bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Nuclear Export Signal in the Matrix Protein of Influenza A Virus Is Required for Efficient Virus Replication
Authors: Cao Shuai , Liu Xiaoling , Yu Maorong , Li Jing , Jia Xiaojuan , Bi Yuhai , Sun Lei , Gao George F. , Liu Wenjun 
Published: February 2012

ABSTRACT
The influenza A virus matrix 1 protein (M1) shuttles between the cytoplasm and the nucleus during the viral life cycle and plays an important role in the replication, assembly, and budding of viruses. Here, a leucine-rich nuclear export signal (NES) was identified specifically for the nuclear export of the M1 protein. The predicted NES, designated the Flu-A-M1 NES, is highly conserved among all sequences from the influenza A virus subtype, but no similar NES motifs are found in the M1 sequences of influenza B or C viruses. The biological function of the Flu-A-M1 NES was demonstrated by its ability to translocate an enhanced green fluorescent protein (EGFP)-NES fusion protein from the nucleus to the cytoplasm in transfected cells, compared to the even nuclear and cytoplasmic distribution of EGFP. The translocation of EGFP-NES from the nucleus to the cytoplasm was not inhibited by leptomycin B. NES mutations in M1 caused a nuclear retention of the protein and an increased nuclear accumulation of NEP during transfection. Indeed, as shown by rescued recombinant viruses, the mutation of the NES impaired the nuclear export of M1 and significantly reduced the virus titer compared to titers of wild-type viruses. The NES-defective M1 protein was retained in the nucleus during infection, accompanied by a lowered efficiency of the nuclear export of viral RNPs (vRNPs). In conclusion, M1 nuclear export was specifically dependent on the Flu-A-M1 NES and critical for influenza A virus replication.
Replicating Adenovirus-Simian Immunodeficiency Virus (SIV) Recombinant Priming and Envelope Protein Boosting Elicits Localized, Mucosal IgA Immunity in Rhesus Macaques Correlated with Delayed Acquisition following a Repeated Low-Dose Rectal SIV
mac251
Challenge
Authors: Xiao Peng , Patterson L. Jean , Kuate Seraphin , Brocca-Cofano Egidio , Thomas Michael A. , Venzon David , Zhao Jun , DiPasquale Janet , Fenizia Claudio , Lee Eun Mi , Kalisz Irene , Kalyanaraman Vaniambadi S. , Pal Ranajit , Montefiori David , Keele Brandon F. , Robert-Guroff Marjorie 
Published: February 2012

ABSTRACT

We have shown that sequential replicating adenovirus type 5 host range mutant human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) recombinant priming delivered first intranasally (i.n.) plus orally and then intratracheally (i.t.), followed by envelope protein boosting, elicits broad cellular immunity and functional, envelope-specific serum and mucosal antibodies that correlate with protection from high-dose SIV and simian/human immunodeficiency virus (SHIV) challenges in rhesus macaques. Here we extended these studies to compare the standard i.n./i.t. regimen with additional mucosal administration routes, including sublingual, rectal, and vaginal routes. Similar systemic cellular and humoral immunity was elicited by all immunization routes. Central and effector memory T cell responses were also elicited by the four immunization routes in bronchoalveolar lavage fluid and jejunal, rectal, and vaginal tissue samples. Cellular responses in vaginal tissue were more compartmentalized, being induced primarily by intravaginal administration. In contrast, all immunization routes elicited secretory IgA (sIgA) responses at multiple mucosal sites. Following a repeated low-dose intrarectal (i.r.) challenge with SIV
mac251
at a dose transmitting one or two variants, protection against acquisition was not achieved except in one macaque in the i.r. immunized group. All immunized macaques exhibited reduced peak viremia compared to that of controls, correlated inversely with prechallenge serum antienvelope avidity, antibody-dependent cellular cytotoxicity (ADCC) titers, and percent antibody-dependent cell-mediated viral inhibition. Both antibody avidity and ADCC titers were correlated with the number of exposures required for infection. Notably, we show for the first time a significant correlation of vaccine-induced sIgA titers in rectal secretions with delayed acquisition. Further investigation of the characteristics and properties of the sIgA should elucidate the mechanism leading to this protective effect.
Draft Genome Sequence of Four Coccolithoviruses: Emiliania huxleyi Virus EhV-88, EhV-201, EhV-207, and EhV-208
Authors: Nissimov Jozef I. , Worthy Charlotte A. , Rooks Paul , Napier Johnathan A. , Kimmance Susan A. , Henn Matthew R. , Ogata Hiroyuki , Allen Michael J. 
Published: February 2012

