bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automatic Detection of Synaptic Partners in a Whole-BrainDrosophilaEM Dataset
Authors: Buhmann Julia , Sheridan Arlo , Gerhard Stephan , Krause Renate , Nguyen Tri , Heinrich Larissa , Schlegel Philipp , Lee Wei-Chung Allen , Wilson Rachel , Saalfeld Stephan , Jefferis Gregory , Bock Davi , Turaga Srinivas , Cook Matthew , Funke Jan 
Published: December 2019

AbstractThe study of neural circuits requires the reconstruction of neurons and the identification of synaptic connections between them. To scale the reconstruction to the size of whole-brain datasets, semi-automatic methods are needed to solve those tasks. Here, we present an automatic method for synaptic partner identification in insect brains, which uses convolutional neural networks to identify post-synaptic sites and their pre-synaptic partners. The networks can be trained from human generated point annotations alone and require only simple post-processing to obtain final predictions. We used our method to extract 244 million putative synaptic partners in the fifty-teravoxel full adult fly brain (FAFB) electron microscopy (EM) dataset and evaluated its accuracy on 146,643 synapses from 702 neurons with a total cable length of 312 mm in four different brain regions. The predicted synaptic connections can be used together with a neuron segmentation to infer a connectivity graph with high accuracy: between 92% and 96% of edges linking connected neurons are correctly classified as weakly connected (less than five synapses) and strongly connected (at least five synapses). Our synaptic partner predictions for the FAFB dataset are publicly available, together with a query library allowing automatic retrieval of up- and downstream neurons.
Humans use a local code for tactile perception
Authors: Bhattacharjee Arindam , Braun Christoph , Schwarz Cornelius 
Published: December 2019

AbstractHumans are classically thought to use either spectral decomposition or averaging to identify vibrotactile signals. These are general purpose ‘global’ codes that require integration of the signal over long stretches of time. Natural vibrotactile signals, however, likely contain short signature events that can be detected and used for inference of textures, instantaneously, with minimal integration, suggesting a hitherto ignored ‘local code’. Here, by employing pulsatile stimuli and a change detection psychophysical task, we studied whether humans make use of local cues. We compared three local cues based on instantaneous skin position and its derivatives, as well as six global cues, calculated as summed powers (with exponents 1,2, and 3) of velocity and acceleration. Deliberate manipulation of pulse width and amplitude (local+global) as well as pulse frequency (global) allowed us to disentangle local from global codes. The results singled out maximum velocity, an instantaneous code, as a likely and dominant coding variable that humans rely on to perform the task. Comparing stimuli containing versus lacking local cues, demonstrated that performances exclusively using global cues are rather poor compared to situations where local ones are available as well. Our results are in line with the notion that humans not only do use local cues but that local cues may even play a dominant role in perception. Our results parallel previous results in rodents, pointing to the possibility that quite similar coding strategies evolved in whisker and finger tactile systems.Significance statementThe brain is believed to select coding symbols in sensory signals that would most efficiently convey functionally relevant information about the world. For instance, the visual system is widely believed to use spatially local features, like edge orientation, to delineate a visual scene. For the tactile system only global, general purpose coding schemes have been discussed so far. Based on the insight that moving contacts, characteristic for active touch, feature short-lived stick-slip events, frictional movements that transfer fair amounts of texture information, one should expect the brain to use a temporally local code, extracting and instantaneously analyzing short snippets of skin movement. Here, we provide the first analytical psychophysical evidence in humans that this indeed is the case.
YbeY is required for ribosome small subunit assembly and tRNA processing in human mitochondria
Authors: D’Souza Aaron R. , Van Haute Lindsey , Powell Christopher A. , Rebelo-Guiomar Pedro , Rorbach Joanna , Minczuk Michal 
Published: December 2019

