bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germinal‐center kinase‐like kinase co‐crystal structure reveals a swapped activation loop and C‐terminal extension
Authors: Marcotte Douglas , Rushe Mia , M. Arduini Robert , Lukacs Christine , Atkins Kateri , Sun Xin , Little Kevin , Cullivan Michael , Paramasivam Murugan , Patterson Thomas A. , Hesson Thomas , D. McKee Timothy , May‐Dracka Tricia L. , Xin Zhili , Bertolotti‐Ciarlet Andrea , Bhisetti Govinda R. , Lyssikatos Joseph P. , Silvian Laura F. 
Published: October 2016

AbstractGerminal‐center kinase‐like kinase (GLK, Map4k3), a GCK‐I family kinase, plays multiple roles in regulating apoptosis, amino acid sensing, and immune signaling. We describe here the crystal structure of an activation loop mutant of GLK kinase domain bound to an inhibitor. The structure reveals a weakly associated, activation‐loop swapped dimer with more than 20 amino acids of ordered density at the carboxy‐terminus. This C‐terminal PEST region binds intermolecularly to the hydrophobic groove of the N‐terminal domain of a neighboring molecule. Although the GLK activation loop mutant crystallized demonstrates reduced kinase activity, its structure demonstrates all the hallmarks of an “active” kinase, including the salt bridge between the C‐helix glutamate and the catalytic lysine. Our compound displacement data suggests that the effect of the Ser170Ala mutation in reducing kinase activity is likely due to its effect in reducing substrate peptide binding affinity rather than reducing ATP binding or ATP turnover. This report details the first structure of GLK; comparison of its activation loop sequence and P‐loop structure to that of Map4k4 suggests ideas for designing inhibitors that can distinguish between these family members to achieve selective pharmacological inhibitors.
Effect of fuel concentration and force on collective transport by a team of dynein motors
Authors: Takshak Anjneya , Roy Tanushree , Tandaiya Parag , Kunwar Ambarish 
Published: October 2016

AbstractMotor proteins are essential components of intracellular transport inside eukaryotic cells. These protein molecules use chemical energy obtained from hydrolysis of ATP to produce mechanical forces required for transporting cargos inside cells, from one location to another, in a directed manner. Of these motors, cytoplasmic dynein is structurally more complex than other motor proteins involved in intracellular transport, as it shows force and fuel (ATP) concentration dependent step‐size. Cytoplasmic dynein motors are known to work in a team during cargo transport and force generation. Here, we use a complete Monte‐Carlo model of single dynein constrained by in vitro experiments, which includes the effect of both force and ATP on stepping as well as detachment of motors under force. We then use our complete Monte‐Carlo model of single dynein motor to understand collective cargo transport by a team of dynein motors, such as dependence of cargo travel distance and velocity on applied force and fuel concentration. In our model, cargos pulled by a team of dynein motors do not detach rapidly under higher forces, confirming the experimental observation of longer persistence time of dynein team on microtubule under higher forces.
The prognostic value of stromal FK506‐binding protein 1 and androgen receptor in prostate cancer outcome
Authors: Leach Damien A. , Trotta Andrew P. , Need Eleanor F. , Risbridger Gail P. , Taylor Renea A. , Buchanan Grant 
Published: October 2016

BACKGROUNDImproving our ability to predict cancer progression and response to conservative or radical intent therapy is critical if we are to prevent under or over treatment of individual patients. Whereas the majority of solid tumors now have a range of molecular and/or immunological markers to help define prognosis and treatment options, prostate cancer still relies mainly on histological grading and clinical parameters. We have recently reported that androgen receptor (AR) expression in stroma inversely associates with prostate cancer‐specific survival, and that stromal AR reduces metastasis. For this paper, we tested the hypothesis that the AR‐regulated gene FKBP51 could be used as a marker of AR activity to better predict outcome.METHODSUsing immunohistochemistry on a cohort of 64 patient‐matched benign and malignant prostate tissues, we assessed patient outcome by FKBP51 and AR levels. Immunoblot and RT‐qPCR were used to demonstrate androgen regulation of FKBP51 in primary and primary human prostatic fibroblasts and fibroblast cell‐lines. RESULTS. As predicted by FKBP51 level, high AR activity in cancer stroma was associated with longer median survival (1,306 days) compared with high AR alone (699 days), whereas those with low AR and/or low FKBP51 did poorly (384 and 338 days, respectively). Survival could not be predicted on the basis cancer epithelial AR levels or activity, and was not associated with immunoreactivity in patient matched benign tissues.CONCLUSIONFKBP51 improves the ability of stromal AR to predict prostate cancer‐specific mortality. By adding additional immunological assessment, similar to what is already in place in a number of other cancers, we could better serve patients with prostate cancer in prognosis and informed treatment choices. Prostate 77:185–195, 2017. © 2016 Wiley Periodicals, Inc.
Detecting pyrethroid resistance in predatory mites inhabiting soil and litter: an in vitro test
Authors: El Adouzi Marine , Bonato Olivier , Roy Lise 
Published: October 2016

