bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presynaptic dysfunction inCASK-related neurodevelopmental disorders
Authors: Becker Martin , Mastropasqua Francesca , Reising Jan Philipp , Maier Simon , Ho Mai-Lan , Rabkina Ielyzaveta , Li Danyang , Neufeld Janina , Ballenberger Lea , Myers Lynnea , Moritz Viveka , Kele Malin , Wincent Josephine , Willfors Charlotte , Sitnikov Rouslan , Herlenius Eric , Anderlid Britt-Marie , Falk Anna , Bölte Sven , Tammimies Kristiina 
Published: December 2019

SummaryCASK-related disorders are a genetically defined group of neurodevelopmental syndromes. There is limited information about the effects ofCASKmutations in human neurons. Therefore, we sought to delineateCASKmutation consequences and neuronal level effects using induced pluripotent stem cell-derived neurons from two mutation carriers; one male diagnosed with ASD and a female with MICPCH. We show a reduction of the CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of gene sets involved in presynaptic development and CASK protein interactors. Furthermore,CASK-deficient neurons showed decreased inhibitory presynapse size as indicated by VGAT staining, which may alter the excitatory-inhibitory (E/I) balance in developing neural circuitries. Usingin vivomagnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validatein vitrocellular data in brain. Our data shows that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments forCASK-related disorders.HighlightsModelling of CASK-related disorders using iPSC-derived human neuronal cellsCASKmutations cause dysregulation of its protein interactor partnersReduced CASK levels primarily affect inhibitory presynapse developmentIn vitroGABAergic phenotype predictsin vivoneurotransmitter levels
Genome variation and population structure among 1,142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii
Authors:   The Anopheles gambiae 1000 Genomes Consortium, Clarkson Chris S , Miles Alistair , Harding Nicholas J , Lucas Eric R , Battey C J , Amaya-Romero Jorge Edouardo , Cano Jorge , Diabate Abdoulaye , Constant Edi , Nwakanma Davis C , Jawara Musa , Essandoh John , Dinis Joao , Le Goff Gilbert , Robert Vincent , Troco Arlete D , Costantini Carlo , Rohatgi Kyanne R , Elissa Nohal , Coulibaly Boubacar , Midega Janet , Mbogo Charles , Mawejje Henry D , Stalker Jim , Rockett Kirk A , Drury Eleanor , Mead Daniel , Jeffreys Anna E , Hubbart Christina , Rowlands Kate , Isaacs Alison T , Jyothi Dushyanth , Malangone Cinzia , Kamali Maryam , Henrichs Christa , Simpson Victoria , Ayala Diego , Besansky Nora J , Burt Austin , Caputo Beniamino , della Torre Alessandra , Fontaine Michael , Godfray H. Charles J , Hahn Matthew W , Kern Andrew D , Lawniczak Mara K N , O’Loughlin Samantha , Pinto Joao , Riehle Michelle M , Sharakhov Igor , Schrider Daniel R , Vernick Kenneth D , White Bradley J , Donnelly Martin J , Kwiatkowski Dominic P 
Published: December 2019

AbstractMosquito control remains a central pillar of efforts to reduce malaria burden in sub-Saharan Africa. However, insecticide resistance is entrenched in malaria vector populations, and countries with high malaria burden face a daunting challenge to sustain malaria control with a limited set of surveillance and intervention tools. Here we report on the second phase of a project to build an open resource of high quality data on genome variation among natural populations of the major African malaria vector species Anopheles gambiae and Anopheles coluzzii. We analysed whole genomes of 1,142 individual mosquitoes sampled from the wild in 13 African countries, and a further 234 individuals comprising parents and progeny of 11 lab crosses. The data resource includes high confidence single nucleotide polymorphism (SNP) calls at 57 million variable sites, genome-wide copy number variation (CNV) calls, and haplotypes phased at biallelic SNPs. We used these data to analyse genetic population structure, and characterise genetic diversity within and between populations. We also illustrate the utility of these data by investigating species differences in isolation by distance, genetic variation within proposed gene drive target sequences, and patterns of resistance to pyrethroid insecticides. This data resource provides a foundation for developing new operational systems for molecular surveillance, and for accelerating research and development of new vector control tools.
Genome compartmentalization predates species divergence in the plant pathogen genus Zymoseptoria
Authors: Feurtey Alice , Lorrain Cécile , Croll Daniel , Eschenbrenner Christoph , Freitag Michael , Habig Michael , Haueisen Janine , Möller Mareike , Schotanus Klaas , Stukenbrock Eva H. 
Published: December 2019

