bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of Zika virus xrRNA1-dependent sfRNA1 production results in tissue-specific attenuated viral replication
Authors: Sparks Hadrian , Monogue Brendan , Akiyama Benjamin , Kieft Jeffrey S. , Beckham J. David 
Published: September 2020

AbstractZika virus (ZIKV), like other flaviviruses, produces several species of sub-genomic RNAs (sfRNAs) during infection, corresponding to noncoding RNA fragments of different lengths derived from the viral 3’ untranslated region (UTR). Over the course of infection, these sfRNAs accumulate in the cell as a result of incomplete viral genome degradation of the 3’UTR by host 5’ to 3’ exoribonuclease (Xrn1). The halting of Xrn1 in the 3’UTR is due to two RNA pseudoknot structures in the 3’UTR termed exoribonuclease-resistant RNA1 and 2 (xrRNA1&2). Studies with related flaviviruses have shown that sfRNAs are important for pathogenicity and inhibiting both mosquito and mammalian host defense mechanisms. However, these investigations have not included ZIKV and there is very limited data addressing how sfRNAs impact infection in a whole animal model or specific tissues. In this study, we rescued a sfRNA1-deficient ZIKV (X1) by targeted mutation in the xrRNA1 3’ UTR structure. We found that virus which lacks the production of the largest ZIKV sfRNA species, sfRNA1. Using the X1 virus to infect adultIFNAR1-/-mice, we found that while the lack of sfRNA1 does not alter ZIKV replication in the spleen, there is a significant reduction of ZIKV genome replication in the brain and placenta compared to WT ZIKV infection. Despite thee attenuated phenotype of the X1 ZIKV, mice develop a robust neutralizing antibody response. We conclude that targeted disruption of xrRNA1 results in tissue-specific attenuation while still supporting robust neutralizing antibody responses. Future studies will need to investigate the tissue-specific mechanisms by which ZIKV sfRNAs influence infection and may utilize targeted xrRNA mutations to develop novel attenuated flavivirus vaccine approaches.
The chromosomal passenger complex establishes chromosome biorientation via two parallel localization pathways
Authors: Marsoner Theodor , Yedavalli Poornima , Masnovo Chiara , Schmitzer Katrin , Campbell Christopher S. 
Published: September 2020

AbstractChromosome biorientation is established by the four-member chromosomal passenger complex (CPC) through phosphorylation of incorrect kinetochore-microtubule attachments. During chromosome alignment, the CPC localizes to the inner centromere, the inner kinetochore and spindle microtubules. Here we show that a small region of the CPC subunit INCENP/Sli15 is required to target the complex to all three of these locations in budding yeast. This region, the SAH, is essential for phosphorylation of outer kinetochore substrates, chromosome segregation, and viability. By restoring the CPC to each of these three locations individually, we found that inner centromere localization is sufficient to establish chromosome biorientation and viability independently of the other two targeting mechanisms. Remarkably, although neither the inner kinetochore nor microtubule binding activities was able to rescue viability individually, they were able to do so when combined. We have therefore identified two parallel pathways by which the CPC can promote chromosome biorientation and proper completion of mitosis.
Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons
Authors: Squires Katherine E , Gerber Kyle J , Tillman Matthew C , Lustberg Daniel J , Montañez-Miranda Carolina , Zhao Meilan , Ramineni Suneela , Scharer Christopher D , Shu Feng-jue , Schroeder Jason P , Ortlund Eric A , Weinshenker David , Dudek Serena M , Hepler John R 
Published: September 2020

