bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison study between RBC folate measured by microbiologic assay and Immulite 2000 immunoassay
Authors: Aufreiter Susanne , Colapinto Cynthia K , Tremblay Mark S , Bushnik Tracey , Pfeiffer Christine M , O'Connor Deborah L 
Published: June 2021

Significant inter‐laboratory differences exist in values obtained for RBC folate (RBF). The objective of this methods comparison study was to generate a conversion equation that describes the relationship between RBF measured by the Immulite 2000 immunoassay and the microbiologic assay (MA). Blood was drawn from 152 healthy participants in Toronto, Canada. Folate concentrations were determined by MA (chloramphenicol‐resistant microorganism [L. Rhamnosus], calibrated with 5‐methyltetrahydrofolate) at The Hospital for Sick Children and by the Immulite 2000 immunoassay at the Health Canada Canadian Health Measures Survey (CHMS) laboratory. A Pearson's coefficient, r, of 0.67 guided the decision to use weighted Deming regression, which accounts for random error of both X and Y and controls for proportional bias. The final weighted Deming regression model was as follows: Predicted microbiologic assay = −22.95 + 0.81*Immunoassay. For validation, the whole sample was randomly split into two groups: 1) estimation 2) validation. The same mean absolute percentage error was obtained in the validation group as in the entire sample set (23%), indicating robustness in the precision of the model's predicted values. This equation will be used to compare the RBF data from the CHMS to the US NHANES (measured by Immulite 2000 immunoassay and MA, respectively).Grant Funding Source: Canadian Institutes for Health Research Fellowship (180375) to C.K.C and Operating Grant (218776) to M.S.T, D.L.O and C.K.C
Differential Capability of Korean Soybean Varieties to Biosynthesize Glyceollins
Authors: Kim Jong‐Sang , Park In Sil , Kim Hyo Jung , Kang Hye Ryung , Seo Ji Yeon , Kim Seong Soon , Kim Bo Ram , Zakaroba Alexandra 
Published: June 2021

Glyceollins synthesized in soybeans exposed to biotic or abiotic stress were reported to have several health benefits. Soybean accumulated glyceollins at widely different levels depending upon the varieties when elicitated with Asp. sojae. Contrary to our hypothesis that high‐isoflavone variety may accumulate glyceollins upon elicitation more efficiently, glyceollin accumulation mediated by fungal elicitation was not significantly affected by the concentration of either total isoflavones or daidzein in soybean. However the levels of glyceollins were also significantly affected by the elicitation methods, showing that fungal stress was most efficient in glyceollin production. Therefore, glyceollin accumulation in soybean seems to be affected by several factors such as the responsiveness of genes involved in glyceollin biosynthesis to elicitors as revealed by comparison of mRNA gene expression involved in glyceollin synthesis by RT‐PCR. This data suggest that glyceollin accumulation in soybean seems to be more affected by other factors such as the responsiveness of genes involved in glyceollin biosynthesis to the elicitors and types of elicitors than isoflavone content.Grant Funding Source: National Research Foundation of Korea
Patterned laminin expression by spheroid‐forming melanoma cells
Authors: Larson Allison R , Lezcano Cecilia , Lee Chung‐Wei , Huang John , Zhan Qian , Murphy George F 
Published: June 2021

