bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling of Nascent Lariat Intermediates Reveals Key Genetic Determinants of the Timing of Human Co-transcriptional Splicing
Authors: Zeng Yi , Zeng Huilin , Fair Benjamin J , Krishnamohan Aiswarya , Hou Yichen , Hall Johnathon M , Ruthenburg Alexander J , Li Yang I , Staley Jonathan P 
Published: October 2021

AbstractAs splicing is intimately coupled with transcription, understanding splicing mechanisms requires an understanding of splicing timing, which is currently limited. Here, we developed CoLa-seq (co-transcriptionallariatsequencing), a genomic assay that reports splicing timing relative to transcription through analysis of nascent lariat intermediates. In human cells, we mapped 165,282 branch points and characterized splicing timing for over 70,000 introns. Splicing timing varies dramatically across introns, with regulated introns splicing later than constitutive introns. Machine learning-based modeling revealed genetic elements predictive of splicing timing, notably the polypyrimidine tract, intron length, and regional GC content, which illustrate the significance of the broader genomic context of an intron and the impact of co-transcriptional splicing. The importance of the splicing factor U2AF in early splicing rationalizes surprising observations that most introns can splice independent of exon definition. Together, these findings establish a critical framework for investigating the mechanisms and regulation of co-transcriptional splicing.HighlightsCoLa-seq enables cell-type specific, genome-wide branch point annotation with unprecedented efficiency.CoLa-seq captures co-transcriptional splicing for tens of thousands of introns and reveals splicing timing varies dramatically across introns.Modeling uncovers key genetic determinants of splicing timing, most notably regional GC content, intron length, and the polypyrimidine tract, the binding site for U2AF2.Early splicing precedes transcription of a downstream 5’ SS and in some cases accessibility of the upstream 3’ SS, precluding exon definition.
Negative catalysis by the editing domain of class I aminoacyl-tRNA synthetases
Authors: Zivkovic Igor , Ivkovic Kate , Cvetesic Nevena , Gruic-Sovulj Ita 
Published: October 2021

ABSTRACTAminoacyl-tRNA synthetases (AARS) translate the genetic code by loading tRNAs with the cognate amino acids. The errors in amino acid recognition are cleared at the AARS editing domain through hydrolysis of misaminoacyl-tRNAs. This ensures faithful protein synthesis and cellular fitness. Using Escherichia coli isoleucyl-tRNA synthetase (IleRS) as a model enzyme, we demonstrated that the class I editing domain clears the non-cognate amino acids well-discriminated at the synthetic site with the same rates as the weakly-discriminated fidelity threats. This unveiled low selectivity suggests that evolutionary pressure to optimize the rates against the amino acids that jeopardize translational fidelity did not shape the editing site. Instead, we propose that editing was shaped to safeguard cognate aminoacyl-tRNAs against hydrolysis. Misediting is prevented by the residues that promote negative catalysis through destabilisation of the transition state comprising cognate amino acid. Such powerful design allows broad substrate acceptance of the editing domain along with its exquisite specificity in the cognate aminoacyl-tRNA rejection. Editing proceeds by direct substrate delivery to the editing domain (in cis pathway). However, we found that class I IleRS also releases misaminoacyl-tRNAIle and edits it in trans. This minor editing pathway was up to now recognized only for class II AARSs.
Increased Functional Connectivity Characterises the Prodromal Phase of the Migraine Cycle
Authors: Stankewitz Anne , Mayr Astrid , Schulz Enrico 
Published: October 2021

AbstractIntroductionEpisodic migraine is reflected by cyclic changes in behaviour and cortical processing. We aimed to identify how Functional connectivities change over the entire migraine cycle.MethodsBy using longitudinal neuroimaging and a whole-brain connectivity analysis approach, we tested 12 episodic migraine patients across 82 FMRI recordings during spontaneous headache attacks with Follow-up measurements over the pain-free interval without any external stimulation.ResultsWe Found that Functional connectivities linearly increased over the interictal interval. In the prodromal phase, we observed the strongest connections between the anterior agranular insula and the posterior orbitofrontal cortex with sensory, motor, and cingulate areas. The strengths of the connections dropped during the headache. Peak connectivity during the prodromal phase and its collapse during the headache can be regarded as a mechanism of normalising cortical processing.ConclusionsThe strongest connections during the ictal phase of the migraine cycle may contribute to the variety of symptoms of migraine attacks including headache, sensory hypersensitivity, and autonomous symptoms. We speculate about a malfunction at the molecular level in agranular frontal and insular regions, which needs to be addressed in subsequent studies.Article highlightsWe investigated functional connectivities over an entire migraine cycle.We found cycle-related connectivity changes for two proximate agranular regions.The prodromal increase and the collapse of connectivity during the headache may reflect normalising cortical processing.
Impact of walking speed and motion adaptation on optokinetic nystagmus-like head movements in the blowfly Calliphora
Authors: Longden Kit D. , Schützenberger Anna , Hardcastle Ben J. , Krapp Holger G. 
Published: October 2021

