bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new member in the Argonaute crew: the mt-miRNAs
Authors: Pozzi Andrea , Dowling Damian K. 
Published: February 2020

SummaryMutations within the mitochondrial genome have been linked to many diverse phenotypes. Moreover, the effects of these mutations have been shown to differ across sexes and environments. The mechanisms that explain the manifold array of mitochondrial genotypic effects on organismal function, and their context-dependency, have however remained a mystery. Here, we present evidence that mitochondria are involved in nuclear gene regulation via RNA interference; transcribing mitochondrial (mt-)miRNAs that may repress the transcription of nuclear genes that previously had no known involvement in mitochondrial function. Our findings uncover a new mechanism by which mitochondria may shape the expression of animal life-histories and health components; implying that the influence of the mitochondria in regulating organismal function extends well beyond the process of energy production.
Distinct regionalization patterns of cortical morphology are associated with cognitive performance across different domains
Authors: Palmer C E , Zhao W , Loughnan R , Zou J , Fan C C , Thompson W K , Dale A M , Jernigan T L 
Published: February 2020

ABSTRACTCognitive performance in children is predictive of academic and social outcomes; therefore, understanding neurobiological mechanisms underlying individual differences in cognition during development may be important for improving quality of life. The belief that a single, psychological construct underlies many cognitive processes is pervasive throughout society. However, it is unclear if there is a consistent neural substrate underlying many cognitive processes. Here we show that a distributed configuration of cortical surface area and apparent thickness, when controlling for global imaging measures, is differentially associated with cognitive performance on different types of tasks in a large sample (N=10,145) of 9-11 year old children from the Adolescent Brain and Cognitive DevelopmentSM(ABCD) study. The minimal overlap in these regionalization patterns of association has implications for competing theories about developing intellectual functions. Surprisingly,notcontrolling for sociodemographic factors increased the similarity between these regionalization patterns. This highlights the importance of understanding the shared variance between sociodemographic factors, cognition and brain structure, particularly with a population-based sample such as ABCD.
Maternal antibodies to gliadin and autism spectrum disorders in offspring - A population-based case-control study in Sweden
Authors: Gardner Renee , Samuelsson Ida , Severance Emily G. , Sjöqvist Hugo , Yolken Robert H. , Dalman Christina , Karlsson Håkan 
Published: February 2020

AbstractObjectiveIndividuals diagnosed with autism spectrum disorders (ASD) are reported to have higher levels of antibodies directed towards gliadin, a component of wheat gluten. However, no study has examined such antibodies in etiologically-relevant periods before diagnosis. The objective of this study is to investigate if maternal levels of immunoglobulin G antibodies directed at gliadin, during pregnancy and at the time of birth, are associated with ASD in offspring.MethodsIn this population-based study set in Sweden with 921 ASD cases and 1090 controls, we analyzed levels of anti-gliadin antibodies (AGA) in archived neonatal dried blood spots (NDBS, as maternal IgG is transferred to the fetus) and in paired maternal sera collected earlier in pregnancy for a subset of 547 cases and 428 controls. We examined associations to any ASD diagnosis and considering common comorbidities (i.e. intellectual disability [ID] and attention-deficit/hyperactivity disorder [ADHD]). We compared 206 ASD cases to their unaffected siblings to examine the potential for confounding by shared familial factors.ResultsHigh levels (≥90thpercentile) of maternal AGA were associated with decreased odds of ASD, particularly ASD with comorbid ID, when measured in NDBS (OR 0.51, 95% CI 0.30–0.87) with a similar trend in maternal sera (0.55, 0.24-1.29). High levels of maternal AGA were similarly associated with lower odds of ASD with ID in the sibling comparison.ConclusionsThis first study of exposure to AGA in the pre- and perinatal periods suggests that high levels of maternal AGA are associated with lower odds of ASD with ID.
Quantifying microbially mediated fitness differences reveals the tendency for plant-soil feedbacks to drive species exclusion among California annual plants
Authors: Kandlikar Gaurav S. , Yan Xinyi , Levine Jonathan M. , Kraft Nathan J.B. 
Published: February 2020

