julilili42/papers huggingface dataset:
Impaired inhibitory control in anorexia nervosa elicited by physical activity stimuli
2013-05-14

Besides food restriction, hyperactivity is considered a key behavioral trait of anorexia nervosa (AN), playing a major role in the pathogenesis and progression of the disorder. However, the underlying neurophysiology remains poorly understood. We used functional magnetic resonance imaging during two affective go/no-go tasks to probe inhibitory control in response to stimuli depicting physical activity vs inactivity and food vs non-food in AN patients compared with 26 healthy athlete and non-athlete controls. We hypothesized that neural correlates of behavioral inhibition are biased by the emotional information of the stimuli in AN patients, leading to a differential neural inhibitory pattern during the two tasks. Indeed, we found reduced response inhibition for food and non-food images in the putamen, while stimuli depicting physical activity resulted in an exaggerated response of the prefrontal cortex (PFC) and cerebellum in AN patients. However, both AN patients and athletes revealed an increased response in the somatosensory cortex to physical activity stimuli. These results suggest that physical activity stimuli might place an increased demand on the inhibitory control system in AN patients. The resulting hyperactivity of the PFC and cerebellum may lead to altered executive function and motor control, sustaining increased physical activity in AN patients.
Neural Correlates of Sound Localization in Complex Acoustic Environments
2013-05-14

Listening to and understanding people in a "cocktail-party situation" is a remarkable feature of the human auditory system. Here we investigated the neural correlates of the ability to localize a particular sound among others in an acoustically cluttered environment with healthy subjects. In a sound localization task, five different natural sounds were presented from five virtual spatial locations during functional magnetic resonance imaging (fMRI). Activity related to auditory stream segregation was revealed in posterior superior temporal gyrus bilaterally, anterior insula, supplementary motor area, and frontoparietal network. Moreover, the results indicated critical roles of left planum temporale in extracting the sound of interest among acoustical distracters and the precuneus in orienting spatial attention to the target sound. We hypothesized that the left-sided lateralization of the planum temporale activation is related to the higher specialization of the left hemisphere for analysis of spectrotemporal sound features. Furthermore, the precuneus - a brain area known to be involved in the computation of spatial coordinates across diverse frames of reference for reaching to objects - seems to be also a crucial area for accurately determining locations of auditory targets in an acoustically complex scene of multiple sound sources. The precuneus thus may not only be involved in visuo-motor processes, but may also subserve related functions in the auditory modality.
SNCA: Major genetic modifier of age at onset of Parkinson's disease
2013-05-14

ABSTRACT Age at onset serves as a predictor of progression and mortality in sporadic Parkinson's disease (PD). Therefore, the identification of genetic modifiers for age at onset might lead to a better understanding of disease pathogenesis. We performed multivariate linear regression analysis in 1396 sporadic PD patients assessing 21 single‐nucleotide polymorphisms (SNPs) that have been previously suggested to be associated with sporadic PD. Moreover, a cumulative risk score was assigned to each patient and correlated with age at onset. We identified the rs356219 risk allele in the SNCA gene as significantly contributing to earlier age at onset. Neither one of the other 21 SNPs tested in this analysis nor the cumulative number of risk alleles showed a significant impact on PD onset. Because sequence variants in the SNCA gene are not only associated with autosomal dominantly inherited PD and increased susceptibility for sporadic PD but also have been found to modify the phenotype such as age at onset in both sporadic and various monogenic forms of PD, this gene serves as an outstanding target for further research on PD pathogenesis, which in return might provide potential therapeutic options. © 2013 Movement Disorder Society
Presence of β-lactamases in extended-spectrum-cephalosporin-resistant Salmonella enterica of 30 different serovars in Germany 2005–11
2013-05-14

The wide spread of ESBL and AmpC genes in Salmonella of various serovars is most probably due to transfer of conjugative plasmids. Furthermore, our data indicate the clonal spread of distinct cephalosporin-resistant Salmonella strains from livestock to humans.
Effect of Timolol on Central Corneal Thickness
2013-05-14

