bluuebunny/crossref_metadata_2025_split huggingface dataset:
The A563T variation of TRPV5 among African Americans significantly enhances TRPV5‐mediated calcium influx
Authors: Na Tao , Zhang Wei , Jiang Yi , Peng Ji‐Bin 
Published: June 2021

The TRPV5 gene, which encodes the renal epithelial Ca2+ channel, exhibits unusual high frequencies of non‐synonymous single nucleotide polymorphisms (SNP) among African Americans. To evaluate the functional impact of the non‐synonymous SNP variations in TRPV5, A8V, C157R, A563T and L712F variations were introduced to TRPV5 individually, and their abilities to mediated Ca2+ influx and Na+ current were tested using X. laevis oocytes. Among these variants, A563T, which localizes in the last transmembrane domain of TRPV5, exhibited a significant increase in Ca2+ influx with a concomitant decrease in Na+ current as determined by radiotracer uptake and two‐microelectrode voltage clamp, respectively. When threonine 563 was replaced by a serine, Na+ current of TRPV5563S was not much altered while the Ca2+ influx was reduced as compared to TRPV5563T. In contrast, when threonine 563 was replaced by a valine, Ca2+ influx of TRPV5563V was not much altered while the Na+ current was increased as compared to TRPV5563T. It appears that the hydroxyl group of Thr563 may hinder the transport of Na+ through the channel while the bulky side chain of Thr563 may facilitate that of Ca2+. In conclusion, the A563T variant of TRPV5 significantly increases Ca2+ influx by altering its cation selectivity. The A563T variation in TRPV5 may contribute to the lower prevalence of hypercalciuria, kidney stone, and osteoporosis among African Americans.Supported by NIH grant DK072154
Activation of cAMP‐dependent protein kinase (PKA) down‐regulates organic anion transporter 6 function
Authors: Schnabolk Gloriane Willene , Youngblood Geri L. , Sweet Douglas H. 
Published: June 2021

Organic anion transporter 6 [Oat6 (Slc22a20)], a member of the Organic Anion Transporter family uniquely expressed in the testis, mediates the transport of sulfated steroid conjugates. Sequence analysis revealed three putative PKA phosphorylation sites within Oat6. In the current study we analyzed the regulation of PKA on Oat6‐mediated transport using a Chinese Hamster Ovary cell line stably expressing murine Oat6 (CHO‐mOat6). The PKA activator 8‐bromoadenosine (8‐Br‐cAMP) inhibited Oat6‐mediated uptake in a dose and time dependent manner. Preliminary results indicated that pre‐incubation (5 min) of CHO‐mOat6 cells with the PKA inhibitor H‐89 fails to block 8‐Br‐cAMP induced inhibition of Oat6. Using site directed mutagenesis, each PKA site was individually altered and transport activity of the mutants analyzed. Two of the three mutants showed unaltered substrate uptake, whereas the third showed a significant decrease. To confirm expression and plasma membrane targeting of the mutant Oat6 proteins a FLAG tag epitope was fused to Oat6. Introduction of the FLAG tag had no effect on Oat6 transport activity. Immunocytochemistry indicated there was no degradation or mis‐targeting of Oat6 as a result of mutation. These findings suggest that Oat6‐mediated transport of steroid conjugates in the testes may be regulated by PKA through an indirect mechanism.Support: NIDDK RO1‐DK067216, T32 ES012878
The human organic cation transporter 2 (hOCT2) transports cadmium (Cd2+) and mediates Cd2+ induced cell death
Authors: Thevenod Frank , Ciarimboli Giuliano , Wolff Natascha A. , Schlatter Eberhard , Koepsell Hermann 
Published: June 2021

