bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct motivations to seek out information in healthy and addicted individuals
Authors: Dezza Irene Cogliati , Noel Xavier , Cleeremans Axel , Yu Angela J. 
Published: February 2020

ABSTRACTAs massive amounts of information are becoming available to people understanding the mechanisms underlying information-seeking is more pertinent today than ever. In this study, we investigate the underlying motivations to seek out information in healthy and addicted individuals. We developed a novel decision-making task and a novel computational model which allow to dissociate the relative contribution of two motivating factors to seek out information: a desire for novelty and a desire to reduce uncertainty. To investigate whether/how the motivations to seek out information vary between healthy and addicted individuals, in addition to healthy controls we included a sample of individuals with gambling disorder- a form of addiction without the confound of substance consumption and characterized by compulsive gambling. Our results indicate that healthy subjects and problem gamblers adopt distinct information-seeking “modes”. Healthy information-seeking behavior was mostly motivated by a desire for novelty. Problem gamblers, on the contrary, displayed reduced novelty-seeking and an increased desire to reduce uncertainty (general information-seeking) compared to healthy controls. Our findings not only shed new light on the motivations driving healthy and addicted individuals to seek out information, but they also have important implications for treatment and diagnosis of behavioral addiction.
Evidence for immediate enhancement of hippocampal memory encoding by network-targeted theta-burst stimulation during concurrent fMRI
Authors: Hermiller Molly S. , Chen Yu Fen , Parrish Todd B. , Voss Joel L. 
Published: February 2020

AbstractThe hippocampus supports episodic memory via interaction with a distributed brain network. Previous experiments using network-targeted noninvasive brain stimulation have identified episodic memory enhancements and modulation of activity within the hippocampal network. However, mechanistic insights were limited because these effects were measured long after stimulation and therefore could have reflected various neuroplastic aftereffects with extended timecourses. In this experiment with human subjects of both sexes, we tested for immediate stimulation impact on encoding-related activity of the hippocampus and immediately adjacent medial-temporal cortex by delivering theta-burst transcranial magnetic stimulation (TBS) concurrent with fMRI, as an immediate impact of stimulation would suggest an influence on neural activity. We reasoned that TBS would be particularly effective for influencing the hippocampus because rhythmic neural activity in the theta band is associated with hippocampal memory processing. First, we demonstrated that it is possible to obtain robust fMRI correlates of task-related activity during concurrent TBS. We then identified immediate effects of TBS on encoding of visual scenes. Brief volleys of TBS targeting the hippocampal network increased activity of the targeted (left) hippocampus during scene encoding and increased subsequent recollection. Stimulation did not influence activity during an intermixed numerical task with no memory demand. Control conditions using beta-band and out-of-network stimulation also did not influence hippocampal activity or recollection. TBS targeting the hippocampal network therefore immediately impacted hippocampal memory processing. This suggests direct, beneficial influence of stimulation on hippocampal neural activity related to memory and supports the role of theta-band activity in human episodic memory.Significance StatementCan noninvasive stimulation directly impact function of indirect, deep-brain targets such as the hippocampus? We tested this by targeting an accessible region of the hippocampal network via transcranial magnetic stimulation during concurrent fMRI. We reasoned that theta-burst stimulation would be particularly effective for impacting hippocampal function, as this stimulation rhythm should resonate with the endogenous theta-nested-gamma activity prominent in hippocampus. Indeed, theta-burst stimulation targeting the hippocampal network immediately impacted hippocampal activity during encoding, improving memory formation as indicated by enhanced later recollection. Rhythm- and location-control stimulation conditions had no such effects. These findings suggest a direct influence of noninvasive stimulation on hippocampal neural activity and highlight that the theta-burst rhythm is relatively privileged in its ability to influence hippocampal memory function.
Common and separable neural alterations in substance use disorders: evidence from coordinate-based meta-analyses of functional neuroimaging studies in human
Authors: Klugah-Brown Benjamin , Di Xin , Zweerings Jana , Mathiak Klaus , Becker Benjamin , Biswal Bharat 
Published: February 2020

