julilili42/papers huggingface dataset:
CTLA-4 Genetic Variants Predict Survival in Patients with Sepsis
2019-01-10

Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a coinhibitory checkpoint protein expressed on the surface of T cells. A recent study by our working group revealed that the rs231775 single nucleotide polymorphism (SNP) in the CTLA-4 gene was associated with the survival of patients with sepsis and served as an independent prognostic variable. To further investigate the impact of CTLA-4 genetic variants on sepsis survival, we examined the effect of two functional SNPs, CTLA-4 rs733618 and CTLA-4 rs3087243, and inferred haplotypes, on the survival of 644 prospectively enrolled septic patients. Kaplan–Meier survival analysis revealed significantly lower 90-day mortality for rs3087243 G allele carriers (n = 502) than for AA-homozygous (n = 142) patients (27.3% vs. 40.8%, p = 0.0024). Likewise, lower 90-day mortality was observed for TAA haplotype-negative patients (n = 197; compound rs733618 T/rs231775 A/rs3087243 A) than for patients carrying the TAA haplotype (n = 447; 24.4% vs. 32.9%, p = 0.0265). Carrying the rs3087243 G allele hazard ratio (HR): 0.667; 95% confidence interval (CI): 0.489–0.909; p = 0.0103) or not carrying the TAA haplotype (HR: 0.685; 95% CI: 0.491–0.956; p = 0.0262) remained significant covariates for 90-day survival in the multivariate Cox regression analysis and thus served as independent prognostic variables. In conclusion, our findings underscore the significance of CTLA-4 genetic variants as predictors of survival of patients with sepsis.
Youth Labor in Transition: Inequalities, Mobility, and Policies in Europe
2019-01-10

"Youth transitions to employment in Europe are increasingly protracted, precarious and differentiated by gender, ethnicity, and socioeconomic status. Examining employment transitions affected by the family and migration the authors argue for an integrated analysis of the sphere of economic production and social reproduction if policy intervention is to be effective"...
Structure of the SLy1 SAM homodimer reveals a new interface for SAM domain self-association.
2019-01-10

Sterile alpha motif (SAM) domains are protein interaction modules that are involved in a diverse range of biological functions such as transcriptional and translational regulation, cellular signalling, and regulation of developmental processes. SH3 domain-containing protein expressed in lymphocytes 1 (SLy1) is involved in immune regulation and contains a SAM domain of unknown function. In this report, the structure of the SLy1 SAM domain was solved and revealed that this SAM domain forms a symmetric homodimer through a novel interface. The interface consists primarily of the two long C-terminal helices, α5 and α5', of the domains packing against each other. The dimerization is characterized by a dissociation constant in the lower micromolar range. A SLy1 SAM domain construct with an extended N-terminus containing five additional amino acids of the SLy1 sequence further increases the stability of the homodimer, making the SLy1 SAM dimer two orders of magnitude more stable than previously studied SAM homodimers, suggesting that the SLy1 SAM dimerization is of functional significance. The SLy1 SAM homodimer contains an exposed mid-loop surface on each monomer, which may provide a scaffold for mediating interactions with other SAM domain-containing proteins via a typical mid-loop-end-helix interface.
Distinct Stress Response and Altered Striatal Transcriptome in Alpha-Synuclein Overexpressing Mice
2019-01-10

Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor symptoms and a plethora of non-motor and neuropsychiatric features that accompany the disease from prodromal to advanced stages. While several genetic defects have been identified in familial forms of PD, the predominance of cases are sporadic and result from a complex interplay of genetic and non-genetic factors. Clinical evidence, moreover, indicates a role of environmental stress in PD, supported by analogies between stress-induced pathological consequences and neuronal deterioration observed in PD. From this perspective, we set out to investigate the effects of chronic stress exposure in the context of PD by using a genetic mouse model that overexpresses human wildtype <i>SNCA</i>. Mimicking chronic stress was achieved by adapting a chronic unpredictable mild stress protocol (CUMS) comprising eight different stressors that were applied randomly over a period of eight weeks starting at an age of four months. A distinctive stress response with an impact on anxiety-related behavior was observed upon <i>SNCA</i> overexpression and CUMS exposure. <i>SNCA</i>-overexpressing mice showed prolonged elevation of cortisol metabolites during CUMS exposure, altered anxiety-related traits, and declined motor skills surfacing with advanced age. To relate our phenotypic observations to molecular events, we profiled the striatal and hippocampal transcriptome and used a 2 × 2 factorial design opposing genotype and environment to determine differentially expressed genes. Disturbed striatal gene expression and minor hippocampal gene expression changes were observed in <i>SNCA</i>-overexpressing mice at six months of age. Irrespective of the CUMS-exposure, genes attributed to the terms neuroinflammation, Parkinson's signaling, and plasticity of synapses were altered in the striatum of <i>SNCA</i>-overexpressing mice.
Serum- and glucocorticoid-inducible kinase 1 and the response to cell stress
2019-01-11

Expression of the serum- and glucocorticoid-inducible kinase 1 (SGK1) is up-regulated by several types of cell stress, such as ischemia, radiation and hyperosmotic shock. The SGK1 protein is activated by a signaling cascade involving phosphatidylinositide-3-kinase (PI3K), 3-phosphoinositide-dependent kinase 1 (PDK1) and mammalian target of rapamycin (mTOR). SGK1 up-regulates Na<sup>+</sup>/K<sup>+</sup>-ATPase, a variety of carriers including Na<sup>+</sup>-,K<sup>+</sup>-,2Cl<sup>-</sup>- cotransporter (NKCC), NaCl cotransporter (NCC), Na<sup>+</sup>/H<sup>+</sup> exchangers, diverse amino acid transporters and several glucose carriers such as Na<sup>+</sup>-coupled glucose transporter SGLT1. SGK1 further up-regulates a large number of ion channels including epithelial Na<sup>+</sup> channel ENaC, voltagegated Na<sup>+</sup> channel SCN5A, Ca<sup>2+</sup> release-activated Ca<sup>2+</sup> channel (ORAI1) with its stimulator STIM1, epithelial Ca<sup>2+</sup> channels TRPV5 and TRPV6 and diverse K<sup>+</sup> channels. Furthermore, SGK1 influences transcription factors such as nuclear factor kappa-B (NF-κB), p53 tumor suppressor protein, cAMP responsive element-binding protein (CREB), activator protein-1 (AP-1) and forkhead box O3 protein (FOXO3a). Thus, SGK1 supports cellular glucose uptake and glycolysis, angiogenesis, cell survival, cell migration, and wound healing. Presumably as last line of defense against tissue injury, SGK1 fosters tissue fibrosis and tissue calcification replacing energy consuming cells.
Subjective Evaluation of a Passive Lower-Limb Industrial Exoskeleton Used During simulated Assembly
2019-01-11

OCCUPATIONAL APPLICATIONSThis study showed an overall positive judgment of users when using a passive lower-limb exoskeleton (Chairless Chair®, noonee AG, Switzerland), in terms of high levels of comfort and low levels of discomfort. These findings are promising with regard to field implementation, although final steps in the exoskeleton design first have to be taken. In future feasibility studies, users' acceptance of the exoskeleton should be investigated in the field. One important question that remains is when and for how long users should wear and use the exoskeleton, and areas of beneficial field application need to be defined with regard to primary, secondary, and tertiary prevention, which may provide guidelines for effective use.
Representing dynamic biological networks with multi-scale probabilistic models
2019-01-11

