julilili42/papers huggingface dataset:
The histone demethylase KDM2B activates FAK and PI3K that control tumor cell motility
2020-03-16

Recent studies revealed that the histone demethylase KDM2B regulates the epithelial markers E-Cadherin and ZO-1, the RhoA/B/C-small-GTPases and actin cytoskeleton organization, in DU-145 prostate- and HCT-116 colon-tumor cells. Here we addressed the role of KDM2B in the activation of Focal Adhesion Kinase (FAK)-signaling and its involvement in regulating tumor cell motility. We used RT-PCR for gene transcriptional analysis, Western blotting for the assessment of protein expression and activity and wound-healing assay for the study of cell migration. KDM2B overexpression or silencing controls the activity of FAK in DU-145 prostate- and HCT-116 colon-tumor cells without affecting gene transcription and protein expression of this kinase. Upon KDM2B overexpression in DU-145 cells, significantly enhanced migration was observed, which was abolished in cells pretreated by the specific phosphoinositide-3 kinase (PI3 K) inhibitor LY294002, implying involvement of FAK/PI3 K signaling in the migration process. In line with this, the p85-PI3 K-subunit was downregulated upon knockdown of KDM2B in DU-145 cells, while the opposite effect became evident in KDM2B-overexpressing cells. These results revealed a novel functional role of KDM2B in regulating the activation of the FAK/PI3 K signaling in prostate cancer cells that participates in the control of cell motility.
Occurrence of human astrovirus associated with gastroenteritis among Congolese children in Brazzaville, Republic of Congo
2020-03-16

In this study, infection with astrovirus was common in acute gastroenteritis cases among children younger than 5 years of age. Drinking treated water and living in non-crowded environments protected the children from infection.
Learning to represent signals spike by spike
2020-03-16

A key question in neuroscience is at which level functional meaning emerges from biophysical phenomena. In most vertebrate systems, precise functions are assigned at the level of neural populations, while single-neurons are deemed unreliable and redundant. Here we challenge this view and show that many single-neuron quantities, including voltages, firing thresholds, excitation, inhibition, and spikes, acquire precise functional meaning whenever a network learns to transmit information parsimoniously and precisely to the next layer. Based on the hypothesis that neural circuits generate precise population codes under severe constraints on metabolic costs, we derive synaptic plasticity rules that allow a network to represent its time-varying inputs with maximal accuracy. We provide exact solutions to the learnt optimal states, and we predict the properties of an entire network from its input distribution and the cost of activity. Single-neuron variability and tuning curves as typically observed in cortex emerge over the course of learning, but paradoxically coincide with a precise, non-redundant spike-based population code. Our work suggests that neural circuits operate far more accurately than previously thought, and that no spike is fired in vain.
Gene family information facilitates variant interpretation and identification of disease-associated genes in neurodevelopmental disorders
2020-03-17

Abstract Background Classifying pathogenicity of missense variants represents a major challenge in clinical practice during the diagnoses of rare and genetic heterogeneous neurodevelopmental disorders (NDDs). While orthologous gene conservation is commonly employed in variant annotation, approximately 80% of known disease-associated genes belong to gene families. The use of gene family information for disease gene discovery and variant interpretation has not yet been investigated on a genome-wide scale. We empirically evaluate whether paralog-conserved or non-conserved sites in human gene families are important in NDDs. Methods Gene family information was collected from Ensembl. Paralog-conserved sites were defined based on paralog sequence alignments; 10,068 NDD patients and 2078 controls were statistically evaluated for de novo variant burden in gene families. Results We demonstrate that disease-associated missense variants are enriched at paralog-conserved sites across all disease groups and inheritance models tested. We developed a gene family de novo enrichment framework that identified 43 exome-wide enriched gene families including 98 de novo variant carrying genes in NDD patients of which 28 represent novel candidate genes for NDD which are brain expressed and under evolutionary constraint. Conclusion This study represents the first method to incorporate gene family information into a statistical framework to interpret variant data for NDDs and to discover new NDD-associated genes.
Functional Characterisation of ClpP Mutations Conferring Resistance to Acyldepsipeptide Antibiotics in Firmicutes
2020-03-17

