bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain activity reveals multiple motor-learning mechanisms in a real-world task
Authors: Haar Shlomi , Faisal A. Aldo 
Published: March 2020

AbstractMany recent studies found signatures of motor learning in neural Beta oscillations (13– 30Hz), and specifically in the post-movement Beta rebound (PMBR). All these studies were in controlled laboratory-tasks in which the task designed to induce the studied learning mechanism. Interestingly, these studies reported opposing dynamics of the PMBR magnitude over learning for the error-based and reward-based tasks (increase versus decrease, respectively). Here we explored the PMBR dynamics during real-world motor-skill-learning in a billiards task using mobile-brain-imaging. Our EEG recordings highlight the opposing dynamics of PMBR magnitudes (increase versus decrease) between different subjects performing the same task. The groups of subjects, defined by their neural dynamics, also showed behavioural differences expected for different learning mechanisms. Our results suggest that when faced with the complexity of the real-world different subjects might use different learning mechanisms for the same complex task. We speculate that all subjects combine multi-modal mechanisms of learning, but different subjects have different predominant learning mechanisms.
Pairwise and Higher-Order Epistatic Interactions Have a Significant Impact on Bronchodilator Drug Response in African American Youth with Asthma
Authors: Magaña J , Contreras MG , Keys KL , Risse-Adams O , Goddard PC , Zeiger AM , Mak ACY , Elhawary JR , Samedy-Bates LA , Lee E , Thakur N , Hu D , Eng C , Salazar S , Huntsman S , Hu T , Burchard EG , White MJ 
Published: March 2020

AbstractBackgroundAsthma is one of the leading chronic illnesses among children in the United States. Asthma prevalence is higher among African Americans (11.2%) compared to European Americans (7.7%). Bronchodilator medications are part of the first-line therapy, and the rescue medication, for acute asthma symptoms. Bronchodilator drug response (BDR) varies substantially among different racial/ethnic groups. Asthma prevalence in African Americans is only 3.5% higher than that of European Americans, however, asthma mortality among African Americans is four times that of European Americans; variation in BDR may play an important role in explaining this health disparity. To improve our understanding of disparate health outcomes in complex phenotypes such as BDR, it is important to consider interactions between environmental and biological variables.ResultsWe evaluated the impact of pairwise and three-variable interactions between environmental, social, and biological variables on BDR in 617 African American youth with asthma using Visualization of Statistical Epistasis Networks (ViSEN). ViSEN is a non-parametric entropy-based approach able to identify interaction effects. We performed analyses in the full dataset and in sex-stratified subsets. Analysis in the full dataset identified six significant interactions associated with BDR, the strongest of which was an interaction between prenatal smoke exposure, age, and global African ancestry (IG: 1.09%, p=0.005). Sex-stratified analyses yielded additional significant, but divergent, results for females and males, indicating the presence of sex-specific effects.ConclusionsOur study identified novel interaction effects significantly influencing BDR in African American children with asthma. Notably, we found that the impact of higher-order interactions was greater than that of pairwise or main effects on BDR highlighting the complexity of the network of genetic and environmental factors impacting this phenotype. Several associations uncovered by ViSEN would not have been detected using regression-based methods emphasizing the importance of employing statistical methods optimized to detect both linear and non-linear interaction effects when studying complex phenotypes such as BDR. The information gained in this study increases our understanding and appreciation of the complex nature of the interactions between environmental and health-related factors that influence BDR and will be invaluable to biomedical researchers designing future studies.
Stream-Specific Feedback Inputs to the Primate Primary Visual Cortex
Authors: Federer Frederick , Ta’afua Seminare , Merlin Sam , Hassanpour Mahlega S. , Angelucci Alessandra 
Published: March 2020