AbstractThe optokinetic nystagmus is a gaze-stabilizing mechanism reducing motion blur by rapid eye rotations against the direction of visual motion, followed by slower syndirectional eye movements minimizing retinal slip speed. Flies control their gaze through head turns controlled by neck motor neurons receiving input directly, or via descending neurons, from well-characterized directional-selective interneurons sensitive to visual wide-field motion. Locomotion increases the gain and speed sensitivity of these interneurons, while visual motion adaptation in walking animals has the opposite effects. To find out whether flies perform an optokinetic nystagmus, and how it may be affected by locomotion and visual motion adaptation, we recorded head movements of blowflies on a trackball stimulated by progressive and rotational visual motion. Flies flexibly responded to rotational stimuli with optokinetic nystagmus-like head movements, independent of their locomotor state. The temporal frequency tuning of these movements, though matching that of the upstream directional-selective interneurons, was only mildly modulated by walking speed or visual motion adaptation. Our results suggest flies flexibly control their gaze to compensate for rotational wide-field motion by a mechanism similar to an optokinetic nystagmus. Surprisingly, the mechanism is less state-dependent than the response properties of directional-selective interneurons providing input to the neck motor system.
Rac1 signaling in microglia is essential for synaptic proteome plasticity and experience-dependent cognitive performance
Authors: Socodato Renato , Almeida Tiago O. , Portugal Camila C. , Santos Evelyn C. S. , Tedim-Moreira Joana , Canedo Teresa , Baptista Filipa I. , Magalhães Ana , Ambrósio António F. , Brakebusch Cord , Rubinstein Boris , Moreira Irina S. , Summavielle Teresa , Pinto Inês Mendes , Relvas João B. 
Published: October 2021

AbstractMicroglial homeostatic functions are fundamental to regulate the central nervous system microenvironment. We use conditional cell-specific gene targeting, RNA-seq profiling, high-throughput proteomics, phosphoproteomics, systems biology, and animal behavior to report a critical role for the RhoGTPase Rac1 in regulating adult microglia physiology. Ablation of Rac1 in adult microglia impaired their ability to sense and interpret the brain microenvironment and affected their capacity to communicate with synapses to drive cognitive performance, both at the steady-state and during experience-dependent plasticity. Overall, our results reveal a novel and central role for Rac1 as a regulator of microglia homeostasis and a molecular driver of the microglia-synapse crosstalk required for context-dependent sociability and learning related to memory.
Nuclear DNA-encoded fragments of mitochondrial DNA (mtDNA) confound analysis of selection of mtDNA mutations in human primordial germ cells
Authors: Fleischmann Zoë , Annis Sofia , Franco Melissa , Oreshkov Sergey , Popadin Konstantin , Woods Dori C. , Tilly Jonathan L. , Khrapko Konstantin 
Published: October 2021

AbstractThe resilience of the mitochondrial genome to a high mutational pressure depends, in part, on purifying selection against detrimental mutations in the germline. It is crucial to understand the mechanisms of this process. Recently, Floros et al. concluded that much of the purifying selection takes place during the proliferation of primordial germ cells (PGCs) because, according to their analysis, the synonymity of mutations in late PGCs was seemingly increased compared to those in early PGCs. We re-analyzed the Floros et al. mutational data and discovered a high proportion of sequence variants that are not true mutations, but originate from NUMTs, the latter of which are segments of mitochondrial DNA (mtDNA) inserted into nuclear DNA, up to millions of years ago. This is a well-known artifact in mtDNA mutational analysis. Removal of these artifacts from the Floros et al. dataset abolishes the reported effect of purifying selection in PGCs. We therefore conclude that the mechanism of germline selection of mtDNA mutations remains open for debate, and more research is needed to fully elucidate the timing and nature of this process.
Genome-wide association study of open field behavior in outbred heterogeneous stock rats identifies multiple loci implicated in psychiatric disorders
Authors: Gunturkun Mustafa Hakan , Wang Tengfei , Chitre Apurva S. , Martinez Angel Garcia , Holl Katie , St. Pierre Celine , Bimschleger Hannah , Gao Jianjun , Cheng Riyan , Polesskaya Oksana , Solberg-Woods Leah C. , Palmer Abraham A. , Chen Hao 
Published: October 2021

