bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative transcriptomics reveal that adaptive evolution in immune genes drives the local adaptation and speciation of schizothoracine fish
Authors: Qi Delin , Wu Rongrong , Chao Yan , Xia Mingzhe , Chen Qichang , Zheng Zhiqin 
Published: July 2019

ABSTRACTTranscriptomic information can increase our understanding of the molecular processes underlying speciation. The schizothoracine fish, the largest and most diverse taxon within the Qinghai-Tibetan Plateau (QTP) ichthyofauna, are widespread in drainages throughout the QTP. These fish thus serve as an ideal model group with which to investigate how molecular evolution drives local adaptation during speciation. Here, we performed an interspecific comparative analysis of the transcriptomes of 13 schizothoracine fish species, and identified the key positively selected genes (PSGs) associated with significantly enriched functions and metabolite pathway acting on the specific lineages (or species) in the schizothoracine fish. We generated 64,637,602–83,968,472 sequence reads per schizothoracine fish species using Illumina sequencing, yielding 95,251–145,805 unigenes per species. We identified 52 out of 2,064 orthologous genes as candidate genes, which have probably been subject to positive selection along the whole schizothoracine fish lineage. Nine of these candidate genes were significantly enriched in key GO functions and metabolite pathways, all of which were associated with the immune system. The lineage-specific evolution test showed species-specific differences among the nine candidate PSGs, probably due to ecological differences among drainages, as well as among micro-habitats in the same drainage (e.g., benthic and pelagic). Here, we provide evidence that the adaptive evolution of immune genes, along with the uplift of the QTP, allowed new schizothoracine species to colonize ecologically novel environments or to exploit vacant ecological niches during speciation.Supplemental material available at FigShare: https://doi.org/10.25387/.
Sensory-modality independent activation of the brain network for language
Authors: Arana Sophie , Marquand André , Hultén Annika , Hagoort Peter , Schoffelen Jan-Mathijs 
Published: July 2019

AbstractThe meaning of a sentence can be understood, whether presented in written or spoken form. Therefore it is highly probable that brain processes supporting language comprehension are at least partly independent of sensory modality. To identify where and when in the brain language processing is independent of sensory modality, we directly compared neuromagnetic brain signals of 200 human subjects (102 males) either reading or listening to sentences. We used multiset canonical correlation analysis to align individual subject data in a way that boosts those aspects of the signal that are common to all, allowing us to capture word-by-word signal variations, consistent across subjects and at a fine temporal scale. Quantifying this consistency in activation across both reading and listening tasks revealed a mostly left hemispheric cortical network. Areas showing consistent activity patterns include not only areas previously implicated in higher-level language processing, such as left prefrontal, superior & middle temporal areas and anterior temporal lobe, but also parts of the control-network as well as subcentral and more posterior temporal-parietal areas. Activity in this supramodal sentence processing network starts in temporal areas and rapidly spreads to the other regions involved. The findings do not only indicate the involvement of a large network of brain areas in supramodal language processing, but also indicate that the linguistic information contained in the unfolding sentences modulates brain activity in a word-specific manner across subjects.
Autophagy dark genes: Can we find them with machine learning?
Authors: Oprea Tudor I. , Yang Jeremy J. , Byrd Daniel R. , Deretic Vojo 
Published: July 2019

