bluuebunny/crossref_metadata_2025_split huggingface dataset:
HSP90 Chaperoning in Addition to Phosphoprotein Required for Folding but Not for Supporting Enzymatic Activities of Measles and Nipah Virus L Polymerases
Authors: Bloyet Louis-Marie , Welsch Jérémy , Enchery François , Mathieu Cyrille , de Breyne Sylvain , Horvat Branka , Grigorov Boyan , Gerlier Denis 
Published: May 2016

ABSTRACT

Nonsegmented negative-stranded RNA viruses, or members of the order
Mononegavirales
, share a conserved gene order and the use of elaborate transcription and replication machinery made up of at least four molecular partners. These partners have coevolved with the acquisition of the permanent encapsidation of the entire genome by the nucleoprotein (N) and the use of this N-RNA complex as a template for the viral polymerase composed of the phosphoprotein (P) and the large enzymatic protein (L). Not only is P required for polymerase function, but it also stabilizes the L protein through an unknown underlying molecular mechanism. By using NVP-AUY922 and/or 17-dimethylaminoethylamino-17-demethoxygeldanamycin as specific inhibitors of cellular heat shock protein 90 (HSP90), we found that efficient chaperoning of L by HSP90 requires P in the measles, Nipah, and vesicular stomatitis viruses. While the production of P remains unchanged in the presence of HSP90 inhibitors, the production of soluble and functional L requires both P and HSP90 activity. Measles virus P can bind the N terminus of L in the absence of HSP90 activity. Both HSP90 and P are required for the folding of L, as evidenced by a luciferase reporter insert fused within measles virus L. HSP90 acts as a true chaperon; its activity is transient and dispensable for the activity of measles and Nipah virus polymerases of virion origin. That the cellular chaperoning of a viral polymerase into a soluble functional enzyme requires the assistance of another viral protein constitutes a new paradigm that seems to be conserved within the
Mononegavirales
order.

IMPORTANCE
Viruses are obligate intracellular parasites that require a cellular environment for their replication. Some viruses particularly depend on the cellular chaperoning apparatus. We report here that for measles virus, successful chaperoning of the viral L polymerase mediated by heat shock protein 90 (HSP90) requires the presence of the viral phosphoprotein (P). Indeed, while P protein binds to the N terminus of L independently of HSP90 activity, both HSP90 and P are required to produce stable, soluble, folded, and functional L proteins. Once formed, the mature P+L complex no longer requires HSP90 to exert its polymerase functions. Such a new paradigm for the maturation of a viral polymerase appears to be conserved in several members of the
Mononegavirales
order, including the Nipah and vesicular stomatitis viruses.
MxA Mediates SUMO-Induced Resistance to Vesicular Stomatitis Virus
Authors: Maarifi Ghizlane , Hannoun Zara , Geoffroy Marie Claude , El Asmi Faten , Zarrouk Karima , Nisole Sébastien , Blondel Danielle , Chelbi-Alix Mounira K. 
Published: May 2016

ABSTRACT

Multiple cellular pathways are regulated by small ubiquitin-like modifier (SUMO) modification, including ubiquitin-mediated proteolysis, signal transduction, innate immunity, and antiviral defense. In the study described in this report, we investigated the effects of SUMO on the replication of two members of the
Rhabdoviridae
family, vesicular stomatitis virus (VSV) and rabies virus (RABV). We show that stable expression of SUMO in human cells confers resistance to VSV infection in an interferon-independent manner. We demonstrate that SUMO expression did not alter VSV entry but blocked primary mRNA synthesis, leading to a reduction of viral protein synthesis and viral production, thus protecting cells from VSV-induced cell lysis. MxA is known to inhibit VSV primary transcription. Interestingly, we found that the MxA protein was highly stabilized in SUMO-expressing cells. Furthermore, extracts from cells stably expressing SUMO exhibited an increase in MxA oligomers, suggesting that SUMO plays a role in protecting MxA from degradation, thus providing a stable intracellular pool of MxA available to combat invading viruses. Importantly, MxA depletion in SUMO-expressing cells abrogated the anti-VSV effect of SUMO. Furthermore, SUMO expression resulted in interferon-regulatory factor 3 (IRF3) SUMOylation, subsequently decreasing RABV-induced IRF3 phosphorylation and interferon synthesis. As expected, this rendered SUMO-expressing cells more sensitive to RABV infection, even though MxA was stabilized in SUMO-expressing cells, since its expression did not confer resistance to RABV. Our findings demonstrate opposing effects of SUMO expression on two viruses of the same family, intrinsically inhibiting VSV infection through MxA stabilization while enhancing RABV infection by decreasing IFN induction.

