bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Role of the Potyviral Helper Component Proteinase Contributes To Enhance the Yield of Viral Particles
Authors: Valli Adrian , Gallo Araíz , Calvo María , Pérez José de Jesús , García Juan Antonio 
Published: June 2014

ABSTRACTThe helper component proteinase (HCPro) is an indispensable, multifunctional protein of members of the genusPotyvirusand other viruses of the familyPotyviridae. This viral factor is directly involved in diverse steps of viral infection, such as aphid transmission, polyprotein processing, and suppression of host antiviral RNA silencing. In this paper, we show that although a chimeric virus based on the potyvirusPlum pox viruslacking HCPro, which was replaced by a heterologous silencing suppressor, caused an efficient infection inNicotiana benthamianaplants, its viral progeny had very reduced infectivity. Making use of different approaches, here, we provide direct evidence of a previously unknown function of HCPro in which the viral factor enhances the stability of its cognate capsid protein (CP), positively affecting the yield of virions and consequently improving the infectivity of the viral progeny. Site-directed mutagenesis revealed that the ability of HCPro to stabilize CP and enhance the yield of infectious viral particles is not linked to any of its previously known activities and helped us to delimit the region of HCPro involved in this function in the central region of the protein. Moreover, the function is highly specific and cannot be fulfilled by the HCPro of a heterologous potyvirus. The importance of this novel requirement in regulating the sorting of the viral genome to be subjected to replication, translation, and encapsidation, thus contributing to the synchronization of these viral processes, is discussed.IMPORTANCEPotyviruses form one of the most numerous groups of plant viruses and are a major cause of crop loss worldwide. It is well known that these pathogens make use of virus-derived multitasking proteins, as well as dedicated host factors, to successfully infect their hosts. Here, we describe a novel requirement for the proper yield and infectivity of potyviral progeny. In this case, such a function is performed by the extensively studied viral factor HCPro, which seems to use an unknown mechanism that is not linked to its previously described activities. To our knowledge, this is the first time that a factor different from capsid protein (CP) has been shown to be directly involved in the yield of potyviral particles. Based on the data presented here, we hypothesize that this capacity of HCPro might be involved in the coordination of mutually exclusive activities of the viral genome by controlling correct assembly of CP in stable virions.
Regulation of Tissue-Dependent Differences in CD8+T Cell Apoptosis during Viral Infection
Authors: Kapoor Varun N. , Shin Hyun Mu , Cho Ok Hyun , Berg Leslie J. , Kang Joonsoo , Welsh Raymond M. 
Published: June 2014

ABSTRACTVirus-specific CD8+T cells in the lymphoid organs contract at the resolution of virus infections by apoptosis or by dissemination into peripheral tissues, and those residing in nonlymphoid organs, including the peritoneal cavity and fat pads, are more resistant to apoptosis than those in the spleen and lymph nodes. This stability of memory T cells in the nonlymphoid tissues may enhance protection to secondary challenges. Here, we show that lymphocytic choriomeningitis virus (LCMV)-specific CD8+T cells in nonlymphoid tissues were enriched for memory precursors (expressing high levels of interleukin-7 receptor and low levels of killer cell lectin-like receptor G1 [IL-7RhiKLRG1lo]) and had higher expression of CD27, CXCR3, and T cell factor-1 (TCF-1), each a marker that is individually correlated with decreased apoptosis. CD8+T cells in the peritoneal cavity of TCF-1-deficient mice had decreased survival, suggesting a role for TCF-1 in promoting survival in the nonlymphoid tissues. CXCR3+CD8+T cells resisted apoptosis and accumulated in the lymph nodes of mice treated with FTY720, which blocks the export of lymph node cells into peripheral tissue. The peritoneal exudate cells (PEC) expressed increased amounts of CXCR3 ligands, CXCL9 and CXCL10, which may normally recruit these nonapoptotic cells from the lymph nodes. In addition, adoptive transfer of splenic CD8+T cells into PEC or spleen environments showed that the peritoneal environment promoted survival of CD8+T cells. Thus, intrinsic stability of T cells which are present in the nonlymphoid tissues along with preferential migration of apoptosis-resistant CD8+T cells into peripheral sites and the availability of tissue-specific factors that enhance memory cell survival may collectively account for the tissue-dependent apoptotic differences.IMPORTANCEMost infections are initiated at nonlymphoid tissue sites, and the presence of memory T cells in nonlymphoid tissues is critical for protective immunity in various viral infection models. Virus-specific CD8+T cells in the nonlymphoid tissues are more resistant to apoptosis than those in lymphoid organs during the resolution and memory phase of the immune response to acute LCMV infection. Here, we investigated the mechanisms promoting stability of T cells in the nonlymphoid tissues. This increased resistance to apoptosis of virus-specific CD8+T cells in nonlymphoid tissues was due to several factors. Nonlymphoid tissues were enriched in memory phenotype CD8+T cells, which were intrinsically resistant to apoptosis irrespective of the tissue environment. Furthermore, apoptosis-resistant CD8+T cells preferentially migrated into the nonlymphoid tissues, where the availability of tissue-specific factors may enhance memory cell survival. Our findings are relevant for the generation of long-lasting vaccines providing protection at peripheral infection sites.
HIV-1 and HIV-2 Vif Interact with Human APOBEC3 Proteins Using Completely Different Determinants
Authors: Smith Jessica L. , Izumi Taisuke , Borbet Timothy C. , Hagedorn Ariel N. , Pathak Vinay K. 
Published: June 2014

