bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole-genome sequencing of bladder cancers reveals somatic CDKN1A mutations and clinicopathological associations with mutation burden
Authors: Cazier J. -B. , Rao S. R. , McLean C. M. , Walker A. K. , Wright B. J. , Jaeger E. E. M. , Kartsonaki C. , Marsden L. , Yau C. , Camps C. , Kaisaki P. ,   The Oxford-Illumina WGS500 Consortium, Allan Christopher , Attar Moustafa , Bell John , Bentley David , Broxholme John , Buck David , Cazier Jean-Baptiste , Copley Richard , Cornall Richard , Donnelly Peter , Fiddy Simon , Green Angie , Gregory Lorna , Grocock Russell , Hatton Edouard , Holmes Chris , Hughes Linda , Humburg Peter , Humphray Sean , Kanapin Alexander , Kingsbury Zoya , Knight Julian , Lamble Sarah , Lise Stefano , Lonie Lorne , Lunter Gerton , Martin Hilary , Murray Lisa , McCarthy Davis , McVean Gil , Pagnamenta Alistair , Piazza Paolo , Polanco Guadelupe , Ratcliffe Peter , Rimmer Andy , Sahgal Natasha , Taylor Jenny , Tomlinson Ian , Trebes Amy , Wilkie Andrew , Wright Ben , Yau Chris , Taylor J. , Catto J. W. , Tomlinson I. P. M. , Kiltie A. E. , Hamdy F. C. 
Published: April 2014

AbstractBladder cancers are a leading cause of death from malignancy. Molecular markers might predict disease progression and behaviour more accurately than the available prognostic factors. Here we use whole-genome sequencing to identify somatic mutations and chromosomal changes in 14 bladder cancers of different grades and stages. As well as detecting the known bladder cancer driver mutations, we report the identification of recurrent protein-inactivating mutations in CDKN1A and FAT1. The former are not mutually exclusive with TP53 mutations or MDM2 amplification, showing that CDKN1A dysfunction is not simply an alternative mechanism for p53 pathway inactivation. We find strong positive associations between higher tumour stage/grade and greater clonal diversity, the number of somatic mutations and the burden of copy number changes. In principle, the identification of sub-clones with greater diversity and/or mutation burden within early-stage or low-grade tumours could identify lesions with a high risk of invasive progression.
Faster growth of the major prokaryotic versus eukaryotic CO2 fixers in the oligotrophic ocean
Authors: Zubkov Mikhail V. 
Published: April 2014

AbstractBecause maintenance of non-scalable cellular components—membranes and chromosomes—requires an increasing fraction of energy as cell size decreases, miniaturization comes at a considerable energetic cost for a phytoplanktonic cell. Consequently, if eukaryotes can use their superior energetic resources to acquire nutrients with more or even similar efficiency compared with prokaryotes, larger unicellular eukaryotes should be able to achieve higher growth rates than smaller cyanobacteria. Here, to test this hypothesis, we directly compare the intrinsic growth rates of phototrophic prokaryotes and eukaryotes from the equatorial to temperate South Atlantic using an original flow cytometric 14CO2-tracer approach. At the ocean basin scale, cyanobacteria double their biomass twice as frequently as the picoeukaryotes indicating that the prokaryotes are faster growing CO2 fixers, better adapted to phototrophic living in the oligotrophic open ocean—the most extensive biome on Earth.
Biochemical analysis of TssK, a core component of the bacterial Type VI secretion system, reveals distinct oligomeric states of TssK and identifies a TssK–TssFG subcomplex
Authors: English Grant , Byron Olwyn , Cianfanelli Francesca R. , Prescott Alan R. , Coulthurst Sarah J. 
Published: April 2014

