julilili42/papers huggingface dataset:
Inhibition of autotransporter biogenesis by small molecules
2019-04-15

Summary Disarming pathogens by targeting virulence factors is a promising alternative to classic antibiotics. Many virulence factors in Gram‐negative bacteria are secreted via the autotransporter (AT) pathway, also known as Type 5 secretion. These factors are secreted with the assistance of two membrane‐based protein complexes: Sec and Bam. To identify inhibitors of the AT pathway, we used transcriptomics analysis to develop a fluorescence‐based high‐throughput assay that reports on the stress induced by the model AT hemoglobin protease (Hbp) when its secretion across the outer membrane is inhibited. Screening a library of 1600 fragments yielded the compound VUF15259 that provokes cell envelope stress and secretion inhibition of the ATs Hbp and Antigen‐43. VUF15259 also impairs β‐barrel folding activity of various outer membrane proteins. Furthermore, we found that mutants that are compromised in outer membrane protein biogenesis are more susceptible to VUF15259. Finally, VUF15259 induces the release of vesicles that appear to assemble in short chains. Taken together, VUF15259 is the first reported compound that inhibits AT secretion and our data are mostly consistent with VUF15259 interfering with the Bam‐complex as potential mode of action. The validation of the presented assay incites its use to screen larger compound libraries with drug‐like compounds.
Contrast-enhanced imaging in hepatic epithelioid hemangioendothelioma: retrospective study of 10 patients
2019-04-15

Abstract Purpose The purpose of this study was to analyze imaging findings in hepatic epithelioid hemangioendothelioma (HEHE) with a particular focus on contrast-enhanced ultrasound (CEUS). Materials and Methods This retrospective multicenter study included 10 patients with histologically proven HEHE from 5 European centers. All existing ultrasound images/videos were independently analyzed by 2 experienced examiners (DEGUM level III, internal medicine) using a standardized evaluation form. Patterns of contrast enhancement were correlated with computed tomography (CT), magnetic resonance imaging (MRI), and pathological findings. Results B-mode ultrasound, CEUS, CT, and MRI were performed in 90 %, 70 %, 100 %, and 90 % of patients, respectively. Multifocal HEHE could be observed in 80 % with affection of both liver lobes in 70 %. Analysis of CEUS revealed 3 characteristic patterns that correlated well with contrast patterns on CT and MRI: (a) peripheral nodular enhancement with centripetal fill-in and wash-out in the portal venous and late venous phase (PVLP), (b) rim-like arterial enhancement with wash-out in the PVLP, and (c) inversed target sign with/without wash-out in the PVLP. Wash-out in the PVLP as a sign suspicious of malignancy was observed in 6/7 patients (85.7 %). Conclusions Knowledge of the different characteristic CEUS patterns is of importance to avoid misdiagnosis due to resemblance of patterns A and B to the much more common focal liver lesions hemangioma and intrahepatic cholangiocarcinoma. Of importance, sonographers should be aware that wash-out in the PVLP might be absent in some patients.
The effects of empathy and circadian preference on cyberbullying of adolescents in Turkey
2019-04-15

In this study, the relationships among empathic tendency and circadian preference on cyberbullying and cybervictimization of adolescents in Turkey were examined. The study group included 1540 adolescents (861 female, 679 male), and anonymous and voluntary participation was sought in forming the study group. Data were collected from each participant by assessing a demographic questionnaire, the Composite Scale of Morningness for circadian preference, Empathy, Cyberbully and Victim Scales. The most important result was that gender, empathy, and Composite Scale of Morningness scores were the predictors for cyberbullying and cybervictimization, and as a consequence, male and evening-oriented adolescents scored higher on cyberbullying and cybervictimization. Additionally, it was observed that cyberbullying and empathy were inversely correlated in adolescents.
Interferon Alpha for Refractory Pseudophakic Cystoid Macular Edema (Irvine-Gass Syndrome)
2019-04-15