Vasculogenic mimicry, a collection of laminin networks within tumors is associated with a poor prognosis in melanoma and other cancers. Cultured melanoma cell lines that form spheroids are associated with increased invasiveness in vitro. Accordingly, we hypothesized that spheroid‐forming melanoma cells may also show patterned laminin networks. By immunohistochemistry, the A2058 melanoma cell line showed prominent patterned laminin networks within spheroids that closely mimicked networks that developed in primary melanoma xenografts to NSG mice. Real time PCR analysis of laminin subunits confirmed that anchorage‐independent spheroid‐forming cells expressed a different laminin profile from non‐spheroid‐forming adherent cells. These findings suggest that melanoma spheroids represent a novel approach to studies concerning the nature and significance of vasculogenic mimicry and associated laminin network formation.Funding provided by NIH Grant SPORE Core: NIH, NCI SPORE in Skin Cancer 5P50CA093683–08, BWH Biomedical Research Institute Microseed Grant, A.L. is supported by BWH Dept of Dermatology NIH Training Grant T32AR007098–38.
The pMAPK/pAMPK ratio modulates the effect of adiponectin on breast cancer cell growth
Authors: Mauro Loredana , Pellegrino Michele , Ricchio Emilia , De Amicis Francesca , Catalano Stefania , Bonofiglio Daniela , Rizza Pietro , Panno Maria Luisa , Ando' Sebastiano 
Published: June 2021

Adiponectin, an adipose tissue‐derived hormone, may influence breast cancer progression. Here, we demonstrated in vitro and in vivo that low concentration of adiponectin at (1–5 μg/ml) induced a dicotomic pattern of effects on breast cancer growth, namely a stimulatory action in MCF‐7 cells, mediated by MAPK activation, and an inhibitory effect in MDA‐MB‐231 cells, through the activation of AMPK signaling. The latter signaling appeared markedly potentiated at higher concentration (20–30 μg/ml) in both cell types. In other words the modulatory effect of adiponectin may be driven by pMAPK/pAMPK ratio, which was enhanced at low concentrations in MCF‐7 cells, while it dropped markedly at higher doses in both cell types, supporting the inhibitory effect on cell growth. In addition, low doses of adiponectin induced a marked IGF‐IR phosphorylation. The latter event occurred at the same concentrations generally found in obese women. So, it is reasonable to postulate that in ERalpha‐positive cell line the well‐known IGF‐IR/ERalpha cross talk may activate MAPK, sustaining cell proliferation. Thus, on the basis of the present findings enhancing the circulating levels of adiponectin may represent an important target for novel therapeutic strategies in the treatment of this obesity‐associated malignancy.The research has been supported by AIRC MFAG 6180.
Dihydrotanshinone induced apoptosis in colon cancer cells by p53‐independent but ROS dependent pathway mediated by mitochondria
Authors: WANG Lin , Yeung J. H. K. , Lee W. Y. W. , Zhou X. L. , Hu T. , Cho C. H. 
Published: June 2021

ObjectiveAnti‐cancer action of dihydrotanshinone (DHTS) in colon cancer was evaluated and its underlying mechanisms were studied.MethodsCytotoxity of DHTS was measured in colon normal and cancer cells by MTT assay. Apoptotic activity of DHTS was evaluated by FCM. Intracellular Ca2+, ROS generation and MMP were detected by FCM or laser confocal microscopy assay.ResultsDHTS produced a selective cytotoxity against colon cancer cells through induction of apoptosis. The IC50 values for cell viability and apoptosis rates induced by DHTS were similar between HCT116 p53+/+ and HCT116 p53−/−cells. In a separate experiment, pretreatment with N‐Acety‐L‐Cysteine (NAC) or catalase‐PEG, both known to be free radical scavengers, significantly decreased apoptosis induced by DHTS. We also found that DHTS produced a time‐ and dose‐dependent increase in intracellular Ca2+ and ROS generation, which were blocked by pretreatment with BAPTA‐AM (a Ca2+ chelator), catalase‐PEG (a hydrogen peroxide inhibitor) or cotreatment with antimycin A or rotenone. Decrease of MMP was significantly blocked by rotenone or antimycin A while that of mitochondrial ROS was found to be postponed only by antimycin A.ConclusionApoptosis induced by DHTS is p53 independent but ROS dependent. This was initiated from mitochondria dysfunction and promoted by increase of intracellular Ca2+.
Constitutive activity of Gs α R201H is suppressed by disruption of either of two hydrophobic pockets within the protein
Authors: Pals‐Rylaarsdam Robin , Turcic Kyle , Carroll Julie , Tobar‐Rubin Raquel , Janevska Daniela , Din Eraj , Alvarez Rebecca , Choudhry Faiza 
Published: June 2021

