bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in resources use lead to coexistence of seed-transmitted microbial populations
Authors: Torres-Cortés G , Garcia BJ , Compant S , Rezki S , Jones P , Préveaux A , Briand M , Roulet A , Bouchez O , Jacobson D , Barret M 
Published: February 2019

ABSTRACTSeeds are involved in the vertical transmission of microorganisms in plants and act as reservoirs for the plant microbiome. They could serve as carriers of pathogens, making the study of microbial interactions on seeds important in the emergence of plant diseases. We studied the influence of biological disturbances caused by seed transmission of two phytopathogenic agents,Alternaria brassicicolaAbra43 (Abra43) andXanthomonas campestrispv.campestris8004 (Xcc8004), on the structure and function of radish seed microbial assemblages, as well as the nutritional overlap between Xcc8004 and the seed microbiome, to find seed microbial residents capable of outcompeting this pathogen. According to taxonomic and functional inference performed on metagenomics reads, no shift in structure and function of the seed microbiome was observed following Abra43 and Xcc8004 transmission. This lack of impact derives from a limited overlap in nutritional resources between Xcc8004 and the major bacterial populations of radish seeds. However, two native seed-associated bacterial strains belonging toStenotrophomonas rhizophiladisplayed a high overlap with Xcc8004 regarding the use of resources; they might therefore limit its transmission. The strategy we used may serve as a foundation for the selection of seed indigenous bacterial strains that could limit seed transmission of pathogens.
Epigenetic inheritance of centromere identity in a heterologous system
Authors: Roure Virginie , Medina-Pritchard Bethan , Anselm Eduard , Arockia Jeyaprakash A. , Heun Patrick 
Published: February 2019

SUMMARYThe centromere is an essential chromosomal region required for accurate chromosome segregation. Most eukaryotic centromeres are defined epigenetically by the histone H3 variant, CENP-A, yet how its self-propagation is achieved remains poorly understood. Here we developed a heterologous system to reconstitute epigenetic inheritance of centromeric chromatin by ectopically targeting the Drosophila centromere proteins dCENP-A, dCENP-C and CAL1 to LacO arrays in human cells. Dissecting the function of these three components uncovers the key role of self-association of dCENP-C and CAL1 for their mutual interaction and dCENP-A deposition. Importantly, we identify the components required for dCENP-C loading onto chromatin, involving a cooperation between CAL1 and dCENP-A nucleosomes, thus closing the epigenetic loop to ensure dCENP-C and dCENP-A replenishment during the cell division cycle. Finally, we show that all three Drosophila factors are sufficient for dCENP-A propagation and propose a model for the epigenetic inheritance of centromere identity.
BORIS/CTCFL promotes a switch from a proliferative towards an invasive phenotype in melanoma cell lines
Authors: Janssen Sanne Marlijn , Moscona Roy , Elchebly Mounib , Papadakis Andreas Ioannis , Redpath Margaret , Wang Hangjun , Rubin Eitan , van Kempen Léon Cornelis , Spatz Alan 
Published: February 2019

AbstractMelanoma is among the most aggressive cancers due to its tendency to metastasize early. Phenotype switching between a proliferative and an invasive state has been suggested as a critical process for metastasis. The mechanisms that regulate these transitions are poorly understood, but are associated with transcriptional changes. Brother of Regulator of Imprinted Sites (BORIS), also known as CCCTC binding factor-Like (CTCFL), is a transcriptional modulator that becomes aberrantly expressed in melanoma. Here, we provide the first evidence that BORIS is involved in phenotype switching in melanoma. Genetic modification of BORIS expression in melanoma cells combined with whole transcriptome analysis indicated that BORIS expression contributes to an invasion-associated transcriptome. In agreement with this finding, inducible BORIS overexpression in melanoma cells reduced proliferation and increased migration and invasion, demonstrating that the transcriptional switch is accompanied by a phenotypic switch. Overall, our study indicates a pro-invasive role for BORIS in melanoma via transcriptional reprogramming.
An Omentum-inspired 3D PEG Hydrogel for Identifying ECM-drivers of Drug Resistant Ovarian Cancer
Authors: Brooks Elizabeth A. , Gencoglu Maria F. , Corbett Daniel C. , Stevens Kelly R. , Peyton Shelly R. 
Published: February 2019

