bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caspase-8 scaffolding function and MLKL regulate NLRP3 inflammasome activation downstream of TLR3
Authors: Kang Seokwon , Fernandes-Alnemri Teresa , Rogers Corey , Mayes Lindsey , Wang Ying , Dillon Christopher , Roback Linda , Kaiser William , Oberst Andrew , Sagara Junji , Fitzgerald Katherine A. , Green Douglas R. , Zhang Jianke , Mocarski Edward S. , Alnemri Emad S. 
Published: June 2015

AbstractTLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3, which together with MLKL provides both signal 1 and 2 for inflammasome assembly. Cytoplasmic dsRNA activates NLRP3 independent of TRIF, RIPK1, RIPK3 or mitochondrial DRP1, but requires FADD/caspase-8 in wildtype macrophages to remove RIPK3 inhibition. Our study provides a comprehensive analysis of pathways that lead to NLRP3 inflammasome activation in response to dsRNA.
Membranes with artificial free-volume for biofuel production
Authors: Petzetakis Nikos , Doherty Cara M. , Thornton Aaron W. , Chen X. Chelsea , Cotanda Pepa , Hill Anita J. , Balsara Nitash P. 
Published: June 2015

AbstractFree-volume of polymers governs transport of penetrants through polymeric films. Control over free-volume is thus important for the development of better membranes for a wide variety of applications such as gas separations, pharmaceutical purifications and energy storage. To date, methodologies used to create materials with different amounts of free-volume are based primarily on chemical synthesis of new polymers. Here we report a simple methodology for generating free-volume based on the self-assembly of polyethylene-b-polydimethylsiloxane-b-polyethylene triblock copolymers. We have used this method to fabricate a series of membranes with identical compositions but with different amounts of free-volume. We use the term artificial free-volume to refer to the additional free-volume created by self-assembly. The effect of artificial free-volume on selective transport through the membranes was tested using butanol/water and ethanol/water mixtures due to their importance in biofuel production. We found that the introduction of artificial free-volume improves both alcohol permeability and selectivity.
Characterization of molecular and cellular phenotypes associated with a heterozygous CNTNAP2 deletion using patient-derived hiPSC neural cells
Authors: Lee Inkyu S , Carvalho Claudia M B , Douvaras Panagiotis , Ho Seok-Man , Hartley Brigham J , Zuccherato Luciana W , Ladran Ian G , Siegel Arthur J , McCarthy Shane , Malhotra Dheeraj , Sebat Jonathan , Rapoport Judith , Fossati Valentina , Lupski James R , Levy Deborah L , Brennand Kristen J 
Published: June 2015

AbstractNeurodevelopmental disorders, such as autism spectrum disorders and schizophrenia, are complex disorders with a high degree of heritability. Genetic studies have identified several candidate genes associated with these disorders, including contactin-associated protein-like 2 (CNTNAP2). Traditionally, in animal models or in vitro, CNTNAP2 has been studied by genetic deletion or transcriptional knockdown, which reduces the expression of the entire gene; however, it remains unclear whether the mutations identified in clinical settings are sufficient to alter CNTNAP2 expression in human neurons. Here, using human induced pluripotent stem cells (hiPSCs) derived from two individuals with a large (289 kb) heterozygous deletion in CNTNAP2 (affecting exons 14–15) and discordant clinical outcomes, we have characterized CNTNAP2 expression patterns in hiPSC neural progenitor cells, two independent populations of hiPSC-derived neurons and hiPSC-derived oligodendrocyte precursor cells. First, we observed exon-specific changes in CNTNAP2 expression in both carriers; although the expression of exons 14–15 is significantly decreased, the expression of other exons is upregulated. Second, we observed significant differences in patterns of allele-specific expression in CNTNAP2 carriers that were consistent with the clinical outcome. Third, we observed a robust neural migration phenotype that correlated with diagnosis and exon- and allele-specific CNTNAP2 expression patterns, but not with genotype. In all, our data highlight the importance of considering the nature, location, and regulation of mutated alleles when attempting to connect genome wide association studies to gene function.
Prediction of structural features and application to outer membrane protein identification
Authors: Yan Renxiang , Wang Xiaofeng , Huang Lanqing , Yan Feidi , Xue Xiaoyu , Cai Weiwen 
Published: June 2015

