julilili42/papers huggingface dataset:
Structural changes of the microplankton community following a pulse of inorganic nitrogen in a eutrophic river
2019-11-07

Abstract Global change will increase the number and severity of extreme events resulting in strongly pulsed nutrient loading to rivers. Recent studies indicate the potential for rapid plankton shifts as short‐term response to storm events and highlight the need for high‐frequency methods to understand these complex processes. Here, we studied the effects of a strong short‐term pulse of ammonium nitrate in a eutrophic temperate river that elevated nitrate‐N concentrations from 3.1 to 10–55 mg L −1 . An intense phytoplankton bloom increased chlorophyll a concentrations from below 10 μ g L −1 to over 140 μ g L −1 despite of high background N concentrations and followed the N‐pulse downstream. High‐throughput sequencing revealed the temporal dynamics of the bacterial (16S rRNA gene) and microeukaryotic (18S rRNA gene) community throughout the event. Bacterial and microeukaryotic community richness was reduced, and community composition changed significantly during the bloom. Few microeukaryote taxa (e.g., Cyclotella meneghiniana , Chlamydomonas ) dominated the bloom and replaced the rich summer phytoplankton community. Long‐term monitoring data (2008–2016) using classical microscope analyses showed that seasonal shifts in phytoplankton community composition were linked to physical parameters and nutrient availability with P‐limitation observed in spring but not in summer. We conclude that a disturbance in abiotic and biotic control factors, such as caused by a nutrient pulse, can induce structural shifts in the microplankton community leading to a phytoplankton bloom, even in eutrophic waters.
PAMOGK: A Pathway Graph Kernel based Multi-Omics Clustering Approach for Discovering Cancer Patient Subgroups
2019-11-07

Abstract Accurate classification of patients into molecular subgroups is critical for the development of effective therapeutics and for deciphering what drives these subgroups to cancer. The availability of multi-omics data cat-alogs for large cohorts of cancer patients provides multiple views into the molecular biology of the tumors with unprecedented resolution. We develop PAMOGK ( Pa thway based M ulti O mic G raph K ernel clustering) that not only integrates multi-omics patient data with existing biological knowledge on pathways. We develop a novel graph kernel that evaluates patient similarities based on a single molecular alteration type in the context of a pathway. To corroborate multiple views of patients evaluated by hundreds of pathways and molecular alteration combinations, we use multi-view kernel clustering. Applying PAMOGK to kidney renal clear cell carcinoma (KIRC) patients results in four clusters with significantly different survival times ( p -value = 1.24 e -11). When we compare PAMOGK to eight other state-of-the-art multi-omics clustering methods, PAMOGK consistently outperforms these in terms of its ability to partition KIRC patients into groups with different survival distributions. The discovered patient subgroups also differ with respect to other clinical parameters such as tumor stage and grade, and primary tumor and metastasis tumor spreads. The pathways identified as important are highly relevant to KIRC. PAMOGK is available at github.com/tastanlab/pamogk
A Supernova Remnant Counterpart for HESS J1832−085
2019-11-07

Abstract We examine the new Galactic supernova remnant (SNR) candidate, G23.11+0.18, as seen by the Murchison Widefield Array radio telescope. We describe the morphology of the candidate and find a spectral index of −0.63 ± 0.05 in the 70–170 MHz domain. Coincident TeV gamma-ray detection in High Energy Stereoscopic System (HESS) data supports the SNR nature of G23.11+0.18 and suggests that G23.11+0.18 is accelerating particles beyond TeV energies, thus making this object a promising new cosmic-ray hadron source candidate. The remnant cannot be seen in current optical, infrared and X-ray data sets. We do find, however, a dip in CO-traced molecular gas at a line-of-sight velocity of ∼85 km s −1 , suggesting the existence of a G23.11+0.18 progenitor wind-blown bubble. Furthermore, the discovery of molecular gas clumps at a neighboring velocity toward HESS J1832−085 adheres to the notion that a hadronic gamma-ray production mechanism is plausible toward the north of the remnant. Based on these morphological arguments, we propose an interstellar medium association for G23.11+0.18 at a kinematic distance of 4.6 ± 0.8 kpc.
The de.NBI / ELIXIR-DE training platform - Bioinformatics training in Germany and across Europe within ELIXIR
2019-11-07

