bluuebunny/crossref_metadata_2025_split huggingface dataset:
The DOE JGI Metagenome Workflow
Authors: Clum Alicia , Huntemann Marcel , Bushnell Brian , Foster Brian , Foster Bryce , Roux Simon , Hajek Patrick P. , Varghese Neha , Mukherjee Supratim , Reddy T.B.K. , Daum Chris , Yoshinaga Yuko , Seshadri Rekha , Kyrpides Nikos C , Eloe-Fadrosh Emiley A. , Chen I-Min A. , Copeland Alex , Ivanova Natalia N. 
Published: October 2020

ABSTRACTThe DOE JGI Metagenome Workflow performs metagenome data processing, including assembly, structural, functional, and taxonomic annotation, and binning of metagenomic datasets that are subsequently included into theIntegrated Microbial Genomes and Microbiomes(IMG/M) comparative analysis system (I. Chen, K. Chu, K. Palaniappan, M. Pillay, A. Ratner, J. Huang, M. Huntemann, N. Varghese, J. White, R. Seshadri, et al, Nucleic Acids Rsearch, 2019) and provided for download via the Joint Genome Institute (JGI) Data Portal (https://genome.jgi.doe.gov/portal/). This workflow scales to run on thousands of metagenome samples per year, which can vary by the complexity of microbial communities and sequencing depth. Here we describe the different tools, databases, and parameters used at different steps of the workflow, to help with interpretation of metagenome data available in IMG and to enable researchers to apply this workflow to their own data. We use 20 publicly available sediment metagenomes to illustrate the computing requirements for the different steps and highlight the typical results of data processing. The workflow modules for read filtering and metagenome assembly are available as a Workflow Description Language (WDL) file (https://code.jgi.doe.gov/BFoster/jgi_meta_wdl.git). The workflow modules for annotation and binning are provided as a service to the user community athttps://img.jgi.doe.gov/submitand require filling out the project and associated metadata descriptions in Genomes OnLine Database (GOLD) (S. Mukherjee, D. Stamatis, J. Bertsch, G. Ovchinnikova, H. Katta, A. Mojica, I Chen, and N. Kyrpides, and T. Reddy, Nucleic Acids Research, 2018).IMPORTANCEThe DOE JGI Metagenome Workflow is designed for processing metagenomic datasets starting from Illumina fastq files. It performs data pre-processing, error correction, assembly, structural and functional annotation, and binning. The results of processing are provided in several standard formats, such as fasta and gff and can be used for subsequent integration into the Integrated Microbial Genome (IMG) system where they can be compared to a comprehensive set of publicly available metagenomes. As of 7/30/2020 7,155 JGI metagenomes have been processed by the JGI Metagenome Workflow.
Aged Breast Extracellular Matrix Drives Mammary Epithelial Cells to an Invasive and Cancer-Like Phenotype
Authors: Bahcecioglu Gokhan , Yue Xiaoshan , Howe Erin , Guldner Ian , Stack M. Sharon , Nakshatri Harikrishna , Zhang Siyuan , Zorlutuna Pinar 
Published: October 2020

AbstractAge is a major risk factor for cancer. While the importance of age related genetic alterations in cells on cancer progression is well documented, the effect of aging extracellular matrix (ECM) has been overlooked. Here, we show for the first time that the aging breast ECM is sufficient to drive normal mammary epithelial cells (KTB21) to a more invasive and cancer-like phenotype, while promoting motility and invasiveness in MDA-MB-231 cells. E-cadherin membrane localization was lost in KTB21 cells cultured on the decellularized breast matrix from aged mice. Cell motility, cell invasion, and inflammatory cytokine and cancer-related protein production were increased significantly on the aged matrix, and many genes related to invasion were upregulated. Strikingly, we showed using single cell RNA sequencing that the aged matrix led to enrichment of a subpopulation of KTB21 cells that highly expressed epithelial-mesenchymal transition (EMT) and invasion-related genes. Lysyl oxidase (LOX) knockdown reverted the aged matrix-induced changes to the young levels;LOXsiRNA treatment prevented the loss of E-cadherin membrane localization, and reduced cell motility, cell invasion, and cytokine and cancer-related protein production. Finally, we showed that the biophysical, mechanical and biochemical properties of the breast ECM were altered dramatically upon aging. Analyzing these factors and studying the differential response of the epithelial cells to young and aged ECMs could lead to identification of new targets for cancer treatment and could pave the way for the discovery of new therapeutic options.
Genome-wide SNP genotyping of DNA pools identifies untapped landraces and genomic regions that could enrich the maize breeding pool
Authors: Arca Mariangela , Gouesnard Brigitte , Mary-Huard Tristan , Le Paslier Marie-Christine , Bauland Cyril , Combes Valérie , Madur Delphine , Charcosset Alain , Nicolas Stéphane D. 
Published: October 2020

