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Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 48,092 bioRxiv papers from 215,637 authors.

Most tweeted bioRxiv papers, last 24 hours

390 results found. For more information, click each entry to expand.

61: Discovery Of UFO Proteins: Human-Virus Chimeric Proteins Generated During Influenza Virus Infection
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Posted to bioRxiv 08 Apr 2019

Discovery Of UFO Proteins: Human-Virus Chimeric Proteins Generated During Influenza Virus Infection
5 tweets microbiology

Yixuan Ma, Matthew Angel, Guojun Wang, Jessica Sook Yuin Ho, Nan Zhao, Justine Noel, Natasha Moshkina, James Gibbs, Jiajie Wei, Brad Rosenberg, Jeffrey Johnson, Max Chang, Zuleyma Peralta, Nevan Krogan, Christopher Benner, Harm van Bakel, Marta Łuksza, Benjamin D. Greenbaum, Emily R. Miraldi, Adolfo Garcia-Sastre, Jonathan W. Yewdell, Ivan Marazzi

Influenza A virus (IAV) is a threat to mankind because it generates yearly epidemics and poorly predictable sporadic pandemics with catastrophic potential. IAV has a small RNA genome composed of 8 mini-chromosomes (segments) that constitute a 5'UTR followed by a coding region and a 3'UTR. Transcription of IAV RNA into mRNA depends on host mRNA, as the viral polymerase cleaves 5'm7G-capped nascent transcripts to use as primers to initiate viral mRNA synthesis. We hypothesized that captured host transcripts bearing AUG could drive the expression of upstream ORFs in the viral segments, a phenomenon that would depend on the translatability of the viral 5'UTRs. Here we report the existence of this mechanism, which generates host-virus chimeric proteins. We label these proteins as Upstream Flu ORFs (UFO). Depending on the frame, two types of host-virus UFO proteins are made: canonical viral proteins with human-derived N term extensions or novel uncharacterized proteins. Here we show that both types are made during IAV infection. Sequences that enable chimeric protein synthesis are conserved across IAV strains, indicating that selection allowed the expansion of the proteome diversity of IAV in infected cells to include multiple human-virus proteins.

62: Enhancers facilitate the birth of de novo genes and their functional integration into regulatory networks
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Posted to bioRxiv 23 Apr 2019

Enhancers facilitate the birth of de novo genes and their functional integration into regulatory networks
5 tweets evolutionary biology

Paco Majic, Joshua Payne

Regulatory networks control the spatiotemporal gene expression patterns that give rise to and define the individual cell types of multicellular organisms. In Eumetazoa, distal regulatory elements called enhancers play a key role in determining the structure of such networks, particularly the wiring diagram of "who regulates whom." Mutations that affect enhancer activity can therefore rewire regulatory networks, potentially causing changes in gene expression that may be adaptive. Here, we use single-cell transcriptomic and chromatin accessibility data from mouse to show that enhancers play an additional role in the evolution of regulatory networks: They facilitate network growth by creating transcriptionally active regions of open chromatin that are conducive to de novo gene evolution. Specifically, our comparative transcriptomic analysis with three other mammalian species shows that young, mouse-specific transcribed open reading frames are preferentially located near enhancers, whereas older open reading frames are not. Interactions with enhancers are then gained incrementally over macro-evolutionary timescales, helping integrate new genes into existing regulatory networks. Taken together, our results highlight a dual role of enhancers in expanding and rewiring gene regulatory networks.

63: Social value unblocks Pavlovian reinforcement learning in male rats
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Posted to bioRxiv 18 Apr 2019

Social value unblocks Pavlovian reinforcement learning in male rats
4 tweets animal behavior and cognition

Sander van Gurp, Jochen Hoog, Tobias Kalenscher, Marijn van Wingerden

Many species, including humans, are sensitive to social signals and the valuation of these social cues is important in maintaining social interactions. Social value, derived from social cues, thus could act as a reinforcer and influence reward learning. Here, we introduce a novel task in rats that investigates if social value can drive reinforcement learning about novel stimuli. Using the blocking/unblocking paradigm originally developed in the (non-social) reinforcement learning literature, we found that when actor rats have fully learned a stimulus-reward association producing reward for themselves, adding a cue that predicted an additional reward delivery to a partner rat unblocked associative learning about this cue in the actor rats. In contrast, additional cues that did not predict additional reward remained blocked from acquiring associative value. In a control experiment where putative social cue exchange between the partnered rats was prevented, the normally unblocked cues now remained blocked as expected. Taken together, these results suggest that social value can drive reinforcement learning in rats, and that the transmission of social cues is necessary for this learning, driven by social value, to occur.

