Miracle-dz/UniFAR-FTUs huggingface dataset:
Explorer SRA Regulates Adipogenesis by Modulating p 38 / JNK Phosphorylation and Stimulating Insulin Receptor Gene Expression and Downstream Signaling

The Steroid Receptor RNA Activator (SRA) enhances adipogenesis and increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. To assess the mechanism, we differentiated ST2 mesenchymal precursor cells that did or did not overexpress SRA into adipocytes using combinations of methylisobutylxanthine, dexamethasone and insulin. These studies showed that SRA overexpression promotes full adipogenesis in part by stimulation of insulin/insulin-like growth factor-1 (IGF-1) signaling. SRA overexpression inhibited phosphorylation of p38 mitogen activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) in the early differentiation of ST2 cells. Conversely, knockdown of endogenous SRA in 3T3-L1 cells increased phosphorylation of JNK. Knockdown of SRA in mature 3T3-L1 adipocytes reduced insulin receptor (IR) mRNA and protein levels, which led to decreased autophosphorylation of IRb and decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt. This likely reflects a stimulatory role of SRA on IR transcription, as transfection studies showed that SRA increased expression of an IR promoter-luciferase reporter construct. Citation: Liu S, Xu R, Gerin I, Cawthorn WP, MacDougald OA, et al. (2014) SRA Regulates Adipogenesis by Modulating p38/JNK Phosphorylation and Stimulating Insulin Receptor Gene Expression and Downstream Signaling. PLoS ONE 9(4): e95416. doi:10.1371/journal.pone. 0095416 Editor: Irina U. Agoulnik, Florida International University, United States of America Received June 24, 2013; Accepted March 27, 2014; Published April 17, 2014 Copyright: 2014 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This research was supported by a Pilot and Feasibility Grant and the Cell and Molecular Biology Core of the Michigan Diabetes Research and Training Center (NIH Grant 5P60-DK020572) (B.X.), and NIH grant DK062876 to O.A.M. I.G. was supported by postdoctoral fellowships from the Belgian Funds National de la Recherche Scientifique and the University of Michigan Training Program in Organogenesis (T32HD007505). W.P.C. was supported by a postdoctoral fellowship from the Royal Commission for the Exhibition of 1851 (United Kingdom) and an Eli Lilly Innovation Fellowship Awarded. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: W.P.C. was supported by a postdoctoral fellowship from the Royal Commission for the Exhibition of 1851 (United Kingdom) and an Eli Lilly Innovation Fellowship Award. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. * E-mail: bxu@umich.edu . These authors contributed equally to this work. ¤ Current address: de Duve Institute, Université Catholique de Louvain, Brussels, Belgium
Blood Pressure Modifies Retinal Susceptibility to Intraocular Pressure Elevation

Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (∼60 mmHg, sodium nitroprusside infusion), moderate (∼100 mmHg, saline), or high levels (∼160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5–10 per group) were subjected to IOP challenge (10–120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow.
GABAergic Signaling at Mossy Fiber Synapses in Neonatal Rat Hippocampus

In the adult rat hippocampus, granule cell mossy fibers (MFs) form excitatory glutamatergic synapses with CA3 principal cells and local inhibitory interneurons. However, evidence has been provided that, in young animals and after seizures, the same fibers can release in addition to glutamate GABA. Here we show that, during the first postnatal week, stimulation of granule cells in the dentate gyrus gave rise to monosynaptic GABAA-mediated responses in principal cells and in interneurons. These synapses were indeed made by MFs because they exhibited strong paired-pulse facilitation, high sensitivity to the metabotropic glutamate receptor agonist l-AP-4, and short-term frequency-dependent facilitation. MF responses were potentiated by blocking the plasma membrane GABA transporter GAT-1 with NO-711 or by allosterically modulating GABAA receptors with flurazepam. Chemical stimulation of granule cell dendrites with glutamate induced barrages of GABAA-mediated postsynaptic currents into target neurons. Furthermore, immunocytochemical experiments demonstrated colocalization of vesicular GABA transporter with vesicular glutamate transporter-1 and zinc transporter 3, suggesting that GABA can be taken up and stored in synaptic vesicles of MF terminals. Additional fibers releasing both glutamate and GABA into principal cells and interneurons were recruited by increasing the strength of stimulation. Both the GABAergic and the glutamatergic component of synaptic currents occurred with the same latency and were reversibly abolished by l-AP-4, indicating that they originated from the MFs. GABAergic signaling may play a crucial role in tuning hippocampal network during postnatal development. Low-threshold GABA-releasing fibers may undergo elimination, and this may occur when GABA shifts from the depolarizing to the hyperpolarizing direction.
Becoming a Vampire Without Being Bitten