ABSTRACTMaize landraces preserved in genebanks have a large genetic diversity that is still poorly characterized and underexploited in modern breeding programs. Here, we genotyped DNA pools from 156 American and European landraces with a 50K SNP Illumina array to study the effect of both human selection and environmental adaptation on the genome-wide diversity of maize landraces. Genomic diversity of landraces varied strongly in different parts of the genome and with geographic origin. We detected selective footprints between landraces of different geographic origin in genes involved in the starch pathway (Su1, Waxy1), flowering time (Zcn8, Vgt3, ZmCCT9) and tolerance to abiotic and biotic stress (ZmASR, NACanddkggenes). Landrace diversity was compared to that of (i) 327 inbred lines representing American and European diversity (“CK lines) and (ii) 103 new lines derived directly from landraces (“DH-SSD lines”). We observed limited diversity loss or selective sweep between landraces and CK lines, except in peri-centromeric regions. However, analysis of modified Roger’s distance between landraces and the CK lines showed that most landraces were not closely related to CK lines. Assignment of CK lines to landraces using supervised analysis showed that only a few landraces, such as Reid’s Yellow Dent, Lancaster Surecrop and Lacaune, strongly contributed to modern European and American breeding pools. Haplotype diversity of CK lines was more enriched by DH-SSD lines that derived from the landraces with no related lines and the lowest contribution to CK lines. Our approach opens an avenue for the identification of promising landraces for pre-breeding.SIGNIFICANCE STATEMENTSMaize landraces are a valuable source of genetic diversity for addressing the challenges of climate change and the requirements of low input agriculture as they have been long selected to be well adapted to local agro-climatic conditions and human uses. However, they are underutilized in modern breeding programs because they are poorly characterized, genetically heterogeneous and exhibit poor agronomic performance compared to elite hybrid material. In this study, we developed a high-throughput approach to identify landraces that could potentially enlarge the genetic diversity of modern breeding pools. We genotyped DNA pools from landraces using 50K array technology, which is widely used by breeders to characterize the genetic diversity of inbred lines. To identify landraces that could enrich the modern maize germplasm, we estimated their contribution to inbred lines using supervised analysis and a new measurement of genetic distance.
Evolution of anticipatory effects mediated by epigenetic changes
Authors: Kronholm Ilkka 
Published: October 2020

AbstractAnticipatory effects mediated by epigenetic changes occur when parents modify the phenotype of their offspring by making epigenetic changes in their gametes guided by information from an environmental cue. To investigate when do anticipatory effects mediated by epigenetic changes evolve in a fluctuating environment, I use an individual based simulation model with explicit genetic architecture. The model allows for the population to respond to environmental changes by evolving plasticity, bet-hedging, or by tracking the environment with genetic adaptation, in addition to the evolution of anticipatory effects. The results show that anticipatory effects evolve when the environmental cue provides reliable information about the environment and the environment changes at intermediate rates, provided that fitness costs of anticipatory effects are rather low. Moreover, evolution of anticipatory effects is quite robust to different genetic architectures when reliability of the environmental cue is high. Anticipatory effects always give smaller fitness benefits than within generation plasticity, suggesting a possible reason for generally small observed anticipatory effects in empirical studies.
Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy
Authors: Verweij Marieke , Hansen Scott G. , Iyer Ravi , John Nessy , Malouli Daniel , Morrow David , Scholz Isabel , Womack Jennie , Abdulhaqq Shaheed , Gilbride Roxanne M. , Hughes Colette M. , Ventura Abigail B. , Ford Julia C. , Selseth Andrea N. , Oswald Kelli , Shoemaker Rebecca , Berkemeier Brian , Bosche William J. , Hull Michael , Shao Jason , Sacha Jonah B. , Axthelm Michael K. , Edlefsen Paul T. , Lifson Jeffrey D. , Picker Louis J. , Früh Klaus 
Published: October 2020