AbstractSoil microorganisms influence a variety of processes in plant communities. Many the-oretical and empirical studies have shown that dynamic feedbacks between plants and soil microbes can stabilize plant coexistence by generating negative frequency-dependent plant population dynamics. However, inferring the net effects of soil microbes on plant coexistence requires also quantifying the degree to which they provide one species an average fitness advantage, an effect that has received little empirical attention. We conducted a greenhouse study to quantify microbially mediated stabilization and fitness differences among fifteen pairs of annual plants that co-occur in southern California grasslands. We found that although soil microbes frequently generate negative frequency-dependent dynamics that stabilize plant interactions, they simultaneously mediate large average fitness differences between species. The net result is that if the plant species are otherwise competitively equivalent, the impact of plant-soil feedbacks is often to favor species exclusion over coexistence, a result that only becomes evident by quantifying the microbially mediated fitness difference. Our work highlights that comparing the stabilizing effects of plant-soil feedbacks to the fitness difference they generate is essential for understanding the influence of soil microbes on plant diversity.
THEHOK/SOKTOXIN/ANTITOXIN LOCUS ENHANCES BACTERIAL SUSCEPTIBILITY TO DOXYCYCLINE
Authors: Chukwudi Chinwe U. , Good Liam 
Published: February 2020

AbstractThe antibacterial efficacy of the tetracycline antibiotics has been greatly reduced by the development of resistance, hence a decline in their clinical use as antibiotics. Thehok/soklocus is a type I toxin/antitoxin plasmid stability element, often associated with multi-drug resistance plasmids, especially ESBL-encoding plasmids. It enhances host cell survivability and pathogenicity in stressful growth conditions, and particularly increases bacterial tolerance to β-lactam antibiotics. Thehok/soklocus forms dsRNA by RNA:RNA interactions of the toxin and antitoxin, and doxycycline has been reported to bind and inhibit dsRNA cleavage/processing. This study investigated the antibacterial efficacy of doxycycline in hok/sok host bacteria cells, the effect onhok/sok-induced growth changes and the potential mechanism of the observed changes. Different strains ofE. coliwith growth characteristics affected by thehok/soklocus were transformed withhok/sokplasmids, and assessed for doxycycline susceptibility and growth changes. The results show that thehok/soklocus increases bacterial susceptibility to doxycycline, especially in strains with more pronouncedhok/sokgrowth effects. The increased doxycycline susceptibility occurs despite β-lactam resistance imparted byhok/sok. Doxycycline was found to induce bacterial death in a manner phenotypically characteristic of Hok toxin expression, suggesting that it inhibits the toxin/antitoxin dsRNA degradation, leading to Hok toxin expression and cell death. In this way, doxycycline could be used to counteract the multi-drug resistance plasmid maintenance/propagation and pathogenicity mechanisms associated with thehok/soklocus. This has great potentials in the global war to contain the rise in antimicrobial resistance.
Tol-Pal system and Rgs proteins interact to promote unipolar growth and cell division inSinorhizobium meliloti
Authors: Krol Elizaveta , Yau Hamish C. L. , Lechner Marcus , Schäper Simon , Bange Gert , Vollmer Waldemar , Becker Anke 
Published: February 2020