AbstractProtein three-dimensional (3D) structures provide insightful information in many fields of biology. One-dimensional properties derived from 3D structures such as secondary structure, residue solvent accessibility, residue depth and backbone torsion angles are helpful to protein function prediction, fold recognition and ab initio folding. Here, we predict various structural features with the assistance of neural network learning. Based on an independent test dataset, protein secondary structure prediction generates an overall Q3 accuracy of ~80%. Meanwhile, the prediction of relative solvent accessibility obtains the highest mean absolute error of 0.164 and prediction of residue depth achieves the lowest mean absolute error of 0.062. We further improve the outer membrane protein identification by including the predicted structural features in a scoring function using a simple profile-to-profile alignment. The results demonstrate that the accuracy of outer membrane protein identification can be improved by ~3% at a 1% false positive level when structural features are incorporated. Finally, our methods are available as two convenient and easy-to-use programs. One is PSSM-2-Features for predicting secondary structure, relative solvent accessibility, residue depth and backbone torsion angles, the other is PPA-OMP for identifying outer membrane proteins from proteomes.
Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A
2
-IIA
Authors: Duchez Anne-Claire , Boudreau Luc H. , Naika Gajendra S. , Bollinger James , Belleannée Clémence , Cloutier Nathalie , Laffont Benoit , Mendoza-Villarroel Raifish E. , Lévesque Tania , Rollet-Labelle Emmanuelle , Rousseau Matthieu , Allaeys Isabelle , Tremblay Jacques J. , Poubelle Patrice E. , Lambeau Gérard , Pouliot Marc , Provost Patrick , Soulet Denis , Gelb Michael H. , Boilard Eric 
Published: June 2015

Significance
On activation, blood platelets package components from their cytoplasm into microparticles (MPs), tiny vesicles released by cytoplasmic membrane budding and shedding. Given that MPs can impact other cellular lineages on internalization, we aimed to decipher the mechanisms promoting MP internalization by cellular recipients. We modeled MP internalization by neutrophils and identified a predominant lipid, 12(S)-hydroxyeicosatetranoic acid, as a mediator critical for the promotion of MP internalization. MPs were found inside neutrophils from individuals with rheumatoid arthritis, and their presence in neutrophils in the joints of mice treated with arthritogenic serum is dependent on the expression of enzymes implicated in the generation of 12(S)-hydroxyeicosatetranoic acid. These findings reveal a unique molecular mechanism implicated in MP internalization relevant to inflammatory processes.
MetaQuery: a web server for rapid annotation and quantitative analysis of specific genes in the human gut microbiome
Authors: Nayfach Stephen , Fischbach Michael A. , Pollard Katherine S. 
Published: June 2015

Abstract
Summary: Microbiome researchers frequently want to know how abundant a particular microbial gene or pathway is across different human hosts, including its association with disease and its co-occurrence with other genes or microbial taxa. With thousands of publicly available metagenomes, these questions should be easy to answer. However, computational barriers prevent most researchers from conducting such analyses. We address this problem with MetaQuery, a web application for rapid and quantitative analysis of specific genes in the human gut microbiome. The user inputs one or more query genes, and our software returns the estimated abundance of these genes across 1267 publicly available fecal metagenomes from American, European and Chinese individuals. In addition, our application performs downstream statistical analyses to identify features that are associated with gene variation, including other query genes (i.e. gene co-variation), taxa, clinical variables (e.g. inflammatory bowel disease and diabetes) and average genome size. The speed and accessibility of MetaQuery are a step toward democratizing metagenomics research, which should allow many researchers to query the abundance and variation of specific genes in the human gut microbiome.
Availability and implementation: http://metaquery.docpollard.org.
Contact: snayfach@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
Lobsters: ocean icons in changing times
Authors: Briones-Fourzán Patricia , Lozano-Álvarez Enrique 
Published: June 2015

