bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiology and lipid accumulation capacity of differentYarrowia lipolyticaandRhodosporidium toruloidesstrains on glycerol
Authors: Azambuja Suellen Patricia Held , Bonturi Nemailla , Miranda Everson Alves , Gombert Andreas Karoly 
Published: March 2018

AbstractObjectiveTo compare physiological and process parameters, as well as lipid accumulation capacity, of six strains ofYarrowia lipolyticaand two strains ofRhodosporidium toruloidesin media containing glycerol as the main carbon and energy source.ResultsThe strainsY. lipolyticaIMUFRJ 50678, Po1g, W29 and CCT 5443 displayed very similar physiological parameters, with µmax,andaverage values of 0.31 h−1, 0.53 (g DW/g S), 0.60 (g S/g DW.h) and 0.46 (g DW/g S), respectively. The two strains ofR. toruloidespresented physiological and process parameters with no significant difference, with average values of 0.084 h−1, 0.53 (g DW/g S), 0.17 (g S/g DW.h) and 0.44 (g DW/g S). Among allY. lipolyticastrains,Y. lipolyticaCCT 5443 strain presented the highestYLip/S, 0.054 (g Lip/g S), andPLipof 0.040 (g Lip/l.h). Among all investigated strains (Y. lipolyticaandR. toruloides), the yeastR. toruloidesCCT 7815 displayed the highest lipid accumulation capacity, withYLip/Sequal to 0.11 (g Lip/g S) andPLipequal to 0.10 (g Lip/l.h).ConclusionAmong all strains investigated in our study, the yeast strainR. toruloidesCCT 7815 presents the most promising characteristics for industrial single cell oil production.List of abbreviationsDWdry weight (g/l)Liplipid (g/l)PLiplipid productivity (g Lip/l.h)maximum specific substrate consumption rate (g S/g DW.h)Ssubstrate (g/l)YLip/Slipid yield on substrate (g Lip/g S)biomass yield on substrate during the exponential growth phase (g DW/g S)global biomass yield on substrate (g DW/g S)µmaxmaximum specific growth rate (h−1)
Species- and C-terminal linker-dependent variations in the dynamic behavior of FtsZ on membranesin vitro
Authors: Sundararajan Kousik , Vecchiarelli Anthony , Mizuuchi Kiyoshi , Goley Erin D. 
Published: March 2018

SummaryBacterial cell division requires the assembly of FtsZ protofilaments into a dynamic structure called the ‘Z-ring’. The Z-ring recruits the division machinery and directs local cell wall remodeling for constriction. The organization and dynamics of protofilaments within the Z-ring coordinate local cell wall synthesis during cell constriction, but their regulation is largely unknown. The disordered C-terminal linker (CTL) region ofCaulobacter crescentusFtsZ (CcFtsZ) regulates polymer structure and turnover in solutionin vitro, and regulates Z-ring structure and activity of cell wall enzymesin vivo. To investigate the contributions of the CTL to the polymerization properties of FtsZ on its physiological platform, the cell membrane, we reconstitutedCcFtsZ polymerization on supported lipid bilayers (SLB) and visualized polymer dynamics and structure using total internal reflection fluorescence microscopy. UnlikeE. coliFtsZ protofilaments that organized into large, bundled patterns,CcFtsZ protofilaments assembled into small, dynamic clusters on SLBs. Moreover,CcFtsZ lacking its CTL formed large networks of straight filament bundles that underwent slower turnover than the dynamic clusters of wildtype FtsZ. Ourin vitrocharacterization provides novel insights into species- and CTL-dependent differences between FtsZ assembly properties that are relevant to Z-ring assembly and function on membranesin vivo.
Epidermal YAP Activity Drives Canonical WNT16/β-catenin Signaling to Promote Keratinocyte Proliferation in vitro and in the Murine Skin
Authors: Mendoza-Reinoso Veronica , Beverdam Annemiek 
Published: March 2018

