bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiota-directed fibre activates both targeted and secondary metabolic shifts in the distal gut
Authors: Michalak Leszek , Gaby John Christian , Lagos Leidy , La Rosa Sabina Leanti , Hvidsten Torgeir R. , Tétard-Jones Catherine , Willats William G.T. , Terrapon Nicolas , Lombard Vincent , Henrissat Bernard , Dröge Johannes , Arntzen Magnus Ø. , Hagen Live Heldal , Øverland Margareth , Pope Phillip B. , Westereng Bjørge 
Published: October 2019

ABSTRACTBeneficial modulation of the gut microbiome has high-impact implications not only in humans, but also in livestock that sustain our current societal needs. In this context, we have tailored an acetylated galactoglucomannan (AcGGM) fibre to match unique enzymatic capabilities of Roseburia and Faecalibacterium species, both renowned butyrate-producing gut commensals. The accuracy of AcGGM was tested within the complex endogenous gut microbiome of pigs, wherein we resolved 355 metagenome-assembled genomes together with quantitative metaproteomes. In AcGGM-fed pigs, both target populations differentially expressed AcGGM-specific polysaccharide utilization loci, including novel, mannan-specific esterases that are critical to its deconstruction. However, AcGGM-inclusion also manifested a “butterfly effect”, whereby numerous metabolic changes and interdependent cross-feeding pathways were detected in neighboring non-mannolytic populations that produce short-chain fatty acids. Our findings show that intricate structural features and acetylation patterns of dietary fibre can be customized to specific bacterial populations, with potential to create greater modulatory effects at large.
Single-nucleus RNA-seq identifies Huntington disease astrocyte states
Authors: Al-Dalahmah Osama , Sosunov Alexander A , Shaik A , Ofori Kenneth , Liu Yang , Vonsattel Jean Paul , Adorjan Istvan , Menon Vilas , Goldman James E 
Published: October 2019

AbstractHuntington Disease (HD) is an inherited movement disorder caused by expanded CAG repeats in the Huntingtin gene. We have used single nucleus RNASeq (snRNASeq) to uncover cellular phenotypes that change in the disease, investigating single cell gene expression in cingulate cortex of patients with HD and comparing the gene expression to that of patients with no neurological disease. In this study, we focused on astrocytes, although we found significant gene expression differences in neurons, oligodendrocytes, and microglia as well. In particular, the gene expression profiles of astrocytes in HD showed multiple signatures, varying in phenotype from cells that had markedly upregulated metallothionein and heat shock genes, but had not completely lost the expression of genes associated with normal protoplasmic astrocytes, to astrocytes that had substantially upregulated GFAP and had lost expression of many normal protoplasmic astrocyte genes as well as metallothionein genes. When compared to astrocytes in control samples, astrocyte signatures in HD also showed downregulated expression of a number of genes, including several associated with protoplasmic astrocyte function and lipid synthesis. Thus, HD astrocytes appeared in variable transcriptional phenotypes, and could be divided into several different “states”, defined by patterns of gene expression. Ultimately, this study begins to fill the knowledge gap of single cell gene expression in HD and provide a more detailed understanding of the variation in changes in gene expression during astrocyte “reactions” to the disease.
Listener’s vmPFC simulates speaker choices when reading between the lines
Authors: Mi Qingtian , Wang Cong , Camerer Colin F. , Zhu Lusha 
Published: October 2019

AbstractHumans possess a remarkable ability to understand what is and is not being said by conservational partners. An important class of models hypothesize that listeners decode the intended meaning of an utterance by assuming speakers speak cooperatively, simulating the speaker’s rational choice process and inverting this process for recovering the speaker’s most probable meaning. We investigated whether and how rational simulations of speakers are represented in the listener’s brain, when subjects participated in a referential communication game inside fMRI. In three experiments, we show that listener’s ventromedial prefrontal cortex encodes the probabilistic inference of what a cooperative speaker should say given a communicative goal and context. The listener’s striatum responds to the amount of update on the intended meaning, consistent with inverting a simulated mental model. These findings suggest a neural generative mechanism subserved by the frontal-striatal circuits that underlies our ability to understand communicative and, more generally, social actions.
Reinforcement Learning for Bio-Retrosynthesis
Authors: Koch Mathilde , Duigou Thomas , Faulon Jean-Loup 
Published: October 2019