AbstractDelineating common and separable neural alterations in substance use disorders (SUD) is imperative to understand the neurobiological basis of the addictive process and to inform substance-specific treatment strategies. Given numerous functional MRI (fMRI) studies in different SUDs, meta-analysis could provide an opportunity to determine robust shared and substance-specific alterations. The present study employed a coordinate-based meta-analysis covering fMRI studies in individuals with addictive cocaine, cannabis, alcohol, and nicotine use. The primary meta-analysis demonstrated common alterations in primary dorsal striatal, and frontal circuits engaged in reward/salience processing, habit formation, and executive control across different substances and task-paradigms. Subsequent sub-analyses revealed substance-specific alterations in frontal and limbic regions, with marked frontal and insula-thalamic alterations in alcohol and nicotine use disorders respectively. Finally, examining task-specific alterations across substances revealed pronounced frontal alterations during cognitive processes yet stronger striatal alterations during reward-related processes. Together the findings emphasize the role of dysregulations in striato-frontal circuits and dissociable contributions of these systems in the domains of reward-related and cognitive processes which may contribute to substance-specific behavioral alterations.
Mucin 4 Protects Female Mice from Coronavirus Pathogenesis
Authors: Plante Jessica A. , Plante Kenneth S. , Gralinski Lisa E. , Beall Anne , Ferris Martin T. , Bottomly Daniel , Green Richard , McWeeney Shannon K. , Heise Mark T. , Baric Ralph S. , Menachery Vineet D. 
Published: February 2020

AbstractUsing incipient lines of the Collaborative Cross (CC), a murine genetic reference population, we previously identified a quantitative trait loci (QTL) associated with low SARS-CoV titer. In this study, we integrated sequence information and RNA expression of genes within the QTL to identify mucin 4 (Muc4) as a high priority candidate for controlling SARS-CoV titer in the lung. To test this hypothesis, we infectedMuc4-/-mice and found that female, but not male,Muc4-/-mice developed more weight loss and disease following infection with SARS-CoV. FemaleMuc4-/-mice also had more difficulty breathing despite reduced lung pathology; however, no change in viral titers was observed. Comparing across viral families, studies with chikungunya virus, a mosquito-borne arthralgic virus, suggests that Muc4’s impact on viral pathogenesis may be widespread. Although not confirming the original titer QTL, our data identifies a role for Muc4 in the SARS-CoV disease and viral pathogenesis.ImportanceGiven the recent emergence of SARS-CoV-2, this work suggest thatMuc4expression plays a protective role in female mice not conserved in male mice following SARS-CoV infection. With the SARS-CoV-2 outbreak continuing, treatments that modulate or enhanceMuc4activity may provide an avenue for treatment and improved outcomes. In addition, the work highlights the importance of studying host factors including host genetics and biological sex as key parameters influencing infection and disease outcomes.
The evolution of bacterial shape complexity by a curvature-inducing module
Authors: Martin Nicholas R. , Blackman Edith , Bratton Benjamin P. , Bartlett Thomas M. , Gitai Zemer 
Published: February 2020

AbstractBacteria can achieve a staggering diversity of cell shapes that promote critical functions like growth, motility, and virulence1-4. Previous studies suggested that bacteria establish complex shapes by co-opting the core machineries essential for elongation and division5,6. In contrast, we discovered a two-protein module, CrvAB, that can curve bacteria autonomously of the major elongation and division machinery by forming a dynamic, asymmetrically-localized structure in the periplasm. CrvAB is essential for curvature in its native species,Vibrio cholerae, and is sufficient to curve multiple heterologous species spanning 2.5 billion years of evolution. Thus, modular shape determinants can promote the evolution of morphological complexity independently of existing cell shape regulation.
GREM1 is epigenetically reprogrammed in muscle cells after exercise training and controls myogenesis and metabolism
Authors: Fabre Odile , Giordani Lorenzo , Parisi Alice , Pattamaprapanont Pattarawan , Ahwazi Danial , Brun Caroline , Chakroun Imane , Taleb Anissa , Blais Alexandre , Andersen Emil , Ingerslev Lars R , Maire Pascal , Rudnicki Michael , Laurens Claire , Citirikkaya Kiymet , Garde Christian , Lundell Leonidas , Deshmukh Atul S , Moro Cédric , Bourlier Virginie , Mounier Rémi , Grand Fabien Le , Barrès Romain 
Published: February 2020

