bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neighbor GWAS: incorporating neighbor genotypic identity into genome-wide association studies of field herbivory
Authors: Sato Yasuhiro , Yamamoto Eiji , Shimizu Kentaro K. , Nagano Atsushi J. 
Published: November 2019

ABSTRACTAn increasing number of field studies have shown that the phenotype of an individual plant depends not only on its genotype but also on those of neighboring plants; however, this fact is not taken into consideration in genome-wide association studies (GWAS). Based on the Ising model of ferromagnetism, we incorporated neighbor genotypic identity into a regression model, named “Neighbor GWAS”. Our simulations showed that the effective range of neighbor effects could be estimated using an observed phenotype from when the proportion of phenotypic variation explained (PVE) by neighbor effects peaked. The spatial scale of the first nearest neighbors gave the maximum power to detect the causal variants responsible for neighbor effects, unless their effective range was too broad. However, if the effective range of the neighbor effects was broad and minor allele frequencies were low, there was collinearity between the self and neighbor effects. To suppress the false positive detection of neighbor effects, the fixed effect and variance components involved in the neighbor effects should be tested in comparison with a standard GWAS model. We applied neighbor GWAS to field herbivory data from 199 accessions of Arabidopsis thaliana and found that neighbor effects explained 8% more of the PVE of the observed damage than standard GWAS. The neighbor GWAS method provides a novel tool that could facilitate the analysis of complex traits in spatially structured environments and is available as an R package at CRAN (https://cran.rproject.org/package=rNeighborGWAS).
Light dependent activation of the GCN2 kinase under cold and salt stress is mediated by the photosynthetic status of the chloroplast
Authors: Lokdarshi Ansul , Morgan Philip W. , Franks Michelle , Emert Zoe , Emanuel Catherine , von Arnim Albrecht G 
Published: November 2019

ABSTRACTRegulation of cytosolic mRNA translation is a key node for rapid adaptation to environmental stress conditions. In yeast and animals, phosphorylation of the α-subunit of eukaryotic translation initiation factor eIF2 is the most thoroughly characterized event in regulating global translation under stress. In plants, the GCN2 kinase (General Control Non-derepressible-2) is the only known kinase for eIF2α. GCN2 is activated under a variety of stresses including reactive oxygen species. Here we provide new evidence that the GCN2 kinase in Arabidopsis is also activated rapidly and in a light dependent manner by cold and salt treatments. These treatments alone did not repress global mRNA ribosome loading in a major way. The activation of GCN2 was attenuated by inhibitors of photosynthesis and antioxidants, suggesting that it is gated by the redox poise or the reactive oxygen status of the chloroplast. In keeping with these results, gcn2 mutant seedlings were more sensitive than wild type to both cold and salt in a root elongation assay. These data suggest that cold and salt stress may both affect the status of the cytosolic translation apparatus via the conserved GCN2-eIF2α module. The potential role of the GCN2 kinase pathway in the global repression of translation under abiotic stress will be discussed.
Climate associated genetic variation in Fagus sylvatica and potential responses to climate change in the French Alps
Authors: Capblancq Thibaut , Morin Xavier , Gueguen Maya , Renaud Julien , Lobreaux Stéphane , Bazin Eric 
Published: November 2019

ABSTRACTLocal adaptation patterns have been found in many plants and animals, highlighting the genetic heterogeneity of species along their range of distribution. In the next decades, global warming must induce a change in the selective pressures that drive this adaptive variation, forcing a reshuffling of the underlying adaptive allele distributions. For species with low dispersion capacity and long generation time such as trees, the rapidity of the change could imped the migration of beneficial alleles and lower their capacity to track the changing environment. Identifying the main selective pressures driving the adaptive genetic variation is thus necessary when investigating species capacity to respond to global warming. In this study, we investigate the adaptive landscape of Fagus sylvatica along a gradient of populations in the French Alps. Using a ddRAD-seq approach, we identified 7,000 SNPs from 570 individuals across 36 different sites. An RDA-derived method allowed us to identify several SNPs that were strongly associated with climatic gradients; moreover, we defined the primary selective gradients along the natural populations of F. sylvatica in the Alps. Strong effects of elevation and humidity, which contrast north-western and south-eastern site, were found and were believed to be important drivers of genetic adaptation. Finally, simulations of future genetic landscapes that used these findings predicted a severe range contraction and a shift towards higher altitudes for F. sylvatica in the Alps and allowed to identify populations at risk, which could be helpful for future management plans.
Microbe-metabolite associations linked to the rebounding murine gut microbiome post-colonization with vancomycin resistant Enterococcus faecium
Authors: Mu Andre , Carter Glen P. , Li Lucy , Isles Nicole S. , Vrbanac Alison F. , Morton James T. , Jarmusch Alan K. , De Souza David P. , Narayana Vinod K. , Kanojia Komal , Nijagal Brunda , McConville Malcolm J. , Knight Rob , Howden Benjamin P. , Stinear Timothy P. 
Published: November 2019

