bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure-based design and functional studies of novel noroviral 3C protease chimaeras offer insights into substrate specificity
Authors: Herod Morgan R. , Prince Cynthia A. , Skilton Rachel J. , Ward Vernon K. , Cooper Jonathan B. , Clarke Ian N. 
Published: October 2014

The norovirus NS6 protease is a key target for anti-viral drug development. Noroviruses encode a 2200 amino acid polyprotein which is cleaved by this critical protease at five defined boundary substrates into six mature non-structural (NS) proteins. Studies of the human norovirus (HNV) NS6 protease, in the context of a full ORF1 polyprotein, have been severely hampered because HNVs are not culturable. Thus, investigations into the HNV NS6 protease have been largely restricted to in vitro assays using Escherichia coli-expressed, purified enzyme. The NS6 protease is formed of two distinct domains joined by a linking loop. Structural data suggest that domain 2 of the protease possesses substantial substrate binding pockets which form the bulk of the interactions with the NS boundaries and largely dictate boundary specificity and cleavage. We have constructed chimaeric murine norovirus (MNV) genomes carrying individual domains from the HNV protease and demonstrated by cell transfection that chimaeric HNV proteases have functional activity in the context of the full-length ORF1 polyprotein. Although domain 2 primarily confers boundary specificity, our data suggest that an inter-domain interaction exists within HNV NS6 protease which influences cleavage of specific substrates. The present study also shows that chimaeric MNVs provide improved models for studying HNV protein function in the context of a full ORF1 polyprotein.
Visualization and quantification of nascent RAD51 filament formation at single-monomer resolution
Authors: Candelli Andrea , Holthausen Jan Thomas , Depken Martin , Brouwer Ineke , Franker Mariëlla A. M. , Marchetti Margherita , Heller Iddo , Bernard Stéphanie , Garcin Edwige B. , Modesti Mauro , Wyman Claire , Wuite Gijs J. L. , Peterman Erwin J. G. 
Published: October 2014

Significance
The mechanism of RAD51-recombinase filament formation is visualized and quantified with single-molecule resolution using a combination of dual optical tweezers, fluorescence microscopy, and microfluidics. With this method, short-lived transient intermediates formed during nascent RAD51 filament assembly were observed directly. It is observed that RAD51 nuclei consisting of a variable number of monomers bind from solution to DNA, with an interaction time that increases with nucleus size. Nuclei that remain bound to DNA long enough can grow by the incorporation of additional RAD51 monomers, stabilizing the RAD51 filament.
A receptor-like protein mediates the response to pectin modification by activating brassinosteroid signaling
Authors: Wolf Sebastian , van der Does Dieuwertje , Ladwig Friederike , Sticht Carsten , Kolbeck Andreas , Schürholz Ann-Kathrin , Augustin Sebastian , Keinath Nana , Rausch Thomas , Greiner Steffen , Schumacher Karin , Harter Klaus , Zipfel Cyril , Höfte Herman 
Published: October 2014

Significance
Plant growth and development depend on the biosynthesis and remodeling of the cell wall. To coordinate these two processes, surveillance mechanisms have evolved to monitor the state of the cell wall. The brassinosteroid (BR) hormone signaling pathway plays an essential role in growth control and regulates the expression of a plethora of cell wall-related genes. We have previously shown that feedback signaling from the wall can modulate the outputs of the BR pathway, ensuring cell wall homeostasis and integrity. Here, we identified a receptor-like protein (RLP44), which mediates the activation of BR signaling through direct interaction with the BR coreceptor BAK1. Thus, RLP44 integrates cell wall surveillance with hormone signaling to control cell wall integrity and growth.
JAK2V617F promotes replication fork stalling with disease-restricted impairment of the intra-S checkpoint response
Authors: Chen Edwin , Ahn Jong Sook , Massie Charlie E. , Clynes David , Godfrey Anna L. , Li Juan , Park Hyun Jung , Nangalia Jyoti , Silber Yvonne , Mullally Ann , Gibbons Richard J. , Green Anthony R. 
Published: October 2014

