bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically Increased Telomere Length and Aging-related Physical and Cognitive Traits in the UK Biobank
Authors: Demanelis Kathryn , Tong Lin , Pierce Brandon L. 
Published: February 2019

ABSTRACTBackgroundTelomere length (TL) shortens over time in most human cell types and is a potential biomarker aging. However, the causal impact of TL on physical and cognitive phenotypes that decline with age has not been extensively examined. Using a Mendelian randomization (MR) approach, we utilized genetically increased TL (GI-TL) to estimate the impact of TL on aging-related traits among UK Biobank (UKB) participants.MethodsWe manually curated >50 aging-related traits from UKB and restricted to unrelated participants of British ancestry (n=337,522). We estimated GI-TL as a linear combination of nine TL-associated SNPs, each weighted by its previously-reported association with leukocyte TL. Regression models were used to assess the associations between GI-TL and each trait. We obtained MR estimates using the two-sample inverse variance weighted (IVW) approach.ResultsWe identified 5 age-related traits associated with GI-TL (Bonferroni-corrected threshold p<0.001): pulse pressure (PP) (p=5.2×10−14), systolic blood pressure (SBP) (p=2.9×10−15), diastolic blood pressure (DBP) (p=5.5×10−6), forced expiratory volume (FEV1) (p= p=0.0001), and forced vital capacity (FVC) (p=3.8×10−6). Under MR assumptions, one standard deviation increase in TL (∼1200 base pairs) increased PP, SBP, and DBP by 1.5, 2.3, and 0.8 mmHg, respectively, while FEV1 and FVC increased by 34.7 and 52.2 mL, respectively. The observed associations appear unlikely to be due to selection bias based on analyses including inverse probability weights and analyses of simulated data.ConclusionsThese findings suggest that longer TL increases pulmonary function and blood pressure traits. Further research is necessary to evaluate TL in cardiovascular and pulmonary age-related decline.KEY MESSAGESTelomere length (TL) is a potential biomarker and cause of aging, however, the causal relationship between TL and aging-related traits has not been thoroughly examined using a Mendelian randomization (MR) approach.We evaluated genetically increased TL (GI-TL) and its association with over 50 aging-related traits in the UK Biobank cohort using regression models and MR approaches.Pulmonary function (FEV1 and FVC) and blood pressure (SBP, DBP, and PP) traits were positively associated with GI-TL in the expected and unexpected direction, respectively.Using inverse probability weights to account for the non-representativeness of the UKB, our observed associations for GI-TL with blood pressure traits and pulmonary function persisted.Using simulated data to examine study selection as a potential source of collider bias, we concluded that selection bias was unlikely to explain the observed associations.
A Stomata Classification and Detection System in Microscope Images of Maize Cultivars
Authors: Aono Alexandre Hild , Nagai James Shiniti , Mendonça Dickel Gabriella da Silva , Marinho Rafaela Cabral , Macedo de Oliveira Paulo Eugênio Alves , Papa João Paulo , Faria Fabio Augusto 
Published: February 2019

AbstractResearch on stomata, i.e., morphological structures of plants, has increased in popularity in the last years. These structures (pores) are in charge of the interaction between the internal plant system and the environment, working on different processes such as photosynthesis and transpiration stream. Besides, a better understanding of the pore mechanism plays a significant role when exploring the evolution process, as well as the behavior of plants. Although the study of stomata in dicots species of plants has advanced considerably in the past years, there is little information about stomata of cereal grasses. Also, automated detection of these structures have been considered in the literature, but some gaps are still uncovered. This fact is motivated by high morphological variation of stomata and the presence of noise from the image acquisition step. In this work, we propose a new methodology for automatic stomata classification and a new detection system in microscope images for maize cultivars. We have achieved an approximated accuracy of 97.1% in the identification of stomata regions using classifiers based on deep learning features, which figures out as a nearly perfect classification system.
Drug-like Fragments Inhibit agr-Mediated Virulence Expression in Staphylococcus aureus
Authors: Bezar Ian F. , Mashruwala Ameya A. , Boyd Jeffrey M. , Stock Ann M. 
Published: February 2019

