bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous CD317/Tetherin Limits Replication of HIV-1 and Murine Leukemia Virus in Rodent Cells and Is Resistant to Antagonists from Primate Viruses
Authors: Goffinet Christine , Schmidt Sarah , Kern Christian , Oberbremer Lena , Keppler Oliver T. 
Published: August 2010

ABSTRACT
Human CD317 (BST-2/tetherin) is an intrinsic immunity factor that blocks the release of retroviruses, filoviruses, herpesviruses, and arenaviruses. It is unclear whether CD317 expressed endogenously in rodent cells has the capacity to interfere with the replication of the retroviral rodent pathogen murine leukemia virus (MLV) or, in the context of small-animal model development, contributes to the well-established late-phase restriction of human immunodeficiency virus type 1 (HIV-1). Here, we show that small interfering RNA (siRNA)-mediated knockdown of CD317 relieved a virion release restriction and markedly enhanced the egress of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) in rat cells, including primary macrophages. Moreover, rodent CD317 potently inhibited MLV release, and siRNA-mediated depletion of CD317 in a mouse T-cell line resulted in the accelerated spread of MLV. Several virus-encoded antagonists have recently been reported to overcome the restriction imposed by human or monkey CD317, including HIV-1 Vpu, envelope glycoproteins of HIV-2 and Ebola virus, Kaposi's sarcoma-associated herpesvirus K5, and SIV Nef. In contrast, both rat and mouse CD317 showed a high degree of resistance to these viral antagonists. These data suggest that CD317 is a broadly acting and conserved mediator of innate control of retroviral infection and pathogenesis that restricts the release of retroviruses and lentiviruses in rodents. The high degree of resistance of the rodent CD317 restriction factors to antagonists from primate viruses has implications for HIV-1 small-animal model development and may guide the design of novel antiviral interventions.
Gag-Protease-Mediated Replication Capacity in HIV-1 Subtype C Chronic Infection: Associations with HLA Type and Clinical Parameters
Authors: Wright Jaclyn K. , Brumme Zabrina L. , Carlson Jonathan M. , Heckerman David , Kadie Carl M. , Brumme Chanson J. , Wang Bingxia , Losina Elena , Miura Toshiyuki , Chonco Fundisiwe , van der Stok Mary , Mncube Zenele , Bishop Karen , Goulder Philip J. R. , Walker Bruce D. , Brockman Mark A. , Ndung'u Thumbi 
Published: August 2010

ABSTRACT
The mechanisms underlying HIV-1 control by protective HLA class I alleles are not fully understood and could involve selection of escape mutations in functionally important Gag epitopes resulting in fitness costs. This study was undertaken to investigate, at the population level, the impact of HLA-mediated immune pressure in Gag on viral fitness and its influence on HIV-1 pathogenesis. Replication capacities of 406 recombinant viruses encoding plasma-derived Gag-protease from patients chronically infected with HIV-1 subtype C were assayed in an HIV-1-inducible green fluorescent protein reporter cell line. Viral replication capacities varied significantly with respect to the specific HLA-B alleles expressed by the patient, and protective HLA-B alleles, most notably HLA-B*81, were associated with lower replication capacities. HLA-associated mutations at low-entropy sites, especially the HLA-B*81-associated 186S mutation in the TL9 epitope, were associated with lower replication capacities. Most mutations linked to alterations in replication capacity in the conserved p24 region decreased replication capacity, while most in the highly variable p17 region increased replication capacity. Replication capacity also correlated positively with baseline viral load and negatively with baseline CD4 count but did not correlate with the subsequent rate of CD4 decline. In conclusion, there is evidence that protective HLA alleles, in particular HLA-B*81, significantly influence Gag-protease function by driving sequence changes in Gag and that conserved regions of Gag should be included in a vaccine aiming to drive HIV-1 toward a less fit state. However, the long-term clinical benefit of immune-driven fitness costs is uncertain given the lack of correlation with longitudinal markers of disease progression.
Side Chain Packing below the Fusion Peptide Strongly Modulates Triggering of the Hendra Virus F Protein
Authors: Smith Everett Clinton , Dutch Rebecca Ellis 
Published: August 2010

