bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cysteines in the Stalk of the Nipah Virus G Glycoprotein Are Located in a Distinct Subdomain Critical for Fusion Activation
Authors: Maar Dianna , Harmon Brooke , Chu David , Schulz Belinda , Aguilar Hector C. , Lee Benhur , Negrete Oscar A. 
Published: April 2012

ABSTRACT

Paramyxoviruses initiate entry through the concerted action of the tetrameric attachment glycoprotein (HN, H, or G) and the trimeric fusion glycoprotein (F). The ectodomains of HN/H/G contain a stalk region important for oligomeric stability and for the F triggering resulting in membrane fusion. Paramyxovirus HN, H, and G form a dimer-of-dimers consisting of disulfide-linked dimers through their stalk domain cysteines. The G attachment protein stalk domain of the highly pathogenic Nipah virus (NiV) contains a distinct but uncharacterized cluster of three cysteine residues (C146, C158, C162). On the basis of a panoply of assays, we report that C158 and C162 of NiV-G likely mediate covalent subunit dimerization, while C146 mediates the stability of higher-order oligomers. For HN or H, mutation of stalk cysteines attenuates but does not abrogate the ability to trigger fusion. In contrast, the NiV-G stalk cysteine mutants were completely deficient in triggering fusion, even though they could still bind the ephrinB2 receptor and associate with F. Interestingly, all cysteine stalk mutants exhibited constitutive exposure of the Mab45 receptor binding-enhanced epitope, previously implicated in F triggering. The enhanced binding of Mab45 to the cysteine mutants relative to wild-type NiV-G, without the addition of the receptor, implicates the stalk cysteines in the stabilization of a pre-receptor-bound conformation and the regulation of F triggering. Sequence alignments revealed that the stalk cysteines were adjacent to a proline-rich microdomain unique to the
Henipavirus
genus. Our data propose that the cysteine cluster in the NiV-G stalk functions to maintain oligomeric stability but is more importantly involved in stabilizing a unique microdomain critical for triggering fusion.
Human Galectin 3 Binding Protein Interacts with Recombinant Adeno-Associated Virus Type 6
Authors: Denard Jerome , Beley Cyriaque , Kotin Robert , Lai-Kuen René , Blot Stéphane , Leh Hervé , Asokan Aravind , Samulski R. Jude , Moullier Philippe , Voit Thomas , Garcia Luis , Svinartchouk Fedor 
Published: April 2012

ABSTRACT

Recombinant adeno-associated viruses (rAAVs) hold enormous potential for human gene therapy. Despite the well-established safety and efficacy of rAAVs for
in vivo
gene transfer, there is still little information concerning the fate of vectors in blood following systemic delivery. We screened for serum proteins interacting with different AAV serotypes in humans, macaques, dogs, and mice. We report that serotypes rAAV-1, -5, and -6 but not serotypes rAAV-2, -7, -8, -9, and -10 interact in human sera with galectin 3 binding protein (hu-G3BP), a soluble scavenger receptor. Among the three serotypes, rAAV-6 has the most important capacities for binding to G3BP. rAAV-6 also bound G3BP in dog sera but not in macaque and mouse sera. In mice, rAAV-6 interacted with another protein of the innate immune system, C-reactive protein (CRP). Furthermore, interaction of hu-G3BP with rAAV-6 led to the formation of aggregates and hampered transduction when the two were codelivered into the mouse. Based on these data, we propose that species-specific interactions of AAVs with blood proteins may differentially impact vector distribution and efficacy in different animal models.
Classical Swine Fever Virus p7 Protein Is a Viroporin Involved in Virulence in Swine
Authors: Gladue Douglas P. , Holinka Lauren G. , Largo Eneko , Fernandez Sainz Ignacio , Carrillo Consuelo , O'Donnell Vivian , Baker-Branstetter Ryan , Lu Zhiqiang , Ambroggio Xavier , Risatti Guillermo R. , Nieva Jose L. , Borca Manuel V. 
Published: April 2012

