Miracle-dz/UniFAR-FTUs huggingface dataset:
Pacemaker channels in mouse thalamocortical neurones are regulated by distinct pathways of cAMP synthesis

A crucial aspect of pacemaker current (Ih) function is the regulation by cyclic nucleotides. To assess the endogenous mechanisms controlling cAMP levels in the vicinity of pacemaker channels, Ih regulation by G‐protein‐coupled neurotransmitter receptors was studied in mouse thalamocortical neurones. Activation of β‐adrenergic receptors with (−)‐isoproterenol (Iso) led to a small steady enhancement of Ih amplitude, whereas activation of GABAB receptors with (±)‐Baclofen (Bac) reduced Ih, consistent with an up‐ and down‐regulation of basal cAMP levels, respectively. In contrast, a transient (τdecay, ∼200 s), supralinear up‐regulation of Ih was observed upon coapplication of Iso and Bac that was larger than that observed with Iso alone. This up‐regulation appeared to involve a cAMP synthesis pathway distinct from that recruited by Iso, as it was associated with a reversible acceleration in Ih activation kinetics and an occlusion of modulation by photolytically released cAMP, yet showed an 11 mV as opposed to a 6 mV positive shift in the activation curve and an at least seven‐fold increase in duration. GABA, in the presence of the GABAA antagonist picrotoxin, mimicked, whereas N‐ethylmaleimide, an inhibitor of Gi‐proteins, blocked the up‐regulation, supporting a requirement for GABAB receptor activation in the potentiation. Activation of synaptic GABAB responses via stimulation of inhibitory afferents from the nucleus reticularis potentiated Iso‐induced increments in Ih, suggesting that synaptically located receptors couple positively to cAMP synthesis induced by β‐adrenergic receptors. These findings indicate that distinct pathways of cAMP synthesis target the pacemaker current and the recruitment of these may be controlled by GABAergic activity within thalamic networks.
Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults.

CONTEXT While parental cardiovascular disease (CVD) doubles the risk for CVD in offspring, the extent of increased risk associated with sibling CVD is unclear. OBJECTIVE To determine, using validated events, whether sibling CVD predicts outcome in middle-aged adults independent of other risk factors. DESIGN, SETTING, AND PARTICIPANTS The Framingham Offspring Study, an inception cohort of the Framingham Heart Study, a prospective population-based cohort study initiated in 1948 with the offspring cohort initiated in 1971. Participants (n = 2475) were members of the offspring cohort aged 30 years or older, free of CVD, and with at least 1 sibling in the study; all were followed up for 8 years. MAIN OUTCOME MEASURES Association of sibling CVD with 8-year personal risk for CVD using pooled logistic regression. A secondary analysis restricted to offspring with both parents in the study assessed the joint impact of parental and sibling CVD occurrence. RESULTS Among 973 person-examinations in the sibling CVD group (mean age, 57 years) and 4506 person-examinations in the no sibling CVD group (mean age, 47 years), 329 CVD events occurred during follow-up. Baseline risk factors were more prevalent in the sibling CVD group compared with the no sibling CVD group. Sibling CVD was associated with a significantly increased risk for incident CVD (age- and sex-adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 1.19-2.03). Adjustment for risk factors did not substantially attenuate the risk (adjusted OR, 1.45; 95% CI, 1.10-1.91). In the analysis restricted to persons with both parents in the study, in models adjusting for both sibling and parental CVD, the multivariable-adjusted OR for sibling CVD (1.99; 95% CI, 1.32-3.00) exceeded that for parental CVD (1.45; 95% CI, 1.02-2.05). CONCLUSION Using validated events, sibling CVD conferred increased risk of future CVD events above and beyond established risk factors and parental CVD in middle-aged adults.
Serum concentrations of insulin-like growth factors (IGFs), IGF binding proteins 1 and 3 and growth hormone binding protein in obese women and the effects of growth hormone administration: a double-blind, placebo-controlled study.

