bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavioural relevance of spontaneous, transient brain network interactions in fMRI
Authors: Vidaurre D. , Llera A. , Smith S.M. , Woolrich M.W. 
Published: September 2019

AbstractHow spontaneously fluctuating functional magnetic resonance imaging (fMRI) signals in different brain regions relate to behaviour has been an open question for decades. Correlations in these signals, known as functional connectivity, can be averaged over several minutes of data to provide a stable representation of the functional network architecture for an individual. However, associations between these stable features and behavioural traits have been shown to be dominated by individual differences in anatomy. Here, using kernel learning tools, we propose methods to assess and compare the relation between time-varying functional connectivity, time-averaged functional connectivity, structural brain data, and non-imaging subject behavioural traits. We applied these methods on Human Connectome Project resting-state fMRI data to show that time-varying fMRI functional connectivity, detected at time-scales of a few seconds, has associations with some behavioural traits that are not dominated by anatomy. Despite time-averaged functional connectivity accounting for the largest proportion of variability in the fMRI signal between individuals, we found that some aspects of intelligence could only be explained by time-varying functional connectivity. The finding that time-varying fMRI functional connectivity has a unique relationship to population behavioural variability suggests that it might reflect transient neuronal communication fluctuating around a stable neural architecture.Significance statementComplex cognition is dynamic and emerges from the interaction between multiple areas across the whole brain, i.e. from brain networks. Hence, the utility of functional MRI to investigate brain activity depends on how well it can capture time-varying network interactions. Here, we develop methods to predict behavioural traits of individuals from either time-varying functional connectivity, time-averaged functional connectivity, or structural brain data. We use these to show that the time-varying nature of functional brain networks in fMRI can be reliably measured and can explain aspects of behaviour not captured by structural data or time-averaged functional connectivity. These results provide important insights to the question of how the brain represents information and how these representations can be measured with fMRI.
Exploring the effect of Relative Language Distance on Bilingual Brain Structure – a cross-sectional VBM study
Authors: Ramanujan Keerthi 
Published: September 2019

AbstractIt is known that bilinguals’ perpetual need for language control influences their brain structure in significant ways. But bilinguals’ language control needs are themselves influenced by key dimensions of the bilingual experience – variation in the age of bilingualism-onset, relative language proficiency, exposure and immersion has indeed been shown to have differential effects on bilingual neurostructural profiles. An under-studied dimension of bilingualism that could also generate differing bilingual language control needs is the extent of similarity between bilinguals’ language pairs, referred to in the present study as Relative Language Distance (RLD). The goal of the present study was to explore whether the experience of managing “close” and “distant” languages has any impact at all on bilingual brain structure. To this end, exploratory morphometric analysis of grey matter volumes was carried out on three groups, all very similar in their bilingual profiles except for the factor of RLD – high-distance Cantonese-English (hd-CE), intermediate distance Hindi-English (id-HE) and low-distance Dutch-English (ld-DE) speakers. The results after controlling for contribution of other bilingual dimensions revealed significant bilateral putaminal volume differences between the groups that varied along the relative language distance gradient in the pattern of CE>HE>DE. This might be attributable to the differing articulatory control needs that variation in L1-L2 RLD generates. The present study reveals how the dimension of Relative Language Distance could impact bilingual brain structure.
Agrobacterium-mediated transient transformation of sorghum leaves for accelerating functional genomics and genome editing studies
Authors: Sharma Rita , Liang Yan , Lee Mi Yeon , Pidatala Venkataramana R. , Mortimer Jenny C. , Scheller Henrik V. 
Published: September 2019

ABSTRACTObjectivesSorghum is one of the most recalcitrant species for transformation. Considering the time and effort required for stable transformation in sorghum, establishing a transient system to screen the efficiency and full functionality of vector constructs is highly desirable.ResultsHere, we report anAgrobacterium-mediated transient transformation assay with intact sorghum leaves using green fluorescent protein as marker. It also provides a good monocot alternative to tobacco and protoplast assays with a direct, native and more reliable system for testing single guide RNA (sgRNA) expression construct efficiency. Given the simplicity and ease of transformation, high reproducibility, and ability to test large constructs, this method can be widely adopted to speed up functional genomic and genome editing studies.
Swimming motility and chemotaxis control the spatial organization, persistence, and inflammatory activity of a model intestinal pathobiont
Authors: Wiles Travis J. , Schlomann Brandon H. , Wall Elena S. , Betancourt Reina , Parthasarathy Raghuveer , Guillemin Karen 
Published: September 2019

