bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resting state cerebral networks in mouse lemur primates: from multilevel validation to comparison with humans
Authors: Garin Clément M. , Nadkarni Nachiket A. , Landeau Brigitte , Chételat Gaël , Picq Jean-Luc , Bougacha Salma , Dhenain Marc 
Published: April 2019

AbstractMeasures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Animal models are critical to further address experimentally the function of brain networks and their roles in pathologies. Here we describe for the first time brain network organization in the mouse lemur (Microcebus murinus), a small primate attracting increased attention as a model for neuroscience. Resting-state functional MR images were recorded at 11.7 Tesla. Forty-eight functional regions were identified and used to identify networks using graph theory, dictionary learning and seed-based analyses. Comparison of results issued from these three complementary methods allowed the description of the most robust networks from mouse lemurs. Large scale networks were then identified from resting-state functional MR images of humans using the same method as for lemurs. Strong homologies were outlined between cerebral networks in mouse lemurs and humans.
Protein structure determination using Riemannian approach
Authors: Wei Xian , Li Zhicheng , Li Shijian , Peng Xubiao , Zhao Qing 
Published: April 2019

AbstractThe protein nuclear magnetic resonance (NMR) structure determination is one of the most extensively studied problems due to its increasing importance in biological function analysis. We adopt a novel method, based on one of the matrix completion (MC) techniques–the Riemannian approach, to solve the protein structure determination problem. We formulate the protein structure in terms of low-rank matrix which can be solved by an optimization problem in the Riemannian spectrahedron manifold whose objective function has been delimited with the derived boundary condition. Two efficient algorithms in Riemannian approach-the trust-region (Tr) algorithm and the conjugate gradient (Cg) algorithm are used to reconstruct protein structures. We first use the two algorithms in a toy model and show that the Tr algorithm is more robust. Afterwards, we rebuild the protein structure from the NOE distance information deposited in NMR Restraints Grid (http://restraintsgrid.bmrb.wisc.edu/NRG/MRGridServlet). A dataset with both X-ray crystallographic structure and NMR structure deposited in Protein Data Bank (PDB) is used to statistically evaluate the performance of our method. By comparing both our rebuilt structures and NMR counterparts with the “standard” X-ray structures, we conclude that our rebuilt structures have similar (sometimes even smaller) RMSDs relative to “standard” X-ray structures in contrast with the reference NMR structures. Besides, we also validate our method by comparing the Z-scores between our rebuilt structures with reference structures using Protein Structure Validation Software suit. All the validation scores indicate that the Riemannian approach in MC techniques is valid in reconstructing the protein structures from NOE distance information. The software based on Riemannian approach is freely available athttps://github.com/xubiaopeng/Protein_Recon_MCRiemman.Author summaryMatrix Completion is a technique widely used in many aspects, such as the global positioning in sensor networks, collaborative filtering in recommendation system for many companies and face recognition, etc. In biology, distance geometry used to be a popular method for reconstructing protein structures related to NMR experiment. However, due to the low quality of the reconstructed results, those methods were replaced by other dynamic methods such as ARIA, CYANA and UNIO. Recently, a new MC technique named Riemannian approach is introduced and proved mathematically, which promotes us to apply it in protein structure determination from NMR measurements. In this paper, by combining the Riemannian approach and some post-processing procedures together, we reconstruct the protein structures from the incomplete distance information measured by NMR. By evaluating our results and comparing with the corresponding PDB NMR deposits, we show that the current Riemannian approach method is valid and at least comparable with (if not better than) the state-of-art methods in NMR structure determination.
Second messengers and divergent HD-GYP enzymes regulate 3’,3’-cGAMP signaling
Authors: Wright Todd A. , Jiang Lucy , Park James J. , Anderson Wyatt A. , Chen Ge , Hallberg Zachary F. , Nan Beiyan , Hammond Ming C. 
Published: April 2019