Gram-negative bacteria use the Type VI secretion system (T6SS) to inject toxic proteins into rival bacteria or eukaryotic cells. However, the mechanism of the T6SS is incompletely understood. In the present study, we investigated a conserved component of the T6SS, TssK, using the antibacterial T6SS of Serratia marcescens as a model system. TssK was confirmed to be essential for effector secretion by the T6SS. The native protein, although not an integral membrane protein, appeared to localize to the inner membrane, consistent with its presence within a membrane-anchored assembly. Recombinant TssK purified from S. marcescens was found to exist in several stable oligomeric forms, namely trimer, hexamer and higher-order species. Native-level purification of TssK identified TssF and TssG as interacting proteins. TssF and TssG, conserved T6SS components of unknown function, were required for T6SS activity, but not for correct localization of TssK. A complex containing TssK, TssF and TssG was subsequently purified in vitro, confirming that these three proteins form a new subcomplex within the T6SS. Our findings provide new insight into the T6SS assembly, allowing us to propose a model whereby TssK recruits TssFG into the membrane-associated T6SS complex and different oligomeric states of TssK may contribute to the dynamic mechanism of the system.
Endoplasmic reticulum stress does not contribute to steatohepatitis in obese and insulin-resistant high-fat-diet-fed foz/foz mice
Authors: Legry Vanessa , Van Rooyen Derrick M. , Lambert Barbara , Sempoux Christine , Poekes Laurence , Español-Suñer Regina , Molendi-Coste Olivier , Horsmans Yves , Farrell Geoffrey C. , Leclercq Isabelle A. 
Published: April 2014

Non-alcoholic fatty liver (steatosis) and steatohepatitis [non-alcoholic steatohepatitis (NASH)] are hepatic complications of the metabolic syndrome. Endoplasmic reticulum (ER) stress is proposed as a crucial disease mechanism in obese and insulin-resistant animals (such as ob/ob mice) with simple steatosis, but its role in NASH remains controversial. We therefore evaluated the role of ER stress as a disease mechanism in foz/foz mice, which develop both the metabolic and histological features that mimic human NASH. We explored ER stress markers in the liver of foz/foz mice in response to a high-fat diet (HFD) at several time points. We then evaluated the effect of treatment with an ER stress inducer tunicamycin, or conversely with the ER protectant tauroursodeoxycholic acid (TUDCA), on the metabolic and hepatic features. foz/foz mice are obese, glucose intolerant and develop NASH characterized by steatosis, inflammation, ballooned hepatocytes and apoptosis from 6 weeks of HFD feeding. This was not associated with activation of the upstream unfolded protein response [phospho-eukaryotic initiation factor 2α (eIF2α), inositol-requiring enzyme 1α (IRE1α) activity and spliced X-box-binding protein 1 (Xbp1)]. Activation of c-Jun N-terminal kinase (JNK) and up-regulation of activating transcription factor-4 (Atf4) and CCAAT/enhancer-binding protein-homologous protein (Chop) transcripts were however compatible with a ‘pathological’ response to ER stress. We tested this by using intervention experiments. Induction of chronic ER stress failed to worsen obesity, glucose intolerance and NASH pathology in HFD-fed foz/foz mice. In addition, the ER protectant TUDCA, although reducing steatosis, failed to improve glucose intolerance, hepatic inflammation and apoptosis in HFD-fed foz/foz mice. These results show that signals driving hepatic inflammation, apoptosis and insulin resistance are independent of ER stress in obese diabetic mice with steatohepatitis.
Turbulent flow in rib-roughened channel under the effect of Coriolis and rotational buoyancy forces
Authors: Coletti Filippo , Jacono David Lo , Cresci Irene , Arts Tony 
Published: April 2014

The turbulent flow inside a rotating channel provided with transverse ribs along one wall is studied by means of two-dimensional time-resolved particle image velocimetry. The measurement set-up is mounted on the same rotating disk with the test section, allowing to obtain the same accuracy and resolution as in a non-rotating rig. The Reynolds number is 15 000, and the rotation number is 0.38. As the ribbed wall is heated, both the Coriolis force and the centrifugal force play a role in the fluid dynamics. The mean velocity fields highlight the major impact of the rotational buoyancy (characterized by a buoyancy number of 0.31) on the flow along the leading side of the duct. In particular, since the flow is directed radially outward, the near-wall layers experience significant centripetal buoyancy. The recirculation area behind the obstacles is enlarged to the point of spanning the whole inter-rib space. Also the turbulent fluctuations are significantly altered, and overall augmented, with respect to the non-buoyant case, resulting in higher turbulence levels far from the rib. On the other hand the centrifugal force has little or no impact on the flow along the trailing wall. Vortex identification, proper orthogonal decomposition, and two-point correlations are used to highlight rotational effects, and in particular to determine the dominant scales of the turbulent unsteady flow, the time-dependent behavior of the shear layer and of the recirculation bubble behind the wall-mounted obstacles, the lifetime and advection velocity of the coherent structures.
Architectures of planetary systems and implications for their formation
Authors: Ford Eric B. 
Published: April 2014

