bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular sequencing of single neurons reveals the dendritic transcriptome of GABAergic interneurons
Authors: Perez Julio D. , tom Dieck Susanne , Alvarez-Castelao Beatriz , Chan Ivy C.W. , Schuman Erin M. 
Published: October 2020

AbstractThe localization and translation of mRNAs to dendrites and axons maintains and modifies the local proteome of neurons, and is essential for synaptic plasticity. Although significant efforts have allowed the identification of localized mRNAs in excitatory neurons, it is still unclear whether interneurons also localize a large population of mRNAs. In addition, the variability in the population of localized mRNAs within and between cell-types is unknown. Here we developed a method for the transcriptomic characterization of a single neuron’s subcellular compartments, which combines laser capture microdissection with scRNA-seq. This allowed us to separately profile the dendritic and somatic transcriptomes of individual rat hippocampal neurons and investigate the relation in mRNA abundances between the soma and dendrites of single glutamatergic and GABAergic neurons. We identified two types of glutamatergic and three types of GABAergic interneurons and we found that, like their excitatory counterparts, interneurons contain a rich repertoire of ~4000 mRNAs. The individual somatic transcriptomes exhibited more cell type-specific features than their associated dendritic transcriptomes. The detection and abundance of dendritic mRNAs was not always simply predicted by their somatic counterparts. Finally, using cell-type specific metabolic labelling of isolated neurites, we demonstrated that the processes not only of Glutamatergic but also of GABAergic neurons are capable of local translation, suggesting mRNA localization and local translation is a general property of neurons.
Stability of ripple events during task engagement in human hippocampus
Authors: Chen Yvonne Y. , Yoshor Daniel , Sheth Sameer A. , Foster Brett L. 
Published: October 2020

AbstractPeriods of cognitive disengagement, such as rest or sleep, are thought to support the progressive consolidation of episodic memories. During these states, the hippocampus displays transient high-frequency oscillatory bursts, known as ripples, which are thought to promote interactions with the neocortex, consolidating memory traces. More recent findings have suggested ripples in the human hippocampus may also occur during task engagement, particularly for tasks requiring episodic memory processes. However, it is unclear if hippocampal ripples occur during other cognitive states or whether ripple properties are modulated by specific types of task demands. In addition, identifying genuine hippocampal ripple events in the human brain can be methodological challenging. To address these questions, we used intracranial recordings from the human hippocampus to quantify ripple events across perceptual, memory and resting task states. Using spectro-temporal identification of hippocampal ripples, we observed highly similar ripple event properties across tasks, with a modest yet significant increase in ripple properties (rate, duration & amplitude) during resting task states. These ripple event attributes did not differ between hemisphere, nor across or within the time of day examined. Supporting data further highlighted that while hippocampal ripples occurred during all task states, these rates were typically lower than that observed during sleep. Together, these findings highlight that hippocampal ripples occur consistently, but sparsely, during a broad range of cognitive task states. Such findings may be incorporated into existing models of systems consolidation, whereby hippocampal ripples help to initially establish latent memory traces.
AniProtDB: A Collection of Uniformly Generated Metazoan Proteomes for Comparative Genomics Studies
Authors: Barreira Sofia N. , Nguyen Anh-Dao , Fredriksen Mark T. , Wolfsberg Tyra G. , Moreland R. Travis , Baxevanis Andreas D. 
Published: October 2020

AbstractTo address the void in the availability of high-quality proteomic data traversing the animal tree, we have implemented a pipeline for generatingde novoassemblies based on publicly available data from the NCBI Sequence Read Archive, yielding a comprehensive collection of proteomes from 100 species spanning 21 animal phyla. We have also created the Animal Proteome Database (AniProtDB), a resource providing open access to this collection of high-quality metazoan proteomes, along with information on predicted proteins and protein domains for each taxonomic classification and the ability to perform sequence similarity searches against all proteomes generated using this pipeline. This solution vastly increases the utility of these data by removing the barrier to access for research groups who do not have the expertise or resources to generate these data themselves and enables the use of data from non-traditional research organisms that have the potential to address key questions in biomedicine.Database URLhttps://research.nhgri.nih.gov/aniprotdb
Mitochondrial fission governed by Drp1 regulates exogenous fatty acid usage and storage
Authors: Song Jae Eun , Alves Tiago C. , Stutz Bernardo , Sestan-Pesa Matija , Kilian Nicole , Diano Sabrina , Kibbey Richard G. , Horvath Tamas L. 
Published: October 2020