Kidney proximal tubule (PT) is a major target of chronic Cd2+ nephrotoxicity and may take up free or bound Cd2+forms. Free Cd2+ uptake pathways are not completely understood. The electrogenic polyspecific OCTs are expressed at the apical and basolateral plasma membrane of PT cells where they translocate small organic cations with one positive charge. Here we investigated Cd2+ as a substrate for OCT using human OCT1‐3 stably transfected in HEK293. 109Cd2+ uptake was only observed in hOCT2 cells, where it was linear at 10 or 100 μM free Cd2+ for < 60 min.However, uptake was saturable with increasing Cd2+ with an apparent Km of 53.7 ± 7.2 μmol/l and Vmax of 481.9 ± 31.34 μmol/l. OCT inhibitors/substrates cimetidine, quinine and choline (IC50 50 nM, 0.4 μM and 0.8 mM) blocked 109Cd2+ uptake. Cu2+ and Zn2+, but not Fe2+ and Al3+, competed 109Cd2+ uptake (IC50 0.5 and 8.0 μM). Uptake of 1 μM ASP+, a model substrate for hOCT, was competed by Cd2+ and Zn2+ (IC50 205 and 60 μM) in hOCT2 cells. 100 μM Cd2+ uptake into hOCT2 cells for 2.5 h significantly increased apoptosis by annexin V labelling. Using MTT assay, cell viability was significantly reduced by 10 or 100 μM Cd2+ for 2.5 h or 16 h in hOCT2 cells. Cd2+ induced cell death was abolished by cimetidine. The data demonstrate for the first time that hOCT2 transports the divalent metal Cd2+, where it could contribute to subsequent toxicity.Funded by DFG TH 345/8‐1 and TH 345/10‐1
Electrophysiological characterization of cells isolated from endarterectomized tissue from patients with chronic thromboembolic pulmonary hypertension (CTEPH).
Authors: Firth Amy L , Yao Weijuan , Ogawa Aiko , Platoshyn Oleksandr , Remillard Carmelle V , Sacks Richard S , Auger William R , Madani Michael , Thistlethwaite Patricia A , Jamieson Stuart W , Yuan Jason X‐J 
Published: June 2021

Despite having well defined clinical directives, the pathogenic mechanisms involved in CTEPH are currently unknown. Ion channels play critical roles in regulating the contractility, proliferation and migration of vascular smooth muscle cells. This study characterizes the electrophysiological profile of cells isolated from endarterectomized and biopsy tissue from patients undergoing pulmonary thromboendarterectomy (PTE). Using patch clamp techniques, currents were recorded from isolated cells using conditions specifically designed to isolate K+, Ca2+ and nonselective cation currents (NSCC).Four kinetically different voltage‐dependent K+ currents, which were inhibited by 4‐AP and TEA, were recorded in the PTE cells. Very large NSCC were present in virtually all cells and had a linear current‐voltage relationship reversing close to 0mV. The currents were sensitive to extracellular H+ and La3+, but relatively insensitive to 2‐APB and niflumic acid. No voltage‐dependent Ca2+ currents were detected.The electrophysiological profile may suggest a novel pathway in the enhancement of intracellular Ca2+ in cells isolated from PTE tissue. NSCC may be enhanced; the resultant rise in cytosolic Na+ may activate the Na+–Ca2+ exchange in the reverse mode to further increase Ca2+ and contribute to vasoconstriction and remodeling of the pulmonary arteries in CTEPH patients.
Ixolaris, a tissue factor inhibitor, reduces vascular pruning and delays death in rats with established pulmonary arterial hypertension
Authors: White R James , Swarthout Robert F , Meoli David F 
Published: June 2021