AbstractBackgroundAntagonistic co-evolution can drive rapid adaptation in pathogens and shape genome architecture. Comparative genome analyses of several fungal pathogens revealed highly variable genomes, for many species characterized by specific repeat-rich genome compartments with exceptionally high sequence variability. Dynamic genome architecture may enable fast adaptation to host genetics. The wheat pathogen Zymoseptoria tritici with its highly variable genome and has emerged as a model organism to study the genomic evolution of plant pathogens. Here, we compared genomes of Z. tritici isolates and genomes of sister species infecting wild grasses to address the evolution of genome composition and structure.ResultsUsing long-read technology, we sequenced and assembled genomes of Z. ardabiliae, Z. brevis, Z. pseudotritici and Z. passerinii, together with two isolates of Z. tritici. We report a high extent of genome collinearity among Zymoseptoria species and high conservation of genomic, transcriptomic and epigenomic signatures of compartmentalization. We identify high gene content variability both within and between species. In addition, such variability is mainly limited to the accessory chromosomes and accessory compartments. Despite strong host specificity and non-overlapping host-range between species, effectors are mainly shared among Zymoseptoria species, yet exhibiting a high level of presence-absence polymorphism within Z. tritici. Using in planta transcriptomic data from Z. tritici, we suggest different roles for the shared orthologs and for the accessory genes during infection of their hosts.ConclusionDespite previous reports of high genomic plasticity in Z. tritici, we describe here a high level of conservation in genomic, epigenomic and transcriptomic signatures of genome architecture and compartmentalization across the genus Zymoseptoria. The compartmentalized genome may reflect purifying selection to retain a functional core genome and relaxed selection on the accessory genome allowing a higher extent of polymorphism.
Choroid-resident macrophages maintain local vasculature and RPE integrity and spontaneously regenerate following depletion
Authors: Yang Xiao , Zhao Lian , Campos Maria M. , Abu-Asab Mones , Ortolan Davide , Hotaling Nathan , Bharti Kapil , Wong Wai T. 
Published: December 2019

AbstractThe choroid of the eye provides necessary vascular supply to the outer retina across the retinal pigment epithelial (RPE) layer and is a locus of progressive degenerative change in aging and age-related macular degeneration (AMD). Cellular mechanisms that maintain or compromise choroidal vasculature homeostasis are not well understood, complicating therapeutic efforts. We discover here that pharmacological ablation of macrophages normally resident in the adult mouse choroid via blockade of the CSF1 receptor resulted in progressive thinning of the choroid layer and atrophy of the choriocapillaris. Concurrently, choroidal macrophage ablation also induced structural disorganization of the RPE cell layer, downregulation of RPE visual cycle genes, and altered RPE angiogenic factor expression. Suspension of CSF1R blockade following ablation conversely enabled spontaneous regeneration of the choroidal macrophage population, restoring original macrophage distribution and morphological features. Macrophage repopulation significantly ameliorated the ablation-induced changes in RPE structure and angiogenic factor expression and arrested choroidal vascular atrophy. These findings reveal a previously unsuspected trophic function of resident choroidal macrophages in the maintenance of choroidal vasculature and the RPE layer, suggesting that insufficiency of macrophage function may contribute to age- and AMD-associated pathology. Modulating choroidal macrophage support function can constitute a strategy for therapeutic preservation of the choroid and RPE in AMD prevention and treatment.Significance StatementChoroidal atrophy is associated with normal aging and progression in age-related macular degeneration (AMD), a leading cause of blindness. Herein, we identify the choroidal macrophage as a critical player in the homeostatic maintenance of choroid-RPE complex of the eye. Depletion of choroidal macrophages resulted in progressive vascular atrophy, altered structure of retinal pigment epithelial (RPE) cells, and dysregulated RPE expression of visual cycle protein and angiogenic factors, VEGF and PEDF. We discovered that choroidal macrophages can regenerate and repopulate the choroid following depletion, ameliorating RPE alterations and arresting vascular atrophy. Our results suggest that insufficiency of macrophage function may contribute to age- and AMD-associated pathology, and modulation of macrophage support functions may be therapeutically useful in AMD prevention and treatment.
Fast and flexible design of novel proteins using graph neural networks
Authors: Strokach Alexey , Becerra David , Corbi-Verge Carles , Perez-Riba Albert , Kim Philip M. 
Published: December 2019

