bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a pre- and in-scan system to minimize head motion in pediatric participants undergoing fMRI scans
Authors: Horien Corey , Fontenelle Scuddy , Joseph Kohrissa , Powell Nicole , Nutor Chaela , Fortes Diogo , Butler Maureen , Powell Kelly , Macris Deanna , Lee Kangjoo , McPartland James C. , Volkmar Fred R. , Scheinost Dustin , Chawarska Katarzyna , Constable R. Todd 
Published: March 2020

AbstractBackgroundPerforming fMRI scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in functional magnetic resonance imaging (fMRI) connectivity analyses, and methods to limit the impact of movement on data quality are needed. One approach has been to use shorter MRI protocols, though this potentially reduces the reliability of the results.ObjectiveHere we describe steps we have taken to limit head motion in an ongoing fMRI study of children undergoing a 60 minute MRI scan protocol. Specifically, we have used a mock scan protocol that trains participants to lie still while being scanned. We provide a detailed protocol and describe other in-scanner measures we have implemented, including an incentive system and the use of a weighted blanket.Materials and methodsParticipants who received a formal mock scan (n = 12) were compared to participants who had an informal mock scan (n = 7). A replication group of participants (n = 16), including five with autism spectrum disorder, who received a formal mock scan were also compared to the informal mock scan group. The primary measure of interest was the mean frame-to-frame displacement across eight functional runs during the fMRI protocol.ResultsParticipants in the formal mock scan and replication group tended to exhibit more low-motion functional scans than the informal mock scan group (P< 0.05). Across different functional scan conditions (i.e. while watching movie clips, performing an attention task, and during resting-state scans), effect sizes tended to be large (Hedge’sg> 0.8).ConclusionResults indicate that with appropriate measures, it is possible to achieve low-motion fMRI data in younger participants undergoing a long scan protocol.
Aberrant Sensory Encoding in Patients with Autism
Authors: Noel Jean-Paul , Zhang Ling-Qi , Stocker Alan A. , Angelaki Dora E. 
Published: March 2020

AbstractPerceptual anomalies in patients with Autism Spectrum Disorder (ASD) have been attributed to irregularities in the Bayesian interpretation (i.e., decoding) of sensory information. Here we show that how sensory information is encoded and adapts to changing stimulus statistics also characteristically differs between healthy and ASD groups. In a visual estimation task, we extracted the accuracy of sensory encoding directly from psychophysical data, bypassing the decoding stage by using information theoretic measures. Initially, sensory representations in both groups reflected the statistics of visual orientations in natural scenes, but encoding capacity was overall lower in the ASD group. Exposure to an artificial statistical distribution of visual orientations altered the sensory representations of the control group toward the novel experimental statistics, while also increasing their total encoding resources. Neither total encoding resources nor their allocation changed significantly in the ASD group. Most interestingly, across both groups the adaptive re-allocation of encoding resources was correlated with subjects’ initial encoding capacity. These findings suggest that neural encoding resources are limited in ASD, and this limitation may explain their reduced perceptual flexibility.
LRP5 promotes adipose progenitor cell fitness and adipocyte insulin sensitivity
Authors: Loh Nellie Y. , Vasan Senthil K. , Verma Manu , Wesolowska-Andersen Agata , Neville Matt J. , Osmond Clive , Gregson Celia L. , Karpe Fredrik , Christodoulides Constantinos 
Published: March 2020

ABSTRACTWNT signalling is a developmental pathway which plays an important role in post-natal bone accrual. We have previously shown, that in addition to exhibiting extreme high bone mass, subjects with rare gain-of-function (GoF) mutations in the WNT co-receptor LRP5 also display increased lower-body fat mass. Here, we demonstrate using human physiological studies in GoF LRP5 mutation carriers and glucose uptake assays in LRP5 knockdown (KD) adipocytes that LRP5 promotes adipocyte insulin sensitivity. We also show that a low frequency missense variant in LRP5 shown to be associated with low heel bone mineral density in a genome wide association study meta-analysis, is associated with reduced leg fat mass. Finally, using genome wide transcriptomic analyses andin vitrofunctional studies in LRP5-KD adipose progenitors (APs) we demonstrate that LRP5 plays an essential role in maintaining AP fitness i.e. functional characteristics. Pharmacological activation of LRP5 signalling in adipose tissue provides a promising strategy to prevent the redistribution of adipose tissue and metabolic sequela associated with obesity and ageing.
Ankhd1enhances polycystic kidney disease development via promoting proliferation and fibrosis
Authors: Patera Foteini , Hautbergue Guillaume M , Wilson Patricia , Evans Paul C , Ong Albert CM , Fragiadaki Maria 
Published: March 2020

ABSTRACTAutosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic kidney disorder resulting in 10% of patients with renal failure. The molecular events responsible for the relentless growth of cysts are not defined. Thus, identification of novel drivers of ADPKD may lead to new therapies. Ankyrin Repeat and Single KH domain-1 (ANKHD1) controls cancer cell proliferation, yet its role in ADPKD is unexplored. Here, we present the first data that identify ANKHD1 as a driver of proliferative growth in cellular and mouse models of ADPKD. Using the firstAnkhd1-deficient mice, we demonstrate thatAnkhd1heterozygosity potently reduces cystic growth and fibrosis, in a genetically orthologous mouse model of ADPKD. We performed transcriptome-wide profiling of patient-derived ADPKD cells with and without ANKHD1 siRNA silencing, revealing a major role for ANKHD1 in the control of cell proliferation and matrix remodelling. We validated the role of ANKHD1 in enhancing proliferation in patient-derived cells. Mechanistically ANKHD1 promotes STAT5 signalling in ADPKD mice. Hence, ANKHD1 is a novel driver of ADPKD, and its inhibition may be of therapeutic benefit.
Fluoxetine treatment prevents cardiovascular changes in baroreflex and chemoreflex in rats subjected to chronic stress
Authors: Firmino Egidi Mayara Silva , Kuntze Luciana Bärg , Lagatta Davi Campos , Dias Daniel Penteado Martins , Resstel Leonardo Barbosa Moraes 
Published: March 2020

AbstractStress may influence the autonomic regulation, pathogenesis of cardiovascular disease and play an important role in animal behavior as depression. Depression is evidenced as a significant risk factor for cardiovascular changes. This is of great importance as some studies show an association between symptoms of depression and increased risk of cardiovascular disease (CVD) morbidity. Additionality, those alterations can be alleviated by use of antidepressants such as fluoxetine, which is a selective serotonin reuptake inhibitor (SSRIs). The link between depression and cardiovascular changes is known to be mediated in part by autonomic mechanisms that contribute to the regulation of cardiovascular function. However, studies on the effects of SSRIs on cardiovascular autonomic function are inconsistent. Thus, in the present study we investigated, in adult male rats, the effect of chronic and acute treatment with fluoxetine on changes in autonomic mechanisms of baroreflex and chemoreflex induced by the repeated restraint stress (RRS) or chronic variable stress (CVS) on baroreflex and chemoreflex in a protocol of 14 days of stress sessions. The results found demonstrated that exposure to chronic stress (RRS and CVS) promove changes on cardiovascular and ventilatory responses controlled by autonomic reflexes, such as baroreflex and chemoreflex. Additionality, that chronic fluoxetine treatment for 21 days was able to prevent not only anhedonic behavior, but also of autonomic changes cardiovascular induced by chronic stress. Taken together, our results show that pharmacological treatment with fluoxetine may be also helpful to prevent cardiovascular events on account of depressive states, by correcting alterations in autonomic function.
Effects of arousal and movement on secondary somatosensory and visual thalamus
Authors: Petty Gordon H. , Kinnischtzke Amanda K. , Hong Y. Kate , Bruno Randy M. 
Published: March 2020