ABSTRACTThe skin constantly self-renews throughout adult life. Wnt/β-catenin signaling plays a key role in promoting keratinocyte proliferation in the hair follicles and in the interfollicular epidermis. A recent report demonstrated that epidermal YAP activity drives β-catenin activation to promote keratinocyte proliferation in the murine skin. However, it remains unclear whether this is caused by paracrine activation of canonical Wnt signaling or through other YAP/β-catenin regulatory interactions. In the present study, we found that XAV939-inhibition of canonical WNT signaling in skin of YAP2-5SA-ΔC mice resulted in diminished β-catenin activation, reduced keratinocyte proliferation, and a mitigation of the hyperplastic abnormalities in the interfollicular epidermis, signifying a canonical WNT ligand-dependent mechanism. Our subsequent analyses determined that WNT16 is produced in response to YAP activity in keratinocytes both in vitro and in vivo, and that WNT16 drives HaCaT keratinocyte proliferation via canonical WNT16/β-catenin signaling. We conclude that under normal physiological conditions WNT16 is the paracrine WNT ligand secreted in response to epidermal YAP activity that promotes cell proliferation in the interfollicular epidermis. This study delineates a fundamental YAP-driven mechanism that controls normal skin regeneration, and that may be perturbed in human regenerative disease displaying increased YAP and WNT signaling activity.
DeepProfile: Deep learning of cancer molecular profiles for precision medicine
Authors: Dincer Ayse Berceste , Celik Safiye , Hiranuma Naozumi , Lee Su-In 
Published: March 2018

AbstractWe present the DeepProfile framework, which learns a variational autoencoder (VAE) network from thousands of publicly available gene expression samples and uses this network to encode a low-dimensional representation (LDR) to predict complex disease phenotypes. To our knowledge, DeepProfile is the first attempt to use deep learning to extract a feature representation from a vast quantity of unlabeled (i.e, lacking phenotype information) expression samples that are not incorporated into the prediction problem. We use Deep-Profile to predict acute myeloid leukemia patients’ in vitro responses to 160 chemotherapy drugs. We show that, when compared to the original features (i.e., expression levels) and LDRs from two commonly used dimensionality reduction methods, DeepProfile: (1) better predicts complex phenotypes, (2) better captures known functional gene groups, and (3) better reconstructs the input data. We show that DeepProfile is generalizable to other diseases and phenotypes by using it to predict ovarian cancer patients’ tumor invasion patterns and breast cancer patients’ disease subtypes.
AIControl: Replacing matched control experiments with machine learning improves ChIP-seq peak identification
Authors: Hiranuma Nao , Lundberg Scott M. , Lee Su-In 
Published: March 2018

AbstractChIP-seq is a technique to determine binding locations of transcription factors, which remains a central challenge in molecular biology. Current practice is to use a “control” dataset to remove background signals from a immunoprecipitation (IP) target dataset. We introduce the AlControl framework, which eliminates the need to obtain a control dataset and instead identifies binding peaks by estimating the distributions of background signals from many publicly available control ChIP-seq datasets. We thereby avoid the cost of running control experiments while simultaneously increasing the accuracy of binding location identification. Specifically, AIControl can (1) estimate background signals at fine resolution, (2) systematically weigh the most appropriate control datasets in a data-driven way, (3) capture sources of potential biases that may be missed by one control dataset, and (4) remove the need for costly and time-consuming control experiments. We applied AIControl to 410 IP datasets in the ENCODE ChIP-seq database, using 440 control datasets from 107 cell types to impute background signal. Without using matched control datasets, AIControl identified peaks that were more enriched for putative binding sites than those identified by other popular peak callers that used a matched control dataset. We also demonstrated that our framework identifies binding sites that recover documented protein interactions more accurately.
Reverse-engineering flow-cytometry gating strategies for phenotypic labelling and high-performance cell sorting
Authors: Becht Etienne , Simoni Yannick , Coustan-Smith Elaine , Evrard Maximilien , Cheng Yang , Ng Lai Guan , Campana Dario , Newell Evan 
Published: March 2018