64: ABioTrans: A Biostatistical tool for Transcriptomics Analysis
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Posted to bioRxiv 23 Apr 2019

ABioTrans: A Biostatistical tool for Transcriptomics Analysis
4 tweets bioinformatics

Zou Yutong, Bui Thuy Tien, Kumar Selvarajoo

Here we report a bio-statistical/informatics tool, ABioTrans, developed in R for gene expression analysis. The tool allows the user to directly read RNA-Seq data files deposited in the Gene Expression Omnibus or GEO database. Operated using any web browser application, ABioTrans provides easy options for multiple statistical distribution fitting, Pearson and Spearman rank correlations, PCA, k-means and hierarchical clustering, differential expression analysis, Shannon entropy and noise (square of coefficient of variation) analyses, as well as Gene ontology classifications.

65: Plant-Necrotroph Co-transcriptome Networks Illuminate a Metabolic Battlefield
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Posted to bioRxiv 04 Dec 2018

Plant-Necrotroph Co-transcriptome Networks Illuminate a Metabolic Battlefield
4 tweets systems biology

WEI Zhang, Jason A Corwin, Daniel Copeland, Julie Feusier, Robert Eshbaugh, David E Cook, Susana Atwell, Daniel J. Kliebenstein

A central goal of studying host-pathogen interaction research is to understand how the host and pathogen manipulate each other to promote their own fitness in a pathosystem. Co-transcriptomic approaches can simultaneously analyze dual transcriptomes during infection and provide a systematic map of the cross-kingdom communication between two species. Here we used the Arabidopsis-B. cinerea pathosystem to test how plant host and fungal pathogen interaction at the transcriptomic level during infection. We assessed the impact of natural genetic diversity in the pathogen and plant host by utilization of a collection of 96 isolates of B. cinerea infection on Arabidopsis wild-type and two mutants with jasmonate or salicylic acid compromised immunities. We identified ten B. cinerea gene co-expression networks (GCNs) that encode known or novel virulence mechanisms. We constructed a dual interaction network by combining four host- and ten pathogen-GCNs into a single network, which revealed potential connections between the fungal and plant GCNs involving both novel and conserved mechanisms. These co-transcriptome data shed lights on the potential mechanisms underlying host-pathogen interaction and illustrate the continued need for advancements of in planta analysis of dual-species dynamics.

66: How much fear is in anxiety?
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Posted to bioRxiv 06 Aug 2018

How much fear is in anxiety?
4 tweets neuroscience

Andreas Genewsky, Nina Albrecht, Simona A. Bura, Paul M. Kaplick, Daniel E. Heinz, Markus Nußbaumer, Mareen Engel, Barbara Grünecker, Sebastian F. Kaltwasser, Caitlin J. Riebe, Benedikt T. Bedenk, Michael Czisch, Carsten T. Wotjak

The selective breeding for extreme behavior on the elevated plus-maze (EPM) resulted in two mouse lines namely high-anxiety behaving (HAB) and low-anxiety behaving (LAB) mice. Using novel behavioral tests we demonstrate that HAB animals additionally exhibit maladaptive escape behavior and defensive vocalizations, whereas LAB mice show profound deficits in escaping from approaching threats which partially results from sensory deficits. We could relate these behavioral distortions to tonic changes in brain activity within the periaqueductal gray (PAG) in HAB mice and the superior colliculus (SC) in LAB mice, using in vivo manganese-enhanced MRI (MEMRI) followed by pharmacological or chemogenetic interventions. Therefore, midbrain-tectal structures govern the expression of both anxiety-like behavior and defensive responses. Our results challenge the uncritical use of the anthropomorphic terms anxiety or anxiety-like for the description of mouse behavior, as they imply higher cognitive processes, which are not necessarily in place.