AbstractAll neocortical sensory areas have an associated primary and secondary thalamic nucleus. While the primary nuclei encode sensory information for transmission to cortex, the nature of information encoded in secondary nuclei is poorly understood. We recorded juxtasomally from neurons in secondary somatosensory (POm) and visual (LP) thalamic nuclei of awake head-fixed mice with simultaneous whisker tracking and pupilometry. POm activity correlated with whether or not a mouse was whisking, but not precise whisking kinematics. This coarse movement modulation persisted after unilateral paralysis of the whisker pad and thus was not due to sensory reafference. POm continued to track whisking even during optogenetic silencing of primary somatosensory and motor cortex and after lesion of superior colliculus, indicating that motor efference copy cannot explain the correlation between movement and POm activity. Whisking and pupil dilation were strongly correlated, raising the possibility that POm may track arousal rather than movement. LP, being part of the visual system, is not expected to encode whisker movement. We discovered, however, that LP and POm track whisking equally well, suggesting a global effect of arousal on both nuclei. We conclude that secondary thalamus is a monitor of behavioral state, rather than movement, and may exist to alter cortical activity accordingly.
PhyloFold: Precise and Swift Prediction of RNA Secondary Structures to Incorporate Phylogeny among Homologs
Authors: Tagashira Masaki 
Published: March 2020

AbstractMotivationThesimultaneous consideration of sequence alignment and RNA secondary structure, or structural alignment, is known to help predict more accurate secondary structures of homologs. However, the consideration is heavy and can be done only roughly to decompose structural alignments.ResultsThe PhyloFold method, which predicts secondary structures of homologs considering likely pairwise structural alignments, was developed in this study. The method shows the best prediction accuracy while demanding comparable running time compared to conventional methods.AvailabilityThe source code of the programs implemented in this study is available on “https://github.com/heartsh/phylofold” and “https://github.com/heartsh/phyloalifold“.Contact“tagashira_masaki_17@stu-cbms.k.u-tokyo.ac.jp”.Supplementary informationSupplementary data are available.
Space-time logic of liver gene expression at sublobular scale
Authors: Droin Colas , Kholtei Jakob El , Halpern Keren Bahar , Hurni Clémence , Rozenberg Milena , Muvkadi Sapir , Itzkovitz Shalev , Naef Felix 
Published: March 2020

AbstractThe mammalian liver performs key physiological functions for maintaining energy and metabolic homeostasis. Liver tissue is both spatially structured and temporally orchestrated. Hepatocytes operate in repeating anatomical units termed lobules and different lobule zones perform distinct functions. The liver is also subject to extensive temporal regulation, orchestrated by the interplay of the circadian clock, systemic signals and feeding rhythms. Liver zonation was previously analyzed as a static phenomenon and liver chronobiology at the tissue level. Here, we use single-cell RNA-seq to investigate the interplay between gene regulation in space and time. Categorizing mRNA expression profiles using mixed-effect models and smFISH validations, we find that many genes in the liver are both zonated and rhythmic, most of them showing multiplicative space-time effects. Such dually regulated genes cover key hepatic functions such as lipid, carbohydrate and amino acid metabolism, but also genes not previously associated with liver zonation such as chaperones. Our data also suggest that rhythmic and localized expression of Wnt targets could be explained by rhythmically expressed Wnt ligands from non-parenchymal cells near the central vein. Core circadian clock genes are expressed in a non-zonated manner, indicating that the liver clock is robust to zonation. Together, our comprehensive scRNA-seq analysis revealed how liver function is compartmentalized spatio-temporally at the sub-lobular scale.
ICELLNET: a transcriptome-based framework to dissect intercellular communication
Authors: Noël Floriane , Massenet-Regad Lucile , Carmi-Levy Irit , Cappuccio Antonio , Grandclaudon Maximilien , Trichot Coline , Kieffer Yann , Mechta-Grigoriou Fatima , Soumelis Vassili 
Published: March 2020

AbstractCell-to-cell communication can be inferred from ligand-receptor expression in cell transcriptomic datasets. However, important challenges remain: 1) global integration of cell-to-cell communication, 2) biological interpretation, and 3) application to individual cell population transcriptomic profiles. We developed ICELLNET, a transcriptomic-based framework integrating: 1) an original expert-curated database of ligand-receptor interactions accounting for multiple subunits expression, 2) quantification of communication scores, 3) the possibility to connect a cell population of interest with 31 reference human cell types (BioGPS), and 4) three visualization modes to facilitate biological interpretation. We applied ICELLNET to uncover different communication in breast cancer associated fibroblast (CAF) subsets. ICELLNET also revealed autocrine IL-10 as a switch to control human dendritic cell communication with up to 12 other cell types, four of which were experimentally validated. In summary, ICELLNET is a global, versatile, biologically validated, and easy-to-use framework to dissect cell communication from single or multiple cell-based transcriptomic profile(s).
redPATH: Reconstructing the Pseudo Development Time of Cell Lineages in Single-Cell RNA-Seq Data and Applications in Cancer
Authors: Xie Kaikun , Liu Zehua , Chen Ning , Chen Ting 
Published: March 2020