ABSTRACTThe sensory neocortex consists of hierarchically-organized areas reciprocally connected via feedforward and feedback circuits. Feedforward connections shape the receptive field properties of neurons in higher areas within parallel streams specialized in processing specific stimulus attributes. Feedback connections, instead, have been implicated in top-down modulations, such as attention, prediction and sensory context. However, their computational role remains unknown, partly because we lack knowledge about rules of feedback connectivity to constrain models of feedback function. For example, it is unknown whether feedback connections maintain stream-specific segregation, or integrate information across parallel streams. Using selective viral-mediated labeling of feedback connections arising from specific cytochrome-oxidase stripes of macaque visual area V2, we find that feedback to the primary visual cortex (V1) is organized into parallel streams resembling the reciprocal feedforward pathways. These results suggest that functionally-specialized V2 feedback channels modulate V1 responses to specific stimulus attributes, an organizational principle that could extend to feedback pathways in other sensory systems.
Genetic elucidation of complex biochemical traits mediating maize innate immunity
Authors: Ding Yezhang , Weckwerth Philipp R. , Poretsky Elly , Murphy Katherine M. , Sims James , Saldivar Evan , Christensen Shawn A. , Char Si Nian , Yang Bing , Tong Anh-dao , Shen Zhouxin , Kremling Karl A. , Buckler Edward S. , Kono Tom , Nelson David R. , Bohlmann Jörg , Bakker Matthew G. , Vaughan Martha M. , Khalil Ahmed S. , Betsiashvili Mariam , Briggs Steven P. , Zerbe Philipp , Schmelz Eric A. , Huffaker Alisa 
Published: March 2020

AbstractSpecialized metabolites constitute key layers of immunity underlying crop resistance; however, challenges in resolving complex pathways limit our understanding of their functions and applications. In maize (Zea mays) the inducible accumulation of acidic terpenoids is increasingly considered as a defense regulating disease resistance. To understand maize antibiotic biosynthesis, we integrated association mapping, pan-genome multi-omic correlations, enzyme structure-function studies, and targeted mutagenesis. We now define ten genes in three zealexin (Zx) gene clusters comprised of four sesquiterpene synthases and six cytochrome P450s that collectively drive the production of diverse antibiotic cocktails. Quadruple mutants blocked in the production of β-macrocarpene exhibit a broad-spectrum loss of disease resistance. Genetic redundancies ensuring pathway resiliency to single null mutations are combined with enzyme substrate-promiscuity creating a biosynthetic hourglass pathway utilizing diverse substrates andin vivocombinatorial chemistry to yield complex antibiotic blends. The elucidated genetic basis of biochemical phenotypes underlying disease resistance demonstrates a predominant maize defense pathway and informs innovative strategies for transferring chemical immunity between crops.
Detection of new Mycobacterium leprae subtype in Bangladesh by genomic characterization to explore transmission patterns
Authors: Tió-Coma Maria , Avanzi Charlotte , Verhard Els M. , Pierneef Louise , van Hooij Anouk , Benjak Andrej , Roy Johan Chandra , Khatun Marufa , Alam Khorshed , Corstjens Paul , Cole Stewart T. , Richardus Jan Hendrik , Geluk Annemieke 
Published: March 2020

AbstractMycobacterium leprae, the causative agent of leprosy, is an unculturable bacterium with a considerably reduced genome (3.27 Mb) compared to homologues mycobacteria from the same ancestry. M. leprae transmission is suggested to occur through aerosols but the exact mechanisms of infection remains unclear. In 2001, the genome of M. leprae was first described and subsequently four genotypes (1-4) and 16 subtypes (A-P) were identified providing means to study global transmission patterns for leprosy.We investigated M. leprae carriage as well as infection in leprosy patients (n=60) and healthy household contacts (HHC; n=250) from Bangladesh using molecular detection of the bacterial element RLEP in nasal swabs (NS) and slit skin smears (SSS). In parallel, we explored bacterial strain diversity by whole-genome sequencing (WGS) and Sanger sequencing.In the studied cohort in Bangladesh, M. leprae DNA was detected in 33.3% of NS and 22.2% of SSS of patients with bacillary index of 0 whilst in HHC 18.0% of NS and 12.3% of SSS were positive.The majority of the M. leprae strains detected in this study belonged to genotype 1D (55%), followed by 1A (31%). Importantly, WGS allowed the identification of a new M. leprae genotype, designated 1B-Bangladesh (14%), which clustered separately between the 1A and 1B strains. Moreover, we established that the genotype previously designated 1C, is not an independent subtype but clusters within the 1D genotype.Intraindividual differences were present between the M. leprae strains obtained including mutations in hypermutated genes, suggesting mixed colonization/infection or in-host evolution.In summary, we observed that M. leprae is present in asymptomatic contacts of leprosy patients fueling the concept that these individuals contribute to the current intensity of transmission. Our data therefore emphasize the importance of sensitive and specific tools allowing post-exposure prophylaxis targeted at M. leprae-infected or -colonized individuals.
Dicere Non Nocere: Public Disclosure of Identifiable Patient Information by Health Professionals on Social Media
Authors: Katz Matthew S. , Ahmed Wasim , Gutheil Thomas G. , Jagsi Reshma 
Published: March 2020

