Miracle-dz/UniFAR-FTUs huggingface dataset:
Exercise intensity‐dependent regulation of peroxisome proliferator‐activated receptor γ coactivator‐1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle

Skeletal muscle contraction increases intracellular ATP turnover, calcium flux, and mechanical stress, initiating signal transduction pathways that modulate peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α)‐dependent transcriptional programmes. The purpose of this study was to determine if the intensity of exercise regulates PGC‐1α expression in human skeletal muscle, coincident with activation of signalling cascades known to regulate PGC‐1α transcription. Eight sedentary males expended 400 kcal (1674 kj) during a single bout of cycle ergometer exercise on two separate occasions at either 40% (LO) or 80% (HI) of . Skeletal muscle biopsies from the m. vastus lateralis were taken at rest and at +0, +3 and +19 h after exercise. Energy expenditure during exercise was similar between trials, but the high intensity bout was shorter in duration (LO, 69.9 ± 4.0 min; HI, 36.0 ± 2.2 min, P < 0.05) and had a higher rate of glycogen utilization (P < 0.05). PGC‐1α mRNA abundance increased in an intensity‐dependent manner +3 h after exercise (LO, 3.8‐fold; HI, 10.2‐fold, P < 0.05). AMP‐activated protein kinase (AMPK) (2.8‐fold, P < 0.05) and calcium/calmodulin‐dependent protein kinase II (CaMKII) phosphorylation (84%, P < 0.05) increased immediately after HI but not LO. p38 mitogen‐activated protein kinase (MAPK) phosphorylation increased after both trials (∼2.0‐fold, P < 0.05), but phosphorylation of the downstream transcription factor, activating transcription factor‐2 (ATF‐2), increased only after HI (2.4‐fold, P < 0.05). Cyclic‐AMP response element binding protein (CREB) phosphorylation was elevated at +3 h after both trials (∼80%, P < 0.05) and class IIa histone deacetylase (HDAC) phosphorylation increased only after HI (2.0‐fold, P < 0.05). In conclusion, exercise intensity regulates PGC‐1α mRNA abundance in human skeletal muscle in response to a single bout of exercise. This effect is mediated by differential activation of multiple signalling pathways, with ATF‐2 and HDAC phosphorylation proposed as key intensity‐dependent mediators.
Negative Regulation of T Cell Antigen Receptor-mediated Crk-L-C3G Signaling and Cell Adhesion by Cbl-b*

It was previously reported that Cbl-b associates with Crk-L in Jurkat T cells. However, the physiological significance of such association remains unclear. Here we examined a regulatory role of Cbl-b in Crk-L-C3G signaling pathway. We found that Cbl-b associates with, and induces, ubiquitin conjugation to Crk-L, which requires a functional RING finger. Cbl-b deficiency does not affect Crk-L stability, but its association with C3G. In Cbl-b–/– T cells, the interaction between Crk-L and C3G, and the activity of the small GTPase Rap1, are increased. Cbl-b–/– T cells also display increased adhesion and cell surface binding to ICAM-1, a finding that is supported by the enhanced clustering of LFA-1 in Cbl-b–/– T cells in response to TCR stimulation. Thus, Cbl-b plays a negative role in Crk-L-C3G-mediated Rap1 and LFA-1 activation in T cells.
Membrane Topology of the Murine Fatty Acid Transport Protein 1*

The murine fatty acid transport protein (FATP1) was identified in an expression cloning screen for proteins that facilitate transport of fatty acids across the plasma membranes of mammalian cells. Hydropathy analysis of this protein suggests a model in which FATP1 has multiple membrane-spanning domains. To test this model, we inserted a hemagglutinin epitope tag at the amino terminus or a FLAG tag at the carboxyl terminus of the FATP1 cDNA and expressed these constructs in NIH 3T3 cells. Both tagged constructs produce proteins of the expected molecular masses and are functional in fatty acid import assays. Indirect immunofluorescence studies with selective permeabilization conditions and protease protection studies of sealed membrane vesicles from cells expressing epitope-tagged FATP1 were performed. These experiments show that the extreme amino terminus of tagged FATP1 is oriented toward the extracellular space, whereas the carboxyl terminus faces the cytosol. Additionally, enhanced green fluorescent protein fusion constructs containing predicted membrane-associated or soluble portions of FATP1 were expressed in Cos7 cells and analyzed by immunofluorescence and subcellular fractionation. These experiments demonstrate that amino acids 1–51, 52–100, and 101–190 contain signals for integral association with the membrane, whereas residues 258–313 and 314–475 are only peripherally membrane-associated. Amino acid residues 191–257 and 476–646 do not direct membrane association and likely face the cytosol. Taken together, these data support a model of FATP1 as a polytopic membrane protein with at least one transmembrane and multiple membrane-associated domains. This study provides the first experimental evidence for topology of a member of the family of plasma membrane fatty acid transport proteins.
World-wide variation in HIV-1 phenotypic susceptibility in untreated individuals: biologically relevant values for resistance testing