AbstractExercise training improves skeletal muscle function, notably through tissue regeneration by muscle stem cells. Here, we hypothesized that exercise training reprograms the epigenome of muscle cell, which could account for better muscle function. Genome-wide DNA methylation of myotube cultures established from middle-aged obese men before and after endurance exercise training identified a differentially methylated region (DMR) located downstream ofGremlin 1(GREM1), which was associated with increasedGREM1expression. GREM1 expression was lower in muscle satellite cells from obese, compared to lean mice, and exercise training restored GREM1 levels to those of control animals. We show that GREM1 regulates muscle differentiation through the negative control of satellite cell self-renewal, and that GREM1 controls muscle lineage commitment and lipid oxidation through the AMPK pathway. Our study identifies novel functions of GREM1 and reveals an epigenetic mechanism by which exercise training reprograms muscle stem cells to improve skeletal muscle function.
Annexin A4 trimers are recruited by high membrane curvatures in Giant Plasma Membrane Vesicles
Authors: Florentsen Christoffer , Kamp-Sonne Alexander , Moreno-Pescador Guillermo , Pezeshkian Weria , Hakami Zanjani Ali Asghar , Khandelia Himanshu , Nylandsted Jesper , Bendix Poul Martin 
Published: February 2020

AbstractThe plasma membrane of eukaryotic cells consists of a crowded environment comprised of a high diversity of proteins in a complex lipid matrix. The lateral organization of membrane proteins in the plasma membrane (PM) is closely correlated with biological functions such as endocytosis, membrane budding and other processes which involve protein mediated shaping of the membrane into highly curved structures. Annexin A4 (ANXA4) is a prominent player in a number of biological functions including plasma membrane repair. Its binding to membranes is activated by Ca2+influx and it is therefore rapidly recruited to the cell surface near rupture sites where Ca2+influx takes place. However, the free edges near rupture sites can easily bend into complex curvatures and hence may accelerate recruitment of curvature sensing proteins to facilitate rapid membrane repair. To analyze the curvature sensing behavior of curvature inducing proteins in crowded membranes, we quantifify the affinity of ANXA4 monomers and trimers for high membrane curvatures by extracting membrane nanotubes from giant plasma membrane vesicles (GPMVs). ANXA4 is found to be a sensor of negative membrane curvatures. Multiscale simulations furthermore predicted that ANXA4 trimers generate membrane curvature upon binding and have an affinity for highly curved membrane regions only within a well defined membrane curvature window. Our results indicate that curvature sensing and mobility of ANXA4 depend on the trimer structure of ANXA4 which could provide new biophysical insight into the role of ANXA4 in membrane repair and other biological processes.
Neuroligin-mediated neurodevelopmental defects are induced by mitochondrial dysfunction and prevented by lutein inC. elegans
Authors: Maglioni Silvia , Schiavi Alfonso , Melcher Marlen , Brinkmann Vanessa , Luo Zhongrui , Laromaine Anna , Raimundo Nuno , Meyer Joel N , Distelmaier Felix , Ventura Natascia 
Published: February 2020

AbstractComplex I deficiency represents the most frequent pathogenetic cause of human mitochondriopathies. Therapeutic options for these neurodevelopmental life-threating disorders do not exist, partly due to the scarcity of appropriate model systems to study them.Caenorhabditis elegansis a genetically tractable model organism widely used to investigate neuronal pathologies. Here, we generated newC. elegansmodels for mitochondriopathies and showed that depletion of Complex I subunits recapitulates biochemical, cellular and neurodevelopmental aspects of the human diseases. Two models,nuo-5/NDUFS1- andlpd-5/NDUFS4-depleted animals, were exploited for a suppressor screening that identified lutein for its ability to rescue animals’ neurodevelopmental deficits. We uncovered overexpression of synaptic neuroligins as an evolutionarily conserved consequence of mitochondrial dysfunction, which we found to mediate an early cholinergic defect inC. elegans. We showed lutein exerts its beneficial effects by restoring neuroligin expression independently from its antioxidant activity, thus pointing to a possible novel pathogenetic target for the human disease.
Classification of multigene families of African swine fever viruses
Authors: Zhu Zhaozhong , Chen Huiting , Cao Yang , Jiang Taijiao , Zou Yuanqiang , Peng Yousong 
Published: February 2020