AbstractVancomycin resistant Enterococcus faecium (VREfm) is an emerging antibiotic resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed amplicon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenerricutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone, and to subsequent VREfm challenge. Using neural networking approaches to find co-occurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides, indicative of a transition towards a pre-antibiotic naïve microbiome. This study shows the impacts of antibiotics on the gut ecosystem, and the progression of the microbiome in response to colonisation with VREfm. Our results offer insights towards identifying potential non-antibiotic alternatives to eliminate VREfm through metabolic re-engineering to preferentially select for Bacteroides.ImportanceThis study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.
Cluster-permutation statistical analysis for high-dimensional brain-wide functional connectivity mapping
Authors: Sanchez-Bornot Jose M. , Lopez Maria E. , Bruña Ricardo , Maestu Fernando , Youssofzadeh Vahab , Yang Su , McLean Paula L. , Prasad Girijesh , Wong-Lin KongFatt 
Published: November 2019

AbstractBrain functional connectivity (FC) analyses based on magnetoencephalographic (MEG) signals have yet to exploit the intrinsic high-dimensional information. Typically, these analyses are constrained to regions of interest to avoid the curse of dimensionality, which leads to conservative hypothesis testing. We removed such constraint by extending cluster-permutation statistics for high-dimensional MEG-FC analyses. We demonstrated the feasibility of this approach by identifying MEG-FC resting-state changes in mild cognitive impairment (MCI), a prodromal stage of Alzheimer’s disease. We found dense clusters of increased connectivity strength in MCI compared to healthy controls (hypersynchronization), in delta (1-4 Hz) and higher-theta (6-8 Hz) bands oscillations. These clusters mainly consisted of interactions between occipitofrontal and occipitotemporal regions in the left hemisphere and could potentially be used as neuromarkers of early progression in Alzheimer’s disease. Our novel approach can be used to generate high-resolution statistical FC maps for neuroimaging studies in general.
Ultrasound Echogenicity is Associated with Achilles Tendon Fatigue Damage in a Cadaveric Loading Model
Authors: Schmidt Elaine C. , Hullfish Todd J. , O’Connor Kathryn M. , Hast Michael W. , Baxter Josh R. 
Published: November 2019

ABSTRACTAchilles tendon disorders are among the most difficult sports-related injuries to predict with current diagnostic tools. The purpose of this study was to identify a clinically useful marker for early tendon damage. We hypothesized that alterations in mean echogenicity are linked with changes in vitro tendon mechanics. To test our hypothesis, we harvested Achilles tendons from 10 fresh-frozen cadaveric feet and cyclically fatigued them using a universal test frame while we continuously acquired ultrasound images. Throughout this fatigue protocol, we applied 2 stress tests every 500 loading cycles to quantify changes in ultrasound imaging echogenicity. We continued this fatigue protocol until each tendon either failed completely or survived 150,000 cycles. Tendons that failed during the fatigue loading (6/10) underwent greater changes in mean echogenicity compared to tendons that did not fail (P = 0.031). These tendons that failed during fatigue loading demonstrated greater changes in mean echogenicity that surpassed 1.0%; whereas survivor tendons exhibited less than 0.5% changes in mean echogenicity. We found that changes in mean echogenicity measured with ultrasound increased proportionally with increased tendon damage. The magnitude of these changes was relatively small (<1.5% change in mean echogenicity) but may be an effective predictor of tendon failure. Mean echogenicity is a promising marker for quantifying fatigue damage in cadaveric Achilles tendons during a stress test. Although these changes cannot be detected with the naked eye, computer-based predictive models may effectively assess risk of tendon damage in physically active adults.Level of evidenceControlled laboratory experiment
FtsW exhibits distinct processive motions driven by either septal cell wall synthesis or FtsZ treadmilling in E. coli
Authors: Yang Xinxing , McQuillen Ryan , Lyu Zhixin , Phillips-Mason Polly , De La Cruz Ana , McCausland Joshua W. , Liang Hai , DeMeester Kristem E. , Santiago Cintia C. , Grimes Catherine L. , de Boer Piet , Xiao Jie 
Published: November 2019