AbstractMany personality traits are influenced by genetic factors. Rodents models provide an efficient system for analyzing genetic contribution to these traits. Using 1,246 adolescent heterogeneous stock (HS) male and female rats, we conducted a genome-wide association study (GWAS) of behaviors measured in an open field, including locomotion, novel object interaction, and social interaction. We identified 30 genome-wide significant quantitative trait loci (QTL). Using multiple criteria, including the presence of high impact genomic variants and co-localization of cis-eQTL, we identified 13 candidate genes (Adarb2, Ankrd26, Cacna1c, Clock, Crhr1, Ctu2, Cyp26b1, Eva1a, Fam114a1, Kcnj9, Mlf2, Rab27b, Sec11a) for these traits. Most of these genes have been implicated by human GWAS of various psychiatric traits. For example, Cacna1c, a gene known to be critical for social behavior in rodents and implicated in human schizophrenia and bipolar disorder, is a candidate gene for distance to the social zone. In addition, the QTL region for total distance to the novel object zone, on Chr1 at 144 Mb, is syntenic to a hotspot on human Chr15 (82.5-90.8 Mb) that contains 14 genes associated with psychiatric or substance abuse traits. Although some of the genes identified by this study appear to replicate findings from prior human GWAS, others likely represent novel findings that can be the catalyst for future molecular and genetic insights into human psychiatric diseases. Together, these findings provide strong support for the use of the HS population to study psychiatric disorders.
Genetic architecture underlying variation in floral meristem termination in Aquilegia
Authors: Min Ya , Ballerini Evangeline S. , Edwards Molly B. , Hodges Scott A. , Kramer Elena M. 
Published: October 2021

ABSTRACTFloral organs are produced by floral meristems (FMs), which harbor stem cells in their centers. Since each flower only has a finite number of organs, the stem cell activity of a FM will always terminate at a specific time point, a process termed floral meristem termination (FMT). Variation in the timing of FMT can give rise to floral morphological diversity, but how this process is fine-tuned at a developmental and evolutionary level is poorly understood. Flowers from the genus Aquilegia share identical floral organ arrangement except for stamen whorl numbers (SWN), making Aquilegia a well-suited system for investigation of this process: differences in SWN between species represent differences in the timing of FMT. By crossing A. canadensis and A. brevistyla, quantitative trait locus (QTL) mapping has revealed a complex genetic architecture with seven QTL. We identified potential candidate genes under each QTL and characterized novel expression patterns of select candidate genes using in situ hybridization. To our knowledge, this is the first attempt to dissect the genetic basis of how natural variation in the timing of FMT is regulated and our results provide insight into how floral morphological diversity can be generated at the meristematic level.
Language experience predicts music processing in ½ million speakers of 54 languages
Authors: Liu Jingxuan , Hilton Courtney B. , Bergelson Elika , Mehr Samuel A. 
Published: October 2021

AbstractTonal languages differ from other languages in their use of pitch (tones) to distinguish words. Lifelong experience speaking and hearing tonal languages has been argued to shape auditory processing in ways that generalize beyond the perception oflinguisticpitch to the perception of pitch in other domains like music. To examine this, we first conducted a meta-analysis, finding moderate evidence for this idea, but in studies strongly limited by mostly small sample sizes in only a few tonal languages and countries. This makes it challenging to disentangle the effects of linguistic experience from variability in music training experience, cultural differences, and other potential confounds. To address these issues, we used web-based citizen science to test this question on a global scale. We assessed music perception skill inn= 34, 034 native speakers of 19 tonal languages (e.g., Mandarin, Yoruba) and compared their performance ton= 459, 066 native speakers of other languages, including 6 pitch-accented (e.g., Japanese) and 29 non-tonal languages (e.g., Hungarian). Whether or not participants had taken music lessons, native speakers of all 19 tonal languages had an improved ability to discriminate musical melodies. But this improvement came with a trade-off: relative to speakers of pitch-accented or non-tonal languages, tonal language speakers were also worse at processing the musical beat. These results, which held across tonal languages from a variety of geographic regions and were robust to geographic and demographic variation, demonstrate that linguistic experience shapes music perception ability, with implications for relations between music, language, and culture in the human mind.
Impacts of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 variants Alpha and Delta on Coronavirus Disease 2019 transmission dynamics in four metropolitan areas of the United States
Authors: Mallela Abhishek , Chen Ye , Lin Yen Ting , Miller Ely F. , Neumann Jacob , He Zhili , Nelson Kathryn E. , Posner Richard G. , Hlavacek William S. 
Published: October 2021

ABSTRACTTo characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.6x to 2.1x. The estimated Alpha takeoff times ranged from February 1 to February 28, 2021. The estimated Delta takeoff times ranged from June 2 to June 26, 2021. Estimated takeoff times are consistent with genomic surveillance data.One-Sentence SummaryUsing a compartmental model parameterized to reproduce available reports of new Coronavirus Disease 2019 (COVID-19) cases, we quantified the impacts of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2) on regional epidemics in the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix.
On the prediction of human intelligence from neuroimaging: A systematic review of methods and reporting
Authors: Vieira Bruno Hebling , Pedro Pamplona Gustavo Santo , Fachinello Karim , Silva Alice Kamensek , Foss Maria Paula , Garrido Salmon Carlos Ernesto 
Published: October 2021