ABSTRACT
Triggering of the Hendra virus fusion (F) protein is required to initiate the conformational changes which drive membrane fusion, but the factors which control triggering remain poorly understood. Mutation of a histidine predicted to lie near the fusion peptide to alanine greatly reduced fusion despite wild-type cell surface expression levels, while asparagine substitution resulted in a moderate restoration in fusion levels. Slowed kinetics of six-helix bundle formation, as judged by sensitivity to heptad repeat B-derived peptides, was observed for all H372 mutants. These data suggest that side chain packing beneath the fusion peptide is an important regulator of Hendra virus F triggering.
Very Few Substitutions in a Germ Line Antibody Are Required To Initiate Significant Domain Exchange
Authors: Huber Michael , Le Khoa M. , Doores Katie J. , Fulton Zara , Stanfield Robyn L. , Wilson Ian A. , Burton Dennis R. 
Published: August 2010

ABSTRACT2G12 is a broadly neutralizing anti-HIV-1 monoclonal human IgG1 antibody reactive with a high-mannose glycan cluster on the surface of glycoprotein gp120. A key feature of this very highly mutated antibody is domain exchange of the heavy-chain variable region (VH) with the VHof the adjacent Fab of the same immunoglobulin, which assembles a multivalent binding interface composed of two primary binding sites in close proximity. A non-germ line-encoded proline in the elbow between VHand CH1 and an extensive network of hydrophobic interactions in the VH/VH′ interface have been proposed to be crucial for domain exchange. To investigate the origins of domain exchange, a germ line version of 2G12 that behaves as a conventional antibody was engineered. Substitution of 5 to 7 residues for those of the wild type produced a significant fraction of domain-exchanged molecules, with no evidence of equilibrium between domain-exchanged and conventional forms. Two substitutions not previously implicated, AH14and EH75, are the most crucial for domain exchange, together with IH19at the VH/VH′ interface and PH113in the elbow region. Structural modeling gave clues as to why these residues are essential for domain exchange. The demonstration that domain exchange can be initiated by a small number of substitutions in a germ line antibody suggests that the evolution of a domain-exchanged antibody responsein vivomay be more readily achieved than considered to date.
Stably Expressed APOBEC3F Has Negligible Antiviral Activity
Authors: Miyagi Eri , Brown Charles R. , Opi Sandrine , Khan Mohammad , Goila-Gaur Ritu , Kao Sandra , Walker Robert C. , Hirsch Vanessa , Strebel Klaus 
Published: August 2010

ABSTRACT
APOBEC3F (A3F) is a member of the family of cytidine deaminases that is often coexpressed with APOBEC3G (A3G) in cells susceptible to HIV infection. A3F has been shown to have strong antiviral activity in transient-expression studies, and together with A3G, it is considered the most potent cytidine deaminase targeting HIV. Previous analyses suggested that the antiviral properties of A3F can be dissociated from its catalytic deaminase activity. We were able to confirm the deaminase-independent antiviral activity of exogenously expressed A3F; however, we also noted that exogenous expression was associated with very high A3F mRNA and protein levels. In analogy to our previous study of A3G, we produced stable HeLa cell lines constitutively expressing wild-type or deaminase-defective A3F at levels that were more in line with the levels of endogenous A3F in H9 cells. A3F expressed in stable HeLa cells was packaged into Vif-deficient viral particles with an efficiency similar to that of A3G and was properly targeted to the viral nucleoprotein complex. Surprisingly, however, neither wild-type nor deaminase-defective A3F inhibited HIV-1 infectivity. These results imply that the antiviral activity of endogenous A3F is negligible compared to that of A3G.
Onchocerciasis in Anambra State, Southeast Nigeria: endemicity and clinical manifestations
Authors: Mbanefo Evaristus Chibunna , Eneanya Christine Ifeoma , Nwaorgu Obioma C , Otiji Moses Obiefuna , Oguoma Victor Mmaduabuchi , Ogolo Bernice Amala 
Published: August 2010

Abstract

Background
A cross-sectional study was performed to determine the current endemicity of onchocerciasis in Ayamelum Local Council, Anambra State, Southeast Nigeria, where community-directed treatment with ivermectin has been implemented for over a decade.

Methods
An estimate of the endemicity of onchocerciasis was obtained using the rapid assessment method in 894 subjects from 13 communities selected by multistage sampling. Dermatological and ocular manifestations were analysed and classified using standard criteria.

