bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of neutral sphingomyelinase-2 facilitates remyelination
Authors: Yoo Seung-Wan , Agarwal Amit , Smith Matthew D. , Khuder Saja S. , Baxi Emily G. , Thomas Ajit G. , Rojas Camilo , Moniruzzman Mohammed , Slusher Barbara S. , Bergles Dwight E. , Calabresi Peter A. , Haughey Norman J. 
Published: June 2019

AbstractFor reasons that are not completely understood, remyelination is often incomplete, producing thin myelin sheaths with disorganized structure. We investigated the cellular basis for this altered myelin structure, and found that the response of oligodendrocyte progenitor cells (OPCs), and mature oligodendrocytes to TNFα and IL-1β is modified by the expression of the sphingomyelin hydrolase nSMase2. OPCs do not express nSMase2, and exhibit a protective response to these cytokines manifest by decreased ceramide, increased sphingosine 1-phosphate, and increased cell motility. Mature oligodendrocytes express nSMase2, and respond to TNFα and IL-1β with a stress phenotype, evidenced by increased ceramide, decreased sphingosine, and active caspase 3. Pharmacological inhibition or a targeted genetic deletion of nSMase2in vivoincreased myelin thickness, and enhanced myelin compaction. These results suggest that inhibition of nSMase2 improves the quality of new myelin by protecting maturing/myelinating oligodendrocytes. Pharmacological inhibition of nSMase2 following a demyelinating event could stabilize the structure of these newly formed myelin sheaths and protect them from secondary demyelination.
Mutational signatures are jointly shaped by DNA damage and repair
Authors: Volkova Nadezda V , Meier Bettina , González-Huici Víctor , Bertolini Simone , Gonzalez Santiago , Voeringer Harald , Abascal Federico , Martincorena Iñigo , Campbell Peter J , Gartner Anton , Gerstung Moritz 
Published: June 2019

AbstractMutations arise when DNA lesions escape DNA repair. To delineate the contributions of DNA damage and DNA repair deficiency to mutagenesis we sequenced 2,717 genomes of wild-type and 53 DNA repair defectiveC. elegansstrains propagated through several generations or exposed to 11 genotoxins at multiple doses. Combining genotoxin exposure and DNA repair deficiency alters mutation rates or leads to unexpected mutation spectra in nearly 40% of all experimental conditions involving 9/11 of genotoxins tested and 32/53 genotypes. For 8/11 genotoxins, signatures change in response to more than one DNA repair deficiency, indicating that multiple genes and pathways are involved in repairing DNA lesions induced by one genotoxin. For many genotoxins, the majority of observed single nucleotide variants results from error-prone translesion synthesis, rather than primary mutagenicity of altered nucleotides. Nucleotide excision repair mends the vast majority of genotoxic lesions, preventing up to 99% of mutations. Analogous mutagenic DNA damage-repair interactions can also be found in cancers, but, except for rare cases, effects are weak owing to the unknown histories of genotoxic exposures and DNA repair status. Overall, our data underscore that mutation spectra are joint products of DNA damage and DNA repair and imply that mutational signatures computationally derived from cancer genomes are more variable than currently anticipated.
Deep in the Bowel: Highly Interpretable Neural Encoder-Decoder Networks Predict Gut Metabolites from Gut Microbiome
Authors: Le Vuong , Quinn Thomas P. , Tran Truyen , Venkatesh Svetha 
Published: June 2019

