bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Domain I-Domain III Linker Plays an Important Role in the Fusogenic Conformational Change of the Alphavirus Membrane Fusion Protein
Authors: Zheng Yan , Sánchez-San Martín Claudia , Qin Zhao-ling , Kielian Margaret 
Published: May 2011

ABSTRACT

The alphavirus Semliki Forest virus (SFV) infects cells through a low-pH-dependent membrane fusion reaction mediated by the virus fusion protein E1. Acidic pH initiates a series of E1 conformational changes that culminate in membrane fusion and include dissociation of the E1/E2 heterodimer, insertion of the E1 fusion loop into the target membrane, and refolding of E1 to a stable trimeric hairpin conformation. A highly conserved histidine (H3) on the E1 protein was previously shown to promote low-pH-dependent E1 refolding. An SFV mutant with an alanine substitution at this position (H3A) has a lower pH threshold and reduced efficiency of virus fusion and E1 trimer formation than wild-type SFV. Here we addressed the mechanism by which H3 promotes E1 refolding and membrane fusion. We identified E1 mutations that rescue the H3A defect. These revertants implicated a network of interactions that connect the domain I-domain III (DI-DIII) linker region with the E1 core trimer, including H3. In support of the importance of these interactions, mutation of residues in the network resulted in more acidic pH thresholds and reduced efficiencies of membrane fusion.
In vitro
studies of truncated E1 proteins demonstrated that the DI-DIII linker was required for production of a stable E1 core trimer on target membranes. Together, our results suggest a critical and previously unidentified role for the DI-DIII linker region during the low-pH-dependent refolding of E1 that drives membrane fusion.
A Reassortment-Incompetent Live Attenuated Influenza Virus Vaccine for Protection against Pandemic Virus Strains
Authors: Hai Rong , García-Sastre Adolfo , Swayne David E. , Palese Peter 
Published: May 2011

ABSTRACT

Although live-attenuated influenza vaccines (LAIV) are safe for use in protection against seasonal influenza strains, concerns regarding their potential to reassort with wild-type virus strains have been voiced. LAIVs have been demonstrated to induce enhanced mucosal and cell-mediated immunity better than inactivated vaccines while also requiring a smaller dose to achieve a protective immune response. To address the need for a reassortment-incompetent live influenza A virus vaccine, we have designed a chimeric virus that takes advantage of the fact that influenza A and B viruses do not reassort. Our novel vaccine prototype uses an attenuated influenza B virus that has been manipulated to express the ectodomain of the influenza A hemagglutinin protein, the major target for eliciting neutralizing antibodies. The hemagglutinin RNA segment is modified such that it contains influenza B packaging signals, and therefore it cannot be incorporated into a wild-type influenza A virus. We have applied our strategy to different influenza A virus subtypes and generated chimeric B/PR8 HA (H1), HK68 (H3), and VN (H5) viruses. All recombinant viruses were attenuated both
in vitro
and
in vivo
, and immunization with these recombinant viruses protected mice against lethal influenza A virus infection. Overall, our data indicate that the chimeric live-attenuated influenza B viruses expressing the modified influenza A hemagglutinin are effective LAIVs.
Absence of XMRV Retrovirus and Other Murine Leukemia Virus-Related Viruses in Patients with Chronic Fatigue Syndrome
Authors: Shin Clifford H. , Bateman Lucinda , Schlaberg Robert , Bunker Ashley M. , Leonard Christopher J. , Hughen Ronald W. , Light Alan R. , Light Kathleen C. , Singh Ila R. 
Published: May 2011

ABSTRACT

Chronic fatigue syndrome (CFS) is a multisystem disorder characterized by prolonged and severe fatigue that is not relieved by rest. Attempts to treat CFS have been largely ineffective primarily because the etiology of the disorder is unknown. Recently, CFS has been associated with xenotropic murine leukemia virus-related virus (XMRV) as well as other murine leukemia virus (MLV)-related viruses, though not all studies have found these associations. We collected blood samples from 100 CFS patients and 200 self-reported healthy volunteers from the same geographical area. We analyzed these in a blind manner using molecular, serological, and viral replication assays. We also analyzed samples from patients in the original study that reported XMRV in CFS patients. We did not find XMRV or related MLVs either as viral sequences or infectious viruses, nor did we find antibodies to these viruses in any of the patient samples, including those from the original study. We show that at least some of the discrepancy with previous studies is due to the presence of trace amounts of mouse DNA in the
Taq
polymerase enzymes used in these previous studies. Our findings do not support an association between CFS and MLV-related viruses, including XMRV, and the off-label use of antiretrovirals for the treatment of CFS does not seem justified at present.
Heliothis zea
Nudivirus 1 Gene
hhi1
Induces Apoptosis Which Is Blocked by the
Hz-iap2
Gene and a Noncoding Gene,
pag1
Authors: Wu Yueh-Lung , Wu Carol P. , Liu Catherine Y. Y. , Lee Song-Tay , Lee Hsiao-Ping , Chao Yu-Chan 
Published: May 2011

