bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of biosensor for protein tyrosine kinases
Authors: Wei Lan-Yi , Yuan Chiun-Jye 
Published: June 2021

Protein tyrosine kinase plays an important role in many cellular events, and many diseases are found to be associated with the dysregulation of various protein tyrosine kinases. However, the conventional methods for the detection of the activity of tyrosine kinase were expensive, specific instrument required, and high risk of radioactive contamination. In this study, A simple, quick and label‐free detection method was developed and developed. The general concept of this detection method is based on the fact that tyrosinase‐based amperometric biosensor can catalyze an electrochemical response of tyrosine but not its phosphorylation form, phosphor‐tyrosine. Further studies showed that the tyrosinase‐based biosensor could recognize tyrosyl residue within either dipeptides or heptapeptide p60c‐src substrate I, a specific peptide substrate for Src kinase. The linear dynamic range of detection to p60c‐src substrate I was studied with a sensitivity of 0.71μA μM‐1cm‐2. The effect of various kinase inhibitors in the Src activity was also studied.Financially supporting by NSC‐97‐2311‐B‐009‐001 MY3.
Anatomy for Physician Assistants: A program director's perspective
Authors: Luke Sharon 
Published: June 2021

The Review Commission on the Education of the Physician Assistant, Inc. (ARC‐PA), the body that accredits physician assistant (PA) programs in the United States, requires that all entry‐level PA programs instruct their students in Anatomy. The commission does not dictate, however, how programs provide that instruction.Students generally complete a didactic phase in physician assistant education that spans 12–15 months. Subsequent to the didactic phase of the program, students complete a clinical phase, in which they apply the principles of medicine they learned during the didactic phase to patient management encounters.This session will review the most popular ways that programs provide Anatomy instruction to their students, and what components of Anatomy instruction are most important to program directors in relation to curriculum mapping and learning outcomes for their programs.
Acyl chain dependent product inhibition by phosphatidylserine synthases
Authors: Kimura Atsuko Kakio , Kim Hee-Yong 
Published: June 2021

Phosphatidylserine (PS), the major anionic phospholipid in eukaryotic cell membranes, is synthesized by PS synthase 1 (PSS1) and PSS2 through the serine‐base exchange reaction from phosphatidylcholine (PC) and phosphatidylethanolamine (PE), respectively. Membrane PS is critically involved in key cell signaling processes such as Akt, PKC and Raf‐1 activation. The membrane PS profile is well maintained although mechanisms for the regulation of the PS profile are not clearly understood. In this study, we investigated the effect of PS acyl chain on the feedback mechanism in which activities of PSSs are inhibited by product PS. We found that PSS1 and PSS2 have significantly different inhibitory response to two PS molecular species, oleic acid (OA, 18:1n‐9) containing (OA‐PS) and docosahexaenoic acid (DHA, 22:6n‐3) containing PS species (DHA‐PS). PSS1 was inhibited more strongly by OA‐PS, while PSS2 was more by DHA‐PS. Together with the differential expression between PSS1 and PSS2 in variety of cells and tissues, these results indicate that the level of individual PS molecular species is regulated through feedback mechanism by which synthetic activity of each enzyme is inhibited differently.Intramural Program of National Institutes of Health
Endoplasmic reticulum stress induces the degradation of stearoyl‐CoA desaturase protein in human retinal pigment epithelial cells via ubiquitin‐proteasome pathway
Authors: Samuel William , Kutty R. Krishnan , Duncan Todd , Redmond T. Michael 
Published: June 2021