AbstractMotivationRecent flow and mass cytometers generate 1,000,000 single cell datasets of dimensions 20 to 40. Many tools facilitate the discovery of new cell populations associated with diseases or physiology. These discoveries require the identification of new gating strategies, but gating strategies become exponentially harder to optimize when dimensionality increases. To facilitate this step we developed Hypergate, an algorithm which given a cell population of interest identifies a gating strategy optimized for high yield and purity.ResultsHypergate achieves higher yield and purity than human experts, Support Vector Machines and Random-Forests on public datasets. We use it to revisit some established gating strategies for the identification of Innate lymphoid cells, which identifies concise and efficient strategies that allow gating these cells with fewer parameters but higher yield and purity than the current standards. For phenotypic description, Hypergate’s outputs are consistent with fields’ knowledge and sparser than those from a competing method.Availability and ImplementationHypergate is implemented in R and available at http://github.com/ebecht/hypergate under an Open Source Initiative-compliant licence.
Bees use anthropogenic habitats despite strong natural habitat preferences
Authors: Collado Miguel Á. , Sol Daniel , Bartomeus Ignasi 
Published: March 2018

ABSTRACTHabitat loss and alteration is widely considered one of the main drivers of the current loss of pollinator diversity. Unfortunately, we still lack a comprehensive analysis of habitat importance, use and preference for major groups of pollinators. Here, we address this gap analysing a large dataset of 15,762 bee specimens (more than 400 species) across northeast USA. We found that natural habitats sustain the highest bee diversity, with many species strongly depending on such habitats. By characterizing habitat use and preference for the 45 most abundant species, we also show that many bee species can use human-altered habitats despite exhibiting strong and clear preferences for forested habitats. However, only a few species appear to do well when the habitat has been drastically modified. We conclude that although altered environments may harbor a substantial number of species, preserving natural areas is still essential to guarantee the conservation of bee biodiversity.
Integration and segregation in Autism Spectrum Disorders modulated by age, disease, and interaction: A graph theoretic study of intrinsic functional connectivity
Authors: Harlalka Vatika , Naik Shruti , Bapi Raju S. , Vinod P.K. , Roy Dipanjan 
Published: March 2018

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 50 children between the ages of 6 and 17 years. Brain connectivity and graph theoretic methods have been particularly very useful in shedding light on the differences between high functioning autistic children compared to typically developing (TD) ones. However, very recent developments in network measures raise a cautionary note by highlighting gross under- and over-connectivity in ASD may be an oversimplified hypothesis. Thus the primary aim of our study is to investigate these notions in functional connectomics of ASD versus TD by subjecting the data to reproducibility experiments using two independent datasets.Further, we tested the hypothesis of alteration in network segregation and integration in the ASD subjects. We have analyzed the resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data from the University of California Los Angeles (UCLA) multimodal connectivity database (n=42 ASD, n=37 TD) and rs-fMRI data from the Autism Brain Imaging Data Exchange (ABIDE) (n=187 ASD, n=176 TD) dataset. We assessed the differences in connection strength between TD and ASD subjects. We also performed graph theoretical analysis to analyze the effect of disease on various network measures. Further, using the larger ABIDE dataset, we performed two-factor ANOVA test, to study the effect of age, disease and their interaction by classifying the TD and ASD participants into two cohorts: children (9-12 years, n=73 TD and n=87 ASD) and adolescents (13-16 years, n=103 TD and n=100 ASD). In ASD, we show the existence of atypical connectivity within and between functional networks as compared to TD. We also found in ASD both hypo-and hyper-connectivity within functional networks such as the default mode network (DMN). Further, graph theoretic analysis showed that there is significant effect of age and disease on modularity, clustering coefficient, and local efficiency. We also identified specific areas within the DMN, sensorimotor, visual and attention networks that are affected by age, disease and their interaction. Overall, our findings suggest that maturation, disease and their interaction are critical for unraveling the biological basis and developmental trajectory in ASD and other neuropsychiatric disorders.
Decomposing the subclonal structure of tumors with two-way mixture models on copy number aberrations
Authors: Tai An-Shun , Peng Chien-Hua , Peng Shih-Chi , Hsieh Wen-Ping 
Published: March 2018

