bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interdependent photo- and chemosensory systems regulate larval settlement in a marine sponge
Authors: Say Tahsha E. , Degnan Sandie M. 
Published: January 2019

AbstractMarine pelagic larvae from throughout the animal kingdom use a hierarchy of environmental cues to identify a suitable benthic habitat on which to settle and metamorphose into the reproductive phase of the life cycle. The majority of larvae are induced to settle by biochemical cues (1) and many species have long been known to preferentially settle in the dark (2). Combined, these data suggest that larval responses to light and biochemical cues may be linked, but this is yet to be explored at the molecular level. Here, we track vertical position of larvae of the sponge Amphimedon queenslandica to show that they descend to the benthos at twilight, by which time they are competent to respond to biochemical cues (3), consistent with them naturally settling in the dark. We then conduct larval settlement assays under three different light regimes (natural day-night, constant dark or constant light), and use transcriptomics on individual larvae to identify candidate molecular pathways underlying the different settlement responses that we observe. We find that constant light prevents larval settlement in response to biochemical cues, likely via actively repressing chemostransduction; this is consistent with the sustained upregulation of a photosensory cryptochrome and two putative inactivators of G-protein signalling in the constant light only. We hypothesise that photo- and chemosensory systems may be hierarchically integrated into ontogeny to regulate larval settlement via nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) signalling in this sponge that belongs to one of the earliest branching of the extant animal lineages.Significance statementIn the ocean, successful recruitment of pelagic larvae into reproductive adult populations enables the survival and connectivity of benthic communities. The majority of invertebrate larvae are induced to settle by biochemical cues, and multiple species preferentially settle in the dark. Here, we explore, for the first time, interactions between light and biochemical cues at behavioural and molecular levels during larval ontogeny in a sponge. We find that light perturbs ontogenetic changes in gene expression and prevents settlement in response to biochemical cues, demonstrating strong interdependencies between photo- and chemosensory systems. Sponges are one of the earliest-branching of the extant animal phyletic lineages, and a valuable comparative model for understanding the origin and evolution of the pelago-benthic life cycle.
Lipid rafts increase to facilitate ectoderm lineage specification of differentiating embryonic stem cells
Authors: Xu Chen , Cao Bo , Huo Ying-dong , Niu Gang , Zhang Michael Q , Mai Zi-lin , Lu Xi-bin , Niu Han-ben , Chen Dan-ni , Ni Yan-xiang 
Published: January 2019

AbstractLipid rafts are packed nanoscopic domains on plasma membrane and essential signalling platforms for transducing extracellular stimuli into cellular responses. Although depletion of raft component glycoshpingolipids causes abnormality particularly in ectoderm layer formation, it remains unclear whether rafts play a role in lineage determination, a critical but less-known stage in lineage commitment. Here, inducing mouse embryonic stem cell (mESC) differentiation with retinoic acid (RA), we observed lipid rafts increased since early stage, especially in ectoderm-like cells. Stochastic optical reconstruction microscopy characterized at super-resolution the distinct raft features in mESCs and the derived differentiated cells. Furthermore, RA-induced commitment of ectoderm-like cells was significantly diminished not only by genetic ablation of rafts but by applying inhibitor for glycosphingolipids or cholesterol at early differentiation stages. Meanwhile, raft inhibition delayed RA-induced pluripotency exit, an early step required for differentiation. Therefore, lipid rafts increase and facilitate ectoderm lineage specification as well as pluripotency exit during mESC differentiation.
Learning in visual regions as support for the bias in future value-driven choice
Authors: Jahfari Sara , Theeuwes Jan , Knapen Tomas 
Published: January 2019