AbstractTechnological advances in next-generation sequencing (NGS) and chromatographic assays [e.g., liquid chromatography mass spectrometry (LC-MS)] have made it possible to identify thousands of microbe and metabolite species, and to measure their relative abundance. In this paper, we propose a sparse neural encoder-decoder network to predict metabolite abundances from microbe abundances. Using paired data from a cohort of inflammatory bowel disease (IBD) patients, we show that our neural encoder-decoder model outperforms linear univariate and multivariate methods in terms of accuracy, sparsity, and stability. Importantly, we show that our neural encoder-decoder model is not simply a black box designed to maximize predictive accuracy. Rather, the network’s hidden layer (i.e., the latent space, comprised only of sparsely weighted microbe counts) actually captures key microbe-metabolite relationships that are themselves clinically meaningful. Although this hidden layer is learned without any knowledge of the patient’s diagnosis, we show that the learned latent features are structured in a way that predicts IBD and treatment status with high accuracy. By imposing a non-negative weights constraint, the network becomes a directed graph where each downstream node is interpretable as the additive combination of the upstream nodes. Here, the middle layer comprises distinct microbe-metabolite axes that relate key microbial biomarkers with metabolite biomarkers. By pre-processing the microbiome and metabolome data using compositional data analysis methods, we ensure that our proposed multi-omics workflow will generalize to any pair of -omics data. To the best of our knowledge, this work is the first application of neural encoder-decoders for the interpretable integration of multi-omics biological data.
Changes in social cohesion in a long-lived species under a perturbation regime
Authors: Genovart M. , Gimenez O. , Bertolero A. , Choquet R. , Oro D. , Pradel R. 
Published: June 2019

AbstractUnderstanding the behaviour of a population under perturbations is crucial and can help to mitigate the effects of global change. Sociality can influence the dynamics of behavioural processes and plays an important role on populations’ resilience. However little is known about the effects of perturbations on the social cohesion of group-living animals.To explore the strength of social cohesion and its dynamics under perturbations, we studied an ecological system involving a colonial, long-lived species living in a site experiencing a shift to a perturbed regime. This regime, caused by the invasion of predators, led this colony to hold from 70% to only 3% of the total world population in only one decade. Because birds breed aggregated in discrete and annually changing patches within large colonies, we could disentangle whether annual aggregation was random or resulted from social bonding among individuals. Our goals were 1) to uncover if there was any long-term social bonding between individuals and 2) to examine whether the perturbation regime affected social cohesion.We explored social cohesion by means of contingency tables and, within the Social Network Analysis framework, by modeling interdependencies among observations using additive and multiplicative effects (AME) and accounted for missing data. We analysed 25 years of monitoring with an individual capture-recapture database of more than 3,500 individuals.We showed that social bonding occurs over years in this species. We additionally show that social bonding strongly decreased after the perturbation regime. We propose that sociality and individual behavioural heterogeneity have been playing a major role driving dispersal and thus population dynamics over the study period.Perturbations may lead not only to changes in individuals’ behaviours and fitness but also to a change in populations’ social cohesion. The demographic consequences of the breaking down of social bonds are still not well understood, but they can be critical for population dynamics of social species. Further studies considering individual heterogeneity, sociality and different types of perturbations should be carried out to improve our understanding on the resilience of social species.
Doublesexmediates the development of sex-specific pheromone organs inBicyclusbutterflies via multiple mechanisms
Authors: Prakash Anupama , Monteiro Antónia 
Published: June 2019

AbstractTheBicycluslineage of satyrid butterflies exhibits male-specific traits, the scent organ complex, used for chemical communication during courtship. This complex consists of tightly packed brush-like scales (hair-pencils) that rub against scent patches to disperse pheromones, but the evolution and molecular basis of the organ’s male-limited development remains unknown. Here, we examine the evolution of the number and location of the scent patches and hair-pencils within 53 species ofBicyclusbutterflies, and the involvement of the sex determinant genedoublesex (dsx)in scent organ development inBicyclus anynanausing CRISPR/Cas9. We show that scent patches and hair-pencils arose via multiple, independent gains, in a correlated manner. Further, an initially non-sex-specific Dsx protein expression pattern in developing wing discs becomes male-specific and spatially refined to areas that develop the scent organ complex over the course of development. Functional perturbations ofdsxshow that this gene is required for male patch development whereas hair-pencils can develop in both sexes without Dsx input. Dsx in females is, instead, required to repress hair-pencils. These findings suggest that the patches and hair-pencils evolve as correlated composite organs that are sex-limited via the spatial regulation ofdsx. Divergence in the function ofdsxisoforms occurs in both sexes, where the male isoform promotes patch development in males and the female isoform represses hair-pencil development in females, both leading to the development of male-limited traits. Furthermore, evolution in number and location of patches, but not of hair-pencils, appears to be regulated by spatial regulation ofdsx.
Neonatal-derived IL-17 producing dermal γδ T cells are required to prevent spontaneous atopic dermatitis
Authors: Spidale Nicholas , Malhotra Nidhi , Sylvia Katelyn , Frascoli Michela , Miu Bing , Stadinski Brian D. , Huseby Eric S. , Kang Joonsoo 
Published: June 2019