AbstractStrain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8+T cells that recognize peptide epitopes presented by major histocompatibility complex (MHC)-II and MHC-E molecules, instead of MHC-Ia, and are uniquely able to mediate stringent control and subsequent clearance of highly pathogenic SIV in ∼50% of vaccinated rhesus macaques (RMs). We show that the MHC-E ligand VMAPRTLLL (VL9), encoded by the Rh67 gene (or its HCMV UL40 counterpart) is required for recognition of RhCMV-infected fibroblasts by MHC-E-restricted CD8+T cells via its ability to promote intracellular MHC-E transport. Moreover, deletion of Rh67 from 68-1 RhCMV/SIV vectors, or mutation of its embedded VL9 ligand, abrogated induction of MHC-E-restricted CD8+T cell responses, leaving responses that exclusively target MHC-II-restricted epitopes. These MHC-II-presented CD8+T cell responses, though comparable in response magnitude and functional differentiation to responses arising from the efficacious 68-1 vector, did not protect RMs against SIV challenge, indicating that Rh67/UL40-enabled direct priming of MHC-E-targeted CD8+T cells is a crucial element of RhCMV/SIV vaccine efficacy.One Sentence SummaryA cytomegalovirus protein (Rh67/UL40) that upregulates MHC-E expression on RhCMV/SIV-vector infected cells is required for induction of MHC-E-restricted CD8+T cells and for protection against SIV.
Circulating Clonally Expanded T Cells Reflect Functions of Tumor Infiltrating T Cells
Authors: Lucca Liliana , Axisa Pierre-Paul , Lu Benjamin , Harnett Brian , Jessel Shlomit , Zhang Le , Raddassi Khadir , Zhang Lin , Olino Kelly , Clune James , Singer Meromit , Kluger Harriet M. , Hafler David A. 
Published: October 2020

AbstractUnderstanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed from matched tumor and blood from patients with metastatic melanoma at the single cell level. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by T cells present only in tumor. Finally, genes associated with a high degree of blood-tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs, identified by TCRs shared with T cells in tumors, have unique transcriptional expression patterns that may have utility for the interrogation of T cell function in cancer immunotherapy.SummaryCombining transcriptomic and TCRαβ repertoire analysis of circulating and tumor-infiltrating CD8 T cells from patients with metastatic melanoma, we identify a blood-based population with effector properties that reflect those of clonally related tumor-resident T cells.
The maize Aliphatic Suberin Feruloyl Transferase genes affect leaf water movement but are dispensable for bundle sheath CO2concentration
Authors: Mertz Rachel A. , Ellsworth Patrick , Ellsworth Patricia , Tausta S. Lori , von Caemmerer Susanne , Berg R. Howard , Nelson Timothy , Carpita Nicholas C. , Brutnell Thomas P. , Cousins Asaph B. 
Published: October 2020

ABSTRACTC4grasses often outperform C3species under hot, arid conditions due to superior water and nitrogen use efficiencies and lower rates of photorespiration. A method of concentrating CO2around the site of carbon fixation in the bundle sheath (BS) is required to realize these gains. In NADP-malic enzyme (NADP-ME)-type C4grasses such as maize, suberin deposition in the BS cell wall is hypothesized to act as a diffusion barrier to CO2escape and O2entry from surrounding mesophyll cells. Suberin is a heteropolyester comprised of acyl-lipid-derived aliphatic and phenylpropanoid-derived aromatic components. To disrupt BS suberization, we mutated two paralogously duplicated, unlinked maize orthologues of Arabidopsis thalianaALIPHATIC SUBERIN FERULOYL TRANSFERASE, ZmAsft1andZmAsft2, using closely linkedDissociationtransposons. Loss-of-function double mutants revealed a 97% reduction in suberin-specific omega-hydroxy fatty acids without a stoichiometric decrease in ferulic acid. However, BS suberin lamellae were deficient in electron opaque material, and cohesion between the suberin lamellae and polysaccharide cell walls was attenuated in double mutants. There were no other morphological phenotypes under ambient conditions. Furthermore, there was no significant effect on net CO2assimilation at any intercellular CO2concentration, and no effect on13C isotope discrimination relative to wild type. Thus,ZmAsftexpression is not required to establish a functional CO2concentrating mechanism in in maize. Double mutant leaves exhibit elevated cell wall elasticity, transpirational, and stomatal conductance relative to WT. Thus, theZmAsftgenes are dispensable for gas exchange barrier function but may be involved in regulation of leaf water movement.One-sentence SummaryDouble mutants of two paralogously duplicated maize Aliphatic Suberin Feruloyl Transferase (ZmAsft) genes exhibit reduced aliphatic suberin content, cell wall cohesion defects, and elevated leaf transpiration, but no changes in CO2 assimilation relative to wild type.
Ontogenetic Oxycodone Exposure Affects Early-Life Communicative Behaviors, Sensorimotor Reflexes, and Weight Trajectory in Mice
Authors: Minakova Elena , Sarafinovska Simona , Mikati Marwa O. , Barclay Kia , McCullough Katherine B. , Dougherty Joseph D. , Al-Hasani Ream , Maloney Susan E. 
Published: October 2020