SignificancePrior to the discovery of exoplanets, astronomers fine tuned theories of planet formation to explain detailed properties of the solar system. The discovery of exoplanets has significantly increased our appreciation for the diversity of planetary systems in nature. In this article we review the current understanding of the late stages of evolution of planetary systems, focusing on observational constraints from radial velocity and transit observations.
Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia
Authors: Meda Shashwath A. , Ruaño Gualberto , Windemuth Andreas , O’Neil Kasey , Berwise Clifton , Dunn Sabra M. , Boccaccio Leah E. , Narayanan Balaji , Kocherla Mohan , Sprooten Emma , Keshavan Matcheri S. , Tamminga Carol A. , Sweeney John A. , Clementz Brett A. , Calhoun Vince D. , Pearlson Godfrey D. 
Published: April 2014

Significance
Connectivity within the brain’s resting-state default mode network (DMN) has been shown to be compromised in multiple genetically complex/heritable neuropsychiatric disorders. Uncovering the source of such alterations will help in developing targeted treatments for these disorders. To our knowledge, this study is the first attempt to do so by using a multivariate data-driven fusion approach. We report five major DMN subnodes, all of which were found to be hypo-connected in probands with psychotic illnesses. Further, we found an overrepresentation of genes in major relevant pathways such as NMDA potentiation, PKA/immune response signalling, synaptogenesis, and axon guidance that influenced altered DMN connectivity in psychoses. The study thus identifies several putative genes and pathways related to an important biological marker known to be compromised in psychosis.
Field experiments of success-breeds-success dynamics
Authors: van de Rijt Arnout , Kang Soong Moon , Restivo Michael , Patil Akshay 
Published: April 2014

Significance
Social scientists have long debated why similar individuals often experience drastically different degrees of success. Some scholars have suggested such inequality merely reflects hard-to-observe personal differences in ability. Others have proposed that one fortunate success may trigger another, thus producing arbitrary differentiation. We conducted randomized experiments through intervention in live social systems to test for success-breeds-success dynamics. Results show that different kinds of success (money, quality ratings, awards, and endorsements) when bestowed upon arbitrarily selected recipients all produced significant improvements in subsequent rates of success as compared with the control group of nonrecipients. However, greater amounts of initial success failed to produce much greater subsequent success, suggesting limits to the distortionary effects of social feedback.
Unusually long-lived pause required for regulation of a Rho-dependent transcription terminator
Authors: Hollands Kerry , Sevostiyanova Anastasia , Groisman Eduardo A. 
Published: April 2014

Significance
Accurate gene expression requires that transcription of DNA into RNA terminate in the correct location. In bacteria, many transcription termination events rely on the termination factor Rho. Rho-dependent terminators perform critical housekeeping functions in the cell and also regulate expression of specific genes. However, the DNA and RNA sequences that promote Rho-dependent termination are poorly understood, particularly for those terminators with regulatory functions. We now define the sequence elements required for transcription termination at a regulated Rho-dependent terminator. These sequences cause RNA polymerase to pause for an unusually long time during transcription. The remarkable longevity of this pause is required for a regulatory signal to stimulate Rho-dependent termination and thereby govern expression of the gene downstream of the pause site.
Rescue of embryonic stem cells from cellular transformation by proteomic stabilization of mutant p53 and conversion into WT conformation
Authors: Rivlin Noa , Katz Shir , Doody Maayan , Sheffer Michal , Horesh Stav , Molchadsky Alina , Koifman Gabriela , Shetzer Yoav , Goldfinger Naomi , Rotter Varda , Geiger Tamar 
Published: April 2014

SignificanceMutations in p53 lead to cell transformation through the elimination of the WT tumor suppressor activities and the gain of oncogenic ones. In contrast, mouse embryos develop normally, despite the expression of mutant p53. Here, we report that, in ES cells, mutant p53 conformation is shifted to a WT form, leading to transcriptionally active p53 and increased genomic integrity of these cells. Using MS-based proteomics, we were able to isolate a network of interacting proteins that bind mutant p53 and stabilize it to the WT form. These results can serve as a potential platform for p53-based cancer therapy development in the future.
A forager–herder trade-off, from broad-spectrum hunting to sheep management at Aşıklı Höyük, Turkey
Authors: Stiner Mary C. , Buitenhuis Hijlke , Duru Güneş , Kuhn Steven L. , Mentzer Susan M. , Munro Natalie D. , Pöllath Nadja , Quade Jay , Tsartsidou Georgia , Özbaşaran Mihriban 
Published: April 2014

