bluuebunny/crossref_metadata_2025_split huggingface dataset:
An improved iCLIP protocol
Authors: Lee Flora C. Y. , Chakrabarti Anob M. , Hänel Heike , Monzón-Casanova Elisa , Hallegger Martina , Militti Cristina , Capraro Federica , Sadée Christoph , Toolan-Kerr Patrick , Wilkins Oscar , Turner Martin , König Julian , Sibley Christopher R. , Ule Jernej 
Published: August 2021

AbstractCrosslinking and Immunoprecipitation (CLIP) is a powerful technique to obtain transcriptome-wide maps of in vivo protein-RNA interactions, which are important to understand the post-transcriptional mechanisms mediated by RNA binding proteins (RBPs). Many variant CLIP protocols have been developed to improve the efficiency and convenience of cDNA library preparation. Here we describe an improved individual nucleotide resolution CLIP protocol (iiCLIP), which can be completed within 4 days from UV crosslinking to libraries for sequencing. For benchmarking, we directly compared PTBP1 iiCLIP libraries with the iCLIP2 protocol produced under standardised conditions, and with public eCLIP and iCLIP PTBP1 data. We visualised enriched motifs surrounding the identified crosslink positions and RNA maps of these crosslinks around the alternative exons regulated by PTBP1. Notably, motif enrichment was higher in iiCLIP and iCLIP2 in comparison to public eCLIP and iCLIP, and we show how this impacts the specificity of RNA maps. In conclusion, iiCLIP is technically convenient and efficient, and enables production of highly specific datasets for identifying RBP binding sites.
Fear of parasitism affects the functional role of ecosystem engineers
Authors: Mouritsen Kim N. , Dalsgaard Nina P. , Flensburg Sarah B. , Madsen Josefine C. , Selbach Christian 
Published: August 2021

AbstractFear is an integrated part of predator-prey interactions with cascading effects on the structure and function of ecosystems. Fear of parasitism holds a similar ecological potential but our understanding of the underlying mechanisms in host-parasite interactions is limited by lack of empirical examples. Here, we experimentally test if blue musselsMytilus edulisrespond behaviourally to the mere presence of infective transmission stages of the trematodeHimasthla elongataby ceasing filtration activity, thereby avoiding infection. Our results show that blue mussels reduced clearance rates by more than 30% in presences of parasites. The reduced filtration activity resulted in lower infection rates in experimental mussels. The identified parasite-specific avoidance behaviour can be expected to play a significant role in regulating the ecosystem engineering function of blue mussels in coastal habitats.
Genome survey sequencing of wild cotton (Gossypium robinsonii) reveals insights into proteomic responses of pollen to extreme heat
Authors: Masoomi-Aladizgeh Farhad , Kamath Karthik Shantharam , Haynes Paul A. , Atwell Brian J. 
Published: August 2021

ABSTRACTHeat stress specifically affects fertility by impairing pollen viability but cotton wild relatives successfully reproduce in hot savannas where they evolved. An Australian heat-tolerant cotton (Gossypium robinsonii) was exposed to heat events during pollen development, then mature pollen was subjected to deep proteomic analysis using 57,023 predicted genes from a genomic database we assembled for the same species. Three stages of pollen development, including tetrads, uninucleate and binucleate microspores were exposed to 36°C or 40°C for 5 d and the resulting mature pollen was collected at anthesis (p-TE, p-UN and p-BN, respectively). Using SWATH-MS proteomic analysis, 2,704 proteins were identified and quantified across all pollen samples analyzed. Proteins predominantly decreased in abundance at all stages in response to heat, particularly after exposure of tetrads to 40°C. Functional enrichment analyses demonstrated that extreme heat increased the abundance of proteins that contributed to increased mRNA splicing via spliceosome, initiation of cytoplasmic translation and protein refolding in p-TE40. However, other functional categories that contributed to intercellular transport were inhibited in p-TE40, linked potentially to Rab proteins. We ascribe the resilience of reproductive processes in G. robinsonii at temperatures up to 40°C, relative to commercial cotton, to a targeted reduction in protein transport.
An integrated model for termination of RNA polymerase III transcription
Authors: Xie Juanjuan , Aiello Umberto , Clement Yves , Haidara Nouhou , Girbig Mathias , Schmitzova Jana , Pena Vlad , Müller Christoph W. , Libri Domenico , Porrua Odil 
Published: August 2021