67: MicroED with the Falcon III direct electron detector
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Posted to bioRxiv 23 Apr 2019

MicroED with the Falcon III direct electron detector
4 tweets biochemistry

Johan Hattne, Michael W. Martynowycz, Tamir Gonen

Microcrystal electron diffraction (MicroED) combines crystallography and electron cryo-microscopy (cryo-EM) into a method that can be used for high-resolution structure determination. In MicroED nanosized crystals, often intractable by other techniques, are probed by high-energy electrons in a transmission electron microscope and the diffracted signal is recorded on an electron detector. Since only a small number of different detectors have been used for MicroED measurements in the past, their impact on data quality has not been investigated. Here we evaluate two different cameras using crystals of the well-characterized serine protease proteinase K. Compared to previously used equipment, the Falcon III direct electron detector and the CMOS-based CetaD camera can collect complete datasets both faster and using lower total exposure. As an effect of the lower dose, radiation damage is reduced, which is confirmed in both real and reciprocal space. The increased speed and lower exposure requirements have implications on model quality and the prospects for further automation of MicroED.

68: A reference map of the human protein interactome
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Posted to bioRxiv 10 Apr 2019

A reference map of the human protein interactome
4 tweets systems biology

Katja Luck, Dae-Kyum Kim, Luke Lambourne, Kerstin Spirohn, Bridget E Begg, Wenting Bian, Ruth Brignall, Tiziana Cafarelli, Francisco J Campos-Laborie, Benoit Charloteaux, Dongsic Choi, Atina G. Cote, Meaghan Daley, Steven Deimling, Alice Desbuleux, Amelie Dricot, Marinella Gebbia, Madeleine F Hardy, Nishka Kishore, Jennifer J Knapp, Istvan A Kovacs, Irma Lemmens, Miles W Mee, Joseph C. Mellor, Carl Pollis, Carles Pons, Aaron D Richardson, Sadie Schlabach, Bridget Teeking, Anupama Yadav, Mariana Babor, Dawit Balcha, Omar Basha, Christian Bowman-Colin, Suet-Feung Chin, Soon Gang Choi, Claudia Colabella, Georges Coppin, Cassandra D'Amata, David De Ridder, Steffi De Rouck, Miquel Duran-Frigola, Hanane Ennajdaoui, Florian Goebels, Liana Goehring, Anjali Gopal, Ghazal Haddad, Elodie Hatchi, Mohamed Helmy, Yves Jacob, Yoseph Kassa, Serena Landini, Roujia Li, Natascha van Lieshout, Andrew MacWilliams, Dylan Markey, Joseph N Paulson, Sudharshan Rangarajan, John Rasla, Ashyad Rayhan, Thomas Rolland, Adriana San-Miguel, Yun Shen, Dayag Sheykhkarimli, Gloria M. Sheynkman, Eyal Simonovsky, Murat Taşan, Alexander Tejeda, Jean-Claude Twizere, Yang Wang, Robert J. Weatheritt, Jochen Weile, Yu Xia, Xinping Yang, Esti Yeger-Lotem, Quan Zhong, Patrick Aloy, Gary D. Bader, Javier De Las Rivas, Suzanne Gaudet, Tong Hao, Janusz Rak, Jan Tavernier, Vincent Tropepe, David E. Hill, Marc Vidal, Frederick P Roth, Michael A. Calderwood

Global insights into cellular organization and function require comprehensive understanding of interactome networks. Similar to how a reference genome sequence revolutionized human genetics, a reference map of the human interactome network is critical to fully understand genotype-phenotype relationships. Here we present the first human "all-by-all" binary reference interactome map, or "HuRI". With ~53,000 high-quality protein-protein interactions (PPIs), HuRI is approximately four times larger than the information curated from small-scale studies available in the literature. Integrating HuRI with genome, transcriptome and proteome data enables the study of cellular function within essentially any physiological or pathological cellular context. We demonstrate the use of HuRI in identifying specific subcellular roles of PPIs and protein function modulation via splicing during brain development. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms underlying tissue-specific phenotypes of Mendelian diseases. HuRI thus represents an unprecedented, systematic reference linking genomic variation to phenotypic outcomes.