<ns4:p>The German Network for Bioinformatics Infrastructure (de.NBI) is a national and academic infrastructure funded by the German Federal Ministry of Education and Research (BMBF). The de.NBI provides (i) service, (ii) training, and (iii) cloud computing to users in life sciences research and biomedicine in Germany and Europe and (iv) fosters the cooperation of the German bioinformatics community with international network structures. The de.NBI members also run the German node (ELIXIR-DE) within the European ELIXIR network. The de.NBI / ELIXIR-DE training platform, also known as special interest group 3 (SIG 3) ‘Training &amp; Education’, coordinates the bioinformatics training of de.NBI and the German ELIXIR node. The network provides a high-quality, coherent, timely, and impactful training program across its eight service centers. Life scientists learn how to handle and analyze biological big data more effectively by applying tools, standards and compute services provided by de.NBI. Since 2015, more than 250 training courses were carried out with more than 5,200 participants and these courses received recommendation rates of almost 90% (status as of October 2019). In addition to face-to-face training courses, online training was introduced on the de.NBI website in 2016 and guidelines for the preparation of e-learning material were established in 2018. In 2016, ELIXIR-DE joined the ELIXIR training platform. Here, the de.NBI / ELIXIR-DE training platform collaborates with ELIXIR in training activities, advertising training courses via TeSS and discussions on the exchange of data for training events essential for quality assessment on both the technical and administrative levels. The de.NBI training program trained thousands of scientists from Germany and beyond in many different areas of bioinformatics.</ns4:p>
Unilateral Hearing Loss Due to Cochlear Nerve Involvement as Isolated Symptom of a Primary Medulloblastoma
2019-11-07

Abstract Unilateral sensorineural hearing loss is a common symptom of vestibular schwannomas in adolescent patients with neurofibromatosis type 2 or sporadic vestibular schwannomas and is often the initial clinical feature. While rare cases of sensorineural impairment presenting as vision or hearing loss due to metastatic medulloblastoma are known, hearing loss as an isolated presenting symptom of primary malignant neuroepithelial tumors of the central nervous system has not been reported in the pediatric population so far. We present two adolescents with unilateral hearing loss due to cochlear nerve dysfunction as the only symptom of a primary nonmetastatic medulloblastoma of the WNT signaling pathway family members subgroup.
Low sense of coherence in long-term follow up of adolescents with anorexia nervosa
2019-11-07

Abstract Background: Sense of coherence is a personal resource known to be low in eating disorders. We wanted to know if sense of coherence is still correlated to anorexia symptoms several years after initial hospitalisation for anorexia. Methods: 86 former female patients diagnosed with anorexia were contacted 5-11 years after hospitalisation in a German hospital; 68 of 149 women (46%) could be contacted and agreed to participate in a survey with the Eating Disorder Inventory (EDI-2) and the Sense of Coherence Questionnaire (SOC-13). Results: 17.6% of participants stated that they suffered from an eating disorder currently, with 7.4% having anorexia nervosa. Mean EDI-2 subscales (except for the bulimia sub-scale) were in the &lt;40th percentile for women with anorexia. Sense of coherence was low (percentile rank 20). All EDI-2 subscales correlated negatively with the SOC-13 score (p&lt;0.01). Conclusions: The sense of coherence is low in long-term follow up of anorexia nervosa and is correlated with on-going anorexia symptoms.
PET/MRI enables simultaneous in vivo quantification of β-cell mass and function
2019-11-08