Results
Onchocerca volvulus nodules were recorded in 86 (9.6±1.9%) of the subjects, and 186 (20.8±3.7%) had one or more of the various classes of onchocercal skin diseases (OSD). Prevalence was dependent on age (p=0.001), but not on sex (p=0.31). There was a total absence of symptoms in the youngest age group and a low prevalence among subjects in their second decade of life. Pearson’s correlation showed a strong positive correlation between nodular rate and prevalence of chronic papular onchodermatitis (r=0.943) and a poor correlation with acute papular onchodermatitis (r=0.259). Age-dependent analysis of various classes of OSDs showed that the rate of acute papular onchodermatitis increased with age up to the third decade of life and decreased steadily thereafter, while the chronic forms of OSD increased with age for both sexes. Infection was dependent on occupation and proximity of the village to the vector breeding sites.

Conclusions
Generally low prevalence in the population and absence of symptoms among the youngest age group emphasise the success of the intervention, but the persistent occurrence of acute disease may suggest a shortfall due to low coverage or non-compliance with the mass chemotherapeutic regimen.
Considerations and proposals for the management of patients after prolonged intensive care unit admission
Authors: Johns Robin H , Dawson Deborah , Ball Jonathan 
Published: August 2010

Abstract
The majority of patients admitted to the intensive care unit (ICU) have a short stay of only a few days. However a small but significant number require prolonged intensive care. This is typically due to persisting, and sometimes complex, medical/surgical problems. Discharge of such ICU patients requires a comprehensive, multidisciplinary, verbal and written handover to the receiving ward team. As with any acutely ill adult in hospital, post-ICU patients should be carefully monitored with ‘track and trigger’ systems such as the Early Warning Score. Those with unexpected physiological deterioration should be promptly reviewed by senior clinicians and/or medical emergency/critical care outreach teams and considered for ICU re-admission where appropriate. Patients who have received prolonged organ support in the ICU are often affected by a number of specific medical problems such as ventilatory insufficiency, cardiac dysfunction, kidney injury, nutritional deficiency, ICU acquired weakness, and brain injury. They also frequently experience physical disability and psychosocial problems including delirium, anxiety, depression, post-traumatic stress disorder, cognitive dysfunction, and disturbed sleep. Structured rehabilitation programmes for post-ICU patients, tailored to individual needs, should be commenced on the ICU and continued through to and beyond hospital discharge. Care bundles, which are widely used on the ICU, are groups of interventions employed to optimise treatments or minimise complication rates. They may be additionally useful in the post-ICU ward setting by prompting clinicians to focus on, and address, commonly occurring medical and psychosocial problems in these patients.
Image-Guided Breast Tumor Therapy Using a Small Interfering RNA Nanodrug
Authors: Kumar Mohanraja , Yigit Mehmet , Dai Guangping , Moore Anna , Medarova Zdravka 
Published: August 2010

Abstract
Iron oxide nanoparticles offer a feasible tool for combined imaging and delivery of small interfering RNA (siRNA) to tumors, stimulating active interest in exploring different imaging and delivery platforms suitable for detection by a variety of modalities. In this study, we describe the synthesis and testing of a tumor-targeted nanodrug (MN-EPPT-siBIRC5) that is designed to specifically shuttle siRNA to human breast tumors. The nanodrug binds the tumor-specific antigen uMUC-1, which is found in &gt;90% of human breast adenocarcinomas. MN-EPPT-siBIRC5 consists of superparamagnetic iron oxide nanoparticles [for magnetic resonance imaging (MRI)], the dye Cy5.5 (for near-IR optical imaging), peptides (EPPT) that specifically target uMUC-1, and a synthetic siRNA that targets the tumor-specific antiapoptotic gene BIRC5. Nanodrug uptake by human breast adenocarcinoma cells resulted in a significant downregulation of BIRC5. Following i.v. delivery into subcutaneous mouse models of breast cancer, the nanodrug showed a preferential tumor uptake, which could be visualized by MRI and near-IR optical imaging. Furthermore, MRI could be used to quantitatively monitor nanodrug bioavailability in the tumor tissue throughout the course of treatment. Intravenous injection of the agent once a week over 2 weeks resulted in the induction of considerable levels of necrosis and apoptosis in the tumors, translating into a significant decrease in tumor growth rate. Our strategy permits the simultaneous tumor-specific delivery of siRNA to tumors and the imaging of the delivery process. More generally, it illustrates the potential to apply this approach to many human cancer studies, including for basic tumor biology and therapy. Cancer Res; 70(19); 7553–61. ©2010 AACR.
Comprehensive Analysis of the MYB-NFIB Gene Fusion in Salivary Adenoid Cystic Carcinoma: Incidence, Variability, and Clinicopathologic Significance
Authors: Mitani Yoshitsugu , Li Jie , Rao Pulivarthi H. , Zhao Yi-Jue , Bell Diana , Lippman Scott M. , Weber Randal S. , Caulin Carlos , El-Naggar Adel K. 
Published: August 2010