We propose the narrative collective-assimilation hypothesis—that experiencing a narrative leads one to psychologically become a part of the collective described within the narrative. In a test of this hypothesis, participants read passages from either a book about wizards (from the Harry Potter series) or a book about vampires (from the Twilight series). Both implicit and explicit measures revealed that participants who read about wizards psychologically became wizards, whereas those who read about vampires psychologically became vampires. The results also suggested that narrative collective assimilation is psychologically meaningful and relates to the basic human need for connection. Specifically, the tendency to fulfill belongingness needs through group affiliation moderated the extent to which narrative collective assimilation occurred, and narrative collective assimilation led to increases in life satisfaction and positive mood, two primary outcomes of belonging. The implications for the importance of narratives, the need to belong to groups, and social surrogacy are discussed.
The Pharmacokinetics, Safety, and Tolerance of Cefepime Administered as an Intravenous Bolus or as a Rapid Infusion

OBJECTIVE: To evaluate the pharmacokinetics, safety, and tolerability of cefepime administered as an intravenous bolus and short infusion. METHODS: A single-dose, pharmacokinetic study was conducted on 16 healthy men. Fifty milliliters of a 40 mg/mL solution of cefepime was administered by continuous infusion in intervals of three, five, 10, or 15 minutes. Blood was sampled three minutes through 12 hours after the end of the infusion. Analysis of cefepime was performed by reverse-phase HPLC with ultraviolet detection. Cefepime plasma concentrations versus time were evaluated by noncompartmental methods. History and physical examinations were conducted within two weeks of the start of the study, 24 hours before dosing, and at the end of the study. Assessments for adverse events were made throughout the study. RESULTS: Maximum concentration (Cmax) increased with decreasing time of infusion and was similar to reference values of Cmax. Pharmacokinetic characteristics of cefepime were not affected by the time of infusion and were on average: mean residence time was 2.3 hours, half-life 1.9 hours, the AUC extrapolated to infinity 239 μg•h/mL, total body clearance 142 mL/min, and steady-state volume of distribution 19 L. No serious adverse events, local tolerance at injection site, or significant laboratory abnormalities were noted. CONCLUSIONS: Cefepime 2 g was safely administered to healthy subjects as a rapid, single bolus, and its key pharmacokinetic parameters were consistent with those from longer infusions and other studies.
Containment and inscribed simplices

Let K and L be compact convex sets in R^n. The following two statements are shown to be equivalent: (i) For every polytope Q inside K having at most n+1 vertices, L contains a translate of Q. (ii) L contains a translate of K. Let 1 <= d <= n-1. It is also shown that the following two statements are equivalent: (i) For every polytope Q inside K having at most d+1 vertices, L contains a translate of Q. (ii) For every d-dimensional subspace W, the orthogonal projection of the set L onto W contains a translate of the corresponding projection of the set K onto W. It is then shown that, if K is a compact convex set in R^n having at least d+2 exposed points, then there exists a compact convex set L such that every d-dimensional orthogonal projection of L contains a translate of the corresponding projection of K, while L does not contain a translate of K. In particular, such a convex body L exists whenever dim(K) > d.
Effect of Poliovirus on Deoxyribonucleic Acid Synthesis in HeLa Cells

Ackermann, W. W. (University of Michigan, Ann Arbor), D. C. Cox, H. Kurtz, C. D. Powers, and S. J. Davies. Effect of poliovirus on deoxyribonucleic acid synthesis in HeLa cells. J. Bacteriol. 91:1943–1952. 1966. —Both poliovirus and arginine stimulated deoxyribonucleic acid (DNA) synthesis in cultures of HeLa cells which were preconditioned by incubation in a medium deficient in arginine. However, the number of cells producing DNA was unaffected. DNA synthesis in such preconditioned cells was 10 to 20% of the maximal value obtained with a full complement of amino acids. Inhibition of DNA synthesis was produced in these cultures either by increasing the multiplicity of exposure above 40 plaque-forming units of virus per cell or by increasing the concentration of the deficient amino acid at the time of virus addition. Inhibition of DNA synthesis resulted from a reduction in the fraction of cells producing DNA. The concentration of arginine required for viral inhibition of DNA synthesis is greater than that for viral multiplication.
Depletion of glycoprotein gp85 from virosomes made with Epstein-Barr virus proteins abolishes their ability to fuse with virus receptor-bearing cells