AbstractBackgroundRespecting patient privacy and confidentiality is critical for doctor-patient relationships and public trust in medical professionals. The frequency of potentially identifiable disclosures online during periods of active engagement is unknown. Our aim was to quantify potentially identifiable content shared by physicians and other health care providers on social media using the hashtag #ShareAStoryInOneTweet.MethodsWe used Symplur Signals software to access Twitter’s API and searched for tweets including the hashtag. We identified 1206 tweets by doctors, nurses, and other health professionals out of 43,374 tweets shared May 1-31, 2018. We evaluated tweet content in January 2019, eight months after the study period. To determine the incidence of sharing names or potentially identifiable information about patients, we performed a content analysis of the 754 tweets in which tweets disclosed information about others. We also evaluated whether participants raised concerns about privacy breaches and estimated the frequency of deleted tweets. We used dual, blinded coding for a 10% sample to estimate inter-coder reliability for potential identifiability of tweet content using Cohen’s kappa statistic.Results656 participants, including 486 doctors (74.1%) and 98 nurses (14.9%), shared 754 tweets disclosing information about others rather than themselves. Professional participants sharing stories about patient care disclosed the time frame in 95 (12.6%) and included patient names in 15 (2.0%) of tweets. We estimated that friends or families could likely identify the clinical scenario described in 32.1% of the 754 tweets. Among 348 tweets about potentially living patients, we estimated 162 (46.6%) were likely identifiable by patients. Inter-coder reliability in rating the potential identifiability demonstrated 86.8% agreement, with a Cohen’s Kappa of 0.8 suggesting substantial agreement Of the 1206 tweets we identified, 78 (6.5%) had been deleted on the website but were still viewable in the analytics software dataset.ConclusionsDuring periods of active sharing online, nurses, physicians, and other health professionals may sometimes share more information than patients or families might expect. More study is needed to determine whether similar events arise frequently online and to understand how to best ensure that patients’ rights are adequately respected.
The architecture of brain co-expression reveals the brain-wide basis of disease susceptibility
Authors: Hartl CL , Ramaswami G , Pembroke WG , Muller S , Pintacuda G , Saha A , Parsana P , Battle A , Lage K , Geschwind DH 
Published: March 2020

AbstractGene networks have proven their utility for elucidating transcriptome structure in the brain, yielding numerous biological insights. Most analyses have focused on expression relationships within a circumspect number of regions – how these relationships vary across a broad array of brain regions is largely unknown. By leveraging RNA-sequencing in 864 samples representing 12 brain regions in a cohort of 131 phenotypically normal individuals, we identify 12 brain-wide, 114 region-specific, and 50 cross-regional co-expression modules. We replicate the majority (81%) of modules in regional microarray datasets. Nearly 40% of expressed genes fall into brain-wide modules corresponding to major cell classes and conserved biological processes. Region-specific modules comprise 25% of expressed genes and correspond to region-specific cell types and processes, such as oxytocin signaling in the hypothalamus, or addiction pathways in the nucleus accumbens. We further leverage these modules to capture cell-type-specific lncRNA and gene isoforms, both of which contribute substantially to regional synaptic diversity. We identify enrichment of neuropsychiatric disease risk variants in brain wide and multi-regional modules, consistent with their broad impact on cell classes, and highlight specific roles in neuronal proliferation and activity-dependent processes. Finally, we examine the manner in which gene co-expression and gene regulatory networks reflect genetic risk, including the recently framed omnigenic model of disease architecture.
Undinarchaeota illuminate the evolution of DPANN archaea
Authors: Dombrowski Nina , Williams Tom A. , Sun Jiarui , Woodcroft Benjamin J. , Lee Jun-Hoe , Minh Bui Quang , Rinke Christian , Spang Anja 
Published: March 2020