AbstractDuring bacterial cell division, synthesis of new septal peptidoglycan (sPG) is crucial for successful cytokinesis and cell pole morphogenesis. FtsW, a SEDS (Shape, Elongation, Division and Sporulation) family protein and an indispensable component of the cell division machinery in all walled bacterial species, was recently identified in vitro as a new monofunctional peptidoglycan glycosyltransferase (PGTase). FtsW and its cognate monofunctional transpeptidase (TPase) class B penicillin binding protein (PBP3 or FtsI in E. coli) may constitute the essential, bifunctional sPG synthase specific for new sPG synthesis. Despite its importance, the septal PGTase activity of FtsW has not been documented in vivo. How its activity is spatiotemporally regulated in vivo has also remained unknown. Here we investigated the septal PGTase activity and dynamics of FtsW in E. coli cells using a combination of single-molecule imaging and genetic manipulations. We show that FtsW exhibits robust activity to incorporate an N-acetylmuramic acid analog at septa in the absence of other known PGTases, confirming FtsW as the essential septum-specific PGTase in vivo. Notably, we identified two populations of processive moving FtsW molecules at septa. A fast-moving population is driven by the treadmilling dynamics of FtsZ and independent of sPG synthesis. A slow-moving population is driven by active sPG synthesis and independent of FtsZ’s treadmilling dynamics. We further identified that FtsN, a potential sPG synthesis activator, plays an important role in promoting the slow-moving, sPG synthesis-dependent population. Our results support a two-track model, in which inactive sPG synthase molecules follow the fast treadmilling “Z-track” to be distributed along the septum; FtsN promotes their release from the “Z-track” to become active in sPG synthesis on the slow “sPG-track”. This model explains how the spatial information is integrated into the regulation of sPG synthesis activity and suggests a new mechanistic framework for the spatiotemporal coordination of bacterial cell wall constriction.
Head Stabilization During Standing in People with Persisting Symptoms after Mild Traumatic Brain Injury
Authors: Fino Peter C. , Raffegeau Tiphanie E , Parrington Lucy , Peterka Robert J , King Laurie A. 
Published: November 2019

ABSTRACTIncreased postural sway is often observed in people with mild traumatic brain injury (mTBI), but our understanding of how individuals with mTBI control their head during stance is limited. The purpose of this study was to determine if people with mTBI exhibit increased sway at the head compared with healthy controls. People with persisting symptoms after mTBI (n = 59, 41 women) and control participants (n = 63, 38 women) stood quietly for one minute in four conditions: eyes open on a firm surface (EO-firm), eyes closed on a firm surface (EC-firm), eyes open on a foam pad (EO-foam), and eyes closed on foam (EC-foam). Inertial sensors at the head, sternum, and lumbar region collected tri-axial accelerations. Root-mean-square (RMS) accelerations in anteroposterior (AP) and mediolateral (ML) directions. Sway ratios between the head and sternum, head and lumbar, and sternum and lumbar region, were compared between groups. Temporal coupling of anti-phase motion between the upper and lower body angular accelerations was assessed with magnitude squared coherence and cross-spectral phase angles. People with mTBI demonstrated greater sway than controls across conditions and directions. During foam-surface conditions, the control group, but not the mTBI group, reduced ML sway at their head and trunk relative to their lumbar by increasing the expression of an anti-phase hip strategy within the frontal plane. These results are consistent with suggestions of inflexible or inappropriate postural control in people with mTBI.
Transcription factors protect from DNA re-methylation during reprograming of primordial germ cells and pre-implantation embryos
Authors: Kremsky Isaac , Corces Victor G. 
Published: November 2019

AbstractA growing body of evidence suggests that certain phenotypic traits of epigenetic origin can be passed across generations via both the male and female germlines of mammals. These observations have been difficult to explain owing to a global loss of the majority of known epigenetic marks present in parental chromosomes during primordial germ cell development and after fertilization. By integrating previously published BS-seq, DNase-seq, ATAC-seq, and RNA-seq data collected during multiple stages of primordial germ cell and preimplantation development, we find that the methylation status of the majority of CpGs genome-wide is restored after global reprogramming, despite the fact that global CpG methylation drops to 10% in primordial germ cells and 20% in the inner cell mass of the blastocyst. We estimate the proportion of such CpGs with preserved methylation status to be 78%. Further, we find that CpGs at sites bound by transcription factors during the global re-methylation phases of germ line and embryonic development remain hypomethylated across all developmental stages observed. On the other hand, CpGs at sites not bound by transcription factors during the global re-methylation phase have high methylation levels prior to global de-methylation, become de-methylated during global de-methylation, and then become re-methylated. The results suggest that transcription factors can act as carriers of epigenetic information during germ cell and pre-implantation development by ensuring that the methylation status of CpGs is maintained after reprogramming of DNA methylation. Based on our findings, we propose a model in which transcription factor binding during the re-methylation phases of primordial germ cell and pre-implantation development allow epigenetic information to be maintained trans-generationally even at sites where DNA methylation is lost during global de-methylation.
Extended access self-administration of methamphetamine is associated with age- and sex-dependent differences in drug taking behavior and recognition memory deficits in rats
Authors: Westbrook Sara R. , Dwyer Megan R. , Cortes Laura R. , Gulley Joshua M. 
Published: November 2019