SUMMARYUnderstanding the processes that spatially restrict resident gut bacteria and the mechanisms by which disease-causing pathobionts escape this control will open new avenues for microbiome-based therapies. Using live imaging and genetically engineered bacteria, we discovered that flagella-based swimming motility and chemotaxis enable a modelVibriopathobiont to govern its own spatial organization within the larval zebrafish gut and to persist in the face of the disruptive forces of intestinal flow. Bacterial mutants lacking motility traits became aggregated and lumenally confined, making them susceptible to periodic expulsion from the host. Consequently, non-motile and non-chemotactic mutants experienced large fluctuations in absolute abundance and impaired interbacterial competition. Further, we found that motile bacterial cells induce expression of the proinflammatory cytokine TNFα in gut-associated macrophages and the liver. Using inducible genetic switches, we demonstrate that swimming motility can be manipulated in situ to modulate the spatial organization, persistence, and inflammatory activity of gut bacteria.
Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling
Authors: Behrens Christian , Zhang Yue , Yadav Shubhash Chandra , Haverkamp Silke , Irsen Stephan , Korympidou Maria M. , Schaedler Anna , Dedek Karin , Smith Robert G. , Euler Thomas , Berens Philipp , Schubert Timm 
Published: September 2019

AbstractIn the outer plexiform layer (OPL) of the mouse retina, two types of cone photoreceptors (cones) provide input to more than a dozen types of cone bipolar cells (CBCs). This transmission is modulated by a single horizontal cell (HC) type, the only interneuron in the outer retina. Horizontal cells form feedback synapses with cones and feedforward synapses with CBCs. However, the exact computational role of HCs is still debated. Along with performing global signaling within their laterally coupled network, HCs also provide local, cone-specific feedback. Specifically, it has not been clear which synaptic structures HCs use to provide local feedback to cones and global forward signaling to CBCs.Here, we reconstructed in a serial block-face electron microscopy volume the dendritic trees of five HCs as well as cone axon terminals and CBC dendrites to quantitatively analyze their connectivity. In addition to the fine HC dendritic tips invaginating cone axon terminals, we also identified “bulbs”, short segments of increased dendritic diameter on the primary dendrites of HCs. These bulbs are located well below the cone axon terminal base and make contact to other cells mostly identified as other HCs or CBCs. Using immunolabeling we show that HC bulbs express vesicular gamma-aminobutyric acid transporters and co-localize with GABA receptor γ2 subunits. Together, this suggests the existence of two synaptic strata in the mouse OPL, spatially separating cone-specific feedback and feedforward signaling to CBCs. A biophysics-based computational model of a HC dendritic branch supports the hypothesis that the spatial arrangement of synaptic contacts allows simultaneous local feedback and global feedforward signaling.
Type IV CRISPR-Cas systems are highly diverse and involved in competition between plasmids
Authors: Pinilla-Redondo Rafael , Mayo-Muñoz David , Russel Jakob , Garrett Roger A. , Randau Lennart , Sørensen Søren J. , Shah Shiraz A. 
Published: September 2019

AbstractCRISPR-Cas systems provide prokaryotes with adaptive immune functions against viruses and other genetic parasites by leveraging small non-coding RNAs for nuclease-dependent degradation of their nucleic acid targets. In contrast to all other types of CRISPR-Cas systems, the mechanisms and biological roles of type IV systems have remained largely overlooked. Here, we describe a previously uncharted diversity of type IV gene cassettes, distributed across diverse prokaryotic genome backgrounds, and propose their classification into subtypes and variants. Congruent with recent findings, type IV modules were primarily found on plasmid-like elements. Remarkably, via a comprehensive analysis of their CRISPR spacer content, these systems were found to exhibit a strong bias towards the targeting of other plasmids. Our data indicate that the functions of type IV systems have diverged from those of other host-related CRISPR-Cas immune systems to adopt a yet unrecognised role in mediating conflicts between plasmids that compete to monopolize their hosts. Furthermore, we find evidence for cross-talk between certain type IV and type I CRISPR-Cas systems that co-exist intracellularly, thus providing an answer to the enigmatic absence of adaptation modules in these systems. Collectively, our results lead to the expansion and reclassification of type IV systems and provide novel insights into the biological function and evolution of these elusive systems.
Single-cell analysis of antiviral neuroinflammatory responses in the mouse dorsal raphe nucleus
Authors: Huang Kee Wui , Sabatini Bernardo L. 
Published: September 2019

