bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agency and responsibility over virtual movements controlled through different paradigms of brain–computer interface
Authors: Nierula Birgit , Spanlang Bernhard , Martini Matteo , Borrell Mireia , Nikulin Vadim V. , Sanchez-Vives Maria V. 
Published: August 2019

AbstractAgency is the attribution of an action to the self and is a prerequisite for experiencing responsibility over its consequences. Here we investigated agency and responsibility by studying the control of movements of an embodied avatar, via brain computer interface (BCI) technology, in immersive virtual reality. After induction of virtual body ownership by visuomotor correlations, healthy participants performed a motor task with their virtual body. We compared the passive observation of the subject’s ‘own’ virtual arm performing the task with (1) the control of the movement through activation of sensorimotor areas (motor imagery) and (2) the control of the movement through activation of visual areas (steady-state visually evoked potentials). The latter two conditions were carried out using a brain–computer interface (BCI) and both shared the intention and the resulting action. We found that BCI-control of movements engenders the sense of agency, which is strongest for sensorimotor areas activation. Furthermore, increased activity of sensorimotor areas, as measured using EEG, correlates with levels of agency and responsibility. We discuss the implications of these results for the neural bases of agency, but also in the context of novel therapies involving BCI and the ethics of neurotechnology.Key points summaryWe induced embodiment of a virtual body and its movements were controlled by two different BCI paradigms – one based on signals from sensorimotor versus one from visual cortical areas.BCI-control of movements engenders agency, but not equally for all paradigms.Cortical sensorimotor activation correlates with agency and responsibility.This has significant implications for neurological rehabilitation and neuroethics.
Ephrin-B1 blocks adult cardiomyocyte proliferation and heart regeneration
Authors: Cauquil Marie , Mias Céline , Guilbeau-Frugier Céline , Karsenty Clément , Seguelas Marie-Hélène , Genet Gaël , Renaud-Gabardos Edith , Prats Anne-Catherine , Pons Véronique , Branchereau Maxime , Heymes Christophe , Calise Denis , Lairez Olivier , Daviaud Danièle , Honton Benjamin , Frongia Céline , Ducommun Bernard , Delisle Marie-Bernadette , Arvanitis Dina N. , Pathak Atul , Sénard Jean-Michel , Galés Céline 
Published: August 2019

AbstractAimsDeciphering the innate mechanisms governing the blockade of proliferation in adult cardiomyocytes (CMs) is challenging for mammalian heart regeneration. Despite the exit of CMs from the cell cycle during the postnatal maturation period coincides with their morphological switch to a typical adult rod-shape, whether these two processes are connected is unknown. Here, we examined the role of ephrin-B1, a CM rod-shape stabilizer, in adult CM proliferation and cardiac regeneration.Methods and resultsTransgenic- or AAV9-based ephrin-B1 repression in adult mouse heart led to substantial proliferation of resident CMs and tissue regeneration to compensate for apex resection, myocardial infarction (MI) and senescence. Interestingly, in the resting state, CMs lacking ephrin-B1 did not constitutively proliferate, indicative of no major cardiac defects. However, they exhibited proliferation-competent signature, as indicated by higher mononucleated state and a dramatic decrease of miR-195 mitotic blocker, which can be mobilized under neuregulin-1 stimulation in vitro and in vivo. Mechanistically, the post-mitotic state of the adult CM relies on ephrin-B1 sequestering of inactive phospho-Yap1, the effector of the Hippo-pathway, at the lateral membrane. Hence, ephrin-B1 repression leads to phospho-Yap1 release in the cytosol but CM quiescence at resting state. Upon cardiac stresses (apectomy, MI, senescence), Yap1 could be activated and translocated to the nucleus to induce proliferation-gene expression and consequent CM proliferationConclusionsOur results identified ephrin-B1 as a new natural locker of adult CM proliferation and emphasize that targeting ephrin-B1 may prove a future promising approach in cardiac regenerative medicine for HF treatment.SignificanceThe mammalian adult heart is unable to regenerate due to the inability of cardiomyocytes (CMs) to proliferate and replace cardiac tissue lost. Exploiting CM-specific transgenic mice or AAV9-based gene therapy, this works identifies ephrin-B1, a specific rod-shape stabilizer of the adult CM, as a natural padlock of adult CM proliferation for compensatory adaptation to different cardiac stresses (apectomy, MI, senescence), thus emphasizing a new link between the adult CM morphology and their proliferation potential. Moreover, the study demonstrates proof-of-concept that targeting ephrin-B1 may be an innovative therapeutic approach for ischemic heart failure.
Disentangling the impact of environmental and phylogenetic constraints on prokaryotic strain diversity
Authors: Maistrenko Oleksandr M. , Mende Daniel R. , Luetge Mechthild , Hildebrand Falk , Schmidt Thomas S. B. , Li Simone S. , Coelho Luis Pedro , Huerta-Cepas Jaime , Sunagawa Shinichi , Bork Peer 
Published: August 2019

