bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regularized selection indices for breeding value prediction using hyper-spectral image data
Authors: Lopez-Cruz Marco , Olson Eric , Rovere Gabriel , Crossa Jose , Dreisigacker Susanne , Mondal Suchismita , Singh Ravi , de los Campos Gustavo 
Published: May 2019

AbstractHigh-throughput phenotyping (HTP) technologies can produce data on thousands of phenotypes per unit being monitored. These data can be used to breed for economically and environmentally relevant traits (e.g., drought tolerance); however, incorporating high-dimensional phenotypes in genetic analyses and in breeding schemes poses important statistical and computational challenges. To address this problem, we developed regularized selection indices; the methodology integrates techniques commonly used in high-dimensional phenotypic regressions (including penalization and rank-reduction approaches) into the selection index (SI) framework. Using extensive data from CIMMYT’s (International Maize and Wheat Improvement Center) wheat breeding program we show that regularized SIs derived from hyper-spectral data offer consistently higher accuracy for grain yield than those achieved by canonical SIs, and by vegetation indices commonly used to predict agronomic traits. Regularized SIs offer an effective approach to leverage HTP data that is routinely generated in agriculture; the methodology can also be used to conduct genetic studies using high-dimensional phenotypes that are often collected in humans and model organisms including body images and whole-genome gene expression profiles.
Significant control of Zika infection in macaques depends on the elapsing time after dengue exposure
Authors: Serrano-Collazo Crisanta , Pérez-Guzmán Erick X. , Pantoja Petraleigh , Hassert Mariah A. , Rodríguez Idia V. , Giavedoni Luis , Hodara Vida , Parodi Laura , Cruz Lorna , Arana Teresa , Martínez Melween I. , White Laura , Brien James D , de Silva Aravinda , Pinto Amelia K. , Sariol Carlos A. 
Published: May 2019

AbstractPrior exposure to a single serotype of dengue virus (DENV) predisposes individuals to severe disease upon secondary heterologous DENV infection. Here we show that the length of time between DENV/Zika (ZIKV) infections has a qualitative impact on controlling ZIKV replication. We identified limited but significant differences in the magnitude of the early humoral immune response associated with a period of twelve months but not three months of DENV convalescence. However, their role limiting ZIKV replication is not conclusive. There was no evidence of in vivo antibody-dependent amplification of ZIKV by DENV immunity in any group. We are also showing that the significant differences among groups may be linked to a pre-existing polyfunctional CD4+ T cells response (increased IFN-g and Cd107a before ZIKV infection) and to an early and continuous expansion of the CD4+ effector memory cells early on after ZIKV infection. Those significant differences were associated with a period of 12 months after DENV infection that were not observed in a span of 3-months. These results suggest that there is a window of optimal cross-protection between ZIKV and DENV with significant consequences. These results have pivotal implications while interpreting ZIKV pathogenesis in flavivirus-experimented populations, diagnostic results interpretation and vaccine designs among others.Author SummarySince its introduction in the Americas region ZIKV virus has been associated to severe birth defects. One of the questions that remains open is the role of previous dengue or any other flavivirus immunity in the pathogenesis of ZIKV and more important, if the time elapse between DENV and ZIKV play a role enhancing ZIKV pathogenesis as it is the case for subsequent DENV infections. On this work, using NHP as a model we compared the effect of a period of 12 months vs. a period of 3 months of DENV immunity in the outcome of ZIKV infection. We found that previous DENV infection, at any of the tested period of time do not induce ZIKV enhancement. More relevant are showing that when the two infection occurs at least one year apart the preexisting DENV immunity is better at controlling ZIKV replication and that the role of the neutralizing antibodies is very limited. On the contrary our results suggest that early after ZIKV infection the cellular immune response, may plays a predominant role. Our findings have critical relevance to understand the dynamic interaction between these two flavivirus, their pathogenies, diagnosis and vaccine design.
Changes in lipid composition and ultrastructure associated with functional maturation of the cuticle during adult maize leaf development
Authors: Bourgault Richard , Matschi Susanne , Vasquez Miguel , Qiao Pengfei , Sonntag Annika , Charlebois Caleb , Mohammadi Marc , Scanlon Michael J. , Smith Laurie G. , Molina Isabel 
Published: May 2019