69: The gut microbiota influences circulatory immune cell dynamics in humans
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Posted to bioRxiv 24 Apr 2019

The gut microbiota influences circulatory immune cell dynamics in humans
4 tweets microbiology

Jonas Schluter, Jonathan U. Peled, Bradford P Taylor, Melody Smith, Ying Taur, Sejal Morjaria, Maly Fenelus, Melissa S. Pessin, Tobias M. Hohl, Miguel-Angel Perales, Marcel R.M. van den Brink, Joao B Xavier

The gut microbiota influences the development and homeostasis of the mammalian immune system and can alter immune cell compositions in mice. However, our understanding of how the microbiota modulates immunity remains limited, particularly in humans where a lack of manipulative experiments makes inference challenging. Here we overcome this challenge by studying hundreds of hospitalized---and closely monitored---bone marrow transplantation patients as they recover from chemotherapy-induced immune ablation. This aggressive treatment causes large shifts in both white blood cell and microbiota populations allowing the relationships between the two to be studied simultaneously over time, with unprecedented resolution. Our analysis shows that the ecological diversity of the gut microbiota had an immunosuppressive effect on circulating lymphocyte counts similar in magnitude to that of anti-inflammatory and immunosuppressive drugs administered to cancer patients. Moreover, by controlling for drug treatments and clinical metadata, we identified several microbiota components strongly associated with white blood cell dynamics: Streptococcaceae associated with lymphocyte increase and Actinomycetaceae with lymphocyte suppression, Prevotellaceae with monocyte increase and Enterobacteriaceae with monocyte suppression, Ruminococcaceae with neutrophil increase and Lachnospiraceae and Bacteroidaceae with neutrophil suppression. Our analysis establishes a direct link between the intestinal microbiota and systemic immunity in humans, with implications on clinical outcomes and microbiota-based therapies.

70: Common DNA sequence variation influences 3-dimensional conformation of the human genome
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Posted to bioRxiv 30 Mar 2019

Common DNA sequence variation influences 3-dimensional conformation of the human genome
4 tweets genomics

David Gorkin, Yunjiang Qiu, Ming Hu, Kipper Fletez-Brant, Tristin Liu, Anthony Schmitt, Amina Noor, Joshua Chiou, Kyle J Gaulton, Jonathan Sebat, Yun Li, Kasper D. Hansen, Bing Ren

The 3-dimensional (3D) conformation of chromatin inside the nucleus is integral to a variety of nuclear processes including transcriptional regulation, DNA replication, and DNA damage repair. Aberrations in 3D chromatin conformation have been implicated in developmental abnormalities and cancer. Despite the importance of 3D chromatin conformation to cellular function and human health, little is known about how 3D chromatin conformation varies in the human population, or whether DNA sequence variation between individuals influences 3D chromatin conformation. To address these questions, we performed Hi-C on Lymphoblastoid Cell Lines (LCLs) from 20 individuals. We identified thousands of regions across the genome where 3D chromatin conformation varies between individuals and found that this conformational variation is often accompanied by variation in gene expression, histone modifications, and transcription factor (TF) binding. Moreover, we found that DNA sequence variation influences several features of 3D chromatin conformation including loop strength, contact insulation, contact directionality and density of local cis contacts. We mapped hundreds of Quantitative Trait Loci (QTLs) associated with 3D chromatin features and found evidence that some of these same variants are associated at modest levels with other molecular phenotypes as well as complex disease risk. Our results demonstrate that common DNA sequence variants can influence 3D chromatin conformation, pointing to a more pervasive role for 3D chromatin conformation in human phenotypic variation than previously recognized.

71: Realistic vOlumetric-Approach to Simulate Transcranial Electric Stimulation — ROAST — a fully automated open-source pipeline
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Posted to bioRxiv 10 Nov 2017

Realistic vOlumetric-Approach to Simulate Transcranial Electric Stimulation — ROAST — a fully automated open-source pipeline
4 tweets biophysics