AbstractRecent advancement of single-cell RNA-seq technology facilitates the study of cell lineages in developmental processes as well as cancer. In this manuscript, we developed a computational method, called redPATH, to reconstruct the pseudo developmental time of cell lineages using a consensus asymmetric Hamiltonian path algorithm. Besides, we implemented a novel approach to visualize the trajectory development of cells and visualization methods to provide biological insights. We validated the performance of redPATH by segmenting different stages of cell development on multiple neural stem cell and cancerous datasets, as well as other single-cell transcriptome data. In particular, we identified a subpopulation of malignant glioma cells, which are stem cell-like. These cells express known proliferative markers such asGFAP(also identifiedATP1A2,IGFBPL1,ALDOC) and remain silenced in quiescent markers such asID3. Furthermore,MCL1is identified as a significant gene that regulates cell apoptosis, andCSF1Rconfirms previous studies for re-programming macrophages to control tumor growth. In conclusion, redPATH is a comprehensive tool for analyzing single-cell RNA-Seq datasets along a pseudo developmental time. The software is available viahttp://github.com/tinglab/redPATH.
Exploring the upper pH limits of nitrite oxidation: diversity, ecophysiology, and adaptive traits of haloalkalitolerantNitrospira
Authors: Daebeler Anne , Kitzinger Katharina , Koch Hanna , Herbold Craig W. , Steinfeder Michaela , Schwarz Jasmin , Zechmeister Thomas , Karst Søren M. , Albertsen Mads , Nielsen Per H. , Wagner Michael , Daims Holger 
Published: March 2020

AbstractNitrite-oxidizing bacteria of the genusNitrospiraare key players of the biogeochemical nitrogen cycle. However, little is known about their occurrence and survival strategies in extreme pH environments. Here, we report on the discovery of physiologically versatile, haloalkalitolerantNitrospirathat drive nitrite oxidation at exceptionally high pH.Nitrospiradistribution, diversity, and ecophysiology were studied in hypo- and subsaline (1.3-12.8 g salt/l), highly alkaline (pH 8.9-10.3) lakes by amplicon sequencing, metagenomics, and cultivation-based approaches. Surprisingly, not only wereNitrospirapopulations detected, but they were also considerably diverse with presence of members ofNitrospiralineages I, II and IV. Furthermore, the ability ofNitrospiraenrichment cultures to oxidize nitrite at neutral to highly alkaline pH of 10.5 was demonstrated. Metagenomic analysis of a newly enrichedNitrospiralineage IV species, “CandidatusNitrospira alkalitolerans”, revealed numerous adaptive features of this organism to its extreme environment. Among them were a sodium-dependent N-type ATPase and NADH:quinone oxidoreductase next to the proton-driven forms usually found inNitrospira. Other functions aid in pH and cation homeostasis and osmotic stress defense. “Ca.Nitrospira alkalitolerans” also possesses group 2a and 3b [NiFe] hydrogenases, suggesting it can use hydrogen as alternative energy source. These results reveal howNitrospiracope with strongly fluctuating pH and salinity conditions and expand our knowledge of nitrogen cycling in extreme habitats.
Pex24 and Pex32 tether peroxisomes to the ER for organelle biogenesis, positioning and segregation
Authors: Wu Fei , de Boer Rinse , Krikken Arjen M. , Akşit Arman , Bordin Nicola , Devos Damien P. , van der Klei Ida J. 
Published: March 2020