Abstract
Purpose: The objectives of this study were to determine the incidence of the MYB-NFIB fusion in salivary adenoid cystic carcinoma (ACC), to establish the clinicopathologic significance of the fusion, and to analyze the expression of MYB in ACCs in the context of the MYB-NFIB fusion.
Experimental Design: We did an extensive analysis involving 123 cancers of the salivary gland, including primary and metastatic ACCs, and non-ACC salivary carcinomas. MYB-NFIB fusions were identified by reverse transcriptase-PCR (RT-PCR) and sequencing of the RT-PCR products, and confirmed by fluorescence in situ hybridization. MYB RNA expression was determined by quantitative RT-PCR and protein expression was analyzed by immunohistochemistry.
Results: The MYB-NFIB fusion was detected in 28% primary and 35% metastatic ACCs, but not in any of the non-ACC salivary carcinomas analyzed. Different exons in both the MYB and NFIB genes were involved in the fusions, resulting in expression of multiple chimeric variants. Notably, MYB was overexpressed in the vast majority of the ACCs, although MYB expression was significantly higher in tumors carrying the MYB-NFIB fusion. The presence of the MYB-NFIB fusion was significantly associated (P = 0.03) with patients older than 50 years of age. No correlation with other clinicopathologic markers, factors, and survival was found.
Conclusions: We conclude that the MYB-NFIB fusion characterizes a subset of ACCs and contributes to MYB overexpression. Additional mechanisms may be involved in MYB overexpression in ACCs lacking the MYB-NFIB fusion. These findings suggest that MYB may be a specific novel target for tumor intervention in patients with ACC. Clin Cancer Res; 16(19); 4722–31. ©2010 AACR.
Numerical Simulations of Island-Scale Airflow over Maui and the Maui Vortex under Summer Trade Wind Conditions
Authors: Carlis DaNa L. , Chen Yi-Leng , Morris Vernon R. 
Published: August 2010

Abstract
The fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) coupled with the Noah land surface model (LSM) is employed to simulate island-scale airflow and circulations over Maui County, Hawaii, under summer trade wind conditions, during July–August 2005. The model forecasts are validated by surface observations with good agreement.
In this study, it is shown that a previously known closed circulation over the Central Valley of Maui, or the Maui vortex, represents the northern cyclonic vortex of the dual-counter-rotating vortices in the lee of Haleakala, which extend up to the base of the trade wind inversion with a westerly reversed flow (&gt;2 m s−1). At low levels, the northern cyclonic vortex is more pronounced than the southern anticyclonic vortex. The asymmetric structure of the dual vortices is related to the shape of Haleakala and the flow deflection by the West Maui Mountains. The Maui vortex has a relatively narrow east–west extent in the lowest levels, especially at night, due to the deflected strong northerly/northeasterly winds from the windward foothills of the West Maui Mountains. Unlike the lee vortices off the leeside coast of the island of Hawaii, the Maui vortex and the westerly return flow in low levels are mainly over land and are strongly modulated by the diurnal heating cycle. In addition, the location and horizontal and vertical extent are affected by the trade wind speed and latent heat release.
Over the West Maui Mountains, with their height below the trade wind inversion, dual-counter-rotating vortices are present below the 1-km level in the wake, with strong downslope flow on the leeside slopes followed by a hydraulic jump. In the afternoon, downslope winds are weak, with combined westerly return/sea-breeze flow along the leeside coast. Orographic blocking is also evident over eastern Molokai with strong downslope winds, especially at night.
Expression of CD200/CD200R regulatory molecules on granulocytes and monocytes is modulated by cardiac surgical operation
Authors: Krejsek Jan , Kolackova Martina , Mandak Jiri , Kunes Pavel , Jankovicova Karolina , Vlaskova Dana , Svitek Vladimir , Andrys Ctirad 
Published: August 2010