In response to the increasingly problematic emergence of antibiotic resistance, novel strategies for combating pathogenic bacteria are being investigated. Targeting the agr quorum sensing system, which regulates expression of virulence in Staphylococcus aureus, is one potentially useful approach for combating drug-resistant pathogens that has not yet been fully explored. A previously published study of a fragment screen resulted in the identification of five compound fragments that interact with the DNA-binding domain of the response regulator AgrA from S. aureus. We have analyzed the ability of these compounds to affect agr-mediated virulence gene expression in S. aureus cells. Three of the compounds demonstrated the ability to reduce agr-driven transcription of at the P2 and P3 promoters of the agr operon and increase biofilm formation, and two of these compounds also showed the ability to reduce levels of secreted toxins. The finding that the compounds tested were able to reduce agr activity suggests that they could be useful tools for probing the effects of agr inhibition.Furthermore, the characteristics of compound fragments make them good starting materials for the development of compound libraries to iteratively improve the inhibitors.
Phantom limb pain intensity is associated with generalized hyperalgesia
Authors: Fuchs Xaver , Diers Martin , Trojan Jörg , Kirsch Pinar , Milde Christopher , Bekrater-Bodmann Robin , Rance Mariela , Foell Jens , Andoh Jamila , Becker Susanne , Flor Herta 
Published: February 2019

AbstractAfter limb amputation, most amputees suffer from phantom limb pain (PLP). The mechanisms underlying this condition are complex and insufficiently understood. Altered somatosensory sensitivity (either heightened or lowered) might contribute to PLP. Recent studies have tested this assumption but mainly focused on the residual limb. However, altered somatosensation in PLP might be generalized. In this study, we applied quantitative sensory testing to 37 unilateral upper-limb amputees (23 with PLP, 14 without PLP) and 19 healthy controls. We assessed thresholds to heat pain (HPT), pressure pain (PPT), warmth detection (WDT), and two-point discrimination (2PDT) at the residual limb, a homologous point and the thenar of the intact limb, and both corners of the mouth. We did not find significant differences in any of the thresholds between the groups. However, higher PLP intensity was significantly related to lower HPT at all measured body sites except for the residual limb. At the residual limb, lower HPT were observed in more distal amputations and in amputees showing a higher degree of prosthesis use. Although WDT did by itself not significantly correlate with PLP intensity at any of the body sites, multiple regression analysis showed the highest multiple correlations with PLP intensity for a combination of high WDT and low HPT at the corners of the mouth. In this model, the combination of HPT and WDT shared 58% of the variance with PLP intensity. Other factors of potential importance, especially residual limb pain, were not significantly associated to any sensory threshold. We conclude that the intensity, but not the presence of PLP is positively associated with higher heat pain sensitivity. Since this association was observed at various, distributed body sites, we suggest that central mechanisms might be underlying such generalized hyperalgesia.
GIT2 is dispensable for normal learning and memory function due to a predominant brain GIT2 splice variant that evades GIT/PIX complexes
Authors: Toth Krisztian , Martyn Amanda C. , Bastrikova Natalia , Kim Woojoo , Rodriguiz Ramona M. , Ahmed Umer , Schmalzigaug Robert , Dudek Serena M. , Wetsel William C. , Premont Richard T. 
Published: February 2019

AbstractG protein-coupled receptor kinase-interacting protein 2 (GIT2) and GIT1 are highly similar, sharing the same domain structure and many binding partners. The most important GIT partners are the p21-activated protein kinase-interacting exchange factor (PIX) proteins, since through homomeric and heteromeric interactions, GIT and PIX proteins form oligomeric GIT/PIX complexes. Oligomeric GIT/PIX complexes function both as regulators of small GTP-binding proteins and as scaffolds for signalling molecules, including p21-activated protein kinases (PAKs). Deficits in learning and memory have been demonstrated in GIT1 knockout mice, and it has been assumed that GIT2 also would affect learning and memory. Unexpectedly, we find that GIT2-deficient mice respond normally in multiple tests of learning and memory, and have normal hippocampal long-term potentiation. Further, we find no evidence that GIT2 regulates ADHD-like phenotypes. To investigate why GIT2 and GIT1 differ so markedly in the brain, we identified the major isoform of GIT2 in the brain as a previously uncharacterized splice variant, GIT2(ΔBCE). This variant cannot dimerize or form oligomeric complexes with PIX proteins, and is thus incapable of regulating PAK in synapses, compared to oligomeric GIT1/PIX complexes. Because localized activation of PAK in synapses is required for structural plasticity underlying cognitive performance, loss of monomeric GIT2(ΔBCE) in the brain does not influence these responses.
Screening for neurotoxic potential of 15 flame retardants using freshwater planarians
Authors: Zhang Siqi , Ireland Danielle , Sipes Nisha S. , Behl Mamta , Collins Eva-Maria S. 
Published: February 2019