<i>Purpose</i>: To assess the efficacy and safety of systemic interferon alpha-2a (IFN) for refractory pseudophakic cystoid macular edema (PCME).<i>Methods</i>: Retrospective observational study. The primary outcome was the decrease of central retinal thickness (CRT). Secondary endpoints were the improvement of best-corrected visual acuity (BCVA) and the assessment of IFN-related side effects.<i>Results</i>: Twenty-four eyes of 20 patients were included. The median CRT was 513 μm (range 220-980 μm) at baseline and decreased to 190 μm (range 140-520 μm) at the last follow-up visit (p < 0.001). Reduction of CRT greater than 100 μm was observed in 22 eyes (92%). The median BCVA (logMAR) increased statistically significant from 0.5 (range 0.2-1.5) at baseline to 0.3 (0-0.8) at the last follow-up (p < 0.001). The BCVA improved in 18 eyes (75%) and remained stable in five eyes (21%). No severe treatment-related side effects occurred.<i>Conclusion</i>: IFN is a very effective agent for treatment of refractory PCME.
Glucose Responsiveness of β-Cells Depends on Fatty Acids
2019-04-15

Abstract Glucose-stimulated insulin secretion (GSIS) is the gold standard for β-cell function. Both experimental and clinical diabetology, i. e., preceding transplantation of isolated human islets, depend on functional testing. However, multiple factors influence GSIS rendering the comparison of different in vitro tests of glucose responsiveness difficult. This study examined the influence of bovine serum albumin (BSA)-coupled fatty acids on GSIS. Isolated islet preparations of human donors and of 12-months old mice displayed impaired GSIS in the presence of 0.5% FFA-free BSA compared to 0.5% BSA (fraction V, not deprived from fatty acids). In aged INS-1E cells, i. e. at a high passage number, GSIS became highly sensitive to FFA-free BSA. Readdition of 30 μM palmitate or 30 μM oleate to FFA-free BSA did not rescue GSIS, while the addition of 100 μM palmitate and the raise of extracellular Ca2+from 1.3 to 2.6 mM improved glucose responsiveness. A high concentration of palmitate (600 μM), which fully activates FFA1, largely restored insulin secretion. The FFA1-agonist TUG-469 also increased insulin secretion but to a lesser extent than palmitate. Glucose- and TUG-induced Ca2+oscillations were impaired in glucose-unresponsive, i. e., aged INS-1E cells. These results suggest that fatty acid deprivation (FFA-free BSA) impairs GSIS mainly through an effect on Ca2+sensitivity.
What Education Means to Us? The Perspective of Underdeveloped Region Community in the Context of Formal Education in Jeneponto Regency, Indonesia
2019-04-15

In Indonesia, education issues continue dynamically increasing following the movement of social, economic, political and cultural changes which forms a new identity that leads the rural community needs educational development. The problem of education in this research focuses on disadvantaged areas in Indonesia, especially in Jeneponto Regency, one of the underdeveloped regencies in Indonesia, which categorized as the lowest human achievement index in South Sulawesi. It also becomes the only one of disadvantaged regencies from 24 regencies in this province in 2017, this based on the data of the central statistical agency, Indonesia which focuses on measuring success in building the quality of human life. Based on this case, through ethnographic approach, I conducted a research on one of the villages in the Jeneponto Regency, namely Pappalluang Village, which is located 70 km from downtown Jeneponto in the mountainous border of three regencies namely Jeneponto, Gowa, and Takalar regency and it is famous as the furthest and most underdeveloped area in Jeneponto. Based on these accounts, this paper investigates by focusing on exploring dipper from the basis of understanding the education paradigm by looking at the perception of people in a rural community in Jeneponto on how they view education and how important is to the community. This study found that the main point on how they interpreted education as an essential thing is that education is for their children's best future life in getting decent jobs because they argued that even as an agricultural region with the majority as farmers, they consider that the work of farmers is menial and puts them in a low social status. I found the ambiguity of the meaning of education by the people of Pappalluang. On the one hand, they consider education to be important. On the other hand, the efforts they have made to support their children's education have not been fully implemented. They only allow being involved in formal education and providing school equipment such as uniforms and stationery, but not by supporting other important things, such as the development of children's potential which these are only given by the teachers in schools due to the fact that parents mostly spend time in rice fields or gardens starting in the morning until the sun sets. There is no deep interaction between parents and children where this is important in developing children's potential.
Pyridinylimidazoles as GSK3β inhibitors: the impact of tautomerism on compound activity via water networks
2019-04-15