ABSTRACT
Human APOBEC3 (A3) restriction factors provide intrinsic immunity against zoonotic transmission of pathogenic viruses. A3D, A3F, A3G, and A3H haplotype II (A3H-hapII) can be packaged into virion infectivity factor (Vif)-deficient HIVs to inhibit viral replication. To overcome these restriction factors, Vif binds to the A3 proteins in viral producer cells to target them for ubiquitination and proteasomal degradation, thus preventing their packaging into assembling virions. Therefore, the Vif-A3 interactions are attractive targets for novel drug development. HIV-1 and HIV-2 arose via distinct zoonotic transmission events of simian immunodeficiency viruses from chimpanzees and sooty mangabeys, respectively, and Vifs from these viruses have limited homology. To gain insights into the evolution of virus-host interactions that led to successful cross-species transmission of lentiviruses, we characterized the determinants of the interaction between HIV-2 Vif (Vif2) with human A3 proteins and compared them to the previously identified HIV-1 Vif (Vif1) interactions with the A3 proteins. We found that A3G, A3F, and A3H-hapII, but not A3D, were susceptible to Vif2-induced degradation. Alanine-scanning mutational analysis of the first 62 amino acids of Vif2 indicated that Vif2 determinants important for degradation of A3G and A3F are completely distinct from these regions in Vif1, as are the determinants in A3G and A3F that are critical for Vif2-induced degradation. These observations suggest that distinct Vif-A3 interactions evolved independently in different SIVs and their nonhuman primate hosts and conservation of the A3 determinants targeted by the SIV Vif proteins resulted in successful zoonotic transmission into humans.

IMPORTANCE
Primate APOBEC3 proteins provide innate immunity against invading pathogens, and Vif proteins of primate lentiviruses have evolved to overcome these host defenses by interacting with them and inducing their proteasomal degradation. HIV-1 and HIV-2 are two human pathogens that induce AIDS, and elucidating interactions between their Vif proteins and human A3 proteins could facilitate the development of novel antiviral drugs. Furthermore, understanding Vif-A3 interactions can provide novel insights into the cross-species transmission events that led to the HIV-1 and HIV-2 pandemics and evolution of host-virus interactions. We carried out mutational analysis of the N-terminal 62 amino acids of HIV-2 Vif (Vif2) and analyzed A3G/A3F chimeras that retained antiviral activity to identify the determinants of the Vif2 and A3 interaction. Our results show that the Vif2-A3 interactions are completely different from the Vif1-A3 interactions, suggesting that these interactions evolved independently and that conservation of the A3 determinants resulted in successful zoonotic transmission into humans.
Introducing a chest pain pathway in the emergency department to improve quality of care for patients with possible cardiac chest pain
Authors: Byrne Jill 
Published: June 2014