Purpose Timolol is an effective and safe medication that is widely used in glaucoma treatment. Although it is known that it is quickly taken up by the cornea following topical administration and that the cornea exhibits β-adrenergic receptors, there are few studies available on the clinical impact of timolol on central corneal thickness (CCT). Methods Twenty healthy subjects were tested in a double-blind, prospective, and randomized study. Intraocular pressure (IOP) and CCT were measured before and during administration of timolol 0.5% eyedrops over 28 days. Results Administration of timolol 0.5% resulted in a reduction of IOP from an initial value of 16 ± 2 mm Hg to 13 ± 0 mm Hg (p&lt;0.001, R 2 = 0.7033) as well as an increase in CCT from 555 ± 11 μm from the time of the baseline examination to 567 ± 9 μm (p = 0.005, R 2 = 0.8754), an increase of epithelial thickness from 53 ± 2 μm to 59 ± 3 μm (p&lt;0.001, R 2 = 0.5063), and an increase of stromal thickness from 494 ± 4 μm to 498 ± 9 μm (p = 0.045, R 2 = 0.4352) after 9 days each. From day 10 on, a decrease in CCT (R 2 = 0.6164), epithelial thickness (R 2 = 0.2216), and stromal thickness (R 2 = 0.2092) was observed. At the end, the values had returned toward the initial values measured (CCT 553 ± 8 μm, p = 0.391; epithelial thickness, 50 ± 2 μm, p = 0.214; and stromal thickness, 493 ± 8 μm, p = 0.483). In contrast, endothelial thickness did not vary following administration of timolol 0.5% (p = 0.727, R 2 = 0.009). Conclusions Topical administration of timolol 0.5% results in a reversible increase in CCT. These modest changes are unlikely to influence tonometry or clinical decision-making.
Detection of X-rays from the jet-driving symbiotic star Hen 3-1341
2013-05-14

\\n Context. Hen 3-1341 is a symbiotic binary system consisting of a white dwarf and a red giant star that is one of about ten symbiotics that show hints of jets. The bipolar jets have been detected through displaced components of emission lines during its outburst from 1998 to 2004. These components disappeared when Hen 3-1341 reached quiescence. On February 23, 2012, Hen 3-1341 started a new outburst with the emergence of new bipolar jets on March 3, 2012.\\n Aims. We observed Hen 3-1341 during quiescence with XMM-Newton in March 2010 with an effective exposure time of 46.8 ks and with Swift on March 8–11, 2012 as ToO observations with an effective exposure time of 10 ks in order to probe the interaction of the jet with the ambient medium and also the accretion onto the white dwarf.\\n Methods. We fitted the XMM-Newton X-ray spectra with XSPEC and examined the X-ray and UV light curves.\\n Results. We report the detection of X-ray emission during quiescence from Hen 3-1341 with XMM-Newton. The spectrum can be fitted with an absorbed one-temperature plasma or an absorbed blackbody. We did not detect Hen 3-1341 during our short Swift exposure. Neither periodic or aperiodic X-ray nor UV variability were found.\\n Conclusions. Our XMM-Newton data suggest that interaction of the residual jet with the interstellar medium might survive for a long time after outbursts and might be responsible for the observed X-ray emission during quiescence. Additional data are strongly needed to confirm these suggestions.\\n
Cloning, chromosomal characterization and FISH mapping of the NAD+-dependent histone deacetylase gene sirtuin 5 in the mouse
2013-05-14

Sirtuin 5 (SIRT5) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, belonging to the silent information regulator 2 (Sir2) family of sirtuin histone deacetylases (sirtuins). The yeast Sir2 protein and its mammalian derivatives are important in epigenetic gene silencing, DNA repair and recombination, cell cycle, microtubule organization and in the regulation of aging. In mammals, 7 sirtuin isoforms have been identified to date of which three (SIRT3, SIRT4 and SIRT5) are localized in the mitochondria, which serve as the center of energy management and the initiation of cellular apoptosis. In the study presented herein, we report the genomic organization and chromosomal localization of the murine sirt5 gene. We have isolated and characterized the murine sirt5 genomic sequence, which spans a region of 24,449 bp and which has one single genomic locus. The murine sirt5 gene consists of 8 exons and encodes a 310-aa protein with a predictive mo-lecular weight of 34.1 kDa and an isoelectric point of 8.90. For the murine sirt5 gene only one single genomic locus has been identified. The gene has been localized to mouse chromosome 13A4 and is flanked by STS-marker 164522 (synonymous WI MRC-RH: 506859).
The CTRB1/2 Locus Affects Diabetes Susceptibility and Treatment via the Incretin Pathway
2013-05-15