AbstractProtein structure and function is determined by the arrangement of the linear sequence of amino acids in 3D space. Despite substantial advances, precisely designing sequences that fold into a predetermined shape (the “protein design” problem) remains difficult. We show that a deep graph neural network, ProteinSolver, can solve protein design by phrasing it as a constraint satisfaction problem (CSP). To sidestep the considerable issue of optimizing the network architecture, we first develop a network that is accurately able to solve the related and straightforward problem of Sudoku puzzles. Recognizing that each protein design CSP has many solutions, we train this network on millions of real protein sequences corresponding to thousands of protein structures. We show that our method rapidly designs novel protein sequences and perform a variety ofin silicoandin vitrovalidations suggesting that our designed proteins adopt the predetermined structures.One Sentence SummaryA neural network optimized using Sudoku puzzles designs protein sequences that adopt predetermined structures.
Dynamic relocalization of the cytosolic type III secretion system components prevents premature protein secretion at low external pH
Authors: Wimmi Stephan , Balinovic Alexander , Jeckel Hannah , Selinger Lisa , Lampaki Dimitrios , Eisemann Emma , Meuskens Ina , Linke Dirk , Drescher Knut , Endesfelder Ulrike , Diepold Andreas 
Published: December 2019

AbstractMany bacterial pathogens use a type III secretion system (T3SS) to manipulate host cells. Protein secretion by the T3SS injectisome is activated upon contact to any host cell, and it has been unclear how premature secretion is prevented during infection. We found that in gastrointestinal pathogens, cytosolic injectisome components are temporarily released from the proximal interface of the injectisome at low external pH, preventing protein secretion in acidic environments, such as the stomach. In Yersinia enterocolitica, low external pH is detected in the periplasm and leads to a partial dissociation of the inner membrane injectisome component SctD, which in turn causes the dissociation of the cytosolic T3SS components. This effect is reversed upon restoration of neutral pH, allowing a fast activation of the T3SS at the native target regions within the host. These findings indicate that the cytosolic components form an adaptive regulatory interface, which regulates T3SS activity in response to environmental conditions.
Draft Genomes of two Artocarpus plants, Jackfruit (A. heterophyllus) and Breadfruit (A. altilis)
Authors: Sahu Sunil Kumar , Liu Min , Yssel Anna , Kariba Robert , Jiang Sanjie , Song Bo , Muthemba Samuel , Hendre Prasad S. , Jamnadass Ramni , Kao Shu-Min , Featherston Jonathan , Zerega Nyree J.C. , Xu Xun , Yang Huanming , Deynze Allen Van , Peer Yves Van de , Liu Xin , Liu Huan 
Published: December 2019

