bluuebunny/crossref_metadata_2025_split huggingface dataset:
Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration
Authors: Dong Yun , Fischer Roman , Naudé Petrus J. W. , Maier Olaf , Nyakas Csaba , Duffey Maëlle , Van der Zee Eddy A. , Dekens Doortje , Douwenga Wanda , Herrmann Andreas , Guenzi Eric , Kontermann Roland E. , Pfizenmaier Klaus , Eisel Ulrich L. M. 
Published: October 2016

SignificanceTNF is known to play an important role in various neurodegenerative diseases. However, anti-TNF therapeutics failed in clinical trials of neurodegenerative diseases. This failure is most likely due to antithetic effects of the TNF receptors in the central nervous system, whereby TNFR1 promotes inflammatory degeneration and TNFR2 neuroprotection. Here we show that novel TNFR-selective therapeutics, i.e., a TNFR1 antagonist and a TNFR2 agonist, block neuroinflammation and promote neuronal survival in a mouse model of neurodegeneration related to Alzheimer disease as well as other neurodegenerative diseases. Most important, neuroprotection mediated by the TNFR1 antagonist is abrogated by simultaneous blockade of TNFR2 activation, revealing that neuroprotection requires TNFR2 signaling and uncover why anti-TNF drugs failed in treatment of neurodegenerative diseases.
A Population of planetary systems characterized by short-period, Earth-sized planets
Authors: Steffen Jason H. , Coughlin Jeffrey L. 
Published: October 2016

SignificanceCharacterizing the variety of planets and planetary systems orbiting distant stars (exoplanets) is a key ingredient to improving our understanding of the Solar System and of planet formation in general. One important observable property of a planetary system is its architecture—the sizes and orbital periods of the planets in a system and how they are related to each other. From a statistical analysis of the planet candidate catalog from NASA’sKeplermission, we identify a population of planetary systems characterized by a unique system architecture. Differences in system architecture indicate different paths in the formation or dynamical history of a planetary system—giving clues to the physical conditions or processes that drive systems along those paths.
Proteolytic processing of Middle East respiratory syndrome coronavirus spikes expands virus tropism
Authors: Park Jung-Eun , Li Kun , Barlan Arlene , Fehr Anthony R. , Perlman Stanley , McCray Paul B. , Gallagher Tom 
Published: October 2016

Significance
Middle East respiratory syndrome coronavirus (MERS-CoV) can cause lethal pneumonia by infecting lung epithelial cells. Infection requires viral “spike” proteins, which catalyze virus–cell membrane fusion during cell entry. Fusion catalysis requires that spikes be first cleaved by cellular proteases. MERS-CoV spikes are cleaved in virus-producing cells before subsequent virus-cell entry, whereas other human coronaviruses have spikes that are cleaved in virus-infecting cells during virus-cell entry. Here, we found that the early MERS-CoV cleavages are required for the subsequent infection of human lung-like cells, but are dispensable for infection of several other cell types. Our findings demonstrate that the spike cleavage status of MERS-CoVs dictates cell tropism, and points to spike proteolytic processing as a correlate of MERS-CoV virulence.
Identifying the elusive link between amino acid sequence and charge selectivity in pentameric ligand-gated ion channels
Authors: Cymes Gisela D. , Grosman Claudio 
Published: October 2016

Significance
The cation-versus-anion selectivity of pentameric ligand-gated ion channels cannot always be predicted on the basis of their amino acid sequences alone. Indeed, the relationship between amino acid sequence and function contains subtle elements that have eluded prior investigation. Here, we found that ion–ion interactions between the passing ions and ionized side chains in the first turn of the M2 α-helices dominate the permeation free-energy landscape, but we also found that the mere presence of an ionized residue in the first turn of M2 does not ensure that its charge is “felt” by permeating ions. Instead, there seems to be a requirement for a proper conformation for a charged side chain to exert its effect on selectivity.
Controlling the mode of operation of organic transistors through side-chain engineering
Authors: Giovannitti Alexander , Sbircea Dan-Tiberiu , Inal Sahika , Nielsen Christian B. , Bandiello Enrico , Hanifi David A. , Sessolo Michele , Malliaras George G. , McCulloch Iain , Rivnay Jonathan 
Published: October 2016