AbstractRNA polymerase III (RNAPIII) synthesizes essential and abundant non-coding RNAs such as tRNAs. Controlling RNAPIII span of activity by accurate and efficient termination is a challenging necessity to ensure robust gene expression and to prevent conflicts with other DNA-associated machineries. The mechanism of RNAPIII termination is believed to be simpler than that of other eukaryotic RNA polymerases, solely relying on the recognition of a T-tract in the non-template strand. Here we combine high-resolution genome-wide analyses and in vitro transcription termination assays to revisit the mechanism of RNAPIII transcription termination in budding yeast. We show that T-tracts are necessary but not always sufficient for termination and that secondary structures of the nascent RNAs are important auxiliary cis-acting elements. Moreover, we show that the helicase Sen1 plays a key role in a fail-safe termination pathway. Our results provide a comprehensive model illustrating how multiple mechanisms cooperate to ensure efficient RNAPIII transcription termination.
Invariant neural dynamics drive commands to control different movements
Authors: Athalye Vivek R. , Khanna Preeya , Gowda Suraj , Orsborn Amy L. , Costa Rui M. , Carmena Jose M. 
Published: August 2021

SummaryIt has been proposed that the nervous system has the capacity to generate a wide variety of movements because it re-uses some invariant code. Previous work has identified that dynamics of neural population activity are similar during different movements, where dynamics refer to how the instantaneous spatial pattern of population activity changes in time. Here we test whether invariant dynamics of neural populations are actually used to issue the commands that direct movement. Using a brain-machine interface that transformed rhesus macaques’ motor cortex activity into commands for a neuroprosthetic cursor, we discovered that the same command is issued with different neural activity patterns in different movements. However, these different patterns were predictable, as we found that the transitions between activity patterns are governed by the same dynamics across movements. These invariant dynamics are low-dimensional, and critically, they align with the brain-machine interface, so that they predict the specific component of neural activity that actually issues the next command. We introduce a model of optimal feedback control that shows that invariant dynamics can help transform movement feedback into commands, reducing the input that the neural population needs to control movement. Altogether our results demonstrate that invariant dynamics drive commands to control a variety of movements, and show how feedback can be integrated with invariant dynamics to issue generalizable commands.
The adaptive role of cell death in yeast communities stressed with macrolide antifungals
Authors: Kireeva N. , Sokolov S.S. , Smirnova E.A. , Galkina K.V. , Severin F.F. , Knorre D.A. 
Published: August 2021

AbstractMicroorganisms cooperate with each other to protect themselves from environmental stressors. An extreme case of such cooperation is regulated cell death for the benefit of other cells. Dying cells can provide surviving cells with nutrients or induce their stress-response by transmitting an alarm signal; however, the role of dead cells in microbial communities is unclear. Here we searched for types of stressors the protection from which can be achieved by death of a subpopulation of cells. Thus, we compared the survival of Saccharomyces cerevisiae cells upon exposure to various stressors in the presence of additionally supplemented living versus dead cells. We found that dead cells contribute to yeast community resistance against macrolide antifungals (e.g. amphotericin B [AmB] and filipin) to a greater extent than living cells. Dead yeast cells absorbed more macrolide filipin than control cells because they exposed intracellular sterol-rich membranes. We also showed that, upon the addition of lethal concentrations of AmB, supplementation with AmB-sensitive cells but not with AmB-resistant cells enabled the survival of wild-type cells. Together, our data suggests that cell-to-cell heterogeneity in sensitivity to AmB can be an adaptive mechanism helping yeast communities to resist macrolides, which are naturally occurring antifungal agents.ImportanceEukaryotic microorganisms harbour elements of programmed cell death (PCD) mechanisms that are homologous to the PCD of multicellular metazoa. However, it is still debated whether microbial PCD has an adaptive role or the processes of cell death are an aimless operation in self-regulating molecular mechanisms. Here, we demonstrated that dying yeast cells provide an instant benefit for their community by absorbing macrolides, which are bacteria-derived antifungals. Our results illustrate the principle that the death of a microorganism can contribute to the survival of its kin and suggest that early plasma membrane permeabilization improves community-level protection. The latter makes a striking contrast to the manifestations of apoptosis in higher eukaryotes, the process by which plasma membranes maintain integrity.
Gene function prediction in five model eukaryotes based on gene relative location through machine learning
Authors: Pazos Obregón Flavio , Silvera Diego , Soto Pablo , Yankilevich Patricio , Guerberoff Gustavo , Cantera Rafael 
Published: August 2021

AbstractMotiviationThe function of most genes is unknown. The best results in gene function prediction are obtained with machine learning-based methods that combine multiple data sources, typically sequence derived features, protein structure and interaction data. Even though there is ample evidence showing that a gene’s function is not independent of its location, the few available examples of gene function prediction based on gene location relay on sequence identity between genes of different organisms and are thus subjected to the limitations of the relationship between sequence and function.ResultsHere we predict thousands of gene functions in five eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens) using machine learning models trained with features derived from the location of genes in the genomes to which they belong. To the best of our knowledge this is the first work in which gene function prediction is successfully achieved in eukaryotic genomes using predictive features derived exclusively from the relative location of the genes.Contactfpazos@iibce.edu.uySupplementary informationhttp://gfpml.bnd.edu.uy
Nuclear soluble cGAS senses DNA virus infection
Authors: Wu Yakun , Song Kun , Hao Wenzhuo , Wang Lingyan , Li Shitao 
Published: August 2021

