bluuebunny/crossref_metadata_2025_split huggingface dataset:
Description of a widespread bacterial secretion system with chemically diverse substrates
Authors: Grossman Alex S. , Mauer Terra J. , Forest Katrina T. , Goodrich-Blair Heidi 
Published: January 2020

AbstractIn host-associated bacteria, surface and secreted proteins mediate acquisition of nutrients, interactions with host cells, and specificity of tissue-localization. In Gram-negative bacteria, the mechanism by which many proteins cross or become tethered to the outer membrane remains unclear. Thedomain ofunknown function (DUF)560 occurs in outer membrane proteins throughout Proteobacteria and has been implicated in host-bacteria interactions and lipoprotein surface exposure. We used sequence similarity networking to reveal three subfamilies of DUF560 homologs. One subfamily includes those DUF560 proteins experimentally characterized to date: NilB, a host-range determinant of the nematode-mutualistXenorhabdus nematophila, and thesurface lipoproteinassemblymodulators Slam1 and Slam2, which facilitate msurface exposure of lipoproteins inNeisseria meningitidis(1, 2). We show that DUF560 proteins from a second subfamily facilitate secretion of soluble, non-lipidated proteins across the outer membrane. Usingin silicoanalysis, we demonstrate that DUF560 gene complement correlates with bacterial environment at a macro level and host association at a species level. The DUF560 protein superfamily represents a newly characterized Gram-negative secretion system capable of lipoprotein surface exposure and soluble protein secretion with conserved roles in facilitating symbiosis. In light of these data, we propose that it be titled the typeeleven secretionsystem (TXISS).ImportanceThe microbial constituents of a host associated microbiome are decided by a complex interplay of microbial colonization factors, host surface conditions, and host immunological responses. Filling such niches requires bacteria to encode an arsenal of surface and secreted proteins to effectively interact with the host and co-occurring microbes. Bioinformatic predictions of the localization and function of putative bacterial colonization factors are essential for assessing the potential of bacteria to engage in pathogenic, mutualistic, or commensal activities. This study uses publicly available genome sequence data, alongside experimental results from representative gene products fromXenorhabdus nematophila, to demonstrate a role for DUF560 family proteins in the secretion of bacterial effectors of host interactions. Our research delineates a broadly distributed family of proteins and enables more accurate predictions of the localization of colonization factors throughout Proteobacteria.
Inhibition and Crystal Structure of the Human DHTKD1-Thiamin Diphosphate Complex
Authors: Leandro João , Khamrui Susmita , Wang Hui , Suebsuwong Chalada , Nemeria Natalia S. , Huynh Khoi , Moustakim Moses , Secor Cody , Wang May , Dodatko Tetyana , Stauffer Brandon , Wilson Christopher G. , Yu Chunli , Arkin Michelle R. , Jordan Frank , Sanchez Roberto , DeVita Robert J. , Lazarus Michael B. , Houten Sander M. 
Published: January 2020

AbstractDHTKD1 is the E1 component of the 2-oxoadipic acid dehydrogenase complex (OADHc), which functions in the L-lysine degradation pathway. Mutations inDHTKD1have been associated with 2-aminoadipic and 2-oxoadipic aciduria, Charcot-Marie-Tooth disease type 2Q (CMT2Q) and eosinophilic esophagitis (EoE). A crystal structure and inhibitors of DHTKD1 could improve the understanding of these clinically distinct disorders, but are currently not available. Here we report the identification of adipoylphosphonic acid and tenatoprazole as DHTKD1 inhibitors using targeted and high throughput screening, respectively. We furthermore elucidate the DHTKD1 crystal structure with thiamin diphosphate bound at 2.1 Å. The protein assembles as a dimer with residues from both monomers contributing to cofactor binding. We also report the impact of tenDHTKD1missense mutations on the encoded proteins by enzyme kinetics, thermal stability and structural modeling. Some DHTKD1 variants displayed impaired folding (S777P and S862I), whereas other substitutions rendered the enzyme inactive (L234G, R715C and R455Q) or affected the thermal stability and catalytic efficiency (V360A and P773L). Three variants (R163Q, Q305H and G729R) surprisingly showed wild type like properties. Our work provides a structural basis for further understanding of the function of DHTKD1 and a starting point for selective small molecule inhibitors of the enzyme, which could help tease apart the role of this enzyme in several human pathologies.
Fast Lasso method for Large-scale and Ultrahigh-dimensional Cox Model with applications to UK Biobank
Authors: Li Ruilin , Chang Christopher , Justesen Johanne Marie , Tanigawa Yosuke , Qian Junyang , Hastie Trevor , Rivas Manuel A. , Tibshirani Robert 
Published: January 2020