ABSTRACTThe bioenergetic function of mitochondrial fission is associated with uncoupled respiration or elimination of damaged mitochondria to maintain a healthy mitochondrial population. In the presence of a high abundance of exogenous fatty acids, cells can either store fatty acids in lipid droplets or oxidize them in mitochondria. Even though carnitine palmitoyltransferase-1 (CPT1) controls the respiratory capacity of mitochondria in fatty acid oxidation, we observed that it did not dictate the balance of storage and usage of lipids in HeLa cells. On the other hand, inhibition of mitochondrial fission by silencing dynamic-related protein 1 (DRP1) resulted in an increase in fatty acid content of lipid droplets and a decrease in fatty acid oxidation. Mitochondrial fission was not only reflective of the amount of exogenous fatty acid being processed by mitochondria, but also found to be actively involved in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.
Strain population structure varies widely across bacterial species and predicts strain colonization in unrelated individuals
Authors: Faith Jeremiah J. , Chen-Liaw Alice , Aggarwala Varun , Kaakoush Nadeem O. , Borody Thomas J. , Mitchell Hazel , Kamm Michael A. , Paramsothy Sudarshan , Snitkin Evan S. , Mogno Ilaria 
Published: October 2020

SummaryThe population structure of strains within a bacterial species is poorly defined, despite the functional importance of strain variation in the human gut microbiota on health. Here we analyzed >1000 sequenced bacterial strains from the fecal microbiota of 47 individuals from two countries and combined them with >150,000 bacterial genomes from NCBI to quantify the strain population size of different bacterial species, as well as the frequency of finding the same strain colonized in unrelated individuals who had no opportunities for direct microbial strain transmission. Strain population sizes ranged from tens to over one-hundred thousand per species. Prevalent strains in common gut microbiota species with small population sizes were the most likely to be harbored in two or more unrelated individuals. The finite strain population size of certain species creates the opportunity to comprehensively sequence the entirety of these species’ prevalent strains and associate their presence in different individuals with health outcomes.
Multiple time-scales of decision making in the hippocampus and prefrontal cortex
Authors: Tang Wenbo , Shin Justin D. , Jadhav Shantanu P. 
Published: October 2020

ABSTRACTThe prefrontal cortex and hippocampus are crucial for memory-guided decision-making. Neural activity in the hippocampus exhibits place-cell sequences at multiple timescales, including slow behavioral sequences (∼seconds) and fast theta sequences (∼100-200 ms) within theta oscillation cycles. How prefrontal ensembles interact with hippocampal sequences to support decision-making is unclear. Here, we examined simultaneous hippocampal and prefrontal ensemble activity during learning of a spatial working-memory decision task. We found clear theta sequences in prefrontal cortex, nested within its behavioral sequences. In both regions, behavioral sequences maintained representations of current goals during navigation. In contrast, hippocampal theta sequences encoded alternatives for deliberation, and were coordinated with prefrontal theta sequences that predicted upcoming choices. During error trials, these representations were preserved to guide ongoing behavior, whereas replay sequences during inter-trial periods were impaired prior to navigation. These results establish cooperative interaction between hippocampal and prefrontal sequences at multiple timescales for memory-guided decision making.
Meta-GWAS for quantitative trait loci identification in soybean
Authors: Shook Johnathon M. , Zhang Jiaoping , Jones Sarah E. , Singh Arti , Diers Brian W. , Singh Asheesh K. 
Published: October 2020