AbstractOvarian cancer (OvCa) is a challenging disease to treat due to poor screening techniques and late diagnosis. There is an urgent need for additional therapy options, as patients recur in 70% of cases. The limited availability of clinical treatment options could be a result of poor predictions in early stage drug screens on standard tissue culture polystyrene (TCPS). TCPS does not capture the mechanical and biochemical cues that cells experiencein vivo, which can impact how cells will respond to a drug. Therefore, anin vitromodel that captures some of the microenvironment features that the cells experiencein vivocould provide better insights into drug response. In this study, we formed 3D multicellular tumor spheroids (MCTS) in microwells, and encapsulated them in 3D omentum-inspired hydrogels. SKOV-3 MCTS were resistant to Paclitaxel in our 3D hydrogels compared to a monolayer on TCPS. Toward clinical application, we tested cells from patients (ovarian carcinoma ascites spheroids (OCAS)), and drug responses predicted by using the 3D omentum-inspired hydrogels correlated with the reported pathology reports of those same patients. Additionally, we observed the presence of collagen production around the encapsulated SKOV-3 MCTS, but not on TCPS. Our results demonstrated that our 3D omentum-inspired hydrogel is an improvedin vitrodrug testing platform to study OvCa drug response for patient-derived cells, and helped us identify collagen 3 as a potential driver of Paclitaxel resistance.
Samovar: Single-sample mosaic SNV calling with linked reads
Authors: Darby Charlotte A. , Fitch James R. , Brennan Patrick J. , Kelly Benjamin J. , Bir Natalie , Magrini Vincent , Leonard Jeffrey , Cottrell Catherine E. , Gastier-Foster Julie M. , Wilson Richard K. , Mardis Elaine R. , White Peter , Langmead Ben , Schatz Michael C. 
Published: February 2019

AbstractWe present Samovar, a mosaic single-nucleotide variant (SNV) caller for linked-read whole-genome shotgun sequencing data. Samovar scores candidate sites using a random forest model trained using the input dataset that considers read quality, phasing, and linked-read characteristics. We show Samovar calls mosaic SNVs within a single sample with accuracy comparable to what previously required trios or matched tumor/normal pairs and outperform single-sample mosaic variant callers at MAF 5%-50% with at least 30x coverage. Furthermore, we use Samovar to find somatic variants in whole genome sequencing of both tumor and normal from 13 pediatric cancer cases that can be corroborated with high recall with whole exome sequencing. Samovar is available open-source at https://github.com/cdarby/samovar under the MIT license.
Task-evoked activity quenches neural correlations and variability across cortical areas
Authors: Ito Takuya , Brincat Scott L. , Siegel Markus , Mill Ravi D. , He Biyu J. , Miller Earl K. , Rotstein Horacio G. , Cole Michael W. 
Published: February 2019

AbstractMany large-scale functional connectivity studies have emphasized the importance of communication through increased inter-region correlations during task states. In contrast, local circuit studies have demonstrated that task states primarily reduce correlations among pairs of neurons, likely enhancing their information coding by suppressing shared spontaneous activity. Here we sought to adjudicate between these conflicting perspectives, assessing whether co-active brain regions during task states tend to increase or decrease their correlations. We found that variability and correlations primarily decrease across a variety of cortical regions in two highly distinct data sets: non-human primate spiking data and human functional magnetic resonance imaging data. Moreover, this observed variability and correlation reduction was accompanied by an overall increase in dimensionality (reflecting less information redundancy) during task states, suggesting that decreased correlations increased information coding capacity. We further found in both spiking and neural mass computational models that task-evoked activity increased the stability around a stable attractor, globally quenching neural variability and correlations. Together, our results provide an integrative mechanistic account that encompasses measures of large-scale neural activity, variability, and correlations during resting and task states.
Undiagnosed and diagnosed hypertension in a community setting at Hosanna town: Uncovering the burden
Authors: Dereje Nebiyu , Earsido Alemu , Abebe Ashenafi , Temam Layla 
Published: February 2019