ABSTRACT3’,3’-cyclic GMP-AMP (cGAMP) is the third cyclic dinucleotide (CDN) to be discovered in bacteria. No activators of cGAMP signaling have yet been identified, and the signaling pathways for cGAMP have appeared narrowly distributed based upon the characterized synthases, DncV and Hypr GGDEFs. Here we report that the ubiquitous second messenger cyclic AMP (cAMP) is an activator of the Hypr GGDEF enzyme GacB from Myxococcus xanthus. Furthermore, we show that GacB is inhibited directly by cyclic di-GMP, which provides evidence for cross-regulation between different CDN pathways. Finally, we reveal that the HD-GYP enzyme PmxA is a cGAMP-specific phosphodiesterase (GAP) that promotes resistance to osmotic stress in M. xanthus. A signature amino acid change in PmxA was found to reprogram substrate specificity and was applied to predict the presence of non-canonical HD-GYP phosphodiesterases in many bacterial species, including phyla previously not known to utilize cGAMP signaling.
OscoNet: Inferring oscillatory gene networks
Authors: Boukouvalas Alexis , Cutillo Luisa , Marinopoulou Elli , Papalopulu Nancy , Rattray Magnus 
Published: April 2019

AbstractMotivationOscillatory genes, with periodic expression at the mRNA and/or protein level, have been shown to play a pivotal role in many biological contexts. However, with the exception of the circadian clock and cell cycle, only a few such genes are known. Detecting oscillatory genes from snapshot single-cell experiments is a challenging task due to the lack of time information. Oscope is a recently proposed method to identify co-oscillatory gene pairs using single-cell RNA-seq data. Although promising, the current implementation of Oscope does not provide a principled statistical criterion for selecting oscillatory genes.ResultsWe improve the optimisation scheme underlying Oscope and provide a well-calibrated non-parametric hypothesis test to select oscillatory genes at a given FDR threshold. We evaluate performance on synthetic data and three real datasets and show that our approach is more sensitive than the original Oscope formulation, discovering larger sets of known oscillators while-avoiding the need for less interpretable thresholds. We also describe how our proposed pseudo-time estimation method is more accurate in recovering the true cell order for each gene cluster while-requiring substantially less computation time than the extended nearest insertion approach.ConclusionOscoNet is a robust and versatile approach to detect oscillatory gene networks from snapshot single-cell data addressing many of the limitations of the original Oscope method.
Measuring shared responses across subjects using intersubject correlation
Authors: Nastase Samuel A. , Gazzola Valeria , Hasson Uri , Keysers Christian 
Published: April 2019

AbstractOur capacity to jointly represent information about the world underpins our social experience. By leveraging one individual’s brain activity to model another’s, we can measure shared information across brains—even in dynamic, naturalistic scenarios where an explicit response model may be unobtainable. Introducing experimental manipulations allows us to measure, for example, shared responses between speakers and listeners, or between perception and recall. In this tutorial, we develop the logic of intersubject correlation (ISC) analysis and discuss the family of neuroscientific questions that stem from this approach. We also extend this logic to spatially distributed response patterns and functional network estimation. We provide a thorough and accessible treatment of methodological considerations specific to ISC analysis, and outline best practices.
Goal congruency dominates reward value in accounting for behavioral and neural correlates of value-based decision-making
Authors: Frömer Romy , Dean Wolf Carolyn K. , Shenhav Amitai 
Published: April 2019