Significance
Side-chain engineering is a versatile tool to modify the processability, as well as the physical, electrical, and optical properties, of conjugated polymers. This approach is used to tailor the operating mechanism of electrolyte-gated organic transistors, allowing for facile bulk doping and therefore efficient modulation of transistor channel conductance. Such transistors combine fast response with high current-to-voltage signal transduction necessary for active sensing and low-power circuit applications.
Herpes simplex virus ICP27 regulates alternative pre-mRNA polyadenylation and splicing in a sequence-dependent manner
Authors: Tang Shuang , Patel Amita , Krause Philip R. 
Published: October 2016

Significance
Although implicated, the role of herpes simplex virus (HSV) infected cell culture polypeptide 27 (ICP27) in cotranscriptional pre-mRNA processing remains poorly understood. We show that ICP27 promotes cotranscriptional cellular pre-mRNA 3′ end formation using cryptic polyadenylation signals in introns, generating hundreds of novel, intronless GC-rich cellular transcripts that resemble HSV genes. ICP27 also causes aberrant pre-mRNA splicing of some genes. ICP27-targeted genes share common features such as high GC content, cytosine-rich sequences, and suboptimal splice sites, providing an explanation for the observed target specificity of ICP27 and suggesting an overlapping mechanism for ICP27-mediated aberrant pre-mRNA splicing and polyadenylation. By specifically modifying pre-mRNA processing of HSV-like GC-rich transcripts that are likely spared by the virion host shutoff protein, ICP27 contributes to virus-induced host shutoff required for efficient viral growth.
Mitotic Golgi disassembly is required for bipolar spindle formation and mitotic progression
Authors: Guizzunti Gianni , Seemann Joachim 
Published: October 2016

SignificanceDuring mammalian cell division, the contiguous Golgi ribbon is first vesiculated and then partitioned into the daughter cells with the aid of the mitotic spindle. Whether Golgi vesiculation is required for cell division is unclear. Here, we show that inhibition of Golgi disassembly by the acute formation of a polymer in the Golgi lumen prior to mitotic entry blocks bipolar spindle formation and arrests cells in early mitosis with an active spindle assembly checkpoint (SAC). Importantly, mitotic progression is fully restored upon depletion of centrosomes. Our work thus reveals that mitotic Golgi disassembly is tightly monitored and acts as an upstream surveillance point for the canonical SAC to ensure the fidelity of Golgi inheritance and cell division.
Extracellular matrix stiffness causes systematic variations in proliferation and chemosensitivity in myeloid leukemias
Authors: Shin Jae-Won , Mooney David J. 
Published: October 2016

Significance
Most chemotherapy drugs treat, but do not cure, cancer patients due to resistance. New high-throughput screening assays are emerging to better predict drug efficacy by recapitulating tumor microenvironments with three-dimensional hydrogels. Our platform exploits the mechanical tunability of alginate hydrogels to introduce biophysical cues into screening assays. The utility of this approach is demonstrated with the findings of unique modes of growth modulation by matrix stiffness and mechanosensitivity of drug actions in different myeloid leukemia subtypes. The same hydrogels were then adapted to confirm in vivo that matrix softening accelerates cancer growth kinetics and causes resistance to standard chemotherapy. We anticipate that this integrative workflow will be broadly useful to discover drugs that target cancer cells in different physical environments.
A conserved αβ transmembrane interface forms the core of a compact T-cell receptor–CD3 structure within the membrane
Authors: Krshnan Logesvaran , Park Soohyung , Im Wonpil , Call Melissa J. , Call Matthew E. 
Published: October 2016

Significance
The T-cell antigen receptor (TCR) is an eight-subunit modular biosensor that detects the presence of pathogen-derived molecular fragments in infected cells and tissues. No atomic-resolution structure has been determined for the intact receptor complex, and the mechanism by which it transmits signals across the cell membrane remains poorly defined. Using a combination of biochemical, biophysical, and computational approaches to study the assembled complex in cellular membranes, we identified an evolutionarily conserved core transmembrane (TM) structure that organizes the complex into an intimately packed eight-helix bundle within the membrane and is critical for the structural integrity of the intact receptor. Our model provides insights into possible structural pathways involved in TM TCR signaling.
Overdrinking, swallowing inhibition, and regional brain responses prior to swallowing
Authors: Saker Pascal , Farrell Michael J. , Egan Gary F. , McKinley Michael J. , Denton Derek A. 
Published: October 2016