Significance
Cancers arise through a succession of enabling genetic lesions, but the consequences of many driver mutations remain unclear, especially in the earliest stages of tumor formation. The myeloproliferative neoplasms (MPNs) encompass a group of chronic hematologic disorders that can collectively provide a window into these early stages of leukemia evolution. This study reveals a role for the JAK2V617F mutation, the most frequent genetic abnormality in MPN patients, in impairing replication fork progression during cell division of MPN patient-derived tumor cells. Moreover, analysis of different MPN disease subtypes reveals unexpected differences in DNA repair activity in response to JAK2V617F-induced perturbations in replication dynamics. These findings have potential implications for tumor clonal evolution and individualized cancer therapy.
Allopolyploidy, diversification, and the Miocene grassland expansion
Authors: Estep Matt C. , McKain Michael R. , Vela Diaz Dilys , Zhong Jinshun , Hodge John G. , Hodkinson Trevor R. , Layton Daniel J. , Malcomber Simon T. , Pasquet Rémy , Kellogg Elizabeth A. 
Published: October 2014

SignificanceDuplication of genomes following hybridization (allopolyploidy) is common among flowering plants, particularly in the grasses that cover vast areas of the world and provide food and fuel. Here, we find that genome duplication has occurred at a remarkable rate, accounting for at least a third of all speciation events in a group of about 1,200 species. Much of this genome duplication occurred during the expansion of the C4grasslands in the Late Miocene. We find no evidence that allopolyploidy leads directly to a change in the net rate of diversification or correlates with the origin of novel morphological characters. However, as a mode of speciation, the frequency of allopolyploidization is surprisingly high.
Neutral molecular cluster formation of sulfuric acid–dimethylamine observed in real time under atmospheric conditions
Authors: Kürten Andreas , Jokinen Tuija , Simon Mario , Sipilä Mikko , Sarnela Nina , Junninen Heikki , Adamov Alexey , Almeida João , Amorim Antonio , Bianchi Federico , Breitenlechner Martin , Dommen Josef , Donahue Neil M. , Duplissy Jonathan , Ehrhart Sebastian , Flagan Richard C. , Franchin Alessandro , Hakala Jani , Hansel Armin , Heinritzi Martin , Hutterli Manuel , Kangasluoma Juha , Kirkby Jasper , Laaksonen Ari , Lehtipalo Katrianne , Leiminger Markus , Makhmutov Vladimir , Mathot Serge , Onnela Antti , Petäjä Tuukka , Praplan Arnaud P. , Riccobono Francesco , Rissanen Matti P. , Rondo Linda , Schobesberger Siegfried , Seinfeld John H. , Steiner Gerhard , Tomé António , Tröstl Jasmin , Winkler Paul M. , Williamson Christina , Wimmer Daniela , Ye Penglin , Baltensperger Urs , Carslaw Kenneth S. , Kulmala Markku , Worsnop Douglas R. , Curtius Joachim 
Published: October 2014

Significance
A significant fraction of atmospheric aerosols is formed from the condensation of low-volatility vapors. These newly formed particles can grow, become seeds for cloud particles, and influence climate. New particle formation in the planetary boundary layer generally proceeds via the neutral channel. However, unambiguous identification of neutral nucleating clusters has so far not been possible under atmospherically relevant conditions. We explored the system of sulfuric acid, water, and dimethylamine in a well-controlled laboratory experiment and measured the time-resolved concentrations of neutral clusters. Clusters containing up to 14 sulfuric acid and 16 dimethylamine molecules were observed. Our results demonstrate that a cluster containing as few as two sulfuric acid and one or two dimethylamine molecules is already stable against evaporation.
Identification and characterization of alphavirus M1 as a selective oncolytic virus targeting ZAP-defective human cancers
Authors: Lin Yuan , Zhang Haipeng , Liang Jiankai , Li Kai , Zhu Wenbo , Fu Liwu , Wang Fang , Zheng Xiaoke , Shi Huijuan , Wu Sihan , Xiao Xiao , Chen Lijun , Tang Lipeng , Yan Min , Yang Xiaoxiao , Tan Yaqian , Qiu Pengxin , Huang Yijun , Yin Wei , Su Xinwen , Hu Haiyan , Hu Jun , Yan Guangmei 
Published: October 2014