ObjectivesTo examine the natural phenotypic variability in drug susceptibility among recombinant HIV-1 isolates from a large number of untreated HIV-positive individuals from wide-ranging geographic locations, and to use this information to establish biologically relevant cut-off values for phenotypic antiretroviral susceptibility testing. MethodsPhenotypic susceptibility to 14 antiretroviral agents was determined for HIV-1 samples from > 1000 treatment-naive individuals in seven clinical trials. Samples were from the USA (n = 351), Germany (n = 306), Canada (n = 265), and South Africa (n = 358). Geometric mean fold-resistance and confidence intervals were determined relative to a standard laboratory wild-type virus. ResultsBaseline fold-resistance was approximately log-normally distributed for all antiretroviral agents examined. There was no evidence of large geographical differences in average antiviral susceptibility. Geometric mean fold-resistance for each of 14 antiviral agents was similar (± 0.5-fold) for samples derived from the USA, Canada, Germany, or South Africa. The non-nucleoside reverse transcriptase inhibitors (NNRTI) exhibited the broadest distribution of susceptibility; approximately 97.5% of all isolates had < 2.5–4.0, < 3.0–4.5, and < 5–10 fold-decrease in susceptibility to five protease inhibitors, six nucleoside analogues, and three NNRTI, respectively. No consistent geographic pattern or clade effect (B versus C) in either the mean or the distribution of baseline antiretroviral susceptibility was observed. ConclusionsPhenotypic drug susceptibility of HIV-1 in untreated individuals varies markedly from drug to drug, with broadly similar patterns world-wide. These results have important implications in defining the ‘normal range’ of phenotypic susceptibility to antiretroviral agents and establish biologically relevant cut-off values for this phenotypic drug susceptibility test.
Suppression of Hepatocellular Carcinoma Growth via Oral Immune Regulation towards Tumor-Associated Antigens Is Associated with Increased NKT and CD8+ Lymphocytes

Background: Oral immune regulation towards viral proteins was previously shown to modulate the anti-HBV immune response. Adoptive transfer of orally immunomodulated lymphocytes suppressed the growth of hepatocellular carcinoma (HCC) expressing HBsAg in athymic mice. NKT lymphocytes play a role in the defense against tumor growth. Aim: To evaluate the effect of oral immune regulation towards HCC-associated antigens or HBV proteins on growth of HBsAg-expressing HCC, and to determine the role of NKT lymphocytes in immune modulation. Methods: Sublethally irradiated athymic Balb/c mice were injected with 107 human hepatoma cells followed 10 days later by transplantation of 2 × 106 splenocytes from naive donor mice. Immune modulation was performed via feeding of HCC-extracted proteins or HBV antigens (HBsAg + Pre S1 + Pre S2). The control group was fed with bovine serum albumin (BSA). Mice were followed for survival, tumor volume, and serum α-fetoprotein levels. To determine the role of NKT cells in tumor suppression, cytokine expression and FACS analysis for CD4+, CD8+, and NK1.1+ T lymphocyte subsets were performed. Results: Oral immune regulation towards HCC-extracted proteins induced complete tumor suppression in recipient mice. Mortality rates were 0% in HCC-immune-regulated mice, compared with an 80% mortality rate using HBV antigens and a 100% mortality rate in control mice. Oral immune regulation towards HCC prevented weight loss. No visible tumor mass was observed in orally immune-regulated mice as compared with 112 mm3 in controls. Serum αFP levels were 0.9, 378 and 1,358 ng/ml in HCC, HBV immune-regulated and controls, respectively. Immune regulation towards HCC antigens significantly increased the NK1.1+ T lymphocytes/CD4+ and CD8+/CD4+ ratios. IFNγ production increased two-fold. Conclusion: Oral immune regulation towards HCC antigens effectively enhanced the anti-tumor immune response, thus suppressing the growth of HCC in mice. This effect was associated with an increased NKT,CD8+/CD4+ lymphocyte ratio and may be mediated via enhancement of IFNγ production.
Spontaneous recovery in human learning.