Obesity is associated with suppressed growth hormone (GH) concentrations but relatively little is known about insulin-like growth factors(IGFs) and binding proteins for GH and IGFs (GHBP and IGFBPs) and the modulatory effect of GH administration. In a double-blind, crossover design we studied the impact of 5 weeks of placebo or GH administration (0.03 mg.kg-1 body wt.day-1) in nine obese women (mean +/- SEM: age 30.4 +/- 2.4 years; body mass index 37.0 +/- 2.8 kg/m2) on IGF-I, IGF-II, IGFBP-1 and -3 and GHBP. Serum IGF-I (microgram/l) levels were subnormal and increased significantly following GH (117 +/- 16 (placebo) vs 434 +/- 33 (GH) vs 198 +/- 15 (control (p < 0.01)). By contrast, serum IGF-II (microgram/l) levels were in the normal range and remained unchanged (608 +/- 20 (placebo) vs 647 +/- 40 (GH) (NS)). Serum IGFBP-3 was in the normal range and increased significantly during GH treatment, although relatively less than IGF-I, such that the molar ratio between IGF-I and IGFBP-3 increased with GH treatment, whereas the ratio between IGF-I + IGF-II and IGFBP-3 remained unchanged. Serum IGFBP-1 was low in the placebo situation but became further and almost completely suppressed during GH treatment. During a 2-h hyperinsulinemic, euglycemic glucose clamp, IGFBP-1 decreased in the placebo study and remained suppressed during GH. Serum GHBP (nmol/l) levels were elevated substantially compared to non-obese controls (p < 0.001) and did not change during GH treatment (2.37 +/- 0.36 (placebo) vs 2.21 +/- 0.25 (GH) vs 0.80 +/- 0.19 (control)). (ABSTRACT TRUNCATED AT 250 WORDS)
Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum‐infected human erythrocytes

After invading human erythrocytes, the malarial parasite Plasmodium falciparum, initiates a remarkable process of secreting proteins into the surrounding erythrocyte cytoplasm and plasma membrane. One of these exported proteins, the knob‐associated histidine‐rich protein (KAHRP), is essential for microvascular sequestration, a strategy whereby infected red cells adhere via knob structures to capillary walls and thus avoid being eliminated by the spleen. This cytoadherence is an important factor in many of the deaths caused by malaria. Green fluorescent protein fusions and fluorescence recovery after photobleaching were used to follow the pathway of KAHRP deployment from the parasite endomembrane system into an intermediate depot between parasite and host, then onwards to the erythrocyte cytoplasm and eventually into knobs. Sequence elements essential to individual steps in the pathway are defined and we show that parasite‐derived structures, known as Maurer's clefts, are an elaboration of the canonical secretory pathway that is transposed outside the parasite into the host cell, the first example of its kind in eukaryotic biology.
The Effect of Participation in a Fitness Rewards Program on Medical Care Expenditures in an Employee Population

Objective: In 2008, the University of Minnesota began offering the Fitness Rewards Program (FRP) that provides a monthly credit toward fitness center dues for individuals who exercise at a participating facility at least 8 times per month. This study evaluates whether participation in the FRP is associated with a decrease in medical spending. Methods: Using a difference-in-differences approach, we estimate multivariate regression models of average monthly medical expenditures for 2006 through 2008. Results: We find positive benefits from reduced medical spending among highly persistent FRP exercisers. However, the results are sensitive to the inclusion or exclusion of individuals who had very high medical expenditures in any year. Conclusions: Offering exercise-focused wellness initiatives may have economic benefits for employers, but further research is needed to understand the sensitivity of results to the inclusion of outliers.
Phosphorylation of Vesicular Stomatitis Virus Phosphoprotein P Is Indispensable for Virus Growth

ABSTRACT The phosphoprotein (P) of vesicular stomatitis virus (VSV) is an essential subunit of the viral RNA-dependent RNA polymerase (RdRp) complex. It is phosphorylated at two different domains. Using defective interfering (DI) RNA or minigenomic RNA templates, we previously demonstrated that phosphorylation within the amino-terminal domain I is essential for transcription, whereas phosphorylation within the carboxy-terminal domain II is necessary for replication. For the present study, we examined the role of the phosphorylation of residues in these domains in the life cycle of VSV. Various mutant P coding sequences were inserted into a full-length cDNA clone of VSV, and the virus recovery, kinetics of growth, and mRNA and protein synthesis were examined. We observed that virus recovery was completely abolished when all three phosphate acceptor sites in domain I or both sites in domain II were replaced with alanine. Single or double mutations in domain I (with the exception of P60/64) or single mutations in domain II had no adverse effect on virus recovery. VSVP227, carrying alanine at position 227, showed reduced kinetics of virus growth but increased kinetics of viral mRNA synthesis in infected cells. More interestingly, this particular virus exhibited a significantly reduced cytopathic effects and apoptosis in infected cells, implying that P may be involved in these processes. Furthermore, we found that DI RNAs of different sizes were generated by high-multiplicity passaging of various mutant VSVs, indicating that the viral RdRp may play a significant role in the process of DI particle generation. Taken together, our results suggest that the phosphorylation of residues in domains I and II of VSV P is indispensable for virus growth.
Influence of Nociception and Stress-induced Antinociception on Genetic Variation in Isoflurane Anesthetic Potency among Mouse Strains