AbstractMetabolic engineering aims to produce chemicals of interest from living organisms, to advance towards greener chemistry. Despite efforts, the research and development process is still long and costly and efficient computational design tools are required to explore the chemical biosynthetic space. Here, we propose to explore the bio-retrosynthesis space using an Artificial Intelligence based approach relying on the Monte Carlo Tree Search reinforcement learning method, guided by chemical similarity. We implement this method in RetroPath RL, an open-source and modular command line tool. We validate it on a golden dataset of 20 manually curated experimental pathways as well as on a larger dataset of 152 successful metabolic engineering projects. Moreover, we provide a novel feature, that suggests potential media supplements to complement the enzymatic synthesis plan.
Spectral Jaccard Similarity: A new approach to estimating pairwise sequence alignments
Authors: Baharav Tavor Z. , Kamath Govinda M. , Tse David N. , Shomorony Ilan 
Published: October 2019

AbstractA key step in many genomic analysis pipelines is the identification of regions of similarity between pairs of DNA sequencing reads. This task, known as pairwise sequence alignment, is a heavy computational burden, particularly in the context of third-generation long-read sequencing technologies, which produce noisy reads. This issue is commonly addressed via a two-step approach: first, we filter pairs of reads which are likely to have a large alignment, and then we perform computationally intensive alignment algorithms only on the selected pairs. The Jaccard similarity between the set of k-mers of each read can be shown to be a proxy for the alignment size, and is usually used as the filter. This strategy has the added benefit that the Jaccard similarities don’t need to be computed exactly, and can instead be efficiently estimated through the use of min-hashes. This is done by hashing all k-mers of a read and computing the minimum hash value (the min-hash) for each read. For a randomly chosen hash function, the probability that the min-hashes are the same for two distinct reads is precisely their k-mer Jaccard similarity. Hence, one can estimate the Jaccard similarity by computing the fraction of min-hash collisions out of the set of hash functions considered.However, when the k-mer distribution of the reads being considered is significantly non-uniform, Jaccard similarity is no longer a good proxy for the alignment size. In particular, genome-wide GC biases and the presence of common k-mers increase the probability of a min-hash collision, thus biasing the estimate of alignment size provided by the Jaccard similarity. In this work, we introduce a min-hash-based approach for estimating alignment sizes called Spectral Jaccard Similarity which naturally accounts for an uneven k-mer distribution in the reads being compared. The Spectral Jaccard Similarity is computed by considering a min-hash collision matrix (where rows correspond to pairs of reads and columns correspond to different hash functions), removing an offset, and performing a singular value decomposition. The leading left singular vector provides the Spectral Jaccard Similarity for each pair of reads. In addition, we develop an approximation to the Spectral Jaccard Similarity that can be computed with a single matrix-vector product, instead of a full singular value decomposition.We demonstrate improvements in AUC of the Spectral Jaccard Similarity based filters over Jaccard Similarity based filters on 40 datasets of PacBio reads from the NCTC collection. The code is available at https://github.com/TavorB/spectral_jaccard_similarity.
Characterization of novel regulators for heat stress tolerance in tomato from Indian sub-continent
Authors: Balyan Sonia , Rao Sombir , Jha Sarita , Bansal Chandni , Das Jaishri Rubina , Mathur Saloni 
Published: October 2019

