bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duration of Untreated Cardiac Arrest and Clinical Relevance of Animal Experiments: The Relationship Between the “No-Flow” Duration and the Severity of Post-Cardiac Arrest Syndrome in a Porcine Model
Authors: Babini Giovanni , Grassi Luigi , Russo Ilaria , Novelli Deborah , Boccardo Antonio , Luciani Anita , Fumagalli Francesca , Staszewsky Lidia , Fiordaliso Fabio , De Maglie Marcella , Salio Monica , Zani Davide D. , Letizia Teresa , Masson Serge , Luini Mario V. , Pravettoni Davide , Scanziani Eugenio , Latini Roberto , Ristagno Giuseppe 
Published: May 2017

ABSTRACT

Introduction:
The study investigated the effect of untreated cardiac arrest (CA), that is, “no-flow” time, on postresuscitation myocardial and neurological injury, and survival in a pig model to identify an optimal duration that adequately reflects the most frequent clinical scenario.

Methods:
An established model of myocardial infarction followed by CA and cardiopulmonary resuscitation was used. Twenty-two pigs were subjected to three no-flow durations: short (8–10 min), intermediate (12–13 min), and long (14–15 min). Left ventricular ejection fraction (LVEF) was assessed together with thermodilution cardiac output (CO) and high sensitivity cardiac troponin T (hs-cTnT). Neurological impairment was evaluated by neurological scores, serum neuron specific enolase (NSE), and histopathology.

Results:
More than 60% of animals survived when the duration of CA was ≤13 min, compared to only 20% for a duration ≥14 min. Neuronal degeneration and neurological scores showed a trend toward a worse recovery for longer no-flow durations. No animals achieved a good neurological recovery for a no-flow ≥14 min, in comparison to a 56% for a duration ≤13 min (P = 0.043). Serum NSE levels significantly correlated with the no-flow duration (r = 0.892). Longer durations of CA were characterized by lower LVEF and CO compared to shorter durations (P < 0.05). The longer was the no-flow time, the higher was the number of defibrillations delivered (P = 0.043). The defibrillations delivered significantly correlated with LVEF and plasma hs-cTnT.

Conclusions:
Longer no-flow durations caused greater postresuscitation myocardial and neurological dysfunction and reduced survival. An untreated CA of 12–13 min may be an optimal choice for a clinically relevant model.
Sepsis-Induced Channelopathy in Skeletal Muscles is Associated with Expression of Non-Selective Channels
Authors: Balboa Elisa , Saavedra-Leiva Fujiko , Cea Luis A. , Vargas Aníbal A. , Ramírez Valeria , Escamilla Rosalba , Sáez Juan C. , Regueira Tomás 
Published: May 2017

ABSTRACT
Skeletal muscles (∼50% of the body weight) are affected during acute and late sepsis and represent one sepsis associate organ dysfunction. Cell membrane changes have been proposed to result from a channelopathy of yet unknown cause associated with mitochondrial dysfunction and muscle atrophy. We hypothesize that the channelopathy might be explained at least in part by the expression of non-selective channels. Here, this possibility was studied in a characterized mice model of late sepsis with evident skeletal muscle atrophy induced by cecal ligation and puncture (CLP). At day seven after CLP, skeletal myofibers were found to present de novo expression (immunofluorescence) of connexins 39, 43, and 45 and P2X7 receptor whereas pannexin1 did not show significant changes. These changes were associated with increased sarcolemma permeability (∼4 fold higher dye uptake assay), ∼25% elevated in intracellular free-Ca2+ concentration (FURA-2), activation of protein degradation via ubiquitin proteasome pathway (Murf and Atrogin 1 reactivity), moderate reduction in oxygen consumption not explained by changes in levels of relevant respiratory proteins, ∼3 fold decreased mitochondrial membrane potential (MitoTracker Red CMXRos) and ∼4 fold increased mitochondrial superoxide production (MitoSox). Since connexin hemichannels and P2X7 receptors are permeable to ions and small molecules, it is likely that they are main protagonists in the channelopathy by reducing the electrochemical gradient across the cell membrane resulting in detrimental metabolic changes and muscular atrophy.
Reversibility of Frailty After Bridge-to-Transplant Ventricular Assist Device Implantation or Heart Transplantation
Authors: Jha Sunita R. , Hannu Malin K. , Newton Phillip J. , Wilhelm Kay , Hayward Christopher S. , Jabbour Andrew , Kotlyar Eugene , Keogh Anne , Dhital Kumud , Granger Emily , Connellan Mark , Jansz Paul , Spratt Phillip M. , Montgomery Elyn , Smith Angela , Harkess Michelle , Tunicliff Peta , Davidson Patricia M. , Macdonald Peter S. 
Published: May 2017

Background
We recently reported that frailty is independently predictive of increased mortality in patients with advanced heart failure referred for heart transplantation (HTx). The aim of this study was to assess the impact of frailty on short-term outcomes after bridge-to-transplant ventricular assist device (BTT-VAD) implantation and/or HTx and to determine if frailty is reversible after these procedures.