Significance
Although oncolytic virotherapy is showing great promise in clinical trials, not all patients are benefiting. Identifying predictors of therapeutic effectiveness for each oncolytic virus would provide a good chance to increase response rate. Here, we describe an alphavirus (M1) that possesses selective and potent antitumor activity through intravenous infusion, whereas its replication is controlled by the zinc-finger antiviral protein (ZAP) gene. A survey of cancer tissue banks reveals that ZAP is commonly deficient in human cancers, suggesting extensive application prospects of M1. Our work provides an example of a potentially personalized cancer therapy using a targeted oncolytic virus that can be selectively administered to patients with ZAP-deficient tumors. We predict that such agents will form the armamentarium of cancer therapy in the future.
Autism spectrum disorder severity reflects the average contribution of de novo and familial influences
Authors: Robinson Elise B. , Samocha Kaitlin E. , Kosmicki Jack A. , McGrath Lauren , Neale Benjamin M. , Perlis Roy H. , Daly Mark J. 
Published: October 2014

Significance
Autism spectrum disorder (ASD) research is complicated by heterogeneity. There are several types of genetic risk factors for ASDs, and that diversity may be reflected in case presentation. This study presents evidence for systematic variation in the genetic architecture of ASDs in which higher functioning cases, defined through cognitive and behavioral assessments, are more likely to manifest familial influences. This finding suggests that genetic and neurobiological research into ASDs and other neuropsychiatric disorders may be pursued more efficiently through greater phenotypic characterization.
Bloom of resident antibiotic-resistant bacteria in soil following manure fertilization
Authors: Udikovic-Kolic Nikolina , Wichmann Fabienne , Broderick Nichole A. , Handelsman Jo 
Published: October 2014

SignificanceThe increasing prevalence of antibiotic-resistant bacteria is one of the most serious threats to public health in the 21st century. One route by which resistance genes enter the food system is through amendment of soils with manure from antibiotic-treated animals, which are considered a reservoir of such genes. Previous studies have associated application of pig manure with the dispersal of sulfonamide-resistance genes to soil bacteria. In this study, we found that dairy cow manure amendment enhanced the proliferation of resident antibiotic-resistant bacteria and genes encoding β-lactamases in soil even though the cows from which the manure was derived had not been treated with antibiotics. Our findings provide previously unidentified insight into the mechanism by which amendment with manure enriches antibiotic-resistant bacteria in soil.
Genetically enhancing mitochondrial antioxidant activity improves muscle function in aging
Authors: Umanskaya Alisa , Santulli Gaetano , Xie Wenjun , Andersson Daniel C. , Reiken Steven R. , Marks Andrew R. 
Published: October 2014

Significance
Age-related muscle weakness has major adverse consequences on quality of life, increasing the risk of falls, fractures, and movement impairments. Albeit an increased oxidative state has been shown to contribute to age-dependent reduction in skeletal muscle function, little is known about the mechanisms connecting oxidation and muscle weakness. We show here that genetically enhancing mitochondrial antioxidant activity causes improved skeletal muscle function and voluntary exercise in aged mice. Our findings have broad implications for both the aging and muscle physiology fields, as we present an important molecular mechanism for muscle weakness in aging and skeletal muscle force regulation.
Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity
Authors: Leclercq Sophie , Matamoros Sébastien , Cani Patrice D. , Neyrinck Audrey M. , Jamar François , Stärkel Peter , Windey Karen , Tremaroli Valentina , Bäckhed Fredrik , Verbeke Kristin , de Timary Philippe , Delzenne Nathalie M. 
Published: October 2014

Significance
Alcohol-dependent subjects frequently develop emotional symptoms that contribute to the persistence of alcohol drinking. These subjects are also characterized by gastrointestinal disturbances. In this study, we showed that alcohol-dependent subjects with altered intestinal permeability had also altered gut-microbiota composition and activity and remained with high scores of depression, anxiety, and alcohol craving after a short-term detoxification program. These results are consistent with the existence of a gut–brain axis in alcohol dependence, in which the gut microbiota could alter the gut-barrier function and influence behavior in alcohol dependence. Therefore, this study opens a previously unidentified field of research for the treatment and the management of alcohol dependence, targeting the gut microbiota.
Public awareness, concerns, and priorities about anthropogenic impacts on marine environments
Authors: Gelcich Stefan , Buckley Paul , Pinnegar John K. , Chilvers Jason , Lorenzoni Irene , Terry Geraldine , Guerrero Matias , Castilla Juan Carlos , Valdebenito Abel , Duarte Carlos M. 
Published: October 2014