AbstractAlthough extensive prior work has characterized cuticle composition, function, ultrastructure and development in many plant species, much remains to be learned about how these features are interrelated. Moreover, very little is known about the adult maize leaf cuticle in spite of its significance for agronomically important traits in this major crop. We analyzed cuticle composition, ultrastructure, and permeability along the developmental gradient of partially expanded adult maize leaves to probe the relationships between these features. The water barrier property is acquired at the cessation of cell expansion. Wax types and chain lengths accumulate asynchronously along the developmental gradient, while overall wax load does not vary. Cutin begins to accumulate prior to establishment of the water barrier and continues thereafter. Ultrastructurally, pavement cell cuticles consist of an epicuticular layer, a thin cuticle proper that acquires an inner, osmiophilic layer during development, and no cuticular layer. Cuticular waxes of the adult maize leaf are dominated by alkanes and wax esters localized mainly in the epicuticular layer. Establishment of the water barrier coincides with a switch from alkanes to esters as the major wax type, and the emergence of an osmiophilic (likely cutin-rich) layer of the cuticle proper.Higlight statementChemical, ultrastructural and functional analysis of cuticle development in partially expanded adult maize leaves revealed important roles for wax esters and an osmiophilic, likely cutin-rich, layer in protection from dehydration.
Multiplexed dissection of a model human transcription factor binding site architecture
Authors: Davis Jessica E. , Insigne Kimberly D. , Jones Eric M. , Hastings Quinn B , Kosuri Sriram 
Published: May 2019

AbstractIn eukaryotes, transcription factors orchestrate gene expression by binding to TF-Binding Sites (TFBSs) and localizing transcriptional co-regulators and RNA Polymerase II to cis-regulatory elements. The strength and regulation of transcription can be modulated by a variety of factors including TFBS composition, TFBS affinity and number, distance between TFBSs, distance of TFBSs to transcription start sites, and epigenetic modifications. We still lack a basic comprehension of how such variables shaping cis-regulatory architecture culminate in quantitative transcriptional responses. Here we explored how such factors determine the transcriptional activity of a model transcription factor, the c-AMP Response Element (CRE) binding protein. We measured expression driven by 4,602 synthetic regulatory elements in a massively parallel reporter assay (MPRA) exploring the impact of CRE number, affinity, distance to the promoter, and spacing between multiple CREs. We found the number and affinity of CREs within regulatory elements largely determines overall expression, and this relationship is shaped by the proximity of each CRE to the downstream promoter. In addition, while we observed expression periodicity as the CRE distance to the promoter varied, the spacing between multiple CREs altered this periodicity. Finally, we compare library expression between an episomal MPRA and a new, genomically-integrated MPRA in which a single synthetic regulatory element is present per cell at a defined locus. We observe that these largely recapitulate each other although weaker, non-canonical CREs exhibited greater activity in the genomic context.
Latent periodic process inference from single-cell RNA-seq data
Authors: Liang Shaoheng , Wang Fang , Han Jincheng , Chen Ken 
Published: May 2019

AbstractConvoluted biological processes underlie the development of multicellular organisms and diseases. Advances in scRNA-seq make it possible to study these processes from cells at various developmental stages. Achieving accurate characterization is challenging, however, particularly for periodic processes, such as cell cycles. To address this, we developed Cyclum, a novel AutoEncoder approach that characterizes circular trajectories in the high-dimensional gene expression space. Cyclum substantially improves the accuracy and robustness of cell-cycle characterization beyond existing approaches. Applying Cyclum to removing cell-cycle effects leads to substantially improved delineations of cell subpopulations, which is useful for establishing various cell atlases and studying tumor heterogeneity. Cyclum is available at https://github.com/KChen-lab/cyclum.
Establishing reference samples for detection of somatic mutations and germline variants with NGS technologies
Authors: Fang Li Tai , Zhu Bin , Zhao Yongmei , Chen Wanqiu , Yang Zhaowei , Kerrigan Liz , Langenbach Kurt , Mars Maryellen de , Lu Charles , Idler Kenneth , Jacob Howard , Yu Ying , Ren Luyao , Zheng Yuanting , Jaeger Erich , Schroth Gary , Abaan Ogan D. , Lack Justin , Shen Tsai-Wei , Talsania Keyur , Chen Zhong , Stanbouly Seta , Shetty Jyoti , Tran Bao , Meerzaman Daoud , Nguyen Cu , Petitjean Virginie , Sultan Marc , Cam Margaret , Hung Tiffany , Peters Eric , Kalamegham Rasika , Ebrahim Sahraeian Sayed Mohammad , Mohiyuddin Marghoob , Guo Yunfei , Yao Lijing , Song Lei , Lam Hugo YK , Drabek Jiri , Maestro Roberta , Gasparotto Daniela , Kõks Sulev , Reimann Ene , Scherer Andreas , Nordlund Jessica , Liljedahl Ulrika , Jensen Roderick V , Pirooznia Mehdi , Li Zhipan , Xiao Chunlin , Sherry Stephen , Kusko Rebecca , Moos Malcolm , Donaldson Eric , Tezak Zivana , Ning Baitang , Li Jing , Duerken-Hughes Penelope , Hong Huixiao , Shi Leming , Wang Charles , Xiao Wenming ,   The Somatic Working Group of SEQC-II Consortium
Published: May 2019