ABSTRACTSinorhizobium melilotiis an α-proteobacterium belonging to the Rhizobiales. Bacteria from this order elongate their cell wall at the new cell pole, generated by cell division. Screening for protein interaction partners of the previously characterized polar growth factors RgsP and RgsM, we identified the inner membrane components of the Tol-Pal system (TolQ and TolR) and novel Rgs (rhizobial growth and septation) proteins with unknown functions. TolQ, Pal and all Rgs proteins, except for RgsE, were indispensable forS. meliloticell growth. Six of the Rgs proteins, TolQ and Pal localized to the growing cell pole in the cell elongation phase and to the septum in pre-divisional cells, and three Rgs proteins localized to growing cell pole only. The FtsN-like protein RgsS contains a conserved SPOR domain and is indispensable at the early stages of cell division. The components of the Tol-Pal system were required at the late stages of cell division. RgsE, a homolog of theAgrobacterium tumefaciensgrowth pole ring protein GPR, has an important role in maintaining the normal growth rate and rod cell shape. RgsD is a novel periplasmic protein with the ability to bind peptidoglycan. Analysis of the phylogenetic distribution of novel Rgs proteins showed that they are conserved in Rhizobiales and mostly absent from other α-proteobacterial orders, suggesting a conserved role of these proteins in polar growth.IMPORTANCEBacterial cell proliferation involves cell growth and septum formation followed by cell division. For cell growth, bacteria have evolved different complex mechanisms. The most prevalent growth mode of rod shaped bacteria is cell elongation by incorporating new peptidoglycan in a dispersed manner along the sidewall. A small share of rod-shaped bacteria, including the α-proteobacterial Rhizobiales, grow unipolarly. Here, we identified and initially characterized a set of Rgs (rhizobial growth and septation) proteins, which are involved in cell division and unipolar growth ofSinorhizobium melilotiand highly conserved in Rhizobiales. Our data expand the knowledge of components of the polarly localized machinery driving cell wall growth and suggest a complex of Rgs proteins with components of the divisome, differing in composition between the polar cell elongation zone and the septum.
A resurrection study reveals limited evolution of thermal performance in response to recent climate change across the geographic range of the scarlet monkeyflower
Authors: Wooliver Rachel , Tittes Silas B. , Sheth Seema N. 
Published: February 2020

AbstractEvolutionary rescue can prevent populations from declining under climate change, and should be more likely at high-latitude, “leading” edges of species’ ranges due to greater temperature anomalies and gene flow from warm-adapted populations. Using a resurrection study with seeds collected before and after a seven-year period of record warming, we tested for thermal adaptation in the scarlet monkeyflowerMimulus cardinalis. We grew ancestors and descendants from northern-edge, central, and southern-edge populations across eight temperatures. Despite recent climate anomalies, populations showed limited evolution of thermal performance curves. However, one southern population evolved a narrower thermal performance breadth by 1.25 °C, which matches the direction and magnitude of the average decrease in seasonality experienced. Consistent with the climate variability hypothesis, thermal performance breadth increased with temperature seasonality across the species’ geographic range. Inconsistent with performance trade-offs between low and high temperatures across populations, we did not detect a positive relationship between thermal optimum and mean temperature. These findings fail to support the hypothesis that evolutionary response to climate change is greatest at the leading edge, and suggest that the evolution of thermal performance is unlikely to rescue most populations from the detrimental effects of rapidly changing climate.
Unified Methods for Feature Selection in Large-Scale Genomic Studies with Censored Survival Outcomes
Authors: Spirko-Burns Lauren , Devarajan Karthik 
Published: February 2020

AbstractOne of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease’s process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards (PH), which is unlikely to hold for each feature. When applied to genomic features exhibiting some form of non-proportional hazards (NPH), these methods could lead to an under- or over-estimation of the effects. We propose a broad array of marginal screening techniques that aid in feature ranking and selection by accommodating various forms of NPH. First, we develop an approach based on Kullback-Leibler information divergence and the Yang-Prentice model that includes methods for the PH and proportional odds (PO) models as special cases. Next, we proposeR2indices for the PH and PO models that can be interpreted in terms of explained randomness. Lastly, we propose a generalized pseudo-R2measure that includes PH, PO, crossing hazards and crossing odds models as special cases and can be interpreted as the percentage of separability between subjects experiencing the event and not experiencing the event according to feature expression. We evaluate the performance of our measures using extensive simulation studies and publicly available data sets in cancer genomics. We demonstrate that the proposed methods successfully address the issue of NPH in genomic feature selection and outperform existing methods. The proposed information divergence,R2and pseudo-R2measures were implemented in R (www.R-project.org) and code is available upon request.
PhyRepID: a comparative phylogenomics approach for large-scale quantification of protein repeat evolution
Authors: van Belzen I.A.E.M. , Deutekom E. S. , Snel B. 
Published: February 2020