AbstractBackgroundHypertension is a leading cause of cardio-vascular diseases and its attributed mortality. No previous study, however, assessed the prevalence and associated factors of hypertension in the study area.MethodsWe recruited a representative sample of 627 adult individuals from selected kebeles of Hosanna town. A multi-stage sampling technique was employed in the study. A structured questionnaire using the WHO STEPS approach was employed to conduct a face to face interview and physical measurements. For each participant, we measured blood pressure two times after giving 10 minutes breaks between the measurements and we took the average. Hypertension status was defined as “systolic blood pressure ≥140mmhg and/or diastolic blood pressure ≥90mmhg”. Undiagnosed hypertension was defined as participants who had raised blood pressure on measurement, but not aware of it before. We used Multivariable logistic regression model to determine factors associated with hypertension.ResultsThe overall prevalence of hypertension was found to be 17.2% (95% CI 14.5 – 19.9), 19.3% among men and 14.2% among women, of which 10.2% were unaware of it before. Hypertension was significantly associated with old age ≥35 years, excess alcohol intake, consumption of saturated oil/fat), consumption of unspecified different types of oil/fat and overweight/obesity.ConclusionThe prevalence of hypertension (both diagnosed and undiagnosed) in the town is unacceptably high. This is also related to modifiable risk factors like excessive alcohol intake, overweight/obesity and consumption of saturated fat/oil. Therefore, designing health information provision systems on the risk factors of hypertension and promotion of good health practices should be considered. Moreover, the health departments should facilitate blood pressure screening programs at community levels to identify and treat undiagnosed hypertension.
Taxonomic survey ofAnadenobolus monilicornisgut microbiota via shotgun nanopore sequencing
Authors: Geli-Cruz Orlando J. , Cafaro Matias J. , Santos-Flores Carlos J. , Ropelewski Alex J. , Van Dam Alex R. 
Published: February 2019

AbstractMillipedes constitute one of many soil-inhabiting organisms that act as important components of litter decomposition and nutrient recycling in terrestrial ecosystems. This is thanks in part to the microbial diversity that they contain in their gut compartments. However, millipedes and their gut microbiota are understudied, compared to other arthropods. For this reason, we partook in a metagenomic analysis of the gut ofAnadenobolus monilicornis. We collected specimens ofA. monilicornis, which were starved for a varying amount of time, from different municipalities of Puerto Rico. Once the DNA from their guts was extracted and sequenced using the MinION nanopore sequencer, we proceeded to analyze and compile the data obtained from the sequencer using programs such as Phylosift and MEGAN6 and the web-based MG-RAST. From our two best samples, we obtained a total of 87,110 and 99,749 reads, respectively. After comparing the data analyses and gene annotation done for both samples, we found that the bacterial phyla Proteobacteria, Bacteroidetes and Firmicutes were consistently well represented; one of our samples had much more Chlamydiae representation than the other, however. Sampled eukaryote phyla include Arthropoda, Chordata and Streptophyta. We would need a greater sample size to better determine differences in microbial diversity between millipede populations across the island; considering our small sample size, however, we were able to broadly reveal the diversity within the microenvironment ofA. monilicornis’s gut.
Leaf Variegation and Impaired Chloroplast Development Caused by a Truncated CCT Domain gene inalbostriansBarley
Authors: Li Mingjiu , Hensel Goetz , Mascher Martin , Melzer Michael , Budhagatapalli Nagaveni , Rutten Twan , Himmelbach Axel , Beier Sebastian , Korzun Viktor , Kumlehn Jochen , Börner Thomas , Stein Nils 
Published: February 2019