ABSTRACT

The nonstructural protein p7 of classical swine fever virus (CSFV) is a small hydrophobic polypeptide with an apparent molecular mass of 6 to 7 kDa. The protein contains two hydrophobic stretches of amino acids interrupted by a short charged segment that are predicted to form transmembrane helices and a cytosolic loop, respectively. Using reverse genetics, partial in-frame deletions of p7 were deleterious for virus growth, demonstrating that CSFV p7 function is critical for virus production in cell cultures. A panel of recombinant mutant CSFVs was created using alanine scanning mutagenesis of the p7 gene harboring sequential three- to six-amino-acid residue substitutions spanning the entire protein. These recombinant viruses allowed the identification of the regions within p7 that are critical for virus production
in vitro. In vivo
, some of these viruses were partially or completely attenuated in swine relative to the highly virulent parental CSFV Brescia strain, indicating a significant role of p7 in CSFV virulence. Structure-function analyses in model membranes emulating the endoplasmic reticulum lipid composition confirmed that CSFV p7 is a pore-forming protein, and that pore-forming activity resides in the C-terminal transmembrane helix. Therefore, p7 is a viroporin which is clearly involved in the process of CSFV virulence in swine.
Cdk1 Inhibition Induces Mutually Inhibitory Apoptosis and Reactivation of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Li Xudong , Chen Shijia , Sun Ren 
Published: April 2012

ABSTRACT
Primary effusion lymphoma (PEL) cells are predominantly infected by the latent form of Kaposi's sarcoma-associated herpesvirus (KSHV), with virus reactivation occurring in a small percentage of cells. Latency enables KSHV to persist in the host cell and promotes tumorigenesis through viral gene expression, thus presenting a major barrier to the elimination of KSHV and the treatment of PEL. Therefore, it is important to identify cellular genes that are essential for PEL cell survival or the maintenance of KSHV latency. Here we report that cyclin-dependent kinase 1 (Cdk1) inhibition can induce both apoptosis and KSHV reactivation in a population of PEL cells. Caspases, but not p53, are required for PEL cell apoptosis induced by Cdk1 inhibition. p38 kinase is activated by Cdk1 inhibition and mediates KSHV reactivation. Interestingly, upon Cdk1 inhibition, KSHV is reactivated predominantly in the nonapoptotic subpopulation of PEL cells. We provide evidence that this is due to mutual inhibition between apoptosis and KSHV reactivation. In addition, we found that KSHV reactivation activates protein kinase B (AKT/PKB), which promotes cell survival and facilitates KSHV reactivation. Our study thus establishes a key role for Cdk1 in PEL cell survival and the maintenance of KSHV latency and reveals a multifaceted relationship between KSHV reactivation and PEL cell apoptosis.
Integrin β1 Mediates Vaccinia Virus Entry through Activation of PI3K/Akt Signaling
Authors: Izmailyan Roza , Hsao Jye-Chian , Chung Che-Sheng , Chen Chein-Hung , Hsu Paul Wei-Che , Liao Chung-Lin , Chang Wen 
Published: April 2012

ABSTRACT
Vaccinia virus has a broad range of infectivity in many cell lines and animals. Although it is known that the vaccinia mature virus binds to cell surface glycosaminoglycans and extracellular matrix proteins, whether additional cellular receptors are required for virus entry remains unclear. Our previous studies showed that the vaccinia mature virus enters through lipid rafts, suggesting the involvement of raft-associated cellular proteins. Here we demonstrate that one lipid raft-associated protein, integrin β1, is important for vaccinia mature virus entry into HeLa cells. Vaccinia virus associates with integrin β1 in lipid rafts on the cell surface, and the knockdown of integrin β1 in HeLa cells reduces vaccinia mature virus entry. Additionally, vaccinia mature virus infection is reduced in a mouse cell line, GD25, that is deficient in integrin β1 expression. Vaccinia mature virus infection triggers the activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling, and the treatment of cells with inhibitors to block P13K activation reduces virus entry in an integrin β1-dependent manner, suggesting that integrin β1-mediates PI3K/Akt activation induced by vaccinia virus and that this signaling pathway is essential for virus endocytosis. The inhibition of integrin β1-mediated cell adhesion results in a reduction of vaccinia virus entry and the disruption of focal adhesion and PI3K/Akt activation. In summary, our results show that the binding of vaccinia mature virus to cells mimics the outside-in activation process of integrin functions to facilitate vaccinia virus entry into HeLa cells.
Comparing two safety culture surveys: Safety Attitudes Questionnaire and Hospital Survey on Patient Safety
Authors: Etchegaray Jason M , Thomas Eric J 
Published: April 2012