Significance
Drinking represents a crucial behavior that subserves the survival of species by maintaining fluid balance within the body. The present study confirms in humans the presence of swallowing inhibition after excess liquid has been drunk, revealing a mechanism important for the regulation of fluid intake. The findings presented here support the view that swallowing inhibition is probably a “hard-wired” process that aids maintenance of fluid balance within the body, thereby avoiding the detrimental effects of overdrinking that can cause water intoxication and eventually death.
Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition
Authors: Zhao Siming , Bellone Stefania , Lopez Salvatore , Thakral Durga , Schwab Carlton , English Diana P. , Black Jonathan , Cocco Emiliano , Choi Jungmin , Zammataro Luca , Predolini Federica , Bonazzoli Elena , Bi Mark , Buza Natalia , Hui Pei , Wong Serena , Abu-Khalaf Maysa , Ravaggi Antonella , Bignotti Eliana , Bandiera Elisabetta , Romani Chiara , Todeschini Paola , Tassi Renata , Zanotti Laura , Odicino Franco , Pecorelli Sergio , Donzelli Carla , Ardighieri Laura , Facchetti Fabio , Falchetti Marcella , Silasi Dan-Arin , Ratner Elena , Azodi Masoud , Schwartz Peter E. , Mane Shrikant , Angioli Roberto , Terranova Corrado , Quick Charles Matthew , Edraki Babak , Bilgüvar Kaya , Lee Moses , Choi Murim , Stiegler Amy L. , Boggon Titus J. , Schlessinger Joseph , Lifton Richard P. , Santin Alessandro D. 
Published: October 2016

Significance
Some cancers, termed carcinosarcomas (CSs), have mixed cell types, with either epithelial or mesenchymal features. Sequencing the genomes of uterine and ovarian CSs demonstrated that these different cell types derive from a common precursor cell that has many mutations typical of epithelial cancers. In addition, we find that these tumors have a significant burden of point mutations and amplification of histone genes, suggesting a potential role of these mutations in sarcomatous transformation. Consistent with this finding, expression of specific histone gene mutations in uterine carcinoma cells changed gene expression toward a mesenchymal state. These findings have potential implications for the treatment of these cancers.
Pronounced Genetic Structure and Site Fidelity among Native Muskellunge Populations in Lake Huron and Georgian Bay
Authors: Wilson Chris C. , Liskauskas Arunas P. , Wozney Kristyne M. 
Published: October 2016

AbstractConservation and management issues related to genetic diversity and stock structure of native populations of Muskellunge Esox masquinongy have largely been unexplored. In Lake Huron's North Channel and Georgian Bay, Muskellunge populations have been impacted by historical commercial fisheries, recreational fisheries, loss of spawning habitat, historical water quality issues, and ecosystem changes. To determine the spatial genetic structure of native Muskellunge in Lake Huron and Georgian Bay, spawning adults were sampled from 10 sites in the North Channel and eastern Georgian Bay. Genotyping with 20 microsatellite DNA loci showed substantial spatial genetic structure, with significant pairwise divergences among spawning sites. Individual‐ and population‐based analyses revealed hierarchical population structuring, with strong patterns of spawning site fidelity and isolation by distance; very low levels of dispersal and gene flow over historical and contemporary timescales were indicated. Estimation of effective population sizes highlighted the limited genetic resources that are present in these localized populations. The present results show that Muskellunge in Lake Huron and Georgian Bay consist of multiple small populations with limited ranges and high site fidelity and should be managed accordingly.Received February 28, 2016; accepted July 1, 2016 Published online October 11, 2016
Global and pedestal confinement and pedestal structure in dimensionless collisionality scans of low-triangularity H-mode plasmas in JET-ILW
Authors: Frassinetti L. , Beurskens M.N.A. , Saarelma S. , Boom J.E. , Delabie E. , Flanagan J. , Kempenaars M. , Giroud C. , Lomas P. , Meneses L. , Maggi C.S. , Menmuir S. , Nunes I. , Rimini F. , Stefanikova E. , Urano H. , Verdoolaege G. 
Published: October 2016