ABSTRACTAtopic Dermatitis (AD) is a T cell-mediated chronic skin disease and is associated with altered skin barrier integrity. Infants with mutations in genes involved in tissue barrier fitness are predisposed towards inflammatory diseases, but most do not develop or sustain the diseases, suggesting that there exist regulatory immune mechanisms to repair tissues and/or prevent aberrant inflammation. The absence of one single murine dermal cell type, the innate neonatal-derived IL-17 producing γδ T (Tγδ17) cells, from birth resulted in spontaneous, highly penetrant AD with all the major hallmarks of human AD. In Tγδ17 cell-deficient mice, basal keratinocyte transcriptome was altered months in advance of AD induction. Fulminant disease is driven by skin commensal bacteria dysbiosis and highly expanded dermal αβ T clonotypes that produce the type three cytokines, IL-17 and IL-22. These results demonstrate that neonatal Tγδ17 cells are innate skin regulatory T cells. The bifurcation of type 3 cytokine producing skin T cells into the homeostatic, early innate and pathogen-sensing, late adaptive T cell compartments underpin healthy skin and accounts for the dual function of type 3 cytokines in skin maintenance and inflammation.
Old Meets New: Combining Herbarium Databases with Genetic Methods to Evaluate the Invasion Status of Baby’s Breath (Gypsophila paniculata) in North America
Authors: Lamar Sarah K. , Partridge Charlyn G. 
Published: June 2019

AbstractAimThis paper aims to inform our knowledge of common baby’s breath’s (Gypsophila paniculata) current population structure and invasion status using a combination of contemporary genetic methods and historical herbarium data.TaxonGypsophila paniculata(Angiosperms: Eudicot, Caryophyllaceae)LocationSamples were collected from seven locations spanning a portion of the plant’s North American range: Washington, North Dakota, Minnesota, and Michigan, United States.MethodsTo analyze contemporary population structure, individuals ofG. paniculatafrom 7 distinct sampling locations were collected and genotyped at 14 microsatellite loci. Population structure was inferred using both Bayesian and multivariate methods. To investigateG. paniculata’s invasion status, public herbarium databases were searched for mention of the species. Records were combined, resulting in a database of 307 herbarium collections dating from the late 1800’s to current day. Using this database, invasion curves were created at different geospatial scales.ResultsResults of genetic analyses suggest the presence of at least two genetic clusters spanning our seven sampling locations. Sampling locations in Washington, North Dakota, Minnesota, and northwestern Michigan form one genetic cluster, distinct from our two more southern sampling locations in Michigan, which form a second cluster with increased relative genetic diversity. Invasion curves created for these two clusters show different time periods of invasion. An invasion curve created for North America suggestsG. paniculata’s range may still be expanding.Main conclusionsGypsophila paniculatahas likely undergone at least two distinct invasions in North America, and its range may still be expanding. Restricted genetic diversity seen across a wide geographic area could be a signature of limited seed distributors present during the early period of this garden ornamental’s invasion.
BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis
Authors: Kim Hyung-Seok , Neugebauer Judith , McKnite Autumn , Tilak Anup , Christian Jan L. 
Published: June 2019