Entry of an enveloped virus such as Epstein-Barr virus (EBV) into host cells involves fusion of the virion envelope with host cell membranes either at the surface of the cell or within endocytic vesicles. Previous work has indirectly implicated the EBV glycoprotein gp85 in this fusion process. A neutralizing monoclonal antibody to gp85, F-2-1, failed to inhibit binding of EBV to its receptor but interfered with virus fusion as measured with the self-quenching fluorophore octadecyl rhodamine B chloride (R18) (N. Miller and L. M. Hutt-Fletcher, J. Virol. 62:2366-2372, 1988). To test further the hypothesis that gp85 functions as a fusion protein, EBV virion proteins including or depleted of gp85 were incorporated into lipid vesicles to form virosomes. Virosomes were labeled with R18, and those that were made with undepleted protein were shown to behave in a manner similar to that of R18-labeled virus. They bound to receptor-positive but not to receptor-negative cells and fused with Raji cells but not with receptor-positive, fusion-incompetent Molt 4 cells; monoclonal antibodies that inhibited binding or fusion of virus inhibited binding and fusion of virosomes, and virus competed with virosomes for attachment to cells. In contrast, virosomes made from virus proteins depleted of gp85 by immunoaffinity chromatography remained capable of binding to receptor-positive cells but failed to fuse. These results are compatible with the hypothesis that gp85 is actively involved in the fusion of EBV with lymphoblatoid cell lines and suggest that the ability of antibody F-2-1 to neutralize infectivity of EBV represents a direct effect on the function of gp85 as a fusion protein.
Evidence-Based Prevention Interventions for People Who Use Illicit Drugs

The World Drug Report of 2012 [1] reports that, globally, illicit drug use is a common occurrence and is a growing health problem in some regions. Global reporting estimates indicate that approximately 230 million people or 5% of the global adult population have used illicit drugs. While somewhat stable use is ongoing in developed countries, resource-limited settings are seeing the growth and emergency of an illicit drug use as a new and significant national health issue. Heroin, cocaine, and other commonly used illicit drugs are particularly destructive to individual livelihoods, families, and neighborhoods with high social impact and increased morbidity and mortality related to the adverse health consequences of their use [2]. These adverse health consequences include addiction, overdose, violence, mental health disorders, suicide, and infectious complications such as HIV, tuberculosis, and hepatitis C [2–4].
Investigation of bacterial attachment on hydroxyapatite-coated titanium and tantalum

Titanium and tantalum have been widely employed in many load-bearing orthopaedic applications due to their excellent strength and corrosion resistance. The bio-function properties of titanium and tantalum can be enhanced to improve the healing process after implantation by incorporating a bioactive coating onto their surfaces. For this purpose, thin films of 200 nm thick silicon dioxide (SiO2) and 2 μm thick hydroxyapatite (HA) were deposited onto titanium and tantalum surfaces using electron beam evaporation and magnetron sputtering, respectively. The surface morphology, elemental composition and crystal structure of HA-SiO2 coated titanium and tantalum were characterised using scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray diffractometry. Pseudomonas aeruginosa and Staphylococcus aureus strains were used to investigate the bacterial attachment onto these surfaces. The HA thin films deposited onto titanium and tantalum surfaces were homogenous. The desirable crystalline phase of HA was also identified on the titanium and tantalum surfaces. Bacterial attachment results indicate that HA-SiO2 coated surfaces were less preferable for the adhesion of bacteria compared to the non-coated surfaces.
BENEFITS OF AN ANIMAL TRACEABILITY SYSTEM FOR A FOOT-AND-MOUTH DISEASE OUTBREAK: A SUPPLY-DRIVEN SOCIAL ACCOUNTING MATRIX APPROACH

Abstract This study reports the findings for an analysis using the computer program NAADSM (North American Animal Disease Spread Model) and a supply-driven social accounting matrix to examine the impact of a hypothetical foot-and-mouth disease (FMD) outbreak in a relatively isolated part of the United States, Utah, under various levels of livestock traceability. The analysis demonstrates that a significant regional economic impact in Utah would result from an FMD outbreak but that improved levels of traceability would be very important in helping to reduce the negative economic consequences of the outbreak.
Receptor Editing and Marginal Zone B Cell Development Are Regulated by the Helix-Loop-Helix Protein, E2A

Previous studies have indicated that the E2A gene products are required to initiate B lineage development. Here, we demonstrate that E2A+/− B cells that express an autoreactive B cell receptor fail to mature due in part to an inability to activate secondary immunoglobulin (Ig) light chain gene rearrangement. Both RAG1/2 gene expression and RS deletion are severely defective in E2A+/− mice. Additionally, we demonstrate that E2A+/− mice show an increase in the proportion of marginal zone B cells with a concomitant decrease in the proportion of follicular B cells. In contrast, Id3-deficient splenocytes show a decline in the proportion of marginal zone B cells. Based on these observations, we propose that E-protein activity regulates secondary Ig gene rearrangement at the immature B cell stage and contributes to cell fate determination of marginal zone B cells. Additionally, we propose a model in which E-proteins enforce the developmental checkpoint at the immature B cell stage.
A Trial of 2 Strategies to Reduce Nocturnal Blood Pressure in Blacks With Chronic Kidney Disease