AbstractTwo of the most economically important plants in the Artocarpus genus are jackfruit (A. heterophyllus Lam.) and breadfruit (A. altilis (Parkinson) Fosberg). Both species are long-lived trees that have been cultivated for thousands of years in their native regions. Today they are grown throughout tropical to subtropical areas as an important source of starch and other valuable nutrients. There are hundreds of breadfruit varieties that are native to Oceania, of which the most commonly distributed types are seedless triploids. Jackfruit is likely native to the western Ghats of India and produces one of the largest tree-borne fruit structures (reaching up to 100 pounds). To date, there is limited genomic information for these two economically important species. Here, we generated 273 Gb and 227 Gb of raw data from jackfruit and breadfruit, respectively. The high-quality reads from jackfruit were assembled into 162,440 scaffolds totaling 982 Mb with 35,858 genes. Similarly, the breadfruit reads were assembled into 180,971 scaffolds totaling 833 Mb with 34,010 genes. A total of 2,822 and 2,034 expanded gene families were found in jackfruit and breadfruit, respectively, enriched in pathways including starch- and sucrose metabolism, photosynthesis and others. The copy number of several starch synthesis related genes were found increased in jackfruit and breadfruit compared to closely related species, and the tissue specific expression might imply their sugar-rich and starch-rich characteristics. Overall, the publication of high-quality genomes for jackfruit and breadfruit provides information about their specific composition and the underlying genes involved in sugar and starch metabolism.
Intranasal oxytocin administration rescues neonatal thermo-sensory deficit in mouse model of Autism
Authors: Da Prato Laura Caccialupi , Abdallah Dina , Point Vanessa , Schaller Fabienne , Pallesi-Pocachard Emilie , Montheil Aurélie , Canaan Stéphane , Gaiarsa Jean-Luc , Muscatelli Françoise , Matarazzo Valéry 
Published: December 2019

ABSTRACTAtypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we identified that neonatal mice lacking the autism-associated gene Magel2 fail to react to cool sensory stimuli, while autonomic thermoregulatory function is active. This neonatal deficit was mimicked in control neonates by chemogenetic inactivation of oxytocin neurons. Importantly, intranasal administration of oxytocin was able to rescue the phenotype and brain Erk signaling impairment in mutants. This preclinical study establishes for the first-time early life impairments in thermosensory integration and shows the therapeutic potential benefits of intranasal oxytocin treatment on neonatal atypical sensory reactivity.
Feature-specific patterns of attention and functional connectivity in human visual cortex
Authors: Wailes-Newson Kirstie , Morland Antony B , Vernon Richard J. W. , Wade Alex R. 
Published: December 2019

AbstractAttending to different features of a scene can alter the responses of neurons in early- and mid- level visual areas but the nature of this change depends on both the (top down) attentional task and the (bottom up) visual stimulus. One outstanding question is the spatial scale at which cortex is modulated by attention to low-level stimulus features such as shape, contrast and orientation. It is unclear whether the recruitment of neurons to particular tasks occurs at an area level or at the level of intra-areal sub-populations, or whether the critical factor is a change in the way that areas communicate with each other. Here we use functional magnetic resonance imaging (fMRI) and psychophysics, to ask how areas known to be involved in processing different visual features (orientation, contrast and shape) are modulated as participants switch between tasks based on those features while the visual stimulus itself is effectively constant. At a univariate level, we find almost no feature-specific bottom-up or top-down responses in the areas we examine. However, multivariate analyses reveal a complex pattern of voxel-level modulation driven by attentional task. Connectivity analyses also demonstrate flexible and selective patterns of connectivity between early visual areas as a function of attentional focus. Overall, we find that attention alters the sensitivity and connectivity of neuronal subpopulations within individual early visual areas but, surprisingly, not the univariate response amplitudes of the areas themselves.
New observations on non-coding RNAs involved in the dual translation system in zebrafish development
Authors: Breit Timo M. , Pagano Johanna F. B. , van der Jagt Pjotr L. , Mittring Ellis , Ensink Wim A. , van Olst Marina , van Leeuwen Selina , de Leeuw Wim , Nehrdich Ulrike , Spaink Herman P. , Rauwerda Han , Dekker Rob J. 
Published: December 2019

AbstractCellular translation relies heavily on the involvements of several types of non-coding RNAs. In previous studies we have identified a dual translation system in zebrafish development, involving maternal-type and somatic-type rRNAs, snoRNAs, and snRNAs. In this study we focused on several remaining non-coding RNAs involved in the translation system; tRNAs, RNase P, and SRP RNA. Even though our studies have been limited in extent, for all three types of non-coding RNA we were able to identify a maternal-specific type, with substantial sequence differences as compared to the somatic-type variant. Hence, these RNA types complement the previously discovered RNA types in the unique dual translation system in zebrafish development.
A closer look at the timecourse of mind wandering: pupillary responses and behaviour
Authors: Pelagatti Claudia , Binda Paola , Vannucci Manila 
Published: December 2019