Introductory paragraphThe evolution and diversification of Archaea is central to the history of life on Earth. Cultivation-independent approaches have revealed the existence of at least ten archaeal lineages whose members have small cell and genome sizes and limited metabolic capabilities and together comprise the tentative DPANN archaea. However, the phylogenetic diversity of DPANN and the placement of the various lineages of this group in the archaeal tree remain debated. Here, we reconstructed additional metagenome assembled genomes (MAGs) of a thus far uncharacterized archaeal phylum-level lineage UAP2 (CandidatusUndinarchaeota) affiliating with DPANN archaea. Comparative genome analyses revealed that members of the Undinarchaeota have small estimated genome sizes and, while potentially being able to conserve energy through fermentation, likely depend on partner organisms for the acquisition of vitamins, amino acids and other metabolites. Phylogenomic analyses robustly recovered Undinarchaeota as a major independent lineage between two highly supported clans of DPANN: one clan comprising Micrarchaeota, Altiarchaeota and Diapherotrites, and another encompassing all other DPANN. Our analyses also suggest that DPANN archaea may have exchanged core genes with their hosts by horizontal gene transfer (HGT), adding to the difficulty of placing DPANN in the archaeal tree. Together, our findings provide crucial insights into the origins and evolution of DPANN archaea and their hosts.
ebonyaffects pigmentation divergence and cuticular hydrocarbons inDrosophila americanaandD. novamexicana
Authors: Lamb Abigail M. , Wang Zinan , Simmer Patricia , Chung Henry , Wittkopp Patricia J. 
Published: March 2020

1AbstractDrosophilapigmentation has been a fruitful model system for understanding the genetic and developmental mechanisms underlying phenotypic evolution. For example, prior work has shown that divergence of thetangene contributes to pigmentation differences between two members of the virilis group:Drosophila novamexicana, which has a light yellow body color, andD. americana, which has a dark brown body color. Quantitative trait locus (QTL) mapping and expression analysis has suggested that divergence of theebonygene might also contribute to pigmentation differences between these two species. Here, we directly test this hypothesis by using CRISPR/Cas9 genome editing to generateebonynull mutants inD. americanaandD. novamexicanaand then using reciprocal hemizygosity testing to compare the effects of each species’ebonyallele on pigmentation. We find that divergence ofebonydoes indeed contribute to the pigmentation divergence between species, with effects on both the overall body color as well as a difference in pigmentation along the dorsal abdominal midline. Motivated by recent work inD. melanogaster, we also used theebonynull mutants to test for effects ofebonyon cuticular hydrocarbon (CHC) profiles. We found thatebonyaffects CHC abundance in both species, but does not contribute to qualitative differences in the CHC profiles between these two species. Additional transgenic resources for working withD. americanaandD. novamexicana, such aswhitemutants of both species andyellowmutants inD. novamexicana, were generated in the course of this work and are also described. Taken together, this study advances our understanding of loci contributing to phenotypic divergence and illustrates how the latest genome editing tools can be used for functional testing in non-model species.
Age-related differences in auditory cortex activity during spoken word recognition
Authors: Rogers Chad S. , Jones Michael S. , McConkey Sarah , Spehar Brent , Van Engen Kristin J. , Sommers Mitchell S. , Peelle Jonathan E. 
Published: March 2020