The occurrence of spontaneous recovery -of unlearned verbal materials was examined. While previous reviews have questioned whether spontaneous recovery actually occurs in the standard A-B, A-C paired-associate paradigm, the present summary suggests that the evidence does support its existence. The following topics related to spontaneous recovery were considered: (a) effects of variations in conditions of learning (original and interpolated), (b) effects of paradigm variation, (c) theoretical interpretations (conditioning versus response set), (d) empirical alternatives to the concept of recovery, and (e) extensions to single-list designs. Whenever material is processed into memory, there are logically only two things which can happen to the information: either it remains retrievable (remembered) or it is lost (forgotten) due to irretrievabil ity or ultimate disappearance. Both of these options are obvious and require no elaboration. There is, however, another process which may occur, involving the forgetting and subsequent recall of information. Although this area has been less systematically studied, it is of interest in two respects: 1. It is an intuitive puzzle of practical interest. Why should memories which were once lost become available again? More importantly, what steps can be followed to reaccess the material? 2. It is a theoretical puzzle. Specifically, it may enable a better understanding of the processes involved with permanent memory loss. Obviously, one cannot examine the properties of unretrievable information to understand better how it was lost. However, by a systematic examination of the conditions under which memory information can be recovered, perhaps some insight into the nature of the initial loss may be gained. This may be accomplished by looking at (a) the
Severity of anaemia in Nigerian children diagnosed with Plasmodium falciparum malaria in the first year of life

The prevalence and severity of anaemia was investigated in 450 Nigerian children aged 3-12 months, who were diagnosed with P. falciparum malaria. The children were grouped into 2 age groups: 3–6 mo and 7–12 mo. Four different Hb concentrations were used as cut-off points to categorise anaemia into mild anaemia (MA), Hb ≤10 g/dl; clear-cut anaemia (CCA), Hb ≤ 9.0 g/dl; severe anaemia (SA), Hb ≤ 7.0 g/dl and critically severe anaemia (CSA), Hb ≤ 5.0 g/dl. The mean Hb concentration of the 3–6 mo group (10.8 ± 1.45 g/dl) was not significantly different from the mean Hb concentration of the corresponding malaria-free controls (11.94 ± 1.4 g/dl), but while the mean Hb of the 7–12 mo group (8.7 ± 1.5 g/dl) was significantly lower than the mean Hb concentration of the corresponding malaria-free controls (11.74 ± 1.5). The prevalence of mild anaemia, clear-cut anaemia, severe anaemia and critically severe anaemia were 40%, 20%, 0% and 0% in the 3–6 mo group and 87%, 62.77%, 12.77% and 3.89% in the 7–12 mo group respectively. In addition, 4.16% had critically severe anaemia in the 7–12 mo group. The results suggest that a significant proportion of children who suffer from malaria in the first year of life develop iron deficiency anaemia despite the iron deposits acquired during uterine life. However, the severity of anaemia suffered is higher in the 7-12 mo group, when the bulk of the deposits would have been used up, and most children weaned from breast milk.
0 dB coupler employing slot technique on planar microstrip

Realization of crossovers is always a problem in the design of microwave integrated circuits. In many cases, when a high isolation between crossing strips is required in a rather large frequency band, it is preferable to avoid a trivial separation of the strips by a dielectric layer. This paper focuses on designing and developing a wideband 0 dB coupler on planar microstrip. in In this paper, the proposed 0 dB coupler is designed using square patch with slotted lines. To compare the performances of the proposed design, a conventional 0 dB coupler using double section branch line coupler is presented as well. A substrate Rogers RO4003C with dielectric constant of 3.38 and thickness of 0.508 mm at center frequency 2.4 GHz are used in both designs. They are compared in terms of the size, and their s-parameter performance. Both couplers developed with the aid of design tool CST Microwave Studio and fabricated using microstrip technology.
The relationship between Helicobacter pylori and DNA hypermethylation in gastric cancer