Perturbations to endoplasmic reticulum (ER), the central organelle for protein biosynthesis and maturation, can cause ER stress, and if unchecked could lead to apoptosis. Stearoyl‐CoA desaturase (SCD), an ER resident protein and a key enzyme in the biosynthesis of monounsaturated fatty acids, is known to regulate cellular functions by controlling the ratio of saturated to monounsaturated fatty acids. SCD has been reported to be degraded through both ubiquitin‐proteasome‐dependent and‐independent pathways when overexpressed in cells. The purpose of this study was to determine whether ER stress affects the expression of SCD protein. Human retinal pigment epithelial (ARPE‐19) cells treated with N‐(4‐hydroxyphenyl)retinamide (4HPR), tunicamycin and thapsigargin, compounds known to induce ER stress, showed a time‐dependent decrease in the expression of SCD protein, while, BiP/GRP78, a protein marker for ER stress, was markedly increased. The decrease in SCD protein expression was completely blocked by the proteasome inhibitor, MG132. Immunoprecipitation analysis of 4HPR‐treated cell lysate using ubiquitin antibody showed that ER stress increased the ubiquitination of proteins including SCD. Thus, these data show that ER stress mediates the degradation of SCD in human RPE cells via the ubiquitin‐proteasome dependent pathwaySupport: Intramural Research Program, NEI, NIH
Further Characterization of a Unique Mycobacterial Heme Uptake System
Authors: Goulding Celia Whitford , Owens Cedric , Chim Nick , Harmston Christine , Iniguez Angelina , Contreras Heidi , Morse Robert 
Published: June 2021

Mycobacterium tuberculosis (Mtb), the primary agent of tuberculosis, is one of the most frequent causes of death by a single infectious agent. Mtb must import iron from its host for survival, and its siderophore‐dependent iron acquisition pathways are well established. Recently, we documented a newly characterized pathway, whereby Mtb can use free heme and heme from hemoglobin as an iron source.Significantly, we identified the genomic region responsible for the passage of heme‐iron across the mycobacterial membrane. For the first time, key players of this heme uptake system were biochemically characterized including a secreted heme‐binding protein and two transmembrane proteins (MmpL3 ad MmpL11), all three specific to mycobacteria. Furthermore, within the Mtb cytosol, we have characterized a heme‐degrading protein MhuD, which releases iron from the heme tetrapyrrole ring for utilization by Mtb. We have extended our studies and will discuss further characterization of genes involved in this heme acquisition pathway, biochemical analysis of heme transfer from the secreted heme carrier protein to soluble domains of the putative heme transporters, as well as confirmation that the Mb essential gene which encodes for MmpL3, plays a role in mycobacterial heme transport.The discovery of this unique mycobacterial heme acquisition pathway opens new avenues of exploration into mycobacterial therapeutics.Sources of research funding are NIH NIAID/NIGMS and the American Lung Association.
Dietary Intake of Omega‐3 Long‐chain Polyunsaturated Fatty Acids (n‐3 LCPUFA) by US Toddlers
Authors: Walsh Kelly Robert , Ye Qian , Piekarz Ana 
Published: June 2021

Backgroundn‐3 LCPUFA, in particular docosahexaenoic acid (DHA), have critical roles in the nervous, visual and immune systems. While studies have addressed DHA intake and functional outcomes in infants, data on dietary intakes of US toddlers are scarce. The NHANES 1999–2000 study showed an average consumption of 20 mg of DHA per day which is less than recommended by international expert groups.ObjectiveTo evaluate the average daily consumption of DHA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) from food and beverages among healthy US toddlers between 12 and 47 month of age based upon the NHANES 2007–2008.MethodsDietary intakes of 741 healthy toddlers from NHANES 2007–2008, a nationally representative survey, were analyzed. Intakes from dietary supplements were excluded from the analysis. Mean usual intakes of DHA, DPA and EPA from food and beverages were calculated using NHANES suggested methodology to ensure a representative sample.ResultsMean (± SE) consumption of DHA, DPA and EPA among US toddlers is 19 (± 1.9) mg/day, 4.5 (± 0.3) mg/day, and 8 (± 0.9) mg/day, respectively.ConclusionDietary intake of n‐3 LCPUFA by US toddlers remains below target recommendations established by international expert groups such as the FAO (2010). Dietary strategies for closing the gap between current intakes and recommended targets are needed.
Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats
Authors: Legette LeeCole L , Moreno Luna Arlyn Y. , Reed Ralph L , Miranda Cristobal L. , Bobe Gerd , Proteau Rosita R. , Stevens Jan F. 
Published: June 2021