AbstractMitochondria contain their own translation apparatus which enables them to produce the polypeptides encoded in their genome. The mitochondrially-encoded RNA components of the mitochondrial ribosome require various post-transcriptional processing steps. Additional protein factors are required to facilitate the biogenesis of the functional mitoribosome. We have characterised a mitochondrially-localized protein, YbeY, which interacts with the assembling mitoribosome through the small subunit. Loss of YbeY leads to a severe reduction in mitochondrial translation and a loss of cell viability, caused by less accurate mitochondrial mt-tRNASer(AGY)processing from the primary transcript and an accumulation of immature mitochondrial small subunit. Our results suggest that YbeY performs a dual function in mitochondria coupling tRNA processing to mitoribosome biogenesis.Issue SectionNucleic Acid EnzymesAbstract Figure
Developmental programming: Transcriptional regulation of visceral and subcutaneous adipose by prenatal bisphenol-A in female sheep
Authors: Dou John F. , Puttabyatappa Muraly , Padmanabhan Vasantha , Bakulski Kelly M. 
Published: December 2019

AbstractBackgroundBisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood.ObjectiveTo determine the impact of prenatal BPA exposure on the transcriptome of VAT and SAT adipose depots.MethodsRNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Differences in transcriptional profiling of SAT and VAT in controls and the effect of prenatal BPA treatment on individual genes and gene pathways were determined.ResultsThere were 179 differentially expressed genes (padjusted<0.05, log2-fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways.ConclusionPrenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.
The mitotic crosslinking protein PRC1 acts as a mechanical dashpot to resist microtubule sliding
Authors: Gaska Ignas , Armstrong Mason , Alfieri April , Forth Scott 
Published: December 2019

AbstractCell division in eukaryotes requires the regulated assembly of the spindle apparatus. The proper organization of microtubules within the spindle is driven by motor proteins that exert forces to push and slide filaments, while non-motor proteins can crosslink filaments into higher order motifs such as overlapping bundles. It has not been clear how active and passive forces are integrated to produce regulated mechanical outputs within spindles. Here we employ a combined optical tweezers and TIRF microscopy instrument to directly measure the resistive forces produced by the mitotic crosslinking protein PRC1. We observe that PRC1 generates frictional forces that resist microtubule sliding. These forces scale with microtubule sliding velocity and the number of PRC1 crosslinks, but do not depend on overlap length or PRC1 density within overlaps. Our results suggest that PRC1 ensembles act like a mechanical dashpot, producing significant resistance against fast motions, but minimal resistance against slow motions, allowing for the integration of diverse motor activities into a single mechanical outcome.
Novel intramolecular base-pairing of the U8 snoRNA underlies a Mendelian form of cerebral small vessel disease
Authors: Badrock Andrew P. , Uggenti Carolina , Wacheul Ludivine , Crilly Siobhan , Jenkinson Emma M. , Rice Gillian I. , Kasher Paul R. , Lafontaine Denis L.J. , Crow Yanick J. , O’Keefe Raymond T. 
Published: December 2019

AbstractHow mutations in the non-coding U8 snoRNA cause the neurological disorder leukoencephalopathy with calcification and cysts (LCC) is poorly understood. We report the first vertebrate mutant U8 animal model for interrogating LCC-associated pathology. Mutant U8 zebrafish exhibit defective central nervous system development and ribosomal RNA (rRNA) biogenesis, with tp53 activation which monitors ribosome biogenesis. Importantly, LCC patient fibroblasts demonstrate rRNA processing defects. Human precursor-U8 (pre-U8) containing a 3’ extension rescued mutant U8 zebrafish, indicating conserved biological function. Analysis of LCC-associated U8 alleles in zebrafish revealed that one null and one hypomorphic, but still functional, allele combine to cause LCC. Mutations involving any one of seven nucleotides within the human pre-U8 3’ extension, or 5’ region of U8, alter processing of pre-U8, and identify a novel base-pairing interaction between the 5’ end and 3’ extension of human pre-U8. Variants in these seven nucleotides, one of which is present on a single allele in almost all patients, act as hypomorphic mutations. Given that biallelic null U8 alleles are likely incompatible with human development, identification of hypomorphic mutations mediating viable embryogenesis furthers understanding of LCC molecular pathology and cerebral vascular homeostasis.
Single cell lineage dynamics of the endosymbiotic cell type in a soft coralXeniaspecies
Authors: Hu Minjie , Zheng Xiaobin , Fan Chen-Ming , Zheng Yixian 
Published: December 2019