ABSTRACT

The
Coccolithoviridae
are a group of viruses which infect the marine coccolithophorid microalga
Emiliania huxleyi
. The
Emiliania huxleyi
viruses (known as EhVs) described herein have 160- to 180-nm diameter icosahedral structures, have genomes of approximately 400 kbp, and consist of more than 450 predicted coding sequences (CDSs). Here, we describe the genomic features of four newly sequenced coccolithoviruses (EhV-88, EhV-201, EhV-207, and EhV-208) together with their draft genome sequences and their annotations, highlighting the homology and heterogeneity of these genomes to the EhV-86 model reference genome.
Complete Genome Sequence of Bacteriophage phiAS7, a T7-Like Virus That Infects Aeromonas salmonicida subsp. salmonicida
Authors: Kim Ji Hyung , Son Jee Soo , Choresca Casiano H. , Shin Sang Phil , Han Jee Eun , Jun Jin Woo , Kang Do-Hyung , Oh Chulhong , Heo Soo-Jin , Park Se Chang 
Published: February 2012

ABSTRACT

To date, a number of
Myoviridae
bacteriophages that infect
Aeromonadaceae
have been identified and characterized. However, the genome sequences of
Aeromonas
phages that not belong to the
Myoviridae
have not been investigated yet. Herein, we report the complete genome sequence of
Aeromonas
phage phiAS7, which belongs to the
Podoviridae
and infects
Aeromonas salmonicida
subsp.
salmonicida
.
Early Events in Alphavirus Replication Determine the Outcome of Infection
Authors: Frolov Ilya , Akhrymuk Maryna , Akhrymuk Ivan , Atasheva Svetlana , Frolova Elena I. 
Published: February 2012

ABSTRACT

Alphaviruses are a group of important human and animal pathogens. They efficiently replicate to high titers
in vivo
and in many commonly used cell lines of vertebrate origin. They have also evolved effective means of interfering with development of the innate immune response. Nevertheless, most of the alphaviruses are known to induce a type I interferon (IFN) response
in vivo
. The results of this study demonstrate that the first hours postinfection play a critical role in infection spread and development of the antiviral response. During this window, a balance is struck between virus replication and spread in vertebrate cells and IFN response development. The most important findings are as follows: (i) within the first 2 to 4 h postinfection, alphavirus-infected cells become unable to respond to IFN-β, and this occurs before the virus-induced decrease in STAT1 phosphorylation in response to IFN treatment. (ii) Most importantly, very low, subprotective doses of IFN-β, which do not induce the antiviral response in uninfected cells, have a very strong stimulatory effect on the cells' ability to express type I IFN and activate interferon-stimulated genes during subsequent infection with Sindbis virus (SINV). (iii) Small changes in SINV nsP2 protein affect its ability to inhibit cellular transcription and IFN release. Thus, the balance between type I IFN induction and the ability of the virus to develop further rounds of infection is determined in the first few hours of virus replication, when only low numbers of cells and infectious virus are involved.
Republished article: The impact of diabetic retinopathy: understanding the patient's perspective
Authors: Fenwick E K , Pesudovs K , Rees G , Dirani M , Kawasaki R , Wong T Y , Lamoureux E L 
Published: February 2012

Abstract
Understanding the impact of a condition from the patient's perspective is important, and different types of patient-reported outcomes or instruments are available to help with this. This review article summarises the current evidence on the impact of diabetic retinopathy (DR) and its associated vision impairment on patient-reported outcomes. We have included research that has used a range of outcome measures to assess the impact of DR on generic health-related quality of life, utility, vision-functioning and vision-specific quality of life. This review also offers clarification on frequently misused psychometric terminologies to help clinicians and researchers better understand the literature associated with patient-reported outcome research. Overall, the evidence suggests that DR, particularly in its vision-threatening stages, has a substantial, negative impact on the patient. However, our understanding of the impact of DR is currently restricted due to limitations inherent in currently available patient-reported outcome measures. We conclude by discussing potential directions for future research in this area, such as item banking and computer adaptive testing.
Supervised blood-based self-sample collection and rapid test performance: a valuable alternative to the use of saliva by HIV testing programmes with no medical or nursing staff: Table 1
Authors: Belza María J , Rosales-Statkus M Elena , Hoyos Juan , Segura Pilar , Ferreras Eva , Sánchez Rebeca , Molist Gemma , de la Fuente Luis ,   the Madrid Rapid HIV testing Group
Published: February 2012