AbstractIndividuals who begin drug use during early adolescence experience more adverse consequences compared to those initiating later, especially if they are female. The mechanisms for these age and gender differences remain obscure, but studies in rodents suggest that psychostimulants may disrupt the normal ontogeny of dopamine and glutamate systems in the prefrontal cortex (PFC). Here, we studied Sprague-Dawley rats of both sexes who began methamphetamine (METH, i.v.) self-administration (SA) in adolescence (postnatal [P] day 41) or adulthood (P91). Rats received seven daily 2-h SA sessions with METH or saccharin as the reinforcer, followed by 14 daily long access (LgA; 6 h) sessions. After 7 and 14 days of abstinence, novel object (OR) or object-in-place (OiP) recognition was assessed. PFC and nucleus accumbens were collected 7 days after the final cognitive test and NMDA receptor subunits and dopamine D1 receptor expression was measured. We found that during LgA sessions, adolescent-onset rats escalated METH intake more rapidly than adult-onset rats, with adolescent-onset females earning the most infusions. Adolescent-onset rats exhibited modest deficits in OiP compared to adult-onset rats, but there was no sex difference in this effect and no groups differed in OR. We found no group differences in D1 and NMDA receptor expression, suggesting no long-lasting alteration of ontogenetic expression profiles. Our findings suggest that adolescent-onset drug use is more likely to lead to compulsive-like patterns of drug-taking and subsequent dysfunction of PFC-dependent cognition.
Extracellular DNA controls expression ofPseudomonas aeruginosagenes involved in nutrient utilization, metal homeostasis, acid pH tolerance, and virulence
Authors: Lewenza Shawn , Johnson Lori , Charron-Mazenod Laetitia , Hong Mia , Mulcahy-O’Grady Heidi 
Published: November 2019

ABSTRACTPseudomonas aeruginosagrows in extracellular DNA-enriched biofilms and infection sites. Extracellular DNA (eDNA) is generally considered a structural biofilm polymer required for aggregation and biofilm maturation. In addition, eDNA can sequester divalent metal cations, acidify the growth media, and serve as a nutrient source. Here we determine the transcriptome of planktonicP. aeruginosagrown in the presence of eDNA using RNA-seq. Transcriptome analysis identified 89 induced genes and 76 repressed genes in the presence of eDNA (FDR<0.05), and transcriptionalluxfusions were used to confirm eDNA regulation. A large number of eDNA-induced genes appear to be involved in utilizing DNA as a nutrient. Several eDNA-induced genes are also induced by acidic pH 5.5, and growth in the presence of eDNA or acidic pH promoted an acid tolerance response inP. aeruginosa. ThecyoABCDEterminal oxidase is induced at pH 5.5 and contributed to the acid tolerance phenotype. Quantitative metal analysis confirmed that DNA binds to diverse metals, which helps explain why many genes involved in a general uptake of metals were controlled by eDNA. Growth in the presence of eDNA also promoted intracellular bacterial survival and influenced virulence and during the acute infection model of fruit flies. The diverse functions of the eDNA-regulated genes underscore the important role of this extracellular polymer in promoting antibiotic resistance, virulence, acid tolerance, and nutrient utilization; phenotypes that contribute to long-term survival.
Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes
Authors: Mordaunt Charles E. , Jianu Julia M. , Laufer Ben , Zhu Yihui , Dunaway Keith W. , Bakulski Kelly M. , Feinberg Jason I. , Volk Heather E. , Lyall Kristen , Croen Lisa A. , Newschaffer Craig J. , Ozonoff Sally , Hertz-Picciotto Irva , Fallin M. Daniele , Schmidt Rebecca J. , LaSalle Janine M. 
Published: November 2019

AbstractBackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. Since the neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development, we performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth.ResultsWe identified differentially-methylated regions (DMRs) stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development.ConclusionsAt birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD, and provides novel insights for early diagnosis and therapy.