AbstractAsexual freshwater planarians are an attractive invertebrate model for high-throughput neurotoxicity screening, because they possess multiple quantifiable behaviors to assess distinct neuronal functions. Planarians uniquely allow direct comparisons between developing and adult animals to distinguish developmentally selective effects from general neurotoxicity. In this study, we used our automated planarian screening platform to compare the neurotoxicity of 15 flame retardants (FRs), consisting of representative phased-out brominated (BFRs) and replacement organophosphorus FRs (OPFRs). OPFRs have emerged as a proposed safer alternative to BFRs; however, limited information is available on their health effects. We found 11 of the 15 FRs (3/6 BFRs, 7/8 OPFRs, and Firemaster 550) caused adverse effects in both adult and developing planarians with similar nominal lowest-effect-levels for BFRs and OPFRs. This suggests that replacement OPFRs are comparably neurotoxic to the phased-out compounds. BFRs were primarily systemically toxic, whereas OPFRs, except Tris(2-chloroethyl) phosphate, shared a behavioral phenotype in response to noxious heat at sublethal concentrations, indicating specific neurotoxic effects. By directly comparing effects on adult and developing planarians, we further found that one BFR (3,3’,5,5’-Tetrabromobisphenol A) caused a developmental selective defect. Together, these results demonstrate that our planarian screening platform yields high content data resulting from assaying various behavioral and morphological endpoints, allowing us to distinguish selective neurotoxic effects and effects specific to the developing nervous system. Ten of these 11 bioactive FRs were previously found to be bioactive in other models, including cell culture and alternative animal models (nematodes and zebrafish). This level of concordance across different platforms emphasizes the urgent need for further evaluation of OPFRs in mammalian systems.
Spontaneous whole-genome duplication restores fertility in interspecific hybrids
Authors: Charron Guillaume , Marsit Souhir , Hénault Mathieu , Martin Hélène , Landry Christian R. 
Published: February 2019

AbstractInterspecies hybrids often show advantages over parents but suffer from reduced fertility, which can sometimes be overcome through sexual reproduction that sorts out incompatibilities. Sex is however inefficient due to the low viability or fertility of hybrid offspring and thus limits their evolutionary potential. Mitotic cell division could be an alternative to fertility recovery in facultative sexual species. To test this, we evolved under relaxed selection more than 600 diploid yeast hybrids between species that span 100,000 to 15 M years of divergence. We find that hybrids can recover fertility spontaneously and rapidly through whole-genome duplication. These events occurred in both hybrids between young and well-established species. Our results show that the instability of hybrid ploidy is a spontaneous path to fertility recovery.One Sentence SummaryPloidy changes potentiate hybrid speciation by leading to fertility recovery.
Task errors drive memories that improve sensorimotor adaptation
Authors: Leow Li-Ann , Marinovic Welber , de Rugy Aymar , Carroll Timothy J 
Published: February 2019

AbstractTraditional views on how humans adapt movements to perturbations of sensory feedback emphasize a fundamental role for automatic, implicit correction of sensory prediction errors. However, it is now clear that adaptive behaviour also involves deliberate, strategic movement corrections. Such strategic processes have recently been argued to underlie the latent retention of sensorimotor adaptation, evident in improved adaptation to previously encountered perturbations; a phenomenon termed “savings”. It remains unclear, however, whether savings results from prior experience of sensory prediction errors, task errors, or both. Here, we used perturbations of target locations and hand position feedback during reaching to dissociate the contributions of task and sensory prediction errors to latent sensorimotor memory. We show that prior learning to correct for task errors is required to improve adaptation to rotated hand position feedback, whereas a history of sensory prediction errors is neither sufficient nor obligatory for savings. A history of correcting for task errors, induced by experimentally perturbing the target location instead of perturbing sensory feedback of movement, improved adaptation to visuomotor perturbations that were never before encountered. Limiting movement preparation time further showed that this learning consists of two distinct components: 1) a strategic component that is flexible enough to facilitate corrective responses in the opposite direction, but that requires substantial preparation time, and 2) a set of inflexible, cached, stimulus-response associations between targets and reach directions, that can be expressed under time-pressure when similar task conditions are experienced. The results emphasise that adaptive responses to sensorimotor perturbations take multiple forms.
Effect of flow rate and freezing on cyanocobalamin recovery using a commercial solid phase extraction cartridge
Authors: Lees Lauren , Bland Alison M. , DiTullio Giacomo R. , Janech Michael G. , Lee Peter A. 
Published: February 2019

