cell model to be produced, which has never been done before via rapid prototyping process. We investigated novel methods to create the most accurate and visually informative 3D cell models possible. Images were further enhanced in the medical imaging program Mimics, resized and oriented in the modeling program Freeform, and converted to the .STL file format prior to production on the rapid prototyping machines. Physical cell models were created using both the Z Corporation's Spectrum Z™ 510 printer and the 3D SystemsTM 250 SLA printer.These new cell models created from microscopic images could benefit research scientists as well as classroom teachers, who can also now explain cellular processes like mitosis kinesthetically by providing hand size models to their students.
Possible role for the adaptor protein complexes in sorting of human papillomavirus
Authors: Schlegel Angela M , Chapman Janice A. , Campos Samuel K. 
Published: June 2021

Human papillomaviruses (HPVs) infect genital and mucosal epithelium and persistent infection with high‐risk strains like HPV16 are associated with cervical, anogenital, and nasopharyngeal cancers. HPV16 particles consist of two structural proteins: the major capsid protein L1 and the minor capsid protein L2. In a previous yeast two hybrid screen using L2 as bait, we identified a potential interaction with a truncated μ chain (μ2) of the adaptor protein complex‐2 (AP2). The AP complex family directs vesicular sorting of cargo via interactions between the AP complex μ subunits and YxxΦ motifs within the cytoplasmic tails of transmembrane receptors. Interestingly L2 contains a number of YxxΦ motifs with variable conservation among different HPV types. The goal of this project is to determine which AP complexes L2 interacts with, how these interactions occur, and the functions of these interactions during infection. Yeast two‐hybrid screens indicate that full‐length L2 interacts with all AP complex μ chains but smaller L2‐YxxΦ peptides have preference for specific μ chains. Infections with YxxΦ‐mutant viruses show decreased infectivity, strongly supporting a role for AP complexes in infection. siRNA single knockdowns of AP complex μ chains show varying effects on infectivity. Current work seeks to understand the nature of these defects and to assess specific roles for L2‐AP complex interactions during infection.Support for this research comes from the Undergraduate Biology Research Program (U. of Arizona UBRP) and the American Cancer Society Research Scholar Grant RSG‐117469.
The molecular determinants for ubiquitin NEDD8 discrimination by human USP2
Authors: Chang Shih‐Chung , Chen Jou‐Han , Shin Yung‐Cheng 
Published: June 2021

Ubiquitin‐like proteins (Ubls) share very high sequence and structural similarity; but conjugation to a protein leads to distinct biological consequences. Ubls are initially synthesized as precursor forms for processing by Ubl‐specific proteases to expose the C‐terminal di‐glycine motif for conjugation to target proteins. Ubiquitin and NEDD8 share 80% sequence identity, however, each exclusive protease can specifically react with ubiquitin or NEDD8. This work is aimed to study the substrate recognition mechanism of USP (ubiquitin‐specific protease) protein family.The crystal structure of USP2‐ubiquitin binding complex showed that residues 4, 12, 14 and 72 of ubiquitin were the major interaction sites. It is also noted that these residues are not conserved in NEDD8. By mutating these sites to the corresponding residues in NEDD8, we found that F4K ubiquitin mutant markedly inhibited its hydrolysis by USP2, and T12E and T14E ubiquitin mutants also showed partial catalytic inhibition due to the steric hindrance and electric repulsion between the mutated residue and USP2. Moreover, mutation of residue 72 further inhibited the hydrolysis of T12E/T14E/R72A ubiquitin mutant than T12E/T14E ubiquitin mutant. Because the key amino acids for interacting with residues 4, 12, 14 and 72 of ubiquitin are conserved in the USP protein family, this study suggests a general recognition mechanism by which USP can specifically discriminate between ubiquitin and NEDD8.
Spatial reorganization of yeast moonlighting protein, enolase, in hypoxia to alter carbon metabolism
Authors: Miura Natsuko , Shinohara Masahiro , Tatsukami Yohei , Morisaka Hironobu , Kuroda Kouichi , Ueda Mitsuyoshi 
Published: June 2021