AbstractChest pain is a common reason for patients to present to an emergency department (ED). It is crucial not to miss presentations of the potentially life-threatening acute coronary syndrome (ACS), although often these people present with a non-diagnostic ECG. This makes recognition of a history consistent with ACS very important. We noted inconsistencies in assessment, with many admissions to cardiology beds who did not prove to have ACS and some erroneous discharges who subsequently did have an ACS.We introduced a history based risk tool as part of a chest pain pathway into the ED for use by medical staff assessing patients presenting with chest pain. The intervention involved a nurse from cardiology engaging with clerical, nursing, and medical staff in the ED to ensure success of this quality improvement project.The project showed a reduction in admissions to cardiology with suspected ACS from 29% to 15%, with a projected saving of £889 per patient who was prevented from being admitted. In addition, admissions became more appropriate, with an increase in the proportion of patients with a final diagnosis of ACS from 25% to 46% and a reduction in admissions with atypical chest pain from 75% to 54%.
A systematic review to establish health-related quality-of-life domains for intervention targets in cancer cachexia
Authors: Wheelwright S J , Darlington A-S , Hopkinson J B , Fitzsimmons D , White A , Johnson C D 
Published: June 2014

ObjectivesTo develop a model of the impact of cancer cachexia on patients by identifying the relevant health-related quality-of-life (HRQOL) issues, and to use the model to identify opportunities for intervention.MethodsStandard systematic review methods were followed to identify papers which included direct quotes from cancer patients with cachexia or problems with eating or weight loss. Following thematic synthesis methodology, the quotes were coded, and themes and metathemes were extracted. The metathemes were used to develop a model of the patient's experience of cachexia.Results18 relevant papers were identified which, in total, contained interviews with more than 250 patients. 226 patient quotes were extracted from the papers and 171 codes. 26 themes and 8 metathemes were formulated. The model developed from the metathemes demonstrated a direct link between eating and food problems and negative emotions and also a link mediated by the associated physical decline. These links provide opportunities for interventions.ConclusionsThere are a vast number of HRQOL issues associated with cancer cachexia as identified from patients’ own words. The model generated from these issues indicates that relationships, coping and knowledge of the condition are important components of new psychosocial interventions.
Impact of unemployment variations on suicide mortality in Western European countries (2000–2010)
Authors: Laanani Moussa , Ghosn Walid , Jougla Eric , Rey Grégoire 
Published: June 2014

BackgroundA scientific debate is currently taking place on whether the 2008 economic crisis caused an increase in suicide rates. Our main objective was to assess the impact of unemployment rate on suicide rate in Western European countries between 2000 and 2010. We then tried to estimate the excess number of suicides attributable to the increase of unemployment during the 2008–2010 economic crisis.MethodsThe yearly suicide rates were modelled using a quasi-Poisson model, controlling for sex, age, country and a linear time trend. For each country, the unemployment–suicide association was assessed, and the excess number of suicides attributable to the increase of unemployment was estimated. Sensitivity analyses were performed, notably in order to evaluate whether the unemployment–suicide association found was biased by a confounding context effect (‘crisis effect’).ResultsA significant 0.3% overall increase in suicide rate for a 10% increase in unemployment rate (95% CI 0.1% to 0.5%) was highlighted. This association was significant in three countries: 0.7% (95% CI 0.0% to 1.4%) in the Netherlands, 1.0% (95% CI 0.2% to 1.8%) in the UK and 1.9% (95% CI 0.8% to 2.9%) in France, with a significant excess number of suicides attributable to unemployment variations between 2008 and 2010 (respectively 57, 456 and 564). The association was modified inconsistently when adding a ‘crisis effect’ into the model.ConclusionsUnemployment and suicide rates are globally statistically associated in the investigated countries. However, this association is weak, and its amplitude and sensitivity to the ‘crisis effect’ vary across countries. This inconsistency provides arguments against its causal interpretation.
Intraperitoneal Oxidative Stress in Rabbits with Papillomavirus-Associated Head and Neck Cancer Induces Tumoricidal Immune Response That Is Adoptively Transferable
Authors: Rossmann Annette , Mandic Robert , Heinis Jochen , Höffken Helmut , Küssner Oliver , Kinscherf Ralf , Weihe Eberhard , Bette Michael 
Published: June 2014

