bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm
Authors: Simek Melissa D. , Rida Wasima , Priddy Frances H. , Pung Pham , Carrow Emily , Laufer Dagna S. , Lehrman Jennifer K. , Boaz Mark , Tarragona-Fiol Tony , Miiro George , Birungi Josephine , Pozniak Anton , McPhee Dale A. , Manigart Olivier , Karita Etienne , Inwoley André , Jaoko Walter , DeHovitz Jack , Bekker Linda-Gail , Pitisuttithum Punnee , Paris Robert , Walker Laura M. , Poignard Pascal , Wrin Terri , Fast Patricia E. , Burton Dennis R. , Koff Wayne C. 
Published: May 2009

ABSTRACTThe development of a rapid and efficient system to identify human immunodeficiency virus type 1 (HIV-1)-infected individuals with broad and potent HIV-1-specific neutralizing antibody responses is an important step toward the discovery of critical neutralization targets for rational AIDS vaccine design. In this study, samples from HIV-1-infected volunteers from diverse epidemiological regions were screened for neutralization responses using pseudovirus panels composed of clades A, B, C, and D and circulating recombinant forms (CRFs). Initially, 463 serum and plasma samples from Australia, Rwanda, Uganda, the United Kingdom, and Zambia were screened to explore neutralization patterns and selection ranking algorithms. Samples were identified that neutralized representative isolates from at least four clade/CRF groups with titers above prespecified thresholds and ranked based on a weighted average of their log-transformed neutralization titers. Linear regression methods selected a five-pseudovirus subset, representing clades A, B, and C and one CRF01_AE, that could identify top-ranking samples with 50% inhibitory concentration (IC50) neutralization titers of ≥100 to multiple isolates within at least four clade groups. This reduced panel was then used to screen 1,234 new samples from the Ivory Coast, Kenya, South Africa, Thailand, and the United States, and 1% were identified as elite neutralizers. Elite activity is defined as the ability to neutralize, on average, more than one pseudovirus at an IC50titer of 300 within a clade group and across at least four clade groups. These elite neutralizers provide promising starting material for the isolation of broadly neutralizing monoclonal antibodies to assist in HIV-1 vaccine design.
Requirements for the Formation of Membrane Pores by the Reovirus Myristoylated μ1N Peptide
Authors: Zhang Lan , Agosto Melina A. , Ivanovic Tijana , King David S. , Nibert Max L. , Harrison Stephen C. 
Published: May 2009

ABSTRACT
The outer capsid of the nonenveloped mammalian reovirus contains 200 trimers of the μ1 protein, each complexed with three copies of the protector protein σ3. Conformational changes in μ1 following the proteolytic removal of σ3 lead to release of the myristoylated N-terminal cleavage fragment μ1N and ultimately to membrane penetration. The μ1N fragment forms pores in red blood cell (RBC) membranes. In this report, we describe the interaction of recombinant μ1 trimers and synthetic μ1N peptides with both RBCs and liposomes. The μ1 trimer mediates hemolysis and liposome disruption under conditions that promote the μ1 conformational change, and mutations that inhibit μ1 conformational change in the context of intact virus particles also prevent liposome disruption by particle-free μ1 trimer. Autolytic cleavage to form μ1N is required for hemolysis but not for liposome disruption. Pretreatment of RBCs with proteases rescues hemolysis activity, suggesting that μ1N cleavage is not required when steric barriers are removed. Synthetic myristoylated μ1N peptide forms size-selective pores in liposomes, as measured by fluorescence dequenching of labeled dextrans of different sizes. Addition of a C-terminal solubility tag to the peptide does not affect activity, but sequence substitution V13N or L36D reduces liposome disruption. These substitutions are in regions of alternating hydrophobic residues. Their locations, the presence of an N-terminal myristoyl group, and the full activity of a C-terminally extended peptide, along with circular dichroism data that indicate prevalence of β-strand secondary structure, suggest a model in which μ1N β-hairpins assemble in the membrane to form a β-barrel pore.
Mumps Virus Matrix, Fusion, and Nucleocapsid Proteins Cooperate for Efficient Production of Virus-Like Particles
Authors: Li Ming , Schmitt Phuong Tieu , Li Zhuo , McCrory Thomas S. , He Biao , Schmitt Anthony P. 
Published: May 2009