AbstractWe develop a scalable and highly efficient algorithm to fit a Cox proportional hazard model by maximizing theL1-regularized (Lasso) partial likelihood function, based on the Batch Screening Iterative Lasso (BASIL) method developed in (Qian et al. 2019). The output of our algorithm is the full Lasso path, the parameter estimates at all predefined regularization parameters, as well as their validation accuracy measured using the concordance index (C-index) or the validation deviance. To demonstrate the effectiveness of our algorithm, we analyze a large genotype-survival time dataset across 306 disease outcomes from the UK Biobank (Sudlow et al. 2015). Our approach, which we refer to as snpnet-Cox, is implemented in a publicly available package.
The yeast mating-type switching endonuclease HO is a domesticated member of an unorthodox homing genetic element family
Authors: Coughlan Aisling Y. , Lombardi Lisa , Braun-Galleani Stephanie , Martos Alexandre A. R. , Galeote Virginie , Bigey Frédéric , Dequin Sylvie , Byrne Kevin P. , Wolfe Kenneth H. 
Published: January 2020

SummaryThe mating-type switching endonuclease HO plays a central role in the natural life cycle ofSaccharomyces cerevisiae, but its evolutionary origin is unknown.HOis a recent addition to yeast genomes, present in only a few genera. It resembles a degenerated intein fused to a zinc finger domain. Here we show thatHOis structurally and phylogenetically related to a family of unorthodox homing genetic elements found inTorulasporaandLachanceayeasts. TheseWHOelements integrate into the aldolase geneFBA1, replacing its 3’ end each time. Their structural organization is different from all known classes of homing elements. We show that a WHO protein cleavesTorulaspora delbrueckii FBA1efficiently and in an allele-specific manner, leading to DNA repair by gene conversion or NHEJ. The DNA rearrangement steps duringWHOelement homing are very similar to those during mating-type switching, and indicate thatHOis a domesticatedWHO-like element.
Effect of Perfluorooctanesulfonic acid (PFOS) on immune cell development and function in mice
Authors: Torres Luisa , Redko Amie , Limper Candice , Imbiakha Brian , Chang Sue , August Avery 
Published: January 2020

AbstractPerfluorinated compounds, such as Perfluoroctane sulfonic acid (PFOS) are compounds containing carbon chains where hydrogens have been replaced with fluorines, and belong to a larger family known as Per- and polyfluoroalkyl substances (PFAS). The strength of the carbon–fluorine bond makes perfluorinated compounds extremely resistant to environmental degradation. Due to the persistent nature of PFOS, research has been directed to elucidating possible health effects of PFOS on humans and laboratory animals. Here we have explored the effects of PFOS exposure on immune development and function in mice. We exposed adult wild-type mice to 3 and 1.5 μg/kg/day of PFOS for 2 and 4 weeks, respectively, and examined the effects of PFOS exposure on populations of T cells, B cells, and granulocytes. These doses of PFOS resulted in serum levels of approximately 100 ng/ml with no weight loss during exposure. We find that PFOS does not affect T-cell development during this time. However, while PFOS exposure reduced immune cell populations in some organs, it also led to an increase in the numbers of cells in others, suggesting possible relocalization of cells. We also examined the effect of PFOS on the response to influenza virus infection. We find that exposure to PFOS at 1.5 μg/kg/day of PFOS for 4 weeks does not affect weight loss or survival, nor is viral clearance affected. Analysis of antibody and T cell specific antiviral responses indicate that at this concentration, PFOS does not suppress the immune cell development or antigen specific immune response.
How Sensitive are EEG Results to Preprocessing Methods: A Benchmarking Study
Authors: Robbins Kay A. , Touryan Jonathan , Mullen Tim , Kothe Christian , Bigdely-Shamlo Nima 
Published: January 2020