AbstractThe human genome contains vast genetic diversity in the form of naturally occurring coding variants, yet the impact of these variants on protein function and physiology is poorly understood. RGS14 is a multifunctional signaling protein that suppresses synaptic plasticity in dendritic spines of hippocampal neurons. RGS14 also is a nucleocytoplasmic shuttling protein, suggesting that balanced nuclear import/export and dendritic spine localization are essential for RGS14 functions. We identified genetic variants L505R (LR) and R507Q (RQ) located within the nuclear export sequence (NES) of humanRGS14. Here we report that RGS14 carrying LR or RQ profoundly impacts protein functions in hippocampal neurons and brain. Following nuclear import, RGS14 nuclear export is regulated by Exportin 1 (XPO1/CRM1). Remarkably, LR and RQ variants disrupt RGS14 binding to Gαi1-GDP and XPO1, nucleocytoplasmic equilibrium, and capacity to inhibit LTP. Variant LR accumulates irreversibly in the nucleus, preventing RGS14 binding to G proteins, localization to dendritic spines, and inhibitory actions on LTP induction, while variant RQ exhibits a mixed phenotype. When introduced into mice by CRISPR/Cas9, RGS14-LR protein expression was detected predominantly in the nuclei of neurons within hippocampus, central amygdala, piriform cortex, and striatum, brain regions associated with learning and synaptic plasticity. Whereas mice completely lacking RGS14 exhibit enhanced spatial learning, mice carrying variant LR exhibit normal spatial learning, suggesting that RGS14 may have distinct functions in the nucleus independent from those in dendrites and spines. These findings show that naturally occurring genetic variants can profoundly alter normal protein function, impacting physiology in unexpected ways.
CD8 T cell epitope generation toward the continually mutating SARS-CoV-2 spike protein in genetically diverse human population: Implications for disease control and prevention
Authors: Guo Elisa , Guo Hailong 
Published: September 2020

AbstractThe ongoing pandemic of SARS-CoV-2 has brought tremendous crisis on global health care systems and industrial operations that dramatically affect the economic and social life of numerous individuals worldwide. Understanding anti-SARS-CoV-2 immune responses in population with different genetic backgrounds and tracking the viral evolution are crucial for successful vaccine design. In this study, we reported the generation of CD8 T cell epitopes by a total of 80 alleles of three major class I HLAs using NetMHC 4.0 algorithm for the spike protein of SARS-CoV-2, a key antigen that is targeted by both B cells and T cells. We found diverse capacities of S protein specific epitope presentation by different HLA alleles with very limited number of predicted epitopes for HLA-B*2705, HLA-B*4402 and HLA-B*4403 and as high as 132 epitopes for HLA-A*6601. Our analysis of 1000 S protein sequences from field isolates collected globally over the past few months identified three recurrent point mutations including L5F, D614G and G1124V. Differential effects of these mutations on CD8 T cell epitope generation by corresponding HLA alleles were observed. Finally, our multiple alignment analysis indicated the absence of seasonal CoV induced cross-reactive CD8 T cells to drive these mutations. Our findings provided molecular explanations for the observation that individuals with certain HLA alleles such as B*44 are more prone to SARS-CoV-2 infection. Studying anti-S protein specific CD8 T cell immunity in diverse genetic background is critical for better control and prevention of the SARS-CoV-2 pandemic.
GABAergic inhibition in the human visual cortex relates to eye dominance
Authors: Ip I. Betina , Lunghi Claudia , Emir Uzay E. , Parker Andrew J. , Bridge Holly 
Published: September 2020