The incretin hormone glucagon-like peptide 1 (GLP-1) promotes glucose homeostasis and enhances β-cell function. GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which inhibit the physiological inactivation of endogenous GLP-1, are used for the treatment of type 2 diabetes. Using the Metabochip, we identified three novel genetic loci with large effects (30–40%) on GLP-1–stimulated insulin secretion during hyperglycemic clamps in nondiabetic Caucasian individuals (TMEM114; CHST3 and CTRB1/2; n = 232; all P ≤ 8.8 × 10−7). rs7202877 near CTRB1/2, a known diabetes risk locus, also associated with an absolute 0.51 ± 0.16% (5.6 ± 1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G-allele carriers, but there was no effect on GLP-1 RA treatment in type 2 diabetic patients (n = 527). Furthermore, in pancreatic tissue, we show that rs7202877 acts as expression quantitative trait locus for CTRB1 and CTRB2, encoding chymotrypsinogen, and increases fecal chymotrypsin activity in healthy carriers. Chymotrypsin is one of the most abundant digestive enzymes in the gut where it cleaves food proteins into smaller peptide fragments. Our data identify chymotrypsin in the regulation of the incretin pathway, development of diabetes, and response to DPP-4 inhibitor treatment.
Numeracy and the Impact of High Food Prices in Industrializing Britain, 1780–1850
2013-05-15

Using census-based data on the ability to recall one's age, we show that low levels of nutrition impaired numeracy in industrializing England, 1780 to 1850: cognitive ability declined among those born during the Napoleonic wars. The effect was stronger in areas where grain was expensive and relief for the poor, an early form of welfare support was limited. Nutritional shortages had a nonlinear effect on numeracy, with, severe shortages impairing numeracy more. Nutrition during childhood also mattered for labor market outcomes: individuals born in periods or counties with low numeracy typically worked in occupations with lower earnings.
Discovery of high and very high-energy emission from the BL Lacertae object SHBL J001355.9–185406
2013-05-15

The detection of the high-frequency peaked BL Lac object (HBL) SHBL J001355.9–185406 (z = 0.095) at high (HE; 100 MeV &lt; E &lt; 300 GeV)and very high-energy (VHE; E &gt; 100 GeV) with the Fermi Large Area Telescope (LAT) and the High Energy Stereoscopic System (H.E.S.S.) isreported. Dedicated observations were performed with the H.E.S.S. telescopes, leading to a detection at the 5.5σ significance level. The measuredflux above 310 GeV is (8.3 ± 1.7stat ± 1.7sys) × 10−13 photons cm−2 s−1 (about 0.6% of that of the Crab Nebula), and the power-law spectrum hasa photon index of Γ = 3.4 ± 0.5stat ± 0.2sys. Using 3.5 years of publicly available Fermi-LAT data, a faint counterpart has been detected in theLAT data at the 5.5σ significance level, with an integrated flux above 300 MeV of (9.3 ± 3.4stat ± 0.8sys) × 10−10 photons cm−2 s−1 and a photonindex of Γ = 1.96 ± 0.20stat ± 0.08sys. X-ray observations with Swift-XRT allow the synchrotron peak energy in νFν representation to be locatedat ∼1.0 keV. The broadband spectral energy distribution is modelled with a one-zone synchrotron self-Compton (SSC) model and the optical databy a black-body emission describing
Remittances, Banking Status and the Usage of Insurance Schemes
2013-05-15

Empirical evidence that migrants send home more remittances after disasters raises the question of whether remittances are used to self-insure, substituting for both formal and informal insurance. We investigate this question using a unique data set on the usage patterns of financial services by households in South Africa. We show that the likelihood that a respondent has a formal funeral cover increases with income and banking status. However, it is lower for individuals receiving remittances, which supports the idea that remittances act as self-insurance. We also show that other risk management strategies influence the purchasing of formal funeral cover. Finally, we find that determinants of informal insurance differ from those of formal insurance.
Identification of M. tuberculosis Thioredoxin Reductase Inhibitors Based on High-Throughput Docking Using Constraints
2013-05-15