ABSTRACTNation-wide, opioid misuse among pregnant women has risen 4-fold from 1999 to 2014, with commensurate increase in neonates hospitalized for Neonatal Abstinence Syndrome (NAS). NAS occurs when a fetus exposed to opioidsin uterogoes into rapid withdrawal after birth. NAS treatment via continued postnatal opioid exposure has been suggested to worsen neurodevelopmental outcomes. We developed a novel model to characterize the impact ofin uteroand postnatal oxycodone (Oxy) exposure on early behavior and development. Via subcutaneous pump implanted before breeding, C57BL/6J dams were infused with oxycodone at 10 mg/kg/day from conception through pup-weaning. At birth,in uterooxy-exposed pups were either cross-fostered (paired with non-oxy exposed dams) to model opioid abstinence (short-oxy) or reared by their biological dams still receiving Oxy to model continued postnatal opioid exposure (long-oxy). Offspring from vehicle-exposed dams served as cross-fostered (short-veh) or biologically-reared (long-veh) controls. Short-oxy exposure resulted in sex-dependent weight reductions and altered spectrotemporal features of isolation-induced ultrasonic vocalization (USV). Meanwhile, long-oxy pups exhibited reduced weight and sex-differential delays in righting reflex. Specifically, long-oxy female offspring exhibited increased latency to righting reflex. Long-oxy pups also showed decreases in number of USV calls, and changes to spectrotemporal USV features. Overall, ontogenetic Oxy exposure was associated with impaired attainment of gross and sensorimotor milestones, as well as alterations in communication and affective behaviors, indicating a need for therapeutic interventions. The model developed here will enable studies of withdrawal physiology and opioid-mediated mechanisms underlying these neurodevelopmental deficits.
Flexible analysis of animal behavior via time-resolved manifold embedding
Authors: York Ryan A. , Carreira-Rosario Arnaldo , Giocomo Lisa M. , Clandinin Thomas R. 
Published: October 2020

AbstractUncovering relationships between neural activity and behavior represents a critical challenge, one that would benefit from facile tools that can capture complex structures within large datasets. Here we demonstrate a generalizable strategy for capturing such structures across diverse behaviors: Time-REsolved BehavioraL Embedding (TREBLE). Using data from synthetic trajectories, adult and larvalDrosophila, and mice we show how TREBLE captures both continuous and discrete behavioral dynamics, can uncover variation across individuals, detect the effects of optogenetic perturbation in unbiased fashion, and reveal structure in pose estimation data. By applying TREBLE to moving mice, and medial entorhinal cortex (MEC) recordings, we show that nearly all MEC neurons encode information relevant to specific movement patterns, expanding our understanding of how navigation is related to the execution of locomotion. Thus, TREBLE provides a flexible framework for describing the structure of complex behaviors and their relationships to neural activity.
Macrophage metallothioneins participate in the antileishmanial activity of antimonials
Authors: Vargas Deninson Alejandro , Gregory David J. , Koren Roni Nitzan , Zilberstein Dan , Belew Ashton Trey , El-Sayed Najib M. , Gómez María Adelaida 
Published: October 2020

