bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Novel Functional Link between Mediator Complex and Histone Modification Enzyme
Authors: Tsutsui Taiki , Shinmyozu Kaori , Ohkuma Yoshiaki 
Published: June 2021

The Mediator complex has been thought as a key regulatory complex of RNA polymerase II (Pol II) and it has been known as bivalent, positive and negative, transcriptional regulator. Mediator complexes were reported to form at least two subtypes, large‐Mediator and small‐Mediator, depending on those subunit compositions. In previous studies, large‐Mediator has been thought to act negatively and small‐Mediator to act positively in transcription. Compared to its roles in transcriptional activation, little has been known in its roles in transcriptional repression. Here I show novel mechanisms of the Mediator complex in transcriptional repression in C/EBPβ target genes. To study a repressive mechanism by large‐Mediator, I purified CDK8 which is the large‐Mediator specific subunit forming complex and discovered PRMT5 as an interaction factor. PRMT5 is known to catalyze repressive histone modification (e.g., H4R3me2s) and recruits DNMT3A to target regions. Therefore, Large‐Mediator specific subunit CDK8 recruits PRMT5 and DNMT3A to certain C/EBPβ target gene promoter regions and represses those genes transcription via epigenetic machinery. This finding highlights a link of the Mediator complex to epigenetic regulation machinery and shows that the Mediator complex acts not only as Pol II recruiter but also as epigenetic regulator in transcription.This study supported by Grant‐in‐Aid for JSPS Fellows.
Vegetable consumption linked to decreased hepatic fat deposition in overweight Latino youth
Authors: Cook Lauren T , O'Reilly Gillian A , Goran Michael I , Weigensberg Marc J , Spruijt‐Metz Donna , Davis Jaimie N 
Published: June 2021

We have previously shown that 38% of overweight Latino youth have Non‐alcoholic fatty liver disease (NAFLD). This study examines the relationship between diet, specifically vegetable consumption, and NAFLD in this high‐risk population.This cross‐sectional study of 172 overweight ([ge]85th percentile BMI) Latino youth (8–18 y) had measures of dietary intake (multiple 24‐h recalls), total body fat (dual‐energy x‐ray absorptiometry), and adipose tissue distribution (magnetic resonance imaging). Analysis of covariance was used with the following a priori covariates: age, gender, energy intake and total body fat.Quartiles of non‐starchy vegetable (NSV) intake were associated with lower hepatic fat fraction (HFF, p=0.01); those who consumed the most NSV (mean intake = 1.7±1.0 serv/d) compared to the least (mean intake = 0.1[plusmn]0.1 serv/d) had 44% less liver fat (10.0[plusmn]8.5 vs. 5.6[plusmn]8.7 % fat, p=0.01). No relationship was found with fruit. These findings suggest that approximately 2 servings of NSV per day by overweight Latino youth may help decrease the risk of NAFLD. Research is supported by U54 CA 116848, RO1 HD/HL 33064, P60 MD002254, R01 HL07953, 1K01DK078858–01.Grant Funding Source: U54 CA 116848, RO1 HD/HL 33064, P60 MD002254, R01 HL07953, 1K01DK078858–01
High Dietary Sodium Reduces Flow Mediated Dilation Similarly in Humans with Salt Sensitive & Salt Resistant Blood Pressure
Authors: Lee Matthews Evan , DuPont Jennifer J , Greaney Jody L , Lennon‐Edwards Shannon L , Edwards David G , Farquhar William B 
Published: June 2021