AbstractUnderstanding spoken words requires the rapid matching of a complex acoustic stimulus with stored lexical representations. The degree to which the brain networks supporting spoken word recognition are affected by adult aging remains poorly understood. In the current study we used fMRI to measure the brain responses to spoken words in two conditions: an attentive listening condition, in which no response was required, and a repetition task. Listeners were 29 young adults (aged 19–30 years) and 32 older adults (aged 65–81 years) without self-reported hearing difficulty. We found largely similar patterns of activity during word perception for both young and older adults, centered on bilateral superior temporal gyrus. As expected, the repetition condition resulted in significantly more activity in areas related to motor planning and execution (including premotor cortex and supplemental motor area) compared to the attentive listening condition. Importantly, however, older adults showed significantly less activity in probabilistically-defined auditory cortex than young adults when listening to individual words in both the attentive listening and repetition tasks. Age differences in auditory cortex activity were seen selectively for words (no age differences were present for 1-channel vocoded speech, used as a control condition), and could not be easily explained by accuracy on the task, movement in the scanner, or hearing sensitivity (available on a subset of participants). These findings indicate largely similar patterns of brain activity for young and older adults when listening to words in quiet, but suggest less recruitment of auditory cortex by the older adults.
Phosphorylation by Aurora B kinase regulates caspase-2 activity and function
Authors: Lim Yoon , De Bellis Dylan , Sandow Jarrod J. , Capalbo Luisa , D’Avino Pier Paolo , Murphy James M. , Webb Andrew I. , Dorstyn Loretta , Kumar Sharad 
Published: March 2020

AbstractMitotic catastrophe (MC) is an important oncosuppressive mechanism that serves to eliminate cells that become polyploid or aneuploidy due to aberrant mitosis. Previous studies have demonstrated that the activation and catalytic function of caspase-2 are key steps in MC to trigger apoptosis and/or cell cycle arrest of mitotically defective cells. However, the molecular mechanisms that regulate caspase-2 activation and its function are unclear. Here we identify six new phosphorylation sites in caspase-2 and show that a key mitotic kinase, Aurora B kinase (AURKB), phosphorylates caspase-2 at the highly conserved residue S384. We demonstrate that phosphorylation at S384 blocks caspase-2 catalytic activity and apoptosis function in response to mitotic insults, without affecting caspase-2 dimerisation. Moreover, molecular modelling suggests that phosphorylation at S384 may affect substrate binding by caspase-2. We propose that caspase-2 S384 phosphorylation by AURKB is a key mechanism that controls caspase-2 activation during mitosis.
Differentiation reveals the plasticity of age-related change in murine muscle progenitors
Authors: Kimmel Jacob C. , Hendrickson David G. , Kelley David R. 
Published: March 2020

AbstractSkeletal muscle experiences a decline in lean mass and regenerative potential with age, in part due to intrinsic changes in progenitor cells. However, it remains unclear if age-related changes in progenitors persist across a differentiation trajectory or if new age-related changes manifest in differentiated cells. To investigate this possibility, we performed single cell RNA-seq on muscle mononuclear cells from young and aged mice and profiled muscle stem cells (MuSCs) and fibro/adipose progenitors (FAPs) after differentiation. Differentiation increased the magnitude of age-related change in MuSCs and FAPs, but also masked a subset of age-related changes present in progenitors. Using a dynamical systems approach and RNA velocity, we found that aged MuSCs follow the same differentiation trajectory as young cells, but stall in differentiation near a commitment decision. Our results suggest that age-related changes are plastic across differentiation trajectories and that fate commitment decisions are delayed in aged myogenic cells.
Multicellular feedback control of a genetic toggle-switch in microbial consortia
Authors: Fiore Davide , Salzano Davide , Cristòbal-Cóppulo Enric , Olm Josep M. , di Bernardo Mario 
Published: March 2020

AbstractWe describe a multicellular approach to control a target cell population endowed with a bistable toggle-switch. The idea is to engineer a synthetic microbial consortium consisting of three different cell populations. In such a consortium, two populations, the Togglers, responding to some reference input, can induce the switch of a bistable memory mechanism in a third population, the Targets, so as to activate or deactivate some additional functionalities in the cells. Communication among the three populations is established by orthogonal quorum sensing molecules that are used to close a feedback control loop across the populations. The control design is validated via in-silico experiments in BSim, a realistic agent-based simulator of bacterial populations.