AbstractBMP7/BMP2 or BMP7/BMP4 heterodimers are more active than homodimers in vitro, but it is not known whether these heterodimers signal in vivo. To test this, we generated knock in mice carrying a mutation (Bmp7R-GFlag) that prevents proteolytic activation of the dimerized BMP7 precursor protein. This mutation eliminates the function of BMP7 homodimers and all other BMPs that normally heterodimerize with BMP7. WhileBmp7null homozygotes are live born,Bmp7R-GFlaghomozygotes are embryonic lethal and have broadly reduced BMP activity. Furthermore, compound heterozygotes carrying theBmp7R-Gallele together with a null allele ofBmp2orBmp4die during embryogenesis with defects in ventral body wall closure and/or the heart. Co-immunoprecipitation assays confirm that endogenous BMP4/7 heterodimers exist. Thus, BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian development, which may explain why mutations in eitherBmp4orBmp7lead to a similar spectrum of congenital defects in humans.
PACSIN2-dependent apical endocytosis regulates the morphology of epithelial microvilli
Authors: Postema Meagan M. , Grega-Larson Nathan E. , Meenderink Leslie M. , Tyska Matthew J. 
Published: June 2019

ABSTRACTApical microvilli are critical for the homeostasis of transporting epithelia, yet mechanisms that control the assembly and morphology of these protrusions remain poorly understood. Previous studies in intestinal epithelial cell lines suggested a role for F-BAR domain protein PACSIN2 in normal microvillar assembly. Here we report the phenotype of PACSIN2 KO mice and provide evidence that through its role in promoting apical endocytosis, this molecule functions in controlling microvillar morphology. PACSIN2 KO enterocytes exhibit reduced numbers of microvilli and defects in microvillar ultrastructure, with membranes lifting away from rootlets of core bundles. Dynamin2, a PACSIN2 binding partner, and other endocytic factors were also lost from their normal localization near microvillar rootlets. To determine if loss of endocytic machinery could explain defects in microvillar morphology, we examined the impact of PACSIN2 KD and endocytosis inhibition on live intestinal epithelial cells. These assays revealed that when endocytic vesicle scission fails, tubules are pulled into the cytoplasm and this, in turn, leads to a membrane lifting phenomenon reminiscent of that observed in PACSIN2 KO brush borders. These findings lead to a new model where inward forces generated by endocytic machinery on the plasma membrane control the membrane wrapping of cell surface protrusions.Highlight for TOCApical microvilli increase the functional surface area of transporting epithelia. Here we report that the F-BAR domain-containing protein PACSIN2, through its ability to promote apical endocytosis, plays a critical role in controlling the morphology of intestinal brush border microvilli.
Monocarboxylate transporter 1 in Schwann cells is critical for maintenance of sensory nerve myelination during aging
Authors: Jha Mithilesh Kumar , Lee Youngjin , Russell Katelyn A. , Yang Fang , Dastgheyb Raha M. , Deme Pragney , Ament Xanthe Heifetz , Chen Weiran , Liu Ying , Guan Yun , Polydefkis Michael J. , Hoke Ahmet , Haughey Norman J. , Rothstein Jeffrey D. , Morrison Brett M. 
Published: June 2019

AbstractSchwann cell (SC)-specific monocarboxylate transporter 1 (MCT1) knockout mice were generated by mating MCT1f/fmice with myelin protein zero (P0)-Cre mice. P0-Cre+/-, MCT1f/fmice have no detectable early developmental defects, but develop hypomyelination and reduced conduction velocity in sensory, but not motor, peripheral nerves during maturation and aging. Furthermore, enlarged node length and reduced mechanical sensitivity were evident in aged P0-Cre+/-, MCT1f/fmice. MCT1 deletion in SCs impairs both their glycolytic and mitochondrial functions, leading to altered lipid metabolism of triacylglycerides, diacylglycerides, and sphingomyelin, decreased expression of myelin-associated glycoprotein (MAG), and increased expression of c-Jun and p75-neurotrophin receptor, suggesting a regression of SCs to a less mature developmental state. Taken together, our results define the essential role of SC MCT1 in both SC metabolism and peripheral nerve maturation and aging.Main PointsSC MCT1 deficiency causes hypomyelination of sensory, but not motor, axons during agingEnlarged node length of sensory axons is evident in mutant mouse with SC-specific MCT1 deletionSelective ablation of MCT1 within SCs impairs glycolytic and mitochondrial functionsSC-specific MCT1 deficiency impairs proteins that regulate myelin and lipid metabolism in peripheral nerves
Polymer-like model to study the dynamics of dynamin filaments on deformable membrane tubes
Authors: Noel Jeffrey K. , Noé Frank , Daumke Oliver , Mikhailov Alexander S. 
Published: June 2019