McCune‐Albright Syndrome (MAS) is a disorder caused by mutations in Gs at R201 that inhibit GTP hydrolysis. We developed a yeast model for MAS using a strain engineered to undergo cell cycle arrest in the presence of constitutively active Gα. We constructed and screened a library of 32,000 additional mutations in a constitutively active Gα gene, and identified 13 potential intragenic suppressor mutations at sites homologous to human Gs. When expressed in HEK cells, three Gs isoforms carrying the MAS (R201H) mutation with one of the 13 substitutions suppressed the MAS mutation's constitutive activity. F142 and L266 participate in hydrophobic packing in the crystal structure. Mutations that reduced the hydrophobicity of either amino acid suppressed the R201H mutation. R231 also suppressed R201H, possibly by altering hydrogen bonds between Switch II and water molecules near the γ phosphate of GTP. The suppressor mutations alone did not alter cellular responses to hormone or constitutively activate the protein. Intragenic suppressor mutations can be used to model potential sites to which small molecule drugs may be targeted to reduce or block the constitutive activity of Gs.Supported by NIH 1R15ED020190–01
GPR158 and GPR179: a subfamily of orphan GPCRs as a new class of G protein signaling modulators
Authors: Orlandi Cesare , Masuho Ikuo , Posokhova Ekaterina , Cao Yan , Ray Thomas , Hasan Nazarul , Gregg Ronald , Martemyanov Kirill 
Published: June 2021

GPR158 and GPR179 are members of a poorly understood subfamily within the class C of GPCRs. Bioinformatics revealed that they share a homology in their 7TM regions, contain several conserved elements at C‐termini, but lack ligand binding domain typical of the class C receptors. GPR158 is broadly distributed across brain regions while GPR179 is specifically expressed in the retina.We found that GPR158/179 bind to the R7 group of Regulator of G protein Signaling (R7RGS), GTPase accelerating proteins that ensure timely deactivation of GPCR signaling. While GPR179 could bind to all members of R7RGS family, GPR158 forms specific complexes with RGS7. In transfected cells, GPR158/179 recruited R7RGS proteins to the plasma membrane enhancing their ability to deactivate G proteins. GPR158 potentiated RGS‐dependent deactivation of the μ‐opioid receptor signaling, while GPR179 facilitated deactivation of mGluR6. We report that GPR179 forms complexes in native retinas with mGluR6 and TRPM1, the main components of the signaling in ON‐bipolar cells (ON‐BC). Removal of either RGS proteins in these cells results in synaptic transmission deficits and lack of GPR179 prevented their targeting to the dendritic tips of ON‐BC. The ability of GPR158/179 to form heteromers with conventional GPCRs and to enhance RGS activity may be important for the modulation of many physiologically relevant G protein signaling pathways.Supported by NIH
Cocaine‐induced locomotor activity in rats selectively‐bred for high and low motivation to voluntarily run
Authors: Brown Jacob Daniel , Green Caroline , Miller Dennis , Booth Frank 
Published: June 2021

This study aimed to further characterize a novel colony of Wistar rats selectively‐bred for high (HVR) and low (LVR) motivation to voluntarily run. We aimed to examine any sex differences and line (LVR vs. HVR) differences in locomotor activity (LA) levels in young, sedentary rats.METHODSEighty minutes of LA were measured on 3 successive days to determine novelty‐seeking (Day 1), habituation (Day 2), and cocaine‐induced (Day 3) LA in young (30–38d), male and female HVR/LVR rats.RESULTSHVR rats demonstrated greater novelty‐seeking (Day 1) and habituated (Day 2) LA than LVR rats. When analyzed as a difference from saline‐treated rats, cocaine‐induced LA (Day 3) was greater in LVR females than in HVR females. Both LVR and HVR females displayed greater cocaine‐induced LA than LVR and HVR males.CONCLUSIONOur results suggest that cocaine‐induced LA is dependent on both sex and voluntary running genetic potential. Sex hormone and/or dopaminergic signaling systems are logical targets for future research to elucidate the mechanisms underlying these observations.Supported by University of Missouri Development Office and the University of Missouri Life Science Fellowship.
The role of nitric oxide in pericyte‐mediated regulation of vasa recta diameter
Authors: Crawford Carol , Pollock Jennifer S , Wildman Scott S P , Peppiatt‐Wildman Claire M 
Published: June 2021