ObjectiveTo examine the reliability and predictive validity of two patient safety culture surveys—Safety Attitudes Questionnaire (SAQ) and Hospital Survey on Patient Safety Culture (HSOPS)—when administered to the same participants. Also to determine the ability to convert HSOPS scores to SAQ scores.MethodEmployees working in intensive care units in 12 hospitals within a large hospital system in the southern United States were invited to anonymously complete both safety culture surveys electronically.ResultsAll safety culture dimensions from both surveys (with the exception of HSOPS's Staffing) had adequate levels of reliability. Three of HSOPS's outcomes—frequency of event reporting, overall perceptions of patient safety, and overall patient safety grade—were significantly correlated with SAQ and HSOPS dimensions of culture at the individual level, with correlations ranging from r=0.41 to 0.65 for the SAQ dimensions and from r=0.22 to 0.72 for the HSOPS dimensions. Neither the SAQ dimensions nor the HSOPS dimensions predicted the fourth HSOPS outcome—number of events reported within the last 12 months. Regression analyses indicated that HSOPS safety culture dimensions were the best predictors of frequency of event reporting and overall perceptions of patient safety while SAQ and HSOPS dimensions both predicted patient safety grade. Unit-level analyses were not conducted because indices did not indicate that aggregation was appropriate. Scores were converted between the surveys, although much variance remained unexplained.ConclusionsGiven that the SAQ and HSOPS had similar reliability and predictive validity, investigators and quality and safety leaders should consider survey length, content, sensitivity to change and the ability to benchmark when selecting a patient safety culture survey.
Maternal mental health and social support: effect on childhood atopic and non-atopic asthma symptoms
Authors: Marques dos Santos Letícia , Neves dos Santos Darci , Rodrigues Laura Cunha , Barreto Maurício Lima 
Published: April 2012

BackgroundAtopic and non-atopic asthma have distinct risk factors and immunological mechanisms, and few studies differentiate between the impacts of psychosocial factors on the prevalence of these disease phenotypes. The authors aimed to identify whether the effect of maternal mental health on prevalence of asthma symptoms differs between atopic and non-atopic children, taking into account family social support.MethodsThis is a cross-sectional study of 1013 children participating in the Social Change Allergy and Asthma in Latin America project. Psychosocial data were collected through a household survey utilising Self-Reporting Questionnaire and Medical Outcome Study Social Support Scale. Socioeconomic and wheezing information was obtained through the questionnaire of the International Study of Allergy and Asthma in Childhood, and level of allergen-specific IgE was measured to identify atopy. Polytomous logistic regression was used to estimate the association between maternal mental health, social support and atopic and non-atopic wheezing. Effect modification was evaluated through stratified polytomous regression according to social support level.ResultsMaternal mental disorder had the same impact on atopic and non-atopic wheezing, even after adjusting for confounding variables. Affective, material and informational supports had protective effects on non-atopic asthma, and there is some evidence that social supports may act as a buffer for the impact of maternal mental disorder on non-atopic wheezing.ConclusionPoor maternal mental health is positively associated with wheezing, independent of whether asthma is atopic or non-atopic, but perception of high levels of social support appears to buffer this relationship in non-atopic wheezers only.
Trends in condom use among female sex workers in Andhra Pradesh, India: the impact of a community mobilisation intervention
Authors: Erausquin Jennifer Toller , Biradavolu Monica , Reed Elizabeth , Burroway Rebekah , Blankenship Kim M 
Published: April 2012

BackgroundCommunity mobilisation interventions for HIV prevention among female sex workers (FSWs) aim to organise FSWs for collective action and challenge the structures of power that underlie HIV risk. Assessing intervention impact is challenging because the importance of direct individual exposure to intervention components may decrease over time as change occurs at social-normative, policy and other structural levels. In this paper, the authors examine changes over time in consistent condom use among FSWs in Rajahmundry, Andhra Pradesh, the location of a long-standing community mobilisation intervention.MethodsThe authors analyse cross-sectional data collected among FSWs at three time points (n=2276) using respondent-driven sampling. Multiple logistic regression was used to assess the association of programme exposure with consistent condom use and whether this association varied over time.ResultsThe proportion of FSWs having no exposure or only receptive exposure to the intervention decreased over time, while active utilisation increased from 19.4% in 2006 to 48.5% in 2009–2010. Consistent condom use with clients also increased from 56.3% in 2006 to 75.3% in 2009–2010. Multivariate analysis showed that age, age at start of sex work, venue, living conditions and programme exposure were significantly associated with condom use. The positive association between programme exposure and consistent condom use did not vary significantly over time.ConclusionsFindings indicate improvements in HIV risk reduction behaviour among FSWs and suggest that the intervention has substantial reach in the FSW population. The intervention's strategies may be contributing to population-level HIV risk reduction among FSWs.
Minding the gap: changes in life expectancy in the Baltic States compared with Finland
Authors: Karanikolos Marina , Leon David A , Smith Peter C , McKee Martin 
Published: April 2012