ABSTRACTChloroplasts fuel plant development and growth by converting solar into chemical energy. They mature from proplastids through the concerted action of genes in both the organellar and the nuclear genome. Defects in such genes impair chloroplast development and may lead to pigment-deficient seedlings or seedlings with variegated leaves. Such mutants are instrumental as tools for dissecting genetic factors underlying the mechanisms involved in chloroplast biogenesis. Characterization of the green-white variegatedalbostriansmutant of barley has greatly broadened the field of chloroplast biology including the discovery of retrograde signaling. Here, we report the identification of theALBOSTRIANSgeneHvASTby positional cloning as well as its functional validation based on independently induced mutants by TILLING and RNA-guided Cas9 endonuclease mediated gene editing. The phenotypes of the independentHvASTmutants imply residual activity of HvAST in the originalalbostriansallele conferring an imperfect penetrance of the variegated phenotype even at homozygous state of the mutation.HvASTis a homolog of theArabidopsis thaliana CCT Motiftranscription factor geneAtCIA2, which was reported to be involved in the expression of nuclear genes essential for chloroplast biogenesis. Interestingly, in barley we localized HvAST to the chloroplast indicating novel without any clear evidence of nuclear localization.One-sentence summaryLeaf variegation in the barley mutantalbostriansis caused by mutation of a single CCT-domain containing gene with residual activity, which is directed to the chloroplast.
Reconstruction of clone- and haplotype-specific cancer genome karyotypes from bulk tumor samples
Authors: Aganezov Sergey , Raphael Benjamin J. 
Published: February 2019

AbstractMany cancer genomes are extensively rearranged with highly aberrant chromosomal karyotypes. These genome rearrangements, or structural variants, can be detected in tumor DNA sequencing data by abnormal mapping of se-quence reads to the reference genome. However, nearly all cancer sequencing to date is of bulk tumor samples which consist of a heterogeneous mixture of normal cells and subpopulations of cancers cells, or clones, that harbor distinct somatic structural variants. We introduce a novel algorithm,ReconstructingCancerKaryotypes (RCK), to reconstruct haplotype-specific karyotypes of one or more rearranged cancer genomes, or clones, that best explain the read alignments from a bulk tumor sample.RCKleverages specific evolutionary constraints on the somatic mutation process in cancer to reduce ambiguity in the deconvolution of admixed DNA sequence data into multiple haplotype-specific cancer karyotypes. In particular,RCKrelies on generalizations of the infinite sites assumption that a genome re-arrangement is highly unlikely to occur at the same nucleotide position more than once during somatic evolution.RCK’s comprehensive model allows us to incorporate information both from short and long-read sequencing technologies and is applicable to bulk tumor samples containing a mixture of an arbitrary number of derived genomes. We comparedRCKto the state-of-the-art methodReMixTon a dataset of 17 primary and metastatic prostate cancer samples. We demonstrate thatReMixT’s limited support for heterogeneity and lack of evolutionary constrains leads to reconstruction of implausible karyotypes. In contrast,RCK’s infers cancer karyotypes that better explain read alignments from bulk tumor samples and are consistent with a reasonable evolutionary model.RCK’s reconstructions of clone- and haplotype-specific karyotypes will aid further studies of the role of intra-tumor heterogeneity in cancer development and response to treatment.RCKis available athttps://github.com/raphael-group/RCK.
Inferring active cis-regulatory modules to predict functional regulatory elements
Authors: Chen Xi , Neuwald Andrew F. , Hilakivi-Clarke Leena , Clarke Robert , Xuan Jianhua 
Published: February 2019

AbstractTranscription factors (TFs) often function as cis-regulatory modules (CRMs) including both master factors and mediator coactivators to activate enhancers or promoters and regulate target gene transcription. Cell type-specific ChIP-seq profiling of multiple TFs makes it feasible to infer functional CRMs for a particular cell type. Yet, approaches based on co-localization of TF ChIP-seq peaks to infer CRMs are applied but many weak binding events, especially of those mediators, are missed by peak callers, resulting in an incomplete identification of CRMs. We developed a ChIP-seq data-based CRM inference approach with Gibbs-Sampling (ChIP-GSM). In a Bayesian framework, ChIP-GSM samples read counts of TFs iteratively for the joint effect of each potential TF combination. Using inferred CRMs as novel features, ChIP-GSM employs a logistic regression model to predict active regulatory elements. Performance validation on FANTOM5 enhancer or promoter regions revealed the superior performance of CRMs on regulatory region activity prediction than TFs. Finally, integrating CRMs inferred for K562 cells and gene expression data we found that CRMs are likely to activate regulatory regions or genes at different time points to mediate distinct cellular functions.Author SummaryAccurately inferring cis-regulatory modules (CRMs) from a large set of TFs is a challenging task because the binding signals of TFs are often weak, noisy and sensitive to the cellular environment. Nevertheless, investigating TF associations may help understand the difference between enhancer and promoter activation mechanisms. In this paper, we develop a computational method (ChIP-GSM) to infer CRMs acting on regulatory elements at enhancer and promote regions. The novel method is built upon a Bayesian framework with Gibbs sampling that can be used to infer CRMs reliably hence to predict regulatory elements. The performance of ChIP-GSM is compared to that of existing methods, demonstrating its improved performance. Experimental results demonstrate that CRMs identified by ChIP-GSM are likely activating regulatory regions at different time points to mediate distinct cellular functions.
A genome-wide screen for ER autophagy highlights key roles of mitochondrial metabolism and ER-resident UFMylation
Authors: Liang Jin Rui , Lingeman Emily , Luong Thao , Ahmed Saba , Nguyen Truc , Olzmann James , Corn Jacob E. 
Published: February 2019