ABSTRACT
Paramyxovirus particles, like other enveloped virus particles, are formed by budding from membranes of infected cells. To define mumps virus (MuV) proteins important for this process, viral proteins were expressed either singly or in combination in mammalian cells to produce virus-like particles (VLPs). Only the MuV matrix (M) protein when expressed by itself was capable of inducing particle release, but the quantity of these M-alone particles was very small. Efficient production of mumps VLPs occurred only when the M protein was coexpressed together with other viral proteins, with maximum production achieved upon coexpression of the viral M, nucleocapsid (NP), and fusion (F) proteins together. Electron microscopy analysis confirmed that VLPs were morphologically similar to MuV virions. The two MuV glycoproteins were not equal contributors to particle formation. The F protein was a major contributor to VLP production, while the hemagglutinin-neuraminidase protein made a smaller contribution. Evidence for the involvement of class E protein machinery in VLP budding was obtained, with mumps VLP production inhibited upon expression of dominant-negative versions of the class E proteins Vps4A and Chmp4b. Disruption of the sequence 24-FPVI-27 within the MuV M protein led to poor VLP production, consistent with findings of earlier studies of a related sequence, FPIV, important for the budding of parainfluenza virus 5. Together, these results demonstrate that different MuV structural proteins cooperate together for efficient particle production and that particle budding likely involves host class E protein machinery.
Nef-Induced CD4 Endocytosis in Human Immunodeficiency Virus Type 1 Host Cells: Role of p56lckKinase
Authors: Laguette Nadine , Brégnard Christelle , Bouchet Jérôme , Benmerah Alexandre , Benichou Serge , Basmaciogullari Stéphane 
Published: May 2009

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) Nef interferes with the endocytic machinery to modulate the cell surface expression of CD4. However, the basal trafficking of CD4 is governed by different rules in the target cells of HIV-1: whereas CD4 is rapidly internalized from the cell surface in myeloid cells, CD4 is stabilized at the plasma membrane through its interaction with the p56lckkinase in lymphoid cells. In this study, we showed that Nef was able to downregulate CD4 in both lymphoid and myeloid cell lines but that an increase in the internalization rate of CD4 could be observed only in lymphoid cells. Expression of p56lckin nonlymphoid CD4-expressing cells restores the ability of Nef in order to increase the internalization rate of CD4. Concurrent with this observation, the expression of a p56lck-binding-deficient mutant of CD4 in lymphoid cells abrogates the Nef-induced acceleration of CD4 internalization. We also show that the expression of Nef causes a decrease in the association of p56lckwith cell surface-expressed CD4. Regardless of the presence of p56lck, the downregulation of CD4 by Nef was followed by CD4 degradation. Our results imply that Nef uses distinct mechanisms to downregulate the cell surface expression levels of CD4 in either lymphoid or myeloid target cells of HIV-1.
Effect of Anterior Cruciate Ligament Injury and Reconstruction on Proprioceptive Acuity of Knee Rotation in the Transverse Plane
Authors: Muaidi Qassim Ibrahim , Nicholson Leslie Lorenda , Refshauge Kathryn Margaret , Adams Roger David , Roe Justin Phillip 
Published: May 2009