SYNOPSISBackgroundHost cell functions that participate in the pharmacokinetics and pharmacodynamics (PK/PD) of pentavalent antimonials for treatment of American cutaneous leishmaniasis (CL) are critical for drug efficacy.ObjectivesIn this study, we investigated whether macrophage mechanisms of xenobiotic detoxification contribute to drug-dependent elimination of intracellularLeishmania.MethodsTranscriptomes of primary macrophages from CL patients (n=6), exposed ex vivo toLeishmaniainfection and SbVwere generated. Candidate genes were selected and validated using short harping RNA interference (shRNA) in THP-1 cells.ResultsStrong induction of metallothionein (MT) genes was observed uponLeishmaniainfection and exposure to SbV, with 7 MT genes (MT1 and MT2 family members) appearing within the top 20 up-regulated genes. Tandem knockdown (KD) of MT2-A and MT1-E, 1F, and 1X in THP-1 cells was achieved using a pan-MT shRNA., Intracellular parasite survival after SbVexposure was unaffected in tandem-KD cells, and this was a consequence of strong transcriptional upregulation of MTs by infection and SbV, overcoming the KD effect. Gene silencing of the metal transcription factor-1 (MTF-1) abrogated expression of MT1 and MT2-A genes. Upon exposure to SbV, intracellular survival ofLeishmaniain MTF-1KDcells was significantly enhanced (p ≤ 0.05).ConclusionsMTs are potent scavengers of heavy metals, and central elements of the mammalian cell machinery for xenobiotic detoxification. Results from this study highlight the participation of macrophage MTs in Sb-dependent parasite killing, revealing novel strategies for host-targeted optimization of antileishmanial drugs.
Astrocytes close the critical period for visual plasticity
Authors: Ribot Jérôme , Breton Rachel , Calvo Charles-Félix , Moulard Julien , Ezan Pascal , Zapata Jonathan , Samama Kevin , Bemelmans Alexis-Pierre , Sabatet Valentin , Dingli Florent , Loew Damarys , Milleret Chantal , Billuart Pierre , Dallérac Glenn , Rouach Nathalie 
Published: October 2020

Summary paragraphBrain postnatal development is characterized by critical periods of experience-dependent remodeling1,2. Termination of these periods of intense plasticity is associated with settling of neuronal circuits, allowing for efficient information processing3. Failure to end critical periods thus results in neurodevelopmental disorders4,5. Yet, the cellular processes defining the timing of these developmental periods remain unclear. Here we show in the mouse visual cortex that astrocytes control the closure of the critical period. We uncover a novel underlying pathway involving regulation of the extracellular matrix that allows interneurons maturation via an unconventional astroglial connexin signaling. We find that timing of the critical period closure is controlled by a marked developmental upregulation of the astroglial protein connexin 30 that inhibits expression of the matrix degrading enzyme MMP9 through the RhoA-GTPase signaling pathway. Our results thus demonstrate that astrocytes not only influence activity and plasticity of single synapses, but are also key elements in the experience-dependent wiring of brain developing circuits. This work, by revealing that astrocytes promote the maturation of inhibitory circuits, hence provide a new cellular target to alleviate malfunctions associated to impaired closure of critical periods.
Biological traits of seabirds predict extinction risk and vulnerability to anthropogenic threats
Authors: Richards Cerren , Cooke Robert S. C. , Bates Amanda E. 
Published: October 2020

ABSTRACTAimHere we aim to: 1) test whether globally-threatened vs non-threatened seabirds are separated in trait space; 2) quantify the redundancy and uniqueness of species trait combinations per IUCN Red List Category; and 3) identify traits that render species vulnerable to anthropogenic threats.LocationGlobalTime periodContemporaryMajor taxa studiedSeabirdsMethodsWe compile and impute eight traits that relate to species’ vulnerabilities and ecosystem functioning across 341 seabird species. Using these traits, we build a mixed data PCA of species’ trait space. We further quantify trait redundancy with a unique trait combinations (UTCs) approach. Finally, we employ a similarity of percentages analysis (SIMPER) to identify which traits explain the greatest difference between threat groups.ResultsWe find seabirds segregate in trait space based on threat status, indicating anthropogenic impacts are selectively removing large, long-lived, pelagic surface feeders with narrow habitat breadths. We further find that globally threatened species have higher trait redundancy, while non-threatened species have relatively unique ecological strategies and limited redundancy. Finally, we find that species with narrow habitat breadths, fast reproductive speeds, and omnivorous diets are more likely to be threatened by habitat-modifying processes (e.g., pollution and natural system modifications); whereas pelagic specialists with slow reproductive speeds and omnivorous diets are vulnerable to threats that directly impact survival and fecundity (e.g., invasive species and biological resource use).Main conclusionsOur results suggest both globally threatened and non-threatened species contribute unique ecological strategies. Consequently, conserving both threat groups, but with contrasting approaches may avoid potential changes in ecosystem functioning and stability.