Recent studies demonstrate that high dietary sodium (HS) impairs endothelial function in those with salt‐resistant (SR) blood pressure (BP), suggesting that the effect of dietary sodium on endothelial function may be independent of BP. We hypothesized that HS would impair flow mediated dilation (FMD) more in those with salt sensitive (SS) BP compared to those with SR BP. Five SS (2M 3W, 43±5yrs) & 7 SR (3M 4W, 45±2.4yrs) subjects were enrolled in a controlled feeding study consisting of a run‐in diet followed by a two phase randomized crossover 7‐day diet perturbation: low dietary sodium (LS) (20 mmol/d) & HS (300 or 350 mmol/d). Brachial artery FMD and 24‐hr BP were assessed on the last day of each diet. SS BP was defined as a change in 24‐hr mean arterial pressure of >; 5 mmHg between LS & HS diets. HS attenuated FMD in both the SS (LS: 12.8±2.4%, HS: 8.2±1.4%, p<0.05) & SR (LS: 10.5±1.8%, HS: 6.9±1.1%, p<0.05) groups. The decline in FMD was not different between groups for the change in FMD (SS: Δ‐4.6±1.2%, SR: Δ‐3.6±1.2%, p>;0.05). These data indicate a HS diet impairs FMD to a similar extent in SS & SR individuals, providing additional evidence suggesting a BP independent effect of dietary sodium on endothelial function.Research funded by NIH grants 2 P20 RR016472–11 & R01 HL104106.
Combined Endothelial and Skeletal Myofiber VEGF Gene Deletion Leads to Capillary Regression in Adult Mouse Hind Limb Muscle
Authors: Sulaeman Alexis Gabriella , Delavar Hamid , Fine Janelle , Wagner Peter D , Breen Ellen C 
Published: June 2021

In adult mice, the importance of vascular endothelial growth factor (VEGF) for maintaining skeletal muscle capillaries is unclear. We hypothesized that deletion of the VEGF gene, targeted simultaneously to both endothelial cells and myofibers, would lead to a loss of capillaries in locomotor muscles.MethodsCapillary to fiber ratio (C:F), fiber‐cross sectional area (FCSA), and fiber‐type composition were measured in soleus, plantaris and gastrocnemius cryo‐sections from wild type (WT) and HSA‐Cre‐ERT2 X VEGFLoxP x PDGFb‐iCre‐ERT2 (EC+MyoVEGF−/−) mice. C:F was decreased in soleus from EC+MyoVEGF−/− mice compared to WT (WT, 1.64 ± 0.19, EC+MyoVEGF−/− 1.20 ± 0.19, n=3–9, p < 0.05). FCSA increased in both EC+MyoVEGF−/− soleus and plantaris (soleus: WT, 1953 ± 347 μm2, EC+MyoVEGF−/−, 3148 ± 543 μm2, plantaris: WT, 1731 ± 189 μm2, EC+MyoVEGF−/−, 3261 ± 803 μm2, n=3–9, p < 0.05). EC+MyoVEGF−/− mice also revealed a shift from type IIB to type IIA fibers in the plantaris (type IIB: WT, 66 ± 7 %, EC+MyoVEGF−/−, 48 ± 8 %, type IIA: WT, 19 ± 4%, EC+MyoVEGF−/−, 36 ± 16%, n=3–9, p < 0.05). Unlike previously reported studies in adult skeletal myofiber VEGF‐deficient mice, capillary regression does occur in adult skeletal muscle when VEGF expression is inhibited in both endothelial cells and myofibers.
Rac1 is a novel regulator of stretch‐induced glucose uptake in muscle
Authors: Sylow Lykke , Kleinert Maximilian , Richter Erik A , Jensen Thomas E 
Published: June 2021

ObjectiveThe actin‐cytoskeleton‐regulating GTPase Rac1 is required for insulin‐stimulated glucose uptake in cultured muscle cells and is dysregulated in insulin resistant states. We previously found that both insulin and exercise activates Rac1 in mouse and human skeletal muscle, and is required for glucose uptake induced by these stimuli. However, it is unknown whether mechanical stress, which is an integrated component of muscle contraction and increases glucose uptake, activates Rac1. Furthermore, the involvement of Rac1 in stretch‐induced glucose uptake has not been investigated.MethodsWe examined the involvement of Rac1 in stretch‐stimulated glucose uptake and signalling in incubated soleus and EDL muscles from tetracycline‐inducible muscle‐specific Rac1 knockout mice.ResultsPassive stretching (15 minutes to 130 mN) increased phosphorylation of Rac1's downstream target, PAKThr423 by ~200% in both soleus and EDL muscles. This response was inhibited by 60% in soleus and 75% in EDL from Rac1 knockout mice. In soleus and EDL, stretch increased 2‐Deoxy‐glucose uptake by 240% and 130%, respectively. This response was decreased in the Rac1 knockout muscles by 30% in soleus and 50% in EDL muscles.ConclusionThese data show that Rac1 and its downstream target, PAK1 are activated by stretching and are important regulators of stretch‐stimulated glucose uptake in skeletal muscle.
Severe left ventricular dysfunction following short‐term high fat feeding in a canine model
Authors: Nelson Michael , Broussard Josiane , Kolka Cathryn , Bediako Isaac Asare , Szczepaniak Lidia S. , Bergman Richard 
Published: June 2021