AbstractAnalysis of vitamin B12 in sea water is laborious, time consuming, and often requires storage of relatively large-volume water samples. Alleviating these major limitations will increase the throughput of samples and, as a consequence, improve our understanding of the distribution and role of vitamin B12 in the oceans. Previous studies have indicated that target analyte recovery is negatively affected at flow rates exceeding 1 mL min−1 using home-made C18 Solid Phase Extraction (SPE) cartridges. In this study, the effect of flow rate on recovery of vitamin B12 was tested across a range of flow rates between 1 and 37 mL min−1 using a commercial SPE cartridge containing surface-modified styrene divinylbenzene. Recovery of vitamin B12 at flow rates up to the maximum rate tested did not statistically differ from 1 mL min 1. A second study was conducted to determine whether storage of the SPE cartridges at −20°C had a negative impact on vitamin B12 recovery. Recovery of vitamin B12 from SPE cartridges stored up to 13 days did not differ from unfrozen SPE cartridges. These data suggest that rapid extraction and cold storage of vitamin B12 on commercial SPE cartridges does not negatively affect recovery and offers an economical alternative to field studies.
Contextual cues as modifiers of cTBS effects on indulgent eating
Authors: Safati Adrian B. , Hall Peter A. 
Published: February 2019

AbstractBackgroundPrior studies have found that continuous theta burst stimulation (cTBS) targeting the left dlPFC results in reliable increases in consumption of calorie-dense food items. However, it is not known to what extent such effects are modified by cues in the immediate eating environment. Tempting environments (i.e., those saturated with appetitive eating cues) may lead to more reliance on cognitive control networks involving the dlPFC, thereby enhancing cTBS on eating.Objective/HypothesisThe objective was to examine the extent to which cTBS effects on eating would be modified by contextual cues. It was hypothesized that cTBS effects on eating would be stronger in the presence of facilitating cues.MethodsUsing a between-subjects factorial design, 107 adults were randomly assigned to one of four conditions: 1) active cTBS + facilitating cues, 2) sham cTBS + facilitating cues, 3) active cTBS + inhibiting cues, 4) sham cTBS + inhibiting cues. Following stimulation participants completed a flanker paradigm and a taste test during which quantity consumed was assessed surreptitiously.ResultsFindings revealed a significant interaction between stimulation and cue type (F(1,102)=6.235, p=.014), such that the effects of cTBS were stronger for those in the facilitating cue condition.ConclusionsThe effects of cTBS on eating are strengthened in the presence of facilitating cues. Methodologically speaking, facilitating cues may be a functional prerequisite for exploring cTBS effects on eating in the laboratory. Substantively, the findings also suggest that facilitating cues in the eating environment may amplify counter-intentional food indulgence in everyday life via cognitive control failure.
The Evolutionary Dynamics of Cooperation in Collective Search
Authors: Tump Alan N. , Wu Charley M. , Bouhlel Imen , Goldstone Robert L. 
Published: February 2019

AbstractHow does cooperation arise in an evolutionary context? We approach this problem using a collective search paradigm where interactions are dynamic and there is competition for rewards. Using evolutionary simulations, we find that the unconditional sharing of information can be an evolutionary advantageous strategy without the need for conditional strategies or explicit reciprocation. Shared information acts as a recruitment signal and facilitates the formation of a self-organized group. Thus, the improved search efficiency of the collective grants byproduct benefits to the original sharer by altering the interaction structure. A key mechanism is a visibility radius, where individuals have access to information about neighbors within a limited distance. Our results show that for a variety of initial conditions and across both static and dynamic fitness landscapes, there is strong selection pressure for unconditional sharing.
Self-reporting transposons enable simultaneous readout of gene expression and transcription factor binding in single cells
Authors: Moudgil Arnav , Wilkinson Michael N. , Chen Xuhua , He June , Cammack Alex J. , Vasek Michael J. , Lagunas Tomas , Qi Zongtai , Morris Samantha A. , Dougherty Joseph D. , Mitra Robi D. 
Published: February 2019