We have observed increased tissue factor (TF) expression in pulmonary arterial hypertension (PAH) patients and in a rat model of severe PAH. We hypothesized that TF, the glycoprotein that initiates coagulation and facilitates angiogenesis, contributes to PAH pathogenesis and that blocking TF activity with the tick peptide Ixolaris (IXO) would delay disease progression.Methods/Results: 34 rats underwent left pneumonectomy followed 7 days later by SQ injection of 50 mg/kg monocrotaline (MCT). On day 11 after MCT (d11, RV pressures generally 60 mmHg), we randomized rats to receive SQ injection of IXO (20 mcg/kg daily) or normal saline (NS) until death. The NS group had 50% mortality by d28; IXO treated animals died an average of 10 days later (p<0.03). In a similar experiment, treatment began at d11 and continued 10 days before rats were acutely vasodilated with sodium nitroprusside and sacrificed for heart weights to measure RV hypertrophy and CT scans to visualize vascular pruning. IXO animals had less RV hypertrophy (p<0.01). IXO prevented macrovascular pruning visualized by CT (Figure, represents 3 pairs of rats). Histology showed reduced neointimal formation in pre‐capillary arterioles.
The exercise pressor reflex in hypertensive humans
Authors: Sausen Mark Thomas , Delaney Erin , Stillabower Michael , Farquhar William 
Published: June 2021

During dynamic handgrip exercise (DHE), there is an increase in blood pressure (BP) mediated by “central command” (a neural drive originating in the brain) and the “exercise pressor reflex (EPR)” (a neural drive originating in skeletal muscle). The EPR has been shown to be overactive in hypertensive rats.Purpose:To examine the EPR in hypertensive (HTN) humans during DHE and post‐exercise ischemia (PEI).Hypothesis:The exercise‐ and ischemia‐induced increase in BP will be greater in HTN compared to normotensive (NTN) adults.Methods:12 HTN (64±1 yrs) and 15 NTN (65±1 yrs) adults were recruited. Beat‐to‐beat mean arterial pressure (MAP), systolic BP (SBP), and diastolic BP (DBP) were measured non‐invasively at the finger (Finometer). DHE at 60% of maximal voluntary contraction was performed for 3 minutes followed by 2 minutes of PEI (upper‐arm occlusion cuff inflated to 200 mmHg to trap metabolites and isolate the EPR). A repeated‐measures ANOVA was used to examine differences between conditions and groups.Results(mean±SEM): DHE resulted in increased MAP that was not different between groups (HTN: Δ=16±3 vs. NTN: Δ=12±3 mmHg). During PEI the change in MAP, SBP, and DBP from baseline was greater in HTN than NTN (MAP: Δ=12±3 vs. Δ=6±1 mmHg, SBP: Δ=17±4 vs. Δ=9±2 mmHg, DBP: Δ=7±2 vs. Δ=3±1 mmHg; p<0.05).Conclusion:These findings suggest HTN humans have an overactive EPR. Supported by NIH grant RO3 AG‐23836.
The use of OsiriX® software and 3d Reconstructions from diagnostic images as an aid to cadaver dissection and surgical planning.
Authors: Swift Andrew 
Published: June 2021

OsiriX® software allows the trained user to render a 3 dimensional virtual representation based on images captured during diagnostic CT and MRI scans. OsiriX® software can assign levels of transparency and color to select tonal values and stack each slice relative to its position during the initial scan to create “3D Reconstructions” that can be manipulated and exported as image files. These 3D Reconstructions improve the understanding of anatomic relationships as they exist in the living body. They may be used to supplement anatomy instruction, provide an adjunct to traditional dissection, and improve surgical planning.Traditional dissection often requires the removal, displacement or distortion of superficial anatomy in order to access deeper structures. The non‐destructive and reversible nature of virtual dissections allows a trained user to remove or isolate structures selectively, permitting the visualization of a particular region or tissue. Measurements of distance and volume are also possible. Diagnostic images of both living patients and cadavers destined for dissection can be reconstructed and used to correlate diagnostic images to the actual anatomy of a patient or cadaver.Cost and practical concerns of setting up a 3D workstation, usability of the OsiriX® software, as well as patient confidentiality issues will be discussed. Several case studies will be presented.
Absorption of Zinc (Zn) from High Zn & Control Wheat
Authors: Hambidge K Michael , Rosado Jorge L , Miller Leland V , Hotz Christine , Westcott Jamie E , Garcia Olga P , Gonzalez Karla , Ortiz‐Monasterio Ivan , Pfeiffer Wolfgang , Krebs Nancy F 
Published: June 2021