SummarySelective degradation of organelles via autophagy is critical for cellular differentiation, homeostasis, and organismal health. Autophagy of the ER (ER-phagy) is implicated in human neuropathy but is poorly understood beyond a few specialized autophagosomal receptors and remodelers. Using an ER-phagy reporter and genome-wide CRISPRi screening, we identified 200 high-confidence factors involved in human ER-phagy. We mechanistically investigated two pathways unexpectedly required for ER-phagy. First, reduced mitochondrial metabolism represses ER-phagy, which reverses the logic of general autophagy. Mitochondrial crosstalk with ER-phagy bypasses the energy sensor AMPK, instead directly impacting ULK1. Second, ER-localized UFMylation is required for ER-phagy that represses the unfolded protein response. The UFL1 ligase is brought to the ER surface by DDRGK1, analogous to PINK1-Parkin regulation during mitophagy. Our data provide insight into the unique cellular logic of ER-phagy, reveal parallels between organelle autophagies, and provide an entry point to the relatively unexplored process of degrading the ER network.
Transcriptomically-guided mesendoderm induction of human pluripotent stem cells using a systematically defined culture scheme
Authors: Carpenedo Richard L , Kwon Sarah Y , Tanner R Matthew , Yockell-Lelièvre Julien , Choey Chandarong , Doré Carole , Ho Mirabelle , Stewart Duncan J , Perkins Theodore J , Stanford William L 
Published: February 2019

SummaryHuman pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling. Efficient, broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field. We describe a simple, robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding (SCS) and BMP4 and Activin A (BA) treatment. Gene sets and gene ontology terms related to mesoderm and endoderm differentiation were enriched after 48 hours of BA treatment. BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation. After prolonged differentiation in vitro or in vivo, BA pre-treatment resulted in higher mesoderm and endoderm levels at the expense of ectoderm formation. These data demonstrate that SCS with BA treatment is a powerful method for induction of mesendoderm that can be integrated into protocols for mesoderm and endoderm differentiation.
Intra-mitochondrial proteostasis is directly coupled to alpha-synuclein and Amyloid β 1-42 pathology
Authors: Lautenschläger Janin , Wagner-Valladolid Sara , Stephens Amberley D. , Fernández-Villegas Ana , Hockings Colin , Mishra Ajay , Manton James D. , Fantham Marcus J. , Lu Meng , Rees Eric J. , Kaminski Clemens F. , Schierle Gabriele S. Kaminski 
Published: February 2019

AbstractMitochondria have long been implicated in Parkinson’s disease (PD), however, it is not clear how mitochondrial impairment and alpha-synuclein pathology are coupled. We report here that intra-mitochondrial protein homeostasis plays a major role in alpha-synuclein fibril elongation, as interference with intra-mitochondrial proteases and mitochondrial protein import significantly aggravate alpha-synuclein aggregation. In contrast, direct inhibition of mitochondrial complex I, increase in intracellular calcium concentration or formation of reactive oxygen species (ROS), all of which have been associated with mitochondrial stress, did not affect alpha-synuclein pathology. We further demonstrate that similar mechanisms are involved in Amyloid β 1-42 (Aβ42) aggregation, suggesting that mitochondria are directly capable of influencing cytosolic protein homeostasis of aggregation-prone proteins.