Abstract Acyldepsipeptide (ADEP) is an exploratory antibiotic with a novel mechanism of action. ClpP, the proteolytic core of the caseinolytic protease, is deregulated towards unrestrained proteolysis. Here, we report on the mechanism of ADEP resistance in Firmicutes. This bacterial phylum contains important pathogens that are relevant for potential ADEP therapy. For Staphylococcus aureus , Bacillus subtilis , enterococci and streptococci, spontaneous ADEP‐resistant mutants were selected in vitro at a rate of 10 −6 . All isolates carried mutations in clpP . All mutated S. aureus ClpP proteins characterised in this study were functionally impaired; this increased our understanding of the mode of operation of ClpP. For molecular insights, crystal structures of S. aureus ClpP bound to ADEP4 were determined. Well‐resolved N‐terminal domains in the apo structure allow the pore‐gating mechanism to be followed. The compilation of mutations presented here indicates residues relevant for ClpP function and suggests that ADEP resistance will occur at a lower rate during the infection process.
Frequency Induced Stiction for MEMS Accelerometers
2020-03-17

With the rising market for inertial MEMS, reliable stiction detection methods at wafer level become increasingly important. This paper describes a new mechanism for producing enhanced stiction results at wafer level testing due to electric stimulation of the electrode fingers of the MEMS devices and provides a new wafer level measurement method to detect critical frequency ranges. Dependent on the architecture of the sensor core the modulation frequency and amplitude have a distinct impact on the stiction results. The effect is studied systematically for two different test device types by variation of the modulation carrier amplitude and frequency. The results are compared to critical modes gained from transient finite element simulations of the sensor cores. Additionally, a mechanical modal analysis has been performed for result verification. The obtained results show a distinct correlation between the resonance frequencies of the electrode fingers and the likelihood of stiction events. [2019-0189].
Remnants of the disappearing critical point in chain-forming patchy fluids
2020-03-17

For a standard model of patchy colloidal fluids with patch number M = 2, where chain formation (polymerization) occurs, we show that Wertheim theory predicts critical behavior at vanishing density and temperature. The analysis is based on determining lines in the phase diagram of maximal correlation length and compressibility. Simulation studies identify the latter line and confirm our prediction of Fisher–Widom crossover, i.e., the asymptotic decay of the pair correlation function changes from monotonic to damped oscillatory as the density is increased. For M &amp;gt; 2, it is known that phase separation occurs with a true critical point. Our results support the notion that a “disappearing” critical point occurs in the limit M = 2 and we uncover its remnants.
Effects of Expectancy on Cognitive Performance, Mood, and Psychophysiology in Healthy Adolescents and Their Parents in an Experimental Study
2020-03-17

Objective Placebo effects on cognitive performance and mood and their underlying mechanisms have rarely been investigated in adolescents. Therefore, the following hypotheses were investigated with an experimental paradigm: (1) placebo effects could be larger in adolescents than in adults, (2) parents’ expectations influence their adolescents’ expectations and placebo effects, and (3) a decrease in stress levels could be an underlying mechanism of placebo effects. Methods Twenty-six healthy adolescents (13.8 ± 1.6 years, 14 girls) each with a parent (45.5 ± 4.2 years, 17 mothers) took part in an experimental within-subjects study. On two occasions, a transdermal patch was applied to their hips and they received an envelope containing either the information that it is a Ginkgo patch to improve cognitive performance and mood, or it is an inactive placebo patch, in counterbalanced order. Cognitive performance and mood were assessed with a parametric Go/No-Go task (PGNG), a modification of California Verbal Learning Test, and Profile of Mood Scales (POMS). Subjects rated their expectations about Ginkgo’s effects before patch application as well as their subjective assessment of its effects after the tests. An electrocardiogram and skin conductance levels (SCLs) were recorded and root mean square of successive differences (RMSSD), high-frequency power (HF), and the area under the curve of the SCL (AUC) were analyzed as psychophysiological stress markers. Results Expectations did not differ between adolescents and parents and were correlated concerning reaction times only. Overall, expectations did not influence placebo effects. There was only one significant placebo effect on the percentage of correct inhibited trials in one level of the PGNG in adolescents, but not in parents. RMSSD and HF significantly increased, and AUC decreased from pre- to post-patch application in adolescents, but not in parents. Conclusion With this experimental paradigm, we could not induce relevant placebo effects in adolescents and parents. This could be due to aspects of the study design such as application form and substance, and that healthy subjects were employed. Nevertheless, we could show that adolescents are more sensitive to psychophysiological reactions related with interventions which could be part of the underlying mechanisms of placebo effects in adolescents.
Impact of reactive surfaces on the abiotic reaction between nitrite and ferrous iron and associated nitrogen and oxygen isotope dynamics
2020-03-17