AbstractIdentifying novel genes associated with autophagy (ATG) in man remains an important task for gaining complete understanding on this fundamental physiological process. A machine-learning guided approach can highlight potentially “missing pieces” linking core autophagy genes with understudied, “dark” genes that can help us gain deeper insight into these processes. In this study, we used a set of 103 (out of 288 genes from the Autophagy Database, ATGdb), based on the presence of ATG-associated terms annotated from 3 secondary sources: GO (gene ontology), KEGG pathway and UniProt keywords, respectively. We regarded these as additional confirmation for their importance in ATG. As negative labels, we used the OMIM list of genes associated with monogenic diseases (after excluding the 288 ATG-associated genes). Data associated with these genes from 17 different public sources were compiled and used to derive a Meta Path/XGBoost (MPxgb) machine learning model trained to distinguish ATG and non-ATG genes (10-fold cross-validated, 100-times randomized models, median AUC = 0.994 +/− 0.0084). Sixteen ATG-relevant variables explain 64% of the total model gain, and 23% of the top 251 predicted genes are annotated in ATGdb. Another 15 genes have potential ATG associations, whereas 193 do not. We suggest that some of these 193 genes may represent “autophagy dark genes”, and argue that machine learning can be used to guide autophagy research in order to gain a more complete functional and pathway annotation of this complex process.
Estrogen deprivation triggers an immunosuppressive phenotype in breast cancer cells
Authors: Hühn Daniela , Martí-Rodrigo Pablo , Mouron Silvana , Hansel Catherine S. , Tschapalda Kirsten , Porebski Bartlomiej , Häggblad Maria , Lidemalm Louise , Quintela-Fandino Miguel A. , Carreras-Puigvert Jordi , Fernandez-Capetillo Oscar 
Published: July 2019

ABSTRACTEstrogen receptor (ER)-positive breast tumors are routinely treated with estrogen-depriving therapies. Despite their effectiveness, patients often progress into a more aggressive form of the disease. Through a chemical screen oriented to identify chemicals capable of inducing the expression of the immune-checkpoint ligand PD-L1, we found antiestrogens as hits. Subsequent validations confirmed that estrogen deprivation or ERα depletion induces PD-L1 expression in ER-positive breast cancer cells, both in vitro and in vivo. Likewise, PD-L1 expression is increased in metastasis arising from breast cancer patients receiving adjuvant hormonal therapy for their local disease. Transcriptome analyses indicate that estrogen deprivation triggers a broad immunosuppressive program, not restricted to PD-L1. Accordingly, estrogen deprived MCF7 cells are resistant to T-cell mediated cell killing, in a manner that can be reverted by estradiol. Our study reveals that while antiestrogen therapies effectively limit tumor growth in ER-positive breast cancers, they also trigger a transcriptional program that favors immune evasion.
Endocytic Clathrin Coats Develop Curvature at Early Stages of Their Formation
Authors: Willy Nathan M. , Ferguson Joshua P. , Silahli Salih , Cakez Cemal , Hasan Farah , Chen Yan , Wu Min , Chang Henry C. , Travesset Alex , Li Siyu , Zandi Roya , Li Dong , Betzig Eric , Cocucci Emanuele , Kural Comert 
Published: July 2019

AbstractSculpting a flat patch of membrane into an endocytic vesicle requires curvature generation on the cell surface, which is the primary function of endocytic protein complexes. The mechanism through which membrane curvature is imposed during formation of clathrin-coated vesicles is an ongoing controversy. Using super-resolved live cell fluorescence imaging, we demonstrate that curvature generation by clathrin-coated pits can be detected in real time within cultured cells and tissues of developing metazoan organisms. We found that the footprint of clathrin coats increase monotonically during formation of curved pits at different levels of plasma membrane tension. Our findings are only compatible with models that predict curvature generation at early stages of endocytic clathrin-coated pit formation. Therefore, clathrin-coated vesicle formation does not necessitate a dynamically unstable clathrin lattice that would allow an abrupt flat-to-curved transition.SummaryEndocytic clathrin coats acquire curvature without a flat-to-curved transition that requires an extensive reorganization of the clathrin lattice.
EEG and fMRI Evidence for Autobiographical Memory Reactivation in Empathy
Authors: Meconi Federica , Linde-Domingo Juan , Ferreira Catarina S. , Michelmann Sebastian , Staresina Bernhard , Apperly Ian , Hanslmayr Simon 
Published: July 2019