BackgroundIn the 20 years since the three Baltic States, Estonia, Latvia and Lithuania, have been independent, they have converged progressively with a Western neighbours, politically economically and socially. In contrast, the health gap has widened.MethodsTrends in life expectancy in the three Baltic States were compared with Finland and were decomposed by age for the years 1994, 1999, 2004 and 2009 and by cause of death for year 2009. 1994 was when life expectancy fell to its lowest level since the three countries regained independence.ResultsFrom the mid-1980s to the mid-1990s, the gap in life expectancy between the three Baltic States and Finland widened, especially for men. It then narrowed progressively, except Lithuania where it widened again after 1999. Decomposition by age reveals that the narrowing gap has been driven largely by reduced mortality at working ages, partly counteracted by a relative failure to improve at older ages, especially in Lithuania. Decomposition by cause of death identifies diseases of the circulatory system as the largest contributor to the gap, with the contribution largest at older ages. However, cancer deaths, especially among men, are also important as are deaths from external causes among younger men.ConclusionsAlthough the gaps in life expectancy between the Baltic States and Finland have reduced, improvements, especially in Latvia and Lithuania, have been fragile. There is a clear need to act on the leading causes of the persisting gap with Finland, in particular through action on hazardous drinking and other risk factors for cardiovascular disease.
A Risk Model for Lung Cancer Incidence
Authors: Hoggart Clive , Brennan Paul , Tjonneland Anne , Vogel Ulla , Overvad Kim , Østergaard Jane Nautrup , Kaaks Rudolf , Canzian Federico , Boeing Heiner , Steffen Annika , Trichopoulou Antonia , Bamia Christina , Trichopoulos Dimitrios , Johansson Mattias , Palli Domenico , Krogh Vittorio , Tumino Rosario , Sacerdote Carlotta , Panico Salvatore , Boshuizen Hendriek , Bueno-de-Mesquita H. Bas , Peeters Petra H.M. , Lund Eiliv , Gram Inger Torhild , Braaten Tonje , Rodríguez Laudina , Agudo Antonio , Sánchez-Cantalejo Emilio , Arriola Larraitz , Chirlaque Maria-Dolores , Barricarte Aurelio , Rasmuson Torgny , Khaw Kay-Tee , Wareham Nicholas , Allen Naomi E. , Riboli Elio , Vineis Paolo 
Published: April 2012

Abstract
Risk models for lung cancer incidence would be useful for prioritizing individuals for screening and participation in clinical trials of chemoprevention. We present a risk model for lung cancer built using prospective cohort data from a general population which predicts individual incidence in a given time period. We build separate risk models for current and former smokers using 169,035 ever smokers from the multicenter European Prospective Investigation into Cancer and Nutrition (EPIC) and considered a model for never smokers. The data set was split into independent training and test sets. Lung cancer incidence was modeled using survival analysis, stratifying by age started smoking, and for former smokers, also smoking duration. Other risk factors considered were smoking intensity, 10 occupational/environmental exposures previously implicated with lung cancer, and single-nucleotide polymorphisms at two loci identified by genome-wide association studies of lung cancer. Individual risk in the test set was measured by the predicted probability of lung cancer incidence in the year preceding last follow-up time, predictive accuracy was measured by the area under the receiver operator characteristic curve (AUC). Using smoking information alone gave good predictive accuracy: the AUC and 95% confidence interval in ever smokers was 0.843 (0.810–0.875), the Bach model applied to the same data gave an AUC of 0.775 (0.737–0.813). Other risk factors had negligible effect on the AUC, including never smokers for whom prediction was poor. Our model is generalizable and straightforward to implement. Its accuracy can be attributed to its modeling of lifetime exposure to smoking. Cancer Prev Res; 5(6); 834–46. ©2012 AACR.
A Novel Taspine Derivative, HMQ1611, Inhibits Breast Cancer Cell Growth via Estrogen Receptor α and EGF Receptor Signaling Pathways
Authors: Zhan Yingzhuan , Zhang Yanmin , Liu Cuicui , Zhang Jie , Smith Wanli W. , Wang Nan , Chen Yinnan , Zheng Lei , He Langchong 
Published: April 2012