Significance
We report the results of a 10,106-person pan-European survey of public awareness, concerns, and priorities about marine anthropogenic impacts as a way to inform both science and policy initiatives in achieving marine sustainability. Results enable scientists and policymakers to understand how the public relates to the marine environment and how they frame impacts and can help make managerial, scientific, and policy priorities more responsive to public values.
Label-free electrochemical detection of human methyltransferase from tumors
Authors: Furst Ariel L. , Muren Natalie B. , Hill Michael G. , Barton Jacqueline K. 
Published: October 2014

Significance
Epigenetic modifications, including DNA methylation, govern gene expression. Aberrant methylation by DNA methyltransferases can lead to tumorigenesis, so that efficient detection of methyltransferase activity provides an early cancer diagnostic. Current methods, requiring fluorescence or radioactivity, are cumbersome; electrochemical platforms, in contrast, offer high portability, sensitivity, and ease of use. We have developed a label-free electrochemical platform to detect the activity of the most abundant human methyltransferase, DNA(cytosine-5)-methyltransferase1 (DNMT1), and have applied this method in detecting DNMT1 in crude lysates from both cultured human colorectal cancer cells (HCT116) and colorectal tissue samples.
Matching and Oddity Learning in the Pigeon: Transfer Effects and the Absence of Relational Learning
Authors: Wilson Bundy , Mackintosh N. J. , Boakes R. A. 
Published: October 2014

Three experiments examined the extent to which pigeons trained on a matching or oddity discrimination with one pair of colours showed transfer when tested on a new matching or oddity discrimination with a new pair of colours. Experiment 1 examined the effects of key spacing and a delay procedure and replicated previous reports that in the transfer stage subjects given the same kind of problem (Non-shift condition) in general learn more rapidly than those given the opposite problem (Shift condition). However, this difference appeared only when pigeons given matching in both training and transfer stages were compared to those shifted from oddity to matching; it did not appear in birds transferred to oddity. Transfer was not significantly affected by key spacing or by the delay. Experiments 2 and 3 examined transfer from a non-relational conditional discrimination based on one set of colours to a subsequent matching or oddity task based on two new colours. Both a comparison between the results of Experiment 1 and 2 and the corresponding within-experiment comparison from Experiment 3 showed that transfer from conditional training to matching was as great as from prior training on matching, while prior training on oddity produced negative transfer on shift to matching. It was suggested that this negative transfer occurs because pigeons trained on oddity have not learned to override an initial bias towards the odd stimulus in an array. Whatever the correct explanation; the present results provide no support for the claim that pigeons solve matching or oddity discriminations relationally.
Thermal effects on the switching kinetics of silver/manganite memristive
systems
Authors: Stoliar P , Sánchez M J , Patterson G A , Fierens P I 
Published: October 2014

Abstract
We investigate the switching kinetics of oxygen vacancy (Ov) diffusion in
La(5/8-y)Pr(y)Ca(3/8)MnO(3)-Ag (LPCMO–Ag) memristive interfaces by performing experiments
on the temperature dependence of the high resistance state under thermal cycling. Experimental
results are well reproduced by numerical simulations based on thermally activated Ov diffusion
processes and fundamental assumptions relying on a recent model proposed to explain bipolar
resistive switching in manganite-based cells. The confident values obtained for activation
energies and the diffusion coefficient associated to Ov dynamics constitute a validation test
for both model predictions and Ov diffusion mechanisms in memristive interfaces.
Computing autocatalytic sets to unravel inconsistencies in metabolic network reconstructions
Authors: Schmidt Ralf , Waschina Silvio , Boettger-Schmidt Daniela , Kost Christian , Kaleta Christoph 
Published: October 2014