Yu Huang, Abhishek Datta, Marom Bikson, Lucas C Parra

Objective: Research in the area of transcranial electrical stimulation (TES) often relies on computational models of current flow in the brain. Models are built based on magnetic resonance images (MRI) of the human head to capture detailed individual anatomy. To simulate current flow on an individual, the subject's MRI is segmented, virtual electrodes are placed on this anatomical model, the volume is tessellated into a mesh, and a finite element model (FEM) is solved numerically to estimate the current flow. Various software tools are available for each of these steps, as well as processing pipelines that connect these tools for automated or semi-automated processing. The goal of the present tool -- ROAST -- is to provide an end-to-end pipeline that can automatically process individual heads with realistic volumetric anatomy leveraging open-source software and custom scripts to improve segmentation and execute electrode placement. Approach: ROAST combines the segmentation algorithm of SPM8, a Matlab script for touch-up and automatic electrode placement, the finite element mesher iso2mesh and the solver getDP. We compared its performance with commercial FEM software, and SimNIBS, a well-established open-source modeling pipeline. Main Results: The electric fields estimated with ROAST differ little from the results obtained with commercial meshing and FEM solving software. We also do not find large differences between the various automated segmentation methods used by ROAST and SimNIBS. We do find bigger differences when volumetric segmentation are converted into surfaces in SimNIBS. However, evaluation on intracranial recordings from human subjects suggests that ROAST and SimNIBS are not significantly different in predicting field distribution, provided that users have detailed knowledge of SimNIBS. Significance: We hope that the detailed comparisons presented here of various choices in this modeling pipeline can provide guidance for future tool development. We released ROAST as an open-source, easy-to-install and fully-automated pipeline for individualized TES modeling.

72: Crosslinking actin networks produces compressive force
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Posted to bioRxiv 19 Apr 2019

Crosslinking actin networks produces compressive force
4 tweets biophysics

Rui Ma, Julien Berro

Actin has been shown to be essential for clathrin-mediated endocytosis in yeast. However, actin polymerization alone is likely insufficient to produce enough force to deform the membrane against the huge turgor pressure of yeast cells. In this paper, we used Brownian dynamics simulations to demonstrate that crosslinking of a meshwork of non-polymerizing actin filaments is able to produce compressive forces. We show that the force can be up to thousands of piconewtons if the crosslinker has a high stiffness. The force decays over time as a result of crosslinker turnover, and is a result of converting chemical binding energy into elastic energy.

73: Cross-modal integration of reward value during oculomotor planning
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Posted to bioRxiv 18 Apr 2019

Cross-modal integration of reward value during oculomotor planning
4 tweets neuroscience

Felicia Pei-Hsin Cheng, Adem Saglam, Selina Andre, Arezoo Pooresmaeili

Reward value guides goal-directed behavior and modulates early sensory processing. Rewarding stimuli are often multisensory but it is not known how reward value is combined across sensory modalities. Here we show that the integration of reward value critically depends on whether the distinct sensory inputs are perceived to emanate from the same multisensory object. We systematically manipulated the congruency in monetary reward values and the relative spatial positions of co-occurring auditory and visual stimuli that served as bimodal distractors during an oculomotor task. The amount of interference induced by the distractors was used as an indicator of their perceptual salience. Our results across two experiments show that when reward value is linked to each modality separately, the value congruence between vision and audition determines the combined salience of the bimodal distractors. However, reward value of vision wins over the value of audition if visual and auditory stimuli have been experienced as belonging to the same audiovisual object prior to the learning of the reward values. The perceived spatial alignment of auditory and visual stimuli is a prerequisite for the integration of their reward values, as no effect of reward value was observed when the two modalities were perceived to be misaligned. These results show that in a task that highly relies on the processing of visual spatial information, the reward values from multiple sensory modalities are integrated with each other, each with their respective weights. This weighting depends on the congruency in reward values, exposure history, and spatial co-localization.

74: In vivo microscopy reveals the impact of Pseudomonas aeruginosa social interactions on host colonization
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Posted to bioRxiv 07 Dec 2018

In vivo microscopy reveals the impact of Pseudomonas aeruginosa social interactions on host colonization
3 tweets microbiology

Chiara Rezzoagli, Elisa T Granato, Rolf Kuemmerli

Pathogenic bacteria engage in social interactions to colonize hosts, which include quorum-sensing-mediated communication and the secretion of virulence factors that can be shared as "public goods" between individuals. While in-vitro studies demonstrated that cooperative individuals can be displaced by "cheating" mutants freeriding on social acts, we know less about social interactions in infections. Here, we developed a live imaging system to track virulence factor expression and social strain interactions in the human pathogen Pseudomonas aeruginosa colonizing the gut of Caenorhabditis elegans. We found that shareable siderophores and quorum-sensing systems are expressed during infections, affect host gut colonization, and benefit non-producers. However, non-producers were unable to cheat and outcompete producers. Our results indicate that the limited success of cheats is due to a combination of the down-regulation of virulence factors over the course of the infection, the fact that each virulence factor examined contributed to but was not essential for host colonization, and the potential for negative-frequency dependent selection. Our findings shed new light on bacterial social interactions in infections and reveal potential limits of therapeutic approaches that aim to capitalize on social dynamics between strains for infection control.