Abstract
Breast cancer is a common cancer with a leading cause of cancer mortality in women. Currently, the chemotherapy for breast cancer is underdeveloped. Here, we report a novel taspine derivative, HMQ1611, which has anticancer effects using in vitro and in vivo breast cancer models. HMQ1611 reduced cancer cell proliferation in four human breast cancer cell lines including MDA-MB-231, SK-BR-3, ZR-75-30, and MCF-7. HMQ1611 more potently reduced growth of estrogen receptor α (ERα)-positive breast cancer cells (ZR-75-30 and MCF-7) than ERα-negative cells (MDA-MB-231 and SK-BR-3). Moreover, HMQ1611 arrested breast cancer cell cycle at S-phase. In vivo tumor xenograft model, treatment of HMQ1611 significantly reduced tumor size and weight compared with vehicles. We also found that HMQ1611 reduced ERα expression and inhibited membrane ERα-mediated mitogen—activated protein kinase (MAPK) signaling following the stimulation of cells with estrogen. Knockdown of ERα by siRNA transfection in ZR-75-30 cells attenuated HMQ1611 effects. In contrast, overexpression of ERα in MDA-MB-231 cells enhanced HMQ1611 effects, suggesting that ERα pathway mediated HMQ1611′s inhibition of breast cancer cell growth in ERα-positive breast cancer. HMQ1611 also reduced phosphorylation of EGF receptor (EGFR) and its downstream signaling players extracellular signal—regulated kinase (ERK)1/2 and AKT activation both in ZR-75-30 and MDA-MB-231 cells. These results showed that the novel compound HMQ1611 had anticancer effects, and partially via ERα and/or EGFR signaling pathways, suggesting that HMQ1611 may be a potential novel candidate for human breast cancer intervention. Cancer Prev Res; 5(6); 864–73. ©2012 AACR.
Chronic Inhibition of cGMP Phosphodiesterase 5A Improves Diabetic Cardiomyopathy
Authors: Giannetta Elisa , Isidori Andrea M. , Galea Nicola , Carbone Iacopo , Mandosi Elisabetta , Vizza Carmine D. , Naro Fabio , Morano Susanna , Fedele Francesco , Lenzi Andrea 
Published: April 2012

Background—
cGMP phosphodiesterase type 5 protein is upregulated in myocardial hypertrophy. However, it has never been ascertained whether phosphodiesterase type 5 inhibition exerts an antiremodeling effect in nonischemic heart disease in humans. We explored the cardioreparative properties of a selective phosphodiesterase type 5 inhibitor, sildenafil, in a model of diabetic cardiomyopathy.

Methods and Results—

Fifty-nine diabetic men (60.3±7.4 years) with cardiac magnetic resonance imaging consistent with nonischemic, nonfailing diabetic cardiomyopathy (reduced circumferential strain [σ], −12.6±3.1; increased left ventricular [LV] torsion [θ], 18.4±4.6°; and increased ratio of LV mass to volume, 2.1±0.5 g/mL) were randomized to receive sildenafil or placebo (100 mg/d). At baseline, the metabolic indices were correlated with torsion, strain, N-terminal pro–B-type natriuretic peptide, vascular endothelial growth factor, monocyte chemotactic protein-1, and blood pressure. After 3 months, sildenafil produced a significant improvement compared with placebo in LV torsion (Δθ: sildenafil, −3.89±3.11° versus placebo, 2.13±2.35°;
P
<0.001) and strain (Δσ: sildenafil, −3.30±1.86 versus placebo, 1.22±1.84;
P
<0.001). Sildenafil-induced improvement of LV contraction was accompanied by consistent changes in chamber geometry and performance, with a 6.5±11 improvement in mass-to-volume ratio over placebo (
P
=0.021). Monocyte chemotactic protein-1 and transforming growth factor-β were the only markers affected by active treatment (Δmonocyte chemotactic protein-1: −75.30±159.28 pg/mL,
P
=0.032; Δtransforming growth factor-β: 5.26±9.67 ng/mL,
P
=0.009). No changes were found in endothelial function, afterload, or metabolism.

Conclusions—
The early features of diabetic cardiomyopathy are LV concentric hypertrophy associated with altered myocardial contraction dynamics. Chronic phosphodiesterase type 5 inhibition, at this stage, has an antiremodeling effect, resulting in improved cardiac kinetics and circulating markers. This effect is independent of any other vasodilatory or endothelial effects and is apparently exerted through a direct intramyocardial action.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00692237.