AbstractMultistage tumorigenesis is a dynamic process characterized by the accumulation of mutations. Thus, a tumor mass is composed of genetically divergent cell subclones. With the advancement of next-generation sequencing (NGS), mathematical models have been recently developed to decompose tumor subclonal architecture from a collective genome sequencing data. Most of the methods focused on single-nucleotide variants (SNVs). However, somatic copy number aberrations (CNAs) also play critical roles in carcinogenesis. Therefore, further modeling subclonal CNAs composition would hold the promise to improve the analysis of tumor heterogeneity and cancer evolution. To address this issue, we developed a two-way mixture Poisson model, named CloneDeMix for the deconvolution of read-depth information. It can infer the subclonal copy number, mutational cellular prevalence (MCP), subclone composition, and the order in which mutations occurred in the evolutionary hierarchy. The performance of CloneDeMix was systematically assessed in simulations. As a result, the accuracy of CNA inference was nearly 93% and the MCP was also accurately restored. Furthermore, we also demonstrated its applicability using head and neck cancer samples from TCGA. Our results inform about the extent of subclonal CNA diversity, and a group of candidate genes that probably initiate lymph node metastasis during tumor evolution was also discovered. Most importantly, these driver genes are located at 11q13.3 which is highly susceptible to copy number change in head and neck cancer genomes. This study successfully estimates subclonal CNAs and exhibit the evolutionary relationships of mutation events. By doing so, we can track tumor heterogeneity and identify crucial mutations during evolution process. Hence, it facilitates not only understanding the cancer development but finding potential therapeutic targets. Briefly, this framework has implications for improved modeling of tumor evolution and the importance of inclusion of subclonal CNAs.
The neuronal ceroid lipofuscinosis protein Cln7 regulates neural development from the post-synaptic cell
Authors: Connolly Kyle J. , O’Hare Megan B. , Mohammed Alamin , Aitchison Katelyn M. , Anthoney Niki C. , Taylor Matthew J. , Stewart Bryan A. , Tuxworth Richard I. , Tear Guy 
Published: March 2018

AbstractThe neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, monogenic neurodegenerative disorders with an early onset in infancy or childhood. Despite identification of the genes disrupted in each form of the disease, their normal cellular role and how their deficits lead to disease pathology is not fully understood. Cln7, a major facilitator superfamily domain-containing protein, is affected in a late infantile-onset form of NCL. Using the Drosophila larval neuromuscular junction as a model to study neural development, we demonstrate that Cln7 is required for the normal growth of synapses. In a Cln7 mutant, synapses fail to develop fully leading to reduced function and behavioral changes with dysregulation of TOR activity. Cln7 expression is restricted to the post-synaptic cell and the protein localizes to vesicles immediately adjacent to the post-synaptic membrane. Our data suggest an involvement for Cln7 in regulating trans-synaptic communication.
The role of stochastic sequestration dynamics for intrinsic noise filtering in signaling network motifs
Authors: Paul Debdas , Radde Nicole 
Published: March 2018

AbstractThe relation between design principles of signaling network motifs and their robustness against intrinsic noise still remains illusive. In this work we investigate the role of cascading for coping with intrinsic noise due to stochasticity in molecular reactions. We use stochastic approaches to quantify fluctuations in the terminal kinase of phosphorylation-dephosphorylation cascade motifs and demonstrate that cascading highly affects these fluctuations. We show that this purely stochastic effect can be explained by time-varying sequestration of upstream kinase molecules. In particular, we discuss conditions on time scales and parameter regimes which lead to a reduction of output fluctuations. Our results are put into biological context by adapting rate parameters of our modeling approach to biologically feasible ranges for general binding-unbinding and phosphorylation-dephosphorylation mechanisms. Overall, this study reveals a novel role of stochastic sequestration for dynamic noise filtering in signaling cascade motifs.
DNA methylation age acceleration and risk factors for Alzheimer’s disease
Authors: McCartney Daniel L , Stevenson Anna J , Walker Rosie M , Gibson Jude , Morris Stewart W , Campbell Archie , Murray Alison D , Whalley Heather C , Porteous David J , McIntosh Andrew M , Evans Kathryn L , Deary Ian J , Marioni Riccardo E 
Published: March 2018