Metabolic syndrome is a leading public health concern with over 50 million Americans being affected and at increased risk for other chronic diseases including cardiovascular disease, obesity and type II diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker obese fa/fa rats. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.69, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN 93G diet for 3 weeks to induce severe obesity followed by a normal AIN‐93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, and triglyceride levels were assessed using commercial assay kits. There was a dose‐dependent effect on body weight and plasma glucose levels. The highest dose group (n=6) had significantly lower plasma glucose levels compared to the control group (n=6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group compared to rats that received no xanthohumol which was also not seen for female rats. Plasma cholesterol, insulin and triglycerides as well as food intake were not affected by treatment. Findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome but may induce gender‐specific responses.Grant Funding Source : National Institutes of Health and USANA Health Sciences
Influence of Exercise and Weight Loss on Glucose Tolerance and Bone Mass in Young Growing Animals
Authors: Hembree Kelsey D , Rendina Elizabeth , Wang Yan , Clark Katie , Davis McKale R , Peterson Sandra K , Clarke Stephen L , Lucas Edralin A , Smith Brenda J 
Published: June 2021

Childhood obesity has been associated with increased fracture incidence, but the effects of weight loss and exercise on the bone health of children remains unknown. Therefore, this study was designed to determine the effects of exercise and weight loss on bone mass and glucose homeostasis in a young growing animal model of diet‐induced obesity. Six wk old male C57BL/6 mice (n=42) were fed a control diet (CON=10% fat) or high fat diet (HF=60%) for 12 wks. The last 4 wks of the study, mice were further divided into exercise (Ex), no exercise (NoEx), or weight loss regimen (HF→CON). At end of the study, body weight was not significantly reduced in the HF+Ex group. In contrast, the 15% reduction in weight in the HF→CON group resulted in similar body weights to mice on the CON diet. Both the HF+Ex and the HF+NoEx groups experienced an increase (P<0.05) in fasting glucose, but the glucose levels of the HF→CON group were normalized to the CON groups. The HF+Ex and HF→CON groups demonstrated a similar response in their glucose tolerance test. The 4 wk exercise protocol increased whole body and femur bone mineral density (BMD), but the HF→CON mice significantly reduced their spine BMD compared to the non‐exercising groups. These data suggest that in obese animals weight loss without exercise results in a negative effect on spine bone density.Grant Funding Source : Oklahoma Agricultural Experiment Station
The association between Serum Estrogen, Fat Mass and Type II Diabetes in the Boston Puerto Rican Health Study (BPRHS)
Authors: Landry Latrice , Tucker Katherine 
Published: June 2021

BackgroundResearch suggests that estrogen modulates adiposity and may be protective against diabetes (T2D). Data on the association between estrogen, obesity and diabetes is limited in Puerto Ricans. This study examines the cross‐sectional relationships between serum estradiol (E2) with gynoid and android fat mass and T2D in Puerto Rican adults in the Boston Puerto Rican Health Study (BPRHS).DesignE2 and android and gynoid fat mass (from DXA) were measured in 538 BPRHS participants. Multivariate regression was used to assess cross sectional relationships between E2 and gynoid and android fat mass. Logistic regression was used to assess the associations with T2D. E2 and total energy intake were log transformed. Covariates included age, sex, pack years, physical activity score, menopausal status, hormone use, and intakes of total energy, fat, and carbohydrate.ResultsE2 was positively associated with gynoid (p<0.0001) and android (p<0.0001) fat and T2D (0.03). Android fat (p<0.0001) was positively associated with T2D. Gynoid fat (p<0.0001) was negatively associated with T2D.ConclusionConsistent with findings from other populations, our findings suggest a positive association between E2 and body fat and T2D. The inverse association between gynoid fat and T2D is novel. Longitudinal studies with adjustment for other metabolic measures are needed to clarify these potential associations.Grant Funding Source : NIH‐P01 AG023394, Pfizer SNMA David E Satcher Fellowship
Grape seed extract and delta tocotrienol alone and in combination ameliorates histopathological features in C57BL/J6 mouse fed high‐fat diet
Authors: Sodhani Shradha , Juma Shanil , Vijayagopal Parakat , Prasad Chandan , Imrhan Victorine , Mills Nathaniel 
Published: June 2021