AbstractReinforcement learning can bias decision-making towards the option with the highest expected outcome. Cognitive learning theories associate this bias with the constant tracking of stimulus values and the evaluation of choice outcomes in the striatum and prefrontal cortex. Decisions however first require processing of sensory input, and to-date, we know far less about the interplay between learning and perception. This fMRI study (N=43), relates visual BOLD responses to value-beliefs during choice, and, signed prediction errors after outcomes. To understand these relationships, which co-occurred in the striatum, we sought relevance by evaluating the prediction of future value-based decisions in a separate transfer phase where learning was already established. We decoded choice outcomes with a 70% accuracy with a supervised machine learning algorithm that was given trial-by-trial BOLD from visual regions alongside more traditional motor, prefrontal, and striatal regions. Importantly, this decoding of future value-driven choice outcomes again highligted an important role for visual activity. These results raise the intriguing possibility that the tracking of value in visual cortex is supportive for the striatal bias towards the more valued option in future choice.
Capturing site-specific heterogeneity with large-scale N-glycoproteome analysis
Authors: Riley Nicholas M. , Hebert Alexander S. , Westphall Michael S. , Coon Joshua J. 
Published: January 2019

ABSTRACTProtein glycosylation is a highly important, yet a poorly understood protein post-translational modification. Thousands of possible glycan structures and compositions create potential for tremendous site heterogeneity and analytical challenge. A lack of suitable analytical methods for large-scale analyses of intact glycopeptides has ultimately limited our abilities to both address the degree of heterogeneity across the glycoproteome and to understand how it contributes biologically to complex systems. Here we show that N-glycoproteome site-specific microheterogeneity can be captured via large-scale glycopeptide profiling with methods enabled by activated ion electron transfer dissociation (AI-ETD), ultimately characterizing 1,545 N-glycosites (>5,600 unique N-glycopeptides) from mouse brain tissue. Moreover, we have used this large-scale glycoproteomic data to develop several new visualizations that will prove useful for analyzing intact glycopeptides in future studies. Our data reveal that N-glycosylation profiles can differ between subcellular regions and structural domains and that N-glycosite heterogeneity manifests in several different forms, including dramatic differences in glycosites on the same protein.
Metastatic breast cancers have reduced immune cell recruitment but harbor increased macrophages relative to their matched primary tumors
Authors: Zhu Li , Narloch Jessica L. , Onkar Sayali , Joy Marion , Luedke Catherine , Hall Allison , Kim Rim , Pogue-Geile Katherine , Sammons Sarah , Nayyar Naema , Chukwueke Ugonma , Brastianos Priscilla K. , Anders Carey K. , Soloff Adam C. , Vignali Dario AA , Tseng George C. , Emens Leisha A. , Lucas Peter C. , Blackwell Kimberly L. , Oesterreich Steffi , Lee Adrian V. 
Published: January 2019

AbstractThe interplay between the immune system and tumor progression is well recognized. However, current human breast cancer immunophenotyping studies are mostly focused on primary tumors with metastatic breast cancer lesions remaining largely understudied. To address this gap, we examined exome-capture RNA sequencing data from 50 primary breast tumors (PBTs) and their patient-matched metastatic tumors (METs) in brain, ovary, bone and gastrointestinal tract. We used gene expression signatures as surrogates for tumor infiltrating lymphocytes (TIL) and compared TIL patterns in PBTs and METs. Enrichment analysis and deconvolution methods both revealed that METs have a significantly lower abundance of total immune cells, including CD8+ T cells, regulatory T cells and dendritic cells. An exception was M2-like macrophages, which were significantly higher in METs across the organ sites examined. Multiplex immunohistochemistry results were consistent with data from the in-silico analysis and showed increased macrophages in METs. We confirmed the finding of a significant reduction in immune cells in brain (BRM) METs by pathologic assessment of TILs in a set of 49 patient-matched pairs of PBT/BRMs. These findings indicate that METs have an overall lower infiltration of immune cells relative to their matched PBTs, possibly due to immune escape. RNAseq analysis suggests that the relative levels of M2-like macrophages are increased in METs, and their potential role in promoting breast cancer metastasis warrants further study.
Automated pupillometry to detect command following in neurological patients: A proof-of-concept study
Authors: Vassilieva Alexandra , Olsen Markus Harboe , Peinkhofer Costanza , Knudsen Gitte Moos , Kondziella Daniel 
Published: January 2019