AbstractHow we engage with a set of options (e.g., items on a menu) is affected both by the rewards they promise and our goal in choosing between them. Typically, our goal is to maximize potential reward and minimize potential punishment. Previous research on value-based decision-making has characterized how people make decisions with this goal in mind, identifying consistent behavioral and neural signatures associated with how rewarding a set of choice options are, overall and relative to one another. However, these studies suffer from a common confound: in each case, more rewarding options were also more congruent with one’s goal of choosing the best option. Previous findings can therefore be accounted for by thereward valueor thegoal congruencyof one’s options. To compare these accounts directly, we had participants make choices while their goal varied between choosing the best or the worst option, resulting in situations where either high-reward or low-reward options were most goal-congruent. We found that goal congruency uniquely accounts for past observations that decision speed varies with the overall value of one’s options. Within brain regions commonly associated with choice value, fMRI activity was associated with both relative and overall goal congruency. These goal congruency correlates were dissociable from separate correlates of the overall reward associated with a choice set (independent of one’s goal). Our findings call for a reinterpretation of previous research on value-based choice, and offer an approach moving forward for disentangling the roles of rewards and goals in how we evaluate our options.Significance StatementWhether it is between restaurants or career paths, to make adaptive decisions we must evaluate our options and identify those that are most conducive to our current goal. Dysfunctional decision-making can therefore result from aberrant reward processing (e.g., impulse disorders) or from aberrant goal processing (e.g., OCD, ADHD). By focusing only on how people choose theirfavoriteoption in a choice set (when rewards and goals are aligned), past research has been unable to distinguish the degree to which behavior and neural activity are determined by reward versus goal processing. We disentangle these processes and show that behavior and fMRI activity are differentially influenced by the promised rewards versus the degree to which those rewards align with one’s current goal.
Transcriptional analysis defines TCR and cytokine-stimulated MAIT cells as rapid polyfunctional effector T cells that can coordinate the immune response
Authors: Lamichhane Rajesh , Schneider Marion , de la Harpe Sara M. , Harrop Thomas W. R. , Hannaway Rachel F. , Dearden Peter , Kirman Joanna R. , Tyndall Joel D. A. , Vernall Andrea J. , Ussher James E. 
Published: April 2019

AbstractMAIT cells are an abundant innate-like T cell population which can be activated via either their T cell receptor (TCR), which recognizes MR1-bound pyrimidine antigens derived from microbial riboflavin biosynthesis, or via cytokines, such as IL-12 and IL-18. In vivo, these two modes of activation may act in concert or independently depending upon the nature of the microbial or inflammatory stimuli. It is unknown, however, how the MAIT cell response differs to the different modes of activation. Here, we define the transcriptional and effector responses of human MAIT cells to TCR and cytokine stimulation. We report that MAIT cells rapidly respond to TCR stimulation through the production of multiple effector cytokines and chemokines, alteration of their cytotoxic granule content and transcription factor expression, and upregulation of co-stimulatory proteins CD40L and 4-1BB. In contrast, cytokine-mediated activation is slower and results in more limited production of cytokines, chemokines, and co-stimulatory proteins; differences in granule content and transcription factor expression are also evident. Therefore, we propose that in infections by riboflavin-synthesizing bacteria, MAIT cells play a key early role in effecting and coordinating the immune response, while in the absence of TCR stimulation (e.g. viral infection) their role is likely to differ.
Optimization and validation of a quadruplex real-time PCR assay for the diagnosis of diphtheria
Authors: Badell Edgar , Guillot Sophie , Tulliez Marie , Pascal Marine , Panunzi Leonardo-Gabriel , Rose Samuel , Litt David , Fry Norman K. , Brisse Sylvain 
Published: April 2019

AbstractDiphtheria is caused by toxigenic strains ofCorynebacterium diphtheriae, Corynebacterium ulceransandCorynebacterium pseudotuberculosis. For diagnostic purposes, species identification and detection of toxigenic strains (diphtheria toxin (tox)-positive strains) is typically performed using end-point PCR. A faster quadruplex real-time PCR (qPCR) was recently developed (De Zoysaet al. J Med Microbiol. 2016 65(12):1521-1527). Here, we present an improvement of the quadruplex method, in which a 16S rRNA gene target was added as an internal processing control, providing confirmation of the presence of bacterial DNA in the assays. This improved qPCR method was validated using 36 bacterial isolates and 16 clinical samples. The method allows detection of thetoxgene and distinguishingC. diphtheriae(including the newly described speciesC. belfantii) fromC. ulceransandC. pseudotuberculosis. Complete diagnostic specificity, sensitivity and experimental robustness of the method to temperature and reagent concentration variations were demonstrated. The lower limit of detection forC. diphtheriae, C. ulceransandtoxtargets was 1.86 genome copies per 5 μL reaction volume. Finally, the method was successfully used on two distinct qPCR technologies (LightCycler 480, Roche Diagnostics and Rotor-Gene Q, Qiagen) and in two laboratories (Institut Pasteur, Paris, France and Public Health England – National Infection Service, London, UK). This work describes validation of the improved qPCR quadruplex method and supports its implementation for the biological diagnosis of diphtheria.
ADSoluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer’s disease progression
Authors: De Suman , Whiten Daniel R. , Ruggeri Francesco S. , Hughes Craig , Rodrigues Margarida , Sideris Dimitrios I. , Taylor Christopher G. , Aprile Francesco A. , Muyldermans Serge , Knowles Tuomas P. J. , Vendruscolo Michele , Bryant Clare , Blennow Kaj , Skoog Ingmar , Kern Silke , Zetterberg Henrik , Klenerman David 
Published: April 2019