ObjectivesSome saliva-based HIV testing programmes have resulted in an unacceptable percentage of false positives. Many countries require blood-based testing programmes to have doctors/nurses. The authors evaluate whether, after brief training and under the supervision of a skilled counsellor, blood-based self-sample collection and rapid test performance could be a valuable alternative.Methods208 Spanish-speaking attendees at a street-based HIV testing programme in Madrid participated in the study. Participants were tested twice, first in the study and then in the programme, using the same finger-stick whole-blood rapid test (Determine HIV-1/2 Ag/Ab Combo®). Based on previously adapted instructions, the study counsellor explained the procedure to follow throughout the test. Participants then performed the test under the guidance of the counsellor. Demographic and risk behaviour data were collected by a self-administered questionnaire. The test results in the programme and the study were read by the study counsellor.Results99.0% (95% CI 96.6% to 99.9%) of participants had a valid result in the study test, the same percentage as in the programme test conducted by the doctor/nurse. Two persons had invalid test results in both the study and the programme, but they were not the same persons.ConclusionThe study provides clear evidence that this methodology is a valuable alternative to saliva for HIV testing programmes when medical or nursing staff required to take blood samples is not available.
Efficiency considerations of donor fatigue, universal access to ARTs and health systems
Authors: Grépin Karen A 
Published: February 2012

ObjectivesTo investigate trends in official development assistance for health, HIV and non-HIV activities over time and to discuss the efficiency implications of these trends in the context of achieving universal access to treatment and health systems.MethodsOfficial development assistance for health, HIV programmes and non-HIV programmes were tracked using data from 2000 to 2009. A review of the literature on efficiency, treatment and health systems was conducted.FindingsThe rate of growth of donor funding to HIV programmes has slowed in recent years at levels below those required to sustain programmes and to move towards universal access to treatment. These trends are likely due to increased pressure on foreign aid budgets and donor fatigue for HIV programmes.ConclusionsThere is great need to consider how the limited resources available can be used most efficiently to increase the number of lives saved and to ensure that these resources also benefit health systems. Improving efficiency is much more than just improving the productive efficiency and also about ensuring that resources are going to where they will be the most beneficial and making investments that are the most efficient over time. These choices may be essential to achieving the goal of universal access to treatment as well as the sustainability of these programmes.
High prevalence of HIV and sexually transmitted infections among male sex workers in Abidjan, Côte d'Ivoire: need for services tailored to their needs
Authors: Vuylsteke Bea , Semde Gisèle , Sika Lazare , Crucitti Tania , Ettiegne Traore Virginie , Buve Anne , Laga Marie 
Published: February 2012

ObjectivesTo assess condom use and prevalence of sexually transmitted infections (STI) and HIV among male sex workers (MSW) in Abidjan, Côte d'Ivoire.MethodsA cross-sectional survey was conducted between October 2007 and January 2008 among MSW attending a sex worker clinic in Abidjan. A short questionnaire was administered in a face-to-face interview, and the participants were asked to provide a urine sample for STI testing and to self-collect transudate of the gingival mucosa for anonymous HIV testing, using a rapid test. A rectal swab for STI testing was taken by a physician. Molecular amplification assays were performed for the detection ofChlamydia trachomatis,Neisseria gonorrhoeaeandTrichomonas vaginalis.Results96 MSW participated in the survey, their median age was 27 years and the median duration of sex work was 5 years. Consistent condom use with clients during the last working day was 86.0%, and consistent condom use with the regular partner during the last week was 81.6%. HIV infection was detected in 50.0% of the participants. The prevalence ofN gonorrhoeaewas 12.8%, chlamydia infection was present in 3.2% andTvaginalisin 2.1% of the study participants.ConclusionsHIV and STI rates found in this study confirm the high risk and vulnerability status of MSW in Côte d'Ivoire. There is a definite need for studies exploring risk and risk perceptions among MSW in more depth and for services tailored to their needs, including developing and validating simple algorithms for the diagnosis of STI in MSW and men who have sex with men.
The expansion of HIV-1 in colonial Léopoldville, 1950s: driven by STDs or STD control?
Authors: Pépin Jacques 
Published: February 2012