AbstractWe analyzed all four Pex23 family proteins of the yeastHansenula polymorpha, which localize to the ER. Of these Pex24 and Pex32, but not Pex23 and Pex29, accumulate at peroxisome-ER contacts, where they are important for normal peroxisome biogenesis and proliferation and contribute to organelle positioning and segregation.Upon deletion ofPEX24andPEX32- and to a lesser extent ofPEX23andPEX29- peroxisome-ER contacts are disrupted, concomitant with peroxisomal defects. These defects are suppressed upon introduction of an artificial peroxisome-ER tether.Accumulation of Pex32 at peroxisomes-ER contacts is lost in the absence of the peroxisomal membrane protein Pex11. At the same time peroxisome-ER contacts are disrupted, indicating that Pex11 contributes to Pex32-dependent peroxisome-ER contact formation.Summarizing, our data indicate thatH. polymorphaPex24 and Pex32 are tethers at peroxisome-ER contacts that are important for normal peroxisome biogenesis and dynamics.SummaryTwoHansenula polymorphaER proteins, Pex24 and Pex32, are tethers at peroxisome-ER contacts and function together with the peroxisomal protein Pex11. Their absence disturbs these contacts leading to multiple peroxisomal defects, which can be restored by an artificial tether.
Mapping the principal gradient onto the corpus callosum
Authors: Friedrich Patrick , Forkel Stephanie J. , de Schotten Michel Thiebaut 
Published: March 2020

AbstractGradients capture some of the variance of the resting-state functional magnetic resonance imaging (rsfMRI) signal. Amongst these, the principal gradient depicts a functional processing hierarchy that spans from sensory-motor cortices to regions of the default-mode network. While the cortex has been well characterised in terms of gradients little is known about its underlying white matter. For instance, comprehensive mapping of the principal gradient on the largest white matter tract, the corpus callosum, is still missing. We hence mapped the principal gradient onto the callosal midsection using the 7T human connectome project dataset. We further explored how quantitative measures and variability in callosal midsection connectivity relate to the principal gradient values. In so doing, we demonstrated that the extreme values of the principal gradient are located within the callosal genu and the posterior body, have lower connectivity variability but a larger spatial extent along the midsection of the corpus callosum than mid-range values. Our results shed light on the relationship between the brain’s functional hierarchy and the corpus callosum. We further speculate about how these results may bridge the gap between functional hierarchy, brain asymmetries, and evolution.
An inducible CRISPR-interference library for genetic interrogation of Saccharomyces cerevisiae biology
Authors: Momen-Roknabadi Amir , Oikonomou Panos , Zegans Maxwell , Tavazoie Saeed 
Published: March 2020

AbstractGenome-scale CRISPR interference (CRISPRi) is widely utilized to study cellular processes in a variety of organisms. Despite its dominance as a model eukaryote, a genome-wide CRISPRi library, optimized for targeting the Saccharomyces cerevisiae genome, has not been presented to date. We have generated a comprehensive, inducible CRISPRi library, based on spacer design rules optimized for yeast. We have validated this library for genome-wide interrogation of gene function across a variety of applications, including accurate discovery of haploinsufficient genes and identification of enzymatic and regulatory genes involved in adenine and arginine biosynthesis. The comprehensive nature of the library also revealed parameters for optimal transcriptional repression, including upstream distance, nucleosomal occupancy, and strand bias. CRISPRi screens, using this library can identify genes and pathways with high precision and low false discovery rate across a variety of experimental conditions, enabling rapid and reliable genome-wide assessment of gene function and genetic interactions in S.cerevisiae.
Transitioning from global to local computational strategies during brain-machine interface learning
Authors: Bridges Nathaniel , Stickle Matthew , Moxon Karen 
Published: March 2020

AbstractWhen learning to use a brain-machine interface (BMI), the brain modulates neuronal activity patterns, exploring and exploiting the state space defined by their neural manifold. Neurons directly involved in BMI control can display marked changes in their firing patterns during BMI learning. However, whether these changes extend to neurons not directly involved in BMI control remains unclear. To clarify this issue, we studied BMI learning in animals that were required to control the position of a platform with their neural signals. Animals that learned to control the platform and improved their performance in the task shifted from a global strategy, where both direct and indirect neurons modified their firing patterns, to a local strategy, where only direct neurons modified their firing rate, as animals became expert in the task. These results provide important insights into what differentiates successful and unsuccessful BMI learning and the computational mechanisms adopted by the neurons.