AbstractMany hard and soft corals harbor algae for photosynthesis. The algae live inside coral cells in a specialized membrane compartment called symbiosome, which shares the photosynthetically fixed carbon with coral host cells, while host cells provide inorganic carbon for photosynthesis1. This endosymbiotic relationship is critical for corals, but increased environmental stresses are causing corals to expel their endosymbiotic algae, i.e. coral bleaching, leading to coral death and degradation of marine ecosystem2. To date, the molecular pathways that orchestrate algal recognition, uptake, and maintenance in coral cells remain poorly understood. We report chromosome-level genome assembly of a fast-growing soft coral,Xeniaspecies (sp.)3, and its use as a model to decipher the coral-algae endosymbiosis. Single cell RNA-sequencing (scRNA-seq) identified 13 cell types, including gastrodermis and cnidocytes, inXenia sp. Importantly, we identified the endosymbiotic cell type that expresses a unique set of genes implicated in the recognition, phagocytosis/endocytosis, maintenance of algae, and host coral cell immune modulation. By applying scRNA-seq to investigate algal uptake in our newXenia sp.. regeneration model, we uncovered a dynamic lineage progression from endosymbiotic progenitor state to mature endosymbiotic and post-endosymbiotic cell states. The evolutionarily conserved genes associated with the endosymbiotic process reported herein open the door to decipher common principles by which different corals uptake and expel their endosymbionts. Our study demonstrates the potential of single cell analyses to examine the similarities and differences of the endosymbiotic lifestyle among different coral species.
TDP-43 dysfunction restricts dendritic complexity by inhibiting CREB activation and altering gene expression
Authors: Herzog Josiah J. , Deshpande Mugdha , Xu Weijin , Rahman Reazur , Suib Hannah , Rosbash Michael , Rodal Avital A. , Paradis Suzanne 
Published: December 2019

AbstractAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative diseases that present with similar TDP-43 pathology in patient tissue. TDP-43 is an RNA-binding protein and forms aggregates in neurons of ALS and FTD patients as well as in a subset of patients diagnosed with other neurodegenerative diseases. Despite our understanding that TDP-43 is essential for many aspects of RNA metabolism, it remains obscure how TDP-43 dysfunction contributes to neurodegeneration. Interestingly, several neurological disorders display altered dendritic morphology and complexity, which are thought to precede neurodegeneration. In this study, we used TRIBE (targets of RNA-binding proteins identified by editing) as a new approach to identify signaling pathways that regulate dendritic branching downstream of TDP-43. We found that TDP-43 targets are enriched for pathways that signal to the CREB transcription factor. We further found that TDP-43 dysfunction inhibits CREB activation and CREB transcriptional output, and restoring CREB signaling rescued defects in dendritic branching. Our data therefore provide a novel mechanism by which TDP-43 dysfunction interferes with dendritic branching, and define new pathways for therapeutic intervention in neurodegenerative diseases.
STING controls Herpes Simplex Virusin vivoindependent of type I interferon induction
Authors: Yamashiro Lívia H. , Wilson Stephen C. , Morrison Huntly M. , Karalis Vasiliki , Chung Jing-Yi J. , Chen Katherine J. , Bateup Helen S. , Szpara Moriah L. , Lee Angus Y. , Cox Jeffery S. , Vance Russell E. 
Published: December 2019