Abstract. Anaerobic nitrate-dependent Fe(II) oxidation (NDFeO) is widespread in various aquatic environments, and plays a major role in iron and nitrogen redox dynamics. However, evidence for truly enzymatic, autotrophic NDFeO remains limited, with alternative explanations involving coupling of heterotrophic denitrification with abiotic oxidation of structurally-bound or aqueous Fe(II) by reactive intermediate N species (chemodenitrification). The extent to which chemodenitrification is caused, or enhanced, by ex vivo surface catalytic effects has, so far, not been directly quantified. To determine whether the presence of either a Fe(II)-bearing mineral or dead biomass (DB) catalyses chemodenitrification, two different sets of anoxic batch experiment were conducted: 2 mM Fe(II) was added to a low-phosphate medium, resulting in the precipitation of vivianite (Fe3(PO4)2), to which later 2 mM nitrite (NO2−) were added, with or without an autoclaved cell suspension (~ 1.96 × 108 cells ml−1) of Shewanella oneidensis MR-1. Concentrations of nitrite, nitrous oxide (N2O) and iron (Fe2+, Fetot) were monitored over time to assess the impact of Fe(II) minerals and/or DB as catalysts of chemodenitrification in the two setups. In addition, the natural-abundance isotope ratios of NO2− and N2O (δ15N and δ18O) were analysed to constrain associated isotope effects. Up to 90 % of the Fe(II) was oxidized in the presence of DB, while only ~ 65 % were oxidized under mineral-only conditions, suggesting an overall lower reactivity of the mineral-only setup. Similarly, the average NO2− reduction rate (0.004 ± 0.003 mmol L−1 day−1) in the mineral-only experiments was much lower compared to experiments with mineral plus dead biomass (0.053 ± 0.013 mmol L−1 day−1), as was N2O production (204.02 ± 60.29 nmol/L*day). The N2O yield per mole NO2− reduced was higher in the mineral-only setups (4 %) compared to the experiments with dead biomass (1 %), suggesting the catalysis-dependent differential formation of NO. N-NO2− isotope ratio measurements indicated a clear difference between both experimental conditions: in contrast to the marked 15N isotope enrichment during active NO2− reduction (−15εNO2 = +10.3 ‰) observed in the presence of DB, NO2− loss in the mineral-only experiments exhibited only a small N isotope effect (
Data and Code for Publication "Testing the Utility of Dental Morphological Trait Combinations for Inferring Human Neutral Genetic Variation"
2020-03-17

