bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viewing one’s body during encoding boosts episodic memory
Authors: Bréchet Lucie , Mange Robin , Herbelin Bruno , Gauthier Baptiste , Serino Andrea , Blanke Olaf 
Published: May 2018

ABSTRACTEpisodic autobiographical memories (EAMs) are recollections of contextually rich and personally relevant past events. EAM has been linked to the sense of self, allowing one to mentally travel back in subjective time and re-experience past events. However, the sense of self has recently been linked to online multisensory processing and bodily self-consciousness (BSC). It is currently unknown whether EAM depends on BSC mechanisms. Here, we used a new immersive virtual reality (VR) system that maintained the perceptual richness of life episodes and fully controlled the experimental stimuli during encoding and retrieval, including the participant’s body. We report that the present VR setup permits to measure recognition memory for complex and embodied 3D scenes during encoding and retrieval, that recognition memory depends on delay and number of changed elements, and that viewing one’s body as part of the virtual scene (as found in BSC studies) enhances delayed retrieval. This body effect was not observed when no virtual body or a moving control object was shown. These data show that embodied views improve recognition memory for 3D life-like scenes, thereby linking the sense of self, and BSC in particular, to episodic memory and the re-experiencing of specific past events in EAM.
PARPi triggers STING-dependent immune response and enhances therapeutic efficacy of immune checkpoint blockade independent of BRCAness
Authors: Shen Jianfeng , Zhao Wei , Ju Zhenlin , Wang Lulu , Peng Yang , Labrie Marilyne , Yap Timothy , Mills Gordon B. , Peng Guang 
Published: May 2018

AbstractPoly-(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have shown remarkable therapeutic efficacy against BRCA1/2 mutant cancers through a synthetic lethal interaction. PARPis are believed to exert their therapeutic effects mainly through the blockade of single-strand DNA damage repair, which leads to the accumulation of toxic DNA double strand breaks, specifically in cancer cells with DNA repair deficiency (BCRAness), including those harboring BRCA1/2 mutations. Here, we show that PARPis modulate immune reposes, which contribute to their therapeutic effects independent of BRCA1/2 mutations. The mechanism underlying this PARPi-induced reprogramming of anti-tumor microenvironment involves a promoted accumulation of cytosolic DNA fragments due to unresolved DNA lesions. This in turn activates the DNA sensing cGAS-STING pathway and stimulates production of type I interferons. Ultimately, these events promote PARPi-induced antitumor immunity independent of BRCAness, which can be further enhanced by immune checkpoint blockade. Our results may provide a mechanistic rationale for using PARPis as immunomodulatory agents to harness therapeutic efficacy of immune checkpoint blockade.
Alginate-regulating genes are identified in the clinical cystic fibrosis isolate ofPseudomonas aeruginosaPA2192
Authors: Colbert Brett , Kumari Hansi , Piñon Ana , Frey Lior , Pandey Sundar , Mathee Kalai 
Published: May 2018

ABSTRACTCystic fibrosis (CF) is a genetic disorder that leads to a buildup of mucus in the lungs ideal for bacterial colonization. WhenPseudomonas aeruginosaenters the CF lung, it undergoes a conversion from nonmucoid to mucoid; colonization by a mucoid strain ofP. aeruginosagreatly increases mortality. The mucoid phenotype is due to the production of alginate. The regulator of alginate production is the AlgT/U sigma factor. The observed phenotypic conversion is due to a mutation in themucAgene coding for an anti-sigma factor, MucA, which sequesters AlgT/U. This mucoid phenotype is unstable when the strains are removed from the lung as they acquire second-site mutations. Thisin vitroreversion phenomenon is utilized to identify novel genes regulating alginate production. Previously, second-site mutations were mapped toalgT/U, algO,andmucP, demonstrating their role in alginate regulation. Most of these studies were performed using a non-CF isolate. It was hypothesized that second site mutations in a clinical strain would be mapped to the same genes. In this study, a clinical, hyper-mucoidP. aeruginosastrain PA2192 was used to study the reversion phenomenon. This study found that PA2192 has a novelmucAmutation which was named themmucA180allele. Twelve colonies were sub-cultured for two weeks without aeration at room temperature in order to obtain nonmucoidsuppressors ofalginateproduction(sap). Only 41sapmutants were stable for more than 48 hours — a reversion frequency of 3.9% as compared to ~90% in laboratory strains showing that PA2192 has a stable mucoid phenotype. This phenotype was restored in 28 of the 41sapmutants when complemented with plasmids harboringalgT/U. Four of thesapmutants are complemented byalgO. Sequence analyses of thealgT/Umutants have found no mutations in the coding region or promoter leading to the hypothesis that there is another, as yet unidentified mechanism of alginate regulation in this clinical strain.
The role of chromatin accessibility in cis-regulatory evolution
Authors: Peng Pei-Chen , Khoueiry Pierre , Girardot Charles , Reddington James P. , Garfield David A. , Furlong Eileen E.M. , Sinha Saurabh 
Published: May 2018