Pericytes are known to regulate vasa recta diameter in response to many different vasoactive agents endogenous to the kidney [1]. Nitric oxide (NO) signaling pathways are important in the renal medulla for regulation of blood flow and natriuresis. Here we use the live kidney slice model to characterize the mechanisms by which NO regulates pericyte‐mediated control of vasa recta diameter and thus medullary blood flow (MBF).Kidney slices (200 μm thick) were obtained from adult, male rats as previously described [1]. Kidney slices were superfused with agents that manipulate endogenous NO signaling pathways: L‐NAME [an inhibitor of nitric oxide synthase (NOS)], or L‐VNIO (a NOS1‐specific inhibitor), or SNAP (a NO donor). DIC video imaging techniques were used to record real‐time changes in vasa recta diameter, in response to bath application of these compounds. SNAP (100 μM) caused a significant dilation of vasa recta specifically at pericyte sites (12.6±2.9% p<0.05 n=15). L‐NAME (1 mM) and L‐VNIO (1 μM) each caused vasoconstriction significantly greater at pericyte sites compared with non‐pericyte sites (8.6±1.1% p<0.05 n=13 and 10.8±2.0% p<0.05 n=6, respectively).Here we demonstrate that NO derived from NOS1 specifically is key in pericyte‐mediated regulation of vasa recta diameter, and thus renal MBF.Research supported by the Medical Research Council
Inhibition of NADPH oxidase improves renal autoregulation in rats fed a high salt diet
Authors: Fellner Robert C. , Giddens Matthew I. , Inscho Edward W. 
Published: June 2021

Previous work shows that a high salt diet (HS) blunts afferent arteriolar (AA) autoregulatory behavior by 83% partly through reactive oxygen species (ROS). Thus, we tested the hypothesis that HS blunts autoregulation by enhancing NADPH‐dependent ROS production. Rats were fed a normal (NS 0.8% NaCl) or HS (8% NaCl) diet for 14 days. A subset of rats, received the NADPH oxidase inhibitor, apocynin (~25mg/kg/day) in the drinking water. Studies were performed in vivo to assess whole kidney autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR) when left kidney perfusion pressure (PP) was reduced to ~95mmHg using an adjustable aortic clamp. Decreasing PP significantly reduced RBF in HS rats by 18%, from a baseline of 12.6 ±0.6 to 10.4±0.6 ml/min (n=8) compared to 2% in NS rats (8.3±0.8 to 8.1±0.9 ml/min; n=10; P<.05 vs. HS). Apocynin treatment improved autoregulatory behavior in HS rats with RBF declining by just 8%, from a baseline of 12.5 ±0.5 to 11.6 ±0.5 ml/min (n=11). Similarly, left kidney GFR declined by 27% (457 ± 24 vs. 335 ± 31 μl/min/100gbw; n=8) in HS rats compared to just 5% (496 ±46 vs. 470± 39 μl/min/100gbw; n=10) in NS rats. Apocynin improved GFR autoregulation in HS rats with only a 12% reduction at 95 mmHg (472±39 vs. 417±21 μl/min/100gbw; n=11). These data suggest that NADPH oxidase‐derived ROS impair renal autoregulatory behavior in rats fed a HS diet.Funding: NIH‐HL098135, NIH‐1PO1HL095499
A clinic‐academic partnership for recruitment using an electronic medical record (EMR) in a trial of diets for treating polycystic ovary syndrome (PCOS) in overweight and obese adolescents and young adults
Authors: Wong Julia M W , Gooding Holly , Gordon Catherine M , Emans S Jean , Ludwig David S , Ebbeling Cara B 
Published: June 2021