AbstractBackgroundLevels of consciousness in patients with acute and chronic brain injury are notoriously underestimated. Paradigms based on electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) may detect covert consciousness in unresponsive patients but are subject to logistical challenges and the need for advanced statistical analysis.MethodsTo assess the feasibility of automated pupillometry for the detection of command following, we enrolled 20 healthy volunteers and 48 patients with a wide range of neurological disorders, including 7 patients in the intensive care unit (ICU), who were asked to engage in mental arithmetic.ResultsFourteen of 20 (70%) healthy volunteers and 17 of 43 (39.5%) neurological patients, including 1 in the ICU, fulfilled prespecified criteria for command following by showing pupillary dilations during ≥4 of 5 arithmetic tasks. None of the 5 sedated and unconscious ICU patients passed this threshold.ConclusionsAutomated pupillometry combined with mental arithmetic appears to be a promising paradigm for the detection of covert consciousness in people with brain injury. We plan to build on this study by focusing on non-communicating ICU patients in whom the level of consciousness is unknown. If some of these patients show reproducible pupillary dilation during mental arithmetic, this would suggest that the present paradigm can reveal conscious awareness in unresponsive patients in whom standard investigations have failed to detect signs of covert consciousness.
Distinct role of flexible and stable encoding in sequential working memory
Authors: Lee Hyeonsu , Choi Woochul , Park Youngjin , Paik Se-Bum 
Published: January 2019

AbstractThe serial-position effect in working memory is considered important for studying how a sequence of sensory information can be retained and manipulated simultaneously in neural memory circuits. Here, via a precise analysis of the primacy and recency effects in human psychophysical experiments, we propose that stable and flexible coding take distinct roles of retaining and updating information in working memory, and that their combination induces serial-position effects spontaneously. We found that stable encoding retains memory to induce the primacy effect, while flexible encoding used for learning new inputs induces the recency effect. A model simulation based on human data, confirmed that a neural network with both flexible and stable synapses could reproduce the major characteristics of serial-position effects. Our new prediction, that the control of resource allocation by flexible-stable coding balance can modulate memory performance in sequence-specific manner, was supported by pre-cued memory performance data in humans.
“Skull base meningiomas have a distinct immune landscape.”
Authors: Zador Zsolt , Landry Alexander P. , Balas Michael , Cusimano Michael D. 
Published: January 2019

AbstractModulation of tumor microenvironment is an emerging frontier for new therapeutics. However in meningiomas, the most frequent adult brain tumor, the correlation of microenvironment with tumor phenotype is scarcely studied. We applied a variety of systems biology approaches to bulk tumor transcriptomics to explore the immune environments of both skull base and convexity (hemispheric) meningiomas. We hypothesized that the more benign biology of skull base meningiomas parallels the relative composition and activity of immune cells that oppose tumor growth and/or survival. We firstly applied gene co-expression networks to tumor bulk transcriptomics from 107 meningiomas (derived from 3 independent studies) and found immune processes to be the sole biological mechanism correlated with anatomical location while correcting for tumour grade. We then derived tumor immune cell fractions from bulk transcriptomics data and examined the immune cell-cytokine interactions using a network-based approach. We demonstrate that oncolytic M1 macrophages dominate skull base meningiomas while mast cells, known to play a role in oncogenesis, show greater activity in convexity tumors. Our results are the first to suggest the importance of tumor microenvironment in meningioma biology in the context of anatomic location and immune landscape. These findings may help better inform surgical decision making and yield location-specific therapies through modulation of immune microenvironment.
A curated collection of transcriptome datasets to investigate the molecular mechanisms of immunoglobulin E-mediated atopic diseases
Authors: Huang Susie S. Y. , Ali Fatima Al , Boughorbel Sabri , Toufiq Mohammed , Chaussabel Damien , Garand Mathieu 
Published: January 2019