ABSTRACTNeuroinflammatory processes have been implicated in neurodegenerative and psychiatric diseases, and limit the utility of viruses for gene delivery. Here we analyzed 60,212 single-cell RNA profiles to assess both global and cell type-specific transcriptional responses in the mouse dorsal raphe nucleus following axonal infection of neurons by rabies viruses. We identified several leukocyte populations, which infiltrate the brain, that are distinct from resident immune cells. Additionally, we uncovered transcriptionally distinct states of microglia along an activation trajectory that may serve different functions, ranging from surveillance to antigen presentation and cytokine secretion. Our study also provides a critical evaluation of the compatibility between rabies-mediated connectivity mapping and single-cell transcriptional profiling. These findings provide additional insights into the distinct contributions of various cell types in the antiviral response, and will serve as a resource for the design of strategies to circumvent immune responses to improve the efficacy of viral gene delivery.
TNF receptor associated factor 6 interacts with ALS-linked misfolded superoxide dismutase 1 and promotes aggregation
Authors: Semmler Sabrina , Gagné Myriam , Garg Pranav , Pickles Sarah , Baudouin Charlotte , Hamon-Keromen Emeline , Destroismaisons Laurie , Khalfallah Yousra , Chaineau Mathilde , Caron Elise , Bayne Andrew N. , Trempe Jean-François , Cashman Neil R. , Star Alexandra T. , Haqqani Arsalan S. , Durcan Thomas M. , Meiering Elizabeth M. , Robertson Janice , Grandvaux Nathalie , Plotkin Steven S. , McBride Heidi M. , Vande Velde Christine 
Published: September 2019

ABSTRACTAmyotrophic lateral sclerosis (ALS) is a fatal disease, characterized by the selective loss of motor neurons leading to paralysis. Mutations in the gene encoding superoxide dismutase1(SOD1) are the second most common cause of familial ALS, and considerable evidence suggests that these mutations result in an increase in toxicity due to protein misfolding. We previously demonstrated in the SOD1G93Arat model that misfolded SOD1 exists as distinct conformers and forms deposits on mitochondrial subpopulations. Here, using SOD1G93Arats and conformation-restricted antibodies specific for misfolded SOD1 (B8H10 and AMF7-63), we identified the interactomes of the mitochondrial pools of misfolded SOD1. This strategy identified binding proteins that uniquely interacted with either AMF7-63 or B8H10-reactive SOD1 conformers as well as with a high proportion of interactors common to both conformers. Of this latter set, we identified the E3 ubiquitin ligase TNF receptor-associated factor 6 (TRAF6) as a SOD1 interactor and determined that exposure of the SOD1 functional loops facilitates this interaction. Of note, this conformational change was not universally fulfilled by all SOD1 variants and differentiated TRAF6-interacting from TRAF6 non-interacting SOD1 variants. Functionally, TRAF6 stimulated polyubiquitination and aggregation of the interacting SOD1 variants. TRAF6 E3 ubiquitin ligase activity was required for the former, but was dispensable for the latter, indicating that TRAF6-mediated polyubiquitination and aggregation of the SOD1 variants are independent events. We propose that the interaction between misfolded SOD1 and TRAF6 may be relevant to the etiology of ALS.
Simultaneous discovery of candidate imprinted genes and Imprinting Control Regions in the mouse genome
Authors: Bina Minou , Wyss Phillip 
Published: September 2019

ABSTRACTIn mammals, parent-of-origin-specific gene expression is regulated by specific genomic DNA segments known as Imprinting Control Regions (ICRs) and germline Differentially Methylated Regions (gDMRs). In the mouse genome, the known ICRs/gDMRs often include clusters of a set of composite-DNA-elements known as ZFBS-morph overlaps. These elements consist of the ZFP57 binding site (ZFBS) overlapping a subset of the MLL1 morphemes. To improve detection of such clusters, we created density-plots. In genome-wide analyses, peaks in these plots pinpointed ∼90% of the known ICRs/gDMRs and located candidate ICRs within relatively long genomic DNA sections. In several cases, the candidate ICRs mapped to chromatin boundaries, to a subset of gene-transcripts, or to both. By viewing the plots at the UCSC genome browser, we could examine the candidate ICRs in the context of the genes in their vicinity. This strategy uncovered several potential imprinted genes with a broad range of physiologically important functions. Examples include: folliculogenesis; lineage commitment of murine embryonic stem cells; the development of the junctional zone of the placenta; left-right patterning of the body axis; the development of the neocortex, hippocampus, and cerebellum; postnatal vision; self-renewal of mouse spermatogonial stem cells; and histone-to-protamine replacement during spermatogenesis.
CpG-ODN 2007 protects zebrafish against Vibrio vulnificus-induced infection
Authors: Chen Hua , Zhang Lijuan , Li Suyi , Ke Ling , Lin Chentao , Chen Xu 
Published: September 2019