ABSTRACTTranscription factor (TF) binding is determined by sequence as well as chromatin accessibility. While the role of accessibility in shaping TF-binding landscapes is well recorded, its role in evolutionary divergence of TF binding, which in turn can alter cis-regulatory activities, is not well understood. In this work, we studied the evolution of genome-wide binding landscapes of five major transcription factors (TFs) in the core network of mesoderm specification, betweenD. melanogasterandD. virilis, and examined its relationship to accessibility and sequence-level changes. We generated chromatin accessibility data from three important stages of embryogenesis in bothD. melanogasterandD. virilis, and recorded conservation and divergence patterns. We then used multi-variable models to correlate accessibility and sequence changes to TF binding divergence. We found that accessibility changes can in some cases, e.g., for the master regulator Twist and for earlier developmental stages, more accurately predict binding change than is possible using TF binding motif changes between orthologous enhancers. Accessibility changes also explain a significant portion of the co-divergence of TF pairs. We noted that accessibility and motif changes offer complementary views of the evolution of TF binding, and developed a combined model that captures the evolutionary data much more accurately than either view alone. Finally, we trained machine learning models to predict enhancer activity from TF binding, and used these functional models to argue that motif and accessibility-based predictors of TF binding change can substitute for experimentally measured binding change, for the purpose of predicting evolutionary changes in enhancer activity.
Error-correcting dynamics in visual working memory
Authors: Panichello Matthew F. , DePasquale Brian , Pillow Jonathan W. , Buschman Timothy J. 
Published: May 2018

AbstractWorking memory is critical to cognition, decoupling behavior from the immediate world. Yet, it is imperfect; internal noise introduces errors into memory representations (1, 2). Such errors accumulate over time (3–5) and increase with the number of items simultaneously held in working memory (6–10). Here, we show that error-correcting attractor dynamics mitigate the impact of noise on working memory. These dynamics pull memories towards a few stable representations in mnemonic space, inducing a bias in memory representations but reducing the effect of noise. Model-based and model-free analyses show attractor dynamics account for the frequency, bias, and precision of working memory reports in both humans and monkeys. Furthermore, attractor dynamics were optimized to the context; they adapted to the statistics of the environment, such that memories drifted towards contextually-predicted values. Our results suggest attractor dynamics mediate errors in working memory by counteracting noise and integrating contextual information into memories.
Activity of Telavancin against S. aureus isolated from cystic fibrosis patients including those with decreased susceptibility to Ceftaroline
Authors: Roch Melanie , Varela Maria Celeste , Taglialegna Agustina , Rose Warren E. , Rosato Adriana E. 
Published: May 2018