Background: Genetic background influences anesthetic potency to suppress motor response to noxious stimulation (minimum alveolar concentration [MAC]) as well as nociceptive sensitivity in unmedicated animals. However, the influence on MAC of baseline sensitivity to the noxious stimuli used to assess MAC has virtually never been studied. The authors assessed room air nociceptive sensitivity and isoflurane MAC in multiple mouse strains. Isoflurane requirement for loss of righting response (MACLORR) was also measured. Methods: One outbred and 10 inbred mouse strains were tested for latency to respond (in room air) to a tail clip (either 500 g or 2,000 g). Naive mice of the same 11 strains were tested for isoflurane MAC and MACLORR. To assess the role of opioid-mediated stress-induced antinociception, mice were also tested for nociceptive sensitivity after injection of naloxone (10 mg/kg) or saline. Results: Robust strain differences were observed for all measures. The authors found that tail-clip latency (using a 500-g or 2,000-g clip, respectively) correlated significantly with MAC (r = −0.76 and −0.58, respectively) but not MACLORR (r = −0.10 and −0.26). Naloxone produced strain-dependent reductions in open air tail-clip latencies, and these reductions were also strongly correlated with MAC (r = −0.67 and −0.71). Conclusions: The authors suggest that genetic variability in isoflurane MAC (but not MACLORR) may reflect genetic variability in the underlying sensitivity to the noxious stimulus being used to measure MAC. This variable sensitivity to nociception in the awake state is at least partially mediated by endogenous antinociceptive mechanisms activated by the tail-clip stimulus itself.
ARAMEMNON, a Novel Database for Arabidopsis Integral Membrane Proteins1

A specialized database (DB) for Arabidopsis membrane proteins, ARAMEMNON, was designed that facilitates the interpretation of gene and protein sequence data by integrating features that are presently only available from individual sources. Using several publicly available prediction programs, putative integral membrane proteins were identified among the approximately 25,500 proteins in the Arabidopsis genome DBs. By averaging the predictions from seven programs, approximately 6,500 proteins were classified as transmembrane (TM) candidate proteins. Some 1,800 of these contain at least four TM spans and are possibly linked to transport functions. The ARAMEMNON DB enables direct comparison of the predictions of seven different TM span computation programs and the predictions of subcellular localization by eight signal peptide recognition programs. A special function displays the proteins related to the query and dynamically generates a protein family structure. As a first set of proteins from other organisms, all of the approximately 700 putative membrane proteins were extracted from the genome of the cyanobacterium Synechocystis sp. and incorporated in the ARAMEMNON DB. The ARAMEMNON DB is accessible at the URL http://aramemnon.botanik. uni-koeln.de.
The EEAG Report on the European Economy 2014: The road towards cohesion

Foreword, The road towards cohesion, Executive Summary, Chapter 1: Macroeconomic Outlook, Chapter 2: Switzerland: Relic of the Past, Model for the Future? *, Chapter 3: Austerity: Hurting but Helping, Chapter 4: Banking Union: Who Should Take Charge? , Authors
Genome-Wide Analysis in Brazilians Reveals Highly Differentiated Native American Genome Regions