ABSTRACTWe report a meta-Genome Wide Association Study involving 73 published studies in soybean (Glycine maxL. [Merr.]) covering 17,556 unique accessions, with improved statistical power for robust detection of loci associated with a broad range of traits.De novoGWAS and meta-analysis were conducted for composition traits including fatty acid and amino acid composition traits, disease resistance traits, and agronomic traits including seed yield, plant height, stem lodging, seed weight, seed mottling, seed quality, flowering timing, and pod shattering. To examine differences in detectability and test statistical power between single- and multi-environment GWAS, comparison of meta-GWAS results to those from the constituent experiments were performed. Using meta-GWAS analysis and the analysis of individual studies, we report 483 quantitative trait loci (QTL) at 393 unique loci. Using stringent criteria to detect significant marker trait associations, 66 candidate genes were identified, including 17 candidate genes for agronomic traits, 19 for seed related traits, and 33 for disease reaction traits. This study identified potentially valuable candidate genes that affect multiple traits. The success in narrowing down the genomic region for some loci through overlapping mapping results of multiple studies is a promising avenue for community-based studies and plant breeding applications.
Global distribution patterns of marine nitrogen-fixers by imaging and molecular methods
Authors: Karlusich Juan José Pierella , Pelletier Eric , Lombard Fabien , Carsique Madeline , Dvorak Etienne , Colin Sébastien , Picheral Marc , Cornejo-Castillo Francisco M. , Acinas Silvia G. , Pepperkok Rainer , Karsenti Eric , de Vargas Colomban , Wincker Patrick , Bowler Chris , Foster Rachel A 
Published: October 2020

AbstractBiological nitrogen fixation plays a critical role in marine primary production, yet, our understanding of marine N2-fixers (diazotrophs) is hindered by limited observations. Here, we developed a quantitative image analysis pipeline in concert with mapping of molecular markers for mining >2,000,000 images and >1,300 metagenomes in surface, deep chlorophyll maximum and mesopelagic samples across 6 size fractions (<0.2-2000 μm). Imaging and PCR-free molecular data were remarkably congruent. Sequences from diazotrophs were detected from the ultrasmall bacterioplankton (<0.2 μm) to mesoplankton (180-2000 μm), while images predicted symbiotic and colonial-forming diazotrophs (>20 µm). Imaging and molecular data estimated that polyploidy can significantly impact gene abundances of symbiotic vs colonial-forming diazotrophs. In general our results support the canonical view that larger sized diazotrophs (>10 μm) dominate the tropical belts, while sequences from unicellular cyanobacterial and non-cyanobacterial diazotrophs were globally distributed in surface and the mesopelagic. Co-occurring diazotrophic lineages of different lifestyles were frequently encountered, and several new high density regions of diazotrophs were identified in the global ocean. Overall, this work provides an update of marine diazotroph biogeographical diversity and contributes a new bio-imaging-informatic workflow.
Subcellular relocalization and nuclear redistribution of the RNA methyltransferases TRMT1 and TRMT1L upon neuronal activation
Authors: Jonkhout Nicky , Cruciani Sonia , Vieira Helaine Graziele Santos , Tran Julia , Liu Huanle , Liu Ganqiang , Pickford Russell , Kaczorowski Dominik , Franco Gloria R. , Vauti Franz , Camacho Noelia , Abedini Seyedeh Sedigheh , Najmabadi Hossein , de Pouplana Lluís Ribas , Christ Daniel , Schonrock Nicole , Mattick John S. , Novoa Eva Maria 
Published: October 2020