Background Studies assessing proprioceptive acuity in anterior cruciate ligament (ACL)–deficient knees have only considered proprioception for knee movements in the sagittal plane rather than in the transverse plane (ie, rotation), despite the fact that the ACL plays a critical role in knee rotational stability and that the ACL is injured almost exclusively with a rotation mechanism. Therefore a test of proprioception is needed that involves movements similar to the mechanism of injury, in this case, rotation. Purpose To determine whether proprioceptive acuity in rotation changes after ACL injury and reconstruction, and to examine differences in proprioceptive acuity, range, laxity, and activity level among injured knees, contralateral knees, and healthy controls. Design Cohort study; Level of evidence, 2. Methods Proprioceptive acuity for active knee rotation movements, passive rotation range of motion, anterior knee laxity, and knee function were measured in 20 consecutive participants with unilateral ACL rupture and 20 matched controls. Reconstruction was performed using a single-incision technique with a 4-strand hamstring tendon autograft. Thirty participants (15 control and 15 ACL reconstructed) were retested at 3 months, and 14 with ACL reconstruction were tested at 6 months. Results A deficit was found in preoperative knee rotation proprioception compared with healthy controls (P =. 031). Three months after reconstruction, there was a significant improvement (P =. 049) in proprioceptive acuity, single-plane anterior laxity (P =. 01), and self-reported knee function (P =. 001). At 3 months after reconstruction, proprioceptive acuity of the ACLreconstructed knee was correlated with reported activity level (r =. 63; P =. 021). Conclusion Knee rotation proprioception is reduced in ACL-deficient participants compared with healthy controls. Three to 6 months after reconstruction, rotation proprioceptive acuity, laxity, and function were improved. While these findings are consistent with a return to previous activity level 6 months after reconstruction, the extent of graft maturation and restoration of kinematics should also inform the decision about return to sport.
Low-Energy Extracorporeal Shock Wave Therapy as a Treatment for Greater Trochanteric Pain Syndrome
Authors: Furia John P. , Rompe Jan D. , Maffulli Nicola 
Published: May 2009

Background Greater trochanteric pain syndrome is often a manifestation of underlying gluteal tendinopathy. Extracorporeal shock wave therapy is effective in numerous types of tendinopathies. Hypothesis Shock wave therapy is an effective treatment for chronic greater trochanteric pain syndrome. Study Design Case control study; Level of evidence, 3. Methods Thirty-three patients with chronic greater trochanteric pain syndrome received low-energy shock wave therapy (2000 shocks; 4 bars of pressure, equal to 0.18 mJ/mm 2; total energy flux density, 360 mJ/mm2). Thirty-three patients with chronic greater trochanteric pain syndrome were not treated with shock wave therapy but received additional forms of nonoperative therapy (control). All shock wave therapy procedures were performed without anesthesia. Evaluation was by change in visual analog score, Harris hip score, and Roles and Maudsley score. Results Mean pretreatment visual analog scores for the control and shock wave therapy groups were 8.5 and 8.5, respectively. One, 3, and 12 months after treatment, the mean visual analog score for the control and shock wave therapy groups were 7.6 and 5.1 (P < .001), 7 and 3.7 (P < .001), and 6.3 and 2.7 (P < .001), respectively. One, 3, and 12 months after treatment, mean Harris hip scores for the control and shock wave therapy groups were 54.4 and 69.8 (P < .001), 56.9 and 74.8 (P < .001), and 57.6 and 79.9 (P < .001), respectively. At final follow-up, the number of excellent, good, fair, and poor results for the shock wave therapy and control groups were 10 and 0 (P < .001), 16 and 12 (P < .001), 4 and 13 (P < .001), and 3 and 8 (P < .001), respectively. Chi-square analysis showed the percentage of patients with excellent (1) or good (2) Roles and Maudsley scores (ie, successful results) 12 months after treatment was statistically greater in the shock wave therapy than in the control group (P < .001). Conclusion Shock wave therapy is an effective treatment for greater trochanteric pain syndrome.
Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation
Authors: van Leeuwen Marina T. , Grulich Andrew E. , Webster Angela C. , McCredie Margaret R.E. , Stewart John H. , McDonald Stephen P. , Amin Janaki , Kaldor John M. , Chapman Jeremy R. , Vajdic Claire M. 
Published: May 2009