AbstractIn situ measurements of transcription factor (TF) binding are confounded by cellular heterogeneity and represent averaged profiles in complex tissues. Single cell RNA-seq (scRNA-seq) is capable of resolving different cell types based on gene expression profiles, but no technology exists to directly link specific cell types to the binding pattern of TFs in those cell types. Here, we present self-reporting transposons (SRTs) and their use in single cell calling cards (scCC), a novel assay for simultaneously capturing gene expression profiles and mapping TF binding sites in single cells. First, we show how the genomic locations of SRTs can be recovered from mRNA. Next, we demonstrate that SRTs deposited by the piggyBac transposase can be used to map the genome-wide localization of the TFs SP1, through a direct fusion of the two proteins, and BRD4, through its native affinity for piggyBac. We then present the scCC method, which maps SRTs from scRNA-seq libraries, thus enabling concomitant identification of cell types and TF binding sites in those same cells. As a proof-of-concept, we show recovery of cell type-specific BRD4 and SP1 binding sites from cultured cells. Finally, we map Brd4 binding sites in the mouse cortex at single cell resolution, thus establishing a new technique for studying TF biology in situ.
Causes and consequences of cellulose production byPseudomonas fluorescensSBW25 at the air-liquid interface
Authors: Ardré Maxime , Rainey Paul B 
Published: February 2019

ABSTRACTCellulose over-producing wrinkly spreader mutants ofPseudomonas fluorescensSBW25 have been the focus of much investigation, but conditions promoting the production of cellulose in ancestral SBW25, its effects and consequences have escaped investigation through lack ofin vitrophenotype. Here, using a custom built device, we reveal that in static broth microcosms ancestral SBW25 encounters environmental signals at the air-liquid interface that activate, via three diguanylate cyclase-encoding pathways (Wsp, Aws and Mws), production of cellulose. Secretion of the polymer at the meniscus leads to modification of the environment and growth of numerous micro-colonies that extend out from the surface. Accumulation of cellulose and associated microbial growth leads to Rayleigh-Taylor instability resulting in bioconvection and rapid transport of water-soluble products over tens of millimetres. Drawing upon data we build a mathematical model that recapitulates experimental results and captures the interactions between biological, chemical and physical processes.IMPORTANCEThis work reveals a new bacterial behaviour that manifests at the air-liquid interface, which depends on production of cellulose, and hints to hitherto unrecognised dimensions to bacterial life at surfaces. Additionally, the study links activation of known diguanylate cyclase-encoding pathways to cellulose expression and to signals encountered at the air-liquid interface. Further significance stems from recognition of the consequences of fluid instabilities arising from surface production of cellulose for transport of water-soluble products over large distances.
Treatment of human cells with 5-aza-dC induces formation of PARP1-DNA covalent adducts at genomic regions targeted by DNMT1
Authors: Kiianitsa Kostantin , Maizels Nancy 
Published: February 2019

ABSTRACTThe nucleoside analog 5-aza-2’-deoxycytidine (5-aza-dC) is used to treat some hematopoietic malignancies. The mechanism of cell killing depends upon DNMT1, but is otherwise not clearly defined. Here we show that PARP1 forms covalent DNA adducts in human lymphoblast or fibroblasts treated with 5-aza-dC. Some adducts recovered from 5-aza-dC-treated cells have undergone cleavage by apoptotic caspases 3/7. Mapping of PARP1-DNA adducts, by a new method, “Adduct-Seq”, demonstrates adduct enrichment at CpG-dense genomic locations that are targets of maintenance methylation by DNMT1. Covalent protein-DNA adducts can arrest replication and induce apoptosis, and these results raise the possibility that induction of PARP1-DNA adducts may contribute to cell killing in response to treatment with 5-aza-dC.