AbstractWe characterized two reference samples for NGS technologies: a human triple-negative breast cancer cell line and a matched normal cell line. Leveraging several whole-genome sequencing (WGS) platforms, multiple sequencing replicates, and orthogonal mutation detection bioinformatics pipelines, we minimized the potential biases from sequencing technologies, assays, and informatics. Thus, our “truth sets” were defined using evidence from 21 repeats of WGS runs with coverages ranging from 50X to 100X (a total of 140 billion reads). These “truth sets” present many relevant variants/mutations including 193 COSMIC mutations and 9,016 germline variants from the ClinVar database, nonsense mutations inBRCA1/2and missense mutations inTP53andFGFR1.Independent validation in three orthogonal experiments demonstrated a successful stress test of the truth set. We expect these reference materials and “truth sets” to facilitate assay development, qualification, validation, and proficiency testing. In addition, our methods can be extended to establish new fully characterized reference samples for the community.
Hepatitis C virus infection is inhibited by a non-canonical antiviral signaling pathway targeted by NS3-NS4A
Authors: Vazquez Christine , Tan Chin Yee , Horner Stacy M. 
Published: May 2019

AbstractThe hepatitis C virus (HCV) NS3-NS4A protease complex is required for viral replication and is the major viral innate immune evasion factor. NS3-NS4A evades antiviral innate immunity by inactivating several proteins, including MAVS, the signaling adaptor for RIG-I and MDA5, and Riplet, an E3 ubiquitin ligase that activates RIG-I. Here, we identified a Tyr-16-Phe (Y16F) change in the NS4A transmembrane domain that prevents NS3-NS4A targeting of Riplet but not MAVS. This Y16F substitution reduces HCV replication in Huh7 cells, but not in Huh-7.5 cells, known to lack RIG-I signaling. Surprisingly, deletion of RIG-I in Huh7 cells did not restore Y16F viral replication. Rather, we found that Huh-7.5 cells lack Riplet expression and that addition of Riplet to these cells reduced HCV Y16F replication. In addition, IRF3 deletion in Huh7 cells was sufficient to restore HCV Y16F replication, and the Y16F protease lacked the ability to prevent IRF3 activation or interferon induction. Taken together, these data reveal that the NS4A Y16 residue regulates a non-canonical Riplet-IRF3-dependent, but RIG-I-MAVS-independent, signaling pathway that limits HCV infection.ImportanceThe HCV NS3-NS4A protease complex facilitates viral replication by cleaving and inactivating the antiviral innate immune signaling proteins MAVS and Riplet, which are essential for RIG-I activation. NS3-NS4A therefore prevents IRF3 activation and interferon induction during HCV infection. Here, we uncover an amino acid residue within the NS4A transmembrane domain that is essential for inactivation of Riplet, but does not affect MAVS cleavage by NS3-NS4A. Our study reveals that Riplet is involved in a RIG-I- and MAVS-independent signaling pathway that activates IRF3 and that this pathway is normally inactivated by NS3-NS4A during HCV infection. Our study selectively uncouples these distinct regulatory mechanisms within NS3-NS4A and defines a new role for Riplet in the antiviral response to HCV. As Riplet is known to be inhibited by other RNA viruses, such as such influenza A virus, this innate immune signaling pathway may also be important in controlling other RNA virus infections.
Charge and hydrophobicity are key features in sequence-trained machine learning models for predicting the biophysical properties of clinical-stage antibodies
Authors: Hebditch Max , Warwicker Jim 
Published: May 2019

