bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortical subnetworks encode context of visual stimulus
Authors: Hamm Jordan P. , Shymkiv Yuriy , Han Shuting , Yang Weijian , Yuste Rafael 
Published: October 2018

AbstractCortical processing of sensory events is significantly influenced by context. For instance, a repetitive or redundant visual stimulus elicits attenuated cortical responses, but if the same stimulus is unexpected or “deviant”, responses are augmented. This contextual modulation of sensory processing is likely a fundamental function of neural circuits, yet an understanding of how it is computed is still missing. Using holographic two-photon calcium imaging in awake animals, here we identify three distinct, spatially intermixed ensembles of neurons in mouse primary visual cortex which differentially respond to the same stimulus under separate contexts, including a subnetwork which selectively responds to deviant events. These non-overlapping ensembles are distributed across layers 2-5, though deviance detection is more common in superficial layers. Contextual preferences likely arise locally since they are not present in bottom up inputs from the thalamus or top-down inputs from prefrontal cortex. The functional parcellation of cortical circuits into independent ensembles that encode stimulus context provides a circuit basis underlying cortically based perception of novel or redundant stimuli, a key deficit in many psychiatric disorders.One Sentence SummaryVisual cortex represents deviant and redundant stimuli with separate subnetworks.
Abnormal LTR retrotransposons formed by the recombination outside the host genome
Authors: Zeng Fanchun , Sun Zhongyi 
Published: October 2018

AbstractLong terminal repeat (LTR) retrotransposons are the dominant feature of higher plant genomes, which have a similar life cycle with retrovirus. Previous studies cannot account for all observed complex LTR retrotransposon patterns. In this study, we first identified 63 complex LTR retrotransposons in rice genome, and most of complex elements harbored flanking target-site duplications (TSDs). But these complex elements in which outermost LTRs had not the most highly homologous can’t be explained. We propose a new model that the homologous recombination of two new different normal LTR retrotransposon elements in the same family can occur before their integration to the rice genome. The model can explain at least fourteen complex retrotransposons formations. We also find that normal LTR retrotransposons can swap their LTRs to generate abnormal LTR retrotransposons in which LTRs are different because of homologous recombination before their integration to the genome.
ADHD: relation between cognitive characteristics and DAT1 / DRD4 dopamine polymorphisms
Authors: Cristina Pinto María , Enrique Ávila Jorge , María Polanco Angela , Antonio Vásquez Rafael , Humberto Arboleda 
Published: October 2018

AbstractAttention deficit hyperactivity disorder (ADHD) is a clinical and diagnostic heterogeneous picture. This study analysed the association of functional polymorphisms in DAT1 VNTR 3’ UTR and DRD4 VNTR Exon III candidate genes, and the neuropsychological characterisation of attention and executive functions of a group of children with ADHD vs. controls. 32 patients and 51 controls were selected. The DAT1 10-repeat allele appeared more frequently in the two groups (cases: 0.93/control: 0.82), showing an OR: 2.5 (IC 95%: 0.684-9.133; p: 0.158). In DRD4, the 4-repeat allele shows the highest occurrence (cases: 0.62/controls: 0.60). None of the markers presented a significant association after a direct analysis, but the DRD4 7-repeat marker showed a positive risk when performing a Bayesian logistic analysis (coefficient: −1.69; OR: 5.39 CI 95%: 1.167-40.97). On the other hand, when considering association with cognitive performance, a positive risk for processing speed and attention tasks was identified.
Demethylmenaquinone methyl transferase is a membrane domain-associated protein essential for menaquinone homeostasis in Mycobacterium smegmatis
Authors: Puffal Julia , A. Mayfield Jacob , Moody D. Branch , S. Morita Yasu 
Published: October 2018

AbstractThe intracellular membrane domain (IMD) in mycobacteria is a spatially distinct region of the plasma membrane with diverse functions. Previous comparative proteomic analysis of the IMD suggested that menaquinone biosynthetic enzymes are associated with this domain. In the present study, we determined the subcellular site of these enzymes using sucrose density gradient fractionation. We found that the last two enzymes, the methyltransferase MenG, and the reductase MenJ, are associated with the IMD. MenA, the prenyltransferase that mediates the first membrane-associated step of the menaquinone biosynthesis, is associated with the conventional plasma membrane. For MenG, we additionally showed the polar enrichment of the fluorescent protein fusion colocalizing with an IMD marker protein in situ. To start dissecting the roles of IMD-associated enzymes, we further tested the physiological significance of MenG. The deletion of menG at the endogenous genomic loci was possible only when an extra copy of the gene was present, indicating that it is an essential gene in M. smegmatis. Using a tetracycline-inducible switch, we achieved gradual and partial depletion of MenG over three consecutive 24 hour subcultures. This partial MenG depletion resulted in progressive slowing of growth, which corroborated the observation that menG is an essential gene. Upon MenG depletion, there was a significant accumulation of MenG substrate, demethylmenaquinone, even though the cellular level of menaquinone, the reaction product, was unaffected. Furthermore, the growth retardation was coincided with a lower oxygen consumption rate and ATP accumulation. These results imply a previously unappreciated role of MenG in regulating menaquinone homeostasis within the complex spatial organization of mycobacterial plasma membrane.
Divergent selection causes whole genome differentiation without physical linkage among the targets in Spodoptera frugiperda (Noctuidae)
Authors: Nam Kiwoong , Nhim Sandra , Robin Stéphanie , Bretaudeau Anthony , Nègre Nicolas , d’Alençon Emmanuelle 
Published: October 2018