AbstractEmpathy relies on the ability to mirror and to explicitly infer others’ inner states. Theoretical accounts suggest that memories play a role in empathy but direct evidence of a reactivation of autobiographical memories (AM) in empathy is yet to be shown. We addressed this question in two experiments. In experiment 1, electrophysiological activity (EEG) was recorded from 28 participants who performed an empathy task in which targets for empathy were depicted in contexts for which participants either did or did not have an AM, followed by a task that explicitly required memory retrieval of the AM and non-AM contexts. The retrieval task was implemented to extract the neural fingerprints of AM and non-AM contexts, which were then used to probe data from the empathy task. An EEG pattern classifier was trained and tested across tasks and showed evidence for AM reactivation when participants were preparing their judgement in the empathy task. Participants self-reported higher empathy for people depicted in situations they had experienced themselves as compared to situations they had not experienced. A second independent fMRI experiment replicated this behavioural finding and showed the predicted activation in the brain networks underlying both AM retrieval and empathy: precuneus, posterior parietal cortex, superior and inferior parietal lobule and superior frontal gyrus. Together, our study reports behavioural, electrophysiological and fMRI evidence that robustly supports the involvement of AM reactivation in empathy.
Insights into actin polymerization and nucleation using a coarse grained model
Authors: Horan Brandon G. , Hall Aaron R. , Vavylonis Dimitrios 
Published: July 2019

ABSTRACTWe studied actin filament polymerization and nucleation with molecular dynamics simulations and a previously established coarse-grained model having each residue represented by a single interaction site located at the Cαatom. We approximate each actin protein as a fully or partially rigid unit to identify the equilibrium structural ensemble of interprotein complexes. Monomers in the F-actin configuration bound to both barbed and pointed ends of a short F-actin filament at the anticipated locations for polymerization. Binding at both ends occurred with similar affinity. Contacts between residues of the incoming subunit and the short filament were consistent with expectation from models based on crystallography, X-ray diffraction and cryo-electron microscopy. Binding at the barbed and pointed end also occurred at an angle with respect to the polymerizable bound structure, and the angle range depended on the flexibility of the D-loop. Additional barbed end bound states were seen when the incoming subunit was in the G-actin form. Consistent with an activation barrier for pointed end polymerization, G-actin did not bind at an F-actin pointed end. In all cases, binding at the barbed end also occurred in a configuration similar to the antiparallel (lower) dimer. Individual monomers bound each other in a short-pitch helix complex in addition to other configurations, with several of them apparently non-productive for polymerization. Simulations with multiple monomers in the F-actin form show assembly into filaments as well as transient aggregates at the barbed end. We discuss the implications of these observations on the kinetic pathway of actin filament nucleation and polymerization and possibilities for future improvements of the coarse-grained model.SIGNIFICANCEControl of actin filament nucleation and elongation has crucial importance to cellular life. We show that coarse-grained molecular dynamics simulations are a powerful tool which can gauge involved mechanisms at reasonable computational cost, while retaining essential features of the fully atomic, yet less computationally tractable, system. Using a knowledge-based potential demonstrates the power of these methods for explaining and reproducing polymerization. Intermediate actin complexes identified in the simulations may play critical roles in the kinetic pathways of actin polymerization which may have been difficult to observe in prior experiments. These methods have been sparsely applied to the actin system, yet have potential to answer many important questions in the field.
A cortex-specific PBP contributes to cephalosporin resistance in Clostridium difficile
Authors: Alabdali Yasir Adil Jabbar , Oatley Peter , Kirk Joseph A. , Fagan Robert P. 
Published: July 2019

AbstractSporulation is a complex cell differentiation programme shared by many members of the Firmicutes, the end result of which is a highly resistant, metabolically inert spore that can survive harsh environmental insults. Clostridium difficile spores are essential for transmission of disease and are also required for recurrent infection. However, the molecular basis of sporulation is poorly understood, despite parallels with the well-studied Bacillus subtilis system. The spore envelope consists of multiple protective layers, one which is a specialised layer of peptidoglycan, called the cortex, that is essential for the resistant properties of the spore. We have identified and characterised a penicillin binding protein (PBP) that is required for cortex synthesis in C. difficile. Surprisingly this PBP was also found to contribute to cephalosporin resistance, indicating an additional role in the synthesis of vegetative cell wall. This is the first description of a cortex-specific PBP in C. difficile and begins the process of unravelling cortex biogenesis in this important pathogen.
Attractor-state itinerancy in neural circuits with synaptic depression
Authors: Chen Bolun , Miller Paul 
Published: July 2019