AbstractPeripheral membrane proteins with intrinsic curvature can act both as sensors of membrane curvature and shape modulators of the underlying membranes. A well-studied example of such proteins is the mechano-chemical GTPase dynamin that assembles into helical filaments around membrane tubes and catalyzes their scission in a GTPase-dependent manner. It is known that the dynamin coat alone, without GTP, can constrict membrane tubes to radii of about 10 nanometers, indicating that the intrinsic shape and elasticity of dynamin filaments should play an important role in membrane remodeling. However, molecular and dynamic understanding of the process is lacking. Here, we develop a dynamical polymer-chain model for a helical elastic filament bound on a deformable membrane tube of conserved mass, accounting for thermal fluctuations in the filament and lipid flows in the membrane. The model is based on a locally-cylindrical helix approximation for dynamin. We obtain the elastic parameters of the dynamin filament by molecular dynamics simulations of its tetrameric building block and also from coarse-grained structure-based simulations of a 17-dimer filament. The results show that the stiffness of dynamin is comparable to that of the membrane. We determine equilibrium shapes of the filament and the membrane, and find that mostly the pitch of the filament, not its radius, is sensitive to variations in membrane tension and stiffness. The close correspondence between experimental estimates of the inner tube radius and those predicted by the model suggests that dynamin’s “stalk” region is responsible for its GTP-independent membrane-shaping ability. The model paves the way for future mesoscopic modeling of dynamin with explicit motor function.
Quantitative Personality Predictions from a Brief EEG Recording
Authors: Li Wenyu , Wu Chengpeng , Hu Xin , Chen Jingjing , Fu Shimin , Wang Fei , Zhang Dan 
Published: June 2019

AbstractThe assessment of personality is crucial not only for scientific inquiries but also for real-world applications such as personnel selection. However, most existing ways to quantify personality traits rely on self-reported scales, which are susceptible to biases such as self-presentational concerns. In this study, we propose and evaluate a novel implicit measure of personality that uses machine learning (ML) algorithms to predict an individual’s levels in the Big Five personality traits from 5 minutes of electroencephalography (EEG) recordings. Results from a large test sample of 196 volunteers indicated that the personality scores derived from the proposed measure converged significantly with a commonly used questionnaire, predicted behavioral indices and psychological adjustment in a manner similar to self-reported scores, and were relatively stable across time. These evaluations suggest that the proposed measure can serve as a viable alternative to conventional personality questionnaires in practice.
Cerebral contribution to the execution, but not recalibration, of motor commands in a novel walking environment
Authors: de Kam D. , Iturralde P.A. , Torres-Oviedo G. 
Published: June 2019

AbstractHuman movements are flexible as they continuously adapt to changes in the environment by updating planned actions and generating corrective movements. Planned actions are updated upon repeated exposure to predictable changes in the environment, whereas corrective responses serve to overcome unexpected environmental transitions. It has been shown that corrective muscle responses are tuned through sensorimotor adaptation induced by persistent exposure to a novel situation. Here, we asked whether cerebral structures contribute to this recalibration using stroke as a disease model. To this end, we characterized changes in muscle activity in stroke survivors and unimpaired individuals before, during, and after walking on a split-belt treadmill moving the legs at different speeds, which has been shown to induce recalibration of corrective responses in walking in healthy individuals. We found that the recalibration of corrective muscle activity was comparable between stroke survivors and controls, which was surprising given then known deficits in feedback responses post-stroke. Also, the intact recalibration in the group of stroke survivors contrasted the patients’ limited ability to adjust their muscle activity during steady state split-belt walking compared to controls. Our results suggest that the recalibration and execution of motor commands in new environments are partially dissociable: cerebral lesions interfere with the execution, but not the recalibration, of motor commands upon novel movement demands.