Data and code for publication: H. Rathmann, H. Reyes-Centeno, Testing the utility of dental morphological trait combinations for inferring human neutral genetic variation. <em>Proc. Natl. Acad. Sci. U.S.A.</em> 117, 10769-10777 (2020). DOI: 10.1073/pnas.1914330117 The repository contains: “R-code.txt”: R code for an exhaustive search algorithm testing the utility of dental morphological traits and trait combinations for inferring human neutral genetic variation. “dental trait frequencies.csv”: Data set with 27 dental morphological trait frequencies for 20 modern human populations worldwide used for analysis. Data from G. R. Scott, C. G. Turner, G. C. Townsend, M. Martinón-Torres, <em>The Anthropology of Modern Human Teeth</em> (Cambridge University Press, 2018). DOI: 10.1017/ 9781316795859 “microsatellite loci mean sizes.csv”: Data set with 645 microsatellite mean allele sizes for 20 modern human populations worldwide used for analysis. Data from T. J. Pemberton, M. DeGiorgio, N. A. Rosenberg, Population structure in a comprehensive genomic data set on human microsatellite variation. <em>G3: Genes Genom. Genet.</em> 3, 891–907 (2013). DOI: 10.1534/g3.113.005728 “utility estimates for 134217727 trait combinations.txt”: A large table with utility estimates for 27 dental morphological traits and all 134,217,700 possible trait combinations. Abbreviations for the 20 population names (rows) in “dental trait frequencies.csv” and “microsatellite loci mean sizes.csv” as follows: AUS = Australia CAS = Central Asia EAF = Eastern Africa EAS = East Asia EEU = Eastern Europe IND = India MAM = Mesoamerica MEL = Melanesia MIC = Micronesia NAF = North Africa NAM = North America NESI = Northeast Siberia NGU = New Guinea NWAM = Na-Dene POL = Polynesia SAM = South America SAN = San SEAS = Southeast Asia WEU = Western Europe WSAF = Sub-Saharan Africa Abbreviations for the 27 dental morphological trait names (columns) in “dental trait frequencies.csv” as follows: T1 = Winging (UI1) T2 = Shoveling (UI1) T3 = Double-Shoveling (UI1) T4 = Interruption Grooves (UI2) T5 = Tuberculum Dentale (UI2) T6 = Mesial Ridge (UC) T7 = Distal Accessory Ridge (UC) T8 = Hypocone (UM2) T9 = Carabelli Trait (UM1) T10 = Cusp 5 (UM1) T11 = Enamel Extensions (UM1) T12 = Peg-Reduced-Missing (UM3) T13 = Lingual Cusp Number (LP2) T14 = Groove Pattern (LM2) T15 = Cusp 6 (LM1) T16 = Cusp Number (LM2) T17 = Deflecting Wrinkle (LM1) T18 = Distal Trigonid Crest (LM1) T19 = Protostylid (LM1) T20 = Cusp 7 (LM1) T21 = Odontomes (UP-LP) T22 = Root Number (UP1) T23 = Root Number (UM2) T24 = Root Number (LC) T25 = Tomes’ Root (LP1) T26 = Root Number (LM1) T27 = Root Number (LM2) Abbreviations for the 645 microsatellite allele locus names (columns) in “microsatellite loci mean sizes.csv” as in T. J. Pemberton, M. DeGiorgio, N. A. Rosenberg, Population structure in a comprehensive genomic data set on human microsatellite variation. <em>G3: Genes Genom. Genet.</em> 3, 891–907 (2013). DOI: 10.1534/g3.113.005728
The shaky ground truth of real-time phase estimation
2020-03-18

Instantaneous phase of brain oscillations in electroencephalography (EEG) is a measure of brain state that is relevant to neuronal processing and modulates evoked responses. However, determining phase at the time of a stimulus with standard signal processing methods is not possible due to the stimulus artifact masking the future part of the signal. Here, we quantify the degree to which signal-to-noise ratio and instantaneous amplitude of the signal affect the variance of phase estimation error and the precision with which "ground truth" phase is even defined, using both the variance of equivalent estimators and realistic simulated EEG data with known synthetic phase. Necessary experimental conditions are specified in which pre-stimulus phase estimation is meaningfully possible based on instantaneous amplitude and signal-to-noise ratio of the oscillation of interest. An open source toolbox is made available for causal (using pre-stimulus signal only) phase estimation along with a EEG dataset consisting of recordings from 140 participants and a best practices workflow for algorithm optimization and benchmarking. As an illustration, post-hoc sorting of open-loop transcranial magnetic stimulation (TMS) trials according to pre-stimulus sensorimotor μ-rhythm phase is performed to demonstrate modulation of corticospinal excitability, as indexed by the amplitude of motor evoked potentials.
Digital Learning Environments in Higher Education: A Literature Review of the Role of Individual vs. Social Settings for Measuring Learning Outcomes
2020-03-18