This study tested the effects of short‐term high fat feeding on left ventricular function. Experiments were conducted in 4 mongrel dogs at baseline (normal chow: 40/30/30 carb/fat/protein), and after 2 and 6 weeks of high fat feeding (30/50/20 carb/fat/protein). Each condition included an intravenous glucose tolerance test for metabolic assessment, along with cardiac magnetic resonance imaging (cMRI) to evaluate left ventricular (LV) volumes, mass, and myocardial deformation (by tissue tagging). Remarkably, 2‐wk of high fat feeding dramatically worsened (all p<0.05) LV ejection fraction (mean+SD;−11.8+6.6%), circumferential strain (CS,+4.6+1.7%), circumferential strain rate (CSR,+34.7+16.0%/s) and LV torsion (−4.3+2.0°), with no changes in LV mass, heart rate, or glucose tolerance. By week 6, LV end‐diastolic volume significantly increased above baseline (+9.3+7.7 mL), returning ejection fraction closer to its basal level (−3.2+1.9%), while CS, CSR, and torsion remained impaired. Mechanisms responsible for impaired cardiac function from a short period of fat feeding with a modest increase in body weight need to be further elucidated.Support: Heart and Stroke Foundation of Canada (MN), Branco Weiss Fellowship (JB), NIH DK27619, DK 29867.
Early intestinal colonization phenotypes predict necrotizing enterocolitis in preterm infants
Authors: Morrow Ardythe L , Lagomarcino Anne J , Schibler Kurt R , Taft Diana H , Yu Zhuoteng , Wang Bo , Gevers Dirk , Ward Doyle V , Kennedy Michael A , Huttenhower Curtis , Newburg David S 
Published: June 2021

Necrotizing enterocolitis (NEC) afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to subsequent NEC onset is not understood. We analyzed prospectively banked samples collected prior to disease onset from infants <29 wks gestational age, including 11 who developed NEC and 21 matched controls who survived free of NEC. Stool bacterial communities were profiled by 16S rRNA gene sequencing. Two forms of dysbiosis preceded NEC. During postnatal days 4 to 9, the samples from 4 NEC cases were dominated by phylum Firmicutes (relative abundance: >;99% vs <15% in the remaining NEC and controls, p<0.001). During days 10 to 16, samples from the remaining NEC cases were dominated by phylum Proteobacteria (relative abundance >;99% vs 39% in the other NEC cases and 84% in controls, p=0.01). NEC preceded by Firmicutes dysbiosis occurred during postnatal days 7 to 21, whereas NEC preceded by Proteobacteria dysbiosis occurred later, days 19 to 39. Metabolomic analysis of urine samples from days 4 to 9 identified metabolites that predicted onset of one the two microbially‐defined NEC types vs controls (p<0.01), but no metabolites differed between all NEC cases and controls. Distinct forms of dysbiosis may help predict NEC well in advance of onset, providing clues to the underlying pathobiology.Project funded by NIH HD 05491, NIH T32 ES 010957–12, and NIAID NIH HHS Contract No. HHSN272200900018C
Effect of Nuts on Coronary Heart Disease Risk Factors in Type 2 Diabetes
Authors: Kendall Cyril WC , Augustin Livia SA , Bashyam Bala , Nishi Stephanie , Jenkins David JA 
Published: June 2021