ABSTRACTThe process of speciation involves whole genome differentiation by overcoming gene flow between diverging populations. We have ample knowledge which evolutionary forces may cause genomic differentiation, and several speciation models have been proposed to explain the transition from genetic to genomic differentiation. However, it is still unclear what are critical conditions enabling genomic differentiation in nature. The Fall armyworm, Spodoptera frugiperda, is observed as two sympatric strains that have different host-plant ranges, suggesting the possibility of ecological divergent selection. In our previous study, we observed that these two strains show genetic differentiation across the whole genome with an unprecedentedly low extent, suggesting the possibility that whole genome sequences started to be differentiated between the strains. In this study, we analyzed whole genome sequences from these two strains from Mississippi to identify critical evolutionary factors for genomic differentiation. The genomic Fst is low (0.017) while 91.3% of 10kb windows have Fst greater than 0, suggesting genome-wide differentiation with a low extent. We identified nearly 400 outliers of genetic differentiation between strains, and found that physical linkage among these outliers is not a primary cause of genomic differentiation. Fst is not significantly correlated with gene density, a proxy for the strength of selection, suggesting that a genomic reduction in migration rate dominates the extent of local genetic differentiation. Our analyses reveal that divergent selection alone is sufficient to generate genomic differentiation, and any following diversifying factors may increase the level of genetic differentiation between diverging strains in the process of speciation.
Alcohol consumption is associated with widespread changes in blood DNA methylation: analysis of cross-sectional and longitudinal data
Authors: Dugué Pierre-Antoine , Wilson Rory , Lehne Benjamin , Jayasekara Harindra , Wang Xiaochuan , Jung Chol-Hee , Joo JiHoon E , Makalic Enes , Schmidt Daniel F , Baglietto Laura , Severi Gianluca , Gieger Christian , Ladwig Karl-Heinz , Peters Annette , Kooner Jaspal S , Southey Melissa C , English Dallas R , Waldenberger Melanie , Chambers John C , Giles Graham G , Milne Roger L 
Published: October 2018

ABSTRACTBackground:DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart.Methods:Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined using baseline peripheral blood samples from 5,606 adult Melbourne Collaborative Cohort Study (MCCS) participants. For a subset of 1,088 of them, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. Independent data from the LOLIPOP (N=4,042) and KORA (N=1,662) cohorts were used to replicate associations discovered in the MCCS.Results:Cross-sectional analyses identified 1,414 CpGs associated with alcohol intake at P<10-7, 1,243 of which had not been reported previously. Of these 1,243 novel associations, 1,078 were replicated (P<0.05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated (P<0.05) 403 of 518 associations that had been reported previously. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1,414 CpGs, 530 were differentially methylated (P<0.05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1,414 cross-sectional associations.Conclusion:Our study indicates that, for middle-aged and older adults, alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with changes in alcohol consumption.
A model of ganglion axon pathways accounts for percepts elicited by retinal implants
Authors: Beyeler Michael , Nanduri Devyani , Weiland James D. , Rokem Ariel , Boynton Geoffrey M. , Fine Ione 
Published: October 2018

AbstractRetinal prostheses, now implanted in over 250 patients worldwide, electrically stimulate surviving cells in order to evoke neuronal responses that are interpreted by the brain as visual percepts (‘phosphenes’). However, instead of seeing focal spots of light, current implant users perceive highly distorted phosphenes that vary in shape both across subjects and electrodes. We characterized these distortions by asking users of the Argus retinal prosthesis system (Second Sight Medical Products) to draw elicited percepts on a touchscreen. We found that phosphene shape could be accurately predicted by simulating the topographic organization of nerve fiber bundles in each subject’s retina. Our model shows that activation of ganglion axons contributes to a rich repertoire of phosphene shapes, successfully replicating percepts ranging from ‘blobs’ to oriented ‘streaks’ and ‘wedges’ depending on electrode location. This work provides a first step towards future devices that incorporate stimulation strategies tailored to each individual patient’s retinal neurophysiology.One Sentence SummaryWe show that the perceptual experience of retinal implant users can be accurately predicted using a computational model that simulates the topographic organization of each individual patient’s retinal ganglion axon pathways.
Bacterial T6SS Effector EvpP Inhibits Neutrophil Recruitment via Jnk-Caspy Inflammasome SignalingIn vivo
Authors: Tan Jinchao , Yang Dahai , Wang Zhuang , Zheng Xin , Zhang Yuanxing , Liu Qin 
Published: October 2018