Data related to publication: Heider et al.: Pyridinylimidazoles as GSK3β inhibitors: the impact of tautomerism on compound activity via water networks. The files include: 1) Output conformations of the QM Tautomer &amp; Conformation Predictor of Maestro (Schrödinger, LLC, New York, NY, 2018) of the compounds <strong>1</strong>, <strong>3a</strong>, <strong>3b</strong>, <strong>3c</strong>, <strong>3d</strong>, <strong>3e</strong>, <strong>3f</strong>, <strong>3g</strong>, <strong>3h</strong>, <strong>3j</strong>, <strong>3k</strong>, <strong>3l</strong>, <strong>3m</strong>, <strong>6f</strong> and <strong>6g</strong> [.mae and .sdf files]. 2) Movies of the MD simulations of compounds <strong>3a</strong>, <strong>3j</strong>, <strong>4a</strong>, <strong>4b</strong>, <strong>6b</strong>, <strong>6g</strong> (6GN1) and movies (*_2) of <strong>3a</strong>, <strong>3j</strong>, <strong>6b</strong>, <strong>6g</strong> (4PTC) [.mpg files] . 3) Raw Desmond trajectory files of the MD simulations of the compounds <strong>3a</strong>, <strong>3j</strong>, <strong>4a</strong>, <strong>4b</strong>, <strong>6b</strong>, <strong>6g</strong> [out.cms and the full trj files]. <br>
Pyridinylimidazoles as GSK3β inhibitors: the impact of tautomerism on compound activity via water networks
2019-04-15

Data related to publication: Heider et al.: Pyridinylimidazoles as GSK3β inhibitors: the impact of tautomerism on compound activity via water networks. The files include: 1) Output conformations of the QM Tautomer &amp; Conformation Predictor of Maestro (Schrödinger, LLC, New York, NY, 2018) of the compounds 2, 15, 16, 17, 18, 19, 20, 21, 24, 41, 42, 43, 44, 51 and 52 (.mae and .sdf files). 2) Movies of the MD simulations of compounds 15, 36, 37, 38, 41, 52 (.mpg files). 3) Raw trajectory files of the Desmond MD simulations of the compounds 15, 36, 37, 38, 41, 52 (out.cms and the full trj files) <br>
Phylogenetic Analyses and GAGA-Motif Binding Studies of BBR/BPC Proteins Lend to Clues in GAGA-Motif Recognition and a Regulatory Role in Brassinosteroid Signaling
2019-04-16

Plant GAGA-motif binding factors are encoded by the BARLEY B RECOMBINANT / BASIC PENTACYSTEINE (BBR/BPC) family, which fulfill indispensable functions in growth and development. BBR/BPC proteins control flower development, size of the stem cell niche and seed development through transcriptional regulation of homeotic transcription factor genes. They are responsible for the context dependent recruitment of Polycomb repressive complexes (PRC) or other repressive proteins to GAGA-motifs, which are contained in Polycomb repressive DNA-elements (PREs). Hallmark of the protein family is the highly conserved BPC domain, which is required for DNA binding. Here we study the evolution and diversification of the BBR/BPC family and its DNA-binding domain. Our analyses supports a further division of the family into four main groups (I-IV) and several subgroups, to resolve a strict monophyletic descent of the BPC domain. We prove a polyphyletic origin for group III proteins, which evolved from group I and II members through extensive loss of domains in the <i>N</i>-terminus. Conserved motif searches lend to the identification of a WAR/KHGTN consensus and a TIR/K motif at the very <i>C</i>-terminus of the BPC-domain. We could show by DPI-ELISA that this signature is required for DNA-binding in AtBPC1. Additional binding studies with AtBPC1, AtBPC6 and mutated oligonucleotides consolidated the binding to GAGA tetramers. To validate these findings, we used previously published ChIP-seq data from GFP-BPC6. We uncovered that many genes of the brassinosteroid signaling pathway are targeted by AtBPC6. Consistently, <i>bpc6, bpc4 bpc6</i>, and <i>lhp1 bpc4 bpc4</i> mutants display brassinosteroid-dependent root growth phenotypes. Both, a function in brassinosteroid signaling and our phylogenetic data supports a link between BBR/BPC diversification in the land plant lineage and the complexity of flower and seed plant evolution.
nf-core: Community curated bioinformatics pipelines
2019-04-16