AbstractImproved understanding of properties that mediate protein solubility and resistance to aggregation are important for developing biopharmaceuticals, and more generally in biotechnology and synthetic biology. Recent acquisition of large datasets for antibody biophysical properties enables the search for predictive models. In this report, machine learning methods are used to derive models for 12 biophysical properties. A physicochemical perspective is maintained in analysing the models, leading to the observation that models cluster largely according to charge (cross-interaction measurements) and hydrophobicity (self-interaction methods). These two properties also overlap in some cases, for example in a new interpretation of variation in hydrophobic interaction chromatography. Since the models are developed from differences of antibody variable loops, the next stage is to extend models to more diverse protein sets.AvailabilityThe web application for the sequence based algorithms are available on the protein-sol webserver, at https://protein-sol.manchester.ac.uk/abpred, with models and virtualisation software available at https://protein-sol.manchester.ac.uk/software.
Overexpression of osmosensitive Ca2+-activated channel TMEM63B promotes migration in HEK293T cells
Authors: Marques Marta C. , Albuquerque Inês S. , Vaz Sandra H. , Bernardes Gonçalo J. L. 
Published: May 2019

AbstractThe recent discovery of the osmosensitive calcium (Ca2+) channel OSCA has revealed the potential mechanism by which plant cells sense diverse stimuli. Osmosensory transporters and mechanosensitive channels can detect and respond to osmotic shifts that play an important role in active cell homeostasis. TMEM63 family of proteins are described as the closest homologues of OSCAs. Here, we characterize TMEM63B, a mammalian homologue of OSCAs, recently classified as mechanosensitive. In HEK293T cells TMEM63B localizes to the plasma membrane and is associated to F-actin. This Ca2+-activated channel specifically induces Ca2+ influx across the membrane in response to extracellular Ca2+ concentration and hyperosmolarity. In addition, overexpression of TMEM63B in HEK293T cells significantly enhanced cell migration and wound healing. The link between Ca2+ osmosensitivity and cell migration might help to establish TMEM63B’s pathogenesis, for example in cancer in which it is frequently overexpressed.
Identification of candidate flowering and sex genes in white Guinea yam (D. rotundata Poir.) by SuperSAGE transcriptome profiling
Authors: Girma Gezahegn , Natsume Satoshi , Carluccio Anna Vittoria , Takagi Hiroki , Matsumura Hideo , Uemura Aiko , Muranaka Satoru , Takagi Hiroko , Stavolone Livia , Gedil Melaku , Spillane Charles , Terauchi Ryohei , Tamiru Muluneh 
Published: May 2019

AbstractDioecy (distinct male and female individuals) combined with scarce to non-flowering are common features of cultivated yam (Dioscorea spp.). However, the molecular mechanisms underlying flowering and sex determination in Dioscorea are unknown. We conducted SuperSAGE transcriptome profiling of male, female and monoecious individuals to identify flowering and sex-related genes in white Guinea yam (D. rotundata). SuperSAGE analysis generated a total of 20,236 unique tags, of which 13,901 were represented by a minimum of 10 tags. Of these, 88 tags were significantly differentially expressed in male, female and monoecious plants. Of the 88 differentially expressed SuperSAGE tags, 18 corresponded to genes previously implicated in flower development and sex determination in multiple plant species. We validated the SuperSAGE data with quantitative real-time PCR (qRT-PCR)-based analysis of the expression of four candidate genes. Our findings suggest that mechanisms of flowering and sex determination are likely conserved in Dioscorea. We further investigated the flowering patterns of 1938 D. rotundata accessions representing diverse geographical origins over two years, revealing that over 85% of the accessions are either male or non-flowering, and that less than 15% are female, while monoecious plants are rare. Intensity of flowering appeared to be a function of sex, with male plants flowering more abundantly than female ones. Candidate genes identified in this study can be targeted with the aim to induce regular flowering in poor to non-flowering cultivars. Findings of the study provide important inputs for further studies aiming to overcome the challenge of flowering in yams and to improve the efficiency of yam breeding.
Using distant supervision to augment manually annotated data for relation extraction
Authors: Su Peng , Li Gang , Wu Cathy , Vijay-Shanker K. 
Published: May 2019