ABSTRACTThe type VI secretion system (T6SS) comprises dynamic complex bacterial contractile nanomachines and is used by many bacteria to inhibit or kill other prokaryotic or eukaryotic cells. Previous studies have revealed that T6SS is constitutively active in response to various stimuli, or fires effectors into host cells during infection. It has been proposed that the T6SS effector EvpP inEdwardsiella piscicidacan inhibit NLRP3 inflammasome activation via the Ca2+-dependent JNK pathways. Here, we developed anin vivoinfection model by microinjecting bacteria into the tail vein muscle of 3-day-post-fertilized zebrafish larvae, and found that both macrophages and neutrophils are essential for bacterial clearance. Further study revealed that EvpP plays a critical role in promoting the pathogenesis ofE. piscicidavia inhibiting the phosphorylation of Jnk signaling to reduce the expression ofcxcl8a,mmp13andIL-1β in vivo.Subsequently, by utilizingTg(mpo:eGFP+/+) zebrafish larvae forE. piscicidainfection, we found that the EvpP-inhibited Jnk-caspy inflammasome signaling axis significantly suppressed the recruitment of neutrophils to infection sites, and thecaspy‐ orIL-1β-MO knockdown larvae were more susceptible to infection and failed to restrict bacterial colonizationin vivo.IMPORTANCEInnate immunity is regulated by phagocytic cells and is critical for host control of bacterial infection. In many bacteria, T6SSs can affect bacterial virulence in certain environments, but little is known about the mechanisms underlying T6SS regulation of innate immune responses during infectionin vivo. Here, we investigated the role of anE. piscicidaT6SS effector EvpP in manipulating the reaction of neutrophilsin vivo.We show that EvpP inhibits the activation of Jnk-caspy inflammasome pathway in zebrafish larvae, and reveal that macrophages are essential for neutrophil recruitmentin vivo. This interaction improves our understanding about the complex and contextual role of a bacterial T6SS effector in modulating the action of myeloid cells during infection, and offers new insights into the warfare between bacterial weapons and host immunological surveillance.
Identifying loci under positive selection in complex population histories
Authors: Refoyo-Martínez Alba , da Fonseca Rute R. , Halldórsdóttir Katrín , Árnason Einar , Mailund Thomas , Racimo Fernando 
Published: October 2018

AbstractDetailed modeling of a species’ history is of prime importance for understanding how natural selection operates over time. Most methods designed to detect positive selection along sequenced genomes, however, use simplified representations of past histories as null models of genetic drift. Here, we present the first method that can detect signatures of strong local adaptation across the genome using arbitrarily complex admixture graphs, which are typically used to describe the history of past divergence and admixture events among any number of populations. The method—called Graph-aware Retrieval of Selective Sweeps (GRoSS)—has good power to detect loci in the genome with strong evidence for past selective sweeps and can also identify which branch of the graph was most affected by the sweep. As evidence of its utility, we apply the method to bovine, codfish and human population genomic data containing multiple population panels related in complex ways. We find new candidate genes for important adaptive functions, including immunity and metabolism in under-studied human populations, as well as muscle mass, milk production and tameness in specific bovine breeds. We are also able to pinpoint the emergence of large regions of differentiation due to inversions in the history of Atlantic codfish.
The Sicilian wolf: Genetic identity of a recently extinct insular population
Authors: Angelici F.M. , Ciucani M.M. , Angelini S. , Annesi F. , Caniglia R. , Castiglia R. , Fabbri E. , Galaverni M. , Palumbo D. , Ravegnini G. , Rossi L. , Siracusa A.M. , Cilli E. 
Published: October 2018

AbstractDuring historical times many local grey wolf (Canis lupus) populations underwent a substantial reduction of their sizes or became extinct. Among these, the wolf population once living in Sicily, the biggest island of the Mediterranean Sea, was completely eradicated by human persecution in the early decades of the XX century.In order to understand the genetic identity of the Sicilian wolf, we applied ancient DNA techniques to analyse the mitochondrial DNA of six specimens actually stored in Italian museums.We successfully amplified a diagnostic mtDNA fragment of the control region (CR) in four of the samples. Results showed that two samples shared the same haplotype, that differed by two substitutions from the currently most diffused Italian wolf haplotype (W14) and one substitution from the only other Italian haplotype (W16). The third sample showed a wolf-like haplotype never described before and the fourth a haplotype commonly found in dogs.Furthermore, all the wolf haplotypes detected in this study belonged to the mitochondrial haplogroup that includes haplotypes detected in all the known European Pleistocene wolves and in several modern southern European populations.Unfortunately, this endemic island population, bearing unique mtDNA variability, was definitively lost before it was possible to understand its taxonomic uniqueness and conservational value.
The art of using t-SNE for single-cell transcriptomics
Authors: Kobak Dmitry , Berens Philipp 
Published: October 2018

