bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA Aptamers Directed to Human Immunodeficiency Virus Type 1 Gag Polyprotein Bind to the Matrix and Nucleocapsid Domains and Inhibit Virus Production
Authors: Ramalingam Dhivya , Duclair Sonald , Datta Siddhartha A. K. , Ellington Andrew , Rein Alan , Prasad Vinayaka R. 
Published: October 2010

ABSTRACT

Gag orchestrates the assembly and release of human immunodeficiency virus type 1 (HIV-1) particles. We explored here the potential of anti-Gag RNA aptamers to inhibit HIV-1 replication.
In vitro
, RNA aptamers raised against an HIV-1 Gag protein, lacking the N-terminal myristate and the C-terminal p6 (DP6-Gag), could bind to matrix protein (MA), nucleocapsid protein (NC), or entire DP6-Gag protein. Upon cotransfection with pNL4-3.Luc molecular clone into 293T cells, six of the aptamers caused mild inhibition (2- to 3-fold) in the extracellular capsid levels, and one aptamer displayed 20-fold inhibition. The reduction was not due to a release defect but reflected Gag mRNA levels. We hypothesized that the aptamers influence genomic RNA levels via perturbation of specific Gag-genomic RNA interactions. Binding studies revealed that the “NC-binders” specifically compete with the packaging signal (ψ) of HIV-1 for binding to DP6-Gag. Therefore, we tested the ability of two NC-binders to inhibit viruses containing ψ-region deletions (ΔSL1 or ΔSL3) and found that the NC-binders were no longer able to inhibit Gag synthesis. The inability of these aptamers to inhibit ψ-deleted viruses correlated with the absence of competition with the corresponding ψ transcripts lacking SL1 or SL3 for binding DP6-Gag
in vitro
. These results indicate that the NC-binding aptamers disrupt Gag-genomic RNA interaction and negatively affect genomic RNA transcription, processing, or stability. Our results reveal an essential interaction between HIV-1 Gag and the ψ-region that may be distinct from that which occurs during the encapsidation of genomic RNA. Thus, anti-Gag aptamers can be an effective tool to perturb Gag-genomic RNA interactions.
Ocular adnexal marginal zone B cell lymphoma infiltrated by IgG4-positive plasma cells
Authors: Kubota Toshinobu , Moritani Suzuko , Yoshino Tadashi , Nagai Hirokazu , Terasaki Hiroko 
Published: October 2010

AimsTo report the clinicopathological characteristics of patients with ocular adnexal marginal zone B cell lymphoma (MZBL) with IgG4-positive plasma cells.Methods114 biopsy samples of ocular adnexal MZBLs were analysed. MZBLs with IgG4-positive plasma cells were included when the IgG4:IgG ratio was >40% (IgG4-related group). The serum levels of each subclass of immunoglobulins and soluble interleukin-2 receptor in the IgG4-related group were compared with those in 61 consecutive patients having MZBL without IgG4-positive plasma cells (IgG4-unrelated group). They were also compared with those in 10 patients having ocular adnexal IgG4-related lymphoplasmacytic disorder (IgG4-related inflammatory group).ResultsTen (9%) of the patients were diagnosed with MZBL with IgG4-positive plasma cells. The IgG4-related group had a significantly greater degree of sclerosis and reactive follicles in the MZBLs (p=0.0004 and p=0.01, respectively). The serum levels of IgG, IgG1, IgG4, IgE and soluble interleukin 2 receptor in the IgG4-related group were significantly higher than those in the IgG4-unrelated group (p=0.003, p=0.009, p<0.0001, p<0.0001 and p=0.0007, respectively). The serum levels did not differ significantly from those of the IgG4-related inflammatory group. The IgG4-related group also had reactive IgG4-positive lymphoplasmacytic infiltrations in the recurrent lesion and in the stomach.ConclusionsIgG4-positive plasma cells had infiltrated into ocular adnexal MZBLs in 9% of cases. It is suggested that ocular adnexal MZBLs with IgG4-positive plasma cells have unique histological and serological characteristics that overlap those of ocular adnexal IgG4-related lymphoplasmacytic infiltrative disorder and systemic conditions.
Urinary 8-hydroxy-2′-deoxyguanosine as a biomarker of oxidative DNA damage induced by ambient pollution in the Normative Aging Study
Authors: Ren Cizao , Fang Shona , Wright Robert O , Suh Helen , Schwartz Joel 
Published: October 2010