AbstractThe footprint of tomato cultivation, a cool region crop that exhibits heat stress (HS) sensitivity, is increasing in the tropics/sub-tropics. Knowledge of novel regulatory hot-spots from varieties growing in the Indian sub-continent climatic zones could be vital for developing HS-resilient crops. Comparative transcriptome-wide signatures of a tolerant (CLN1621L) and sensitive (CA4) cultivar-pair short-listed from a pool of varieties exhibiting variable thermo-sensitivity using physiological, survival and yield-related traits revealed redundant to cultivar-specific HS-regulation with more up-regulated genes for CLN1621L than CA4. The anatgonisiticly-expressing genes include enzymes; have roles in plant defense and response to different abiotic stresses. Functional characterization of three antagonistic genes by overexpression and TRV-VIGS silencing established Solyc09g014280 (Acylsugar acyltransferase) and Solyc07g056570 (Notabilis), that are up-regulated in tolerant cultivar, as positive regulators of HS-tolerance and Solyc03g020030 (Pin-II proteinase inhibitor), that is down-regulated in CLN1621L, as negative regulator of thermotolerance. Transcriptional assessment of promoters of these genes by SNPs in stress-responsivecis-elements and promoter swapping experiments in opposite cultivar background showed inherent cultivar-specific orchestration of transcription factors in regulating transcription. Moreover, overexpression of three ethylene response transcription factors (ERF.C1/F4/F5) also improved HS-tolerance in tomato. This study identifies several novel HS-tolerance genes and provides proof of their utility in tomato-thermotolerance.HighlightNovel heat stress regulatory pathways uncovered by comparative transcriptome profiling between contrasting tomato cultivars from Indian sub-continent for improving thermotolerance. (20/30)
Freezing displayed by others is a learned cue of danger resulting from co-experiencing own-freezing and shock
Authors: Cruz Andreia , Heinemans Mirjam , Marquez Cristina , Moita Marta A. 
Published: October 2019

SUMMARYSocial cues of threat are widely reported [1–3], whether actively produced to trigger responses in others, such as the emission of alarm calls, or by-products of an encounter with a predator, like the defensive behaviors themselves, such as an escape flight [4–14]. Although the recognition of social alarm cues is often innate [15–17], in some instances it requires experience to trigger defensive responses [4,7]. One mechanism proposed for how learning from self-experience contributes to social behavior is that of auto-conditioning, whereby subjects learn to associate their own behaviors with the relevant trigger events. Through this process the same behaviors, now displayed by others, gain meaning. [18,19 but see: 20]. Although it has been shown that only animals with prior experience with shock display observational freezing [21–25] suggesting that auto-conditioning could mediate this process, evidence for this hypothesis was lacking. Previously we found that when a rat freezes, the silence that results from immobility triggers observational freezing in its cage-mate, provided the cage-mate had experienced shocks before [24]. Hence, in our study auto-conditioning would correspond to rats learning to associate shock with their own response to it – freezing. Using a combination of behavioral and optogenetic manipulations, here we show that freezing becomes an alarm cue by a direct association with shock. Our work shows that auto-conditioning can indeed modulate social interactions, expanding the repertoire of cues that mediate social information exchange, providing a framework to study how the neural circuits involved in the self-experience of defensive behaviors overlap with the ones involved in socially triggered defensive behaviors.
Deciphering the transcriptomic landscape of tumor-infiltrating CD8 lymphocytes in B16 melanoma tumors with single-cell RNA-Seq
Authors: Carmona Santiago J. , Siddiqui Imran , Bilous Mariia , Held Werner , Gfeller David 
Published: October 2019

ABSTRACTRecent studies have proposed that tumor-specific tumor-infiltrating CD8+T lymphocytes (CD8 TIL) can be classified into two main groups: “exhausted” TILs, characterized by high expression of the inhibitory receptors PD-1 and TIM-3 and lack of transcription factor 1 (Tcf1); and “memory-like” TILs, with self-renewal capacity and co-expressing Tcf1 and PD-1. However, a comprehensive definition of the heterogeneity existing within both tumor-specific and total CD8 TILs has yet to be clearly established.To investigate this heterogeneity at the transcriptomic level, we performed paired single-cell RNA and TCR sequencing of CD8 T cells infiltrating B16 murine melanoma tumors, including cells of known tumor specificity. Unsupervised clustering and gene signature analysis revealed four distinct CD8 TIL states - exhausted, memory-like, naïve and effector memory-like (EM-like) - and predicted novel markers, including Ly6C for the EM-like cells, that were validated by flow cytometry. Tumor-specific PMEL T cells were predominantly found within the exhausted and memory-like states but also within the EM-like state. Further, TCR repertoire sequencing revealed a large clonal expansion of exhausted, memory-like and EM-like cells with partial clonal relatedness between them. Finally, meta-analyses of public bulk and single-cell RNA-seq data suggested that anti-PD-1 treatment induces expansion of EM-like cells.Our reference map of the transcriptomic landscape of murine CD8 TILs will help interpreting future bulk and single-cell transcriptomic studies and may guide the analysis of CD8 TIL subpopulations in response to therapeutic interventions.
Neurodevelopmental shifts in learned value transfer on cognitive control during adolescence
Authors: Insel Catherine , Charifson Mia , Somerville Leah H. 
Published: October 2019