AbstractMicrobial organisms inhabit virtually all environments and encompass a vast biological diversity. The pan-genome concept aims to facilitate an understanding of diversity within defined phylogenetic groups. Hence, pan-genomes are increasingly used to characterize the strain diversity of prokaryotic species. To understand the interdependency of pan-genome features (such as numbers of core and accessory genes) and to study the impact of environmental and phylogenetic constraints on the evolution of conspecific strains, we computed pan-genomes for 155 phylogenetically diverse species using 7000 high-quality genomes. We show that many pan-genome features such as functional diversity and core genome nucleotide diversity are correlated to each other. Further, habitat flexibility as approximated by species ubiquity is associated with several pan-genome features, particularly core genome size. In general, environment had a stronger impact on pan-genome features than phylogenetic signal. Similar environmental preferences led to convergent evolution of pan-genomic features in distant phylogenetic clades. For example, the soil environment promotes expansion of pan-genome size, while host-associated habitats lead to its reduction.
Response-related signals increase confidence but not metacognitive performance
Authors: Filevich Elisa , Koß Christina , Faivre Nathan 
Published: August 2019

AbstractConfidence judgements are a central tool for research in metacognition. In a typical task, participants first perform perceptual (first-order) decisions and then rate their confidence in these decisions. The relationship between confidence and first-order accuracy is taken as measure of metacognitive performance. Confidence is often assumed to stem from decision-monitoring processes alone, but processes that co-occur with the first-order decision may also play a role in confidence formation. In fact, across a broad range of tasks, trials with quick reaction times to the first-order task are often judged with relatively higher confidence than those with slow responses. This robust finding suggests that confidence could be informed by a readout of reaction times in addition to decision-monitoring processes. To test this possibility, we assessed the contribution of response-related signals to confidence and, in particular, to metacognitive performance (i.e., a measure of the adequacy of these confidence judgements). In a factorial design, we measured the effect of making an overt (vs. covert) decision, as well as the effect of pairing a motor action to the stimulus about which the first-order decision is made. Against our expectations, we found no differences in overall confidence or metacognitive performance when first-order responses were covert as opposed to overt. Further, actions paired to visual stimuli presented led to higher confidence ratings, but did not affect metacognitive performance. These results suggest that some of the relationships between first-order decisional signals and confidence might indeed be correlational, and attributable to an upstream cognitive process, common to the two of them.
Pan-active imidazolopiperazine antimalarials target thePlasmodium falciparumintracellular secretory pathway
Authors: LaMonte Gregory M. , Marapana Danushka S. , Gnadig Nina , Ottilie Sabine , Luth Madeline R. , Worgall Tilla S. , Rocamora Frances , Goldgof Gregory M. , Mohunlal Roxanne , Kumar T.R Santha , Thompson Jenny K. , Vigil Edgar , Yang Jennifer , Hutson Dylan , Johnson Trevor , Huang Jianbo , Williams Roy M. , Zou Bing Yu , Cheung Andrea L. , Kumar Prianka , Egan Timothy J. , Lee Marcus C.S. , Siegel Dionicio , Cowman Alan F. , Fidock David A. , Winzeler Elizabeth A. 
Published: August 2019