Abstract The standardization, portability, and reproducibility of analysis pipelines is a renowned problem within the bioinformatics community. Most pipelines are designed for execution on-premise, and the associated software dependencies are tightly coupled with the local compute environment. This leads to poor pipeline portability and reproducibility of the ensuing results - both of which are fundamental requirements for the validation of scientific findings. Here, we introduce nf-core : a framework that provides a community-driven, peer-reviewed platform for the development of best practice analysis pipelines written in Nextflow. Key obstacles in pipeline development such as portability, reproducibility, scalability and unified parallelism are inherently addressed by all nf-core pipelines. We are also continually developing a suite of tools that assist in the creation and development of both new and existing pipelines. Our primary goal is to provide a platform for high-quality, reproducible bioinformatics pipelines that can be utilized across various institutions and research facilities.
Altered proteasome function in right ventricular hypertrophy
2019-04-16

Our data demonstrate that alterations in expression and activity of proteasomal subunits play a critical role in the development of RVH. Moreover, this study provides an improved understanding on the selective activation of the 26S proteasome in RVH that might be driven by the rate-limiting subunit Rpn6. In RVH, Rpn6 therefore represents a more specific target to interfere with proteasome function than the commonly used catalytic proteasome inhibitors.
Motor Abilities in Adolescents Born Preterm Are Associated With Microstructure of the Corpus Callosum
2019-04-16

<b>Background:</b> Preterm birth is associated with increased risk of neuromotor impairment. Rates of major neuromotor impairment (cerebral palsy) have decreased; however, in a large proportion of those who do not develop cerebral palsy impaired neuromotor function is observed and this often has implications for everyday life. The aim of this study was to investigate motor performance in preterm born adolescents without cerebral palsy, and to examine associations with alterations of motor system pathway structure. <b>Design/Methods:</b> Thirty-two adolescents (12 males) without cerebral palsy, born before 33 weeks of gestation (mean 27.4 weeks, SD 2.4; birth weight mean 1,084.5 g; SD 387.2), treated at a single tertiary unit, were assessed (median age 16 years; min 14, max 18). Timed performance and quality of movements were assessed with the Zürich Neuromotor Assessment. Neuroimaging included Diffusion Magnetic Resonance Imaging for tractography of the major motor tracts and measurement of fractional anisotropy as a measure of microstructure of the tracts along the major motor pathways. Separate analyses were conducted for areas with predominantly single and predominantly crossing fiber regions. <b>Results:</b> Motor performance in both tasks assessing timed performance and quality of movements, was poorer than expected in the preterm group in relation to norm population. The strongest significant correlations were seen between performance in tasks assessing movement quality and fractional anisotropy in corpus callosum fibers connecting primary motor, primary somatosensory and premotor areas. In addition, timed motor performance was significantly related to fractional anisotropy in the cortico-spinal and thalamo-cortical to premotor area fibers, and the corpus callosum. <b>Conclusions:</b> Impairments in motor abilities are present in preterm born adolescents without major neuromotor impairment and in the absence of focal brain injury. Altered microstructure of the corpus callosum microstructure appears a crucial factor, in particular for movement quality.
Probing and predicting ganglion cell responses to smooth electrical stimulation in healthy and blind mouse retina
2019-04-16

ABSTRACT Retinal implants are used to replace lost photoreceptors in blind patients suffering from retinopathies such as retinitis pigmentosa. Patients wearing implants regain some rudimentary visual function. However, it is severely limited compared to normal vision because non-physiological stimulation strategies fail to selectively activate different retinal pathways at sufficient spatial and temporal resolution. The development of improved stimulation strategies is rendered difficult by the large space of potential stimuli. Here we systematically explore a subspace of potential stimuli by electrically stimulating healthy and blind mouse retina in epiretinal configuration using smooth Gaussian white noise delivered by a high-density CMOS-based microelectrode array. We identify linear filters of retinal ganglion cells (RGCs) by fitting a linear-nonlinear-Poisson (LNP) model. Our stimulus evokes fast, reliable, and spatially confined spiking responses in RGC which are accurately predicted by the LNP model. Furthermore, we find diverse shapes of linear filters in the linear stage of the model, suggesting diverse preferred electrical stimuli of RGCs. Our smooth electrical stimulus could provide a starting point of a model-guided search for improved stimuli for retinal prosthetics.
Defecatory urge increases cognitive control and intertemporal patience in healthy volunteers
2019-04-16