AbstractProtein repeats consisting of domains or motifs are involved in key biological processes such as neural development, host-pathogen interactions, and speciation. Expansion and contraction of these repeats can strongly impact protein function as was shown for KNL1 and PRDM9. However, these known cases could only be identified manually and were previously incorrectly reported as conserved in large-scale analyses, because signatures of repeat evolution are difficult to resolve automatically.We developed PhyRepID to compare protein domain repeat evolution and analysed 4939 groups of orthologous proteins (OGs) from 14 vertebrate species. Our main contributions are 1) detecting a wide scope of repeats consisting of Pfam structural domains and motifs, 2) improving sensitivity and precision of repeat unit detection through optimization for the OGs, 3) using phylogenetic analysis to detect evolution within repeat regions. From these phylogenetic signals, we derived a “protein repeat duplication” (PRD) score that quantifies evolution in repeat regions and thereby enables large-scale comparison of protein families. Zinc finger repeats show remarkably fast evolution, comprising 25 of 100 fastest evolving proteins in our dataset, whilst cooperatively-folding domain repeats like beta-propellers are mostly conserved. Motif repeats have a similar PRD score distribution as domain repeats and also show a large diversity in evolutionary rates. A ranking based on the PRD score reflects previous manual observations of both highly conserved (CDC20) and rapidly evolving repeats (KNL1, PRDM9) and proposes novel candidates (e.g. AHNAK, PRX, SPATA31) showing previously undescribed rapid repeat evolution. PhyRepID is available onhttps://github.com/ivanbelzen/PhyRepID/.
HIV-1-infected human macrophages, by secreting RANKL, contribute to enhanced osteoclastogenesis
Authors: Mascarau Rémi , Bertrand Florent , Labrousse Arnaud , Gennero Isabelle , Poincloux Renaud , Maridonneau-Parini Isabelle , Raynaud-Messina Brigitte , Vérollet Christel 
Published: February 2020

AbstractHIV-1 infection is frequently associated with low bone density, which can progress to osteoporosis leading to a high risk of fractures. Only a few mechanisms have been proposed to explain the enhanced osteolysis in the context of HIV-1 infection. As macrophages are involved in bone homeostasis and are critical cell hosts for HIV-1, we asked whether HIV-1-infected macrophages could participate in bone degradation. Upon infection, human macrophages acquired some osteoclast features: they became multinucleated, upregulated the osteoclast markers RhoE and β3 integrin, and organized their podosomes as ring superstructures resembling osteoclast sealing zones. However, HIV-1 infected macrophages were not fully differentiated in osteoclasts as they did not upregulate NFATc-1 transcription factor and were unable to degrade bone. Investigating whether infected macrophages participate indirectly to virus-induced osteolysis, we showed that they produce RANKL, the key osteoclastogenic cytokine. RANK-L secreted by HIV-1-infected macrophages was not sufficient to stimulate multinucleation, but promoted the protease-dependent migration of osteoclast precursors. In conclusion, we propose that, by stimulating RANKL secretion, HIV-1-infected macrophages contribute to create a microenvironment that favors the recruitment of osteoclasts, participating to bone disorders observed in HIV-1+patients.
Fine-scale computations for adaptive processing in the human brain
Authors: Zamboni E , Kemper VG , Goncalves NR , Jia K , Karlaftis VM , Bell SJ , Giorgio JJ , Rideaux R , Goebel R , Kourtzi Z 
Published: February 2020

AbstractAdapting to the environment statistics by reducing brain responses to repetitive sensory information is key for efficient information processing. Yet, the fine-scale computations that support this adaptive processing in the human brain remain largely unknown. Here, we capitalize on the sub-millimetre resolution afforded by ultra-high field imaging to examine BOLD-fMRI signals across cortical depth and discern competing hypotheses about the brain mechanisms (feedforward vs. feedback) that mediate adaptive visual processing. We demonstrate suppressive recurrent processing within visual cortex, as indicated by stronger BOLD decrease in superficial than middle and deeper layers for gratings that were repeatedly presented at the same orientation. Further, we show dissociable connectivity mechanisms for adaptive processing: enhanced feedforward connectivity within visual cortex, while feedback occipito-parietal connectivity, reflecting top-down influences on visual processing. Our findings provide evidence for a circuit of local recurrent and feedback interactions that mediate rapid brain plasticity for adaptive information processing.
Conditional Analysis Cakewalk
Authors: French Jennifer N. , Gaynor Brady J. , Perry James A. 
Published: February 2020