Significance
This article provides original results on the formative conditions of sheep domestication in the Near East. To our knowledge, none of the results has been published before, and the results are expected to be of wide interest to archaeologists, biologists, and other professionals interested in evolutionary and cultural processes of animal domestication.
Genesis and pathogenesis of the 1918 pandemic H1N1 influenza A virus
Authors: Worobey Michael , Han Guan-Zhu , Rambaut Andrew 
Published: April 2014

Significance
The origin of the 1918 pandemic influenza A virus (IAV) and the reasons for its unusual severity are two of the foremost biomedical mysteries of the past century. We infer that the virus arose via reassortment between a preexisting human H1 IAV lineage and an avian virus. Phylogenetic, seroarcheological, and epidemiological evidence indicates those born earlier or later than ∼1880–1900 would have had some protection against the 1918 H1N1 virus, whereas many young adults born from ∼1880–1900 may have lacked such protection because of childhood exposure to an antigenically distinct H3N8 virus. Our findings suggest that better understanding of how initial exposure shapes lifetime immunity may enhance the prediction and control of future IAV pandemics and seasonal epidemics.
Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques
Authors: Safronetz David , Prescott Joseph , Feldmann Friederike , Haddock Elaine , Rosenke Rebecca , Okumura Atsushi , Brining Douglas , Dahlstrom Eric , Porcella Stephen F. , Ebihara Hideki , Scott Dana P. , Hjelle Brian , Feldmann Heinz 
Published: April 2014

SignificanceHantavirus pulmonary syndrome (HPS) is a rare but often fatal disease caused by infection with New World hantaviruses. A limitation to understanding the pathogenesis of HPS and developing medical countermeasures against this disease is a lack of experimental disease models. In this study we describe the characterization of a novel nonhuman primate model of HPS. After infection with deer mouse-only–passaged Sin Nombre virus, macaques developed severe respiratory disease indicative of HPS. Viremia and hematological abnormalities were the earliest markers of ensuing disease, and the hyperpermeability associated with the onset of respiratory distress coincided with dysregulation of host responses exclusively in the pulmonary endothelium. This model will help advance our understanding of HPS and preclinical development of therapeutic strategies.
Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution
Authors: Tang Xian-Chun , Agnihothram Sudhakar S. , Jiao Yongjun , Stanhope Jeremy , Graham Rachel L. , Peterson Eric C. , Avnir Yuval , Tallarico Aimee St. Clair , Sheehan Jared , Zhu Quan , Baric Ralph S. , Marasco Wayne A. 
Published: April 2014

Significance
The recently emerged Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes severe respiratory disease with ∼43% mortality. There is no licensed vaccine or antiviral for MERS. Here we identified seven human neutralizing Abs (nAbs) against MERS-CoV. These nAbs bind to three epitope groups in the viral Spike protein–receptor interface, blocking virus attachment. Five residues in the viral receptor-binding domain critical for neutralization escape were identified. Further study indicated that four of five mutations not only confer neutralization resistance but also impair receptor binding and viral fitness. This panel of nAbs offers the possibility of developing human mAb-based immunotherapy.
Endophilin A1 induces different membrane shapes using a conformational switch that is regulated by phosphorylation
Authors: Ambroso Mark R. , Hegde Balachandra G. , Langen Ralf 
Published: April 2014

Significance
BIN/amphiphysin/Rvs (BAR) proteins shape lipid membranes into functional shapes and compartments in a broad range of cellular processes. However, how a protein generates distinct forms of membrane curvature and how these states are regulated is unknown. We find that endophilin A1 uses different structures and mechanisms to generate tubes or vesicles. Phosphorylation toggles a conformational switch between these two structures, potentially acting as a regulator of membrane curvature in vivo. These findings may also explain how other proteins, including the BAR protein family, generate different shapes and are regulated in a large number of membrane remodeling processes.
A rifamycin inactivating phosphotransferase family shared by environmental and pathogenic bacteria
Authors: Spanogiannopoulos Peter , Waglechner Nicholas , Koteva Kalinka , Wright Gerard D. 
Published: April 2014