ABSTRACTOur binocular world is seamlessly assembled from two retinal images that remain segregated until the cerebral cortex. Despite the coherence of this input, there is often an imbalance between the strength of these connections in the brain. ‘Eye dominance’ provides a measure of the perceptual dominance of one eye over the other. Theoretical models suggest that eye dominance is related to reciprocal inhibition between monocular units in the primary visual cortex, the first location where the binocular input is combined. As the specific inhibitory interactions in the binocular visual system critically depend on the presence of visual input, we sought to test the role of inhibition by measuring the concentrations of inhibitory (GABA) neurotransmitters during monocular visual stimulation of the dominant and the non-dominant eye. GABA-levels were acquired in V1 using a combined functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) sequence on a 7-Tesla MRI scanner. Individuals with stronger eye dominance had a greater difference in GABAergic inhibition between the eyes. This relationship was present only when the visual system was actively processing sensory input and was not present at rest. We provide the first evidence that imbalances in GABA levels during ongoing sensory processing are related to eye dominance in the human visual cortex. This provides strong support to the view that intracortical inhibition underlies normal eye dominance.SIGNIFICANCE STATEMENTWhat we see is shaped by excitation and inhibition in our brain. We investigated how eye dominance, the perceptual preference of one eye’s input over the other, is related to levels of inhibitory neurotransmitter GABA during monocular visual stimulation. GABAergic inhibition is related to eye dominance, but only when the visual system is actively processing sensory input. This provides key support for the view that imbalances in visual competition that are observed in the normal visual system arise from an inability of GABA signalling to suppress the stronger sensory representation.
Structure of the Human Secretory Immunoglobulin M Core
Authors: Kumar Nikit , Arthur Christopher P. , Ciferri Claudio , Matsumoto Marissa L. 
Published: September 2020

AbstractImmunoglobulins (Ig) A and M are the only human antibodies that form oligomers and undergo transcytosis to mucosal secretions via the polymeric Ig receptor (pIgR). When complexed with the J-chain (JC) and the secretory component (SC) of pIgR, secretory IgA and IgM (sIgA and sIgM) play critical roles in host-pathogen defense. Recently, we determined the structure of sIgA-Fc which elucidated the mechanism of polymeric IgA assembly and revealed an extensive binding interface between IgA-Fc, JC, and SC. Despite low sequence identity shared with IgA-Fc, IgM-Fc also undergoes JC-mediated assembly and binds pIgR. Here, we report the structure of sIgM-Fc and carryout a systematic comparison to sIgA-Fc. Our structural analysis reveals a remarkably conserved mechanism of JC-templated oligomerization and SC recognition of both IgM and IgA through highly a conserved network of interactions. These studies reveal the structurally conserved features of sIgM and sIgA required for function in mucosal immunity.
Evolution of research in biomedical sciences - a network-based characterization based on PubMed
Authors: Friedrichs Karla , Spranger Michael , Palaniappan Sucheendra K. 
Published: September 2020

AbstractThe rapid growth of scientific publications every year makes it infeasible to keep pace with and survey manually, even for a specific field. Keeping up with literature and gaining a birds-eye view in a timely manner is crucial to the pursuit of scientific discovery and innovation. To help gain a clearer understanding of the state and progress of science and the nature of discovery, one can encode key information from these publications and represent them as a network. Observations on the structural evolution of these graphs can offer valuable insights on the dynamics at play. This work describes the construction and analyses the temporal evolution of a knowledge network of keywords (specifically focusing on genes/proteins, diseases and chemicals) from publications in the biomedical sciences domain. We compare and contrast the representations and evolution of these keyword networks types and find significant differences in the network growth, largely corresponding to our intuition. Furthermore, we focus on the formation and evolution of new links, which we argue corresponds to new scientific discoveries. Our findings suggest that these links are progressively formed in short network distance, leading to clusters of extensively studied keywords. This strategy, however, seems to impede ground-breaking innovation, which could be beneficial for research progress.
Brain Connectivity Patterns in Children Linked to Neurocognitive Abilities
Authors: Sripada Chandra , Angstadt Mike , Rutherford Saige , Taxali Aman , Clark D. Angus , Greathouse Tristan , Weigard Alex , Hyde Luke , Heitzeg Mary 
Published: September 2020