Abstract
The 10th International Conference and Workshop on Lobster Biology and Management was held in Cancún, Mexico, in May 2014. The papers included in this supplementary issue of the ICES Journal of Marine Science are a sample of the multidisciplinary nature of the conference and provide new knowledge of the biology, ecology, fisheries, and management and aquaculture of clawed, spiny, and slipper lobsters. The emphasis of the conference was climate change and its consequences for lobster biology, population dynamics, ecology, and fisheries. As noted in several papers, climate change is already affecting different lobster species by altering growth rates, sizes at maturity, the timing of reproductive processes, duration of larval development, and the timing and levels of settlement; by affecting key benthic habitat-forming species in settlement habitats; by increasing the risk of disease and impacting the behavioural ecology of lobsters, and by changing the spatial distribution of the stocks and, hence, affecting catches and the territorial behaviour of fishers. Other issues addressed at the conference included aquaculture and enhancement—the holy grails of lobster management—sustainable management strategies, and a fascinating review of the use of lobsters through human history. In addition to their economic importance, lobsters continue to provide valuable information to understand different marine environments in a changing climate.
Stocking is essential to meet the silver eel escapement target in a river system with currently low natural recruitment
Authors: Brämick Uwe , Fladung Erik , Simon Janek 
Published: June 2015

Abstract
Under the European Eel Regulation EG 1100/2007, Member States exhibiting natural habitats for the European eel (Anguilla anguilla) on their territory are obliged to prepare Eel Management Plans (EMP) containing appropriate measures to safeguard the escapement of a river system specific silver eel target biomass. Stocking is one management option to reach this target. We used various methodical approaches to study population parameters in a large lowland river under the application of a multi-annual intense stocking programme. The approaches were used to further enhance modelling of stock dynamics and silver eel escapement, in particular. Parameterizing the German Eel Model III (GEM III) with values and functions obtained for recruitment, growth, and mortality resulted in an annual escapement estimate of roughly 32 000–64 000 silver eels from 2010 to 2012. Escapement estimates based on a mark-recapture study conducted in parallel revealed somewhat lower values (11 000–25 000) for the same years. In view of the small number of natural recruits, such values are only contingent if stocking had a profound effect on silver eel production. Results from modelling annual silver eel escapement values indicate that escapement targets set in the EMP for this tributary cannot be reached without stocking. This constellation is likely to apply to other Eel Management Units with low current natural immigration values as well, and might be considered a key dilemma in eel management in such catchments due to the current confusion whether translocation of recruits yields a net benefit to the panmictic stock of the European eel.
Design and implementation of a privacy preserving electronic health record linkage tool in Chicago
Authors: Kho Abel N , Cashy John P , Jackson Kathryn L , Pah Adam R , Goel Satyender , Boehnke Jörn , Humphries John Eric , Kominers Scott Duke , Hota Bala N , Sims Shannon A , Malin Bradley A , French Dustin D , Walunas Theresa L , Meltzer David O , Kaleba Erin O , Jones Roderick C , Galanter William L 
Published: June 2015