Hypoxic conditions have critical effects on physiology of organisms. Using Saccharomyces cerevisiae, we have found that glycolytic enzymes conjugated with GFP formed cellular foci in hypoxic conditions. Enolase is one of foci‐forming glycolytic enzymes under hypoxia and is one of moonlighting proteins. Previously, we have found that N‐terminal part of enolase conjugated with EGFP formed cellular foci [1]. The foci formation of both full‐length and N‐terminal part of enolase was inhibited by single alanine substitution.In this study we tried to reveal the mechanisms of regulation and the biological function of enolase foci. The formation of enolase foci was inhibited by treatment with N‐acetylcysteine, AntimycinA and by knocking out SNF1. Interestingly, after forming, foci were retained in the cell even in subsequent aerobic culture. Foci‐carrying cells in presence of oxygen could assimilate [U‐13C]‐glucose more rapidly to produce aspartate, compared to cells which have no foci. These results suggest that in response to hypoxia, S. cerevisiae sensed mitochondrial ROS by activating SNF1/AMPK pathway to form complex of glycolytic proteins in cytosol [2]. The formation of foci may facilitate alternative use of carbon sources of hypoxia‐experienced cells.This work was supported by the Grant‐in‐ Aid for JSPS Fellows [09J02920 to NM].
Vitamin D Supplementation as Influenced by Diabetic Therapies
Authors: Alkharfy Khalid , Al‐Daghri Nasser , Al‐Othman Abdulaziz , Moharram Osama , Alokail Majed , Al‐Saleh Yousef , Sabico Shaun 
Published: June 2021

ObjectiveTo the best of our knowledge, no research has determined the effect of vitamin D3 supplementation in conjunction with existing pharmacological and non‐pharmacological approaches to the diabetes mellitus type 2 (DMT2) population. Hence, this study will primarily determine the effect of vitamin D3 supplementation in a cohort of Saudi DMT2 population on different oral hypoglycemic agents and compare them with a non‐DMT2 control.MethodsA total of 499 randomly selected DMT2 subjects divided into 8 groups [Non‐DMT2 Control = 151; Rosiglitazone (Avandia) = 49; Diet = 15; Insulin alone = 55; Insulin + Orals = 12; Metformin alone = 121; Oral agents combination = 37; Sulphonylurea = 59] were included in this 12‐month interventional study. All subjects were given 2000IU vitamin D3 daily except the control group. Anthropometrics, glucose, lipid profile and 25‐OH Vitamin D were measured at baseline, 6 and 12 months.ResultsMetformin group showed the highest change in vitamin D levels in both 6 months (62.6%) and 12 months (50.6%) as compared to baseline (p< 0.001). No significant changes were observed in the BMI, glucose, total‐ and HDL‐cholesterol in all DMT2 groups. Significant decreases in triglycerides were observed in both the rosiglitazone and insulin + orals group in both 6 and 12 months supplementation (both p‐values < 0.001).ConclusionWhile all groups seemed to increase in levels of vitamin D following supplementation, it appears that DMT2 patients on insulin in combination with other drugs are the group that will benefit the most as compared to other groups in terms of improving cardiovascular risk. Metformin favorably improves vitamin D levels but do not seem to confer other added cardiometabolic benefits.
Structural basis of human cannabinoid CB1 G protein‐coupled receptor activation
Authors: Scott Caitlin Eileen , Abrol Ravinder , Ahn Kwang H. , Huang Yuehan , Kendall Debra A. , Goddard William A. 
Published: June 2021