ABSTRACTPrevalence of allergies has reached ~50% of industrialized populations and with children under ten being the most susceptible. However, the combination of the complexity of atopic allergy susceptibility/development and environmental factors has made identification of gene biomarkers challenging. The amount of publicly accessible transcriptomic data presents an unprecedented opportunity for mechanistic discoveries and validation of complex disease signatures across studies. However, this necessitates structured methodologies and visual tools for the interpretation of results. Here, we present a curated collection of transcriptomic datasets relevant to immunoglobin E (IgE)-mediated atopic diseases (ranging from allergies to primary immunodeficiencies). 30 datasets from the Gene Expression Omnibus (GEO), encompassing 1761 transcriptome profiles, were made available on the Gene Expression Browser (GXB), an online and open-source web application that allows for the query, visualization, and annotation of metadata. The thematic compositions, disease categories, sample number, and platforms of the collection are described. Ranked gene lists and sample grouping are used to facilitate data visualization/interpretation and are available online via GXB (http://ige.gxbsidra.org/dm3/geneBrowser/list). Dataset validation using associated publications showed good concordance in GXB gene expression trend and fold-change.Database URL: http://ige.gxbsidra.org/dm3/geneBrowser/list
DISPOT: A simple knowledge-based protein domain interaction statistical potential
Authors: Narykov Oleksandr , Korkin Dmitry 
Published: January 2019

AbstractMotivationThe complexity of protein-protein interactions (PPIs) is further compounded by the fact that an average protein consists of two or more domains, structurally and evolutionary independent subunits. Experimental studies have demonstrated that an interaction between a pair of proteins is not carried out by all domains constituting each protein, but rather by a select subset. However, finding which domains from each protein mediate the corresponding PPI is a challenging task.ResultsHere, we present Domain Interaction Statistical POTential (DISPOT), a simple knowledge-based statistical potential that estimates the propensity of an interaction between a pair of protein domains, given their SCOP family annotations. The statistical potential is derived based on the analysis of more than 352,000 structurally resolved protein-protein interactions obtained from DOMMINO, a comprehensive database on structurally resolved macromolecular interactionsAvailability and implementationDISPOT is implemented in Python 2.7 and packaged as an open-source tool. DISPOT is implemented in two modes, basic and auto-extraction. The source code for both modes is available on Github: (https://github.com/KorkinLab/DISPOT) and standalone docker images on DockerHub: (https://cloud.docker.com/u/korkinlab/repository/docker/korkinlab/dispot).
Multiple selection signatures in farmed Atlantic salmon adapted to different environments across Hemispheres
Authors: López M.E. , Linderoth T. , Norris A. , Lhorente J.P. , Neira R. , Yáñez J.M. 
Published: January 2019

1.ABSTRACTDomestication of Atlantic salmon started approximately forty years ago, using both artificial and natural selection strategies. Such selection methods are likely to have imposed distinctive selection signatures on the salmon genome. Therefore, identifying differences in selection signatures may give insights into the mechanism of selection and candidate genes of biological and productive interest. Here, we used two complementary haplotype-based statistics, the within-population integrated Haplotype Score test (|iHS|) and the cross-population Extended Haplotype Homozygosity test (XP-EHH) to compare selection signatures in four populations of Atlantic salmon with a common genetic origin. Using |iHS| we found 24, 14, 16 and 26 genomic regions under selection in Pop-A, Pop-B, Pop-C, and Pop-D, respectively. While using the XP-EHH test we identified 27, 25 and 15 potential selection regions in Pop-A/Pop-B, Pop-A/Pop-C and Pop-A/Pop-D, respectively. These genomic regions harbor important genes suchigf1randsh3rf1which have been associated with growth related traits in other species. Our results contribute to the detection of candidate genes of interest and help to understand the evolutionary and biological mechanisms for controlling complex traits under selection in Atlantic salmon.
Differential effects of emerging broad-spectrum streetlight technologies on landscape-scale bat activity
Authors: Williams Rowland , Walters Charlotte , Gibb Rory , Browning Ella , Tipping David , Jones Kate E. 
Published: January 2019