ABSTRACTThe cytosolic DNA sensor cGAS detects foreign DNA from pathogens or self-DNA from cellular damage and instigates type I interferon (IFN) expression. Recent studies find that cGAS also localizes in the nucleus and binds the chromatin. Despite how cGAS is inhibited in the nucleus is well elucidated, whether nuclear cGAS participates in DNA sensing is not clear. Here, we report that herpes simplex virus 1 (HSV-1) infection caused the release of cGAS from the chromatin into the nuclear soluble fraction. Like its cytosolic counterpart, the leaked nuclear soluble cGAS could sense viral DNA, produce cGAMP, and induce mRNA expression of type I IFN and interferon-stimulated genes. Furthermore, the nuclear cGAS limited HSV-1 infection. Taken together, our study demonstrates that HSV-1 infection releases cGAS from the chromatin tethering and, in turn, the nuclear soluble cGAS activates type I IFN production.
mobileOG-db: a manually curated database of protein families mediating the life cycle of bacterial mobile genetic elements
Authors: Brown Connor L. , Mullet James , Hindi Fadi , Stoll James E. , Gupta Suraj , Choi Minyoung , Keenum Ishi , Vikesland Peter , Pruden Amy , Zhang Liqing 
Published: August 2021

ABSTRACTCurrently available databases of bacterial mobile genetic elements (MGEs) contain both “core” and accessory MGE functional modules, the latter of which are often only transiently associated with the element. The presence of these accessory genes, which are often close homologs to primarily immobile genes, limits the usability of these databases for MGE annotation. To overcome this limitation, we analysed 10,776,212 protein sequences derived from seven MGE databases to compile a comprehensive database of 6,140 manually curated protein families that are linked to the “life cycle” (integration, excision, replication/recombination/repair, transfer, and stability/defense) of all major classes of bacterial MGEs. We overlay experimental information where available to create a tiered annotation scheme of high-quality annotations and annotations inferred exclusively through bioinformatic evidence. We additionally provide an MGE-class label for each entry (e.g., plasmid, integrative element) derived from the source database, and assign a list of keywords to each entry to delineate different MGE functional modules and to facilitate annotation. The resulting database, mobileOG-db (for mobile orthologous groups), provides a simple and readily interpretable foundation for an array of MGE-centred analyses. mobileOG-db can be accessed at mobileogdb.flsi.cloud.vt.edu/, where users can browse and design, refine, and analyse custom subsets of the dynamic mobilome.
Multi-omic brain and behavioral correlates of cell-free fetal DNA methylation in macaque maternal obesity models
Authors: Laufer Benjamin I. , Hasegawa Yu , Zhang Zhichao , Hogrefe Casey E. , Del Rosso Laura A. , Haapanan Lori , Hwang Hyeyeon , Bauman Melissa D. , Van de Water Judy A. , Taha Ameer Y. , Slupsky Carolyn M. , Golub Mari S. , Capitanio John P. , VandeVoort Catherine A. , Walker Cheryl K. , LaSalle Janine M. 
Published: August 2021

AbstractMaternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. Ultimately, maternal obesity altered infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic biomarkers.
Temporal scaling of dopamine neuron firing and dopamine release by distinct ion channels shape behavior
Authors: Juarez Barbara , Kong Mi-Seon , Jo Yong S. , Elum Jordan E. , Yee Joshua X. , Ng-Evans Scott , Cline Marcella , Hunker Avery C. , Quinlan Meagan A. , Baird Madison A. , Elerding Abigail J. , Johnson Mia , Ban Derek , Mendez Adriana , Goodwin Nastacia L. , Soden Marta E. , Zweifel Larry S. 
Published: August 2021

AbstractDespite the widely known role of dopamine in reinforcement learning, how the patterns of dopamine release that are critical to the acquisition, performance, and extinction of conditioned responses are generated is poorly resolved. Here, we demonstrate that the coordinated actions of two ion channels, Kv4.3 and BKCa1.1, control the pattern of dopamine neuron firing and dopamine release on different time scales to regulate separate phases of reinforced behavior in mice. Inactivation of Kv4.3 in VTA dopamine neurons increasesex vivopacemaker activity and excitability that is associated with increasedin vivoramping dynamics prior to lever press in a learned instrumental response paradigm. Loss of Kv4.3 enhances performance of the learned response and facilitates extinction. In contrast, loss of BKCa1.1 increases burst firing and phasic dopamine release that enhances learning of an instrumental response. Inactivation of BKCa1.1 enhances extinction burst lever pressing in early extinction training that is associated with increased reward prediction error signals. These data demonstrate that temporally distinct patterns of dopamine release are governed by the intrinsic regulators of the cell to shape behavior.TeaserWe show that ion channels in midbrain dopamine neurons are critical for patterning action potential firing at the cell body and governing neurotransmitter release to regulate reinforcement learning.
Binary outcomes of enhancer activity underlie stable random monoallelic expression
Authors: Kissiov Djem U. , Ethell Alexander , Chen Sean , Wolf Natalie K. , Zhang Chenyu , Dang Susanna M. , Jo Yeara , Madsen Katrine N. , Paranjpe Ishan D. , Lee Angus Y. , Chim Bryan , Muljo Stefan A. , Raulet David H. 
Published: August 2021