AbstractPurpose: How tumors evade or suppress immune surveillance is a key question in cancer research, and overcoming immune escape is a major goal for lengthening remission after cancer treatment. Here, we used the papillomavirus-associated rabbit auricular VX2 carcinoma, a model for studying human head and neck cancer, to reveal the mechanisms underlying the antitumorigenic effects of intraperitoneal oxidative stress following O3/O2-pneumoperitoneum (O3/O2-PP) treatment.Experimental Design: Solid auricular VX2 tumors were induced in immune-competent adult New Zealand White Rabbits. Animals were O3/O2-PP- or sham-treated, after which they underwent tumor ablation upon reaching no-go criteria. CD3+ tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry, and expression levels of 84 immune response genes were measured by quantitative real-time PCR. Adoptive transfer of peripheral blood leukocytes (PBL)—derived from animals with tumor regression—into control animals with progressing tumors was implemented to assess acquired tumor resistance functionally.Results: Auricular VX2 tumors regressing after O3/O2-PP treatment exhibited increased levels of CD3+ TILs; they also exhibited enhanced expression of genes that encode receptors involved in pattern recognition, molecules that are required for antigen presentation and T cell activation, and inflammatory mediators. Adoptive cell transfer of PBLs from donor rabbits with regressing tumors to recipient rabbits with newly implanted VX2 carcinoma resulted in acquired tumor resistance of the host and tumor regression.Conclusion: Intraperitoneal oxidative stress effectively converts the immune response against the papillomavirus-associated rabbit VX2 carcinoma from tumor permissive to tumoricidal and leads to a sustainable, adoptively transferable oncolytic immune response. Clin Cancer Res; 20(16); 4289–301. ©2014 AACR.
Snail Cooperates with KrasG12D In Vivo to Increase Stem Cell Factor and Enhance Mast Cell Infiltration
Authors: Knab Lawrence M. , Ebine Kazumi , Chow Christina R. , Raza Sania S. , Sahai Vaibhav , Patel Akash P. , Kumar Krishan , Bentrem David J. , Grippo Paul J. , Munshi Hidayatullah G. 
Published: June 2014

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced fibro-inflammatory stromal reaction that contributes to tumor progression. A critical step in invasion and metastasis is the epithelial-to-mesenchymal transition (EMT), which can be regulated by the Snail family of transcription factors. Overexpression of Snail (Snai1) and mutant KrasG12D in the pancreas of transgenic mice, using an elastase (EL) promoter, resulted in fibrosis. To identify how Snail modulates inflammation in the pancreas, we examined the effect of expressing Snail in EL-KrasG12D mice (KrasG12D/Snail) on mast cell infiltration, which has been linked to PDAC progression. Using this animal model system, it was demonstrated that there are increased numbers of mast cells in the pancreas of KrasG12D/Snail mice compared with control KrasG12D mice. In addition, it was revealed that human primary PDAC tumors with increased Snail expression are associated with increased mast cell infiltration, and that Snail expression in these clinical specimens positively correlated with the expression of stem cell factor (SCF/KITLG), a cytokine known to regulate mast cell migration. Concomitantly, SCF levels are increased in the KrasG12D/Snail mice than in control mice. Moreover, overexpression of Snail in PDAC cells increased SCF levels, and the media conditioned by Snail-expressing PDAC cells promoted mast cell migration. Finally, inhibition of SCF using a neutralizing antibody significantly attenuated Snail-induced migration of mast cells.
Implications: Together, these results elucidate how the EMT regulator Snail contributes to inflammation associated with PDAC tumors. Mol Cancer Res; 12(10); 1440–8. ©2014 AACR.
Lifetime Prevalence of Congenital Heart Disease in the General Population From 2000 to 2010
Authors: Marelli Ariane J. , Ionescu-Ittu Raluca , Mackie Andrew S. , Guo Liming , Dendukuri Nandini , Kaouache Mohammed 
Published: June 2014

Background—
Our objective was to obtain contemporary lifetime estimates of congenital heart disease (CHD) prevalence using population-based data sources up to year 2010.

Methods and Results—
The Quebec CHD database contains 28 years of longitudinal data on all individuals with CHD from 1983 to 2010. Severe CHD was defined as tetralogy of Fallot, truncus arteriosus, transposition complexes, endocardial cushion defects, and univentricular hearts. We used latent class bayesian models combining case definitions from physician claims, hospitalization, and surgical data to obtain point and interval prevalence estimates of CHD in the first year of life, in children (<18 years of age) and in adults. We identified 107 559 CHD patients from 1983 to 2010. Prevalence of CHD in the first year of life was 8.21 per 1000 live births (95% confidence interval, 7.47–9.02) from 1998 to 2005. In 2010, overall prevalence of CHD was 13.11 per 1000 (95% confidence interval, 12.43–13.81) in children and 6.12 per 1000 (95% confidence interval, 5.69–6.57) in adults. CHD prevalence increased by 11% in children and 57% in adults from 2000 to 2010. Prevalence in the severe CHD subgroup increased by 19% (95% confidence interval, 17%–21%) in children and 55% (51%–62%) in adults. By 2010, adults accounted for 66% of the entire CHD population.