AbstractNeural populations with strong excitatory recurrent connections can support bistable states in their mean firing rates. Multiple fixed points in a network of such bistable units can be used to model memory retrieval and pattern separation. The stability of fixed points may change on a slower timescale than that of the dynamics due to short-term synaptic depression, leading to transitions between quasi-stable point attractor states in a sequence that depends on the history of stimuli. To better understand these behaviors, we study a minimal model, which characterizes multiple fixed points and transitions between them in response to stimuli with diverse time- and amplitude-dependences. The interplay between the fast dynamics of firing rate and synaptic responses and the slower timescale of synaptic depression makes the neural activity sensitive to the amplitude and duration of square-pulse stimuli in a non-trivial, history-dependent manner. Weak cross-couplings further deform the basins of attraction for different fixed points into intricate shapes. Our analysis provides a natural explanation for the system’s rich responses to stimuli of different durations and amplitudes while demonstrating the encoding capability of bistable neural populations for dynamical features of incoming stimuli.
Adolescent Stress Increases Adult Ethanol Self-administration and Alters Ventral Tegmental Area GABA Signaling
Authors: Connor David A , Wittenberg Ruthie E , Drogin Jillian , Mak Allison , Dani John A 
Published: July 2019

AbstractAlcohol use disorders (AUDs) continue to be a significant public health problem. Early life stress and adversity have long-lasting effects on a wide range of behaviors, including responses to drugs of abuse. Epidemiological evidence indicates that exposure to early life stress contributes to alcohol use disorders and, while it is known that stress and alcohol both act on overlapping mesolimbic circuitry, the cellular mechanisms underlying the relationship between stress and alcohol intake are not well understood. Previous work has demonstrated that acute stress increases ethanol intake mediated by changes in GABA signaling within the ventral tegmental area (VTA). Here we investigated if adolescent stress exposure might elicit long-term, persistent increases in ethanol self-administration associated with altered VTA GABA signaling. To this end, we exposed adolescent postnatal day (PND) 28 male rats to 14 days of chronic variable stress (CVS) and then examined operant ethanol self-administration begun at least 30 days later. We found that adolescent stress exposure resulted in significantly increased ethanol self-administration in adulthood. In contrast, adult (PND 82) male rats exposed to the same CVS protocol did not display increased ethanol self-administration that was begun 30 days later. Furthermore, we found that adolescent stress exposure resulted in enhancement of ethanol-induced GABA signaling onto VTA dopamine neurons and impairments in VTA GABA chloride homeostasis. The results indicate that adolescence is a period vulnerable to stress, which produces long-term changes in VTA GABA signaling associated with increased ethanol self-administration behavior.
Efficientde novoassembly of eleven human genomes using PromethION sequencing and a novel nanopore toolkit
Authors: Shafin Kishwar , Pesout Trevor , Lorig-Roach Ryan , Haukness Marina , Olsen Hugh E. , Bosworth Colleen , Armstrong Joel , Tigyi Kristof , Maurer Nicholas , Koren Sergey , Sedlazeck Fritz J. , Marschall Tobias , Mayes Simon , Costa Vania , Zook Justin M. , Liu Kelvin J. , Kilburn Duncan , Sorensen Melanie , Munson Katy M. , Vollger Mitchell R. , Eichler Evan E. , Salama Sofie , Haussler David , Green Richard E. , Akeson Mark , Phillippy Adam , Miga Karen H. , Carnevali Paolo , Jain Miten , Paten Benedict 
Published: July 2019