AbstractAfrican swine fever virus (ASFV) is a large and complex double-stranded DNA virus that poses serious threats to the pig industry. It is well-accepted that the multigene family (MGF) proteins are extensively distributed in ASFVs and are generally classified into five families, including MGF-100, MGF-110, MGF-300, MGF-360 and MGF-505. Most MGF proteins, however, have not been well characterized and classified within each family. To bridge this gap, this study first classified the MGF proteins into 35 groups based on protein sequence homology. A web server for classifying the MGF proteins was then established and available for free athttp://www.computationalbiology.cn/MGF/home.html. Results showed that the genetic diversity of the MGF groups varied widely, mainly due to the occurrence of indels. In addition, the MGF proteins were predicted to have large structural and functional diversity, and the MGF proteins of the same MGF family tended to have similar structure, location and function. Evolutionary analysis revealed the dynamic changes of the MGF proteins in the ASFV genomes, and more than half of MGF groups were presented in all ASFV genomes, which indicated the important role of MGF proteins in ASFVs. Overall, it is expected that the work would not only provide a detailed classification for MGF proteins, but also facilitate further research on MGF proteins.
Identification of novel mitochondrial and mitochondrial related genetic loci associated with exercise response in the Gene SMART study
Authors: Harvey NR , Voisin S , Lea RA , Yan X , Benton MC , Papadimitriou ID , Jacques M , Haupt LM , Ashton KJ , Eynon N , Griffiths LR 
Published: February 2020

ABSTRACTMitochondria supply intracellular energy requirements during exercise. Specific mitochondrial haplogroups and mitochondrial genetic variants have been associated with athletic performance, and exercise responses. However, these associations were discovered using underpowered, candidate gene approaches, and consequently have not been replicated. Here, we used whole-mitochondrial genome sequencing, in conjunction with high-throughput genotyping arrays, to discover novel genetic variants associated with exercise responses in the Gene SMART (Skeletal Muscle Adaptive Response to Training) cohort (n=62 completed). We performed a Principal Component Analysis of cohort aerobic fitness measures to build composite traits and test for variants associated with exercise outcomes. None of the mitochondrial genetic variants but nine nuclear encoded variants in eight separate genes were found to be associated with exercise responses (FDR<0.05)(rs11061368: DIABLO, rs113400963: FAM185A, rs6062129 and rs6121949: MTG2, rs7231304: AFG3L2, rs2041840: NDUFAF7, rs7085433: TIMM23, rs1063271: SPTLC2, rs2275273: ALDH18A1).Additionally, we outline potential mechanisms by which these variants may be contributing to exercise phenotypes. Our data suggest novel nuclear-encoded SNPs and mitochondrial pathways associated with exercise response phenotypes. Future studies should focus on validating these variants across different cohorts and ethnicities.AUTHOR SUMMARYPrevious exercise genetic studies contain many flaws that impede the growth in knowledge surrounding change in exercise outcomes. In particular, exercise studies looking at mtDNA variants have looked at very small portions of the mitochondrial genome. Mitochondria are the ‘power house’ of the cell and therefore understanding the mitochondrial genetics behind adaptations to training can help us fill knowledge gaps in current research. Here, we utilised a new mitochondrial genetic sequencing technique to examine all mitochondrial and mitochondrial related genetic variations. We have shown that there were no mitochondrial specific variants that influenced exercise training however there were 9 related variants that were significantly associated with exercise phenotypes. Additionally, we have shown that building composite traits increased the significance of our association testing and lead to novel findings. We will be able to understand why response to training is so varied and increase the effectiveness of exercise training on a host of metabolic disorders.
Altered synaptic plasticity and central pattern generator dysfunction in aDrosophilamodel of PNKD3 paroxysmal dyskinesia
Authors: Lowe Simon , Kratschmer Patrick , Jepson James E.C. 
Published: February 2020