Abstract Dynamic models analyzing gene regulation and metabolism face challenges when adapted to modeling signal transduction networks. During signal transduction, molecular reactions and mechanisms occur in different spatial and temporal frames and involve feedbacks. This impedes the straight-forward use of methods based on Boolean networks, Bayesian approaches, and differential equations. We propose a new approach, ProbRules, that combines probabilities and logical rules to represent the dynamics of a system across multiple scales. We demonstrate that ProbRules models can represent various network motifs of biological systems. As an example of a comprehensive model of signal transduction, we provide a Wnt network that shows remarkable robustness under a range of phenotypical and pathological conditions. Its simulation allows the clarification of controversially discussed molecular mechanisms of Wnt signaling by predicting wet-lab measurements. ProbRules provides an avenue in current computational modeling by enabling systems biologists to integrate vast amounts of available data on different scales.
Heavy-flavour production in the SACOT-mT scheme
2019-01-11

The hadroproduction of heavy-flavoured mesons has recently attracted a growing interest e.g. within the people involved in global analysis of proton and nuclear parton distribution functions, saturation physics, and physics of cosmic rays. In particular, the D- and B-meson measurements of LHCb at forward direction are sensitive to gluon dynamics at small x and are one of the few perturbative small-x probes before the next generation deep-inelastic-scattering experiments. In this talk, we will concentrate on the collinear-factorization approach to inclusive D-meson production and describe a novel implementation — SACOT-mT — of the general-mass variable flavour number scheme (GM-VFNS). In the GM-VFNS framework the cross sections retain the full heavy-quark mass dependence at pT = 0, but gradually reduce to the ordinary zero-mass results towards asymptotically high pT. However, the region of small (but non-zero) pT has been somewhat problematic in the previous implementations of GM-VFNS, leading to divergent cross sections towards pT → 0, unless the QCD scales are set in a particular way. Here, we provide a solution to this problem. In essence, the idea is to consistently account for the underlying energy-momentum conservation in the presence of a final-state heavy quark-antiquark pair. This automatically leads to a well-behaved GM-VFNS description of the cross sections across all pT without a need to fine tune the QCD scales. The results are compared with the LHCb data and a very good agreement is found. We also compare to fixed-order based calculations and explain why they lead to approximately a factor of two lower D-meson production cross sections than the GM-VFNS approach.
Macrophage Phosphoproteome Analysis Reveals MINCLE-dependent and -independent Mycobacterial Cord Factor Signaling
2019-01-12

Immune sensing of <i>Mycobacterium tuberculosis</i> relies on recognition by macrophages. Mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM), is the most abundant cell wall glycolipid and binds to the C-type lectin receptor (CLR) MINCLE. To explore the kinase signaling linking the TDM-MINCLE interaction to gene expression, we employed quantitative phosphoproteome analysis. TDM caused upregulation of 6.7% and suppressed 3.8% of the 14,000 phospho-sites identified on 3727 proteins. MINCLE-dependent phosphorylation was observed for canonical players of CLR signaling (<i>e.g.</i> PLCγ, PKCδ), and was enriched for PKCδ and GSK3 kinase motifs. MINCLE-dependent activation of the PI3K-AKT-GSK3 pathway contributed to inflammatory gene expression and required the PI3K regulatory subunit p85α. Unexpectedly, a substantial fraction of TDM-induced phosphorylation was MINCLE-independent, a finding paralleled by transcriptome data. Bioinformatics analysis of both data sets concurred in the requirement for MINCLE for innate immune response pathways and processes. In contrast, MINCLE-independent phosphorylation and transcriptome responses were linked to cell cycle regulation. Collectively, our global analyses show substantial reprogramming of macrophages by TDM and reveal a dichotomy of MINCLE-dependent and -independent signaling linked to distinct biological responses.
Risk of Dengue Transmission in Cocody (Abidjan, Ivory Coast)
2019-01-14