Transmembrane signal transduction is achieved by activation of G protein‐coupled receptors (GPCRs) like the human cannabinoid CB1 receptor. These receptors exist in an ensemble of conformations, each of which might bind to different signaling molecules. Mutating a single residue, Thr 210, to Ile in the third transmembrane (TM3) domain, makes it more active then WT, whereas mutating it to Ala makes it fully inactive. We used the Gensemble method to predict 3D structures of these receptors. We find conformational differences that explain the CB1 receptor's activation mechanism. These predictions were validated by designing double mutants that were expected to switch the inactive T210A back to WT levels of activation. The 2nd mutation for T210A is predicted to cause an important salt‐bridge between TMs 2 and 6 to break. GTPδS binding assays show a large increase in G protein‐coupling for the double mutants indicating increased activation. We docked known agonists to these receptors and then performed 50 ns of molecular dynamics. The inactive T210A receptor with the docked agonist WIN55212‐2 maintains two stable interhelical salt‐bridges. Similarly, the WT receptor maintains a salt‐bridge between TMs 3 and 6, which suggests that a G protein is necessary to stabilize the active conformation.This work was funded by gifts from PharmSelex/Accelerator and NIH grants (R01NS071112, R01NS073115, R01AI040567, and DA020763).
Regulation of ATP‐dependent Chromatin Remodeling
Authors: Cairns Bradley , Clapier Cedric 
Published: June 2021

The objective of our research is to understand how ATP‐dependent chromatin remodeling machines (Remodelers) are regulated. Remodelers contain a catalytic ATPase subunit that conducts DNA translocation, used to pump DNA around the nucleosome. Here, we define and characterize new domains/regions present on the ATPases of the RSC and ISWI remodelers, and show how they regulate ATPase, translocase and nucleosome remodeling activities.The catalytic ATPase of the RSC remodeler is bound by a heterodimer of actin‐related proteins (ARPs). Here, we present a crystal structure of the ARP module at high resolution. In order to understand how ARPs regulate DNA translocation, we applied genetic, biophysical and biochemical approaches. Here, we reveal a new domain that functions as a negative regulator, restricting ATPase and DNA translocation activities, which is antagonized by the ARP/HSA module. For ISWI remodelers, we reveal an autoinhibition mechanism for ISWI regulation involving an N‐terminal domain, and also define a novel region in the C‐terminus of the ISWI enzyme important for the coupling of energy‐consumption with DNA translocation. Together, these discoveries emphasize the importance of the regulation of ATPase, translocase and remodeling activities by an elaborate network of domains. This work is supported by NIH GM60415 and HHMI.
Developing Mass in Motion Kids: A multi‐sector intervention to reduce childhood obesity using community‐clinical partnerships
Authors: Blaine Rachel , Taveras Elsie , Davison Kirsten , Gortmaker Steven , Anand Shikha , Falbe Jennifer , Criss Shaniece , Perkins Meghan , Kwass Jo‐Ann , Land Thomas , Smith Lauren 
Published: June 2021

As part of a state‐community‐university partnership, Mass In Motion Kids (MiM Kids) was designed as a community‐based intervention to prevent and reduce obesity among primarily low‐income children ages 2–12. Two intervention communities in MA were identified by demographic features and community interest. MiM Kids addresses key behaviors, including screen time, consumption of sugar sweetened beverages, physical activity, sleep duration/sleep quality, and replacement of calorically‐dense foods with fruits and vegetables. Using the Obesity Chronic Care Model as a foundation, literature review and stakeholder feedback informed selection of evidence‐based interventions targeting primary health care (High Five for Kids; Healthy Weight Collaborative), child care (I Am Moving, I am Learning; NAP SACC) and schools/after‐school programs (Food & Fun, Eat Well and Keep Moving, and Planet Health). Environmental policy change (e.g. healthy dining, park space), technical assistance and training, and a youth‐driven communication campaign were also identified as strategies to engage residents. Since MiM Kids was built upon an existing statewide initiative, it is well positioned to be replicated throughout MA if found to be efficacious.Grant Funding Source: Centers for Disease Control and Prevention: U18DP003370–01
Restaurant meals ‐ almost a full day's worth of calories, fats and sodium
Authors: Scourboutakos Mary J. , L'Abbe Mary R. 
Published: June 2021