Background: One goal of HarvestPlus is to increase the Zn content of crops by selective plant breeding.The objective of this study was to assess the efficacy of moderately high‐Zn wheat by measuring Zn absorption from a quantity of wheat (300 g) likely to be consumed daily by adult women who depend on wheat as a major food staple.Study Design: Randomized double blind cross‐over design within extraction groups (95% and 80%). 28 healthy women were randomized to consume tortillas prepared from either high or control Zn wheat on day 1 or 2 as their primary source of energy and Zn. Total absorbed Zn (TAZ, mg) from high Zn wheat tortillas was compared with control wheat tortillas and with the predicted TAZ from a model of TAZ as a function of total ingested Zn (TIZ, mg) and phytate (TIP, mg) at 2 extraction levels. TIZ was measured by extrinsic labeling with stable Zn isotopes and a dual isotope tracer ratio technique. Salient data, means (SD), are given in the table.Conclusion: A significant increase in TAZ is achieved with selection of moderately high Zn wheat. The increase in absorbed Zn is compatible with that predicted from a model of TAZ as a function of TIZ and TIP. Variation in extraction between 95% and 80% does not alter TAZ. Supported by HarvestPlus & IAEA.
Sall genes regulates limb patterning through modulation of region‐specific Hox activities in mice
Authors: Kawakami Yasuhiko , Nishinakamura Ryuichi , Belmonte Juan Carlos Izpisua 
Published: June 2021

Sall genes encode zinc finger transcription factors, and Sall1 and Sall4 are causative genes for human syndromes, such as Towns‐Brocks syndrome and Okihiro syndromes, respectively. Patients with these syndromes show multiple defects including those in limbs. In order to understand the molecular mechanisms by which Sall genes control limb development, we have analyzed mice with targeted mutations in Sall1 and Sall3. While a single knockout of Sall1 and Sall3 shows subtle defects, double mutants exhibited severe defects in autopod development. We found that Sall1 interacts with Hoxa13 and Hoxd13, important genes controlling proper development of the autopod. Further analyses suggest that the coordinated action of Sall and Hox regulates target gene expression and patterning of the autopod. Our study provides molecular insights into how region‐specific morphogenesis is regulated in the autopod.Supported by NIH (5 R01 HD034538‐10) and Grant‐in‐aid by the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
Green tea (GT) extract lowers the lymphatic absorption of benzo[a]pyrene (BaP) in rats
Authors: Noh Sang K. , Kim Juyeon , Seo Yunjung , Koo Sung I. 
Published: June 2021

Recently, we have shown that GT extract (GTE) or its catechins markedly lower the intestinal absorption of cholesterol and fat in rats. BaP is a lipophilic organic pollutant. The present study was conducted to examine the effect of enteral infusion of GTE on the lymphatic absorption of BaP in rats. Adult male rats with lymph cannulae were infused at 3.0 mL/h for 8 h via a duodenal catheter with a lipid emulsion containing 1.0 mg BaP labeled with 14C (14C‐BaP), 452 μmol triolein (oleic acid, OA), 20.7 μmol cholesterol, and 3.1 μmol α‐tocopherol (αTP), and 396.0 μmol Na‐taurocholate without (control) or with 76.0 mg GTE in PBS buffer (pH, 6.4). Lymph was collected hourly for 8 h. No significant difference was noted in lymph flow (14.5 ± 2.9 mL/8 h in GTE vs. 15.0 ± 1.8 mL in control). However, the infusion of GTE markedly lowered the lymphatic absorption of 14C‐BaP (7.6 ± 3.2% dose/8 h) compared with controls infused with the lipid emulsion alone (14.4 ± 2.7%). The results indicate that GTE has a profound inhibitory effect on the intestinal absorption of BaP in rats. The mechanism(s) by which GTE reduces BaP absorption remains to be determined. A study is currently underway examining whether GTE would affect the biliary secretion of BaP in rats.Supported by the Korea Research Foundation Grant funded by Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF‐2006‐003‐C00312)
Food group consumption patterns in a sample of predominantly low‐income children
Authors: Kranz Sibylle , Mitchell Diane , Kumanyika Shiriki K. , Stettler Nicolas 
Published: June 2021