AbstractOne of the most promising new compound classes in clinical development for the treatment of malaria is the imidazolopiperazines (IZPs) class. Human trials have demonstrated that members of the IZP series, which includes KAF156 (Ganaplacide) and GNF179, are potent and effective againstPlasmodiumsymptomatic asexual blood-stage infections. Unlike other commonly used antimalarials, they also prevent transmission and block future infection in animal models. Despite the identification of severalPlasmodium falciparumresistance mechanisms including mutations in ER-localized PfCARL (PfEMP65), Acetyl-coA transporter, and PfUGT transporter, IZP’s mechanism of action remains unknown.To investigate, we combinedin vitroevolution and whole-genome analysis in the model organismSaccharomyces cerevisiaewith molecular, metabolomic, and chemogenomic methods, inP. falciparum.S. cerevisiaeclones that resist IZP activity carry multiple mutations in genes that encode endoplasmic reticulum(ER)-based lipid homeostasis and autophagy includingelo2,elo3,sur2,atg15andlcb4, as well as ER-basedsec66.InPlasmodium, IZPs cause inhibition of protein trafficking, block the establishment of new permeation pathways and result in ER expansion. We also observe sensitization with other secretion inhibitors such as brefeldin A and golgicidin as well as synthetic lethality with PfSEC62. Our data show that IZPs target the secretory pathway and highlight a novel mechanism for blocking parasite growth and development that is distinct from those of standard compounds used to treat malaria. In addition, we provide physiological signatures and hallmarks for inhibitors that work through this mechanism of action and show that IZPs are tool compounds for studying ER-dependent protein processing in different species.
The transcription factor E2A drives neural differentiation in pluripotent cells
Authors: Rao Chandrika , Malaguti Mattias , Mason John O. , Lowell Sally 
Published: August 2019

AbstractThe intrinsic mechanisms that link extracellular signalling to the onset of neural differentiation are not well understood. In pluripotent mouse cells, BMP blocks entry into the neural lineage via transcriptional upregulation of Inhibitor of Differentiation (Id) factors. We have previously identified that the major binding partner of Id proteins in pluripotent cells is the basic helix-loop-helix (bHLH) transcription factor (TF), E2A. Id1 can prevent E2A from forming heterodimers with bHLH TFs or from forming homodimers. Here, we show that overexpression of a forced E2A homodimer is sufficient to drive robust neural commitment in pluripotent cells, even under non-permissive conditions. Conversely, we find that E2A null cells display a defect in their neural differentiation capacity. E2A acts as an upstream activator of neural lineage genes, includingSox1andFoxd4, and as a repressor of Nodal signalling. Our results suggest a crucial role for E2A in establishing neural lineage commitment in pluripotent cells.
Population genomics of a bioluminescent symbiosis sheds light on symbiont transmission and specificity
Authors: Gould A.L. , Dunlap P.V. 
Published: August 2019

AbstractAll organisms depend on symbiotic associations with bacteria for their success, yet the processes by which specific symbioses are established and persist remain largely undescribed. To examine the ecological mechanisms involved in maintaining symbiont specificity over host generations, we examined the population genomics of a binary symbiosis involving the coral reef cardinalfishSiphamia tubiferand the luminous bacteriumPhotobacterium mandapamensis. Using restriction site-associated sequencing (RAD-Seq) methods we demonstrate that the facultative symbiont ofS. tubiferexhibits genetic structure at spatial scales of tens of kilometers in Okinawa, Japan in the absence of physical dispersal barriers and in contrast to the host fish. These results suggest the host’s behavioral ecology help structure symbiont populations at a reef site by symbiont enrichment, consequently fostering symbiont specificity. This approach also revealed several symbiont genes that were divergent between host populations including genes known to play a role in other host-bacteria associations.
Aberrant newborn T cell and microbiota developmental trajectories predict respiratory compromise during infancy
Authors: Grier Alex , Laniewski Nathan , Gill Ann L. , Kessler Haeja A. , Huyck Heidie , Carbonell Elizabeth , Holden-Wiltse Jeanne , Bandyopadhyay Sanjukta , Carnahan Jennifer , Dylag Andrew M. , Topham David J. , Falsey Ann R. , Caserta Mary T. , Pryhuber Gloria S. , Gill Steven R. , McDavid Andrew , Scheible Kristin M. 
Published: August 2019