Significance
Environmental microorganisms are a source of diverse antibiotic resistance determinants. With the appropriate selection pressure, these resistance genes can be mobilized to clinically relevant pathogens. Identifying and characterizing elements of the environmental antibiotic resistome provides an early warning of what we may expect to encounter in the clinic. We uncover a conserved genetic element associated with various rifamycin antibiotic-inactivating mechanisms. This element led to the identification of a new resistance gene and associated enzyme responsible for inactivating rifamycin antibiotics by phosphorylation. Cryptic orthologous genes are also found in pathogenic bacteria but remain susceptible to the drug. This study reveals a new antibiotic resistance protein family and the unexpected prevalence of a silent rifamycin resistome among pathogenic bacteria.
A 9,000-year-old caribou hunting structure beneath Lake Huron
Authors: O’Shea John M. , Lemke Ashley K. , Sonnenburg Elizabeth P. , Reynolds Robert G. , Abbott Brian D. 
Published: April 2014

SignificanceSome of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. These contexts have unique potentials for preserving ancient sites without disturbance from later human occupation. The Alpena-Amberley Ridge beneath modern Lake Huron in the Great Lakes offers unique evidence of prehistoric caribou hunters for a time period that is very poorly known on land. The newly discovered Drop 45 Drive Lane and associated artifacts presented here provide unprecedented insight into the social and seasonal organization of early peoples in the Great Lakes region, while the interdisciplinary research program provides a model for the archaeological investigation of submerged prehistoric landscapes.
Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF
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Authors: Sacchi Veronica , Mittermayr Rainer , Hartinger Joachim , Martino Mikaël M. , Lorentz Kristen M. , Wolbank Susanne , Hofmann Anna , Largo Remo A. , Marschall Jeffrey S. , Groppa Elena , Gianni-Barrera Roberto , Ehrbar Martin , Hubbell Jeffrey A. , Redl Heinz , Banfi Andrea 
Published: April 2014

Significance
Inducing the growth of new blood vessels by specific factors is an attractive strategy to restore blood flow in ischemic tissues. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, yet clinical trials of VEGF gene delivery failed. Major challenges include the need to control the tissue distribution of factor dose and the duration of expression. Here, we developed a highly tunable fibrin-based platform to precisely control the dose and duration of VEGF protein delivery in tissues. Optimized delivery of fibrin-bound VEGF ensured normal, stable, and functional angiogenesis and improved perfusion of ischemic tissues, without genetic modification and with limited duration of VEGF delivery. These findings suggest a strategy to improve both safety and efficacy of therapeutic angiogenesis.
Bacterial scaffold directs pole-specific centromere segregation
Authors: Ptacin Jerod L. , Gahlmann Andreas , Bowman Grant R. , Perez Adam M. , von Diezmann Lexy , Eckart Michael R. , Moerner W. E. , Shapiro Lucy 
Published: April 2014

SignificanceBacteria use molecular partitioning systems based on the ATPase ParA to segregate chromosome centromeres before cell division, but how these machines target centromeres to specific locations is unclear. This study shows that, inCaulobacter crescentus, a multimeric complex composed of the PopZ protein directs the ParA machine to transfer centromeres to the cell pole. Spent ParA subunits released from the mitotic apparatus during segregation are recruited throughout a 3D PopZ matrix at the pole. ParA recruitment and sequestration by PopZ stimulates the cell-pole proximal recycling of ParA into a nucleoid-bound complex to ensure pole-specific centromere transfer. PopZ therefore utilizes a 3D scaffolding strategy to create a subcellular microdomain that directly regulates the function of the bacterial centromere segregation machine.
Patrones conductuales en el terrorismo actual: un análisis empírico
Authors: Garzón A. , Garcés J. , Herrera M. 
Published: April 2014

El análisis del terrorismo, como campo distinto de investigation, es un fenómeno relativamente reciente. El estudio del Terrorismo ha sido un fenómeno de interés para las ciencias políticas, psicológicas, sociológicas centradas en el estudio de los fenómenos internacionales y la justicia criminal. Este artículo es una revisión empírica y conceptual del Terrorismo. Es una aproximación conceptual y tipológica del fenómeno terrorista y de los fenómenos internacionales a través del análisis de las actividades terroristas y sus objetivos-estímulos.