Research on digital learning environments has traditionally applied either an individual perspective or a social perspective to learning. Based on a literature review, we examined to what extent individual or social perspectives determined the learning outcome variables that researchers have used as measurements in existing studies. We analyzed prototypical approaches to operationalize learning settings (individual vs. social) published in peer-reviewed journals and identified their relation to several measures of learning outcomes. We rated n = 356 articles and included n = 246 articles in the final analysis. A total of 159 studies (64.6%) used an individual learning setting, while 87 studies (35.4%) used a social learning setting. As learning outcome measures, we observed self-reports, observable behavior, learning skills, elaboration, personal initiatives, digital activity, and social interactions. The two types of learning settings differed regarding the measurement of elaboration and social interactions. We discuss of the implications of our findings for future research and conclude that researchers should investigate further measures of learning outcomes in digital learning settings.
Systematic Review and Meta-Analysis Comparing Percutaneous Nephrolithotomy, Retrograde Intrarenal Surgery and Shock Wave Lithotripsy for Lower Pole Renal Stones Less Than 2 cm in Maximum Diameter
2020-03-18

The pooled analysis of the eligible studies showed that the management of lower pole stones should probably be percutaneous nephrolithotripsy or retrograde intrarenal surgery to achieve stone-free status over a short period and minimal number of sessions. For stones smaller than 10 mm, retrograde intrarenal surgery is more efficient in comparison to shock wave lithotripsy. The decision between the 2 approaches (percutaneous nephrolithotripsy or retrograde intrarenal surgery) should be individual, based on the anatomical parameters, the comorbidity and the preferences of each patient.
Dendritic cell development in infection
2020-03-18

The immune system protects from infections primarily by detecting and eliminating invading pathogens. This is predominantly mediated by innate immune cells like neutrophils, monocytes and dendritic cells (DCs) expressing specific receptors recognizing pathogen-associated molecular patterns. DC activation by pathogens leads to the initiation of antigen-specific adaptive immune responses, thereby bridging the innate and adaptive immune systems. However, various pathogens have evolved immune evasion strategies to ensure their survival. In this review, we highlight recent findings on how various microorganisms or their structural features affect or modulate DC development and whether this has any consequences for a protective immune response.
Does Device Selection Impact Recanalization Rate and Neurological Outcome?
2020-03-18

Background and Purpose— The recent Save ChildS study provides multicenter evidence for the use of mechanical thrombectomy in children with large vessel occlusion arterial ischemic stroke. However, device selection for thrombectomy may influence rates of recanalization, complications, and neurological outcomes, especially in pediatric patients of different ages. We, therefore, performed additional analyses of the Save ChildS data to investigate a possible association of different thrombectomy techniques and devices with angiographic and clinical outcome parameters. Methods— The Save ChildS cohort study (January 2000–December 2018) analyzed data from 27 European and United States stroke centers and included all pediatric patients (&lt;18 years), diagnosed with arterial ischemic stroke who underwent endovascular recanalization. Patients were grouped into first-line contact aspiration (A Direct Aspiration First Pass Technique [ADAPT]) and non-ADAPT groups as well as different stent retriever size groups. Associations with baseline characteristics, recanalization rates (modified Treatment in Cerebral Infarction), complication rates, and neurological outcome parameters (Pediatric National Institutes of Health Stroke Scale after 24 hours and 7 days; modified Rankin Scale and Pediatric Stroke Outcome Measure at discharge, after 6 and 24 months) were investigated. Results— Seventy-three patients with a median age of 11.3 years were included. Currently available stent retrievers were used in 59 patients (80.8%), of which 4×20 mm (width×length) was the most frequently chosen size (36 patients =61%). A first-line ADAPT approach was used in 7 patients (9.6%), and 7 patients (9.6%) were treated with first-generation thrombectomy devices. In this study, a first-line ADAPT approach was neither associated with the rate of successful recanalization (ADAPT 85.7% versus 87.5% No ADAPT) nor with the complication rate or the neurological outcome. Moreover, there were no associations of stent retriever sizes with rates of recanalization, complication rates, or outcome parameters. Conclusions— Our study suggests that neurological outcomes are generally good regardless of any specific device selection and suggests that it is important to offer thrombectomy in eligible children regardless of technique or device selection. Registration— URL: https://www.drks.de/ ; Unique identifier: DRKS00016528.