AbstractBACKGROUNDWhile resistance against insecticides is widely known in pest arthropods, it remains poorly known in non‐target arthropods of the same agrosystems. This may be of crucial importance in the context of organic pest management or integrated pest management. First, stopping of pesticide pressure during farm conversion may lead to important rearrangements of non‐target communities due to fitness cost of resistance in populations of some species. Second, resistant biological agents may be useful to farms with low synthetic pesticide use. Communities of mesostigmatid mites, encompassing numerous predatory species, are supposed to be involved in important ecological processes in both crop soils and animal litter/manure.RESULTSHere we provide a tarsal contact method for assessing resistance in different populations from various species of mesostigmatid mites. Analyses of data from repeated tests on three populations from different mesostigmatid families proved the method to be robust and able to generate consistent and reliable mortality percentages according to insecticide concentration.CONCLUSIONOur bioassay system allows for both one‐shot estimate of pyrethroid sensitivity in mite populations and estimation of how it changes over time, making possible survival analyses and assessment of recovery from knockdown. The rating system retained makes it possible to score response to insecticides in a consistent and standard way in species from different mesostigmatid families. © 2016 Society of Chemical Industry
Fabrication of hydrophilic graphene film by molecular functionalization
Authors: Taniguchi Yoshiaki , Miki Tsubasa , Mitsuno Takanori , Ohno Yasuhide , Nagase Masao , Minagawa Keiji , Yasuzawa Mikito 
Published: October 2016

We demonstrated the fabrication of a hydrophilic graphene film by functionalization using a phosphorylcholine group. Since the phosphorylcholine group retains water molecules, it is expected that a hydrophilic graphene film can be realized from the initial hydrophobic characteristic. To evaluate the molecular functionalization, the contact angle and four‐terminal resistivity were measured after every 1 min of phosphorylcholine group functionalization. The contact angle showed a sudden decrease of approximately 20° after 3 min. On the other hand, the resistivity gradually increased in accordance with the Langmuir adsorption isotherm. These results indicate that the phosphorylcholine group successfully modified the surface of graphene, and a hydrophilic graphene film was obtained without significant degradation of the electrical characteristics.Time dependence of the net contact angle change and resistivity change. The insets show the photographs of the contact angle measurement for the initial hydrophobic film and for the hydrophilic film obtained by functionalization.
Mechanism for odd‐electron anion generation of dihydroxybenzoic acid isomers in matrix‐assisted laser desorption/ionization mass spectrometry with density functional theory calculations
Authors: Yamagaki Tohru , Takeuchi Michika , Watanabe Takehiro , Sugahara Kohtaro , Takeuchi Takae 
Published: October 2016

RationaleProton and radical are transferred between matrices and matrix and analyte in matrix‐assisted laser desorption/ionization (MALDI) and these transfers drive ionization of analytes. The odd‐electron anion [M–2H]•– was generated in dihydroxybenzoic acids (DHBs) and the ion abundance of the 2,5‐DHB was the highest among six DHB isomers. We were interested in the mechanism of the ion generation of the odd‐electron anion.MethodsThe observed [M–2H]•– and [M–3H]− ions, which were generated with the hydrogen radical removed from the phenolic hydroxyl groups (OH) in DHB isomers, were analyzed using negative‐ion MALDI‐MS. The enthalpy for ion generation and their stable structures were calculated using the density functional theory (DFT) calculation program Gaussian 09 with the B3LYP functional and the 6–31+G(d) basis set.ResultsThe number of observed [M–2H]•– and [M–3H]− ions of the DHB isomers was dependent on the positions of the phenolic OH groups in the DHB isomers because the carboxy group interacts with the ortho OH group due to neighboring group participation, as confirmed from the stable structures of the [M–2H]•– anions calculated with the Gaussian 09 program. The DHB isomers were placed into three categories according to the number of the ions.ConclusionsOdd‐electron anions ([M–2H]•–) and [M–2H•–H]− ([M–3H]−) ions were generated from DHB isomers due to removal of the hydrogen radical from the phenolic groups. The enthalpy for ion generation revealed that ion formation proceeds via a two‐step pathway through the [M–M]− ion as an intermediate. © 2016 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.
Work stressors, sleep quality, and alcohol‐related problems across deployment: A parallel process latent growth modeling approach among Navy members
Authors: Bravo Adrian J. , Kelley Michelle L. , Hollis Brittany F. 
Published: October 2016