The objective of our study was to determine the effects of 2 antihypertensive drug dose schedules (PM dose and add-on dose) on nocturnal blood pressure (BP) in comparison with usual therapy (AM dose) in blacks with hypertensive chronic kidney disease and controlled office BP. In a 3-period, crossover trial, former participants of the African American Study of Kidney Disease were assigned to receive the following 3 regimens, each lasting 6 weeks, presented in random order: AM dose (once-daily antihypertensive medications taken in the morning), PM dose (once-daily antihypertensives taken at bedtime), and add-on dose (once-daily antihypertensives taken in the morning and an additional antihypertensive medication before bedtime [diltiazem 60–120 mg, hydralazine 25 mg, or additional ramipril 5 mg]). Ambulatory BP monitoring was performed at the end of each period. The primary outcome was nocturnal systolic BP. Mean age of the study population (n=147) was 65.4 years, 64% were men, and mean estimated glomerular filtration rate was 44.9 mL/min per 1.73 m2. At the end of each period, mean (SE) nocturnal systolic BP was 125.6 (1.2) mm Hg in the AM dose, 123.9 (1.2) mm Hg in the PM dose, and 123.5 (1.2) mm Hg in the add-on dose. None of the pairwise differences in nocturnal, 24-hour, and daytime systolic BP was statistically significant. Among blacks with hypertensive chronic kidney disease, neither PM (bedtime) dosing of once-daily antihypertensive nor the addition of drugs taken at bedtime significantly reduced nocturnal BP compared with morning dosing of antihypertensive medications.
Residual venous obstruction in patients with a single episode of deep vein thrombosis and in patients with recurrent deep vein thrombosis

Summary Residual venous obstruction (RVO) in patients with previous deep vein thrombosis (DVT) of the lower limbs has been suggested as an independent risk factor for recurrent venous thromboembolism (VTE). RVO could be a marker of a persistent prothrombotic state. We have compared the rate of RVO in patients with DVT and a personal history of at least one previous episode of VTE to the rate of RVO among patients with a first episode of DVT. All patients underwent compression ultrasonography (CUS) of the lower limbs 1 year after index DVT. RVO was arbitrarily defined as a thrombus occupying, at maximal compressibility, more than 20% of the vein area in the absence of compression. 50 consecutive patients with recurrent DVT and 50 age and sex-matched patients with a single episode of DVT were enrolled. The index event was idiopathic in 62% of patients with recurrent DVT and in 60% of patients with a single episode. In 74% of patients with recurrent DVT the index event occurred in either the contralateral leg or in a different segment of the ipsilateral leg. RVO was detected in 50% of patients with a single episode of DVT and in 88% of patients with recurrent DVT (p<0.00001). The prevalence of RVO is significantly higher in patients with recurrent DVT than in patients with a single episode. This finding supports the importance of RVO as a potential marker of a persistent prothrombotic state.
Irrational fixed dose combinations & need for intervention: understanding of dental clinicians and residents.

CONTEXT There is a growing concern about ever-burgeoning list of irrational fixed dose combinations (FDCs) which have flooded pharmaceutical market recently in India. Till date no structured study has evaluated the level of understanding among the dental clinicians and residents about these concepts. The present study is designed to fulfil that lacuna. OBJECTIVE To evaluate the knowledge, attitude and practice, regarding the use of FDCs by the dental residents and dental clinicians in a tertiary care teaching dental hospital. MATERIALS AND METHODS The present study was carried out among postgraduate students and dental clinicians working at Rajasthan Dental College, a tertiary care teaching dental hospital, in Jaipur, India. Sixty residents and 77 dental clinicians from the departments of Orthodontics, Prosthodontics, Oral Medicine, Periodontology, Conservative Dentistry & Endodontics, Oral & Maxillofacial Surgery, Pedodontics who gave their informed consent were enrolled. A prevalidated questionnaire regarding knowledge, attitude and prescribing practice of fixed dose combinations was filled up. Data was analysed with suitable statistical tests. RESULTS Out of the 60 residents and 77 dental clinicians recruited for the study, none of them were aware about all of the advantages and disadvantages of FDCs. On an average, only 47% of residents and 61% dental clinicians were aware of FDC included in WHO Essential Medicines List (EML). Only 47% residents and 58% dental clinicians could recall a single banned FDC in India. Common sources of information about FDCs were Monthly Index of Medical Specialities (MIMS), medical representatives and internet. The most commonly prescribed irrational FDC was diclofenac + paracetamol combination, 42% residents and 41% dental clinicians and residents believed that regular Continuous Medical Education (CMEs) stressing upon rational use of medicine could reduce the magnitude of this problem. CONCLUSION It is the need of the hour to reduce the magnitude of this problem by sensitizing dental residents and prescribers regarding the efficacy, safety, suitability, rationality and cost benefit of FDCs available for patient use.