A virtual screening campaign is presented that led to small molecule inhibitors of thioredoxin reductase of Mycobacterium tuberculosis (MtTrxR) that target the protein-protein interaction site for the substrate thioredoxin (Trx). MtTrxR is a promising drug target because it dominates the Trx-dependent hydroperoxide metabolism and the reduction of ribonucleotides, thus facilitating survival and proliferation of M. tuberculosis. Moreover, MtTrxR sufficiently differs from its human homologs to suggest the possibility of selective inhibition if the MtTrxR-Trx interaction site is targeted. To this end, high-throughput docking of 6.5 million virtual compounds to the thioredoxin binding site of MtTrxR combined with constraints as filtering steps was applied. A total of 170 high-scoring compounds yielded 18 compounds that inhibited MtTrxR with IC50 values up to the low micromolar range, thus revealing that the protein-protein interaction site of MtTrxR is indeed druggable. Most importantly, selectivity toward MtTrxR in comparison to human TrxR (HsTrxR) is also demonstrated.
Evaluation of the Role of Heterogeneities on Transverse Mixing in Bench‐Scale Tank Experiments by Numerical Modeling
2013-05-15

Abstract In this work, numerical modeling is used to evaluate and interpret a series of detailed and well‐controlled two‐dimensional bench‐scale conservative tracer tank experiments performed to investigate transverse mixing in porous media. The porous medium used consists of a fine matrix and a more permeable lens vertically aligned with the tracer source and the flow direction. A sensitivity analysis shows that the tracer distribution after passing the lens is only slightly sensitive to variations in transverse dispersivity, but strongly sensitive to the contrast of hydraulic conductivities. A unique parameter set could be calibrated to closely fit the experimental observations. On the basis of calibrated and validated model, synthetic experiments with different contrasts in hydraulic conductivity and more complex setups were performed and the efficiency of mixing evaluated. Flux‐related dilution indices derived from these simulations show that the contrasts in hydraulic conductivity between matrix and high‐permeable lenses as well as the spatial configuration of tracer plumes and lenses dominate mixing, rather than the actual pore scale dispersivities. These results indicate that local material distributions, the magnitude of permeability contrasts, and their spatial and scale relation to solute plumes are more important for macro‐scale transverse dispersion than the micro‐scale dispersivities of individual materials. Local material characterization by thorough site investigation hence is of utmost importance for the evaluation of mixing‐influenced or ‐governed problems in groundwater, such as tracer test evaluation or an assessment of contaminant natural attenuation.
Melanoma inhibitory activity promotes melanoma development through activation of YBX1
2013-05-15

Summary Melanoma inhibitory activity ( MIA ), a small soluble secreted protein, is functionally important for progression of malignant melanoma. We recently revealed that p54 nrb acts as a mediator of MIA action. In this study, we characterize the transcriptional regulation of p54 nrb by MIA to explain MIA 's molecular action. We identified one highly conserved region in the p54 nrb promoter that is necessary and sufficient for MIA ‐dependent activation. Functional promoter analysis identified the transcription factor YBX 1 as the mediator of MIA activation of p54 nrb transcription. We screened the genome for further potential MIA ‐regulated genes carrying the element in their promoter regions. Integrating our sequence data with expression data from human melanomas identified a list of 23 potential MIA ‐ YBX 1 targets in melanomas. In summary, we present for the first time effects of MIA on transcriptional regulation. Uncovering new potential downstream effectors working via activation of YBX 1 supports the important role of MIA in melanoma.
Plea for a Modular Design of Business Ethics - Basics of the Ethical Substantiation of Economic Decisions
2013-05-15