BackgroundNut consumption has been associated with a reduced risk of coronary heart disease (CHD). In a recently completed clinical study we found that nut consumption significantly improved glycemic control and blood lipid risk factors for CHD compared to a healthy control.ObjectivesTo determine if tree nuts improve other markers of cardiovascular risk including serum fatty acid profile, LDL particle sixe, clotting factors and markers of oxidative stress.Methods117 subjects with type 2 diabetes were randomized to a 3‐month parallel design study. Subjects were randomized to one of three treatments: 1) Test (Full Dose Nut Diet): 75g/d for 2,000kcal/d; 2) Test (Half Dose Nut Diet): half‐dose of nuts and half‐dose of control muffin; and 3) Control: whole wheat muffins matched with energy content of nut supplements. Fasting blood samples were collected at baseline and weeks 2, 4, 8, 10 and 12 for markers of glycemic control and CHD risk factors.ResultsCompared to the control, the full dose nut supplement significantly lowered HbA1c (P=0.039), total‐C (P=0.002), LDL‐C (P=0.007), total‐C:HDL‐C (P=0.015), and LDL‐C:HDL‐C (P=0.028). Data on other markers of cardiovascular risk will be presented.
Leptin as a marker of undernutrition in breast cancer recurrence
Authors: Bard Jean‐Marie , Lefrançois Armelle , Jaffre Isabelle , Joalland Marie‐Pierre , Classe Jean‐Marc , Campone Mario , Bobin‐Dubigeon Christine 
Published: June 2021

ObjectiveTo relate leptin concentration with undernutrition and survival time in breast cancer recurrence.Design and methodsLeptin and other markers of undernutrition were measured in 49 patients who experienced disease recurrence for breast cancer. Undernutrition was clinically assessed by a weight loss of ≥10% between primary diagnosis and recurrence or ≥5% within the last month and/or the prescription of food supplements. Results were compared between patients with (21) or without (28) undernutrition by logistic regression models. The effect of biological variables on survival rate was assessed by the Kaplan‐Meier method.ResultsLeptin was significantly and negatively associated with undernutrition (OR=0.45 [0.23–0.87], p=0.018), while PINI (Prognostic Inflammatory and Nutritional Index, OR=1.24 [0.94–1.63], p=0.130) did not reach significance. The survival distributions across quartiles of leptin (Log rang test, p=0.048) and PINI (Log rank test, p=0.0001) were significantly different. However, as assessed by the Cox proportional hazards models, quartiles of leptin did not differ between each other while quartiles of PINI were all significantly different from quartile 1.ConclusionIn case of breast cancer recurrence, leptin is a good marker of undernutrition but is a poor marker of survival time, while PINI is a poor marker of undernutrition but is a good marker of survival time.
Model‐based Compartmental Analysis of Vitamin A Kinetics in Vitamin A‐Supplemented Neonatal Rats Predicts Extensive Recycling and Altered Inter‐compartmental Exchange Rates
Authors: Tan Libo , Green Michael H , Ross A. Catharine 
Published: June 2021

Compartmental modeling has contributed greatly to our understanding of vitamin A (VA) metabolism in adult animals and humans. However, VA metabolism in neonates is virtually uncharacterized. Our objective was to develop a whole‐body model of VA metabolism in placebo and VA‐supplemented neonatal rats, taking into account their inherent metabolic non‐steady state. We hypothesized that VA supplementation perturbs retinol kinetics and alters tissue VA distribution in neonates. On postnatal day 4, pups (n=3/time point) received 11,12‐[3H]retinol orally, admixed with either oil (placebo) or VARA (VA+10% retinoic acid [RA]). Plasma and tissues were collected at selected time points. A multi‐compartmental model as viewed from the “plasma space” indicated extensive recycling of retinol between plasma and tissues in neonates, as in adults. The recycling was, however, much faster in neonates. VARA decreased the turnover of retinol between plasma and extravascular tissues. Compartmental models for various organs were also developed. The models indicated that, in neonates, tissues other than liver are important in taking up retinyl ester from chylomicrons, and this is further stimulated by VARA supplementation. NIH HD‐66982Grant Funding Source: NIH
Educational internships: Extra‐curricular opportunities to enhance graduate employability
Authors: Lewis David Ian 
Published: June 2021