Methods
Between August 2013 and August 2016, 100 of 126 consecutive patients underwent frailty assessment using Fried’s Frailty Phenotype before surgical intervention: 40 (21 nonfrail, 19 frail) BTT-VAD and 77 (60 nonfrail, 17 frail) HTx—including 17 of the 40 BTT-VAD supported patients. Postprocedural survival, intubation time, intensive care unit, and hospital length of stay were compared between frail and nonfrail groups. Twenty-six frail patients were reassessed at 2 months or longer postintervention.

Results
Frail patients had lower survival (63 ± 10% vs 94 ± 3% at 1 year, P = 0.012) and experienced significantly longer intensive care unit (11 vs 5 days, P = 0.002) and hospital (49 vs 25 days, P = 0.003) length of stay after surgical intervention compared with nonfrail patients. Twelve of 13 frail patients improved their frailty score after VAD (4.0 ± 0.8 to 1.4 ± 1.1, P < 0.001) and 12 of 13 frail patients improved their frailty score after HTx (3.2 ± 0.4 to 0.9 ± 0.9, P < 0.001). Handgrip strength and depression improved postintervention. Only a slight improvement in cognitive function was seen postintervention.

Conclusions
Frail patients with advanced heart failure experience increased mortality and morbidity after surgical intervention with BTT-VAD or HTx. Among those who survive frailty is partly or completely reversible underscoring the importance of considering this factor as a dynamic not fixed entity.
Aluminum Resistance Transcription Factor 1 (ART1)contributes to natural variation in rice Al resistance
Authors: Arbelaez Juan David , Maron Lyza G. , Jobe Timothy O. , Piñeros Miguel A. , Famoso Adam N. , Rebelo Ana Rita , Singh Namrata , Ma Qiyue , Fei Zhangjun , Kochian Leon V. , McCouch Susan R. 
Published: May 2017

ABSTRACTTranscription factors (TFs) mediate stress resistance indirectly via physiological mechanisms driven by the genes they regulate. When studying TF-mediated stress resistance, it is important to understand how TFs interact with different genetic backgrounds. Here, we fine-mapped the aluminum (Al) resistance QTLAlt12.1to a 44 Kb region containing six gene models. Among them isART1, which encodes a C2H2-type zinc finger TF required for Al resistance in rice. The parents of the mapping population, Al-resistant Azucena (tropical japonica) and Al-sensitive IR64 (indica), showed similarART1expression levels but extensive sequence polymorphism within theART1coding region. Using reciprocal near-isogenic lines (NILs) in the Azucena and IR64 genetic backgrounds, we examined how allele-swappingAlt12.1would affect plant responses to Al. Analysis of global transcriptional responses to Al stress in roots of the NILs alongside their recurrent parents demonstrated that the ART1 from Al-resistant Azucena led to greater changes in gene expression in response to Al when compared to the ART1 from IR64 in both genetic backgrounds. The presence of the ART1 allele from the opposite parent affected the expression of several genes not previously implicated in rice Al tolerance. We highlight examples where putatively functional variation incis-regulatory regions of ART1-regulated genes interacts with ART1 to determine gene expression in response to Al. This ART1-promoter interaction may be associated with transgressive variation for Al resistance in the Azucena × IR64 population. These results illustrate how ART1 interacts with the genetic background to contribute to quantitative phenotypic variation in rice Al resistance.
Structure ofAlliumlachrymatory factor synthase elucidates catalysis on sulfenic acid substrate
Authors: Arakawa Takatoshi , Sato Yuta , Takabe Jumpei , Masamura Noriya , Kato Masahiro , Aoyagi Morihiro , Kamoi Takahiro , Tsuge Nobuaki , Imai Shinsuke , Fushinobu Shinya 
Published: May 2017