AbstractSoluble aggregates of amyloid-β (Aβ) have been associated with neuronal and synaptic loss in Alzheimer’s disease (AD). However, despite significant recent progress, the mechanisms by which these aggregated species contribute to disease progression are not fully determined. As the analysis of human cerebrospinal fluid (CSF) provides an accessible window into the molecular changes associated with the disease progression, we studied the soluble Aβ aggregates present in CSF samples from individuals with AD, mild cognitive impairment (MCI) and healthy controls. We found that these aggregates vary structurally and in their mechanisms of toxicity. More small aggregates of Aβ that can cause membrane permeabilization already found in MCI; in established AD, the aggregates were larger and more prone to elicit a pro-inflammatory response in glial cells. These results suggest that different neurotoxic mechanisms are prevalent at different stages of AD.
Solving the first novel protein structure by 3D micro-crystal electron diffraction
Authors: Xu H. , Lebrette H. , Clabbers M.T.B. , Zhao J. , Griese J.J. , Zou X. , Högbom M. 
Published: April 2019

AbstractMicro-crystal electron diffraction (MicroED) has recently shown potential for structural biology. It enables studying biomolecules from micron-sized 3D crystals that are too small to be studied by conventional X-ray crystallography. However, to the best of our knowledge, MicroED has only been applied to re-determine protein structures that had already been solved previously by X-ray diffraction. Here we present the first unknown protein structure – an R2lox enzyme – solved using MicroED. The structure was phased by molecular replacement using a search model of 35% sequence identity. The resulting electrostatic scattering potential map at 3.0 Å resolution was of sufficient quality to allow accurate model building and refinement. Our results demonstrate that MicroED has the potential to become a widely applicable tool for revealing novel insights into protein structure and function, opening up new opportunities for structural biologists.
Drosophilaribosomal protein S5b is essential for oogenesis and interacts with distinct RNAs
Authors: Kong Jian , Han Hong , Bergalet Julie , Benoit Bouvrette Louis Philip , Hernández Greco , Moon Nam-Sung , Vali Hojatollah , Lécuyer Éric , Lasko Paul 
Published: April 2019

AbstractInDrosophila melanogasterthere are two genes encoding ribosomal protein S5,RpS5aandRpS5b.Here, we demonstrate thatRpS5bis required for oogenesis. Females lackingRpS5bproduce ovaries with numerous developmental defects that undergo widespread apoptosis in mid-oogenesis. Females lacking germlineRpS5aare fully fertile, but germline expression of interfering RNA targeting germlineRpS5ain anRpS5bmutant background worsened theRpS5bphenotype and blocked oogenesis before egg chambers form. A broad spectrum of mRNAs co-purified in immunoprecipitations with RpS5a, while RpS5b-associated mRNAs were specifically enriched for GO terms related to mitochondrial electron transport and cellular metabolic processes. Consistent with this,RpS5bmitochondrial fractions are depleted for proteins linked to oxidative phosphorylation and mitochondrial respiration, andRpS5bmitochondria tended to form large clusters and had more heterogeneous morphology than those from controls. We conclude that RpS5b-containing ribosomes preferentially associate with particular mRNAs and serve an essential function in oogenesis.
Composition and structure of synaptic ectosomes exporting antigen receptor linked to functional CD40 ligand from helper T-cells
Authors: Saliba David G. , Céspedes-Donoso Pablo F. , Bálint Štefan , Compeer Ewoud B. , Valvo Salvatore , Korobchevskaya Kseniya , Mayya Viveka , Peng Yanchun , Dong Tao , Tognoli Maria-Laura , O’Neill Eric , Bonham Sarah , Fischer Roman , Kessler Benedikt M. , Dustin Michael L. 
Published: April 2019