Aims: Cardiac surgical operation is inseparably linked to the induction of an inflammatory response. Both humoral and cellular regulatory mechanisms are operating to maintain body homeostasis. We followed the changes in the expression of CD200/CD200R regulatory molecules on monocytes and granulocyte of cardiac surgical patients operated on using either standard (OP) or modified “mini-invasive” cardiopulmonary bypass (MOP). Methods: Expression of CD200/CD200R regulatory molecules was determined by flow cytometry. Results: The expression of CD200R on granulocytes was increased after surgery in both groups of patients, but the increase was statistically significant only in OP patients (p<0.01). At this time point, there was a significant difference in CD200R expression on granulocytes when comparing OP to MOP patients, being higher in the former group (p<0.01). The expression of CD200R on monocytes was diminished after surgery and during an early postoperative period in both groups of patients. The expression of CD200 on monocytes was significantly diminished after surgery in both groups (p<0.01). Nonetheless, we observed an increase in CD200 expression in OP patients at the 3rd postoperative day. There was a statistically significantly increased CD200 expression on monocytes of OP patients (p<0.001) at the 3rd postoperative day when we compared OP and MOP groups. The expression of CD200 on granulocytes was significantly higher after surgery and at the 3rd postoperative day in OP when compared to MOP patients. Conclusions: CD200R expression on granulocytes was significantly increased, while CD200 and CD200R expression on monocytes was decreased after cardiac surgery.
Evidence of disagreement between patient-perceived change and conventional longitudinal evaluation of change in health-related quality of life among older adults
Authors: McPhail Steven , Comans Tracy , Haines Terry 
Published: August 2010

Objective: To identify agreement levels between conventional longitudinal evaluation of change (post—pre) and patient-perceived change (post—then test) in health-related quality of life. Design: A prospective cohort investigation with two assessment points (baseline and six-month follow-up) was implemented. Setting: Community rehabilitation setting. Subjects: Frail older adults accessing community-based rehabilitation services. Intervention: Nil as part of this investigation. Main measures: Conventional longitudinal change in health-related quality of life was considered the difference between standard EQ-5D assessments completed at baseline and follow-up. To evaluate patient-perceived change a ‘then test’ was also completed at the follow-up assessment. This required participants to report (from their current perspective) how they believe their health-related quality of life was at baseline (using the EQ-5D). Patient-perceived change was considered the difference between ‘then test’ and standard follow-up EQ-5D assessments. Results: The mean (SD) age of participants was 78.8 (7.3). Of the 70 participants 62 (89%) of data sets were complete and included in analysis. Agreement between conventional (post—pre) and patient-perceived (post—then test) change was low to moderate (EQ-5D utility intraclass correlation coefficient (ICC) = 0.41, EQ-5D visual analogue scale (VAS) ICC = 0.21). Neither approach inferred greater change than the other (utility P =0.925, VAS P =0.506). Mean (95% confidence interval (CI)) conventional change in EQ-5D utility and VAS were 0.140 (0.045,0.236) and 8.8 (3.3,14.3) respectively, while patient-perceived change was 0.147 (0.055,0.238) and 6.4 (1.7,11.1) respectively. Conclusions: Substantial disagreement exists between conventional longitudinal evaluation of change in health-related quality of life and patient-perceived change in health-related quality of life (as measured using a then test) within individuals.
Effects of tai chi exercise on posturography, gait, physical function and quality of life in postmenopausal women with osteopaenia: a randomized clinical study
Authors: Chyu Ming-Chien , James C. Roger , Sawyer Steven F , Brismée Jean-Michel , Xu Ke T , Poklikuha Glen , Dunn Dale M , Shen Chwan-Li 
Published: August 2010

Objective: To evaluate the effects of tai chi exercise on risk factors for falls in postmenopausal women with osteopaenia through measurements of balance, gait, physical function and quality of life. Design: A randomized, controlled, single-blinded, 24-week trial with stratification by age and bone mass. Setting: General community. Participants: Sixty-one independently living elderly females aged 65 years and older with low bone mass. Interventions: Subjects were recruited and randomly assigned to 24 weeks of tai chi (60 minutes/session, three sessions/week, n = 30) or a control group (n = 31). Outcome measures: Computerized dynamic posturography, gait, ‘timed up and go’, five-chair sit-to-stand and quality of life assessed at baseline, 12 and 24 weeks. Results: After 24 weeks, subjects in the tai chi group demonstrated an increase in stride width (P = 0.05) and improvement in general health (P = 0.008), vitality (P = 0.02) and bodily pain (P = 0.03) compared with those in the control group. There was no significant difference in balance parameters, ‘timed up and go’, five-chair sit-to-stand and other domains of quality of life. Conclusion: Tai chi exercise may reduce risk factors for falls by increasing the stride width, and may improve quality of life in terms of general health, vitality and bodily pain in postmenopausal women with osteopaenia.