AbstractHuman intelligence is one of the main objects of study in cognitive neuroscience. Reviews and meta-analyses have proved to be fundamental to establish and cement neuroscientific theories on intelligence. The prediction of intelligence using in vivo neuroimaging data and machine learning has become a widely accepted and replicated result. Here, we present a systematic review of this growing area of research, based on studies that employ structural, functional, and/or diffusion MRI to predict human intelligence in cognitively normal subjects using machine-learning. We performed a systematic assessment of methodological and reporting quality, using the PROBAST and TRIPOD assessment forms and 30 studies identified through a systematic search. We observed that fMRI is the most employed modality, resting-state functional connectivity (RSFC) is the most studied predictor, and the Human Connectome Project is the most employed dataset. A meta-analysis revealed a significant difference between the performance obtained in the prediction of general and fluid intelligence from fMRI data, confirming that the quality of measurement moderates this association. The expected performance of studies predicting general intelligence from fMRI was estimated to be r = 0.42 (CI95% = [0.35, 0.50]) while for studies predicting fluid intelligence obtained from a single test, expected performance was estimated as r = 0.15 (CI95% = [0.13, 0.17]). We further enumerate some virtues and pitfalls we identified in the methods for the assessment of intelligence and machine learning. The lack of treatment of confounder variables, including kinship, and small sample sizes were two common occurrences in the literature which increased risk of bias. Reporting quality was fair across studies, although reporting of results and discussion could be vastly improved. We conclude that the current literature on the prediction of intelligence from neuroimaging data is reaching maturity. Performance has been reliably demonstrated, although extending findings to new populations is imperative. Current results could be used by future works to foment new theories on the biological basis of intelligence differences.
Single-Cell Analysis of Human Testis Aging, and Impact of Elevated Body Mass Index
Authors: Nie Xichen , Munyoki Sarah K. , Sukhwani Meena , Schmid Nina , Missel Annika , Emery Benjamin R. , Connect Donor , Stukenborg Jan-Bernd , Mayerhofer Artur , Orwig Kyle E. , Aston Kenneth I. , Hotaling James M. , Cairns Bradley R. , Guo Jingtao 
Published: October 2021

SUMMARYAging human males display reduced reproductive health, however testis aging is poorly understood at the molecular and genomic level. Here, we utilized single-cell RNA-seq to profile over 44,000 cells from both young and older men (>60 years old) – and examined age-related changes in germline development and in the somatic niche. Interestingly, age-related changes in spermatogonial stem cells appeared modest, whereas age-related dysregulation of spermatogenesis and the somatic niche ranged from moderate to severe. Altered pathways included signaling and inflammation in multiple cell types, metabolic signaling in Sertoli cells, hedgehog signaling and testosterone production in Leydig cells, cell death and growth in testicular peritubular cells, and possible developmental regression in both Leydig and peritubular cells. Remarkably, the extent of dysregulation correlated with body mass index in older, but not younger men. Taken together, we reveal candidate molecular mechanisms underlying the complex testicular changes conferred by aging, and their exacerbation by concurrent chronic conditions such as obesity.
Influence of DNA extraction kits on freshwater fungal DNA metabarcoding
Authors: Matsuoka Shunsuke , Sugiyama Yoriko , Nagano Mariko , Doi Hideyuki 
Published: October 2021

AbstractBackgroundEnvironmental DNA (eDNA) metabarcoding is a common technique for efficient biodiversity monitoring, especially of microbes. Recently, the usefulness of aquatic eDNA in monitoring the diversity of both terrestrial and aquatic fungi has been suggested. In eDNA studies, different experimental factors, such as DNA extraction kits or methods, can affect the subsequent analyses and the results of DNA metabarcoding. However, few methodological studies have been carried out on eDNA of fungi, and little is known about how experimental procedures can affect the results of biodiversity analysis. In this study, we focused on the effect of DNA extraction method on fungal DNA metabarcoding using freshwater samples obtained from rivers and lakes.MethodsDNA was extracted from freshwater samples using the DNeasy PowerSoil kit, which is mainly used to extract microbial DNA from soil, and the DNeasy Blood & Tissue kit, which is commonly used for eDNA studies on animals. We then compared PCR inhibition and fungal DNA metabarcoding results; i.e., operational taxonomic unit (OTU) number and composition of the extracted samples.ResultsNo PCR inhibition was detected in any of the samples, and no significant differences in the number of OTUs and OTU compositions were detected between the samples processed using different kits. These results indicate that both DNA extraction kits may provide similar diversity results for the river and lake samples evaluated in this study. Therefore, it may be possible to evaluate the diversity of fungi using a unified experimental method, even with samples obtained for diversity studies on other taxa such as those of animals.