The objective was to systematically analyze the nutritional profile (calories, fat, saturated fat, trans fat, sodium and cholesterol) of meals from chain sit‐down/family style restaurants. Using the “U of T Restaurant Database”, the nutritional profile of 3507 meals from 19 restaurants was calculated and analyzed. This included all potential meal combinations from restaurants that provided nutrition information online and had 10 or more locations nationally. On average, breakfast, lunch and dinner meals contained: 1129 calories (56% of the average daily 2000 calorie recommendation), 151% of the amount of sodium an adult should consume in a single day (2263 mg), 89% of the recommended daily fat intake level (58 g), 83% of the recommended daily saturated and trans fat intake level (16 g saturated fat and 0.6 g trans fat) and 60% of the daily value for cholesterol (179 mg). More than 80% of meals exceeded the daily recommended intake level for sodium (1500mg). Only 1% of meals had less than 600 mg of sodium, the “healthy level” for meals, according to the FDA. Meals identified by the restaurants as being “healthy” contained on average 474 calories, 13 g of fat (20% DV), 3 g of saturated fat (17% DV) and 752 mg of sodium (50% AI). These data demonstrate that addressing the nutritional profile of restaurant meals should be a major public health priority.Grant Funding Source: MS: CIHR/PICDP Fellowship, Ontario Graduate Scholarship, ML: U of T McHenry Grant, Canadian Stroke Network
Interrelationships of growth, development and biomarkers of iron status
Authors: Balakrishna N , Radhakrishna KV , Nair K Madhavan , Fernandez‐Rao S , Ravinder P , Hurley K M , Tilton N , Harding K , Reinhart G , Black M M 
Published: June 2021

ObjectiveTo study the relationships between a set of observed variables and a set of continuous latent variables among growth, development and iron statues in rural infants using confirmatory factor analysis.MethodsZ scores of height for age, weight for age and arm mid‐upper arm circumference for age were calculated. Motor, language and visual reception were in 497 infants of 6–12 months using Mullen Scales of Early Learning. Indicators of iron status, hemoglobin, ferritin and sTfR were analyzed. Comparative fit index (CFI), goodness of fit index (GFI), normed fit index (NFI) and root mean square error of approximation (RMSEA) were used for testing the model.ResultsCFI (0.962), GFI (0.966) and NFI (0.935) values met the criteria for an acceptable model fit ¡Ý0.90. The RMSEA obtained was 0.052 which is close to a cut‐off value of ¡Ü0.05 suggesting a good fit. The relationship between development, and indictors of iron status was significant r=0.130 (p<0.05). Fine motor and visual reception showed higher loadings for development. Other contributing variables were found to be weight and sTfR.ConclusionsThe results suggest that the model is valid to establish the interaction between iron status and development. Research support: Mathile Institute & Micronutrient Initiative
Dietary energy density as a risk factor for obesity and cancer
Authors: VERNARELLI JACQUELINE Andrea , Mitchell Diane C , Rolls Barbara J , Hartman Terry J 
Published: June 2021

Obesity is an established risk factor for cancer. The objectives of the current study are first to determine whether dietary ED is related to obesity‐related cancer risk factors, and then to evaluate what dietary patterns contribute to this relationship.Data from a nationally representative sample of 8,550 adults ≥18y who participated in the 2005–2008 NHANES were analyzed. Food energy density (ED, energy per weight of food, kcal/g) was calculated and categorized into one of five categories. Age‐ and sex‐specific quartiles of ED were created to examine the relationship between ED and other obesity‐related risk factors for cancer.ED was positively associated with abdominal obesity in both men and women in multivariate models. Adults in the highest ED quartile had a 55% increase in risk for abdominal obesity (WC >;88cm in women; 102cm in men) compared to those in the lowest quartile (OR=1.2, 95%CI 1.1–1.4) after adjusting for relevant cofactors. When investigating dietary trends contributing to this relationship, it was observed that lean individuals consume significantly more low‐ED foods (<2.25kcal/g) and fewer high‐ED foods (≥2.25kcal/g) than obese persons.Overall dietary ED and consumption of high‐ED foods were both positively associated with established obesity‐related risk factors for cancer in a nationally representative sample of US adults.