We regard this article as a plea for the modular design of a practice-related discipline of business ethics, in which we analyse under what conditions economic decisions and actions in firms – regardless of their content – are to be understood as morally right. Following the clarification of certain fundamentals of the ethical substantiation of economic decisions, we describe a system of modules as the epistemological frame of reference that designs the formal analysis. We examine in detail the contribution of the descriptive module (as a conception of representation), the theoretical module (as a conception of explanation and prediction), the pragmatic module (as a conception of designing) and the normative module (as a conception of value-judgment) to the ethical substantiation of economic decisions and actions. As a conclusion of the formal analysis, we show that the ideal of the virtuous merchant as a basis of the ethics of conviction for the substantiation of economic decisions offers, at best, an imperfect solution. Following this, we give reasons why a practice-related discipline of business ethics as ethics of responsibility for the substantiation of economic decisions is particularly efficient. The main reason for this lies in the fact that this discipline integrates relevant insights (statements) from the descriptive, theoretical, pragmatic and normative modules into a self-contained system of statements. We ensure the systematic complementation of business administration by the discipline of business ethics by relating the statements of both systems to the same decisions concerning scarce goods that form the subject of business administration, and close factual and methodical relations between the two systems.
Apel o modułowe ujmowanie etyki biznesu. Podstawy etycznego uzasadniania decyzji ekonomicznych
2013-05-15

We regard this article as a plea for the modular design of a practice-related discipline of business ethics, in which we analyse under what conditions economic decisions and actions in firms – regardless of their content – are to be understood as morally right. Following the clarification of certain fundamentals of the ethical substantiation of economic decisions, we describe a system of modules as the epistemological frame of reference that designs the formal analysis. We examine in detail the contribution of the descriptive module (as a conception of representation), the theoretical module (as a conception of explanation and prediction), the pragmatic module (as a conception of designing) and the normative module (as a conception of value-judgment) to the ethical substantiation of economic decisions and actions. As a conclusion of the formal analysis, we show that the ideal of the virtuous merchant as a basis of the ethics of conviction for the substantiation of economic decisions offers, at best, an imperfect solution. Following this, we give reasons why a practice-related discipline of business ethics as ethics of responsibility for the substantiation of economic decisions is particularly efficient. The main reason for this lies in the fact that this discipline integrates relevant insights (statements) from the descriptive, theoretical, pragmatic and normative modules into a self-contained system of statements. We ensure the systematic complementation of business administration by the discipline of business ethics by relating the statements of both systems to the same decisions concerning scarce goods that form the subject of business administration, and close factual and methodical relations between the two systems.
High-Resolution Transcriptome Maps Reveal Strain-Specific Regulatory Features of Multiple Campylobacter jejuni Isolates
2013-05-16

Campylobacter jejuni is currently the leading cause of bacterial gastroenteritis in humans. Comparison of multiple Campylobacter strains revealed a high genetic and phenotypic diversity. However, little is known about differences in transcriptome organization, gene expression, and small RNA (sRNA) repertoires. Here we present the first comparative primary transcriptome analysis based on the differential RNA-seq (dRNA-seq) of four C. jejuni isolates. Our approach includes a novel, generic method for the automated annotation of transcriptional start sites (TSS), which allowed us to provide genome-wide promoter maps in the analyzed strains. These global TSS maps are refined through the integration of a SuperGenome approach that allows for a comparative TSS annotation by mapping RNA-seq data of multiple strains into a common coordinate system derived from a whole-genome alignment. Considering the steadily increasing amount of RNA-seq studies, our automated TSS annotation will not only facilitate transcriptome annotation for a wider range of pro- and eukaryotes but can also be adapted for the analysis among different growth or stress conditions. Our comparative dRNA-seq analysis revealed conservation of most TSS, but also single-nucleotide-polymorphisms (SNP) in promoter regions, which lead to strain-specific transcriptional output. Furthermore, we identified strain-specific sRNA repertoires that could contribute to differential gene regulation among strains. In addition, we identified a novel minimal CRISPR-system in Campylobacter of the type-II CRISPR subtype, which relies on the host factor RNase III and a trans-encoded sRNA for maturation of crRNAs. This minimal system of Campylobacter, which seems active in only some strains, employs a unique maturation pathway, since the crRNAs are transcribed from individual promoters in the upstream repeats and thereby minimize the requirements for the maturation machinery. Overall, our study provides new insights into strain-specific transcriptome organization and sRNAs, and reveals genes that could modulate phenotypic variation among strains despite high conservation at the DNA level.