Abstract
A dimensionless collisionality scan in low-triangularity plasmas in the Joint European Torus with the ITER-like wall (JET-ILW) has been performed. The increase of the normalized energy confinement (defined as the ratio between thermal energy confinement and Bohm confinement time) with decreasing collisionality is observed. Moreover, at low collisionality, a confinement factor H98, comparable to JET-C, is achieved. At high collisionality, the low normalized confinement is related to a degraded pedestal stability and a reduction in the density-profile peaking.
The increase of normalized energy confinement is due to both an increase in the pedestal and in the core regions. The improvement in the pedestal is related to the increase of the stability. The improvement in the core is driven by (i) the core temperature increase via the temperature-profile stiffness and by (ii) the density-peaking increase driven by the low collisionality.
Pedestal stability analysis performed with the ELITE (edge-localized instabilities in tokamak equilibria) code has a reasonable qualitative agreement with the experimental results. An improvement of the pedestal stability with decreasing collisionality is observed. The improvement is ascribed to the reduction of the pedestal width, the increase of the bootstrap current and the reduction of the relative shift between the positions of the pedestal density and pedestal temperature.
The EPED1 model predictions for the pedestal pressure height are qualitatively well correlated with the experimental results. Quantitatively, EPED1 overestimates the experimental pressure by 15–35%. In terms of the pedestal width, a correct agreement (within 10–15%) between the EPED1 and the experimental width is found at low collisionality. The experimental pedestal width increases with collisionality. Nonetheless, an extrapolation to low-collisionality values suggests that the width predictions from the KBM constraint are reasonable for ITER.
gsrc: an R package for genome structure rearrangement calling
Authors: Grandke Fabian , Snowdon Rod , Samans Birgit 
Published: October 2016

Abstract

Summary
Genome structure rearrangements are a common phenomenon in allopolyploid species. Deletions, duplications and homeologous non-reciprocal translocations (HNRT) between the highly similar subgenomes can be observed, which are known to have a large impact on phenotypic traits. Current research is limited because these rearrangements can be located genome wide only by cost intensive sequencing approaches and not reliably in high-density array genotyping data. We developed gsrc, an R-package to detect genome structure rearrangements from genotyping data in allopolyploid species including exchanges between subgenomes. We exemplarily apply gsrc to a publicly available Brassica napus dataset.

Availability and Implementation
The compiled R-package and source code are available at http://cran.r-project.org/web/packages/gsrc/.

Supplementary information
Supplementary data are available at Bioinformatics online.
Transfer learning across ontologies for phenome–genome association prediction
Authors: Petegrosso Raphael , Park Sunho , Hwang Tae Hyun , Kuang Rui 
Published: October 2016

Abstract

Motivation
To better predict and analyze gene associations with the collection of phenotypes organized in a phenotype ontology, it is crucial to effectively model the hierarchical structure among the phenotypes in the ontology and leverage the sparse known associations with additional training information. In this paper, we first introduce Dual Label Propagation (DLP) to impose consistent associations with the entire phenotype paths in predicting phenotype–gene associations in Human Phenotype Ontology (HPO). DLP is then used as the base model in a transfer learning framework (tlDLP) to incorporate functional annotations in Gene Ontology (GO). By simultaneously reconstructing GO term–gene associations and HPO phenotype–gene associations for all the genes in a protein–protein interaction network, tlDLP benefits from the enriched training associations indirectly through relation with GO terms.

Results
In the experiments to predict the associations between human genes and phenotypes in HPO based on human protein–protein interaction network, both DLP and tlDLP improved the prediction of gene associations with phenotype paths in HPO in cross-validation and the prediction of the most recent associations added after the snapshot of the training data. Moreover, the transfer learning through GO term–gene associations significantly improved association predictions for the phenotypes with no more specific known associations by a large margin. Examples are also shown to demonstrate how phenotype paths in phenotype ontology and transfer learning with gene ontology can improve the predictions.

Availability and Implementation
Source code is available at http://compbio.cs.umn.edu/ontophenome.