SummaryUrbanization has greatly reduced the extent of high quality habitat available to wildlife with detrimental consequences documented across a range of taxa. Roads and artificial lighting regimes are dominant features of the modern environment, and there is currently a rapid worldwide transition towards energy-efficient, broad-spectrum white-light streetlight technologies such as metal halide (MH) and more recently, light-emitting diode (LED), despite little being known about their broad ecological impacts. Here, in a five-year citizen science study across the island of Jersey, we combine detailed lighting and habitat data with ultrasonic bat survey data collected from 2011 to 2015 (before and after a LED lighting technology transition), to analyse the landscape-scale effects of different broad-spectrum streetlight technologies on activity of a widespread, generalist bat species. In contrast to many experimental studies, we show that the local density of both traditional yellow high-pressure sodium (HPS) and more modern LED streetlights have significant negative effects on activity of the common pipistrelle (Pipistrelluspipistrellus) compared to unlit areas, while accounting for spatial bias, bat population trends over time, surrounding habitat type and road-type. In contrast, we find no discernable impact of the density of ultra-violet emitting MH lighting on bat activity. This is the first large-scale evidence that emerging artificial lighting technologies have differential impacts on activity, even for a bat species generally characterised as light-tolerant and commonly found in urban areas. Importantly, our landscape-level approach also demonstrates that the degree of urbanization and road type have even larger negative impacts on bat activity, independent of artificial lighting regime. Our findings emphasise the need for improving landscape-scale understanding of the ecological impacts of new lighting technologies prior to widespread uptake, and have important implications for future streetlight installation programmes and urban planning more generally.
p63 cooperates with CTCF to modulate chromatin architecture in skin keratinocytes
Authors: Qu Jieqiong , Yi Guoqiang , Zhou Huiqing 
Published: January 2019

AbstractThe transcription factor p63 regulates epidermal genes and the enhancer landscape in skin keratinocytes. Its molecular function in controlling the chromatin structure is however not yet completely understood. Here we integrated multi-omics profiles, including the transcriptome, transcription factor DNA-binding and chromatin accessibility, in skin keratinocytes isolated from EEC syndrome patients carrying p63 mutations, to examine the role of p63 in shaping the chromatin architecture. We found decreased chromatin accessibility in p63-and CTCF-bound open chromatin regions that potentially contributed to gene deregulation in mutant keratinocytes. Cooperation of p63 and CTCF seemed to assist chromatin interactions between p63-bound enhancers and gene promoters in skin keratinocytes. Our study suggests an intriguing model where cell type-specific transcription factors such as p63 cooperate with the genome organizer CTCF in the three-dimensional chromatin space to regulate the transcription program important for the proper cell identity.
Accurate detection of m6A RNA modifications in native RNA sequences
Authors: Liu Huanle , Begik Oguzhan , Lucas Morghan C , Mason Christopher E. , Schwartz Schraga , Mattick John S. , Smith Martin A. , Novoa Eva Maria 
Published: January 2019

ABSTRACTThe field of epitranscriptomics has undergone an enormous expansion in the last few years; however, a major limitation is the lack of generic methods to map RNA modifications transcriptome-wide. Here we show that using Oxford Nanopore Technologies, N6-methyladenosine (m6A) RNA modifications can be detected with high accuracy, in the form of systematic errors and decreased base-calling qualities. Our results open new avenues to investigate the universe of RNA modifications with single nucleotide resolution, in individual RNA molecules.
Synapse-specific Opioid Modulation of Thalamo-cortico-striatal Circuits
Authors: Birdsong William T. , Jongbloets Bart C. , Engeln Kim A. , Wang Dong , Scherrer Gregory , Mao Tianyi 
Published: January 2019

AbstractThe medial thalamus (MThal), anterior cingulate cortex (ACC) and striatum play important roles in affective-motivational pain processing and reward learning. Opioids affect both pain and reward through uncharacterized modulation of this circuitry. This study examined opioid actions on glutamate transmission between these brain regions in mouse. Mu-opioid receptor (MOR) agonists potently inhibited MThal inputs without affecting ACC inputs to individual striatal medium spiny neurons (MSNs). MOR activation also inhibited MThal inputs to the pyramidal neurons in the ACC. In contrast, delta-opioid receptor (DOR) agonists disinhibited ACC pyramidal neuron responses to MThal inputs by suppressing local feed-forward GABA signaling from parvalbumin-positive interneurons. As a result, DOR activation in the ACC facilitated poly-synaptic (thalamo-cortico-striatal) excitation of MSNs by MThal inputs. These results suggest that opioid effects on pain and reward may be shaped by the relative selectivity of opioid drugs to the specific circuit components.