Abstract
Non-Hodgkin lymphoma (NHL) incidence is greatly increased after kidney transplantation. NHL risk was investigated in a nationwide cohort of 8164 kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry. NHL diagnoses were ascertained using linkage with national cancer registry records. Multivariate Poisson regression was used to compute incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing risk by transplant function, and risk factors for early (< 2 years) and late (≥ 2 years) NHL during the first transplantation. NHL occurred in 133 patients. Incidence was strikingly lower after transplant failure and cessation of immunosuppression than during transplant function (IRR, 0.25; 95% CI, 0.08-0.80; P = .019). Early NHL (n = 27) was associated with Epstein-Barr virus (EBV) seronegativity at transplantation (IRR, 4.66; 95% CI, 2.10-10.36, P < .001) and receipt of T cell–depleting antibodies (IRR, 2.39; 95% CI, 1.08-5.30; P = .031). Late NHL (n = 79) was associated with increasing year of age (IRR, 1.02; 95% CI, 1.01-1.04; P = .006), increasing time since transplantation (P < .001), and current use of calcineurin inhibitors (IRR, 3.13; 95% CI, 1.53-6.39; P = .002). These findings support 2 mechanisms of lymphomagenesis, one predominantly of primary EBV infection in the context of intense immunosuppression, and another of dysregulated lymphoid proliferation in a prolonged immunosuppressed state.
Complete sequence determination of a novel reptile iridovirus isolated from soft-shelled turtle and evolutionary analysis of Iridoviridae
Authors: Huang Youhua , Huang Xiaohong , Liu Hong , Gong Jie , Ouyang Zhengliang , Cui Huachun , Cao Jianhao , Zhao Yingtao , Wang Xiujie , Jiang Yulin , Qin Qiwei 
Published: May 2009

Abstract

Background
Soft-shelled turtle iridovirus (STIV) is the causative agent of severe systemic diseases in cultured soft-shelled turtles (Trionyx sinensis). To our knowledge, the only molecular information available on STIV mainly concerns the highly conserved STIV major capsid protein. The complete sequence of the STIV genome is not yet available. Therefore, determining the genome sequence of STIV and providing a detailed bioinformatic analysis of its genome content and evolution status will facilitate further understanding of the taxonomic elements of STIV and the molecular mechanisms of reptile iridovirus pathogenesis.

Results
We determined the complete nucleotide sequence of the STIV genome using 454 Life Science sequencing technology. The STIV genome is 105 890 bp in length with a base composition of 55.1% G+C. Computer assisted analysis revealed that the STIV genome contains 105 potential open reading frames (ORFs), which encode polypeptides ranging from 40 to 1,294 amino acids and 20 microRNA candidates. Among the putative proteins, 20 share homology with the ancestral proteins of the nuclear and cytoplasmic large DNA viruses (NCLDVs). Comparative genomic analysis showed that STIV has the highest degree of sequence conservation and a colinear arrangement of genes with frog virus 3 (FV3), followed by Tiger frog virus (TFV), Ambystoma tigrinum virus (ATV), Singapore grouper iridovirus (SGIV), Grouper iridovirus (GIV) and other iridovirus isolates. Phylogenetic analysis based on conserved core genes and complete genome sequence of STIV with other virus genomes was performed. Moreover, analysis of the gene gain-and-loss events in the family Iridoviridae suggested that the genes encoded by iridoviruses have evolved for favoring adaptation to different natural host species.

Conclusion
This study has provided the complete genome sequence of STIV. Phylogenetic analysis suggested that STIV and FV3 are strains of the same viral species belonging to the Ranavirus genus in the Iridoviridae family. Given virus-host co-evolution and the phylogenetic relationship among vertebrates from fish to reptiles, we propose that iridovirus might transmit between reptiles and amphibians and that STIV and FV3 are strains of the same viral species in the Ranavirus genus.
The CD-loop of PAI-2 (SERPINB2) is redundant in the targeting, inhibition and clearance of cell surface uPA activity
Authors: Cochran Blake J , Gunawardhana Lakshitha P , Vine Kara L , Lee Jodi A , Lobov Sergei , Ranson Marie 
Published: May 2009

Abstract

Background
Plasminogen activator inhibitor type-2 (PAI-2, SERPINB2) is an irreversible, specific inhibitor of the urokinase plasminogen activator (uPA). Since overexpression of uPA at the surface of cancer cells is linked to malignancy, targeting of uPA by exogenous recombinant PAI-2 has been proposed as the basis of potential cancer therapies. To this end, reproducible yields of high purity protein that maintains this targeting ability is required. Herein we validate the use in vitro of recombinant 6 × His-tagged-PAI-2 lacking the intrahelical loop between C and D alpha-helices (PAI-2 ΔCD-loop) for these purposes.