Abstract
Objective To design and implement a tool that creates a secure, privacy preserving linkage of electronic health record (EHR) data across multiple sites in a large metropolitan area in the United States (Chicago, IL), for use in clinical research.
Methods The authors developed and distributed a software application that performs standardized data cleaning, preprocessing, and hashing of patient identifiers to remove all protected health information. The application creates seeded hash code combinations of patient identifiers using a Health Insurance Portability and Accountability Act compliant SHA-512 algorithm that minimizes re-identification risk. The authors subsequently linked individual records using a central honest broker with an algorithm that assigns weights to hash combinations in order to generate high specificity matches.
Results The software application successfully linked and de-duplicated 7 million records across 6 institutions, resulting in a cohort of 5 million unique records. Using a manually reconciled set of 11 292 patients as a gold standard, the software achieved a sensitivity of 96% and a specificity of 100%, with a majority of the missed matches accounted for by patients with both a missing social security number and last name change. Using 3 disease examples, it is demonstrated that the software can reduce duplication of patient records across sites by as much as 28%.
Conclusions Software that standardizes the assignment of a unique seeded hash identifier merged through an agreed upon third-party honest broker can enable large-scale secure linkage of EHR data for epidemiologic and public health research. The software algorithm can improve future epidemiologic research by providing more comprehensive data given that patients may make use of multiple healthcare systems.
National Veterans Health Administration inpatient risk stratification models for hospital-acquired acute kidney injury
Authors: Cronin Robert M , VanHouten Jacob P , Siew Edward D , Eden Svetlana K , Fihn Stephan D , Nielson Christopher D , Peterson Josh F , Baker Clifton R , Ikizler T Alp , Speroff Theodore , Matheny Michael E 
Published: June 2015

AbstractObjective Hospital-acquired acute kidney injury (HA-AKI) is a potentially preventable cause of morbidity and mortality. Identifying high-risk patients prior to the onset of kidney injury is a key step towards AKI prevention.Materials and Methods A national retrospective cohort of 1,620,898 patient hospitalizations from 116 Veterans Affairs hospitals was assembled from electronic health record (EHR) data collected from 2003 to 2012. HA-AKI was defined at stage 1+, stage 2+, and dialysis. EHR-based predictors were identified through logistic regression, least absolute shrinkage and selection operator (lasso) regression, and random forests, and pair-wise comparisons between each were made. Calibration and discrimination metrics were calculated using 50 bootstrap iterations. In the final models, we report odds ratios, 95% confidence intervals, and importance rankings for predictor variables to evaluate their significance.Results The area under the receiver operating characteristic curve (AUC) for the different model outcomes ranged from 0.746 to 0.758 in stage 1+, 0.714 to 0.720 in stage 2+, and 0.823 to 0.825 in dialysis. Logistic regression had the best AUC in stage 1+ and dialysis. Random forests had the best AUC in stage 2+ but the least favorable calibration plots. Multiple risk factors were significant in our models, including some nonsteroidal anti-inflammatory drugs, blood pressure medications, antibiotics, and intravenous fluids given during the first 48 h of admission.Conclusions This study demonstrated that, although all the models tested had good discrimination, performance characteristics varied between methods, and the random forests models did not calibrate as well as the lasso or logistic regression models. In addition, novel modifiable risk factors were explored and found to be significant.
Clinical implications of motor deficits related to brain tumors†
Authors: Amidei Christina , Kushner David S. 
Published: June 2015

Abstract
Motor deficits, including unilateral or bilateral weakness, plegia, ataxia, spasticity, and loss of complex movement execution, can occur during any brain tumor illness. Tumor location, treatment effects, and medications contribute to these deficits. Motor dysfunction has been associated with significant deterioration in health-related quality of life in patients with primary and metastatic brain tumors. Significant decrease in median overall survival has been reported in patients with motor deficits, although the reasons for this are unclear. Motor deficits, particularly gait impairment, contribute to significant symptom burden at end of life, and are the most common reasons for initiation of hospice care. Interventions must focus on prevention and amelioration of motor dysfunction throughout the disease course in order to preserve quality of life. The impact of exercise in prolonging survival and improving quality of life requires further study.
Physical conditions of the interstellar medium in star-forming galaxies at z ∼ 1.5
Authors: Hayashi Masao , Ly Chun , Shimasaku Kazuhiro , Motohara Kentaro , Malkan Matthew A. , Nagao Tohru , Kashikawa Nobunari , Goto Ryosuke , Naito Yoshiaki 
Published: June 2015