Despite its population, geographic size, and emerging economic importance, disproportionately little genome-scale research exists into genetic factors that predispose Brazilians to disease, or the population genetics of risk. After identification of suitable proxy populations and careful analysis of tri-continental admixture in 1,538 North-Eastern Brazilians to estimate individual ancestry and ancestral allele frequencies, we computed 400,000 genome-wide locus-specific branch length (LSBL) Fst statistics of Brazilian Amerindian ancestry compared to European and African; and a similar set of differentiation statistics for their Amerindian component compared with the closest Asian 1000 Genomes population (surprisingly, Bengalis in Bangladesh). After ranking SNPs by these statistics, we identified the top 10 highly differentiated SNPs in five genome regions in the LSBL tests of Brazilian Amerindian ancestry compared to European and African; and the top 10 SNPs in eight regions comparing their Amerindian component to the closest Asian 1000 Genomes population. We found SNPs within or proximal to the genes CIITA (rs6498115), SMC6 (rs1834619), and KLHL29 (rs2288697) were most differentiated in the Amerindian-specific branch, while SNPs in the genes ADAMTS9 (rs7631391), DOCK2 (rs77594147), SLC28A1 (rs28649017), ARHGAP5 (rs7151991), and CIITA (rs45601437) were most highly differentiated in the Asian comparison. These genes are known to influence immune function, metabolic and anthropometry traits, and embryonic development. These analyses have identified candidate genes for selection within Amerindian ancestry, and by comparison of the two analyses, those for which the differentiation may have arisen during the migration from Asia to the Americas.
The Research and Application of a Novel Time Domain Hybrid Method for EMI Analysis of Lumped Circuits in a Shielded Device

This paper presents a novel time domain hybrid method consisting of finite-difference time domain (FDTD) method, transmission line (TL) equations, and circuit-based method, which can be directly applied in time domain for the electromagnetic interference (EMI) analysis of the lumped circuits in a shielded device excited by ambient electromagnetic wave. The FDTD method coupled with the TL equations is utilized to model the electromagnetic properties of arbitrary structures containing transmission lines and shielded enclosure of the electronic device with any ambient excitation. With numerical simulation, an equivalent circuit model considering the external EMI effects is extracted as an excitation source for the internal lumped circuit according to Thevenin's theorem. Then, the state variable approach is used for the further EMI analysis of the internal lumped circuit in time domain. Two cases, in which a transmission line and/or a transmission line network are connected to a lumped circuit within a shielded enclosure excited by an intense electromagnetic pulse, are computed with the proposed method. The numerical results are compared with those obtained by using the FDTD method, and they are almost in perfect agreements. Meanwhile, at last, an example of this method applied for the EMI protection of an electronic device is given.
Function of alpha beta TCR+ intestinal intraepithelial lymphocytes: Th1- and Th2-type cytokine production by CD4+CD8- and CD4+CD8+ T cells for helper activity.

The immunobiological function of lymphocytes within the epithelium (IELs) of the small intestine is incompletely understood; however, it has been shown that intestinal IEL T cells exhibit cytotoxicity, produce cytokines, and perform some regulatory roles. In this study, we have focused on CD4+, alpha beta TCR+ IELs, which comprise approximately 15-20% of the total population, for helper functions. We have assessed the profile of type 1 or type 2 Th cell cytokines produced in alpha beta TCR bearing CD4+CD8- and CD4+CD8+ (double positive, DP) intestinal IELs by cytokine-specific ELISPOT and by reverse transcription-polymerase chain reaction. Help for B cells taken from Peyer's patches (PP) allowed us to assess IEL function for mucosal antibody responses. Freshly isolated CD4+CD8- IEL T cells contain Th2-type cells, e.g. high numbers of IL-5 secreting (spot forming) cells (SFC) followed by IL-4 and IL-6, while DP T cells have IL-5 and IL-6 producing cells, but not IL-4. In addition to Th2-like cytokine producing T cells, both CD4+ T cell subsets contain IFN-gamma secreting Th1-type cells but neither subset synthesizes IL-2. Stimulation of CD4+CD8- and DP T cells with solid phase mAb anti-CD3 resulted in production of IL-2 in addition to IFN-gamma, IL-5, and IL-6, and this treatment stimulated DP T cells to produce IL-4. When freshly isolated intestinal IEL T cells were separated into CD4+ and CD4- cells, and co-cultured with PP B cells, the former subset supported Ig synthesis including IgA responses, while the later fraction did not. (ABSTRACT TRUNCATED AT 250 WORDS)
The siesta and mortality in the elderly: effect of rest without sleep and daytime sleep duration.