AbstractSummarySequential conditional analysis is an important tool for identifying the unique signals in single-variant association analysis between genomic variants and various phenotypic outcomes. With large datasets, it is tedious and time-consuming to manually run the sequential steps which require the association analysis, computation of linkage disequilibrium (LD) between the variants, generation of a visualization graphic, and identification of the “top hit” to be inserted as an additional covariate for the next iteration. The Conditional Analysis Cakewalk automates this process, making it easy and fast, while only requiring user input in the initial configuration steps.Availability and ImplementationThe Conditional Analysis Cakewalk is implemented as a Linux shell script utilizing MMAP or PLINK and LocusZoom. Source code and documentation are available athttps://github.com/jennetics/Cakewalk.
TRMIntegrins CD103 and CD49a Differentially Support Adherence and Motility After Resolution of Influenza Virus Infection
Authors: Reilly Emma C , Emo Kris Lambert , Buckley Patrick M , Reilly Nicholas S , Chaves Francisco A , Yang Hongmei , Oakes Patrick W , Topham David J 
Published: February 2020

AbstractTissue resident memory CD8 T (TRM) cells are a unique immune memory subset that develops and remains in peripheral tissues at the site of infection, providing future host resistance upon re-exposure to that pathogen. In the pulmonary system, TRMare identified through S1P antagonist CD69 and expression of integrins CD103/β7 and CD49a/CD29(β1). Contrary to the established role of CD69 on CD8 T cells, the functions of CD103 and CD49a on this population are not well defined. This study examines the expression patterns and functions of CD103 and CD49a with a specific focus on their impact on T cell motility during influenza virus infection. We show that the TRMcell surface phenotype develops by two-weeks post-infection and that each integrin contributes a distinct function regulating CD8 T cell motility bothin vitroandin vivo, with CD49a facilitating migration and CD103 limiting motility through tethering. These results demonstrate for the first time how CD103 and CD49a differentially impact adherence and migration in the tissue, likely affecting overall retention, maintenance of TRM, and host protection.Significance StatementCurrent influenza vaccination strategies require annual immunizations, with fairly low efficacy rates. One technique to improve protection against a greater breadth of influenza viruses is to elicit broadly cross-reactive cell-mediated immunity and generate a local population of cytotoxic T cells to respond to conserved regions of circulating viruses. However, this approach requires improved understanding of how these cells migrate within and attach to the tissue, in order to persist and offer long-term immunity. This study investigates how receptors on the T cell surface impact the cell’s ability to interact with the tissue and provide evidence for which of these receptors are essential for protection. Furthermore, these studies reveal functionalin vivomechanisms of cellular markers used to characterize TRM.
ATRIP protects progenitor cells against DNA damagein vivo
Authors: Matos-Rodrigues Gabriel E. , Grigaravicius Paulius , Lopez Bernard S. , Hofmann Thomas , Frappart Pierre-Olivier , Martins Rodrigo A. P. 
Published: February 2020

AbstractThe maintenance of genomic stability during the cell cycle of progenitor cells is essential for the faithful transmission of genetic information. Mutations in genes that ensure genome stability lead to human developmental syndromes. Mutations in Ataxia Telangiectasia and Rad3-related (ATR) or in ATR-interacting protein (ATRIP) lead to Seckel syndrome, which is characterized by developmental malformations and short life expectancy. While the roles of ATR in replicative stress response and chromosomal segregation are well established, it is unknown how ATRIP contributes to maintaining genomic stability in progenitor cellsin vivo. Here, we generated the first mouse model to investigate ATRIP function. Conditional inactivation ofAtripin progenitor cells of the CNS and eye led to microcephaly, microphthalmia and postnatal lethality. To understand the mechanisms underlying these malformations, we used lens progenitor cells as a model and found that ATRIP loss promotes replicative stress and TP53-dependent cell death.Trp53inactivation inAtrip-deficient progenitor cells rescued apoptosis but increased mitotic DNA damage and mitotic defects. Our findings demonstrate an essential role of ATRIP in preventing DNA damage accumulation during unchallenged replication.