Results
We show that PAI-2 ΔCD-loop expressed and purified from the pQE9 vector system presents an easier purification target than the previously used pET15b system. Additionally, PAI-2 ΔCD-loop gave both higher yield and purity than wild-type PAI-2 expressed and purified under identical conditions. Importantly, absence of the CD-loop had no impact on the inhibition of both solution phase and cell surface uPA or on the clearance of receptor bound uPA from the cell surface. Furthermore, uPA:PAI-2 ΔCD-loop complexes had similar binding kinetics (KD ~5 nM) with the endocytosis receptor Very Low Density Lipoprotein Receptor (VLDLR) to that previously published for uPA:PAI-2 complexes.

Conclusion
We demonstrate that the CD-loop is redundant for the purposes of cellular uPA inhibition and cell surface clearance (endocytosis) and is thus suitable for the development of anti-uPA targeted cancer therapeutics.
The use of herbal medicines by people with cancer: a qualitative study
Authors: Gratus Christine , Wilson Sue , Greenfield Sheila M , Damery Sarah L , Warmington Sally A , Grieve Robert , Steven Neil M , Routledge Philip 
Published: May 2009

Abstract

Background
Between 7% and 48% of cancer patients report taking herbal medicines after diagnosis. Because of the possibility of unwanted side effects or interactions with conventional treatments, people with cancer are generally advised to tell the professionals treating them if they are taking any form of medication, including herbal medicines and supplements. Studies suggest that only about half do so and that the professionals themselves have at best very limited knowledge and feel unable to give informed advice. This study is intended to inform the future development of information resources for cancer patients, survivors and healthcare professionals including tools for use before or during consultation to make it easier for patients to mention, and for healthcare professionals to ask about, use of herbal medications.

Methods/design
This is a three-phase study. In phase 1, a systematic review of the literature on self-medication with herbal medicines among UK populations living with cancer will establish the current evidence base on use of herbal medicine, sources of information, characteristics and motivations. This will allow us to better understand what aspects need further investigation and inform the topic guide for a qualitative study (phase 2). Six focus groups of six to eight cancer patients who have used at least one herbal preparation since diagnosis will explore behaviour, beliefs, knowledge, information sources and needs in an informal conversational setting.
Informed by the findings of the systematic review and qualitative study, in phase 3 we will construct and pilot a questionnaire for a future large-scale survey to quantify and prioritise people's beliefs, needs and information preferences.

Discussion
Despite known interactions with conventional cancer treatments and contraindications for some herbal remedies with specific cancers, reliable information resources for patients are very limited. Identifying cancer patients' information needs and preferences is the first step in creating a suitable resource for both the public and the professionals advising them.
Influence of human chorionic gonadotropin (hCG) on in vitro growth of Plasmodium falciparum
Authors: Pong Clinton K , Thévenon Audrey Davidson , Zhou James Ainong , Taylor Diane Wallace 
Published: May 2009

Abstract

Background
During pregnancy, women are more susceptible to Plasmodium falciparum infections and frequently have a higher parasitaemia than non-pregnant women. Several mechanisms are responsible for their increased susceptibility, including down-modulation of immune responses that aid in parasite clearance and sequestration of infected erythrocytes in the placenta. Early in pregnancy, a third mechanism may contribute to higher parasitaemia, since it has been reported that addition of human chorionic gonadotropin (hCG) to in vitro cultures of the NF54-strain of P. falciparum results in increased parasite growth rates. The goal of this study was to further examine the effect of hCG on P. falciparum growth.

Methods
The NF54-3D7, FVO and 7G8 strains of P. falciparum were cultured in vitro with various physiological concentrations of hCG purchased from three sources. Infected erythrocytes were also co-cultured with a human cell line that naturally secretes hCG.

Results
Results from 14 experiments using different combinations of parasite strains and concentrations of hCG from different sources, as well as the co-culture studies, failed to provide convincing evidence that hCG enhances parasite growth in vitro.

Conclusion
Based on these data, it seems unlikely that hCG has a direct effect on the rate of parasite growth early in pregnancy.