AbstractINTRODUCTIONThe ‘epigenetic clock’ is a DNA methylation-based estimate of biological age and is correlated with chronological age – the greatest risk factor for Alzheimer’s disease (AD). Genetic and environmental risk factors exist for AD, several of which are potentially modifiable. Here, we assess the relationship associations between the epigenetic clock and AD risk factors.METHODSLinear mixed modelling was used to assess the relationship between age acceleration (the residual of biological age regressed onto chronological age) and AD risk factors relating to cognitive reserve, lifestyle, disease, and genetics in the Generation Scotland study (n=5,100).RESULTSWe report significant associations between the epigenetic clock and BMI, total:HDL cholesterol ratios, socioeconomic status, and smoking behaviour (Bonferroni-adjusted P<0.05).DISCUSSIONAssociations are present between environmental risk factors for AD and age acceleration. Measures to modify such risk factors might improve the risk profile for AD and the rate of biological ageing. Future longitudinal analyses are therefore warranted.
Can Actin Depolymerization Actually Result in Increased Plant Resistance to Pathogens?
Authors: Krutinová Hana , Trdá Lucie , Kalachova Tetiana , Lamparová Lucie , Pospíchalová Romana , Dobrev Petre I. , Malínská Kateřina , Burketová Lenka , Valentová Olga , Janda Martin 
Published: March 2018

Introductory paragraphThe integrity of the actin cytoskeleton is essential for plant immune signalling1. Consequently, it is generally assumed that actin disruption reduces plant resistance to pathogen attack2-4. However, in a previous study, it was shown that actin depolymerisation triggers the salicylic acid (SA) signalling pathway5, which is interesting because increased SA is associated with enhanced plant resistance to pathogen attack6,7. Here, we attempt to resolve this seeming inconsistency by showing that the relationship between actin depolymerization and plant resistance is more complex than currently thought. We investigate the precise nature of this relationship using two completely different plant pathosystems: i) a model plant (Arabidopsis thaliana) and a bacterial pathogen (Pseudomonas syringae), and ii) an important crop (Brassica napus) and a fungal pathogen (Leptosphaeria maculans). We demonstrate that actin depolymerization induces a dramatic increase in SA levels and that the increased SA is biosynthesized by the isochorismate synthase pathway. In both pathosystems, this phenomenon leads to increased plant resistance.
Mobile genetic element-encoded hypertolerance to copper protectsStaphylococcus aureusfrom killing by host phagocytes
Authors: Zapotoczna Marta , Pelicioli-Riboldi Gus , Moustafa Ahmed M , Dickson Elizabeth , Narechania Apurva , Morrissey Julie A. , Planet Paul J. , Holden Matthew T.G. , Waldron Kevin J. , Geoghegan Joan A. 
Published: March 2018

AbstractPathogens are exposed to toxic levels of copper during infection and copper tolerance may be a general virulence mechanism used by bacteria to resist host defences. In support of this, inactivation of copper-exporter genes has been found to reduce the virulence of bacterial pathogensin vivo. Here we investigate the role of copper-hypertolerance in methicillin resistantStaphylococcus aureus. We show that a copper-hypertolerance locus (copB-mco), carried on a mobile genetic element, is prevalent in a collection of invasiveS. aureusstrains and more widely among clonal complex 22, 30 and 398 strains. ThecopBandmcogenes encode a copper efflux pump and a multicopper oxidase, respectively. Isogenic mutants lackingcopBormcohad impaired growth in subinhibitory concentrations of copper. Transfer of acopB-mcoencoding plasmid to a naive clinical isolate resulted in a gain of copper hypertolerance and enhanced bacterial survival inside primed macrophages. ThecopBandmcogenes were upregulated within infected macrophages and their expression was dependent on the copper sensitive operon repressor CsoR. IsogeniccopBandmcomutants were impaired in their ability to persist intracellularly in macrophages and were less resistant to phagocytic killing in human blood than the parent strain. The importance of copper-regulated genes in resistance to phagocytic killing was further elaborated using mutants expressing a copper-insensitive variant of CsoR. Our findings suggest that the gain of mobile genetic elements carrying copper-hypertolerance genes contributes to the evolution of virulent strains ofS. aureus, better equipped to resist killing by host immune cells.