BACKGROUNDThe Androgen Excess and PCOS Society Position Statement specifies lifestyle modification as the primary therapy for obesity in PCOS. However, consensus on optimal diet is lacking. Routine clinical care often includes OCPs and/or insulin sensitizers to lower androgens.OBJECTIVETo recruit girls with PCOS in a tertiary care center for a 6‐mo pilot RCT of low‐fat vs. low‐glycemic load diets on bioavailable testosterone (primary outcome). Use of medications that mask dietary effects is exclusionary.METHODSA partnership between the clinic and research teams facilitated recruitment using a flagging protocol to identify potentially eligible patients based on age (13–21y), BMI (≥85th percentile), and PCOS‐related keywords pertaining to visit reason in an EMR. When appropriate, providers presented the RCT as a first‐line non‐pharmacologic treatment option.RESULTSOver a 2‐y period, 1026 girls have been flagged, with the majority identified from the Division of Adolescent Medicine at BCH and its Reproductive Endocrinology Clinic (>;40%). Primary visit reasons were irregular menses (46%) and PCOS (34%). Medication use was the most frequent reason for exclusion (26%).CONCLUSIONPartnerships using an EMR offer a contemporary approach to recruitment for RCTs of non‐routine clinical therapies. The ongoing RCT will examine the effects of different macronutrient diets on hyperandrogenism in PCOS.Grant Funding Source: Thrasher Research Fund
Effect of sugar‐sweetened soft drinks on serum uric acid and associated metabolic risk factors.
Authors: Crutchley Peter William , Morenga Lisa Te 
Published: June 2021

Excess dietary fructose can lead to elevated serum uric acid (SUA) concentrations which could in turn increase the risk of metabolic syndrome. An important source of fructose worldwide is sugar or high fructose corn syrup sweetened beverages (SSBs). SSB intakes have increased in parallel with obesity and type 2 diabetes, and may have displaced milk beverages. Fruit juice, despite containing similar amounts of fructose has not been shown to elevate SUA, while milk may reduce SUA concentrations.The aim of our 8 week, randomised controlled trial was to determine the effects on SUA and metabolic syndrome risk factors of replacing SSBs with non‐sugar sweetened beverages including diet soft drink, orange juice, or low‐fat milk in a relatively insulin resistant population with high habitual SSB intakes (≥500ml/d). Blood and anthropometric data were collected at week 0, 4, and 8. Dietary data and 24‐hour urine samples were collected at week 0 and 8. There were significant reductions in serum uric acid levels in the diet soft drinks, orange juice, and milk groups compared to SSBs (39, 44, & 44μmol/L; p<0.01). C‐reactive protein concentrations were significantly reduced in the juice group but not in the others (−1.8mg/L; p=0.025). No significant differences were found between interventions for fasting glucose, TAG, or HDL cholesterol concentrations, weight, BMI, blood pressure, or waist circumference. Our findings indicate that reducing SSB intakes by exchanging SSBs for non‐sugar sweetened beverages lowers serum uric acid concentrations, and improves some features of the metabolic syndrome independently of changes in adiposity.
Role of sphingolipids in fibrinogen‐induced cerebrovascular permeability
Authors: Muradashvili Nino , Khundmiri Syed Jalal , Tyagi Reeta , Lee Menq‐Jer , Lominadze David 
Published: June 2021