Non-invasive imaging of β-cells represents a desirable preclinical and clinical tool to monitor the change of β-cell mass and the loss of function during pre-diabetic stages. Although it is widely accepted that manganese (Mn) ions are actively gated by voltage-dependent calcium channels (VDCC) in response to glucose metabolism, little is known on its specificity <i>in vivo</i> for quantification of islet β-cell function using Mn and magnetic resonance imaging (MRI). On the other hand, glucagon-like-peptide-1 receptor (GLP-1R) represents a validated target for the estimation of β-cell mass using radiolabeled exendin-4 (Ex4) and positron emission tomography (PET). However, a multiparametric imaging workflow revealing β-cell mass and function quantitatively is still missing. <b>Methods:</b> We developed a simultaneous PET/MRI protocol to comprehensively quantify <i>in vivo</i> changes in β-cell mass and function by targeting, respectively, GLP-1R and VDCC coupled with insulin secretion. Differences in the spatial distribution of Mn and radiolabeled Ex4 were monitored overtime in native and transgenic pancreata, characterized by spontaneous pancreatic neuroendocrine tumor development. Follow-up with mass spectrometry imaging (MSI) and autoradiography allowed the ex vivo validation of the specificity of Mn and PET tracer uptake and the detection of endogenous biometals, such as calcium and zinc, throughout the endocrine and exocrine pancreas. <b>Results:</b> Our <i>in vivo</i> data based on a volumetric PET/MRI readout for native pancreata and insulinomas connects uptake of Mn measured at early imaging time points to high non-specific binding by the exocrine tissue, while specific retention was only found 24 h post injection. These results are supported by cross-validation of the spatial distribution of exogenous <sup>55</sup>Mn and endogenous <sup>44</sup>Ca and <sup>64</sup>Zn as well with the specific internalization of the radiolabeled peptide targeting GLP-1R. Conclusion: Simultaneous PET/MR imaging of the pancreas enabled the comprehensive <i>in vivo</i> quantification of β-cell function and mass using Mn and radiolabeled Ex4. Most important, our data revealed that only late time-point measurements reflect the Mn uptake in the islet β-cells, while early time points detect non-specific accumulation of Mn in the exocrine pancreas.
Fast Iterative Synthetic Approach toward Identification of Novel Highly Selective p38 MAP Kinase Inhibitors
2019-11-08

p38 mitogen-activated protein kinases are key mediators of environmental stress response and are promising targets for treatment of inflammatory diseases and cancer. Numerous efforts have led to the discovery of several potent inhibitors; however, so far no highly selective type-II inhibitors have been reported. We previously identified VPC-00628 as a potent and selective type-II inhibitor of p38α/β with few off-targets. Here we analyzed the chemical building blocks of VPC-00628 that played a key role in achieving potency and selectivity through targeting an inactive state of the kinases induced by a unique folded P-loop conformation. Using a rapid, systematic combinatorial synthetic approach, we identified compound <b>93</b> (<b>SR-318</b>) with excellent potency and selectivity for p38α/β, which potently inhibited the TNF-α release in whole blood. <b>SR-318</b> therefore presents a potent and selective type-II inhibitor of p38α/β that can be used as a chemical probe for targeting this particular inactive state of these two p38 isoforms.
EZH2 Loss Drives Resistance to Carboplatin and Paclitaxel in Serous Ovarian Cancers Expressing ATM
2019-11-08

Abstract Mechanisms of intrinsic resistance of serous ovarian cancers to standard treatment with carboplatin and paclitaxel are poorly understood. Seventeen primary serous ovarian cancers classified as responders or nonresponders to standard treatment were screened with DigiWest protein array analysis for 279 analytes. Histone methyl transferase EZH2, an interaction partner of ataxia telangiectasia mutated (ATM), was found as one of the most significantly represented proteins in responsive tumors. Survival analysis of 616 patients confirmed a better outcome in patients with high EZH2 expression, but a worse outcome in patients with low EZH2 and high-ATM–expressing tumors compared with patients with low EZH2 and low-ATM–expressing tumors. A proximity ligation assay further confirmed an association between ATM and EZH2 in tumors of patients with an increased disease-free survival. Knockdown of EZH2 resulted in treatment-resistant cells, but suppression of both EZH2 and ATM, or ATM alone, had no effect. DigiWest protein analysis of EZH2-knockdown cells revealed a decrease in proteins involved in mitotic processes and checkpoint regulation, suggesting that deregulated ATM may induce treatment resistance. Implications: Ovarian cancer is a malignancy with high mortality rates, with to date, no successful molecular characterization strategies. Our study uncovers in a comprehensive approach the involvement of checkpoint regulation via ATM and EZH2, potentially providing a new therapeutic perspective for further investigations.
Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease
2019-11-08