The “Working towards your Future” report recommended that Universities provide opportunities, both within and outside of the curriculum, for students to develop employability skills and gain work experience. We therefore developed a programme of educational research internships, outside of the taught curriculum, which enable students develop a different set of employability skills to those gained within the laboratory.Students undertaking these internships contribute to ongoing programmes of educational research e.g. evaluation of young people's opinions of the use of research animals; use of tablet devices in practicals; development of a wiki of ethics OERs.Students are required to regularly reflect during their internship and write a short case study on completion. In these, they recognise the skills gained and the benefit of these to their future employability; they also have a tangible outcome or resource they can show to prospective employers. Educational research internships are therefore a valuable means outside of the taught curriculum for students to develop employability skills and to gain work experience. They also provide significant benefits for the Faculty in enhancing the student learning experience, facilitating pedagogical and educational research and in the external promotion of its activities.The financial support of the Leeds for Life Foundation is gratefully acknowledged.
“Sex‐specific microRNA networks in cardiac hypertrophy”
Authors: Burton Tyler , Malone Payton , Baute Audrey , Waikel Rebekah 
Published: June 2021

Sex differences in cardiovascular disease, susceptibly and progressively, including left ventricular hypertrophy (LVH) and subsequent heart failure, have been well documented. MicroRNAs (miRNAs), which have been shown to be regulated during LVH, might provide insight into these sex differences. To establish sex‐specific miRNA profiles in LVH, male and female C57BL6 mice were subjected to transaortic constriction (TAC). Two‐weeks postsurgery, mice were euthanized and heart weights were determined. Male mice had significantly greater levels of cardiac hypertrophy as compared to female mice. Total RNA was isolated from left ventricular tissue samples, and next generation sequencing was performed on small RNAs. Comparing miRNA expression data from TAC, sham surgical, and non‐surgical animals, we have established unique sex‐specific miRNA expression profiles in left ventricular hypertrophy and in a non‐surgical state. We have used these profiles to establish potential signaling networks responsible for sex‐differences. Functional significance of networks known to influence cardiac hypertrophy, including TGFβ and MCIP1, are currently being investigated. It is anticipated that establishment of sex‐specific miRNA networks will aid in the use of miRNAs as diagnostic and therapeutic targets for LVH.NIH 5P20RR016481–12, 8P20GM103436–12, R15HL108192–02
Dietary Micronutrient Intake of Pulmonary TB patients in Tbilisi, Georgia
Authors: Frediani Jennifer K , Tukvadze Nestani , Sanikidze Eka , Gegechkori Maia , Kempker Russell R , Millson Erin C , Hebbar Gautam , Blumberg Henry M , Ziegler Thomas R 
Published: June 2021

AimTo obtain information on habitual dietary intake of selected micronutrients in TB patients in Tbilisi, Georgia.MethodDietary intake was obtained from patients at TB diagnosis using a tool that captures specific foods common in Georgian culture. Foods consumed during the previous 3 days were determined by one‐on‐one interviews. Food intake data was entered into the NDS‐R software program and mean daily micronutrient intake determined. Descriptive statistics and intake of micronutrients compared to the United States Dietary Reference Intake (US DRI) guidelines for adults and food group frequency were evaluated.ResultsA total of 199 subjects were studied (mean age 34 y; 64% male). No subject consumed specific micronutrient supplements. Mean daily intake of vitamin D 186±173(SD) IU/day (31% of US RDA); retinol (vitamin A) 686±600 mcg/day (84% of US RDA), vitamin E 19±9 IU/day (85% of US RDA); manganese 4.56±1.74 mg/day (217% of US AI); copper 2.28±1.01 mg/day (253% of US RDA), selenium 147±65 mcg/day (267% of US RDA) and zinc 12.2±5.3 mg/day (125% of US RDA). Dietary intake of both thiamine (vitamin B1) and riboflavin (vitamin B2) was adequate at 2.4±0.9 mg/day (209% of US RDA) and 2.6±1.0 (216% of US RDA), respectively.ConclusionsDietary intake data from these Georgian TB patients revealed adequate intake of the B vitamins thiamine and riboflavin, and specific trace elements linked to human immune function (copper, selenium, and zinc). In contrast, dietary intake of several vitamins linked to immune function (vitamin D, retinol and vitamin E) was inadequate.Grant Funding Source: NIH D43 TW007124, D43 TW007124‐06S, K24 RR023356, UL1 RR025008, Emory Global Health Institute
Modulation Of The Baroreflex Depressant Effect Of Chronic Nicotine In Female Rats By Nitric Oxide Synthase And Heme Oxygenase
Authors: El‐Mas Mahmoud M , El‐Gowelli Hanan M , Fouda Mohamed A , El‐Gowilly Sahar M 
Published: June 2021