AbstractAlthough several guidelines for best practices in EEG preprocessing have been released, even those studies that strictly adhere to those guidelines contain considerable variation in the ways that the recommended methods are applied. An open question for researchers is how sensitive the results of EEG analyses are to variations in preprocessing methods and parameters. To address this issue, we analyze the effect of preprocessing methods on downstream EEG analysis using several simple signal and event-related measures. Signal measures include recording-level channel amplitudes, study-level channel amplitude dispersion, and recording spectral characteristics. Event-related methods include ERPs and ERSPs and their correlations across methods for a diverse set of stimulus events. Our analysis also assesses differences in residual signals both in the time and spectral domains after blink artifacts have been removed. Using fully automated pipelines, we evaluate these measures across 17 EEG studies for two ICA-based preprocessing approaches (LARG, MARA) plus two variations of Artifact Subspace Reconstruction (ASR). Although the general structure of the results is similar across these preprocessing methods, there are significant differences, particularly in the low-frequency spectral features and in the residuals left by blinks. These results argue for detailed reporting of processing details as suggested by most guidelines, but also for using a federation of automated processing pipelines and comparison tools to quantify effects of processing choices as part of the research reporting.
scIGANs: single-cell RNA-seq imputation using generative adversarial networks
Authors: Xu Yungang , Zhang Zhigang , You Lei , Liu Jiajia , Fan Zhiwei , Zhou Xiaobo 
Published: January 2020

ABSTRACTSingle-cell RNA-sequencing (scRNA-seq) enables the characterization of transcriptomic profiles at the single-cell resolution with increasingly high throughput. However, it suffers from many sources of technical noises, including insufficient mRNA molecules that lead to excess false zero values, termed dropouts. Computational approaches have been proposed to recover the biologically meaningful expression by borrowing information from similar cells in the observed dataset. However, these methods suffer from oversmoothing and removal of natural cell-to-cell stochasticity in gene expression. Here, we propose the generative adversarial networks (GANs) for scRNA-seq imputation (scIGANs), which uses generated cells rather than observed cells to avoid these limitations and balances the performance between major and rare cell populations. Evaluations based on a variety of simulated and real scRNA-seq datasets show that scIGANs is effective for dropout imputation and enhances various downstream analysis. ScIGANs is robust to small datasets that have very few genes with low expression and/or cell-to-cell variance. ScIGANs works equally well on datasets from different scRNA-seq protocols and is scalable to datasets with over 100,000 cells. We demonstrated in many ways with compelling evidence that scIGANs is not only an application of GANs in omics data but also represents a competing imputation method for the scRNA-seq data.
Phylogenetic relationships among haloalkaliphilic archaea of the familyNatrialbaceae
Authors: Siddaramappa Shivakumara 
Published: January 2020

ABSTRACTThe familyNatrialbaceaeis a member of the classHalobacteriaof the archaeal phylumEuryarchaeota. Seventeen genera with validly or effectively published names are currently included within this family. In this study, using pairwise average nucleotide identity and average amino acid identity comparisons in conjunction with phylogenetic analysis, it has been shown that the familyNatrialbaceaeis highly diverse and contains several potentially novel species and genera that are yet to be fully characterized. The deduced proteome sequence-based phylogenetic tree, constructed using the alignment- and parameter-free method CVTree3, contained six major clades, withSalinarchaeumsp. Harcht-Bsk1 being the only representative within clade 1. Furthermore,Haloterrigena daqingensiswas found to be closely related toNatronorubrum sediminis, and it is proposed that these archaea together represent a novel genus. Interestingly,Haloterrigena jeotgali,Haloterrigena thermotolerans, andNatrinema pellirubrumwere found to be very closely related to each other, and it is proposed that they be merged into a single species. Notably, the type genusNatrialbaitself appeared to be heterogenous and contains species that could be broadly classified among two genera. Likewise, the genusNatrinemais also heterogenous and contains species that could be classified among six genera. Altogether, 19 novel genera have been proposed to be created, and four haloalkaliphilic archaea hitherto recognized only using genus names are confirmed to represent novel species.
Vegetation and seed bank dynamics highlight the importance of post-restoration management in sown grasslands
Authors: Valkó Orsolya , Deák Balázs , Török Péter , Tóth Katalin , Kiss Réka , Kelemen András , Miglécz Tamás , Sonkoly Judit , Tóthmérész Béla 
Published: January 2020