AbstractVibrio vulnificus (V. vulnificus) is an aquatic pathogen that can cause primary sepsis and soft tissue infection. CpG oligodeoxynucleotides (CpG-ODN) are a type of essential immunomodulators, which can trigger or enhance immune responses in mammals, fish, and humans. In this study, we evaluated the effect of CpG-ODN 2007 as a potential immunostimulant for zebrafish infected with V. vulnificus (FJ03-X2). Fish injected with the CpG-ODN 2007 showed lower mortality rate compared with the fish that did not receive treatment. The survival rates of CpG-ODN 2007-treated group and PBS-treated group were 85% and 57.9%, respectively. In addition, our in vitro results demonstrated that CpG-ODN 2007 can effectively reduce the toxicity of V. vulnificus (FJ03-X2) to zebrafish embryonic fibroblast (ZF4) cells. Furthermore, we assessed immune-related genes expression patterns in FJ03-X2 infected zebrafish or ZF4 cells with and without CpG-ODN 2007 treatment, such as TLRs and IL-1β. To sum up, our data indicated that CpG-ODN 2007 protects zebrafish against Vibrio vulnificus induced infection.
Generalized Multi-SNP Mediation Intersection-Union Test
Authors: Zhong Wujuan , Darville Toni , Zheng Xiaojing , Fine Jason , Li Yun 
Published: September 2019

SummaryTo elucidate the molecular mechanisms underlying genetic variants identified from genome-wide association studies (GWAS) for a variety of phenotypic traits encompassing binary, continuous, count, and survival outcomes, we propose a novel and flexible method to test for mediation that can simultaneously accommodate multiple genetic variants and different types of outcome variables. Specifically, we employ the intersection-union test approach combined with likelihood ratio test to detect mediation effect of multiple genetic variants via some mediator (for example, the expression of a neighboring gene) on outcome. We fit high-dimensional generalized linear mixed models under the mediation framework, separately under the null and alternative hypothesis. We leverage Laplace approximation to compute the marginal likelihood of outcome and use coordinate descent algorithm to estimate corresponding parameters. Our extensive simulations demonstrate the validity of our proposed method and substantial, up to 97%, power gains over alternative methods. Applications to real data for the study ofChlamydia trachomatisinfection further showcase advantages of our method. We believe our proposed method will be of value and general interest in this post-GWAS era to disentangle the potential causal mechanism from DNA to phenotype for new drug discovery and personalized medicine.
Genomic characterization and computational phenotyping of nitrogen-fixing bacteria isolated from Colombian sugarcane fields
Authors: Medina-Cordoba Luz K. , Chande Aroon T. , Rishishwar Lavanya , Mayer Leonard W. , Valderrama-Aguirre Lina C. , Valderrama-Aguirre Augusto , Gaby John Christian , Kostka Joel E. , Jordan I. King 
Published: September 2019

ABSTRACTPrevious studies have shown that the sugarcane microbiome harbors diverse plant growth promoting (PGP) microorganisms, including nitrogen-fixing bacteria, and the objective of this study was to design a genome-enabled approach to prioritize sugarcane associated nitrogen-fixing bacteria according to their potential as biofertilizers. Using a systematic high throughput approach, 22 pure cultures of nitrogen-fixing bacteria were isolated and tested for diazotrophic potential by PCR amplification of nitrogenase (nifH) genes, common molecular markers for nitrogen fixation capacity. Genome sequencing confirmed the presence of intact nitrogenasenifHgenes and operons in the genomes of 18 of the isolates. Isolate genomes also encoded operons for phosphate solubilization, siderophore production operons, and other PGP phenotypes.Klebsiella pneumoniaestrains comprised 14 of the 22 nitrogen-fixing isolates, and four others were members of closely related genera toKlebsiella. A computational phenotyping approach was developed to rapidly screen for strains that have high potential for nitrogen fixation and other PGP phenotypes while showing low risk for virulence and antibiotic resistance. The majority of sugarcane isolates were below a genotypic and phenotypic threshold, showing uniformly low predicted virulence and antibiotic resistance compared to clinical isolates. Six prioritized strains were experimentally evaluated for PGP phenotypes: nitrogen fixation, phosphate solubilization, and the production of siderophores, gibberellic acid and indole acetic acid. Results from the biochemical assays were consistent with the computational phenotype predictions for these isolates. Our results indicate that computational phenotyping is a promising tool for the assessment of benefits and risks associated with bacteria commonly detected in agricultural ecosystems.IMPORTANCEA genome-enabled approach was developed for the prioritization of native bacterial isolates with the potential to serve as biofertilizers for sugarcane fields in Colombia’s Cauca Valley. The approach is based on computational phenotyping, which entails predictions related to traits of interest based on bioinformatic analysis of whole genome sequences. Bioinformatic predictions of the presence of plant growth promoting traits were validated with experimental assays and more extensive genome comparisons, thereby demonstrating the utility of computational phenotyping for assessing the benefits and risks posed by bacterial isolates that can be used as biofertilizers. The quantitative approach to computational phenotyping developed here for the discovery of biofertilizers has the potential for use with a broad range of applications in environmental and industrial microbiology, food safety, water quality, and antibiotic resistance studies.