IMPORTANCE
We report that SUMO expression reduces interferon synthesis upon RABV or VSV infection. Therefore, SUMO renders cells more sensitive to RABV but unexpectedly renders cells resistant to VSV by blocking primary mRNA synthesis. Unlike the interferon-mediated innate immune response, intrinsic antiviral resistance is mediated by constitutively expressed restriction factors. Among the various anti-VSV restriction factors, only MxA is known to inhibit VSV primary transcription, and we show here that its expression does not alter RABV infection. Interestingly, MxA depletion abolished the inhibition of VSV by SUMO, demonstrating that MxA mediates SUMO-induced intrinsic VSV resistance. Furthermore, MxA oligomerization is known to be critical for its protein stability, and we show that higher levels of oligomers were formed in cells expressing SUMO than in wild-type cells, suggesting that SUMO may play a role in protecting MxA from degradation, providing a stable intracellular pool of MxA able to protect cells from viral infection.
Structured, supported feeding admissions for restrictive eating disorders on paediatric wards
Authors: Street Karen , Costelloe Susie , Wootton Michelle , Upton Sonja , Brough Julie 
Published: May 2016

BackgroundRestrictive eating disorders in young people are increasingly requiring admission to the hospital and can be a challenge to manage on acute general paediatric wards.MethodsWe have developed a joint working model with Child and Adolescent Mental Health services (CAMHS) using short, structured, supported feeding admissions to supplement outpatient treatment in high risk or ‘stuck’ cases.ResultsWe have successfully managed the majority of young people in the community avoiding lengthy, expensive, specialist CAMHS eating disorder inpatient unit admissions (tier 4). Local ward admissions are easier to manage and the attitudes of nursing and medical staff towards these young people have changed.DiscussionJoint working between paediatric and CAMHS teams enables shorter, more manageable local ward admissions, reducing the need for tier-4 units.
Canada's residential school system: measuring the intergenerational impact of familial attendance on health and mental health outcomes
Authors: Hackett Christina , Feeny David , Tompa Emile 
Published: May 2016

BackgroundWe estimate the intergenerational relationship between the residential school (RS) attendance of an older generation family member and the physical and mental health of a younger generation.MethodsData from the 2012 Aboriginal Peoples Survey (APS) is used to examine the relationship between previous generational family RS attendance and the current physical and mental health of off-reserve First Nations, Métis and Inuit Canadians. Five outcomes are considered (self-perceived health, mental health, distress, suicidal ideation and suicide attempt). Direct (univariate) and indirect (multivariate) effects of family RS attendance are examined for each dependent variable. We draw from the general and indigenous-specific social determinants of health literature to inform the construction of our models.ResultsFamilial RS attendance is shown to affect directly all five health and mental health outcomes, and is associated with lower self-perceived health and mental health, and a higher risk for distress and suicidal behaviours. Background, mediating and structural-level variables influence the strength of association. Odds of being in lower self-perceived health remain statistically significantly higher with the presence of familial attendance of RS when controlling for all covariates. The odds of having had a suicide attempt within the past 12 months remain twice as high for those with familial attendance of RS.ConclusionsHealth disparities exist between indigenous and non-indigenous Canadians, an important source of which is a family history of RS attendance. This has implications for clinical practice and Canadian public health, as well as countries with similar historical legacies.
Tension-induced mechanical properties of stanene
Authors: Tao Lele , Yang Chuanghua , Wu Liyuan , Han Lihong , Song Yuxin , Wang Shumin , Lu Pengfei 
Published: May 2016

In this paper, elastic properties of stanene under equiaxial or uniaxial tensions along armchair and zigzag directions are investigated by first-principles calculations. The stress–strain relation is calculated and the relaxation of the internal atom positions is analyzed. The high-order elastic constants are calculated by fitting the polynomial expressions. The Young’s modulus and Poisson ratio of the stanene is calculated to be 24.14 N/m and 0.39 N/m, respectively. The stanene exhibits lower Young’s modulus than those of the proceeding group IV elements, which is attributed to the smaller [Formula: see text]–[Formula: see text] bond energy in stanene than those of silicene and germanene. Calculated values of ultimate stresses and strains, second-order elastic constants (SOCEs) and the in-plane Young’s modulus are all positive. It proves that stanene is mechanically stable.
The electronic structure of graphene tuned by hexagonal boron nitrogen layers: Semimetal–semiconductor transition
Authors: Liu Ming-Yang , Chen Qing-Yuan , Ma Tai , He Yao , Cao Chao 
Published: May 2016