In recent years, an upsurge of vector-borne diseases has been reported in several parts of the world. Among these is dengue fever, the first arbovirus transmitted by mosquitoes of the genus Aedes . After the detection of the dengue virus serological types (type 1, 2, and 3) in the health district of Cocody-Bingerville in Ivory Coast, entomological investigations were carried out in the city of Cocody (host of most cases) to evaluate the risk of transmission of the disease in view of an effective vector control. Larval prospection together with the pitching of emergence traps was carried out in Caféier 5, Sideci-Coteau, Danga, Ecole de police, Gobelet village, Laurier 9, Lemania, Perles, 7 ème tranche, and 12 ème arrondissement. Entomological prospections revealed the predominance of Aedes aegypti (97.38%) as the main vector species of dengue viruses in Cocody. The Kruskall-Wallis test showed no statistically significant difference (KW = 1.8, p = 0.407) in the proportions of the vector species collected from the sampled sites. The risk of an outbreak of dengue fever in Cocody and other municipalities in the city of Abidjan is very certain insofar as the larval epidemic risk indices (Habitat Index, HI = 70.9; Container Index, CI = 40.26; and Breteau Index, BI= 21.3) reflect a very high epidemic risk (4 to 9) on the WHO density scale. The occurrence of Aedes aegypti in Cocody indicates the risk of transmission of the Dengue fever virus.
The Positive Brain – Resting State Functional Connectivity in Highly Vital and Flourishing Individuals
2019-01-14

The World Health Organization has defined health as "complete physical, mental and social well-being and not merely the absence of disease or infirmity" (World Health Organization, 1948). An increasing number of studies have therefore started to investigate "the good life." However, the underlying variation in brain activity has rarely been examined. The goal of this study was to assess differences in resting state functional connectivity (RSFC) between regular healthy individuals and healthy individuals with a high occurrence of flourishing and subjective vitality. Together, flourishing, a broad measure of psycho-social functioning and subjective vitality, an organismic marker of subjective well-being comprise the phenomenological opposite of a major depressive disorder. Out of a group of 43 participants, 20 high-flourishing (highFl) and 18 high-vital (highSV) individuals underwent a 7-min resting state period, where cortical activity in posterior brain areas was assessed using functional near-infrared spectroscopy (fNIRS). Network-based statistics (NBS) of FC yielded significantly different FC patterns for the highFl and highSV individuals compared to their healthy comparison group. The networks converged at areas of the posterior default mode network and differed in hub nodes in the left middle temporal/fusiform gyrus (flourishing) and the left primary/secondary somatosensory cortex (subjective vitality). The attained networks are discussed with regard to recent neuroscientific findings for other well-being measures and potential mechanisms of action based on social information processing and body-related self-perception.
Effects of the equation of state on the core-crust interface of slowly rotating neutron stars
2019-01-14

We systematically study the symmetry energy effects of the transition density\\n and the transition pressure around the crust-core\\ninterface of a neutron star in the framework of the dynamical and the\\nthermodynamical method respectively. We employ both the parabolic approximation\\nand the full expansion, for the definition of the symmetry energy. We use\\nvarious theoretical nuclear models, which are suitable for reproducing the bulk\\nproperties of nuclear matter at low densities, close to saturation density as\\nwell as the maximum observational neutron star mass. Firstly we derive and\\npresent an approximation for the transition pressure and crustal\\nmass . Secondly, we explore the effects of the Equation of State\\n(EoS) on a few astrophysical applications which are sensitive to the values of\\n and including neutron star oscillation frequencies,\\nthermal relaxation of the crust, crustal fraction of the moment of inertia and\\nthe r-mode instability window of a rotating neutron star. We found that the\\nabove quantities are sensitive mainly on the applied approximation for the\\nsymmetry energy (confirming previous results). Furthermore, an additional\\nsensitivity also exists, depending on the used method (dynamical or\\nthermodynamical). The above findings lead us to claim that the determination of\\nthe and must be reliable and accurate before they are\\nused to constrain relevant neutron star properties.\\n
Fine-mapping of 150 breast cancer risk regions identifies 178 high confidence target genes
2019-01-15