Gastric cancer (GC) is one of the most common types of cancer across the world. GC carcinogenesis demonstrates a multi-step progression with the accumulation of genetic and epigenetic changes. The genetic changes on gene expression, without any change on deoxyribonucleic acid (DNA) sequencing, are named as “epigenetic”. DNA methylation is the most commonly studied epigenetic modification in mammalians. Hypermethylation is observed on CpG (—C— phosphate—G—) islands In GC, promoter regions of genes. This is a significant mechanism that causes functional losses in tumor suppressor genes. In gastric cancer, DNA hypermethylation is seen in many genes. Helicobacter pylori (H. pylori) are a type of spiral-shaped Gram-negative bacteria. It infects approximately half of the world’s population. H. pylori is an important etiological factor that causes GC in human beings. Chronic H. pylori infection in human is associated with hypermethylation of promoter sequences of different genes. This paper provides a review of the current literature on the relationship between H. pylori infection and DNA hypermethylation in GC. J Microbiol Infect Dis 2015;5(4): 187-190 Key words: Gastric cancer, Helicobacter pylori, DNA hypermethylation.
Containing antibiotic resistance: decreased antibiotic-resistant coliform urinary tract infections with reduction in antibiotic prescribing by general practices.

BACKGROUND GPs are urged to prescribe antibiotics less frequently, despite lack of evidence linking reduced antibiotic prescribing with reductions in resistance at a local level. AIM To investigate associations between changes in antibiotic dispensing and changes in antibiotic resistance at general-practice level. DESIGN OF STUDY Seven-year study of dispensed antibiotics and antibiotic resistance in coliform isolates from urine samples routinely submitted from general practice. SETTING General practices in Wales. METHOD Multilevel modelling of trends in resistance to ampicillin and trimethoprim, and changes in practice total antibiotic dispensing and amoxicillin and trimethoprim dispensing. RESULTS The primary analysis included data on 164 225 coliform isolates from urine samples submitted from 240 general practices over the 7-year study period. These practices served a population of 1.7 million patients. The quartile of practices that had the greatest decrease in total antibiotic dispensing demonstrated a 5.2% reduction in ampicillin resistance over the 7-year period with changes of 0.4%, 2.4%, and -0.3% in the other three quartiles. There was a statistically significant overall decrease in ampicillin resistance of 1.03% (95% confidence interval [CI] = 0.37 to 1.67%) per decrease of 50 amoxicillin items dispensed per 1000 patients per annum. There were also significant reductions in trimethoprim resistance in the two quartiles of practices that reduced total antibiotic dispensing most compared with those that reduced it least, with an overall decrease in trimethoprim resistance of 1.08% (95% CI = 0.065 to 2.10%) per decrease of 20 trimethoprim items dispensed per 1000 patients per annum. Main findings were confirmed by secondary analyses of 256 370 isolates from 527 practices that contributed data at some point during the study period. CONCLUSION Reducing antibiotic dispensing at general-practice level is associated with reduced local antibiotic resistance. These findings should further encourage clinicians and patients to use antibiotics conservatively.
Renal osteodystrophy in chronic renal failure.

Bone disease develops relatively early in the development of chronic renal failure. Much of what is known about the evaluation and management of renal osteodystrophy in chronic renal failure is based on knowledge obtained in the dialysis population. The classic bone lesion found in the dialysis population is osteitis fibrosa, the high turnover lesion of secondary hyperparathyroidism. Clearly, hypocalcemia, hyperphosphatemia, and calcitriol deficiency play major roles in the development and maintenance of the high turnover disease. Interestingly, in both the dialysis and nondialysis patients, the incidence of adynamic bone disease, a low turnover lesion, is increasing. It is postulated that the aggressive use of calcium-containing phosphate binders and the use of calcitriol and other vitamin D analogs to treat secondary hyperparathyroidism may contribute to this shift in bone lesions. Treatment in the nondialysis kidney disease patient remains aggressive correction of hypocalcemia and hyperphosphatemia. The use of calcitriol and other agents to maintain serum calcium and to suppress elevated parathyroid hormone remains well supported. However, the increase in extraskeletal calcifications and incidence of adynamic bone disease in these patients raises concern about current management techniques.
A rapid multiresidual determination of type A and type B trichothecenes in wheat flour by HPLC-ESI-MS