Abstract Machado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study. Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci ( P &lt; 1 × 10 −5 ). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.
Mixed Methyl Aryloxy Rare-Earth-Metal Complexes Stabilized by a Superbulky Tris(pyrazolyl)borato Ligand
2019-11-08

Various mixed methyl aryloxide complexes TptBu,MeLnMe(OAr) (Ln = Y, Lu) were obtained in moderate to high yields according to distinct synthesis protocols dependent on the metal size and sterics of the phenolic proligand. The reaction of TptBu,MeLuMe2 and TptBu,MeYMe(AlMe4) via protonolysis with 1 or 2 equiv HOC6H2tBu2-2,6-Me-4 in n-hexane gave the desired complexes TptBu,MeLnMe(OAr). Corresponding treatment of TptBu,MeLuMe2 with the sterically less demanding HOC6H3Me2-2,6, HOC6H3iPr2-2,6 and HOC6H3(CF3)2-3,5 led to the formation of the bis(aryloxy) lutetium complexes TptBu,MeLu(OAr)2. Application of a salt-metathesis protocol employing TptBu,MeLnMe(AlMe4) and the potassium aryloxides KOAr made complexes TptBu,MeLnMe(OAr) accessible for the smaller aryloxy ligands as well. All complexes were analyzed by X-ray crystallography to compare the terminal Ln–Me bond lengths and to evaluate the implication of the methyl/aryloxy coordination for the exact cone angles Θ° of the [TptBu,Me] ancillary ligand. Treatment of TptBu,MeLnMe(AlMe4) (Ln = Lu, Y) with HOC6H2tBu2-2,6-Me-4 in the presence of 4-(dimethylamino)pyridine (dmap) produced ion-separated complexes [TptBu,MeLnMe(dmap)2][Me3AlOC6H2tBu2-2,6-Me-4)]. The thermal instability of TptBu,MeLuMe(OC6H2tBu2-2,6-Me-4) was revealed by the formation of (Tp(tBu-H)/(tBu)2,Me)Lu(OC6H2tBu2-2,6-Me-4) via intramolecular C–H-bond activation.
Fast fitting of reflectivity data of growing thin films using neural networks
2019-11-08

X-ray reflectivity (XRR) is a powerful and popular scattering technique that can give valuable insight into the growth behavior of thin films. This study shows how a simple artificial neural network model can be used to determine the thickness, roughness and density of thin films of different organic semiconductors [diindenoperylene, copper(II) phthalocyanine and α-sexithiophene] on silica from their XRR data with millisecond computation time and with minimal user input or a priori knowledge. For a large experimental data set of 372 XRR curves, it is shown that a simple fully connected model can provide good results with a mean absolute percentage error of 8–18% when compared with the results obtained by a genetic least mean squares fit using the classical Parratt formalism. Furthermore, current drawbacks and prospects for improvement are discussed.
Sprachalltag II: Sprachatlas – Digitalisierung – Nachhaltigkeit und das Arno-Ruoff-Archiv am Ludwig-Uhland-Institut für Empirische Kulturwissenschaft der Universität Tübingen.
2019-11-08