The electronic structure of graphene and hexagonal boron nitrogen (G/h-BN) systems have been carefully investigated using the pseudo-potential plane-wave within density functional theory (DFT) framework. We find that the stacking geometries and interlayer distances significantly affect the electronic structure of G/h-BN systems. By studying four stacking geometries, we conclude that the monolayer G/h-BN systems should possess metallic electronic properties. The monolayer G/h-BN systems can be transited from metallicity to semiconductor by increasing h-BN layers. It reveals that the alteration of interlayer distances 2.50–3.50 Å can obtain the metal–semiconductor–semimetal variation and a tunable band gap for G/h-BN composite systems. The band dispersion along [Formula: see text]–[Formula: see text] direction is analogous to the band of rhombohedral graphite when the G/h-BN systems are semiconducting.
Regulation of GLI Underlies a Role for BET Bromodomains in Pancreatic Cancer Growth and the Tumor Microenvironment
Authors: Huang Yinshi , Nahar Sabikun , Nakagawa Akifumi , Fernandez-Barrena Maite G. , Mertz Jennifer A. , Bryant Barbara M. , Adams Curtis E. , Mino-Kenudson Mari , Von Alt Kate N. , Chang Kevin , Conery Andrew R. , Hatton Charlie , Sims Robert J. , Fernandez-Zapico Martin E. , Wang Xingpeng , Lillemoe Keith D. , Fernández-del Castillo Carlos , Warshaw Andrew L. , Thayer Sarah P. , Liss Andrew S. 
Published: May 2016

Abstract
Purpose: The initiation, progression, and maintenance of pancreatic ductal adenocarcinoma (PDAC) results from the interplay of genetic and epigenetic events. While the genetic alterations of PDAC have been well characterized, epigenetic pathways regulating PDAC remain, for the most part, elusive. The goal of this study was to identify novel epigenetic regulators contributing to the biology of PDAC.
Experimental Design: In vivo pooled shRNA screens targeting 118 epigenetic proteins were performed in two orthotopic PDAC xenograft models. Candidate genes were characterized in 19 human PDAC cell lines, heterotopic xenograft tumor models, and a genetically engineered mouse (GEM) model of PDAC. Gene expression, IHC, and immunoprecipitation experiments were performed to analyze the pathways by which candidate genes contribute to PDAC.
Results: In vivo shRNA screens identified BRD2 and BRD3, members of the BET family of chromatin adaptors, as key regulators of PDAC tumor growth. Pharmacologic inhibition of BET bromodomains enhanced survival in a PDAC GEM model and inhibited growth of human-derived xenograft tumors. BET proteins contribute to PDAC cell growth through direct interaction with members of the GLI family of transcription factors and modulating their activity. Within cancer cells, BET bromodomain inhibition results in downregulation of SHH, a key mediator of the tumor microenvironment and canonical activator of GLI. Consistent with this, inhibition of BET bromodomains decreases cancer-associated fibroblast content of tumors in both GEM and xenograft tumor models.
Conclusions: Therapeutic inhibition of BET proteins offers a novel mechanism to target both the neoplastic and stromal components of PDAC. Clin Cancer Res; 22(16); 4259–70. ©2016 AACR.
EGFR-Mediated Reactivation of MAPK Signaling Induces Acquired Resistance to GSK2118436 in BRAF V600E–Mutant NSCLC Cell Lines
Authors: Kim Sung-Moo , Kim Hwan , Jang Kang Won , Kim Min Hwan , Sohn Jinyoung , Yun Mi Ran , Kang Han Na , Kang Chan Woo , Kim Hye Ryun , Lim Sun Min , Moon Yong Wha , Kim Joo Hang , Paik Soonmyung , Cho Byoung Chul 
Published: May 2016