AbstractCell communication through extracellular vesicles is an emerging topic in biology, including communication between cells of the immune system. Planar supported lipid bilayers (PSLBs) presenting T cell receptor (TCR) ligands and intercellular adhesion molecule-1 (ICAM-1) induce budding of extracellular microvesicles enriched in functional TCR, defined here as synaptic ectosomes (SE), from helper T cells. SE bind peptide-MHC directly exporting TCR into the synaptic cleft, but their ability to incorporate other effectors is unknown. Here, we utilized bead supported lipid bilayers (BSLB) to capture SE from single immunological synapses (IS), determined SE composition by immunofluorescence flow cytometry and enriched SE for proteomic analysis by particle sorting. Our results demonstrate selective enrichment of CD40 ligand (CD40L) and inducible T-cell costimulator (ICOS) in SE in response to addition of CD40 and ICOS ligand (ICOSL), respectively, to SLB presenting TCR ligands and ICAM-1. TCR triggering mobilized intracellular CD40L to the T cells surface at the IS, where it engaged CD40 to enable sorting into SE. SEs were enriched in tetraspanins and bone marrow stromal cell antigen 2 (BST-2) by immunofluorescence and TCR signalling and endosomal sorting complexes required for transport by proteomics. Super-resolution microscopy demonstrated that CD40L is present in microclusters within CD81 defined SE that are spatially segregated from TCR/ICOS/BST-2 microclusters. CD40L in SE retains the capacity to induce dendritic cell (DC) maturation and cytokine production. SE enabled helper T cells to release effectors physically linked to TCR.One Sentence SummaryTCR and CD40L microclusters can be linked in synaptic ectosomes (extracellular vesicles) that are released in the immunological synapse by helper T cells and induce dendritic cell maturation and cytokine production.
Interplay Between Short-range Attraction and Long-range Repulsion Controls Reentrant Liquid Condensation of Ribonucleoprotein-RNA Complexes
Authors: Alshareedah Ibraheem , Kaur Taranpreet , Ngo Jason , Seppala Hannah , Djomnang Kounatse Liz-Audrey , Wang Wei , Moosa Mahdi Muhammad , Banerjee Priya R. 
Published: April 2019

AbstractIn eukaryotic cells, ribonucleoproteins (RNPs) form mesoscale condensates by liquid-liquid phase separation that play essential roles in subcellular dynamic compartmentalization. The formation and dissolution of many RNP condensates are finely dependent on the RNA-to-RNP ratio, giving rise to a window-like phase separation behavior. This is commonly referred to as reentrant liquid condensation (RLC). Here, using RNP-inspired polypeptides with low-complexity RNA-binding sequences as well as the C-terminal disordered domain of the ribonucleoprotein FUS as model systems, we investigate the molecular driving forces underlying this non-monotonous phase transition. We show that an interplay between short-range cation-π attractions and long-range electrostatic forces governs the heterotypic RLC of RNP-RNA complexes. Short-range attractions, which can be encoded by both polypeptide chain primary sequence and nucleic acid base sequence, are activated by RNP-RNA condensate formation. After activation, the short-range forces regulate material properties of polypeptide-RNA condensates and subsequently oppose their reentrant dissolution. In the presence of excess RNA, a competition between short-range attraction and long-range electrostatic repulsion drives the formation of a colloid-like cluster phase. With increasing short-range attraction, the fluid dynamics of the cluster phase is arrested, leading to the formation of a colloidal gel. Our results reveal that phase behavior, supramolecular organization, and material states of RNP-RNA assemblies are controlled by a dynamic interplay between molecular interactions at different length scales.