Since 2015, the project Sprachalltag II has been running at the Institute of Historical and Cultural Anthropology in Tübingen. In addition to the final processing of the Sprachatlas von Nord Baden-Württemberg (SNBW), begun in 2009, and the creation of a popular, online Sprechender Sprachatlas von Baden-Württemberg, the goal is to research and digitize the extensive material of the Arno-Ruoff archive for further linguistic and ethnologic studies.&#x0D; This project in particular includes the transcription and alignment of the dialect recordings collected by Ruoff and Bausinger since 1955 for the so called Zwirner corpus as well as the publication of the edited texts in a database in cooperation with the IDS Mannheim. After researching mainly on the morphological and syntactic level of the corpus, the project now also enables phonological examinations of the spoken language throughout the federal state of Baden-Württemberg and the area of Bavarian Swabia via the database.&#x0D; This report will introduce the nature and extent of the hitherto edited recordings in more detail and show how, in the sense of a cross-disciplinary collaboration, Empirical Cultural Studies can benefit from the content development of the Tübingen corpus. In the course of editing, the transcripted dialect recordings are assigned to thematic categories by using keywords such as leisure or modernization. This includes the means of enquiry of the corpus to a content-related level that can serve the research fields of Historical and Cultural Anthropology.
Faculty Opinions recommendation of Allelic Variation in the Chloroplast Division Gene FtsZ2-2 Leads to Natural Variation in Chloroplast Size.
2019-11-08

Chloroplast size varies considerably in nature, but the underlying mechanisms are unknown. By exploiting a near-isogenic line population derived from a cross between the Arabidopsis (Arabidopsis thaliana) accessions Cape Verde Islands (Cvi-1), which has larger chloroplasts, and Landsberg erecta (Ler-0), with smaller chloroplasts, we determined that the large-chloroplast phenotype in Cvi-1 is associated with allelic variation in the gene encoding the chloroplast-division protein FtsZ2-2, a tubulin-related cytoskeletal component of the contractile FtsZ ring inside chloroplasts. Sequencing revealed that the Cvi-1 FtsZ2-2 allele encodes a C-terminally truncated protein lacking a region required for FtsZ2-2 interaction with inner-envelope proteins, and functional complementation experiments in a Columbia-0 ftsZ2-2 null mutant confirmed this allele as causal for the increased chloroplast size in Cvi-1. Comparison of FtsZ2-2 coding sequences in the 1001 Genomes database showed that the Cvi-1 allele is rare and identified additional rare loss-of-function alleles, including a natural null allele, in three other accessions, all of which had enlarged-chloroplast phenotypes. The ratio of nonsynonymous to synonymous substitutions was higher among the FtsZ2-2 genes than among the two other FtsZ family members in Arabidopsis, FtsZ2-1, a close paralog of FtsZ2-2, and the functionally distinct FtsZ1-1, indicating more relaxed constraint on the FtsZ2-2 coding sequence than on those of FtsZ2-1 or FtsZ1-1 Our results establish that allelic variation in FtsZ2-2 contributes to natural variation in chloroplast size in Arabidopsis, and they also demonstrate that natural variation in Arabidopsis can be used to decipher the genetic basis of differences in fundamental cell biological traits, such as organelle size.© 2019 American Society of Plant Biologists. All Rights Reserved. PMID: 31488573
Arabidopsis FHY1 and FHY1-LIKE Are Not Required for Phytochrome A Signal Transduction in the Nucleus
2019-11-09

Photoreceptors of the phytochrome family control a multitude of responses in plants. Phytochrome A (phyA) is essential for far-red light perception, which is important for germination and seedling establishment in strong canopy shade. Translocation of phyA from the cytosol into nucleus is a key step in far-red light signaling and requires FAR-RED ELONGATED HYPOCOTYL 1 (FHY1) and FHY1-LIKE (FHL). FHY1/FHL bind to phyA downstream signaling components. Therefore, it has been suggested that FHY1/FHL also have a function in assembling phyA transcription factor complexes in the nucleus. Yet, in this study, we show that constitutively nuclear-localized phyA is active in the absence of FHY1 and FHL. Furthermore, an artificial FHY1, consisting of an SV40 NLS, a phyA binding site, and a YFP tag as spacer between them, complements the <i>fhy1-3 fhl-1</i> double mutant. These findings show that FHY1 and FHL are not required for phyA downstream signaling in the nucleus. However, we found that lines expressing phyA-NLS-YFP are hypersensitive to red and far-red light and that slightly increased levels of constitutively nuclear-localized phyA result in photomorphogenic development in the dark. Thus, restricting phyA to the cytosol and inducing nuclear transport in light by interaction with FHY1/FHL might be important to suppress photomorphogenesis in the dark.