75: Modeling implicates inhibitory network bistability as an underpinning of seizure initiation
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Posted to bioRxiv 18 Apr 2019

Modeling implicates inhibitory network bistability as an underpinning of seizure initiation
3 tweets neuroscience

Scott Rich, Homeira Moradi Chameh, Marjan Rafiee, Katie Ferguson, Frances K Skinner, Taufik Valiante

A plethora of recent experimental literature implicates the abrupt, synchronous activation of GABAergic interneurons in driving the sudden change in brain activity that heralds seizure initiation. However, the mechanisms predisposing an inhibitory network toward sudden coherence specifically during ictogenesis remain unknown. We address this question by comparing simulated inhibitory networks containing control interneurons and networks containing hyper-excitable interneurons modeled to mimic treatment with 4-Aminopyridine (4-AP), an agent commonly used to model seizures \textit{in vivo} and \textit{in vitro}. Our \textit{in silico} study demonstrates that model inhibitory networks with 4-AP interneurons are more prone than their control counterparts to exist in a bistable state in which asynchronously firing networks can abruptly transition into synchrony due to a brief perturbation. We further show that perturbations driving this transition could reasonably arise \textit{in vivo} based on models of background excitatory synaptic activity in the cortex. Thus, these results propose a mechanism by which an inhibitory network can transition from incoherent to coherent dynamics in a fashion that may precipitate seizure as a downstream effect. Moreover, this mechanism specifically explains why inhibitory networks containing hyper-excitable interneurons are more vulnerable to this state change, and how such networks can undergo this transition without a permanent change in the drive to the system. This, in turn, potentially explains such networks' increased vulnerability to seizure initiated by GABAergic activity.

76: In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation
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Posted to bioRxiv 18 Apr 2019

In vivo Firre and Dxz4 deletion elucidates roles for autosomal gene regulation
3 tweets genetics

Daniel Andergassen, Zachary D Smith, Jordan P. Lewandowski, Chiara Gerhardinger, Alexander Meissner, John L. Rinn

Recent evidence has determined that the conserved X chromosome mega-structures controlled by the Firre and Dxz4 alleles are not required for X chromosome inactivation (XCI) in cell lines. Here we determined the in vivo contribution of these alleles by generating mice carrying a single or double deletion of Firre and Dxz4. We found that these mutants are viable, fertile and show no defect in random or imprinted XCI. However, the lack of these elements results in many dysregulated genes on autosomes in an organ-specific manner. By comparing the dysregulated genes between the single and double deletion, we identified superloop, megadomain, and Firre locus dependent gene sets. The largest transcriptional effect was observed in all strains lacking the Firre locus, indicating that this locus is the main driver for these autosomal expression signatures. Collectively, these findings suggest that these X-linked loci are involved in autosomal gene regulation rather than XCI biology.

77: Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism
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Posted to bioRxiv 30 Nov 2018

Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism
3 tweets genetics

F. Kyle Satterstrom, Jack A. Kosmicki, Jiebiao Wang, Michael S. Breen, Silvia De Rubeis, Joon-Yong An, Minshi Peng, Ryan Lewis Collins, Jakob Grove, Lambertus Klei, Christine Stevens, Jennifer Reichert, Maureen Mulhern, Mykyta Artomov, Sherif Gerges, Brooke Sheppard, Xinyi Xu, Aparna Bhaduri, Utku Norman, Harrison Brand, Grace Schwartz, Rachel Nguyen, Elizabeth Guerrero, Caroline Dias, Branko Aleksic, Richard Anney, Mafalda Barbosa, Somer Bishop, Alfredo Brusco, Jonas Bybjerg-Grauholm, Angel Carracedo, Marcus C. Y. Chan, Andreas Chiocchetti, Brian Chung, Hilary Coon, Michael Cuccaro, Aurora Curró, Bernardo Dalla Bernardina, Ryan Doan, Enrico Domenici, Shan Dong, Chiara Fallerini, Montserrat Fernández-Prieto, Giovanni Battista Ferrero, Christine M. Freitag, Menachem Fromer, J. Jay Gargus, Daniel Geschwind, Elisa Giorgio, Javier González-Peñas, Stephen Guter, Danielle Halpern, Emily Hassen-Kiss, Xin He, Gail Herman, Irva Hertz-Picciotto, David M Hougaard, Christina M Hultman, Iuliana Ionita-Laza, Suma Jacob, Jesslyn Jamison, Astanand Jugessur, Miia Kaartinen, Gun Peggy Knudsen, Alexander Kolevzon, Itaru Kushima, So Lun Lee, Terho Lehtimäki, Elaine T Lim, Carla Lintas, W. Ian Lipkin, Diego Lopergolo, Fátima Lopes, Yunin Ludena, Patricia Maciel, Per Magnus, Behrang Mahjani, Nell Maltman, Dara S Manoach, Gal Meiri, Idan Menashe, Judith Miller, Nancy Minshew, Eduarda Montenegro M. de Souza, Danielle Moreira, Eric M Morrow, Ole Mors, Preben Bo Mortensen, Matthew Mosconi, Pierandrea Muglia, Benjamin Neale, Merete Nordentoft, Norio Ozaki, Aarno Palotie, Mara Parellada, Maria Rita Passos-Bueno, Margaret Pericak-Vance, Antonio Persico, Isaac Pessah, Kaija Puura, Abraham Reichenberg, Alessandra Renieri, Evelise Riberi, Elise Robinson, Kaitlin E. Samocha, Sven Sandin, Susan L Santangelo, Gerry Schellenberg, Stephen Scherer, Sabine Schlitt, Rebecca Schmidt, Lauren Schmitt, Isabela Maya W. Silva, Tarjinder Singh, Paige Siper, Moyra Smith, Gabriela Soares, Camilla Stoltenberg, Pål Suren, Ezra Susser, John Sweeney, Peter Szatmari, Lara Tang, Flora Tassone, Karoline Teufel, Elisabetta Trabetti, Maria del Pilar Trelles, Christopher Walsh, Lauren Weiss, Thomas Werge, Donna Werling, Emilie M. Wigdor, Emma Wilkinson, Jeremy A Willsey, Timothy Yu, Mullin H.C. Yu, Ryan Yuen, Elaine Zachi, Catalina Betancur, Edwin H. Cook, Louise Gallagher, Michael Gill, Thomas Lehner, Geetha Senthil, James S Sutcliffe, Audrey Thurm, Michael E. Zwick, Anders D. Børglum, Matthew W State, A. Ercument Cicek, Michael E. Talkowski, David J. Cutler, Bernie Devlin, Stephan Sanders, Kathryn Roeder, Joseph D. Buxbaum, Mark J. Daly

We present the largest exome sequencing study of autism spectrum disorder (ASD) to date (n=35,584 total samples, 11,986 with ASD). Using an enhanced Bayesian framework to integrate de novo and case-control rare variation, we identify 102 risk genes at a false discovery rate ≤ 0.1. Of these genes, 49 show higher frequencies of disruptive de novo variants in individuals ascertained for severe neurodevelopmental delay, while 53 show higher frequencies in individuals ascertained for ASD; comparing ASD cases with mutations in these groups reveals phenotypic differences. Expressed early in brain development, most of the risk genes have roles in regulation of gene expression or neuronal communication (i.e., mutations effect neurodevelopmental and neurophysiological changes), and 13 fall within loci recurrently hit by copy number variants. In human cortex single-cell gene expression data, expression of risk genes is enriched in both excitatory and inhibitory neuronal lineages, consistent with multiple paths to an excitatory/inhibitory imbalance underlying ASD.