AbstractNatural lachrymatory effects are invoked by small volatileS-oxide compounds. They are produced through alkene sulfenic acids by the action of lachrymatory factor synthase (LFS). Here we present the crystal structures of onion LFS (AcLFS) revealed in solute-free and two solute-stabilized forms. Each structure adopts a single seven-stranded helix-grip fold possessing an internal pocket. Mutagenesis analysis localized the active site to a layer near the bottom of the pocket, which is adjacent to the deduced key residues Arg71, Glu88, and Tyr114. Solute molecules visible on the active site have suggested thatAcLFS accepts various small alcohol compounds as well as its natural substrate, and they inhibit this substrate according to their chemistry. Structural homologs have been found in the SRPBCC superfamily, and comparison of the active sites has demonstrated that the electrostatic potential unique toAcLFS could work in capturing the substrate in its specific state. Finally, we propose a rational catalytic mechanism based on intramolecular proton shuttling in which the microenvironment ofAcLFS can bypass the canonical [1,4]-sigmatropic rearrangement principle established by microwave studies. Beyond revealing howAcLFS generates the lachrymatory compound, this study provides insights into the molecular machinery dealing with highly labile organosulfur species.Significance statementCrushing of onion liberates a volatile compound,syn-propanethialS-oxide (PTSO), which causes lachrymatory effect on humans. We present the crystal structures of onion LFS (AcLFS), the enzyme responsible for natural production of PTSO.AcLFS features a barrel-like fold, and mutagenic and inhibitory analyses revealed that the key residues are present in the central pocket, harboring highly concentrated aromatic residues plus a dyad motif. The architecture ofAcLFS is widespread among proteins with various biological functions, such as abscisic acid receptors and polyketide cyclases, and comparisons with these homologs indicate that unique steric and electronic properties maintain the pocket as a reaction compartment. We propose the molecular mechanism behind PTSO generation and shed light on biological decomposition of short-lived sulfur species.
Time-course analysis of early meiotic prophase events informs mechanisms of homolog pairing and synapsis inCaenorhabditis elegans
Authors: Mlynarczyk-Evans Susanna , Villeneuve Anne M 
Published: May 2017

AbstractSegregation of homologous chromosomes during meiosis depends on their ability to reorganize within the nucleus, discriminate among potential partners, and stabilize pairwise associations through assembly of the synaptonemal complex (SC). Here we report a high-resolution time-course analysis of these key early events duringCaenorhabditis elegansmeiosis. Labeled nucleotides are incorporated specifically into the X chromosomes during the last two hours of S phase, a property we exploit to identify a highly synchronous cohort of nuclei. By tracking X-labeled nuclei through early meiotic prophase, we define the sequence and duration of chromosome movement, nuclear reorganization, pairing at pairing centers (PCs), and SC assembly. Appearance of ZYG-12 foci (marking attachment of PCs to the nuclear envelope) and onset of active mobilization occur within an hour after S phase completion. Movement occurs for nearly 2 hours before stable pairing is observed at PCs, and autosome movement continues for roughly 4 hours thereafter. Chromosomes are tightly clustered during a 2-3 hour post-pairing window, during which the bulk of SC assembly occurs; however, initiation of SC assembly can precede evident chromosome clustering. SC assembly on autosomes begins immediately after PC pairing is detected and is completed within about 3.5 hours. For the X chromosomes, PC pairing is contemporaneous with autosomal pairing, but autosomes complete synapsis earlier (on average) than X chromosomes, implying that X chromosomes have a delay in onset and/or a slower rate of SC assembly. Additional evidence suggests that transient association among chromosomes sharing the same PC protein may contribute to partner discrimination.
Prediction (or not) during language processing. A commentary on Nieuwland et al. (2017) and DeLong et al. (2005)
Authors: Yan Shaorong , Kuperberg Gina R. , Jaeger T. Florian 
Published: May 2017