ABSTRACTMethicillin-resistant Staphylococcus aureus (MRSA) acquisition in cystic fibrosis (CF) patients confers a worse clinical outcome with increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to S. aureus has a dual mode of action causing inhibition of the peptidoglycan synthesis and membrane depolarization. CF-associated MRSA infections remain an important problem with no foreseeable decline in prevalence rates. Although telavancin is currently in clinical use for complicated skin infections and hospital-acquired pneumonia, the activity against CF-associated S. aureus infections has not been investigated. In this work, we studied the activity of telavancin against CF S. aureus strains collected from diverse geographical CF centers in the USA. We found that telavancin-MIC90 was 0.06 μg/ml, 8-fold lower than ceftaroline or daptomycin and 25-fold lower than linezolid and vancomycin. We demonstrate that telavancin at serum-free concentrations has rapid bactericidal activity with a decrease of more than 3 log10 CFU/ml during the first 4 to 6 hours of treatment, performing better in this assay than vancomycin and ceftaroline, including S. aureus resistant to ceftaroline.Telavancin resistance was infrequent (0.3%), although we found that it can occur in-vitro in both CF-and non-CF S. aureus strains by progressive passages with sub-inhibitory concentrations. Genetic analysis of telavancin in-vitro mutants showed gene polymorphisms in cell wall and virulence genes, and increased survival in a Galleria mellonella infection model. Thus, we conclude that telavancin represents a promising therapeutic option for CF infections with potent in-vitro activity and low resistance potential.
GABAergic malfunction underlying maternal immune activation-induced social deficits
Authors: Okamoto Kazuki , Hitora-Imamura Natsuko , Hioki Hiroyuki , Ikegaya Yuji 
Published: May 2018

AbstractSocial deficits are one of the major symptoms of psychiatric disorders, including autism spectrum disorders (ASDs) and schizophrenia. However, the underlying mechanism remains ill-defined. Here, we focused on the anterior cingulate cortex (ACC), a brain region that is related to social behaviors, of mice that received poly(I:C)-induced maternal immune activation. Using whole-cell patch clamp recordings, we found that layer 2/3 pyramidal cells were hyperactive in acute ACC slices prepared from poly(I:C)-treated mice compared to those from saline-treated mice. The hyperexcitation was associated with a reduction in inhibitory synapse activity. Local injection of the GABAA receptor enhancer clonazepam into the ACC of poly(I:C)-treated mice restored the social behaviors of the mice. These results suggest that the balanced excitability of ACC neurons is essential for social ability.
Harvesting information from ultra-short ancient DNA sequences
Authors: de Filippo Cesare , Meyer Matthias , Prüfer Kay 
Published: May 2018

AbstractThe study of ancient DNA is hampered by degradation, resulting in short DNA fragments. Advances in laboratory methods have made it possible to retrieve short DNA fragments, thereby improving access to DNA preserved in highly degraded, ancient material. However, such material contains large amounts of microbial contamination in addition to DNA fragments from the ancient organism. The resulting mixture of sequences constitute a challenge for computational analysis, since microbial sequences are hard to distinguish from the ancient sequences of interest, especially when they are short. Here, we develop a method to quantify spurious alignments based on the presence or absence of rare variants. We find that spurious alignments are enriched for mismatches and insertion/deletion differences and lack substitution patterns typical of ancient DNA. The impact of spurious alignments can be reduced by filtering on these features and by imposing a sample-specific minimum length cutoff. We apply this approach to sequences from the ~430,000 year-old Sima de los Huesos hominin remains, which contain particularly short DNA fragments, and increase the amount of usable sequence data by 17-150%. This allows us to place a third specimen from the site on the Neandertal lineage. Our method maximizes the sequence data amenable to genetic analysis from highly degraded ancient material and avoids pitfalls that are associated with the analysis of ultra-short DNA sequences.
Contrasting effects of acute and chronic stress on the transcriptome, epigenome, and immune response of Atlantic salmon
Authors: Uren Webster Tamsyn M. , Rodriguez-Barreto Deiene , Martin Samuel A.M. , Oosterhout Cock van , Orozco-terWengel Pablo , Cable Joanne , Hamilton Alastair , de Leaniz Carlos Garcia , Consuegra Sofia 
Published: May 2018