AbstractValue-associated cues in the environment often enhance subsequent goal-directed behaviors in adults, a phenomenon supported by integration of motivational and cognitive neural systems. Given the interactions among these systems change throughout adolescence, we tested when beneficial effects of value associations on subsequent cognitive control performance emerge during adolescence. Participants (N=81) aged 13-20 completed a reinforcement learning task with four cue-incentive pairings that could yield high gain, low gain, high loss, or low loss outcomes. Next, participants completed a Go/NoGo task during fMRI where the NoGo targets comprised the previously learned cues, which tested how prior value associations influence cognitive control performance. Improved accuracy for previously learned high gain relative to low gain cues emerged with age. Older adolescents exhibited enhanced recruitment of the dorsal striatum and ventrolateral prefrontal cortex during cognitive control execution to previously learned high gain relative to low gain cues. Older adolescents also expressed increased coupling between the dorsal striatum and dorsolateral prefrontal cortex for high gain cues, whereas younger adolescents expressed increased coupling between the striatum and ventromedial prefrontal cortex. These findings reveal that learned high value cue-incentive associations enhance cognitive control in late adolescence in parallel with value-selective recruitment of corticostriatal systems.
A high-content screen identifies the vulnerability of MYC-overexpressing cells to dimethylfasudil
Authors: Zhang Jing , Zhang Shenqiu , Shi Qiong , Allen Thaddeus D. , You Fengming , Yang Dun 
Published: October 2019

AbstractA synthetic lethal effect arises when a cancer-associated change introduces a unique vulnerability to cancer cells that makes them unusually susceptible to a drug’s inhibitory activity. The synthetic lethal approach is attractive because it enables targeting of cancers harboring specific genomic alterations, the products of which may have proven refractory to direct targeting. An example is cancer driven by overexpression of MYC. Here, we conducted a high-content screen for compounds that are synthetic lethal to elevated MYC using a small-molecule library to identify compounds that are closely related to, or are themselves, regulatory-approved drugs. The screen identified dimethylfasudil, a potent and reversible inhibitor of Rho-associated kinases ROCK1 and ROCK2. Close analogs of dimethylfasudil are used clinically to treat neurologic and cardiovascular disorders. The synthetic lethal interaction was conserved in rodent and human cell lines and could be observed with activation of either MYC or its paralog MYCN. The synthetic lethality seems specific to MYC overexpressing cells as it could not be substituted by a variety of oncogenic manipulations and synthetic lethality was diminished by RNAi-mediated depletion of MYC in human cancer cell lines. Collectively, these data support investigation of the use of dimethylfasudil as a drug that is synthetic lethal for malignancies that specifically overexpress MYC.Significance StatementSynthetic lethal targeting of tumors overexpressing MYC holds promise for attacking aggressive malignancies. Here we describe a synthetic lethal interaction between dimethylfasudil and overexpression of MYC. Uniquely, this novel synthetic lethal interaction points toward an opportunity for synthetic lethality with a molecule likely to harbor favorable drug-like properties that enable systemic use.
A G-protein-coupled receptor mediates neuropeptide-induced oocyte maturation in the jellyfish Clytia
Authors: Quiroga Artigas Gonzalo , Lapébie Pascal , Leclère Lucas , Bauknecht Philip , Uveira Julie , Chevalier Sandra , Jékely Gáspár , Momose Tsuyoshi , Houliston Evelyn 
Published: October 2019