ABSTRACTRNA modifications are dynamic chemical entities that regulate RNA fate, and an avenue for environmental response in neuronal function. However, which RNA modifications may be playing a role in neuronal plasticity and environmental responses is largely unknown. Here we characterize the biochemical function and cellular dynamics of two human RNA methyltransferases previously associated with neurological dysfunction, TRMT1 and its homolog, TRMT1-like(TRMT1L). Using a combination of next-generation sequencing, LC-MS/MS, patient-derived cell lines and knockout mouse models, we confirm the previously reported dimethylguanosine (m2,2G) activity of TRMT1 in tRNAs, as well as reveal that TRMT1L, whose activity was unknown, is responsible for methylating a subset of cytosolic tRNAAla(AGC) isoacceptors at position 26. Using a cellularin vitromodel that mimics neuronal activation and long term potentiation, we find that both TRMT1 and TRMT1L change their subcellular localization upon neuronal activation. Specifically, we observe a major subcellular relocalization from mitochondria and other cytoplasmic domains (TRMT1) and nucleoli (TRMT1L) to different small punctate compartments in the nucleus, which are as yet uncharacterized. This phenomenon does not occur upon heat shock, suggesting that the relocalization of TRMT1 and TRMT1L is not a general reaction to stress, but rather a specific response to neuronal activation. Our results suggest that subcellular relocalization of RNA modification enzymes play a role in neuronal plasticity and transmission of information, presumably by addressing new targets.
PATRIOT: A pipeline for tracing identical-by-descent chromosome segments to improve genomic prediction in self-pollinating crop species
Authors: Shook Johnathon M. , Lourenco Daniela , Singh Asheesh K. 
Published: October 2020

ABSTRACTThe lowering genotyping cost is ushering in a wider interest and adoption of genomic prediction and selection in plant breeding programs worldwide. However, improper conflation of historical and recent linkage disequilibrium between markers and genes restricts high accuracy of genomic prediction (GP). Multiple ancestors may share a common haplotype surrounding a gene, without sharing the same allele of that gene. This prevents parsing out genetic effects associated with the underlying allele of that gene among the set of ancestral haplotypes. We present ‘Parental Allele Tracing, Recombination Identification, and Optimal predicTion’ (i.e., PATRIOT) approach that utilizes marker data to allow for a rapid identification of lines carrying specific alleles, increases the accuracy of genomic relatedness and diversity estimates, and improves genomic prediction. Leveraging identity by descent, PATRIOT showed an improvement in GP accuracy by 16.6% compared to the traditional rrBLUP method. This approach will help to increase the rate of genetic gain and allow available information to be more effectively utilized within breeding programs.
Meet me in the middle: brain-behavior mediation analysis for fMRI experiments
Authors: Brochard Jules , Daunizeau Jean 
Published: October 2020

AbstractFunctional outcomes (e.g., subjective percepts, emotions, memory retrievals, decisions, etc…) are partly determined by external stimuli and/or cues. But they may also be strongly influenced by (trial-by-trial) uncontrolled variations in brain responses to incoming information. In turn, this variability provides information regarding how stimuli and/or cues are processed by the brain to shape behavioral responses. This can be exploited by brain-behavior mediation analysis to make specific claims regarding the contribution of brain regions to functionally-relevant input-output transformations. In this work, we address four challenges of this type of approach, when applied in the context of mass-univariate fMRI data analysis: (i) we quantify the specificity and sensitivity profiles of different variants of mediation statistical tests, (ii) we evaluate their robustness to hemo-dynamic and other confounds, (iii) we identify the sorts of brain mediators that one can expect to detect, and (iv) we disclose possible interpretational issues and address them using complementary information-theoretic approaches.En passant, we propose a computationally efficient algorithmic implementation of the approach that is amenable to whole-brain exploratory analysis. We also demonstrate the strengths and weaknesses of brain-behavior mediation analysis in the context of an fMRI study of decision under risk. Finally, we discuss the limitations and possible extensions of the approach.
Chromatin conformation capture (Hi-C) sequencing of patient-derived xenografts: analysis guidelines
Authors: Dozmorov Mikhail G. , Tyc Katarzyna M. , Sheffield Nathan C. , Boyd David C. , Olex Amy L. , Reed Jason , Harrell J. Chuck 
Published: October 2020