78: Characterising the vocal repertoire of the Indian wolf (Canis lupus pallipes)
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Posted to bioRxiv 18 Apr 2019

Characterising the vocal repertoire of the Indian wolf (Canis lupus pallipes)
3 tweets animal behavior and cognition

Sougata Sadhukhan, Lauren Hennelly, Bilal Habib

Vocal communication in social animals plays a crucial role in mate choice, maintaining social structure, and foraging strategy. The Indian grey wolf, among the less studied subspecies, is a social carnivore that lives in groups called packs and has many types of vocal communication. In this study, we characterise harmonic vocalisation types in the Indian wolf using howl survey responses and opportunistic recordings from captive and nine packs (each pack contains 2-9 individuals) of free-ranging Indian wolves. Using principal component analysis, hierarchical clustering, and discriminant function analysis, we found four vocal types using 270 recorded vocalisations (Average Silhouette width Si = 0.598) which include howls and howl-bark (N=238), whimper (N=2), social squeak (N=28), and whine (N=2). Although having a smaller body size, Indian wolf howls have an average mean fundamental frequency of 0.422KHz (±0.126), which is similar to other Holarctic clade subspecies. The whimper showed the highest frequency modulation (37.296±4.601 KHz) and the highest mean fundamental frequency (1.708±0.524 KHz) compared to other call types. Less information is available on the third vocalisation type, i.e. ‘Social squeak’ or ‘talking’ (Mean fundamental frequency =0.461±0.083 KHz), which is highly variable (coefficient of frequency variation = 18.778±3.587 KHz). Our study’s characterisation of the Indian wolf’s harmonic vocal repertoire provides a first step in understanding the function and contextual use of vocalisations in this social mammal.

79: Predicting cognitive and mental health traits and their polygenic architecture using large-scale brain connectomics
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Posted to bioRxiv 16 Apr 2019

Predicting cognitive and mental health traits and their polygenic architecture using large-scale brain connectomics
3 tweets neuroscience

Luigi A. Maglanoc, Tobias Kaufmann, Dennis van der Meer, Andre F. Marquand, Thomas Wolfers, Rune Jonassen, Eva Hilland, Ole A Andreassen, Nils Inge Landrø, Lars T. Westlye

Cognitive abilities and mental disorders are complex traits sharing a largely unknown neuronal basis and aetiology. Their genetic architectures are highly polygenic and overlapping, which is supported by heterogeneous phenotypic expression and substantial clinical overlap. Brain network analysis provides a non-invasive means of dissecting biological heterogeneity yet its sensitivity, specificity and validity in clinical applications remains a major challenge. We used machine learning on static and dynamic temporal synchronization between all brain network nodes in 10,343 healthy individuals from the UK Biobank to predict (i) cognitive and mental health traits and (ii) their genetic underpinnings. We predicted age and sex to serve as our reference point. The traits of interest included individual level educational attainment and fluid intelligence (cognitive) and dimensional measures of depression, anxiety, and neuroticism (mental health). We predicted polygenic scores for educational attainment, fluid intelligence, depression, anxiety, and different neuroticism traits, in addition to schizophrenia. Beyond high accuracy for age and sex, permutation tests revealed above chance-level prediction accuracy for educational attainment and fluid intelligence. Educational attainment and fluid intelligence were mainly negatively associated with static brain connectivity in frontal and default mode networks, whereas age showed positive correlations with a more widespread pattern. In comparison, prediction accuracy for polygenic scores was at chance level across traits, which may serve as a benchmark for future studies aiming to link genetic factors and fMRI-based brain connectomics.

80: miR-9 mediated noise optimization of the her6 oscillator is needed for cell state progression in the Zebrafish hindbrain
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Posted to bioRxiv 15 Apr 2019

miR-9 mediated noise optimization of the her6 oscillator is needed for cell state progression in the Zebrafish hindbrain
3 tweets developmental biology

Ximena Soto, Veronica Biga, Jochen Kursawe, Robert Lea, Parnian Doostdar, Nancy Papalopulu

Ultradian oscillations of key transcription factors, such as members of the Hes family, are thought to be important in Neural Progenitor Cell (NPC) maintenance and miR-9 acts as a tuner of these oscillations in vitro. However, the existence and the role of such dynamic oscillatory expression in vivo is poorly understood. Here, we have generated a Zebrafish CRISPR knock-in Her6::venus fusion (Hes1 orthologue) to study endogenous dynamic gene expression in the embryonic hindbrain. We show that Her6 undergoes a transition from irregular, noisy, fluctuations to periodic oscillations as neurogenesis proceeds. In the absence of miR-9 input, noise in the Her6 oscillator increases and NPCs are unable to transit away from an intermediary state where they co-express progenitor and early differentiation markers. Thus, Her6 oscillations are facilitated by noise optimization mediated by miR-9 and this noise-tuning step is functionally important for cells to transition to differentiation.

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