AbstractEarly-life stress can have long-lasting effects on immunity, but the underlying molecular mechanisms are unclear. We examined the effects of acute stress (cold-shock during embryogenesis) and chronic stress (absence of tank enrichment during larval-stage) on the gill transcriptome and methylome of Atlantic salmon four months after hatching. While only chronic stress induced pronounced transcriptional effects, both acute and chronic stress caused lasting, and contrasting, changes in the methylome. Crucially, we found that acute stress enhanced immune response to a pathogenic challenge (lipopolysaccharide), while chronic stress suppressed it. We identified stress-induced changes in promoter or gene-body methylation that were associated with altered expression for a small proportion of genes, and also evidence of wider epigenetic regulation within signalling pathways involved in immune response. Our study suggests that early-life stress can affect immuno-competence through epigenetic mechanisms, a finding that could open the way for improved stress and disease management of farmed fish.
The variations of human miRNAs and Ising like base pairing models
Authors: Banerjee Jyoti Prasad , Das Jayanta Kumar , Pal Choudhury Pabitra , Mukherjee Sayak , Hassan Sk. Sarif , Basu Pallab 
Published: May 2018

AbstractmiRNAs are small about 22-base pair long, RNA molecules are of extreme biological importance. Like other longer RNA molecules, messages in miRNAs are encoded by the permutations of only four nucleotide bases represented by A, U, C and G. However, just like words in any language, not all combination of these alphabets make a meaningful word. In fact, we find that the distributions of nucleotides bases in human miRNAs show significant deviation from randomness. First, a miRNA sequence containing four bases are mapped into a binary string with three kinds of classifications according to their chemical properties. Then, we propose a simple nearest neighbor model (Ising model) to understand the statistical variations in human miRNAs.
Tissue-specific BMAL1 cistromes reveal that enhancer-enhancer interactions regulate rhythmic transcription
Authors: Beytebiere Joshua R , Trott Alexandra J , Greenwell Ben , Osborne Collin A , Vitet Helene , Spence Jessica , Yoo Seung-Hee , Chen Zheng , Takahashi Joseph S , Ghaffari Noushin , Menet Jerome S 
Published: May 2018

AbtsractThe mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of thousands of genes. Consistent with the various biological functions under clock control, rhythmic gene expression is tissue-specific despite an identical clockwork mechanism in every cell. Here we show that BMAL1 DNA binding is largely tissue-specific, due to differences in chromatin accessibility between tissues and co-binding of tissue-specific transcription factors. Our results also indicate that BMAL1 ability to drive tissue-specific rhythmic transcription not only relies on the activity of BMAL1 cis-regulatory elements (CREs), but also on the activity of neighboring CREs. Characterization of the physical interactions between BMAL1 CREs and other CREs in the mouse liver reveals that interactions are quite stable, and that BMAL1 controls rhythmic transcription by regulating the activity of other CREs. This supports that much of BMAL1 target gene transcription depends on BMAL1 capacity to rhythmically regulate a network of enhancers.
Group size effects in social evolution
Authors: Peña Jorge , Nöldeke Georg 
Published: May 2018

AbstractHow the size of social groups affects the evolution of cooperative behaviors is a classic question in evolutionary biology. Here we investigate group size effects in the evolutionary dynamics of games in which individuals choose whether to cooperate or defect and payoffs do not depend directly on the size of the group. We find that increasing the group size decreases the proportion of cooperators at both stable and unstable rest points of the replicator dynamics. This implies that larger group sizes can have negative effects (by reducing the amount of cooperation at stable polymorphisms) and positive effects (by enlarging the basin of attraction of more cooperative outcomes) on the evolution of cooperation. These two effects can be simultaneously present in games whose evolutionary dynamics feature both stable and unstable rest points, such as public goods games with participation thresholds. Our theory recovers and generalizes previous results and is applicable to a broad variety of social interactions that have been studied in the literature.
Determination of novel members in theDrosophila melanogasteranteriorposterior patterning system using natural variation
Authors: Jermusyk Ashley A. , Gharavi Sarah E. , Tingare Aslesha S. , Reeves Gregory T. 
Published: May 2018