AbstractSowing grass seeds generally supports the rapid development of a closed perennial vegetation, which makes the method universally suitable for fast and effective landscape-scale restoration of grasslands. However, sustaining the recovered grasslands, and increasing their diversity is a challenging task. Understanding the role of seed bank compositional changes and vegetation dynamics contributes to designating management regimes that support the establishment of target species and suppress weeds. Our aim was to reveal the effect of post-restoration management on the vegetation and seed bank dynamics in grasslands restored in one of the largest European landscape-scale restoration projects. Eight years after restoration we sampled the vegetation and seed bank in a total of 96 plots located in 12 recovered grasslands in the Great Hungarian Plain. In each recovered grassland stand we designated a mown (mown from Year 1 to Year 8) and an abandoned sample site (mown from Year 1 to Year 3 then abandoned from Year 4 to Year 8). Mown and abandoned sites showed divergent vegetation and seed bank development. Abandonment led to the decline of sown grasses and higher cover of weeds, especially in the alkaline grasslands. Our study confirmed that seed bank has a limited contribution to the maintenance of biodiversity in both grassland types. We found that five years of abandonment had a larger effect on the seed bank than on the vegetation. We stress that long-term management is crucial for controlling the emergence of the weeds from their dense seed bank in restored grasslands.Implications for practiceSeed sowing of grass mixtures can be a feasible tool for restoring grasslands at large scales. However, the developed vegetation usually has low biodiversity and a high seed density of weeds is typical in the soil seed bank even several years after the restoration. Therefore, post-restoration management is necessary for suppressing weeds both aboveground and belowground.We recommend to design the long-term management of the sites subjected to grassland restoration already in the planning phase of the restoration projects and ensure that the management plan is ecologically and economically feasible.We recommend to complement the monitoring of vegetation with the analysis of soil seed bank for evaluating restoration success.
Bioconjugation of AuNPs with HPV 16/18 E6 antibody through physical adsorption technique
Authors: Mwai Lucy Muthoni , Kyama Mutinda C. , Ngugi Caroline W. , Walong Edwin 
Published: January 2020

AbstractGold nanoparticle (AuNP) bioconjugates are increasingly being utilised in biomedicine due to their low toxicity on biological tissues and unique electronic and chemical properties. They have been utilised in several biological applications namely manufacture of nanomaterials, biosensing, electron microscopy and drug delivery systems. Particularly, immuno-assays often employ gold nanoparticles (AuNPs) to enhance detection of a biological component. This paper presents a study on the bioconjugation of AuNPs with Horse Radish Peroxidase conjugated Human Papilloma Virus 16/18 Early 6 antibodies (CIP5) against Early 6 (E6) oncoprotein that is overexpressed in cervical carcinoma progression through physical adsorption. This bioconjugate can be employed in diagnostic immunoassay for cervical cancer screening. The study also demonstrated that the antibody pI, gold colloidal solution pH and amount of antibody determine the generation of stable Antibody–AuNPs bioconjugates.
Patterns of DNA variation between the autosomes, the X chromosome and the Y chromosome inBos taurusgenome
Authors: Czech Bartosz , Guldbrandtsen Bernt , Szyda Joanna 
Published: January 2020