ABSTRACT

Heliothis zea
nudivirus 1 (
Hz
NV-1 or
Hz
-1 virus), previously regarded as a nonoccluded baculovirus, recently has been placed in the
Nudivirus
genus. This virus generates
Hz
NV-1 HindIII-I 1 (
hhi1
) and many other transcripts during productive viral infection; during latent viral infection, however, persistency-associated gene 1 (
pag1
) is the only gene expressed. In this report, we used transient expression assays to show that
hhi1
can trigger strong apoptosis in transfected cells, which can be blocked, at least partially, by the inhibitor of apoptosis genes
Autographa californica iap2 (Ac-iap2
) and
H. zea iap2
(
Hz-iap2)
. In addition to these two genes, unexpectedly,
pag1
, which encodes a noncoding RNA with no detectable protein product, was found to efficiently suppress
hhi1
-induced apoptosis. The assay of pro-
Sf
-caspase-1 processing by
hhi1
transfection did not detect the small P12 subunit at any of the time intervals tested, suggesting that
hhi1
of
Hz
NV-1 induces apoptosis through alternative caspase pathways.
Peptides Derived from a Distinct Region of GB Virus C Glycoprotein E2 Mediate Strain-Specific HIV-1 Entry Inhibition
Authors: Koedel Yvonne , Eissmann Kristin , Wend Holger , Fleckenstein Bernhard , Reil Heide 
Published: May 2011

ABSTRACT

The nonpathogenic human GB virus C (GBV-C), a member of the
Flaviviridae
, is highly prevalent in individuals with HIV-1 infections or with parenteral and sexual risk factors. Long-term GBV-C viremia has been associated with better survival or improved diagnosis in several epidemiological studies. In a previous study we reported that the E2 glycoprotein of GBV-C interferes with HIV-1 entry
in vitro
. To address the question what region of the E2 protein is involved in suppression of HIV-1 replication, we performed an E2-derived peptide scanning and determined the HIV-inhibitory activity of each peptide in HIV replication assays. We demonstrate here that peptides representing the N-terminal part of the E2 protein from amino acids (aa) 29 to 72 are able to inhibit efficiently HIV-1 replication
in vitro
. In particular, the peptides P6-2 (representing the E2-region from aa 45 to 64) and P4762 (aa 37 to 64) showed the highest potency in HIV replication assays performed on TZM-bl cells with 50% inhibitory concentrations between 0.1 and 2 μM. However, primary HIV-1 isolates representing clades A to H showed a high variability in their sensitivity to E2 peptides. Pseudovirus inhibition assays revealed that the sensitivity is determined by the gp120/gp41 envelope proteins. Using HIV-1 BlaM-Vpr-based fusion assays, we demonstrate that the E2-derived peptides prevent HIV-1 binding or fusion, presumably via interaction with the HIV-1 particle. Together, these findings reveal a new mechanism of viral interference, suggesting that the envelope protein E2 of GBV-C target directly HIV-1 particles to avoid entry of these virions.
Role of CD4
+
and CD8
+
T-Cell Responses against JC Virus in the Outcome of Patients with Progressive Multifocal Leukoencephalopathy (PML) and PML with Immune Reconstitution Inflammatory Syndrome
Authors: Gheuens Sarah , Bord Evelyn , Kesari Santosh , Simpson David M. , Gandhi Rajesh T. , Clifford David B. , Berger Joseph R. , Ngo Long , Koralnik Igor J. 
Published: May 2011