Abstract
Motivation : Genome-scale metabolic network reconstructions have been established as a powerful tool for the prediction of cellular phenotypes and metabolic capabilities of organisms. In recent years, the number of network reconstructions has been constantly increasing, mostly because of the availability of novel (semi-)automated procedures, which enabled the reconstruction of metabolic models based on individual genomes and their annotation. The resulting models are widely used in numerous applications. However, the accuracy and predictive power of network reconstructions are commonly limited by inherent inconsistencies and gaps.
Results : Here we present a novel method to validate metabolic network reconstructions based on the concept of autocatalytic sets. Autocatalytic sets correspond to collections of metabolites that, besides enzymes and a growth medium, are required to produce all biomass components in a metabolic model. These autocatalytic sets are well-conserved across all domains of life, and their identification in specific genome-scale reconstructions allows us to draw conclusions about potential inconsistencies in these models. The method is capable of detecting inconsistencies, which are neglected by other gap-finding methods. We tested our method on the Model SEED, which is the largest repository for automatically generated genome-scale network reconstructions. In this way, we were able to identify a significant number of missing pathways in several of these reconstructions. Hence, the method we report represents a powerful tool to identify inconsistencies in large-scale metabolic networks.
Availability and implementation : The method is available as source code on http://users.minet.uni-jena.de/∼m3kach/ASBIG/ASBIG.zip .
Contact : christoph.kaleta@uni-jena.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Deviance residuals-based sparse PLS and sparse kernel PLS regression for censored data
Authors: Bastien Philippe , Bertrand Frédéric , Meyer Nicolas , Maumy-Bertrand Myriam 
Published: October 2014

AbstractMotivation : A vast literature from the past decade is devoted to relating gene profiles and subject survival or time to cancer recurrence. Biomarker discovery from high-dimensional data, such as transcriptomic or single nucleotide polymorphism profiles, is a major challenge in the search for more precise diagnoses. The proportional hazard regression model suggested by Cox (1972), to study the relationship between the time to event and a set of covariates in the presence of censoring is the most commonly used model for the analysis of survival data. However, like multivariate regression, it supposes that more observations than variables, complete data, and not strongly correlated variables are available. In practice, when dealing with high-dimensional data, these constraints are crippling. Collinearity gives rise to issues of over-fitting and model misidentification. Variable selection can improve the estimation accuracy by effectively identifying the subset of relevant predictors and enhance the model interpretability with parsimonious representation. To deal with both collinearity and variable selection issues, many methods based on least absolute shrinkage and selection operator penalized Cox proportional hazards have been proposed since the reference paper of Tibshirani. Regularization could also be performed using dimension reduction as is the case with partial least squares (PLS) regression. We propose two original algorithms named sPLSDR and its non-linear kernel counterpart DKsPLSDR, by using sparse PLS regression (sPLS) based on deviance residuals. We compared their predicting performance with state-of-the-art algorithms on both simulated and real reference benchmark datasets.Results : sPLSDR and DKsPLSDR compare favorably with other methods in their computational time, prediction and selectivity, as indicated by results based on benchmark datasets. Moreover, in the framework of PLS regression, they feature other useful tools, including biplots representation, or the ability to deal with missing data. Therefore, we view them as a useful addition to the toolbox of estimation and prediction methods for the widely used Cox’s model in the high-dimensional and low-sample size settings.Availability and implementation : The R-package plsRcox is available on the CRAN and is maintained by Frédéric Bertrand. http://cran.r-project.org/web/packages/plsRcox/index.html .Contact : pbastien@rd.loreal.com or fbertran@math.unistra.fr .Supplementary information : Supplementary data are available at Bioinformatics online.
Chimera: a Bioconductor package for secondary analysis of fusion products
Authors: Beccuti Marco , Carrara Matteo , Cordero Francesca , Lazzarato Fulvio , Donatelli Susanna , Nadalin Francesca , Policriti Alberto , Calogero Raffaele A. 
Published: October 2014

Abstract
Summary: Chimera is a Bioconductor package that organizes, annotates, analyses and validates fusions reported by different fusion detection tools; current implementation can deal with output from bellerophontes, chimeraScan, deFuse, fusionCatcher, FusionFinder, FusionHunter, FusionMap, mapSplice, Rsubread, tophat-fusion and STAR. The core of Chimera is a fusion data structure that can store fusion events detected with any of the aforementioned tools. Fusions are then easily manipulated with standard R functions or through the set of functionalities specifically developed in Chimera with the aim of supporting the user in managing fusions and discriminating false-positive results.
Availability and implementation: Chimera is implemented as a Bioconductor package in R. The package and the vignette can be downloaded at bioconductor.org.
Contact: raffaele.calogero@unito.it
Supplementary information: Supplementary data are available at Bioinformatics online.