This study analyzed dietary and anthropometric data of 2–11 years olds at five community health centers (CHC) from medically underserved areas of in the U.S. Northeast. Children provided two (n = 24) or three days (n = 190) of 24‐hour recalls. Half of the children were males; half were 2–5 years old; 70% were low‐income; and 64% were at risk for overweight or overweight. Intake reports were disaggregated and average daily intake of total energy (kcal) and MyPyramid food groups (fruit, vegetable, grain, dairy, and meat/meat alternatives in cups or ounces) calculated. Approximately 9% of the sample met all food group recommendations while 6% met none. Half of the sample met the intake recommendation for grains. More preschoolers than 6–11 year olds met the remaining food groups (36% vs. 23% for vegetables, 64% vs. 45% for fruits, 72% vs. 55% for meat, and 55% vs. 49% for dairy). Sixty‐three percent of the children had energy intakes >110% the age‐and gender‐specific Estimated Energy Requirements. In this sample, 73% of the children meeting at least four out of the five recommendations had healthy body weight. Thus, younger children were more likely to meet the intake recommendations and meeting food group recommendations was associated with healthy body weight.This study was supported by a seed grant from the Children, Youth, and Family Consortium at the Pennsylvania State University.
Effect of a culturally and language‐sensitive diabetes education on dietary changes and plasma lipid profile in Hispanic diabetics
Authors: Ojo Emmanuel , Beeson Lawrence , DeLeon Marino , Cordero‐MacIntyre Zaida 
Published: June 2021

O: To assess effects of diabetes education on dietary changes and plasma lipid profile.M: Hispanic subjects(n=13 F and 13 M, mean age=53.8±12.7) participated in a 3‐month study. Spearman correlation coefficient was used to evaluate correlations between dietary intake and laboratory measurements.R: At baseline, % calories, protein(r=0.408, p=0.038) was correlated with plasma HDL(mg/dL). At 3 months, plasma triglycerides(mg/dL) correlated with protein(g)(r=−0.43, p=0.03), % calories, protein(r=−0.43, p=0.028), and % calories, carbohydrate(r=0.41, p=0.039); plasma HDL was correlated with % calories, total fat(r=0.56, p=0.003), % calories, saturated fat(r=0.48, p=0.012), % calories, monounsaturated fatty acids(r=0.587, p=0.002), supplementary chromium(μg)(r=0.56, p=0.003), % calories, protein(r=−0.57, p=0.002), % calories, carbohydrate(r=−0.67, p=0.0002). A decrease in alcohol(g)(r=−0.46, p=0.02), % calories, alcohol(r=−0.43, p=0.03) and increase in % calories, protein(r=0.39, p=0.046), was associated with a significant increase in plasma HDL. Decrease in alcohol (r=0.44, p=0.025), % calories, carbohydrate (r=0.45, p=0.02), and % calories, alcohol (r=0.45, p=0.02) was associated with a significant decrease in plasma triglycerides.C: Dietary changes were significantly associated with some lipid profile parameters after a 3‐month diabetes education.
The effect of increased dietary calcium on fecal fat excretion in overweight and obese adolescents
Authors: Martin Berdine R , Singh Rajni , Campbell Wayne W , Teegarden Dorothy , Weaver Connie 
Published: June 2021