AbstractThis study examined how work stressors were associated with sleep quality and alcohol‐related problems among U.S. Navy members over the course of deployment. Participants were 101 U.S. Navy members assigned to an Arleigh Burke‐class destroyer who experienced an 8‐month deployment after Operational Enduring Freedom/Operation Iraqi Freedom. Approximately 6 weeks prior to deployment, 6 weeks after deployment, and 6 months reintegration, participants completed measures that assessed work stressors, sleep quality, and alcohol‐related problems. A piecewise latent growth model was conducted in which the structural paths assessed if work stressors influenced sleep quality or its growth over time, and in turn if sleep quality influenced alcohol‐related problems intercepts or growth over time. A significant indirect effect was found such that increases in work stressors from pre‐ to postdeployment predicted decreases in sleep quality, which in turn were associated with increases in alcohol‐related problems from pre‐ to postdeployment. These effects were maintained from postdeployment through the 6‐month reintegration. Findings suggest that work stressors may have important implications for sleep quality and alcohol‐related problems. Positive methods of addressing stress and techniques to improve sleep quality are needed as both may be associated with alcohol‐related problems among current Navy members.
Adipose Stromal Vascular Fraction-Mediated Improvements at Late-Stage Disease in a Murine Model of Multiple Sclerosis
Authors: Bowles Annie C. , Strong Amy L. , Wise Rachel M. , Thomas Robert C. , Gerstein Brittany Y. , Dutreil Maria F. , Hunter Ryan S. , Gimble Jeffrey M. , Bunnell Bruce A. 
Published: October 2016

Abstract
Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes. The SVF can be culture expanded to generate ASC lines. Clinical trials continue to demonstrate the safety and efficacy of ASC therapies for treating several diseases. However, little is known about the effectiveness of the SVF for neurodegenerative diseases, such as MS. At late-stage disease, EAE mice show severe motor impairment. The goal for these studies was to test the effectiveness of SVF cells and ASC in EAE mice after the onset of neuropathology. The clinical scoring, behavior, motor function, and histopathologic analyses revealed significant improvements in EAE mice treated with the SVF or ASC. Moreover, SVF treatment mediated more robust improvements to CNS pathology than ASC treatment based on significant modulations of inflammatory factors. The most pronounced changes following SVF treatment were the high levels of interleukin-10 in the peripheral blood, lymphoid and CNS tissues along with the induction of regulatory T cells in the lymph nodes which indicate potent immunomodulatory effects. The data indicate SVF cells effectively ameliorated the EAE immunopathogenesis and supports the potential use of SVF for treating MS.
Acute mercury exposition of virgin, pregnant, and lactating rats: Histopathological kidney and liver evaluations
Authors: Oliveira Vitor Antunes , Favero Gaia , Stacchiotti Alessandra , Giugno Lorena , Buffoli Barbara , de Oliveira Claudia Sirlene , Lavazza Antonio , Albanese Massimo , Rodella Luigi Fabrizio , Pereira Maria Ester , Rezzani Rita 
Published: October 2016

ABSTRACTThis work investigated the effects of mercury chloride (HgCl2) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18th gestation day) and lactating (7th lactation day) were injected once with HgCl2 (5 mg/kg) or saline (controls). We observed that HgCl2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl2‐exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500–1512, 2017.
Wireless resource virtualization: opportunities, challenges, and solutions
Authors: Kalil M. , Youssef M. , Shami A. , Al‐Dweik A. , Ali S. 
Published: October 2016

AbstractWireless resource virtualization (WRV) is currently emerging as a key technology to overcome the major challenges facing the mobile network operators (MNOs) such as reducing the capital, minimizing the operating expenses, improving the quality of service, and satisfying the growing demand for mobile services. Achieving such conflicting objectives simultaneously requires a highly efficient utilization of the available resources including the network infrastructure and the reserved spectrum. In this paper, the most dominant WRV frameworks are discussed where different levels of network infrastructure and spectrum resources are shared between multiple MNOs. Moreover, we summarize the major benefits and most pressing business challenges of deploying WRV. We further highlight the technical challenges and requirements for abstraction and sharing of spectrum resources in next generation networks. In addition, we provide guidelines for implementing comprehensive solutions that are able to abstract and share the spectrum resources in next generation network. The paper also presents an efficient algorithm for base station virtualization in long‐term evolution (LTE) networks to share the wireless resources between MNOs who apply different scheduling polices. The proposed algorithm maintains a high‐level of isolation and offers throughput performance gain. Copyright © 2016 John Wiley & Sons, Ltd.
Cover Image, Volume 7, Issue 6
Authors: Petitto L. A. , Langdon C. , Stone A. , Andriola D. , Kartheiser G. , Cochran C. 
Published: October 2016