AbstractThe Stimulator of Interferon Genes (STING) pathway initiates potent immune responses upon recognition of DNA derived from bacteria, viruses and tumors. To signal, the C-terminal tail (CTT) of STING recruits TBK1, a kinase that phosphorylates serine 365 (S365) in the CTT. Phospho-S365 acts as a docking site for IRF3, a transcription factor that is phosphorylated and activated by TBK1, leading to transcriptional induction of type I interferons (IFNs). IFNs are essential for antiviral immunity and are widely viewed as the primary output of STING signaling in mammals. However, other more evolutionarily ancestral responses, such as induction of NF-κB or autophagy, also occur downstream of STING. The relative importance of the various outputs of STING signaling duringin vivoinfections is unclear. Here we report that mice harboring a serine 365-to-alanine (S365A) point mutation in STING exhibit normal susceptibility toMycobacterium tuberculosisinfection but, unexpectedly, are resistant to Herpes Simplex Virus (HSV)-1, despite lacking STING-induced type I IFN responses. Likewise, we findIrf3-/-mice exhibit resistance to HSV-1. By contrast, resistance to HSV-1 is abolished in mice lacking the STING CTT or TBK1, suggesting that STING protects against HSV-1 upon TBK1 recruitment by the STING CTT, independent of IRF3 or type I IFNs. Interestingly, we find that STING-induced autophagy is a TBK1-dependent IRF3-independent process that is conserved in the STING S365A mice, and autophagy has previously been shown to be required for resistance to HSV-1. We thus propose that autophagy and perhaps other ancestral interferon-independent functions of STING are required for STING-dependent antiviral responsesin vivo.
Lateralized alpha activity and slow potentials shifts over visual cortex track the time course of both endogenous and exogenous orienting of attention
Authors: Keefe Jonathan M. , Störmer Viola S. 
Published: December 2019

AbstractSpatial attention can be oriented endogenously, based on current task goals, or exogenously, triggered by salient events in the environment. Based upon literature demonstrating differences in the time course and neural substrates of each type of orienting, these two attention systems are often treated as fundamentally distinct. However, recent studies suggest that rhythmic neural activity in the alpha band (8-13Hz) and slow waves in the event-related potential (ERP) may emerge over parietal-occipital cortex following both endogenous and exogenous attention cues. To assess whether these neural changes index common processes of spatial attention, we conducted two within-subject experiments varying the two main dimensions over which endogenous and exogenous attention tasks typically differ: cue informativity (spatially predictive vs. non-predictive) and cue format (centrally vs. peripherally presented). This task design allowed us to tease apart neural changes related to top-down goals and those driven by the reflexive orienting of spatial attention, as well as examine their interactions in a novel hybrid cross-modal attention task. Our data demonstrate that both central and peripheral cues elicit lateralized ERPs over parietal-occipital cortex, though at different points in time, consistent with these ERPs reflecting the orienting of spatial attention. Lateralized alpha activity was also present across all tasks, emerging rapidly for peripheral cues and sustaining only for spatially informative cues. Overall, these data indicate that distinct slow-wave ERPs index the spatial orienting of endogenous and exogenous attention, while lateralized alpha activity represents a common signature of visual enhancement in anticipation of potential targets across both types of attention.
Fast and accurate defocus for improved tunability of cryo-EM experiments
Authors: Danev Radostin , Iijima Hirofumi , Matsuzaki Mizuki , Motoki Sohei 
Published: December 2019

AbstractCurrent data collection strategies in electron cryo-microscopy (cryo-EM) record multiframe movies with static optical settings. This limits the number of adjustable parameters that can be used to optimize the experiment. Here, we propose a method for fast and accurate defocus (FADE) modulation during movie acquisition. It uses the objective lens aperture as an electrostatic pole that locally modifies the electron beam potential. The beam potential variation is converted to defocus modulation by the typically undesired chromatic aberration of the objective lens. The simplicity, electrostatic principle and low electrical impedance of the device will allow fast switching speeds that will enable per-frame defocus values in cryo-EM movies. Researchers will be able to define custom defocus “recipes” and tailor the experiment for optimal information extraction from their sample. The FADE method could help to convert the microscope into a more dynamic and flexible optical platform that delivers better performance in cryo-EM single particle analysis and electron cryo-tomography.
Extended synaptotagmin regulates plasma membrane-endoplasmic reticulum contact site structure and lipid transfer functionin vivo
Authors: Nath Vaisaly R , Mishra Shirish , Basak Bishal , Trivedi Deepti , Raghu Padinjat 
Published: December 2019