AbstractNeonatal immune-microbiota co-development is poorly understood, yet appropriate recognition of – and response to – pathogens and commensal microbiota is critical to health. In this longitudinal study of 148 pre- and 119 full-term infants from birth through one year of age we found that postmenstrual age, or weeks from conception, not post-natal age, is the dominant factor influencing T cell and mucosal microbiota development. Numerous features of the T cell and microbiota functional development remain unexplained, however, by either age metric and are instead shaped by discrete peri- and post-natal events. Most strikingly, we establish that prenatal antibiotics or infection disrupt the normal T cell population developmental trajectory, influencing subsequent respiratory microbial colonization and predicting respiratory morbidity. In this way, early exposures imprint the postnatal immune-microbiota axis and place an infant at significant risk for respiratory morbidity in early childhood.One Sentence SummaryT cells and microbiota follow predictable, coordinated trajectories in newborns, and their coordination is an important determinant of illness in the first year.Graphical AbstractNasal and rectal microbiome was assessed weekly in the NICU, monthly post-discharge, and when respiratory illness symptoms occurred. T cells were characterized at birth (cord blood), 36-42 weeks postmenstrual age, and at 12 months. Quarterly respiratory morbidity surveys determined the 12-month outcome of persistent respiratory disease. More frequent illnesses and chronic disease outcomes occurred by one year of age if development of these systems was discordant or disrupted.
BET proteins are required for transcriptional activation of the senescent beta cell secretome in Type 1 Diabetes
Authors: Thompson Peter J. , Shah Ajit , Apostolopolou Charalampia-Christina , Bhushan Anil 
Published: August 2019

AbstractOBJECTIVEType 1 Diabetes (T1D) results from progressive loss of pancreatic beta cells due to autoimmune destruction. We recently reported that during the natural history of T1D in humans and the female nonobese diabetic (NOD) mouse model, beta cells acquire a senescence-associated secretory phenotype (SASP) that is a major driver of disease onset and progression, but the mechanisms that activate SASP in beta cells were not explored. The objective of this study was to identify transcriptional mechanisms of SASP activation in beta cells.METHODSWe used the female NOD mouse model of spontaneous autoimmune T1D and ex vivo experiments on NOD mouse and human islets to test the hypothesis that Bromodomain Extra-Terminal domain (BET) proteins activate the beta cell SASP transcriptional program.RESULTSHere we show that beta cell SASP is transcriptionally controlled by BET proteins, including BRD4. Chromatin analysis of key beta cell SASP genes in NOD islets revealed binding of BRD4 at active regulatory regions. BET protein inhibition in NOD islets diminished not only the transcriptional activation and secretion of SASP factors but also the non-cell autonomous activity. BET protein inhibition also decreased the extent of SASP induction in human islets exposed to DNA damage. The BET protein inhibitor iBET-762 prevented diabetes in NOD mice and also attenuated SASP in beta cells in vivo.CONCLUSIONSTaken together, our findings support a crucial role for BET proteins in the activation of the beta cell SASP transcriptional program. These studies suggest avenues for preventing T1D by transcriptional inhibition of SASP.
Size and mass prediction of almond kernels using machine learning image processing
Authors: Vidyarthi Sriram K , Tiwari Rakhee , Singh Samrendra K 
Published: August 2019

AbstractAfter harvesting almond crop, accurate measurement of almond kernel sizes is a significant specification to plan, develop and enhance almond processing operations. The size and mass of the individual almond kernels are vital parameters usually associated with almond quality, particularly head almond yield. In this study, we propose a novel methodology that combines image processing and machine-learning ensemble that accurately measures the size and mass of whole raw almond kernels (classification - Nonpareil) simultaneously. We have developed an image-processing algorithm using recursive method to identify the individual almond kernels from an image and estimate the size of the kernels based on the occupied pixels by a kernel. The number of pixels representing an almond kernel was used as its digital fingerprint to predict its size and mass. Various popular machine learning (ML) models were implemented to build a stacked ensemble model (SEM), predicting the mass of the individual almond kernels based on the features derived from the pixels of the individual kernels in the image. The prediction accuracy and robustness of image processing and SEM were analyzed using uncertainty quantification. The mean error in estimating the average length of 1000 almond kernel was 3.12%. Similarly, mean errors associated with predicting the 1000 kernel mass were 0.63%. The developed algorithm in almond imaging in this study can be used to facilitate a rapid almond yield and quality appraisals.
M-GWAS for the gut microbiome in Chinese adults illuminates on complex diseases
Authors: Liu Xiaomin , Tang Shanmei , Zhong Huanzi , Tong Xin , Jie Zhuye , Ding Qiuxia , Wang Dan , Guo Ruidong , Xiao Liang , Xu Xun , Yang Huanming , Wang Jian , Zong Yang , Liu Xiao , Zhang Yong , Brix Susanne , Kristiansen Karsten , Hou Yong , Jia Huijue , Zhang Tao 
Published: August 2019