AbstractThe anterior-posterior axis of the developingDrosophila melanogasterembryo is patterned by a well-studied gene regulatory network called the Gap Gene Network. This network acts to buffer the developing pattern against noise, thereby minimizing errors in gene expression and preventing patterning defects.In this paper, we sought to discover novel regulatory regions and transcription factors acting in a subset of the Gap network using a selection of wild-caught fly lines derived from the Drosophila Genetic Reference Panel (DGRP). The fly lines in the DGRP contain subtle genomic differences due to natural variation; we quantified the differences in positioning of gene expression borders of two anterior-poster patterning genes,Krüppel(Kr) and Even-skipped in 13 of the DGRP lines. The differences in the positions ofKrüppeland Even-skipped were then correlated to specific single nucleotide polymorphisms and insertions/deletions within the select fly lines. Putative enhancers containing these genomic differences were validated for their ability to produce expression using reporter constructs and analyzed for possible transcription factor binding sites. The identified transcription factors were then perturbed and the resulting Eve andKrpositioning was determined. In this way, we foundmedea, ultraspiracle, glial cells missing, andorthopediaeffectKrand Eve positioning in subtle ways, while knock-down ofpangolinproduces significant shifts inKrand subsequent Eve expression patterns. Most importantly this study points to the existence of many additional novel members that have subtle effects on this system and the degree of complexity that is present in patterning the developing embryo.
Facility ownership and mortality among older adults residing in care homes
Authors: Damián Javier , Pastor-Barriuso Roberto , García-López Fernando José , Ruigómez Ana , Martínez-Martín Pablo , de Pedro-Cuesta Jesús 
Published: May 2018

ABSTRACTBackground and ObjectivesNursing or care home characteristics may have a long-term impact on the residents’ mortality risks that has not been studied previously. The study’s main objective was to assess the association between facility ownership and long-term, all-cause mortality. Research Design and Methods. We conducted a mortality follow-up study on a cohort of 611 nursing-home residents in the city Madrid, Spain, from their 1998–1999 baseline interviews up to September 2013. Residents lived in three types of facilities: public, subsidized and private, which were also sub-classified according to size (number of beds). Residents’ information was collected by interviewing the residents themselves, their caregivers and facility physicians. We used time-to-event multivariable models and inverse probability weighting to estimate standardized mortality risk differences.ResultsAfter a 3728 person-year follow-up (median/maximum of 4.8/15.2 years), 519 participants had died. In fully-adjusted models, the standardized mortality risk difference at 5 years of follow-up between large-sized public facilities and medium-sized private facilities was 18.9% (95% confidence interval [CI]: −33.4 to −4.5%), with a median survival (95% CI) of 3.6 (0.5 to 6.8) additional years. The fully-standardized 5-year mortality difference (95% CIs) comparing for-profit private facilities with not-for-profit public institutions was −15.1% (−31.1% to 0.9%), and the fully-standardized median survival difference (95% CIs) was 3.0 (-1.7 to 7.7) years.Discussion and ImplicationsThese results are highly compatible with an effect on the long-term mortality risk for residents due to factors associated with the ownership of their facilities.
Single-cell heterogeneity in the chloroplast redox state mediates acclimation to stress in a marine diatom
Authors: Mizrachi Avia , van Creveld Shiri Graff , Shapiro Orr H. , Rosenwasser Shilo , Vardi Assaf 
Published: May 2018

AbstractDiatoms are photosynthetic microorganisms of great ecological and biogeochemical importance, forming vast blooms in diverse aquatic ecosystems. Current understanding of phytoplankton acclimation to stress is based on population-level analysis, masking cell-to-cell variability. Here we investigated heterogeneity within Phaeodactylum tricornutum populations in response to oxidative stress, which is induced by environmental stress conditions. We combined flow cytometry and a microfluidics system for live imaging to measure redox dynamics at the single-cell level using the roGFP sensor. Chloroplast-targeted roGFP exhibited a light-dependent, bi-stable oxidation pattern in response to H2O2, revealing distinct subpopulations of sensitive oxidized cells and resilient reduced cells. Subpopulation proportions depended on growth phase, linking the bi-stable phenotype to proliferation. Oxidation of chloroplast-targeted roGFP preceded commitment to cell death and was used as a novel cell fate predictor. We propose that light-dependent metabolic heterogeneity results in differential stress responses that regulate cell fate within diatom populations.