We showed that at an elevated level fibrinogen (Fg), a marker of inflammation, compromises endothelial cell (EC) layer integrity and increases cerebrovascular permeability. Since we found that Fg increases level of sphingolipids in mouse brain ECs (MBECs), we tested the role of cholesterol and sphingolipids in Fg‐induced permeability of MBECs.Role of cholesterol and sphingolipids in Fg‐induced albumin crossing of MBECs layer was evaluated with a dual‐tracer probing method (allows differentiation of paracellular and transcellular transports). We found that chelation of cholesterol by methyl‐beta‐cyclodextrin (MβCD) inhibited leakage of both low molecular weight (LMW) and high molecular weight (HMW) tracers through EC layer. However, inhibition of sphingolipid de‐novo synthesis by myriocin inhibited Fg‐induced overall leakage (assessed by crossing of HMW tracer through MBECs), but did not affect leakage of LMW tracer. In addition, myriocin inhibited cerebrovascular leakage of albumin in mice with elevated blood level of Fg.The present study suggests that at high level Fg increases cerebrovascular permeability altering mainly the transendothelial transport by enhancing formation of functional caveolae via sphingolipid signaling. Thus, sphingolipids can be identified as new targets for therapeutic intervention that can modulate inflammation‐induced cerebrovascular permeability
Impact of Exercise Training on Cardiovascular Risk and Anti‐Risk Factors in Adolescent Boys
Authors: Koozehchian Majid , Nazem Farzad , Kreider Richard B 
Published: June 2021

Adolescence is a critical period in the formation of cardiovascular risk factors (RF). Long‐term exercise training has been found to be reversely related to RF levels in adolescents.PURPOSETo investigate the effects of training over a 12‐week timeframe on cardiovascular RFs in adolescent boys.METHODSForty two boys, including swimmers (SW, n=14), soccer players (SO, n=13), and a control group (C, n=15) (Age=11.8±1.38yrs; Ht=149±.8.38cm; Wt=40±7.8kg) volunteered for this study. Fasting blood samples were obtained prior to initiation of training, at weeks 4, 8, and 12. A 3×4 repeated measures ANOVA with LSD post hoc analysis was conducted to determine the difference between three groups in total cholesterol (TC), LDL, HDL, TC/HDL, HDL/TC, LDL/HDL and triglyceride (TG).RESULTSResults showed greater reduction in LDL/HDL and TG in SO compared to C group (p ≤ 0.05). No significant difference was observed in TC, LDL, HDL, TC/HDL, and HDL/TC across all three groups.CONCLUSIONExercise training had a significant effect to lower LDL/HDL and TG in adolescent athletes. Participation in regular training is recommended for adolescents to improve cardiovascular RF profiles. Significant effects of training on TC, LDL, HDL, TC/HDL, and HDL/TC levels were inconclusive for 12‐week training period.
The Effect of L‐arginine Supplementation & Voluntary Wheel Running on Vascular Function in Rats with Chronic Kidney Disease
Authors: Martens Christopher R , Kuczmarski James M , Lennon‐Edwards Shannon , Edwards David G 
Published: June 2021

Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor L‐arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 weeks of voluntary wheel running (RUN) and/or ARG supplementation on vascular function in rats with CKD. 12 week old male Sprague Dawley rats underwent 5/6 ablation infarction surgery to induce CKD, or SHAM surgery as a control. CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined ARG+RUN. Interventions began 4 weeks after surgery to allow time for disease progression. Animals were sacrificed 8 weeks after surgery and endothelium dependent relaxation (EDR) was assessed by dose response to acetylcholine in aortic rings. EDR was significantly impaired in SED vs. SHAM animals after 8 weeks, demonstrated by an attenuated maximal response (Emax; 66.87% ± 6.43 vs 96.79% ± 1.27, p <0.05) and rightward shifted LogEC50 (−6.83 ± 0.08 vs −7.54 ± 0.04, p<0.05). EDR was not significantly improved by ARG or RUN alone, but was improved by combined ARG+RUN (p< 0.05 vs SED). The results suggest a synergistic effect between L‐arginine and exercise that may act as a novel therapy to reduce cardiovascular risk in CKD.Supported by ACSM Foundation Grant