SummaryThe gut microbiome has been established as a key environmental factor to health. Genetic influences on the gut microbiome have been reported, yet, doubts remain as to the significance of genetic associations. Here, we provide shotgun data for whole genome and whole metagenome from a Chinese cohort, identifying no less than 20% genetic contribution to the gut microbiota. Using common variants-, rare variants- and copy number variations (CNVs)-based association analyses, we identified abundant signals associated with the gut microbiome especially in metabolic, neurological and immunological functions. The controversial concept of enterotypes may have a genetic attribute, with the top 2 loci explaining 11% of the Prevotella-Bacteroides variances. Stratification according to gender led to the identification of differential associations in males and females. Genetically encoded responses to ectopic presence of oral bacteria in the gut appear to be a common theme in a number of diseases investigated by MWAS (Metagenome-wide association studies). Our two-stage M-GWAS (Microbiome genome-wide association studies) on a total of 1295 individuals unequivocally illustrates that neither microbiome nor GWAS studies could overlook one another in our quest for a better understanding of human health and diseases.HighlightsM-GWAS using high-depth whole genome identifies contributions from rare variants and CNVs.Gut microbial modules such as butyrate, amino acids, mucin degradation show genetic associations.Gender differential M-GWAS underscores differences in metabolic and psychological predispositions.Some of the MWAS markers for colorectal cancer and cardiometabolic diseases show genetic associations.
N-terminal autoprocessing and acetylation of MARTX Makes-Caterpillars Floppy-like effector is stimulated by ADP-Ribosylation Factor 1 in advance of Golgi fragmentation
Authors: Herrera Alfa , Muroski John , Sengupta Ranjan , Nguyen Hong Hanh , Agarwal Shivangi , Ogorzalek Loo Rachel R. , Mattoo Seema , Loo Joseph A. , Satchell Karla J. F. 
Published: August 2019

ABSTRACTStudies have successfully elucidated the mechanism of action of several effector domains that comprise the MARTX toxins ofVibrio vulnificus. However, the biochemical linkage between the cysteine proteolytic activity of Makes Caterpillars Floppy-like (MCF) effector and its cellular effects remains unknown. In this study, we identify the host cell factors that activatein vivoandin vitroMCF autoprocessing as ADP-Ribosylation Factor 1 (ARF1) and ADP-ribosylation Factor 3 (ARF3). Autoprocessing activity is enhanced when ARF1 is in its active (GTP-bound) form compared to the inactive (GDP-bound) form. Subsequent to auto-cleavage, MCF is acetylated on its exposed N-terminal glycine residue. Acetylation apparently does not dictate subcellular localization, as MCF is found localized throughout the cell. However, the cleaved form of MCF gains the ability to bind to the specialized lipid phosphatidylinositol 5-phosphate enriched in Golgi and other membranes necessary for endocytic trafficking, suggesting a fraction of MCF may be subcellular localized. Traditional thin-section electron microscopy, high-resolution cryoAPEX localization, and fluorescent microscopy show that MCF causes Golgi dispersal resulting in extensive vesiculation. In addition, host mitochondria are disrupted and fragmented. Surprisingly, ARF1 is not itself processed or post-translationally modified by MCF. Further, only catalytically inactive MCF stably associates with ARF1, thus serving as a substrate trap. Our data indicate that ARF1 is a cross-kingdom activator of MCF, but reveal that MCF mediates cytotoxicity likely by directly targeting another yet to be identified protein. This study begins to elucidate the biochemical activity of this important domain and gives insight into how it may promote disease progression.