A new, rapid and sensitive method is reported for the multiresidual determination of type A (diacetoxyscirpenol, HT-2 toxin, T-2 toxin) and type B (nivalenol, deoxynivalenol, fusarenon X, 15-O-acetyl-4-deoxynivalenol) trichothecenes in wheat flour samples. Sample extraction was performed with acetonitrile/water mixtures. Mycosep© columns were used for a fast and effective clean-up procedure. The analytes were separated by HPLC with a RP C18 column by means of a gradient elution and detected in an ESI-interfaced single quadrupole mass spectrometer. Type B and type A trichothecenes were monitored in the negative and in the positive ion mode, respectively. The method performance is reported in terms of linearity (r 2 = 0.999), specificity, accuracy (recoveries from 70–120%) and precision (CV% = 5), the LOQs are in the range 10–20 µg/Kg.
Genome-Scale Metabolic Reconstruction and Hypothesis Testing in the Methanogenic Archaeon Methanosarcina acetivorans C2A

ABSTRACT Methanosarcina acetivorans strain C2A is a marine methanogenic archaeon notable for its substrate utilization, genetic tractability, and novel energy conservation mechanisms. To help probe the phenotypic implications of this organism's unique metabolism, we have constructed and manually curated a genome-scale metabolic model of M. acetivorans, iMB745, which accounts for 745 of the 4,540 predicted protein-coding genes (16%) in the M. acetivorans genome. The reconstruction effort has identified key knowledge gaps and differences in peripheral and central metabolism between methanogenic species. Using flux balance analysis, the model quantitatively predicts wild-type phenotypes and is 96% accurate in knockout lethality predictions compared to currently available experimental data. The model was used to probe the mechanisms and energetics of by-product formation and growth on carbon monoxide, as well as the nature of the reaction catalyzed by the soluble heterodisulfide reductase HdrABC in M. acetivorans. The genome-scale model provides quantitative and qualitative hypotheses that can be used to help iteratively guide additional experiments to further the state of knowledge about methanogenesis.
Online Mentioning Behavior during Hurricane Sandy: References, Recommendations, and Rebroadcasts

Large-scale crisis events require coordination between the many responding stakeholders to provide timely, relevant, and accurate information to the affected public. In this paper, we examine how social media can support these coordinated public information efforts. This research considers how emergency responders mentioned different organizations, institutions, and individuals by examining the social media communications of police and fire departments during Hurricane Sandy. We find that these departments use mentions to reference other sources of information, recommend credible information and sources, and rebroadcast information. These mentions offer insight into how emergency responders fit within a broader crisis information network and the types of entities that responders trust and recommend to provide information to the public.
Apoptosis Inhibitor as a Suppressor of Tumor Progression: Expression of Bcl-2 Eliminates Selective Advantages for p53-Deficient Cells in the Tumor

Inactivation of p53 and expression of Bcl-2, frequently occurring during tumor progression, have different prognostic value: while inactivation of p53 is generally associated with unfavorable prognosis, expression of Bcl-2 often correlates with better clinical outcome and delays selection of metastatic variants of experimental tumors. To analyze the mechanisms underlying the “anti-progression” function of Bcl-2, we engineered tumor cell variants differing in their p53 status and Bcl-2 expression and compared their expansion in experimental tumors. Although neither p53 suppression nor Bcl-2-expression altered cell growth properties in vitro, both variants showed rapid accumulation in growing tumors in vivo, presumably due to their resistance to hypoxia. However, no expansion of p53-deficient variants occurred in the tumors formed by Bcl-2-overexpressing cells, indicating that p53 deficiency has no selective advantages in the Bcl-2-expressing environment. Importantly, expression of Bcl-2, unlike p53 suppression, did not lead to genomic instability as judged by the frequencies of gene amplification. Thus, acquisition of Bcl-2 expression is as advantageous for tumor cell growth in vivo as is p53 inactivation but does not affect genomic stability and creates the environment restrictive for the expansion of genetically unstable and potentially malignant p53-deficient cells, causing a delay in tumor progression and explaining the different prognostic value of Bcl-2 and p53.
Impact of Financial Crises on Growth and Investment : An Analysis of Panel Data

This paper examines the impact of financial crises on GDP growth and investment. These relationships are analyzed through a dynamic panel model. The model also includes control variables that may explain variations in growth and investment. Our panel consists of twenty-five countries and the study period lasted from 1998 to 2009. This period can follow the changes in growth and investment over the last decade and make us understand the impact of financial crisis on them. The main results show that the presence of a financial crisis in one country has a negative and significant impact on GDP growth and its level of investment.