ABSTRACT

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the brain caused by JC virus (JCV). To assess the role of CD4
+
and CD8
+
T-cells against JCV in the clinical outcome of PML and PML in the setting of immune reconstitution inflammatory syndrome (IRIS), we tested gamma interferon (IFN-γ) response by enzyme-linked immunosorbent spot (ELISpot) and intracellular cytokine staining (ICS) in 117 subjects, including 66 PML patients with different clinical outcomes. Both assays were concordant and demonstrated that the cellular immune response against JCV is associated with better clinical outcome. PML survivors had an early CD8
+
T-cell response more frequently than PML progressors (100% versus 27.3%;
P
= 0.001), while only a trend was observed for the early CD4
+
T-cell response between these two groups (80% versus 45.5%;
P
= 0.18). Although IRIS itself was more frequent in the PML survivor group, there was no difference in IFN-γ-producing CD4
+
and CD8
+
T-cells between IRIS and non-IRIS PML patients, suggesting that T-cells expressing other cytokines likely have a role in the immunopathogenesis of IRIS. ELISpot and ICS assays are useful prognostic markers of PML evolution and may help in the clinical management of these patients.
Injection treatments for patellar tendinopathy
Authors: van Ark Mathijs , Zwerver Johannes , van den Akker-Scheek Inge 
Published: May 2011

ObjectiveInjection treatments are increasingly used as treatment for patellar tendinopathy. The aim of this systematic review is to describe the different injection treatments, their rationales and the effectiveness of treating patellar tendinopathy.MethodsA computerised search of the Medline, Embase, CINAHL and Web of Knowledge databases was conducted on 1 May 2010 to identify studies on injection treatments for patellar tendinopathy.Results11 articles on seven different injection treatments (dry needling, autologous blood, high-volume, platelet-rich plasma, sclerosis, steroids and aprotinin injections) were found: 4 randomised controlled trials (RCTs), 1 non-RCT, 4 prospective cohort studies and 2 retrospective cohort studies. All studies reported positive results. The Delphi scores of the four RCTs ranged from 5 to 8 out of 9. Different and sometimes contradictory rationales were used for the injection treatments.ConclusionAll seven different injection treatments seem promising for treating patellar tendinopathy. Unlike the other injection treatments, steroid treatment often shows a relapse of symptoms in the long term. Results should be interpreted with caution as the number of studies is low, few high-quality studies have been conducted and the studies are hard to compare due to different methodology. More high-quality studies using the same cross-cultural reliable and valid outcome measure are needed, as well as further research into the pathophysiology. Finally, some implications are provided for clinicians who want to use injection treatments as a part of their treatment for patellar tendinopathy, distinguishing between reactive and degenerative phase of patellar tendinopathy.
Obesity and Prostate Cancer Aggressiveness among African and Caucasian Americans in a Population-Based Study
Authors: Su L. Joseph , Arab Lenore , Steck Susan E. , Fontham Elizabeth T.H. , Schroeder Jane C. , Bensen Jeannette T. , Mohler James L. 
Published: May 2011

Abstract
Background: This study evaluated obesity and prostate cancer aggressiveness relationship in a population-based incident prostate cancer study.
Methods: The North Carolina–Louisiana Prostate Cancer Project includes medical records data for classification of prostate cancer aggressiveness at diagnosis by using clinical criteria for 1,049 African American (AA) and 1,083 Caucasian American (CA) participants. An association between prostate cancer aggressiveness and obesity, measured using body mass indices (BMI) and waist-to-hip ratio (WHR), was assessed using ORs and 95% CIs adjusted for confounders.
Results: A significantly positive association was found between prostate cancer aggressiveness and obesity. The ORs for high aggressive prostate cancer among prediagnosis obese and severely obese were 1.48 (95% CI = 1.02–2.16) and 1.98 (95% CI = 1.31–2.97), respectively, compared with normal weight research subjects. Race-stratified results suggested the association is stronger among CAs. Interaction model showed that normal weight AAs had more aggressive prostate cancer than normal weight CAs (OR = 2.69, 95% CI = 1.36–5.30); severe obesity was associated with aggressive disease in AAs (OR = 3.90, 95% CI = 1.97–7.75). WHR &gt; 0.98 among all research subjects adjusted for race was significantly associated with high aggressive prostate cancer (OR = 1.42, 95% CI = 1.00–2.00) when compared with WHR &lt; 0.90. The stratified result is less clear among AAs.
Conclusions: This study shows a positive association between obesity and aggressive prostate cancer. AAs have more aggressive prostate cancer in general than CAs even at normal weight. Therefore, the association between obesity and aggressiveness is not as evident in AAs as in CAs.
Impact: This study provides a unique opportunity to examine impact of race on obesity and high aggressive prostate cancer relationship. Cancer Epidemiol Biomarkers Prev; 20(5); 844–53. ©2011 AACR.
What If I Don't Treat My PSA-Detected Prostate Cancer? Answers from Three Natural History Models
Authors: Gulati Roman , Wever Elisabeth M. , Tsodikov Alex , Penson David F. , Inoue Lurdes Y.T. , Katcher Jeffrey , Lee Shih-Yuan , Heijnsdijk Eveline A.M. , Draisma Gerrit , de Koning Harry J. , Etzioni Ruth 
Published: May 2011