Conclusions—
With an increase of >50% in CHD prevalence since 2000, by 2010 adults accounted for two thirds of patients with severe and other forms of CHD in the general population. Our findings should inform allocation of resources and the planning of workforce needs for the predominantly adult CHD population.
Sex and Age Differences in the Association of Depression With Obstructive Coronary Artery Disease and Adverse Cardiovascular Events
Authors: Shah Amit J. , Ghasemzadeh Nima , Zaragoza‐Macias Elisa , Patel Riyaz , Eapen Danny J. , Neeland Ian J. , Pimple Pratik M. , Zafari A. Maziar , Quyyumi Arshed A. , Vaccarino Viola 
Published: June 2014

Background

Young women with coronary heart disease have high rates of depression and a higher risk of adverse events than men of similar age. Whether depression has a higher prognostic value in this group than in men and older women is not known. Our objective was to assess whether depression in young women is associated with higher risk of coronary artery disease (
CAD
) and adverse outcomes compared with similarly aged men and older women.

Methods and Results

We examined 3237 patients undergoing coronary angiography for evaluation of
CAD
and followed them for 2.9 years (median). Depressive symptoms were assessed with the Patient Health Questionnaire (
PHQ
)‐9, and
CAD
burden was dichotomized based on its presence or absence. After multivariable adjustment for
CAD
risk factors, depressive symptoms predicted
CAD
presence in women aged ≤55 years (odds ratio=1.07 95% confidence interval [
CI
] 1.02 to 1.13 per 1 point increase in
PHQ
‐9 score), but not in men aged ≤55 years or women aged >55 years. Depressive symptoms also predicted increased risk of death in women aged ≤55 years (adjusted hazard ratio=1.07, 95%
CI
1.02 to 1.14, per 1 point increase in
PHQ
‐9 score), but not in men aged ≤55 years and women aged >55 years, with
P
=0.02 for the depression‐sex interaction and
P
=0.02 for depression‐sex‐age interaction.

Conclusions

Among patients with suspected or established
CAD
, depressive symptoms are associated with increased risk of death, particularly in young women. This group may be especially vulnerable to the adverse cardiovascular effects of depression.
Hydroclimate Variability and Change in the Prairie Pothole Region, the “Duck Factory” of North America*
Authors: Ballard Tristan , Seager Richard , Smerdon Jason E. , Cook Benjamin I. , Ray Andrea J. , Rajagopalan Balaji , Kushnir Yochanan , Nakamura Jennifer , Henderson Naomi 
Published: June 2014

Abstract
The Prairie Pothole Region (PPR) of the northern Great Plains is a vital ecosystem responsible each year for producing 50%–80% of new recruits to the North American duck population. Climate variability and change can impact the hydrology and ecology of the region with implications for waterfowl populations. The historical relationship between PPR wetlands, duck populations, and seasonal hydroclimate are explored. Model experiments from phase 5 of the Coupled Model Intercomparison Project are used to determine whether a recent wetting trend is due to natural variability or changing climate and how PPR hydroclimate will change into the future. Year-to-year variations in May duck populations, pond numbers, and the Palmer drought severity index are well correlated over past decades. Pond and duck numbers tend to increase in spring following La Niña events, but the correlation is not strong. Model simulations suggest that the strengthening of the precipitation gradient across the PPR over the past century is predominantly due to natural variability and therefore could reverse. Model projections of future climate indicate precipitation will increase across the PPR in all seasons except summer, but this gain for surface moisture is largely offset by increased evapotranspiration because of higher temperatures and increased atmospheric evaporative demand. In summer, the combined effects of warming and precipitation changes indicate seasonal surface drying in the future. The presented hydroclimate analyses produce potential inputs to ecological and hydrological simulations of PPR wetlands to inform risk analysis of how this North American waterfowl habitat will evolve in the future, providing guidance to land managers facing conservation decisions.