Abstract
We present results from Subaru Fiber Multi Object Spectrograph near-infrared spectroscopy of 118 star-forming galaxies at z ∼ 1.5 in the Subaru Deep Field. These galaxies are selected as [O ii]λ3727 emitters at z ≈ 1.47 and 1.62 from narrow-band imaging. We detect the Hα emission line in 115 galaxies, the [O iii]λ5007 emission line in 45 galaxies, and Hβ, [N ii]λ6584, and [S ii]λλ6716, 6731 in 13, 16, and 6 galaxies, respectively. Including the [O ii] emission line, we use the six strong nebular emission lines in the individual and composite rest-frame optical spectra to investigate the physical conditions of the interstellar medium in star-forming galaxies at z ∼ 1.5. We find a tight correlation between Hα and [O ii], which suggests that [O ii] can be a good star formation rate indicator for galaxies at z ∼ 1.5. The line ratios of Hα/[O ii] are consistent with those of local galaxies. We also find that [O ii] emitters have strong [O iii] emission lines. The [O iii]/[O ii] ratios are larger than normal star-forming galaxies in the local universe, suggesting a higher ionization parameter. Less massive galaxies have larger [O iii]/[O ii] ratios. With evidence that the electron density is consistent with local galaxies, the high ionization of galaxies at high redshifts may be attributed to a harder radiation field by a young stellar population and/or an increase in the number of ionizing photons from each massive star.
Extending Lévy search theory from one to higher dimensions: Lévy walking favours the blind
Authors: Reynolds A. M. 
Published: June 2015

A diverse range of organisms, including T cells,
E. coli
, honeybees, sharks, turtles, bony fish, jellyfish, wandering albatrosses and even human hunter–gatherers have movement patterns that can be approximated by Lévy walks (LW; sometimes called Lévy flights in the biological and ecological literature). These observations lend support to the ‘Lévy flight foraging hypothesis’ which asserts that natural selection should have led to adaptations for Lévy flight foraging, because Lévy flights can optimize search efficiencies. The hypothesis stems from a rigorous theory of one-dimensional searching and from simulation data for two-dimensional searching. The potential effectiveness of three-dimensional Lévy searches has not been examined but is central to a proper understanding of marine predators and T cells which have provided the most compelling empirical evidence for LW. Here I extend Lévy search theory from one to three dimensions. The new theory predicts that three-dimensional Lévy searching can be advantageous but only when targets are large compared with the perceptual range of the searchers, i.e. only when foragers are effectively blind and need to come into contact with a target to establish its presence. This may explain why effective blindness is a common factor among three-dimensional Lévy walkers.
Effects of MDMA on socioemotional feelings, authenticity, and autobiographical disclosure in healthy volunteers in a controlled setting
Authors: Baggott Matthew J. , Coyle Jeremy R. , Siegrist Jennifer D. , Garrison Kathleen , Galloway Gantt , Mendelson John E. 
Published: June 2015

AbstractThe drug 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”, “molly”) is a widely used illicit drug and experimental adjunct to psychotherapy. MDMA has unusual, poorly understood socioemotional effects, including feelings of interpersonal closeness and sociability. To better understand these effects, we conducted a within-subjects double-blind placebo controlled study of the effects of 1.5 mg/kg oral MDMA on social emotions and autobiographical disclosure in a controlled setting. MDMA displayed both sedative- and stimulant-like effects, including increased self-report anxiety. At the same time, MDMA positively altered evaluation of the self (i.e., increasing feelings of authenticity) while decreasing concerns about negative evaluation by others (i.e., decreasing social anxiety). Consistent with these feelings, MDMA increased how comfortable participants felt describing emotional memories. Overall, MDMA produced a prosocial syndrome that seemed to facilitate emotional disclosure and that appears consistent with the suggestion that it represents a novel pharmacological class.