ABSTRACTThe development of objective brain-based measures of individual differences in psychological traits is a longstanding goal of clinical neuroscience. Here we show that reliable objective markers of children’s neurocognitive abilities can be built from measures of brain connectivity. The sample consists of 5,937 9- and 10-year-olds in the Adolescent Brain Cognitive Development multi-site study with high-quality functional connectomes that capture brain-wide connectivity. Using multivariate methods, we built predictive neuromarkers for a general factor of neurocognitive ability as well as for a number of specific cognitive abilities (e.g., spatial reasoning, working memory). Neuromarkers for the general neurocognitive factor successfully predicted scores for held-out participants at 19 out of 19 held-out sites, explaining over 14% of the variance in their scores. Neuromarkers for specific neurocognitive abilities also exhibited statistically reliable generalization to new participants. This study provides the strongest evidence to date that objective quantification of psychological traits is possible with functional neuroimaging.
FreshwaterChlorobiaexhibit metabolic specialization among cosmopolitan and endemic populations
Authors: Garcia Sarahi L. , Mehrshad Maliheh , Buck Moritz , Tsuji Jackson M. , Neufeld Josh D. , McMahon Katherine D. , Bertilsson Stefan , Greening Chris , Peura Sari 
Published: September 2020

AbstractPhotosynthetic bacteria from the classChlorobia(formerly phylumChlorobi) sustain carbon fixation in anoxic water columns. They harvest light at extremely low intensities and use various inorganic electron donors to fix carbon dioxide into biomass. Until now, most information on their functional ecology and local adaptations came from isolates and merely 26 sequenced genomes that are poor representatives of natural populations. To address these limitations, we analyzed global metagenomes to profile planktonicChlorobiacells from the oxyclines of 42 freshwater bodies, spanning subarctic to tropical regions and encompassing all four seasons. We assembled and compiled over 500 genomes, including metagenome-assembled genomes (MAGs), single-cell genomes (SAGs), and reference genomes from cultures, clustering them into 71 metagenomic operational taxonomic units (mOTUs) or “species”. Of the 71 mOTUs, 57 were classified as genusChlorobiumand these mOTUs varied in relative abundance up to ~60% of the microbial communities in the sampled anoxic waters. SeveralChlorobium-associated mOTUs were globally distributed whereas others were endemic to individual lakes. Although most clades encoded the ability to oxidize hydrogen, many were lacking genes for the oxidation of specific sulfur and iron substrates. Surprisingly, one globally distributed ScandinavianChlorobiumclade encoded the ability to oxidize hydrogen, sulfur, and iron, suggesting that metabolic versatility facilitated such widespread colonization. Overall, these findings provide new insights into the biogeography of theChlorobiaand the metabolic traits that facilitate niche specialization within lake ecosystems.ImportanceThe reconstruction of genomes from metagenomes has enabled unprecedented insights into the ecology and evolution of environmental microbiomes. We applied this powerful approach to 274 metagenomes collected from diverse freshwater habitats that spanned oxic and anoxic zones, sampling seasons, and latitudes. We demonstrate widespread and abundant distributions of planktonicChlorobia-associated bacteria in hypolimnetic waters of stratified freshwater ecosystems and pinpoint nutrients that likely fuel their electron chains. Being photoautotrophs, theseChlorobiaorganisms also have the potential to serve as carbon sources that support metalimnetic and hypolimnetic food webs.
Frequency-resolved functional connectivity: Role of delay and the strength of connections
Authors: Ziaeemehr Abolfazl , Valizadeh Alireza 
Published: September 2020