The condition of non‐alcoholic steatohepatitis (NASH) presents a progressive pathology leading to steatotic fibrosis and potentially hepatic cancer. Polyphenols in grape seed extract (GSE) and fat soluble vitamin E (ä tocotrienol, ä3T) may play a beneficial role in hepatic fibrosis. In this study we examined the effects of dietary GSE and ä3T in C57BL/6J mice fed high‐fat diet (n=8/group) for 20 weeks. Post necropsy general histology and immunohistochemical analyses were performed with alpha‐smooth muscle actin (á‐SMA) as a biomarker in liver fibrosis. Mice in the high fat diet control group (HFD‐C) had increased fat accumulation and NASH‐like histopathological features. Histological data analysis of H&E stained liver sections showed that steatosis and lipid droplets were reduced in HFD+GSE group compared to HFD‐C group. Immunohistochemical staining and analysis of photomicrographs led to observable reduction of á‐SMA in HFD+GSE supplemented group compared to HFD‐C group. Our data shows that dietary GSE and ä‐tocotrienol alone and in combination may ameliorate the NASH‐like histopathological features including fibrosis in C57BL/6J mice.Supported by Research Enhancement Program, TWU
Consumption of dehydrated Opuntia ficus Indica (nopal) prevents the development of fatty liver by modifying hepatic lipid metabolism in obese Zucker fa/fa rats
Authors: Moran-Ramos Sofia , López-Romero Patricia , Tovar Armando R , Torres Nimbe 
Published: June 2021

Opuntia ficus indica (nopal), a plant rich in bioactive compounds, has been widely used in the traditional Mexican medicine to treat diabetes. Therefore in the present study, we investigated the effect of nopal consumption in the prevention of fatty liver in obese Zucker rats.Six weeks old male Zucker (fa/fa) rats (n=12 per group) were fed with a control diet (AIN‐93G; C) or C+ Nopal for 7 weeks. After 7 weeks of dietary treatment, rats fed C+nopal decreased by 50% hepatic triglycerides with respect to control and reduced hepatomegaly and macrovesicular steatosis. In addition, increased serum levels of adiponectin, mRNA expression of genes involved in lipid oxidation (PPARα, CPT1 and ACOX) and lipid export (MTTP and PLTP), hepatic CPT1 and MTTP protein levels. Furthermore, rats fed C+nopal decreased postprandial serum insulin levels; increased liver pAkt/Akt ratio in the postprandial state and significantly decreased serum ALT and AST levels.This study shows that nopal consumption prevents the development of fatty liver in obese Zucker rats by increasing fatty acid oxidation and VLDL synthesis,, improving liver insulin signaling. Supported by Grupo Produce DF 2010 (to NT)Grant Funding Source: Produce
Fetal overgrowth (FOG) is associated with early perturbations in amniotic fluid (AF) glucose, insulin and insulin like growth factors (IGF) in mothers with and without gestational diabetes (GDM)
Authors: Tisi Daniel K , Koski Kristine G 
Published: June 2021

FOG occurs in mothers with and without GDM. Few biochemical markers have been identified. We investigated the possibility that perturbations in 2nd trimester AF glucose, insulin, IGF 2 or its binding proteins (BP) 1 or 3 might underscore FOG and that these early AF disturbances might differ in mothers with or without GDM. Our study population (n=701) was stratified as follows: mothers were classified as GDM or NON GDM and their offspring as appropriate (AGA) or large for gestational age (LGA). ANCOVA, multiple linear and logistic regressions were performed and, using pairs of AF constituents, 2D Bayesian probability plots were created to predict LGA. In the GDM population AF insulin was positively and IGF 2 was negatively associated with growth centile, while elevated AF glucose increased the odds of neonates being born LGA. In the NON GDM population AF insulin was positively and BP 3 negatively associated with growth centile, but the likelihood of LGA was not increased by AF glucose. Bayesian probability plots showed that specific AF constituents separated LGA from AGA infants in GDM mothers but were less discriminating in NON GDM mothers. In conclusion, fetal exposure to increased AF glucose in the first trimester increases the risk of delivery of an LGA infant in GDM mothers. Lower BP 3 in NON GDM mothers and IGF 2 in GDM mothers provide further evidence that perturbations in growth factors may underscore FOG. [Funded by CIHR]Grant Funding Source: CIHR
Differential binding of low molecular weight heparins with antithrombin and platelet factor 4 as measured by surface enhanced laser desorption ionization (SELDI)
Authors: Kahn Daniel , Hoppensteadt Debra , Hejna Matthew , Jeske Walter , Walenga Jeanine M , Fareed Jawed 
Published: June 2021