AbstractSequencing of patient-derived xenograft (PDX) mouse models allows investigation of the molecular mechanisms of human tumor samples engrafted in a mouse host. Thus, both human and mouse genetic material is sequenced. Several methods have been developed to remove mouse sequencing reads from RNA-seq or exome sequencing PDX data and improve the downstream signal. However, for more recent chromatin conformation capture technologies (Hi-C), the effect of mouse reads remains undefined.We evaluated the effect of mouse read removal on the quality of Hi-C data using in silico created PDX Hi-C data with 10% and 30% mouse reads. Additionally, we generated two experimental PDX Hi-C datasets using different library preparation strategies. We evaluated three alignment strategies (Direct, Xenome, Combined) and three processing pipelines (Juicer, HiC-Pro, HiCExplorer) on the quality of Hi-C data.Removal of mouse reads had little-to-no effect on data quality than the results obtained with Direct alignment strategy. Juicer pipeline extracted the most useful information from PDX Hi-C data. However, library preparation strategy had the largest effect on all quality metrics. Together, our study presents comprehensive guidelines on PDX Hi-C data processing.
Key Nucleation Stages and Associated Molecular Determinants and Processes in pH-Induced Formation of Amyloid Beta Oligomers as Revealed by High-Speed AFM
Authors: Feng Lei , Watanabe Hiroki , Molino Paul J. , Wallace Gordon G. , Phung Son L. , Uchihashi Takayuki , Higgins Michael J. 
Published: October 2020

AbstractNon-fibrillar oligomers formed via nucleation from amyloid beta (AB) peptides are currently implicated in the neurotoxicity of Alzheimer’s disease. Thus, shedding light on the molecular mechanisms underlying their formation is important for identifying targets for drug therapies. This is however an enduring challenge due to the inability to detect AB nucleation processes in the lag phase from bulk kinetic assays, while time-course analyses using a series of peptide solutions involve the discontinuous observation of dynamic nucleation processes and pathways. In this study, by adjusting the pH of AB42 peptide samples while simultaneously imaging with high-speed atomic force microscopy (HS-AFM), we show the in-situ, continuous visualization of dynamic AB42 nucleation at the molecular level. The process reveals a pH-induced saturation regime, enabling a critical monomer substrate concentration to initiate the birth of nucleation. A number of key nucleation phases are identified, including pre-nucleation, saturation regime (mass surface adsorption), nucleation and post-nucleation growth, eventually leading to the formation of predominately oligomer species. HS-AFM observations further reveal the distinct, molecular processes associated with each nucleation phase that constitute the path-dependent formation of different AB species, namely an intial monomer “diffuse-like” surface layer, followed by the emergence of nuclei and then subsequent formation and growth of new complexes and oligomers. In particular, the ability of individual nuclei to undergo surface diffusion and establish new complexes via binding interactions with other species encountered in the system was found to be a significant mechanism influencing the growth of oligomers. Herein, the study contributes to current AB nucleation theories by ascribing new molecular mechanisms. More generally, the knowledge gained from single molecule techniques can greatly assist in our current understanding of various biological processes of AB peptide such as nucleation, growth, aggregation and their related kinetic pathways.
Relative time constraints improve molecular dating
Authors: Szöllősi Gergely J. , Höhna Sebastian , Williams Tom A. , Schrempf Dominik , Daubin Vincent , Boussau Bastien 
Published: October 2020

ABSTRACTDating the tree of life is central to understanding the evolution of life on Earth. Molecular clocks calibrated with fossils represent the state of the art for inferring the ages of major groups. Yet, other information on the timing of species diversification can be used to date the tree of life. For example, horizontal gene transfer events and ancient coevolutionary relationships such as (endo)symbioses can imply temporal relationships between two nodes in a phylogeny (Davín et al. 2018). These alternative sources of temporal constraints can be particularly helpful when the geological record is sparse, e.g. for microorganisms, which represent the vast majority of extant and extinct biodiversity.Here, we present a new method to combine fossil calibrations and relative age constraints to estimate chronograms. We provide an implementation of relative age constraints in RevBayes (Höhna et al. 2016) that can be combined in a modular manner with the wide range of molecular dating methods available in the software.We use both realistic simulations and empirical datasets of 40 Cyanobacteria and 62 Archaea to evaluate our method. We show that the combination of relative age constraints with fossil calibrations significantly improves the estimation of node ages.