ObjectivesTo understand the factors that drove the exponential spread of HIV-1 in Léopoldville (Kinshasa) in the 1950s.MethodsA review of colonial and post-colonial health service reports, medical publications, and demographic and social science research in Léopoldville.ResultsSex work appeared early in the history of Léopoldville, driven by a strong gender imbalance. Throughout the colonial era, sex work was of a low-risk type, with ‘free women’ having a few regular clients. This sufficed for the persistence of HIV-1, but probably not for the dramatic expansion that occurred in the 1950s. During that decade, genital ulcerative diseases were uncommon and their effect on HIV-1 transmission must have been modest. Circumstantial evidence indicates that this expansion may have been related to parenteral transmission of HIV-1 in the city's sexually transmitted disease clinic, where up to 500 injections were administered daily using syringes and needles that were merely rinsed between patients. Most intravenous injections were given to treat syphilis in patients who never had any clinical evidence of this disease but only had a positive non-treponemal serology, often because of prior yaws infection. An outbreak of ‘inoculation hepatitis’ was reported among these patients in 1951–1952. It is only after the Congo's independence (1960) that, in a context of pauperisation, a pattern of sex work appeared in Léopoldville wherein women had sex with more than 1000 clients each year, allowing the sexual amplification of the virus.ConclusionsIt is plausible that the exponential amplification of HIV-1 in Léopoldville occurred mostly parenterally in the 1950s and sexually in the 1960s.
Cancer Vaccination Drives Nanog-Dependent Evolution of Tumor Cells toward an Immune-Resistant and Stem-like Phenotype
Authors: Noh Kyung Hee , Lee Young-Ho , Jeon Ju-Hong , Kang Tae Heung , Mao Chih-Ping , Wu T.-C. , Kim Tae Woo 
Published: February 2012

Abstract
Due to the exquisite specificity and potency of the immune system, vaccination is in theory the most precise and powerful approach for controlling cancer. However, current data from clinical trials indicate that vaccination rarely yields significant benefits for cancer patients in terms of tumor progression and long-term survival. The poor clinical outcomes of vaccination are primarily caused by mechanisms of immune tolerance, especially within the tumor microenvironment. Here, we report that vaccination drives the evolution of tumor cells toward an immune-resistant and stem-like phenotype that promotes tumor growth and nullifies the CTL response. The emergence of this phenotype required the transcription factor Nanog, which is induced as a consequence of immune selection. Nanog expression enhanced the stem-like features of tumor cells and protected them from killing by tumor-reactive CTLs. Delivery of siNanog into tumor-bearing mice rendered the tumor vulnerable to immune surveillance and strongly suppressed its growth. Together, our findings show tumor adaptation to vaccination through gain of an immune-resistant, stem-like phenotype and identify Nanog as a central molecular target in this process. Future vaccination technology should consider Nanog an important target to enhance the immunotherapeutic response. Cancer Res; 72(7); 1717–27. ©2012 AACR.
Akt Inhibitors MK-2206 and Nelfinavir Overcome mTOR Inhibitor Resistance in Diffuse Large B-cell Lymphoma
Authors: Petrich Adam M. , Leshchenko Violetta , Kuo Pei-Yu , Xia Bing , Thirukonda Venu K. , Ulahannan Netha , Gordon Shanisha , Fazzari Melissa J. , Ye B. Hilda , Sparano Joseph A. , Parekh Samir 
Published: February 2012