ABSTRACTBackgroundParoxysmal non-kinesigenic dyskinesia type-3 (PNKD3) has been linked to gain-of-function (GOF) mutations in the hSlo1 BK potassium channel, in particular a dominant mutation (D434G) that enhances Ca2+-sensitivity. However, while BK channels play well-known roles in regulating neurotransmitter release, it is unclear whether the D434G mutation alters neurotransmission and synaptic plasticity in vivo. Furthermore, the subtypes of movement-regulating circuits impacted by this mutation are unknown.ObjectivesWe aimed to use a larvalDrosophilamodel of PNKD3 (sloE366G/+) to examine how BK channel GOF in dyskinesia alters synaptic properties and motor circuit function.MethodsWe used video-tracking to test for movement defects insloE366G/+larvae, and sharp-electrode recordings to assess the fidelity of Ca2+-dependent neurotransmitter release and short-term plasticity at the neuromuscular junction. We then combined sharp-electrode recording with ex vivo Ca2+-imaging to investigate the functionality of the central pattern generator (CPG) driving foraging behavior insloE366G/+larvae.ResultsWe show that the PNKD3 mutation leads to Ca2+-dependent alterations in synaptic release and paired-pulse facilitation. Furthermore, we identify robust alterations in locomotor behaviors insloE366G/+larvae which were mirrored by dysfunction of the upstream, movement-generating CPG in the larval ventral nerve cord.ConclusionOur results demonstrate that a BK channel GOF mutation can alter neurotransmitter release and short-term synaptic plasticity, and result in CPG dysfunction, inDrosophilalarvae. These data add to a growing body of work linking paroxysmal dyskinesias to aberrant neuronal excitability and synaptic plasticity in pre-motor circuits.
Expression of a Barhl1a reporter in subsets of retinal ganglion cells and commissural neurons of the developing zebrafish brain
Authors: Albadri Shahad , Armant Olivier , Aljand-Geschwill Tairi , Del Bene Filippo , Carl Matthias , Strähle Uwe , Poggi Lucia 
Published: February 2020

AbstractPromoting the regeneration or survival of retinal ganglion cells (RGCs) is one focus of regenerative medicine. Homeobox Barhl transcription factors might be instrumental in these processes. In mammals, onlybarhl2is expressed in the retina and is required for both subtype identity acquisition of amacrine cells and for the survival of RGCs downstream of Atoh7, a transcription factor necessary for RGC genesis. The underlying mechanisms of this dual role of Barhl2 in mammals have remained elusive. Whole genome duplication in the teleost lineage generated thebarhl1aandbarhl2paralogues. In the Zebrafish retina, Barhl2 functions as determinant of subsets of amacrine cells lineally related to RGCs independently of Atoh7. In contrast,barhl1aexpression depends on Atoh7 but its expression dynamics and function have not been studied. Here we describe for the first time a Barhl1a:GFP reporter linein vivoshowing that Barhl1a turns on exclusively in subsets of RGCs and their post-mitotic precursors. We also show transient expression of Barhl1a:GFP in diencephalic neurons extending their axonal projections as part of the post-optic commissure, at the time of optic chiasm formation. This work sets the ground for future studies on RGC subtype identity, axonal projections and genetic specification of Barhl1a-positive RGCs and commissural neurons.
Phe-Gly motifs drive fibrillization of TDP-43’s prion-like domain droplets
Authors: Pantoja-Uceda David , Stuani Cristiana , Laurents Douglas V. , McDermott Ann E. , Buratti Emanuele , Mompeán Miguel 
Published: February 2020

AbstractTDP-43 assembles various aggregate forms, including biomolecular condensates or functional and pathological amyloids, with roles in disparate scenarios (e.g. muscle regeneration versus neurodegeneration). The link between condensates and fibrils remains unclear, just as the factors controlling conformational transitions within these aggregate species: salt- or RNA-induced droplets may evolve into fibrils or remain in the droplet form, suggesting distinct endpoint species of different aggregation pathways. Using microscopy and NMR methods, we unexpectedly observedin vitrodroplet formation in the absence of salts or RNAs, and provided visual evidence for fibrillization at the droplet surface/solvent interface but not the droplet interior. Our NMR analyses unambiguously uncovered a distinct amyloid conformation in which Phe-Gly motifs are key elements of the reconstituted fibril form, suggesting a pivotal role for these residues in creating the fibril core. This contrasts the minor participation of Phe-Gly motifs in initiation of the droplet form. Our results point to an intrinsic (i.e., non-induced) aggregation pathway that may exist over a broad range of conditions, and illustrate structural features that distinguishes between aggregate forms.