AbstractPresent workflows for producing human genome assemblies from long-read technologies have cost and production time bottlenecks that prohibit efficient scaling to large cohorts. We demonstrate an optimized PromethION nanopore sequencing method for eleven human genomes. The sequencing, performed on one machine in nine days, achieved an average 63x coverage, 42 Kb read N50, 90% median read identity and 6.5x coverage in 100 Kb+ reads using just three flow cells per sample. To assemble these data we introduce new computational tools: Shasta - ade novolong read assembler, and MarginPolish & HELEN - a suite of nanopore assembly polishing algorithms. On a single commercial compute node Shasta can produce a complete human genome assembly in under six hours, and MarginPolish & HELEN can polish the result in just over a day, achieving 99.9% identity (QV30) for haploid samples from nanopore reads alone. We evaluate assembly performance for diploid, haploid and trio-binned human samples in terms of accuracy, cost, and time and demonstrate improvements relative to current state-of-the-art methods in all areas. We further show that addition of proximity ligation (Hi-C) sequencing yields near chromosome-level scaffolds for all eleven genomes.
PsyMuKB: A De Novo Variant Knowledge Base Integrating Transcriptional and Translational Information to Identify Isoform-specific Mutations in Developmental Disorders
Authors: Lin Guan Ning , Guo Sijia , Tan Xian , Wang Weidi , Qian Wei , Song Weichen , Wang Jingru , Yu Shunying , Wang Zhen , Cui Donghong , Wang Han 
Published: July 2019

AbstractDe novo variants (DNVs) are one of the most significant contributors to severe early-onset genetic disorders such as autism spectrum disorder, intellectual disability, and other developmental and neuropsychiatric (DNP) disorders. Currently, a plethora of DNVs have being identified through the use of next-generation sequencing and much effort has been made to understand their impact at the gene level; however, there has been little exploration of the impact at the isoform level. The brain contains a high level of alternative splicing and regulation, and exhibits a more divergent splicing program than other tissues; therefore, it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders. To facilitate better usage and improve the isoform-level interpretation of variants, we developed the PsyMuKB (NeuroPsychiatric Mutation Knowledge Base), a knowledge base containing a comprehensive, carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoform-specific mutations. PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations, such as expression, transcript genomic structures, protein interactions, and the mutation sites mapped on the protein structures. It also provides an easy-to-use web interface, allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms. PsyMuKB thus constitutes a valuable resource for identifying tissue-specific de novo mutations for further functional studies of related disorders. PsyMuKB is freely accessible at http://psymukb.net.
Soil chloride content influences the response of bacterial but not fungal diversity to silver nanoparticles entering soil via wastewater treatment processing
Authors: Forstner Christian , Orton Thomas G. , Wang Peng , Kopittke Peter M. , Dennis Paul G. 
Published: July 2019

AbstractSilver nanoparticles (NPs) are among the most widely used nanomaterials and are entering soil ecosystems, mainly via biosolids in agriculture. When added directly to soils, metallic Ag-NPs have been shown to affect microbial communities, which underpin important ecosystem functions. During wastewater treatment processing, metallic Ag-NPs are rapidly converted to Ag2S, which is relatively insoluble and less toxic. Furthermore, recent evidence indicates that silver bioavailability is influenced by soil chloride content. Hence there is a need to understand the impacts of wastewater treatment processed Ag-NPs at varying levels of salinity on soil microbial diversity. In this study, we examined how the application of 0 g, 1 g and 2 g kg−1 NaCl to soil influence the effects of 0 mg, 1 mg and 10 mg kg−1 Ag, applied as wastewater treatment processed Ag-NPs, on bacterial and fungal diversity over time. Using high-throughput phylogenetic marker gene sequencing we demonstrate that, despite being theoretically less toxic, wastewater treatment processed Ag-NPs can affect the composition of soil bacterial and fungal communities, and influence bacterial alpha diversity. In addition, we found that silver-associated changes in bacterial community composition were affected by soil chloride content, with more acute responses to silver being observed in more saline soils. This work highlights that the release of Ag-NPs into soils via realistic exposure pathways can alter microbial diversity and that these effects may be influenced by soil chloride content.Summary capsuleSoil chloride content influences the response of bacterial but not fungal diversity to wastewater treatment processed silver nanoparticles.