AbstractMitotically stable random monoallelic gene expression (RME) is documented for a small percentage of autosomal genes. Here we investigated the role of enhancers in the RME of natural killer (NK) cell receptor genes. Enhancers were accessible and enriched in H3K27ac on silent and active alleles alike, decoupling enhancer activation and expression. Enhancers controlled gene expression frequency, as predicted by the binary model of enhancer action, and enhancer deletion converted the broadly expressedNkg2dinto an RME gene, recapitulating natural variegation. The results suggested that RME is a consequence of general enhancer properties and therefore many genes may be subject to some degree of RME, which was borne out by analysis of a panel of genes previously thought to be universally expressed within defined hematopoietic lineages:Nkg2d,Cd45, Cd8aandThy1. We propose that previously documented RME is an extreme on a continuum of intrinsically probabilistic gene expression.
What do we gain when tolerating loss? The information bottleneck wrings out recombination
Authors: Narechania Apurva , Bobo Dean , DeSalle Rob , Mathema Barun , Kreiswirth Barry , Planet Paul J. 
Published: August 2021

AbstractMost microbes have the capacity to acquire genetic material from their environment. Recombination of foreign DNA yields genomes that are, at least in part, incongruent with the vertical history of their species. Dominant approaches for detecting these transfers are phylogenetic, requiring a painstaking series of analyses including alignment and phylogenetic tree reconstruction. These traditional pan-genomic methods do not scale. Here we propose an unsupervised, alignment-free and tree-free technique based on the sequential information bottleneck (SIB), an optimization procedure designed to extract some portion of relevant information from one random variable conditioned on another. In our case, this joint probability distribution tabulates occurrence counts of k-mers against their genomes of origin with the expectation that recombination will create a strong signal that unifies certain sets of co-occuring k-mers. We conceptualize the technique as a rate-distortion problem, measuring distortion in the relevance information as k-mers are compressed into clusters based on their co-occurrence in the source genomes. The result is fast, model-free, lossy compression of k-mers into groups that learns tracts of shared genome sequence differentiating recombined elements from the vertically inherited core. We show that the technique yields a new recombination measure based purely on information, divorced from any biases and limitations inherent to alignment and phylogeny.SignificanceThe information bottleneck, a lossy compression technique borrowed from the information theoretic and Natural Langauge Processing literature, is well suited to detecting evolutionary patterns in sets of co-occuring k-mers. Here we show that we can detect simulated and real recombination events while highlighting a core set of k-mers that comprise the vertically inherited portion of any set of genomes. Moreover, the compressibility of any given set of genomes offers a new way to compare the pangenomes of clades across the microbial tree of life. In our application, the bottleneck is informed by genome origin, our relevance variable, but the technique is general. The information bottleneck can be used for any biological contingency matrix where the goal is to learn groups from unstructured data.
Temporally dynamic antagonism between transcription and chromatin compaction controls stochastic photoreceptor specification
Authors: Voortman Lukas , Anderson Caitlin , Urban Elizabeth , Yuan Mini , Tran Sang , Neuhaus-Follini Alexandra , Derrick Josh , Gregor Thomas , Johnston Robert J. 
Published: August 2021

AbstractStochastic mechanisms diversify cell fates during development. How cells randomly choose between two or more fates remains poorly understood. In the Drosophila eye, the random mosaic of two R7 photoreceptor subtypes is determined by expression of the transcription factor Spineless (Ss). Here, we investigated how cis-regulatory elements and trans factors regulate nascent transcriptional activity and chromatin compaction at the ss gene locus during R7 development. We find that the ss locus is in a compact state in undifferentiated cells. An early enhancer drives ss transcription in all R7 precursors to open the ss locus. In differentiating cells, transcription ceases and the ss locus stochastically remains open or compacts. In SsON R7s, ss is open and competent for activation by a late enhancer, whereas in SsOFF R7s, ss is compact and repression prevents expression. Our results suggest that a temporally dynamic antagonism, in which transcription drives decompaction and then compaction represses transcription, controls stochastic cell fate specification.