Abstract Background Past research has demonstrated that moderate urge to urinate improves inhibitory control, specifically among participants with higher behavioral inhibition sensitivity (BIS). The effect was absent when the urge exceeded intolerable level. The present research examines whether rectal distension‐induced urge to defecate has similar effects. Methods The moderate and high defecatory urge were induced by rectal distension in healthy volunteers (n = 35), while they completed Stroop task and monetary delay discounting task. The difference of average reaction time between incongruent and congruent trials in the Stroop task (Stroop interference) and the preference for larger‐later rewards in the delay discounting task were the primary outcomes. Key Results Participants with high BIS (n = 17) showed greater ability to inhibit their automatic response tendencies, as indexed by their Stroop interference, under moderate urge relative to no urge (128 ± 41 ms vs 202 ± 37 ms, t 64 = 2.07; P = 0.021, Cohen's d : 0.44), but not relative to high urge (154 ± 45 ms, t 64 = 1.20; P = 0.12, Cohen's d : 0.30). High BIS participants also showed a higher preference for larger‐later reward in the delay discounting task under high (odds ratio = 1.51 [1.02‐2.25], P = 0.039) relative to no urge, but not relative to moderate urge (odds ratio = 1.02 [0.73‐1.42], P = 0.91). In contrast, rectal distension did not influence performance on either of the tasks in participants with low BIS (n = 18). Conclusions and inference These findings may be interpreted as a “spill‐over” effect of inhibition of the urge to defecate to volitional cognitive control among healthy participants with high BIS.
antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline
2019-04-17

Abstract Secondary metabolites produced by bacteria and fungi are an important source of antimicrobials and other bioactive compounds. In recent years, genome mining has seen broad applications in identifying and characterizing new compounds as well as in metabolic engineering. Since 2011, the ‘antibiotics and secondary metabolite analysis shell—antiSMASH’ (https://antismash.secondarymetabolites.org) has assisted researchers in this, both as a web server and a standalone tool. It has established itself as the most widely used tool for identifying and analysing biosynthetic gene clusters (BGCs) in bacterial and fungal genome sequences. Here, we present an entirely redesigned and extended version 5 of antiSMASH. antiSMASH 5 adds detection rules for clusters encoding the biosynthesis of acyl-amino acids, β-lactones, fungal RiPPs, RaS-RiPPs, polybrominated diphenyl ethers, C-nucleosides, PPY-like ketones and lipolanthines. For type II polyketide synthase-encoding gene clusters, antiSMASH 5 now offers more detailed predictions. The HTML output visualization has been redesigned to improve the navigation and visual representation of annotations. We have again improved the runtime of analysis steps, making it possible to deliver comprehensive annotations for bacterial genomes within a few minutes. A new output file in the standard JavaScript object notation (JSON) format is aimed at downstream tools that process antiSMASH results programmatically.
Bifidobacterium longum 1714™ Strain Modulates Brain Activity of Healthy Volunteers During Social Stress
2019-04-17

OBJECTIVES: Accumulating evidence indicates that the gut microbiota communicates with the central nervous system, possibly through neural, endocrine, and immune pathways, and influences brain function. B. longum 1714TM has previously been shown to attenuate cortisol output and stress responses in healthy subjects exposed to an acute stressor. However, the ability of B. longum 1714TM to modulate brain function in humans is unclear. METHODS: In a randomized, double-blinded, placebo-controlled trial, the effects of B. longum 1714TM on neural responses to social stress, induced by the “Cyberball game,” a standardized social stress paradigm, were studied. Forty healthy volunteers received either B. longum 1714TM or placebo for 4 weeks at a dose of 1 × 10 9 cfu/d. Brain activity was measured using magnetoencephalography and health status using the 36-item short-form health survey. RESULTS: B. longum 1714TM altered resting-state neural oscillations, with an increase in theta band power in the frontal and cingulate cortex ( P &lt; 0.05) and a decrease in beta-3 band in the hippocampus, fusiform, and temporal cortex ( P &lt; 0.05), both of which were associated with subjective vitality changes. All groups showed increased social stress after a 4-week intervention without an effect at behavioral level due to small sample numbers. However, only B. longum 1714TM altered neural oscillation after social stress, with increased theta and alpha band power in the frontal and cingulate cortex ( P &lt; 0.05) and supramarginal gyrus ( P &lt; 0.05). DISCUSSION: B. longum 1714TM modulated resting neural activity that correlated with enhanced vitality and reduced mental fatigue. Furthermore, B. longum 1714TM modulated neural responses during social stress, which may be involved in the activation of brain coping centers to counter-regulate negative emotions.