AbstractThe extent to which language processing involves prediction of upcoming inputs remains a question of ongoing debate. One important data point comes from DeLong et al. (2005) who reported that an N400-like event-related potential correlated with a probabilistic index of upcoming input. This result is often cited as evidence for gradient probabilistic prediction of form and/or semantics, prior to the bottom-up input becoming available. However, a recent multi-lab study reports a failure to find these effects (Nieuwland et al., 2017). We review the evidence from both studies, including differences in the design and analysis approach between them. Building on over a decade of research on prediction since DeLong et al. (2005)’s original study, we also begin to spell out the computational nature of predictive processes that one might expect to correlate with ERPs that are evoked by a functional element whose form is dependent on an upcoming predicted word. For paradigms with this type of design, we propose an index of anticipatory processing, Bayesian surprise, and apply it to the updating of semantic predictions. We motivate this index both theoretically and empirically. We show that, for studies of the type discussed here, Bayesian surprise can be closely approximated by another, more easily estimated information theoretic index, the surprisal (or Shannon information) of the input. We re-analyze the data from Nieuwland and colleagues using surprisal rather than raw probabilities as an index of prediction. We find that surprisal is gradiently correlated with the amplitude of the N400, even in the data shared by Nieuwland and colleagues. Taken together, our review suggests that the evidence from both studies is compatible with anticipatory semantic processing. We do, however, emphasize the need for future studies to further clarify the nature and degree of form prediction, as well as its neural signatures, during language comprehension.
Precentral gyrus abnormal connectivity in male and female schizophrenia patients
Authors: Zarei Mahdi 
Published: May 2017

AbstractThe present study demonstrates the Precentral gyrus (PreCG) alteration and its abnormal connectivities in Schizophrenia (SCH) patients. The resting-sate functional magnetic resonance imaging (rs-fMRI) data of healthy control subjects and SCH patients (Centre for Biomedical Research Excellence data set) are used to examine the aberrant functional brain connectome in SCH which contains raw anatomical and functional MR data from 72 patients with Schizophrenia and 75 healthy controls, ranging in age from 18 to 65 years old. Our results show that PreCG has abnormal communication with Thalamus, Hippocampus, Parahippocampal Gyrus (pPaHC), posterior division of Supramarginal Gyrus (pSMG) and medial prefrontal cortex (mPFC) (p-FDR=0.05).
Lipid transfer from plants to arbuscular mycorrhiza fungi
Authors: Keymer Andreas , Pimprikar Priya , Wewer Vera , Huber Claudia , Brands Mathias , Bucerius Simone L. , Delaux Pierre-Marc , Klingl Verena , Röpenack-Lahaye Edda von , Wang Trevor L. , Eisenreich Wolfgang , Dörmann Peter , Parniske Martin , Gutjahr Caroline 
Published: May 2017

AbstractArbuscular mycorrhiza (AM) symbioses contribute to global carbon cycles as plant hosts divert up to 20% of photosynthate to the obligate biotrophic fungi. Previous studies suggested carbohydrates as the only form of carbon transferred to the fungi. However,de novofatty acid (FA) synthesis has not been observed in AM fungi in absence of the plant. In a forward genetic approach, we identified twoLotus japonicusmutants defective in AM-specific paralogs of lipid biosynthesis genes (KASIandGPAT6). These mutants perturb fungal development and accumulation of emblematic fungal 16:1ω5 FAs. Using isotopolog profiling we demonstrate that13C patterns of fungal FAs recapitulate those of wild-type hosts, indicating cross-kingdom lipid transfer from plants to fungi. This transfer of labelled FAs was not observed for the AM-specific lipid biosynthesis mutants. Thus, growth and development of beneficial AM fungi is not only fueled by sugars but depends on lipid transfer from plant hosts.
Skeletal cell YAP and TAZ redundantly promote bone development by regulation of collagen I expression and organization
Authors: Kegelman Christopher D. , Mason Devon E. , Dawahare James H. , Vigil Genevieve D. , Howard Scott S. , Bellido Teresita M. , Robling Alexander G. , Boerckel Joel D. 
Published: May 2017

ABSTRACTThe functions of the transcriptional co-activators YAP and TAZ in bone are controversial. Each has been observed to either promote or inhibit osteogenesisin vitro, while their roles in bone development are unknown. Here we report that combinatorial YAP/TAZ deletion from skeletal cells in mice caused osteogenesis imperfecta with severity dependent on targeted cell lineage and allele dosage. Osteocyte-conditional deletion impaired bone accrual and matrix collagen, while allele dosage-dependent deletion from all osteogenic lineage cells caused spontaneous fractures, with neonatal lethality only in dual homozygous knockouts. We identified putative target genes whose mutation in humans causes osteogenesis imperfecta and which contain promoter-proximate binding domains for the YAP/TAZ co-effector, TEAD4. Two candidates, Col1a1 and SerpinH1, exhibited reduced expression upon either YAP/TAZ deletion or YAP/TAZ-TEAD inhibition by verteporfin. Together, these data demonstrate that YAP and TAZ redundantly promote bone matrix development and implicate YAP/TAZ-mediated transcriptional regulation of collagen in osteogenesis imperfecta.
Cyclin G and the Polycomb Repressive Complexes PRC1 and PR-DUB cooperate for developmental stability
Authors: Dardalhon-Cuménal Delphine , Deraze Jérôme , Dupont Camille A , Ribeiro Valérie , Coléno-Costes Anne , Pouch Juliette , Le Crom Stéphane , Thomassin Hélène , Debat Vincent , Randsholt Neel B , Peronnet Frédérique 
Published: May 2017