AbstractThe reproductive hormones that trigger oocyte meiotic maturation and release from the ovary vary greatly between animal species. Identification of receptors for these Maturation Inducing Hormones (MIHs), and understanding how they initiate the largely conserved maturation process, remain important challenges. In hydrozoan cnidarians including the jellyfish Clytia hemisphaerica, MIH comprises neuropeptides released from somatic cells of the gonad. We identified the receptor (MIHR) for these MIH neuropeptides in Clytia using cell culture-based “deorphanization” of candidate oocyte-expressed GPCRs. MIHR mutant jellyfish generated using CRISPR-Cas9 had severe defects in gamete development or in spawning both in males and females. Female gonads, or oocytes isolated from MIHR mutants, failed to respond to synthetic MIH. Treatment with the cAMP analogue 5’Br-cAMP to mimic cAMP rise at maturation onset rescued meiotic maturation and spawning. Injection of inhibitory antibodies to GαS into wild type oocytes phenocopied the MIHR mutants. These results provide the molecular links between MIH stimulation and meiosis initiation in hydrozoan oocytes. Molecular phylogeny grouped Clytia MIHR with a subset of bilaterian neuropeptide receptors including Neuropeptide Y, Gonadotropin Inhibitory Hormone, pyroglutamylated RFamide and Luqin, all upstream regulators of sexual reproduction. This identification and functional characterisation of a cnidarian peptide GPCR advances our understanding of oocyte maturation initiation and sheds light on the evolution of neuropeptide-hormone systems.
Single-cell Transcriptomics Identify Extensive Heterogeneity in the Cellular Composition of Mouse Achilles Tendons
Authors: De Micheli Andrea J , Swanson Jacob B , Disser Nathaniel P , Martinez Leandro M , Walker Nicholas R , Oliver David J , Cosgrove Benjamin D , Mendias Christopher L 
Published: October 2019

AbstractTendon is a connective tissue that transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, but little is known about the diversity of cells that populate tendon. Our objective was to explore the heterogeneity of cells in mouse Achilles tendons using single-cell RNA sequencing. We assembled a transcriptomic atlas and identified 11 distinct cell types in tendons, including 3 previously undescribed populations of fibroblasts. Using trajectory inference analysis, we provide additional support for the notion that pericytes are progenitor cells for the fibroblasts that compose adult tendons. We also modeled cell-interactions and identified ligand-receptor pairs involved in tendon homeostasis. Our findings highlight notable heterogeneity between and within tendon cell populations, which may contribute to our understanding of tendon extracellular matrix assembly and maintenance, and inform the design of therapies to treat tendinopathies.
Does researcher activity affect Dromiciops gliroides capture rates? A test in two contrasting forest habitats
Authors: Salazar Daniela A. , Fontúrbel Francisco E. 
Published: October 2019

AbstractAiming to understand the low D. gliroides capture rates at the Valdivian Coastal Reserve, we disposed camera-traps at two contrasting forest habitats: a native forest habitat and a transformed habitat composed by a Eucalyptus globulus plantation with native understory vegetation. Camera-trap survey was conducted before and during live-trap operation. We found a large number of photographic records at the pre-bait period (41 photos at the native habitat and 22 at the transformed habitat). Then, when we conducted the live-trapping survey, photographic records decrease to 7 at the native habitat and 5 at the transformed habitat. Compared to similar locations in southern Chile, our study site shows low sampling effectiveness and capture success values, which could be explained by the disturbance generated by the researcher by checking the trap grid in a daily basis in a remote place where human presence is sporadic.
A Distinctive Pattern of Hippocampal-Prefrontal Cortical Network Activity during Stress Predicts Learned Resistance
Authors: Marques Danilo Benette , Ruggiero Rafael Naime , Bueno-Junior Lezio Soares , Rossignoli Matheus Teixeira , Leite João Pereira 
Published: October 2019

AbstractThe perception of control over a stressful experience may determine its impacts and generate resistance against future stressors. Although the medial prefrontal cortex (mPFC) and the hippocampus are implicated in the encoding of stressor controllability, the neural dynamics underlying this process are unknown. Here, we recorded CA1 and mPFC neural activities in rats during the exposure to controllable, uncontrollable, or no shocks, and investigated electrophysiological predictors of escape performance upon exposure to subsequent uncontrollable shocks. We were able to accurately discriminate stressed from non-stressed animals and predict resistant or helpless individuals based on neural oscillatory dynamics. We identified a pattern of enhanced CA1-mPFC theta power, synchrony, cross-frequency interaction, and neuronal coupling that strongly predicted learned resistance, and that was lacking in helpless individuals. Our findings suggest that hippocampal-prefrontal network theta activity supports cognitive mechanisms of stress coping, and its impairment may underlie vulnerability to stress-related disorders.