AbstractMind wandering (MW) refers to the shift of attention away from a primary task and/or external environment towards thoughts unrelated to the task. Recent evidence has shown that pupillometry can be used as an objective marker of the onset and maintenance of externally-driven MW episodes. In the present study we aimed to further investigate pupillary changes associated with the onset and duration of self-reported MW episodes.We used a modified version of the joint behavioural-pupillometry paradigm we recently introduced. Participants were asked to perform a monotonous vigilance task which was intermixed with task-irrelevant cue-phrases (visually presented verbal cues); they were instructed to interrupt the task whenever a thought came to mind (self-caught method) and to indicate the trigger of their thought, if any. We found systematic pupil dilation after the presentation of verbal cues reported to have triggered MW, compared with other verbal cues presented during a supposedly on-task period (i.e., the period immediately following the resuming of the task after a self-caught interruption and MW report). These results confirm that pupil diameter is sensitive to the changes associated with the onset of MW and its unfolding over time.Moreover, by computing the latency between the trigger presentation and the task interruption (self-catch), we could also estimate the duration of MW episodes triggered by verbal cues. However, a high variability was found, implying very large inter-event variability, which could not be explained by any of the MW properties we acquired (including: temporal focus, specificity, emotional valence). Our behavioural and pupillometry findings stress the need for objective measures about the temporal unfolding of MW (while most studies focus on arbitrary time-window preceding self-reports of MW).
Worldwide occurrence records reflect a global decline in bee species richness
Authors: Zattara Eduardo E. , Aizen Marcelo A. 
Published: December 2019

AbstractWild and managed bees are key pollinators, providing ecosystem services to a large fraction of the world’s flowering plants, including ∼85% of all cultivated crops. Recent reports of wild bee decline and its potential consequences are thus worrisome. However, evidence is mostly based on local or regional studies; global status of bee decline has not been assessed yet. To fill this gap, we analyzed publicly available worldwide occurrence records from the Global Biodiversity Information Facility spanning more than a century of specimen collection. We found that after the 1980’s the number of collected bee species declines steeply, and approximately 25% fewer species were reported between 2006 and 2015 relative to the number of species counted before the 1990’s. These trends are alarming and encourage swift action to avoid further decline of these key pollinators.
Sequence-to-function deep learning frameworks for synthetic biology
Authors: Valeri Jacqueline , Collins Katherine M. , Lepe Bianca A. , Lu Timothy K. , Camacho Diogo M. 
Published: December 2019

AbstractWhile synthetic biology has revolutionized our approaches to medicine, agriculture, and energy, the design of novel circuit components beyond nature-inspired templates can prove itself challenging without well-established design rules. Toehold switches — programmable nucleic acid sensors — face an analogous prediction and design bottleneck: our limited understanding of how sequence impacts functionality can require expensive, time-consuming screens for effective switches. Here, we introduce the Sequence-based Toehold Optimization and Redesign Model (STORM), a deep learning architecture that applies gradient ascent to re-engineer poorly-performing toeholds. Based on a dataset of 91,534 toehold switches, we examined convolutional filters and saliency maps of sequences to interpret our sequence-to-function model, identifying hot spots where mutations change toehold effectiveness and features unique to high-performing switches. Our modeling platform provides frameworks for future toehold selection, augmenting our ability to construct potent synthetic circuit components and precision diagnostics, and enabling straightforward translation of thisin silicoworkflow to other circuitries.
Reconciling author names in taxonomic and publication databases
Authors: Page Roderic D. M. 
Published: December 2019

AbstractTaxonomic names remain fundamental to linking biodiversity data, but information on these names resides in separate silos. Despite often making their contents available in RDF, records in these taxonomic databases are rarely linked to identifiers in external databases, such as DOIs for publications, or ORCIDs for people. This paper explores how author names in publication databases such as CrossRef and ORCID can be reconciled with author names in a taxonomic database using existing vocabularies and SPARQL queries.