ABSTRACTThe new ARS-UCD1.2 assembly of the bovine genome has considerable improvements. That might be assumed that a more accurate identification of patterns of genetic variation can be achieved with it. We explored differences in genetic variation between autosomes, the X chromosome, and the Y chromosome. In particular, densities of variants, annotation, lengths (only for InDels), nucleotide divergence, and Tajima’s D statistic between chromosomes. Whole-genome DNA sequences of 217 individuals representing different cattle breeds were examined. The analysis included the alignment to the new reference genome and variant calling. 23,655,295 SNPs and 3,758,781 InDels were detected. In contrast to autosomes, both sex chromosomes had negative values of Tajima’s D and lower nucleotide divergence. That implies a correlation between nucleotide diversity and recombination rate, which is obviously reduced for sex chromosomes. Moreover, accumulation of nonsynonymous mutations on the Y chromosome could be associated with loss of recombination. Also, the relatively lower effective population size for sex chromosomes leads to a lower expected density of variants.
Deciphering the Signaling Network Landscape of Breast Cancer Improves Drug Sensitivity Prediction
Authors: Tognetti Marco , Gabor Attila , Yang Mi , Cappelletti Valentina , Windhager Jonas , Charmpi Konstantina , de Souza Natalie , Beyer Andreas , Picotti Paola , Saez-Rodriguez Julio , Bodenmiller Bernd 
Published: January 2020

ABSTRACTAlthough genetic and epigenetic abnormalities in breast cancer have been extensively studied, it remains difficult to identify those patients who will respond to particular therapies. This is due in part to our lack of understanding of how the variability of cellular signaling affects drug sensitivity. Here, we used mass cytometry to characterize the single-cell signaling landscapes of 62 breast cancer cell lines and five lines from healthy tissue. We quantified 34 markers in each cell line upon stimulation by the growth factor EGF in the presence or absence of five kinase inhibitors. These data – on more than 80 million single cells from 4,000 conditions – were used to fit mechanistic signaling network models that provide unprecedented insights into the biological principles of how cancer cells process information. Our dynamic single-cell-based models more accurately predicted drug sensitivity than static bulk measurements for drugs targeting the PI3K-MTOR signaling pathway. Finally, we identified genomic features associated with drug sensitivity by using signaling phenotypes as proxies, including a missense mutation inDDIT3predictive of PI3K-inhibition sensitivity. This provides proof of principle that single-cell measurements and modeling could inform matching of patients with appropriate treatments in the future.One-linerSingle-cell proteomics coupled to perturbations improves accuracy of breast tumor drug sensitivity predictions and reveals mechanisms of sensitivity and resistance.HIGHLIGHTSMass cytometry study of signaling responses of 62 breast cancer cell lines and five lines from healthy tissue to EGF stimulation with or without perturbation with five kinase inhibitors.Single-cell signaling features and mechanistic signaling network models predicted drug sensitivity.Mechanistic signaling network models deepen the understanding of drug resistance and sensitivity mechanisms.We identify drug sensitivity-predictive genomic features via proxy signaling phenotypes.
An anti-amyloidogenic treatment to specifically block the consolidation of traumatic events in mouse
Authors: López-García Paula , de Mingo Daniel Ramírez , McGreevy Kerry R. , Pallé Anna , Popiel Helena Akiko , Santi Andrea , Nagai Yoshitaka , Trejo José Luís , Carrión-Vázquez Mariano 
Published: January 2020

AbstractPost-traumatic stress disorder (PTSD) is a mental health disorder triggered by the exposure to a traumatic event that manifests with anguish, intrusive memories and negative mood changes. So far, there is no efficient treatment for PTSD other than symptomatic palliative care. Based on the implication of the functional amyloid cytoplasmic polyadenylation element binding protein-3 (CPEB3) in the consolidation of memory, we propose its active amyloid state as a possible therapeutic target by blocking the consolidation of traumatic memories through polyglutamine binding peptide 1 (QBP1), an inhibitor of the amyloid oligomerization previously investigated inDrosophila.To test this idea in mammals, here we have developed a transgenic mouse that constitutively expresses QBP1 peptide. We first assessed the innocuousness of this peptide for the normal development of the animal, which also showed normal locomotor activity and anxiety. By performing a battery of standard memory paradigms, we then showed that hippocampal-dependent and aversive memories were impaired in the QBP1 mice. Furthermore, protein expression in the hippocampi of experienced mice showed that QBP1 mice do not increase their levels of amyloid oligomerization, evincing the blockade of the CPEB3 protein in its inactive state. The ability of QBP1 to block aversive memories in mice represents the proof of concept of a novel pharmacological approach for prophylaxis and therapy of acute stress and post-traumatic stress disorders.