Supplementary information
Supplementary data are available at Bioinformatics online.
Seasonal movements and connectivity of an Atlantic cod (Gadus morhua) spawning component in the western Gulf of Maine
Authors: Zemeckis Douglas R. , Liu Chang , Cowles Geoffrey W. , Dean Micah J. , Hoffman William S. , Martins David , Cadrin Steven X. 
Published: October 2016

AbstractMovement patterns of marine fishes can have considerable impacts on their population dynamics. A thorough understanding of fish movements is therefore required for informing stock identification, stock assessment, and fishery management. This study investigated the seasonal movements and connectivity of a spring-spawning component of Atlantic cod (Gadus morhua) in the western Gulf of Maine. From 2010 through 2013, spawning cod were sampled within an inshore spawning closure and tagged with conventional tags (n = 2368), acoustic transmitters (n = 106), and archival data storage tags (n = 266). Acoustic receivers were deployed on three inshore spawning sites to test for connectivity among sites. Data from archival tags were used to describe seasonal habitat occupancy and movement patterns via geolocation to statistical areas. Tagging data indicated that cod were primarily residential in the western Gulf of Maine, moving inshore to spawn during the spring (April–July), followed by an offshore migration to their feeding grounds for summer and fall. Cod generally inhabited waters from 45 to 175 m, with the deep offshore basins (&gt;150 m) serving as overwintering habitat. Occupied water temperatures ranged from 4.0 to 13.3 °C, with the coldest temperatures experienced from March through July and the warmest temperatures experienced from September through January. Results provided evidence of spawning site fidelity and connectivity among spawning sites, with some fish visiting multiple spawning sites within or between years. The movements observed during and after the spring-spawning season serve as important mechanisms influencing metapopulation dynamics in the Gulf of Maine region, including both fine- and broad-scale population structure. The improved understanding of cod movement patterns will assist fishery managers in developing management plans, including spawning protection measures, and help to address remaining uncertainties with respect to cod population structure in the Gulf of Maine and other regions.
To Boldly Go: Social Clauses in Public Procurement
Authors: Barnard Catherine 
Published: October 2016

Abstract
Public procurement has become exciting for labour lawyers. With the adoption of three new ‘revised and modernised’ directives on public procurement in 2014, whose express aims include enabling ‘procurers to make better use of public procurement to support common societal goals’, labour lawyers need to start taking procurement law seriously. At a time when the EU and domestic legislative cupboard in the social field is pretty bare, public procurement may offer a lever to deliver social change. This article will explore some of the potential offered by procurement law to achieve employment law objectives.
A management method for the statistical results of patient-specific quality assurance for intensity-modulated radiation therapy
Authors: Nakamura Satoshi , Okamoto Hiroyuki , Wakita Akihisa , Umezawa Rei , Takahashi Kana , Inaba Koji , Murakami Naoya , Kato Toru , Igaki Hiroshi , Ito Yoshinori , Abe Yoshihisa , Itami Jun 
Published: October 2016

Abstract
There are many reports concerning patient-specific quality assurance (QA) for intensity-modulated radiation therapy (IMRT). However, reports about the statistical results of QA are lacking. Management methods for the results of the QA are needed, even though we have the ESTRO group recommendation that a tolerance limit of 1.96 standard deviation (SD) be established in each institution. The purpose of this study was to establish a management method for determining the tolerance limit and to report the statistical results of patient-specific QA. From April 2006 to March 2015, five linacs in the National Cancer Center, Tokyo, Japan, were used to treat 1185 patients with IMRT. Patient-specific QA was performed using an ion chamber, films, and some detectors. To establish a management method for the results, differences between the measured and calculated doses in the ion chamber were analyzed for each linac, each phantom, and each treatment site. The overall mean dose difference was 0.5 ± 1.3%, and the mean dose difference in each linac was 0.6 ± 1.2%, 0.9 ± 1.3%, −0.4 ± 1.4%, −0.1 ± 1.2% and −0.1 ± 0.9%. The difference between linacs and between treatment sites was significant (P &lt; 0.001 and 0.01, respectively). The proportion of the dose difference within ±3% was 97.7%, and that was improved from 2006 to 2014. The results of the patient-specific QA should be managed for each linac and each treatment site in order to decide the suitable tolerance limit. Reports of statistical results will be helped if a new tolerance limit and action level will be considered.