SummaryInter-organelle communication between closely apposed membranes is proposed at Membrane Contact Sites (MCS). However the regulation of MCS structure and their functional relevancein vivoremain debated. The extended synaptotagmins (Esyt) are evolutionarily conserved proteins proposed to function at MCS. However, loss of all three Esyts in yeast or mammals shows minimal phenotypes questioning the functional importance of Esyt. We report that inDrosophilaphotoreceptors, MCS number is regulated by PLCβ activity. Photoreceptors of a null allele ofDrosophilaextended synaptotagmin(dEsyt)show loss of ER-PM MCS. Loss of dEsyt results in mislocalization of RDGB, an MCS localized lipid transfer protein, required for photoreceptor structure and function, ultimately leading to retinal degeneration.dEsytdepletion enhanced the retinal degeneration, reduced light responses and slower rates of plasma membrane PIP2resynthesis seen inrdgBmutants. Thus, dEsyt function and PLCβ signaling regulate ER-PM MCS structure and lipid transfer inDrosophilaphotoreceptors.
Water uptake analysis in Japanese mustard spinach: A numerical approach
Authors: Shimada Aoi , Seki Takuya , Ichikawa Musubu 
Published: December 2019

AbstractWe constructed an experimental system consisting of a syringe pump and water level feedback control to reveal the dynamics of water uptake in Japanese mustard spinach. We also analyzed differences in time-lapse images to quantify turgor movement in these plants. By performing harmonic analysis using the discrete Fourier transform on these dynamics, the frequency domain was obtained. These methods enabled the detailed visualization of plant dynamics.HighlightIn this study, the water uptake dynamics of Japanese mustard spinaches were measured in detail and image difference analysis was performed to investigate the plants’ turgor movements. Frequency domain analysis of the plant dynamics was carried out using a discrete Fourier transform.
Human defensive freezing is associated with acute threat coping, long term hair cortisol levels and trait anxiety
Authors: Hashemi Mahur M. , Zhang Wei , Kaldewaij Reinoud , Koch Saskia B.J. , Jonker Rosa , Figner Bernd , Klumpers Floris , Roelofs Karin 
Published: December 2019

AbstractThe detection and anticipation of threat facilitates innate defensive behaviours including freezing reactions. Freezing in humans is characterized by reductions in body sway and heart rate and limited evidence suggests that individual differences in freezing reactions are associated with hypothalamic-pituitary-adrenal (HPA) axis activity and anxiety. However, previous measurements of human freezing reactions were largely based on passive threat contexts where natural variations in adaptive threat coping could not be assessed. In a well powered sample (N=419), we studied individual differences in anticipatory freezing reactions, by measuring body sway and heart rate, during an active shooting task where shooting decisions had to be taken under threat of shock. We linked freezing measures to subsequent actions and predictors of anxiety-related psychopathology, including accumulated long-term (3 months) hair cortisol concentrations (HCC) and trait anxiety. The anticipation of threat of shock elicited significant body sway- and heart rate reductions consistent with freezing. Whereas both freezing-related reductions in body sway and heart rate were associated with faster correct shooting decisions, body sway reductions were additionally related to more impulsive shooting (false alarms). Individual differences in threat-related reductions in body sway but not heart rate were further associated to lower HCC and higher trait anxiety. The observed links between freezing and subsequent defensive actions as well as predictors of stress-related psychopathology suggest the potential value of defensive freezing reactions as somatic marker for stress-vulnerability and resilience.