AbstractSignificant progress has been made in applying deep learning on natural language processing tasks recently. However, deep learning models typically require a large amount of annotated training data while often only small labeled datasets are available for many natural language processing tasks in biomedical literature. Building large-size datasets for deep learning is expensive since it involves considerable human effort and usually requires domain expertise in specialized fields. In this work, we consider augmenting manually annotated data with large amounts of data using distant supervision. However, data obtained by distant supervision is often noisy, we first apply some heuristics to remove some of the incorrect annotations. Then using methods inspired from transfer learning, we show that the resulting models outperform models trained on the original manually annotated sets.
A Circuit Model of Auditory Cortex
Authors: Park Youngmin , Geffen Maria N. 
Published: May 2019

AbstractThe mammalian sensory cortex is composed of multiple types of inhibitory and excitatory neurons, which form sophisticated microcircuits for processing and transmitting sensory information. Despite rapid progress in understanding the function of distinct neuronal populations, the parameters of connectivity that are required for the function of these microcircuits remain unknown. Recent studies found that two most common inhibitory interneurons, parvalbumin- (PV) and somatostatin-(SST) positive interneurons control sound-evoked responses, temporal adaptation and network dynamics in the auditory cortex (AC). These studies can inform our understanding of parameters for the connectivity of excitatory-inhibitory cortical circuits. Specifically, we asked whether a common microcircuit can account for the disparate effects found in studies by different groups. By starting with a cortical rate model, we find that a simple current-compensating mechanism accounts for the experimental findings from multiple groups. They key mechanisms are two-fold. First, PVs compensate for reduced SST activity when thalamic inputs are strong with less compensation when thalamic inputs are weak. Second, SSTs are generally disinhibited by reduced PV activity regardless of thalamic input strength. These roles are augmented by plastic synapses. These differential roles reproduce the differential effects of PVs and SSTs in stimulus-specific adaptation, forward suppression and tuning-curve adaptation, as well as the influence of PVs on feedforward functional connectivity in the circuit. This circuit exhibits a balance of inhibitory and excitatory currents that persists on stimulation. This approach brings together multiple findings from different laboratories and identifies a circuit that can be used in future studies of upstream and downstream sensory processing.Significance StatementThe mammalian auditory cortex is composed of multiple types of inhibitory and excitatory neurons, which form sophisticated microcircuits for processing and transmitting sensory information. Distinct inhibitory neuron subtypes play distinct functions in auditory processing, but it remains unknown what simple set of underlying mechanisms is responsible for inhibitory cortical function. Here, we built minimal rate and spiking models and identified a specific set of synaptic mechanisms that could best reproduce the broad set of experimental results in the auditory cortex. The simplicity of our model provides an understanding of inhibitory cortical processing at the circuit level, which explains results from different laboratories, and provides for a novel computational framework for future studies of cortical function.
A metabolic pathway for glucosinolate activation by the human gut symbiontBacteroides thetaiotaomicron
Authors: Liou Catherine S. , Sirk Shannon J. , Diaz Camil A.C. , Klein Andrew P. , Fischer Curt R. , Higginbottom Steven K. , Sonnenburg Justin L. , Sattely Elizabeth S. 
Published: May 2019

ABSTRACTDiet is the largest source of plant-derived metabolites that influence human health. The gut microbiota can metabolize these molecules, altering their biological function. However, little is known about the gut bacterial pathways that process plant-derived molecules. Glucosinolates are well-known metabolites in brassica vegetables and metabolic precursors to cancer-preventive isothiocyanates. Here, we identify a genetic and biochemical basis for isothiocyanate formation byBacteroides thetaiotaomicron,a prominent gut commensal species. Using a genome-wide transposon insertion screen, we identified an operon required for glucosinolate metabolism inB. thetaiotaomicron.Expression of BT2159-BT2156 in a non-metabolizing relative,Bacteroides fragilis, resulted in gain of glucosinolate metabolism. We show that isothiocyanate formation requires the action of BT2158 and either BT2156 or BT2157in vitro. Monocolonization of mice with mutantBtΔ2157showed reduced isothiocyanate production in the gastrointestinal tract. These data provide insight into the mechanisms by which a common gut bacterium processes an important dietary nutrient.