Abstract
Background: Making an informed decision about treating a prostate cancer detected after a routine prostate-specific antigen (PSA) test requires knowledge about disease natural history, such as the chances that it would have been clinically diagnosed in the absence of screening and that it would metastasize or lead to death in the absence of treatment.
Methods: We use three independently developed models of prostate cancer natural history to project risks of clinical progression events and disease-specific deaths for PSA-detected cases assuming they receive no primary treatment.
Results: The three models project that 20%–33% of men have preclinical onset; of these 38%–50% would be clinically diagnosed and 12%–25% would die of the disease in the absence of screening and primary treatment. The risk that men age less than 60 at PSA detection with Gleason score 2–7 would be clinically diagnosed in the absence of screening is 67%–93% and would die of the disease in the absence of primary treatment is 23%–34%. For Gleason score 8 to 10 these risks are 90%–96% and 63%–83%.
Conclusions: Risks of disease progression among untreated PSA-detected cases can be nontrivial, particularly for younger men and men with high Gleason scores. Model projections can be useful for informing decisions about treatment.
Impact: This is the first study to project population-based natural history summaries in the absence of screening or primary treatment and risks of clinical progression events following PSA detection in the absence of primary treatment. Cancer Epidemiol Biomarkers Prev; 20(5); 740–50. ©2011 AACR.
Evaluating the Efficacy of Lay Health Advisors for Increasing Risk-Appropriate Pap Test Screening: A Randomized Controlled Trial among Ohio Appalachian Women
Authors: Paskett Electra D. , McLaughlin John M. , Lehman Amy M. , Katz Mira L. , Tatum Cathy M. , Oliveri Jill M. 
Published: May 2011

Abstract
Background: Cervical cancer is a significant health disparity among women in Ohio Appalachia. The goal of this study was to evaluate the efficacy of a lay health advisor (LHA) intervention for improving Papanicolaou (Pap) testing rates, to reduce cervical cancer, among women in need of screening.
Methods: Women from 14 Ohio Appalachian clinics in need of a Pap test were randomized to receive either usual care or an LHA intervention over a 10-month period. The intervention consisted of two in-person visits with an LHA, two phone calls, and four postcards. Both self-report and medical record review (MRR) data (primary outcome) were analyzed.
Results: Of the 286 women, 145 and 141 were randomized to intervention and usual care arms, respectively. According to MRR, more women in the LHA arm had a Pap test by the end of the study compared with those randomized to usual care (51.1% vs. 42.0%; OR = 1.44, 95% CI: 0.89–2.33; P = 0.135). Results of self-report were more pronounced (71.3% vs. 54.2%; OR = 2.10, 95% CI: 1.22–3.61; P = 0.008).
Conclusions: An LHA intervention showed some improvement in the receipt of Pap tests among Ohio Appalachian women in need of screening. Although biases inherent in using self-reports of screening are well known, this study also identified biases in using MRR data in clinics located in underserved areas.
Impact: LHA interventions show promise for improving screening behaviors among nonadherent women from underserved populations. Cancer Epidemiol Biomarkers Prev; 20(5); 835–43. ©2011 AACR.
Genetic Polymorphisms in Inflammation Pathway Genes and Prostate Cancer Risk
Authors: Kwon Erika M. , Salinas Claudia A. , Kolb Suzanne , Fu Rong , Feng Ziding , Stanford Janet L. , Ostrander Elaine A. 
Published: May 2011