AbstractThe brain functional network extracted from the BOLD signals reveals the correlated activity of the different brain regions, which is hypothesized to underlie the integration of the information across functionally specialized areas. Functional networks are not static and change over time and in different brain states, enabling the nervous system to engage and disengage different local areas in specific tasks on demand. Due to the low temporal resolution, however, BOLD signals do not allow the exploration of spectral properties of the brain dynamics over different frequency bands which are known to be important in cognitive processes. Recent studies using imaging tools with a high temporal resolution has made it possible to explore the correlation between the regions at multiple frequency bands. These studies introduce the frequency as a new dimension over which the functional networks change, enabling brain networks to transmit multiplex of information at any time. In this computational study, we explore the functional connectivity at different frequency ranges and highlight the role of the distance between the nodes in their correlation. We run the generalized Kuramoto model with delayed interactions on top of the brain’s connectome and show that how the transmission delay and the strength of the connections, affect the correlation between the pair of nodes over different frequency bands.
Reef Cover: a coral reef classification to guide global habitat mapping from remote sensing
Authors: Kennedy Emma , Roelfsema Chris , Lyons Mitchell , Kovacs Eva , Borrego-Acevedo Rodney , Roe Meredith , Phinn Stuart , Larsen Kirk , Murray Nicholas , Yuwono Doddy , Wolff Jeremy , Tudman Paul 
Published: September 2020

AbstractCoral reef management and conservation stand to benefit from improved high-resolution global mapping. Yet classifications employed in large-scale reef mapping to date are typically poorly defined, not shared or region-specific. Here we presentReef Cover, a new coral reef geomorphic zone classification, developed to support global-scale coral reef habitat mapping in a transparent and version-based framework. We developed scalable classes by focusing on attributes that can be observed remotely, but whose membership rules also reflect knowledge of reef formation, growth and functioning. Bridging the divide between earth observation data and geo-ecological knowledge of reefs,Reef Covermaximises the trade-off between applicability at global scales, and relevance and accuracy at local scales. We use the Caroline and Mariana Island chains in the Pacific as a case study to demonstrate use of the classification scheme and its scientific and conservation applications. The primary application ofReef Cover is theAllen Coral Atlasglobal coral reef mapping project, but the system will support bespoke reef mapping conducted at a variety of spatial scales.
LIONirs: flexible Matlab toolbox for fNIRS data analysis
Authors: Tremblay Julie , Martínez-Montes Eduardo , Hüsser Alejandra , Caron-Desrochers Laura , Pouliot Philippe , Vannasing Phetsamone , Gallagher Anne 
Published: September 2020

AbstractBackgroundFunctional near-infrared spectroscopy (fNIRS) is a suitable tool for recording brain function in pediatric or challenging populations. As with other neuroimaging techniques, the scientific community is engaged in an evolving debate regarding the most adequate methods for performing fNIRS data analyses.New methodWe introduce LIONirs, a neuroinformatics toolbox for fNIRS data analysis, designed to follow two main goals: (1) flexibility, to explore several methods in parallel and verify results using 3D visualization; (2) simplicity, to apply a defined processing pipeline to a large dataset of subjects by using the MATLAB Batch System.ResultsWithin the graphical user interfaces (DisplayGUI), the user can reject noisy intervals and correct artifacts, while visualizing the topographical projection of the data onto the 3D head representation. Data decomposition methods are available for the identification of relevant signatures, such as brain responses or artifacts. Multimodal data recorded simultaneously to fNIRS, such as physiology, electroencephalography or audio-video, can be visualized using the DisplayGUI. The toolbox includes several functions that allow one to read, preprocess, and analyze fNIRS data, including task-based and functional connectivity measures.Comparison with existing methodsSeveral good neuroinformatics tools for fNIRS data analysis are currently available. None of them emphasize multimodal visualization of the data throughout the preprocessing steps and multidimensional decomposition, which are essential for understanding challenging data. Furthermore, LIONirs provides compatibility and complementarity with other existing tools by supporting common data format.ConclusionsLIONirs offers a flexible platform for basic and advanced fNIRS data analysis, shown through real experimental examples.HighlightsThe LIONirs toolbox is designed for fNIRS data inspection and visualization.Methods are integrated for isolation of relevant activity and correction of artifacts.Multimodal auxiliary, EEG or audio-video are visualized alongside the fNIRS data.Task-based and functional connectivity measure analysis tools are available.The code structure allows to automated and standardized analysis of large data set.Graphical abstract