This study was designed to measure the effect of calcium supplementation from a dairy vs. calcium carbonate source on fecal fat excretion in overweight and obese adolescent boys and girls. Twenty girls (BMI 34+/−5 kg/m2) and fourteen boys (BMI 28 +/−5 kg/m2), aged 12–15 y, participated in two 3 week controlled feeding trials separated by a 3‐week washout period. Total dietary intakes during both sessions were eucaloric and macronutrient matched for energy needs. Intake included a basal diet containing 759 mg Ca/d plus frozen products based on soy protein with no added Ca (control) or the basal diet plus frozen products based on either dairy or soy protein containing added Ca (714 mg/d) in a cross‐over design. All urine and feces were collected during each session. Twenty‐four h diet and fecal samples were analyzed for Ca by inductively coupled plasma spectrophotometry. Crude fat of dried diet and feces was extracted using an automated Soxhlet type system. Fractional fecal fat was not influenced by increased Ca intake from dairy or CaCO3. However, pooled data indicated that fractional fecal fat excretion was positively related to fecal Ca excretion.Supported by NIH DK066108, National Dairy Council and test products were a gift from The Schwan Food Company.
Short‐term Changes in Lipoprotein Subclasses and C‐reactive Protein Levels with the Low Carbohydrate and Low‐Fat Diets
Authors: Tangney Christy C , Stoernell Colene Renee , Rockway Susie W 
Published: June 2021

Background: Diets designed to promote weight loss and improve atherogenic lipid profiles traditionally include a reduction in total fat and in particular, saturated fats. This study was designed to test the efficacy of a low‐fat diet vs. a carbohydrate restricted (low‐CHO) diet in hypertriglyceridemic patients on lipid profile, weight loss, C‐reactive protein (CRP) and satiety.Methods: Twenty‐eight hypertriglyceridemic subjects (with fasting triglyceride (TG) levels exceeding 1.69 mmol/L) were randomized to either the low‐CHO or low‐fat diet for 8 weeks. Fasting bloods were drawn at weeks 0 and 8 and analyzed for lipids via NMR and CRP. Anthropometric measurements were also obtained. Three random 24‐hr food recalls were used to assess compliance during the trial.Results: Based on the 23 subjects who completed the protocol, small LDL particles of the low‐CHO subjects fell by 46% after 8 weeks, while those on the low‐fat plan exhibited an increase (36.5%), p=0.045. An average decrease in TG of 18% among low‐CHO subjects in contrast to an increase of 4% for low‐fat group was not significantly different. Nor were there significant differences in CRP, overall dietary compliance, satiety or the magnitude of body weight lost between groups (low‐CHO group, −3.8% vs low‐Fat group, −1.6%).Conclusion: Favorable reductions in small LDL concentrations after 8 weeks suggest that a moderately restricted carbohydrate diet (less than 20% CHO as energy) can promote a healthier, less atherogenic lipid profile when compared to the low‐fat diet.
Effects of n‐3 PUFA supplementation with or without low‐calorie cranberry juice cocktail on flow‐mediated vasodilation in men
Authors: Couillard Charles , Riopel‐Meunier Julie , Lamarche Benoît , Couture Patrick 
Published: June 2021

Consumption of fish as well as fruits and vegetables have been shown to have favorable effects on CVD risk. The present study was therefore undertaken in order to compare the effects of fish oil (FO) w/wo cranberry juice cocktail (CJC) supplementation on flow‐mediated vasodilation (FMD) in men. A group of 53 men was divided into 4 groups: 1) placebo, n=11, 2) 500 mL/day CJC, n=13, 3) 2.4 g/day of FO, n=15 and 4) CJC+FO, n=14. Before and after the intervention, FMD was measured by ultrasound echography of the brachial artery at 60 and 90 seconds after hyperemia. We found no difference in baseline brachial artery diameter (AD), FMD60 and FMD90 between the four groups. We noted that FMD60 (1.2 ± 1.8 %, p=0.029) and FMD90 (+2.5 ± 3.2 %, p=0.013) were significantly improved following the intervention in CJC+FO individuals only. CJC subjects showed no improvement in FMD but displayed a significantly increased resting brachial AD (+0.20 ± 0.24 mm, p=0.013) after the intervention. We also found that changes in FMD60 and FMD90 were negatively associated with brachial AD. In summary, we found that CJC+FO supplementation improved FMD in healthy overweight subjects and that drinking CJC on daily basis for 12 weeks was associated with an increase in resting brachial AD. Further studies are needed to confirm our results and verify the clinical relevance of our observations.Supported by the Canadian Institutes of Health Research (MOP‐64438)