IntroductionHeparin (H) and low molecular weight heparins (LMWHs) are composed of multiple chain components varying in their physicochemical and biologic profile. LMWHs are derived by depolymerization of heparin and differ in their composition and biologic profiles. Antithrombin (AT) and platelet factor 4 (PF4) represent two of the major modulators of heparin oligosaccharides. Protein chip array technology is useful in the binding of proteins to various ligands. In this study SELDI is utilized to investigate the differential binding of H and various LMWHs.Materials and methodsH and various branded LMWHs such as Enoxaparin, Dalteparin, Tinzaparin and generic versions of Enoxaparin were studied for their complexation with purified human AT and PF4. All agents were mixed in Tris HCl buffer matrix at equigravimetric amounts. Gold chips were employed to determine the molecular profile and the binding ratios were determined by measuring peak intensities. The relative suppression of peak intensities were proportional to the binding profile of each of these agents.ResultsFor both the AT and PF4 binding on a gravimetric basis, H was found to bind much higher than the LMWHs. Significant differences in the binding profiles for the AT and PF4 were noted among different LMWHs. These binding differences may be due to the compositional differences in these drugs.
Overexpression of claudin‐6, ‐7 or ‐9 modifies the activation of MMP‐2 and MMP‐9
Authors: Martinez Ana Cristina Torres , Estrada Luis Felipe Montaño , Rendon-Huerta Erika P. 
Published: June 2021

Tight junctions (TJ) have a critical role in the control of paracellular transport and in the maintenance of cell polarity. Claudin family is essential to confer different properties to epithelial cell permeability; however their expression is altered in several tumors and is associated with increased invasive capacity as a result of increased activity of metaloproteinases (MMPs). Claudins ‐1, ‐2, ‐3 and ‐4 can recruit and promote the activation of MMP‐2. Decrease in claudin 10 expression diminishes cell invasiveness through down‐regulation of MMP‐2 and MT1‐MMP in hepatocellular carcinoma. Our group has reported that CLDN 6, 7 and 9 are overexpressed in human gastric adenocarcinomas and these claudins promote cell proliferation and invasiveness, however the mechanisms involved are unknown. To determine whether overexpression of claudins‐6, ‐7 or ‐9 leads to activation of MMPs, we evaluate changes in metalloproteinases expression and activation by immunoprecipitation and zymography assays in claudin‐transfected human gastric adenocarcinoma (AGS) and breast cancer (MCF‐7) cells. The results show a probable interaction of claudin‐9 with MMP‐2 and MMP‐9 in AGS cells and a correlation between overexpression of claudin‐7 and ‐9 with a decrease in the activity of MMP‐2. Similarly colocalization of claudin‐6 and ‐7 with MMP‐2 and claudin ‐6, ‐7 and ‐9 with MMP‐9 was observed in MCF‐7 cells. These results suggest an important role for claudin‐7 and ‐ 9 in the activation of these metalloproteinases.This work was supported by PAPIIT‐IN208910‐2.
Tectonics form a transition zone complex of ciliopathy proteins that regulate ciliary composition
Authors: Reiter Jeremy , Garcia-Gonzalo Francesc , Corbit Kevin , Dowdle William , Yee Laura 
Published: June 2021

Primary cilia are projections found on many human cells. These cilia do not move, but function as cellular antennae to receive and interpret signals. For example, olfactory cilia sense signals from the environment, such as odorants. Other cilia sense cues from other cells, such as Hedgehog proteins, to coordinate tissue patterning and growth. We have identified mechanisms of ciliary signaling, cilium formation, and the regulation of ciliary composition. Defects in ciliary signaling cause some forms of birth defects, cancer, polycystic kidney disease, and other disorders collectively called ciliopathies. Investigating ciliopathies is illuminating how disturbing the function of a single organelle can give rise to diverse human diseases.We have found that two ciliary proteins of the Tectonic family, Tctn1 and Tctn2, form part of the transition zone, a region at the base of the cilium. Tctn1 is an extracytosolic glycoprotein that interacts with transmembrane components of the transition zone such as Tmem67 to connect to a cytosolic transition zone complex comprised of most known Joubert‐ and Meckel‐associated proteins. Loss of components of the Tectonic transition zone complex in mice compromise ciliogenesis in some tissues, and deregulate ciliary protein composition in others. We hypothesize that transition zone defects disrupt intercellular signaling, causing the multiorgan disease observed in ciliopathies, including polycystic kidney disease and birth defects such as polydactyly.