ABSTRACT Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants (CCVs) in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium, and enriched genomic features to determine variants with high posterior probabilities (HPPs) of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of potentially causal variants, using gene expression (eQTL), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways, were over-represented among the 178 highest confidence target genes.
User activity recognition system to improve the performance of environmental control interfaces: a pilot study with patients
2019-01-15

The environment analysis and the identification of the user's behaviors can be used to predict the user intention opening a new paradigm in the design of the ECIs. Although the developed ECI was tested only in a simulated home environment, it can be easily adapted to a real environment increasing the user independence at home.
Attitude confidence and source credibility in information foraging with social tags
2019-01-15

There is growing concern that online information searchers are overconfident and therefore largely search for information which reinforces their prior attitudes, blinded by confirmation bias. This study tests if this effect can be reduced in content aggregation platforms, when social tag clouds show popular topics among experts. We manipulated (1) confidence in prior attitudes, and (2) the credibility of the expert community that tagged the content. We found that both factors influence navigation in different ways. First, attitude confidence moderated the influence of prior attitudes when choosing how much attitude-consistent content in blog posts to read. When attitude confidence was high, prior attitudes were positively associated with selection of blog posts, when low, not positively associated. After navigation, when confidence was high, the content of attitude-consistent blog posts was more favourably evaluated, whereas when confidence was low, attitude inconsistent blog posts were more favourably evaluated. Second, source credibility moderated the influence of prior attitudes on tag selection. When source credibility was low, prior attitudes did guide tag selection, when high, they did not. With low source credibility, people selected more attitude-consistent content. The findings advance social tagging theories by showing that not only semantic associations, but also attitudes play a role when people select and process tags and related content. The findings also show that credibility and confidence have a different impact on different stages of information selection and evaluation. Whereas credibility is more important when switching among pages, attitude confidence is more important when reading and evaluating the content of one page.
The sinemydid turtleOrdosemysfrom the Lower Cretaceous Mengyin Formation of Shandong, China and its implication for the age of the Luohandong Formation of the Ordos Basin
2019-01-15

Chronostratigraphic correlation of terrestrial Early Cretaceous biotas in China is highly problematic due to the lack of marine deposits, few absolute dates, and limited number of index fossils. This often leaves vertebrate faunas as one of the few potential tools for a preliminary biostratigraphy. Taxonomic identity of fragmentary fossils is, however, often uncertain and many faunas are insufficiently sampled. Turtles are one of the most common elements of Early Cretaceous biotas of Asia and their skeleton is frequently preserved more completely than that of other vertebrates- they yet receive little attention from vertebrate paleontologists. We here record the presence of the sinemydid turtle Ordosemys leios from the Lower Cretaceous Mengyin Formation of Shandong Province, China, best known for the first dinosaurs and Mesozoic turtles described from the country. Ordosemys is the third turtle reported from the Mengyin Formation along with Sinemys lens and Sinochelys applanata and the only other formation where Ordosemys is known to co-occur with Sinemys is the Luohandong Formation of the Ordos Basin (Inner Mongolia), the type and so far only horizon of Ordosemys leios . The presence of the crocodyliform Shantungosuchus may further define a fauna that is so far only known from these two formations. The stratigraphic position of the Luohandong Formation is poorly controlled and it has been placed anywhere between the Valanginian and Aptian. Published absolute dates from the Mengyin Formation and the numerous shared vertebrate and invertebrate taxa (now also including turtles) implies a Valanginian—early Hauterivian age for the Luohandong Formation—in contrast to late Hauterivian-Albian as previously proposed using the temporal distribution of Psittacosaurus . The new specimen of Ordosemys leios preserves the only known manus of this species and ecomorphological analysis of limb proportions implies that it was a less capable swimmer compared to Ordosemys liaoxiensis coming from the younger Jehol Biota.