Abstract
Background: Chronic inflammation is an important mechanism for the development and progression of prostate cancer (PC). To better understand the potential relationship between genes in the inflammation pathway and PC risk, we evaluated variants in 16 candidate genes.
Methods: A total of 143 tagging and amino acid altering single nucleotide polymorphisms (SNPs) were genotyped in Caucasian and African American men participating in one of two population-based, case–control studies (n = 1,458 cases and 1,351 controls). The relative risk of PC was estimated using logistic and polytomous regression models.
Results: Ten SNPs in seven genes (CXCL12, IL4, IL6, IL6ST, PTGS2, STAT3, and TNF) were nominally associated (P &lt; 0.05) with risk of PC in Caucasians. The most significant effect on risk was seen with rs11574783 in the interleukin 6 signal transducer (IL6ST) gene (OR = 0.08, 95% CI: 0.01–0.63). Cumulatively, four SNPs in genes interleukin 4 (IL4), IL6ST, PTGS2, and signal transducer and activator of transcription 3 (STAT3) conferred a three-fold elevation in PC risk among men carrying the maximum number of high-risk alleles (OR = 2.97, 95% CI: 1.41–6.25, Ptrend = 0.0003). Risk estimates for seven SNPs varied significantly according to disease aggressiveness (Phomogeneity &lt; 0.05), with SNPs in AKT1, PIK3R1, and STAT3 independently associated with more aggressive PC; OR = 5.1 (95% CI: 2.29–11.40, Ptrend = 3.8 × 10−5) for carriers of all high-risk genotypes.
Conclusions: These results suggest that variants in genes within the inflammation pathway may play a role in the development of PC, however, further studies are needed to replicate our findings.
Impact: These results underline the potential importance of the inflammation pathway in PC development and progression. Cancer Epidemiol Biomarkers Prev; 20(5); 923–33. ©2011 AACR.
Healthy Lifestyle on the Risk of Breast Cancer
Authors: Sánchez-Zamorano Luisa María , Flores-Luna Lourdes , Ángeles-Llerenas Angélica , Romieu Isabelle , Lazcano-Ponce Eduardo , Miranda-Hernández Hernando , Mainero-Ratchelous Fernando , Torres-Mejía Gabriela 
Published: May 2011

AbstractBackground: Many studies have analyzed the effect of behavioral risk factors such as common lifestyle patterns on the risk of disease. The aim of this study was to assess the effect of a healthy lifestyle index on the risk of breast cancer.Methods: A population-based case–control study was conducted in Mexico from 2004 to 2007. One thousand incident cases and 1,074 controls, matched to cases by 5-year age category, region, and health institution, participated in the study. A healthy lifestyle index was developed by means of principal components by using dietary pattern, physical activity, alcohol consumption, and tobacco smoking. A conditional logistic regression model was used to assess this association.Results: The healthy lifestyle index was defined as the combined effect of moderate and/or vigorous-intensity physical activity, low consumption of fat, processed foods, refined cereals, complex sugars, and the avoidance of tobacco smoking and alcohol consumption. Results showed a protective effect on both pre- (OR = 0.50, 95% CI: 0.29–0.84) and postmenopausal women (OR = O.20, 95% CI: 0.11–0.37) when highest versus lowest index quintiles were compared.Conclusions: Healthy lifestyle was associated with a reduction in the odds of having breast cancer. Primary prevention of this disease should be promoted in an integrated manner. Effective strategies need to be identified to engage women in healthy lifestyles.Impact: This study is the first to assess a healthy lifestyle index in relation to the risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 20(5); 912–22. ©2011 AACR.
Soy Food Consumption and Breast Cancer Prognosis
Authors: Caan Bette J. , Natarajan Loki , Parker Barbara , Gold Ellen B. , Thomson Cynthia , Newman Vicky , Rock Cheryl L. , Pu Minya , Al-Delaimy Wael , Pierce John P. 
Published: May 2011

Abstract
Background: Contrary to earlier clinical studies suggesting that soy may promote breast tumor growth, two recent studies show that soy-containing foods are not adversely related to breast cancer prognosis. We examined, using data from the Women's Healthy Eating and Living (WHEL) study, the effect of soy intake on breast cancer prognosis.
Methods: Three thousand eighty-eight breast cancer survivors, diagnosed between 1991 and 2000 with early-stage breast cancer and participating in WHEL, were followed for a median of 7.3 years. Isoflavone intakes were measured postdiagnosis by using a food frequency questionnaire. Women self-reported new outcome events semiannually, which were then verified by medical records and/or death certificates. HRs and 95% CIs representing the association between either a second breast cancer event or death and soy intake were computed, adjusting for study group and other covariates, using the delayed entry Cox proportional hazards model.
Results: As isoflavone intake increased, risk of death decreased (P for trend = 0.02). Women at the highest levels of isoflavone intake (&gt;16.3 mg isoflavones) had a nonsignificant 54% reduction in risk of death.
Conclusion: Our study is the third epidemiologic study to report no adverse effects of soy foods on breast cancer prognosis.
Impact: These studies, taken together, which vary in ethnic composition (two from the United States and one from China) and by level and type of soy consumption, provide the necessary epidemiologic evidence that clinicians no longer need to advise against soy consumption for women with a diagnosis of breast cancer. Cancer Epidemiol Biomarkers Prev; 20(5); 854–8. ©2011 AACR.