AbstractSingle-cell transcriptomics yields ever growing data sets containing RNA expression levels for thousands of genes from up to millions of cells. Common data analysis pipelines include a dimensionality reduction step for visualising the data in two dimensions, most frequently performed using t-distributed stochastic neighbour embedding (t-SNE). It excels at revealing local structure in high-dimensional data, but naive applications often suffer from severe shortcomings, e.g. the global structure of the data is not represented accurately. Here we describe how to circumvent such pitfalls, and develop a protocol for creating more faithful t-SNE visualisations. It includes PCA initialisation, a high learning rate, and multi-scale similarity kernels; for very large data sets, we additionally use exaggeration and downsampling-based initialisation. We use published single-cell RNA-seq data sets to demonstrate that this protocol yields superior results compared to the naive application of t-SNE.
Turbulence in the Hippocampus: An Ansatz for the Energy Cascade Hypothesis
Authors: Sheremet Alex , Qin Yu , Kennedy Jack P. , Zhou Yuchen , Maurer Andrew P. 
Published: October 2018

ABSTRACTMesoscopic neural activity may play an important role in the cross-scale integration of brain activity and in the emergence of cognitive behavior. Mesoscale activity in the cortex can be defined as the organization of activity of large populations of neurons into collective actions, such as traveling waves in the hippocampus. A comprehensive description of collective activity is still lacking, in part because it cannot be built directly with methods and models developed for the microscale (individual neurons): the laws governing mesoscale dynamics are different from those governing a few neurons. To identify the characteristic features of mesoscopic dynamics, and to lay the foundations for a theoretical description of mesoscopic activity in the hippocampus, we conduct a comprehensive examination of observational data of hippocampal local field potential (LFP) recordings. We use the strong correlation between rat running-speed and the LFP power to parameterize the energy input into the hippocampus, and show that both the power, and the nonlinearity of mesoscopic scales of collective action (e.g., theta and gamma rhythms) increase as with energy input. Our results point to a few fundamental characteristics: collective-action dynamics are stochastic (the precise state of a single neuron is irrelevant), weakly nonlinear, and weakly dissipative. These are the principles of the theory of weak turbulence. Therefore, we propose weak turbulence as an ansatz for the development of a theoretical description of mesoscopic activity. The perspective of weak turbulence provides simple and meaningful explanations for the major features observed in the evolution of LFP spectra and bispectra with energy input, such as spectral slopes and their evolution, the increased nonlinear coupling observed between theta and gamma, as well as specific phase lags associated with their interaction. The weak turbulence ansatz is consistent with the theory of self organized criticality, which provides a simple explanation for the existence of the power-law background spectrum, and could provide a unifying approach to modeling the dynamics of mesoscopic activity.
Physiological variation reflects bioclimatic differences in theDrosophila americanaspecies complex
Authors: Davis Jeremy S. , Moyle Leonie C. 
Published: October 2018

AbstractBackgroundDisentangling the selective factors shaping adaptive trait variation is an important but challenging task. Many studies—especially inDrosophila—have documented trait variation along latitudinal or altitudinal clines, but frequently lack resolution about specific environmental gradients that could be causal selective agents, and often do not investigate covariation between traits simultaneously. Here we examined variation in multiple macroecological factors across geographic space and their associations with variation in three physiological traits (desiccation resistance, UV resistance, and pigmentation) at both population and species scales, to address the role of abiotic environment in shaping trait variation.ResultsUsing environmental data from collection locations of three North AmericanDrosophilaspecies—D. americana americana, D. americana texanaandD. novamexicana—we identified two primary axes of macroecological variation; these differentiated species habitats and were strongly loaded for precipitation and moisture variables. In nine focal populations (three per species) assayed for each trait, we detected significant species-level variation for both desiccation resistance and pigmentation, but not for UV resistance. Species-level trait variation was consistent with differential natural selection imposed by variation in habitat water availability, although patterns of variation differed between desiccation resistance and pigmentation, and we found little evidence for pleiotropy between traits.ConclusionsOur multi-faceted approach enabled us to identify potential agents of natural selection and examine how they might influence the evolution of multiple traits at different evolutionary scales. Our findings highlight that environmental factors influence functional trait variation in ways that can be complex, and point to the importance of studies that examine these relationships at both population- and species-levels.