Abstract
Although treatment of BRAF V600E–mutant non–small cell lung cancer (NSCLCV600E) with GSK2118436 has shown an encouraging efficacy, most patients develop resistance. To investigate the mechanisms of acquired resistance to GSK2118436 in NSCLCV600E, we established GSK2118436-resistant (GSR) cells by exposing MV522 NSCLCV600E to increasing GSK2118436 concentrations. GSR cells displayed activated EGFR–RAS–CRAF signaling with upregulated EGFR ligands and sustained activation of ERK1/2, but not MEK1/2, in the presence of GSK2118436. Treatment of GSR cells with GSK2118436 enhanced EGFR-mediated RAS activity, leading to the formation of BRAF–CRAF dimers and transactivation of CRAF. Interestingly, sustained activation of ERK1/2 was partly dependent on receptor-interacting protein kinase-2 (RIP2) activity, but not on MEK1/2 activity. Combined BRAF and EGFR inhibition blocked reactivation of ERK signaling and improved efficacy in vitro and in vivo. Our findings support the evaluation of combined BRAF and EGFR inhibition in NSCLCV600E with acquired resistance to BRAF inhibitors. Mol Cancer Ther; 15(7); 1627–36. ©2016 AACR.
An Integrative Approach Uncovers Biomarkers that Associate with Clinically Relevant Disease Outcomes in Vulvar Carcinoma
Authors: Lavorato-Rocha Andre M. , Akagi Erica M. , de Melo Maia Beatriz , Rodrigues Iara S. , Botelho Mayara Caroline Silva , Marchi Fabio A. , Fernandes Gabriel , Baiocchi Glauco , Soares Fernando A. , Rogatto Silvia Regina , Sato-Kuwabara Yukie , Rocha Rafael M. 
Published: May 2016

Abstract
Vulvar squamous cell carcinoma (VSCC) is a rare disease that has a high mortality rate (∼40%). However, little is known about its molecular signature. Therefore, an integrated genomics approach, based on comparative genome hybridization (aCGH) and genome-wide expression (GWE) array, was performed to identify driver genes in VSCC. To achieve that, DNA and RNA were extracted from frozen VSCC clinical specimens and examined by aCGH and GWE array, respectively. On the basis of the integration of data using the CONEXIC algorithm, PLXDC2 and GNB3 were validated by RT-qPCR. The expression of these genes was then analyzed by IHC in a large set of formalin-fixed paraffin-embedded specimens. These analyses identified 47 putative drivers, 46 of which were characterized by copy number gains that were concomitant with overexpression and one with a copy number loss and downregulation. Two of these genes, PLXDC2 and GNB3, were selected for further validation: PLXDC2 was downregulated and GNB3 was overexpressed compared with non-neoplastic tissue. By IHC, both proteins were ubiquitously expressed throughout vulvar tissue. High expression of GNB3 and low PLXDC2 immunostaining in the same sample was significantly associated with less lymph node metastasis and greater disease-free survival. On the basis of a robust methodology never used before for VSCC evaluation, two novel prognostic markers in vulvar cancer are identified: one with favorable prognosis (GNB3) and the other with unfavorable prognosis (PLXDC2).
Implications: This genomics study reveals markers that associate with prognosis and may provide guidance for better treatment in vulvar cancer. Mol Cancer Res; 14(8); 720–9. ©2016 AACR.
МЕДСЕСТРИНСЬКИЙ ПРОЦЕС У КЛІНІЧНІЙ ФАРМАКОЛОГІЇ
Authors: Lomova N. O. 
Published: May 2016

<p class="NoSpacing">У статті розглянуто роль медичної сестри у виконанні лікарських призначень з позиції медсестринського процесу. В Україні ця тема нова, тоді як у США та Канаді клінічна фармакологія для медсестер викладається саме таким чином. Розглянуто основні моменти, на які нееобхідно звертати увагу медичним сестрам, коли вони роздають або вводять лікарські засоби пацієнтам.</p><p class="NoSpacing">Стаття буде корисною як практикуючим медсестрам, так і студентам та викладачам клінічної фармакології в медичних коледжах, училищах.</p>
НЕГАТИВНИЙ ВПЛИВ ХІМІЧНИХ ЧИННИКІВ НА МЕДИЧНУ СЕСТРУ В УМОВАХ ЛІКУВАЛЬНОГО ЗАКЛАДУ ТА ЗАХОДИ ЩОДО ЇХ ПРОФІЛАКТИКИ
Authors: Lytvynyuk V. V. 
Published: May 2016

<p>У статті розглянуто вплив хімічних речовин на здоров’я медичних працівників середньої ланки різних клінічних закладів та заходи щодо їх профілактиці. </p>
ПЕРСПЕКТИВИ ПІДГОТОВКИ МЕДИЧНОЇ СЕСТРИ-БАКАЛАВРА З ДИСЦИПЛІНИ «АНЕСТЕЗІОЛОГІЯ ТА РЕАНІМАТОЛОГІЯ»
Authors: Ryzhkovskyi A. V. , Hrubska O. S. , Nosko H. V. 
Published: May 2016