Abstract
Purpose: The mTOR pathway is constitutively activated in diffuse large B-cell lymphoma (DLBCL). mTOR inhibitors have activity in DLBCL, although response rates remain low. We evaluated DLBCL cell lines with differential resistance to the mTOR inhibitor rapamycin: (i) to identify gene expression profile(s) (GEP) associated with resistance to rapamycin, (ii) to understand mechanisms of rapamycin resistance, and (iii) to identify compounds likely to synergize with mTOR inhibitor.
Experimental Design: We sought to identify a GEP of mTOR inhibitor resistance by stratification of eight DLBCL cell lines with respect to response to rapamycin. Then, using pathway analysis and connectivity mapping, we sought targets likely accounting for this resistance and compounds likely to overcome it. We then evaluated two compounds thus identified for their potential to synergize with rapamycin in DLBCL and confirmed mechanisms of activity with standard immunoassays.
Results: We identified a GEP capable of reliably distinguishing rapamycin-resistant from rapamycin-sensitive DLBCL cell lines. Pathway analysis identified Akt as central to the differentially expressed gene network. Connectivity mapping identified compounds targeting Akt as having a high likelihood of reversing the GEP associated with mTOR inhibitor resistance. Nelfinavir and MK-2206, chosen for their Akt-inhibitory properties, yielded synergistic inhibition of cell viability in combination with rapamycin in DLBCL cell lines, and potently inhibited phosphorylation of Akt and downstream targets of activated mTOR.
Conclusions: GEP identifies DLBCL subsets resistant to mTOR inhibitor therapy. Combined targeting of mTOR and Akt suppresses activation of key components of the Akt/mTOR pathway and results in synergistic cytotoxicity. These findings are readily adaptable to clinical trials. Clin Cancer Res; 18(9); 2534–44. ©2012 AACR.
Cytokine BAFF Gene Variation Is Associated with Survival of Patients with T-cell Lymphomas
Authors: Zhai Kan , Tian Xiaobo , Wu Chen , Lu Ning , Chang Jiang , Huang Liming , Zhang Tongwen , Zhou Yuling , Qiao Yan , Yu Dianke , Tan Wen , Chen Jieping , Lin Dongxin 
Published: February 2012

Abstract
Purpose: Cytokine BAFF is a potent molecule for the activation and survival of B cells, and it also plays an important role in T-cell function. Genetic polymorphism (rs9514828C&gt;T) in BAFF has been associated with elevated BAFF transcription. We sought to determine whether rs9514828 is associated with T-cell lymphoma (TCL) survival.
Experimental Design: BAFF rs9514828 genotypes and survival of TCL were analyzed in the discovery group including 150 patients, and the results were replicated in an independent validation group of 120 patients. Kaplan–Meier analysis was conducted to compare survival among different genotypes. Cox proportional hazard models were used to identify independent significant variables. Luciferase reporter gene assays were conducted to examine the function of rs9514828 variant.
Results: We found that BAFF rs9514828 polymorphism was significantly associated with TCL survival. In pooled analysis of two independent groups, the favorable rs9514828 TC and TT genotypes had significantly better five-year survival rates compared with the CC genotype (47% and 53% vs. 22%, P = 2.27 × 10−5 for log-rank test). Multivariate Cox regression analysis showed that rs9514828 was an independent prognostic factor, with HRs for patient death being 0.48 [95% confidence interval (CI), 0.32–0.71] for the CT and 0.47 (95% CI, 0.23–0.93) for the TT genotypes. Reporter gene assays indicated that the rs9514828T allele had significantly higher promoter activity than the rs9514828C counterpart.
Conclusion: These findings suggest that functional polymorphism in BAFF might be a genetic determinant for the survival of patients with TCL. Clin Cancer Res; 18(8); 2250–6. ©2012 AACR.
The Play Experience Scale
Authors: Pavlas Davin , Jentsch Florian , Salas Eduardo , Fiore Stephen M. , Sims Valerie 
Published: February 2012

Objective: A measure of play experience in video games was developed through literature review and two empirical validation studies. Background: Despite the considerable attention given to games in the behavioral sciences, play experience remains empirically underexamined. One reason for this gap is the absence of a scale that measures play experience. Method: In Study 1, the initial Play Experience Scale (PES) was tested through an online validation that featured three different games ( N = 203). In Study 2, a revised PES was assessed with a serious game in the laboratory ( N = 77). Results: Through principal component analysis of the Study 1 data, the initial 20-item PES was revised, resulting in the 16-item PES-16. Study 2 showed the PES-16 to be a robust instrument with the same patterns of correlations as in Study 1 via (a) internal consistency estimates, (b) correlations with established scales of motivation, (c) distributions of PES-16 scores in different game conditions, and (d) examination of the average variance extracted of the PES and the Intrinsic Motivation Scale. Conclusion: We suggest that the PES is appropriate for use in further validation studies. Additional examinations of the scale are required to determine its applicability to other contexts and its relationship with other constructs. Application: The PES is potentially relevant to human factors undertakings involving video games, including basic research into play, games, and learning; prototype testing; and exploratory learning studies.