The cover image, created by Laura‐Ann Petitto, is based on the article Visual Sign Phonology: Insights into Human Reading and Language from a Natural Soundless Phonology, DOI: 10.1002/wcs.1404. Design Credit: Laura‐Ann Petitto, Graphic Artist Yiqiao Wang, and Tara Congdon.
image
Employment and Social Trends by Region
Authors:   Research Department
Published: October 2016

Labour market and social conditions vary considerably across regions. In terms of unemployment, the short‐term outlook shows that Europe and Central Asia and Northern America will do relatively well in comparison to other regions, including Latin America and the Caribbean, the Arab States, Asia, and Sub‐Saharan Africa. However, unemployment levels and rates do not often capture well the extent of the labour market and social challenges. This is particularly the case in the emerging and developing economies, where the persistence of vulnerable employment, informal employment and working poverty is of key concern (ILO, 2015i). Even in Europe and Central Asia and Northern America, where unemployment is expected to decline, long‐term unemployment and youth unemployment remain significant labour market and social challenges. In this respect, all countries and regions of the world are confronting the challenge of creating sufficient quality employment.With that in mind, this chapter will assess both across and within regions (i) recent economic and labour market developments; (ii) short‐term employment and social prospects; and (iii) major deficits and challenges to achieving success in terms of the SDGs.
Cover Image, Volume 8, Issue 6
Authors: Cardozo Timothy , Gupta Priyanka , Ni Eric , Young Lauren M. , Tivon Doreen , Felsovalyi Klara 
Published: October 2016

The cover image, by Timothy Cardozo et al., is based on the Advanced Review Data sources for in vivo molecular profiling of human phenotypes, DOI: 10.1002/wsbm.1354.
image
A&nbsp;five-year retrospective evaluation of a&nbsp;faculty research fellowship programme at the medical college of Georgia
Authors: Wyatt Tasha R. , Braun Kelli , Evans Lance , Rossi Alexis , Wallach Paul M. , Stepleman Lara M. 
Published: October 2016

Introduction In institutional assessments of faculty, scholarly activity is often cited as a deficiency. Faculty lack the training and resources needed to produce peer-reviewed, quality scholarship. Although a variety of formats have been suggested and used to fill this void, fellowships are a commonly used format to foster educational leaders within institutions. In 2010, the Educational Innovation Institute at the Medical College of Georgia created an educational research fellowship to address this need.
Methods To assess the success of our programme, we compared all graduating fellows’ current curriculum vitae (CVs) with the version submitted at the time of their application, looking for educational scholarship produced during and after their participation in the fellowship. Qualitative data sources, such as article reflections, mid-fellowship surveys, and exit surveys were analyzed to identify the mechanisms that contributed to their success. The constant comparative method was used to identify themes and patterns.
Results A comparison of CVs collected at the time of application with a current CV indicate the 11 participants produced: 60 presentations at regional or national meetings, 16 peer reviewed publications, received funding for 7 grants supporting educational research, and won 7 national research awards. Our qualitative analysis identified three major mechanisms: 1) dedicated time to conducting educational research, 2) opportunities to engage with others, and 3 ) understanding the differences between educational and clinical research.
Discussion Previous criticisms of fellowships include faculty not producing educational scholarship after completing their programme.
Loss of Rictor with aging in osteoblasts promotes age-related bone loss
Authors: Lai Pinling , Song Qiancheng , Yang Cheng , Li Zhen , Liu Sichi , Liu Bin , Li Mangmang , Deng Hongwen , Cai Daozhang , Jin Dadi , Liu Anling , Bai Xiaochun 
Published: October 2016

AbstractOsteoblast dysfunction is a major cause of age-related bone loss, but the mechanisms underlying changes in osteoblast function with aging are poorly understood. This study demonstrates that osteoblasts in aged mice exhibit markedly impaired adhesion to the bone formation surface and reduced mineralization in vivo and in vitro. Rictor, a specific component of the mechanistic target of rapamycin complex 2 (mTORC2) that controls cytoskeletal organization and cell survival, is downregulated with aging in osteoblasts. Mechanistically, we found that an increased level of reactive oxygen species with aging stimulates the expression of miR-218, which directly targets Rictor and reduces osteoblast bone surface adhesion and survival, resulting in a decreased number of functional osteoblasts and accelerated bone loss in aged mice. Our findings reveal a novel functional pathway important for age-related bone loss and support for miR-218 and Rictor as potential targets for therapeutic intervention for age-related osteoporosis treatment.