Nicotine impairs reflex chronotropic activity in female rats. Here, we sought evidence to implicate nitric oxide synthase (NOS) and/or heme oxygenase (HO) in the nicotine effect. Baroreflex curves relating chronotropic responses to reciprocal changes in blood pressure were generated by the vasoactive method (phenylephrine and nitroprusside) in nicotine‐treated female rats in absence and presence of NOS/HO pharmacological modulators. Slopes of the curves served as a measure of baroreflex sensitivity (BRS). Nicotine (2 mg/kg/day for 14 days) reduced BRS compared with saline‐treated rats. Findings that favor the involvement of NOS inhibition in the nicotine attenuation of BRS were (i) NOS inhibition (L‐NAME) reduced BRS in saline‐ but not in nicotine‐treated rats, and (ii) L‐arginine, NO donor, reversed the BRS inhibitory effect of nicotine. HO inhibition (protoporphyrin IX, ZnPP) had no effect on BRS in nicotine‐ or saline‐treated rats; it also failed to reverse the beneficial effect of L‐arginine on nicotine‐BRS interaction. Hemin (HO inducer) but not CORM‐2 (carbon monoxide releasing molecule) abolished the BRS attenuating effect of nicotine. Thus, the inhibition of NOS, but not HO, is causally related to nicotine‐evoked BRS depression. The latter can also be alleviated after HO induction.This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No. 502.
Baroreceptor unloading converts depressor responses elicited from the hypothalamic arcuate nucleus to pressor responses
Authors: Kawabe Tetsuya , Kawabe Kazumi , Sapru Hreday N 
Published: June 2021

The type of response elicited from the hypothalamic arcuate nucleus (ARCN) depends on the level of baroreceptor activity. It was hypothesized that baroreceptor unloading may determine the type of response elicited from the ARCN. This hypothesis was tested in urethane‐anesthetized adult male Wistar rats. Bilateral barodenervation converted decreases in mean arterial pressure (MAP) and greater splanchnic nerve activity (GSNA) elicited by chemical stimulation of the ARCN to increases in MAP and GSNA and exaggerated tachycardia. Microinjections of ionotropic glutamate receptor antagonists into the paraventricular nucleus (PVN) in barodenervated rats converted increases in MAP and GSNA elicited by the ARCN stimulation to decreases in MAP and GSNA and attenuated tachycardia. Microinjections of a melanocortin 3/4 receptor antagonist into the PVN in barodenervated rats attenuated increases in MAP, GSNA and heart rate elicited by the ARCN stimulation. ARCN neurons projecting to the PVN were immunoreactive for proopiomelanocortin, alphamelanocyte stimulating hormone (alpha‐MSH) and adrenocorticotropic hormone (ACTH).Conclusionincreases in MAP and GSNA and exaggeration of tachycardia elicited by the ARCN stimulation in barodenervated rats may be mediated via release of alpha‐MSH and/or ACTH and glutamate from the ARCN neurons projecting to the PVN. Support: NIH grants HL024347 and HL076248(HNS).