STUDY OBJECTIVE To examine the effects of daytime rest without sleep and duration of the siesta on mortality. DESIGN Longitudinal observation. SETTING AND PARTICIPANTS Population sample of 442 community-dwelling 70-year-old subjects examined both at home and in a geriatric hospital. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Overall mortality for those who neither rested nor slept was 9.3%, for those who rested without sleep 10.9%, and for those who slept 19%, p<0.02. Males had higher mortality (19%) than females (10%), p<0.006. Rest without sleep had no effect on mortality: in males, 13%, 21%, 18% for no rest, rest of less than one hour, or more than one hour with respective 8%, 6% and 4% in females. However, daytime sleep in males of more than one hour had 28.2% mortality, whereas sleep of one hour or less had 13.6% mortality, p=0.02. In females mortality rate was not different by sleep duration: 16% and 13.6% for those who slept for one hour or less, or more than one hour, respectively. In a multivariate analysis in females, a siesta of one hour or less was associated with risk odds ratio (ROR) of 4.67 and 95% confidence interval (CI) 1.22-17.80 and of one to two hours, ROR was 5.57 and 95% CI 1.05-29.49. For males, siesta of less than one hour was not associated with excess risk, ROR 0.9 and 95% CI 0.39-2.38; a siesta of one to two hours with ROR of 2.61 and 95% CI 1.01-6.80; and two hours or more ROR 13.6 and 95% CI 0.98-2.10. CONCLUSIONS Rest without sleep is not associated with excess risk of mortality. However, siesta of one to two hours is associated with increased mortality in males whereas, in women, a siesta of less than one hours confers the excess risk.
Calcium signalling in cells of oligodendroglial lineage

Intracellular Ca2+ is the key signal that regulates the efficacy of neurotransmitter release and synaptic plasticity in neurons but is also an important second messenger involved in the signal transduction and modulation of gene expression in both excitable and non‐excitable cells. Glial cells, including cells of oligodendroglial (OLG) lineage, are capable of responding to extracellular stimuli via changes in the intracellular Ca2+. This review article focuses on the mechanisms of Ca2+ signalling in cells of OLG lineage with the goal of providing the basis for understanding the relevance of receptor‐ and non‐receptor‐mediated signalling to oligodendroglial development, myelination, and demyelination. Conclusions to date indicate that cells of OLG lineage exhibit remarkable plasticity with regard to the expression of ion channels and receptors linked to Ca2+ signalling and that perturbation of [Ca2+]i homeostasis contributes to the pathogenesis of demyelinating diseases. Microsc. Res. Tech. 52:672–679, 2001. © 2001 Wiley‐Liss, Inc.
A novel image steganography method based on DCT and LSB

Image steganography is the study of embedding sensitive information in images without distorting their visual quality. In this paper, we have proposed an efficient image steganography algorithm to embed the secret image in the cover image. In this scheme, the secret image is encrypted that refers to the transformation of the secret data with Discrete Cosine Transform (DCT) compound with its hash file that is secured by a secret key. By this means, the embedded image is transformed into a noise-like cipher image called random noise in steganography methods with its HMAC file. The randomness property of the resultant image reduces the possibility of its detection by the human visual system (HVS) and steganalysis techniques. Next, LSB substitution method is employed to embed the transformed image in the cover image. To authenticate the image at the receiver side, the HMAC of the secret image is embedded in the cover image using LSB method. Simulation results have verified the effectiveness of the proposed algorithm.
Effect of exercise on depression in university students: a meta-analysis of randomized controlled trials.

INTRODUCTION The aim of this study was to assess the effect of exercise on depression in university students. EVIDENCE ACQUISITION A systematic literature search was conducted in PubMed, EMBASE and the Cochrane library from their inception through December 10, 2014 to identify relevant articles. The heterogeneity across studies was examined by Cochran's Q statistic and the I2 statistic. Standardized mean difference (SMD) and 95% confidence interval (CI) were pooled to evaluate the effect of exercise on depression. Then, sensitivity and subgroup analyses were performed. In addition, publication bias was assessed by drawing a funnel plot. EVIDENCE SYNTHESIS A total of 352 participants (154 cases and 182 controls) from eight included trials were included. Our pooled result showed a significant alleviative depression after exercise (SMD=-0.50, 95% CI: -0.97 to -0.03, P=0.04) with significant heterogeneity (P=0.003, I2=67%). Sensitivity analyses showed that the pooled result may be unstable. Subgroup analysis indicated that sample size may be a source of heterogeneity. Moreover, no publication bias was observed in this study. CONCLUSIONS Exercise may be an effective therapy for treating depression in university students. However, further clinical studies with strict design and large samples focused on this specific population should be warranted in the future.