AbstractInDrosophila, ubiquitous expression of a short Cyclin G isoform generates extreme developmental noise estimated by fluctuating asymmetry (FA), providing a model to tackle developmental stability. This transcriptional cyclin interacts with chromatin regulators of the Enhancer of Trithorax and Polycomb (ETP) and Polycomb families. We investigate here the importance of these interactions in developmental stability. Deregulation of Cyclin G highlights an organ intrinsic control of developmental noise, linked to the ETP-interacting domain, and enhanced by mutations in genes encoding members of the Polycomb Repressive complexes PRC1 and PR-DUB. Deep-sequencing of wing imaginal discs deregulatingCycGreveals that high developmental noise correlates with up-regulation of genes involved in translation and down-regulation of genes involved in energy production. Most Cyclin G direct transcriptional targets are also direct targets of PRC1, ASX and RNAPolII in the developing wing. Altogether, our results suggest that Cyclin G, PRC1 and PR-DUB cooperate for developmental stability.
The influence of study characteristics on coordinate-based fMRI meta-analyses
Authors: Bossier Han , Seurinck Ruth , Kühn Simone , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L.W. , Martinot Jean-Luc , Lemaitre Herve , Paus Tomáš , Millenet Sabina , Moerkerke Beatrijs ,   The IMAGEN Consortium
Published: May 2017

AbstractGiven the increasing amount of neuroimaging studies, there is a growing need to summarize published results. Coordinate-based meta-analyses use the locations of statistically significant local maxima with possibly the associated effect sizes to aggregate studies. In this paper, we investigate the influence of key characteristics of a coordinate-based meta-analysis on (1) the balance between false and true positives and (2) the reliability of the outcome from a coordinate-based meta-analysis. More particularly, we consider the influence of the chosen group level model at the study level (fixed effects, ordinary least squares or mixed effects models), the type of coordinate-based meta-analysis (Activation Likelihood Estimation, fixed effects and random effects meta-analysis) and the amount of studies included in the analysis (10, 20 or 35). To do this, we apply a resampling scheme on a large dataset (N= 1400) to create a test condition and compare this with an independent evaluation condition. The test condition corresponds to subsampling participants into studies and combine these using meta-analyses. The evaluation condition corresponds to a high-powered group analysis. We observe the best performance when using mixed effects models in individual studies combined with a random effects meta-analysis. This effect increases with the number of studies included in the meta-analysis. We also show that the popular Activation Likelihood Estimation procedure is a valid alternative, though the results depend on the chosen threshold for significance. Furthermore, this method requires at least 20 to 35 studies. Finally, we discuss the differences, interpretations and limitations of our results.
Evaluating strategies for reversing CRISPR-Cas9 gene drives
Authors: Vella Michael R. , Gunning Christian E. , Lloyd Alun L. , Gould Fred 
Published: May 2017

AbstractA gene drive biases inheritance of a gene so that it increases in frequency within a population even when the gene confers no fitness benefit. There has been renewed interest in environmental releases of engineered gene drives due to recent proof of principle experiments with the CRISPR-Cas9 system as a drive mechanism. Release of modified organisms, however, is controversial, especially when the drive mechanism could theoretically alter all individuals of a species. Thus, it is desirable to have countermeasures to reverse a drive if a problem arises. Several genetic mechanisms for limiting or eliminating gene drives have been proposed and/or developed, including synthetic resistance, reversal drives, and immunizing reversal drives. While predictions about efficacy of these mechanisms have been optimistic, we lack detailed analyses of their expected dynamics. We develop a discrete time model for population genetics of a drive and proposed genetic countermeasures. Efficacy of drive reversal varies between countermeasures. For some parameter values, the model predicts unexpected behavior including polymorphic equilibria and oscillatory dynamics. The timing and number of released individuals containing a genetic countermeasure can substantially impact outcomes. The choice among countermeasures by researchers and regulators will depend on specific goals and population parameters of target populations.