<p>У статті проведено порівняльний аналіз систем професійної підготовки медсестер України і Канади з метою удосконалення вітчизняної системи підготовки медсестер. Окреслено основні відмінності у специфіці роботи і обов’язками медсестер реанімаційних відділень України і Канади. Вказано на гостру необхідність удосконалення професійної підготовки українських медсестер зі спеціальності «Анестезіологія і реаніматологія» і запропоновано кроки для досягнення цієї мети. </p>
СТАНДАРТИЗАЦІЯ ДІЯЛЬНОСТІ МЕДСЕСТРИНСЬКОЇ СЛУЖБИ ЛЬВІВСЬКОЇ ОБЛАСТІ
Authors: Galapats N. B. 
Published: May 2016

<p>Впровадження медсестринського процесу в практичну охорону здоров'я – це необхідна умова для створення науково-обгрунтованого професійного догляду за пацієнтом. Медсестринський процес як універсальна технологія медсестринської справи може і повинен використовуватись медсестрами у своїй повсякденній діяльності для своєчасного виявлення та усунення ризику розвитку захворювань, зменшення ускладнень, що дозволить підвищити якість життя пацієнта. </p>
Impact of New-Onset Left Bundle Branch Block and Periprocedural Permanent Pacemaker Implantation on Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Regueiro Ander , Abdul-Jawad Altisent Omar , Del Trigo María , Campelo-Parada Francisco , Puri Rishi , Urena Marina , Philippon François , Rodés-Cabau Josep 
Published: May 2016

Background—
Available data on the clinical impact of new-onset left bundle branch block (LBBB) and permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) remains controversial. We aimed to evaluate the impact of (1) periprocedural new-onset LBBB or PPI post-TAVR on cardiac mortality and all-cause 1-year mortality and (2) new-onset LBBB on the need for PPI at 1-year follow-up.

Methods and Results—
We performed a systematic search from PubMed and EMBASE databases for studies reporting raw data on new-onset LBBB post-TAVR and the need for PPI or mortality at 1-year follow-up, or on 1-year mortality according to the need for periprocedural PPI post-TAVR. Data from 17 studies, including 4756 patients (8 studies) and 7032 patients (11 studies) for the evaluation of the impact of new-onset LBBB and periprocedural PPI post-TAVR were sourced, respectively (with 2 studies used for both outcomes). New-onset LBBB post-TAVR was associated with a higher risk of PPI (risk ratio [RR], 2.18; 95% confidence interval [CI], 1.28–3.70) and cardiac death (RR, 1.39; 95% CI, 1.04–1.86) during follow-up, as well with a tendency toward an increase in all-cause mortality (RR, 1.21; 95% CI, 0.98–1.50). Periprocedural PPI post-TAVR was not associated with any increased risk of all-cause mortality at 1 year (RR, 1.03; 95% CI, 0.9–1.18), yet a tendency toward a protective effect on cardiac death was observed (RR, 0.78; 95% CI, 0.60–1.03).

Conclusions—
New-onset LBBB post-TAVR is a marker of an increased risk of cardiac death and need for PPI at 1-year follow-up. The need for PPI early post-TAVR did not increase the risk of death.
A Model for the Complete Radial Structure of the Tropical Cyclone Wind Field. Part II: Wind Field Variability
Authors: Chavas Daniel R. , Lin Ning 
Published: May 2016

Abstract
Part I of this work developed a simple physical model for the complete radial structure of the low-level azimuthal wind field in a tropical cyclone that compared well with observations. However, wind field variability in the model is tied principally to its external parameters given by the maximum wind speed and the radius of maximum wind, the latter of which lacks a credible independent physical model for its variability. Here the authors explore the modes of variability that arise from the alternative specification of the model, which takes the outer radius in lieu of the radius of maximum wind. Nondimensionalization of the model reveals two theoretical modes of structural variability in absolute angular momentum that are shown to closely match observations. These two modes correspond to three modes of wind field variability associated with variations in intensity, outer storm size, and latitude. These wind field modes are demonstrated to mirror the dominant modes of variability found in nature, in particular the intrastorm variation of inner-core structure and the interstorm variation of overall storm size. In combination, the model offers a credible physical solution for the complete time-dependent tropical cyclone wind field in conjunction with the external specification of intensity, outer size, and latitude. More broadly, the model offers theoretical and conceptual insight into the nature of the tropical cyclone wind field, including the oft-conflated terms “size” and “structure” and their distinct variabilities.