BackgroundStudies show that exposure to air pollution damages human health, but the mechanisms are not fully understood. One suggested pathway is via oxidative stress.ObjectivesThis study examines associations between exposure to air pollution and oxidative DNA damage, as indicated by urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations in ageing participants during 2006–2008.MethodsWe fit linear regression models to examine associations between air pollutants and 8-OHdG adjusting for potential confounders.Results8-OHdG was significantly associated with ambient particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), maximal 1 h ozone (O3), sulphate (SO42−) and organic carbon (OC), but not with black carbon (BC), carbon monoxide (CO), the number of particles (PN) or elemental carbon (EC). Effects were more apparent with multi-week averages of exposures. Per IQR increases in 21-day averages of PM2.5, PN, BC, EC, OC, CO, SO42−, NO2and maximal 1 h O3were associated with 30.8% (95% CI 9.3% to 52.2%), −13.1% (95% CI −41.7% to 15.5%), 3.0% (95% CI −19.8% to 25.8%), 5.3% (95% CI −23.6% to 34.2%), 24.4% (95% CI 1.8% to 47.1%), −2.0% (95% CI −12.4% to 8.3%), 29.8% (95% CI 6.3% to 53.3%), 32.2% (95% CI 7.4% to 56.9%) and 47.7% (95% CI 3.6% to 91.7%) changes in 8-OHdG, respectively.ConclusionsThis study suggests that ageing participants experienced an increased risk of developing oxidative DNA injury after exposure to secondary, but not primary, ambient pollutants.
Rethinking the systems review process
Authors: Lau Tessa 
Published: October 2010

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Tessa Lau launches a discussion about the acceptance criteria for HCI systems papers at CHI, UIST, and other conferences.
Downregulation of c-MYC Protein Levels Contributes to Cancer Cell Survival under Dual Deficiency of Oxygen and Glucose
Authors: Okuyama Hiroaki , Endo Hiroko , Akashika Tamaki , Kato Kikuya , Inoue Masahiro 
Published: October 2010

Abstract
The c-MYC protein participates in energy-consuming processes such as proliferation and ribosome biosynthesis, and its expression is often dysregulated in human cancers. Cancer cells distant from blood vessels in solid tumors are in short supply of oxygen and nutrition yet can adapt to the microenvironment and survive under metabolic stress. The role and regulation of c-MYC protein in the tumor microenvironment of limited energy sources are poorly understood. Here, we show that c-MYC protein levels in cancer cells are strikingly reduced in the area distant from the blood vessels in vivo and also under oxygen- and glucose-deprived conditions in vitro. The rapid reduction of c-MYC protein levels requires low levels of both oxygen and glucose, and under these conditions, downregulation is mainly achieved by enhanced degradation. Suppression of c-MYC protein levels by small hairpin RNA decreases the necrotic cell death induced by oxygen and glucose deprivation. Thus, the environmental milieu regulates c-MYC protein levels, and downregulation of c-MYC might be a strategy for cancer cells to survive under conditions of limited energy sources. Cancer Res; 70(24); 10213–23. ©2010 AACR.
Australian dental students views on a compulsory internship scheme
Authors: Lalloo Ratilal , Johnson Newell W , Blinkhorn Anthony S , Ichim Paul 
Published: October 2010

Objective: The National Health and Hospitals Reform Commission Report suggests introducing an internship period for all newly qualified dental/oral health practitioners in Australia. This study gauged the opinions of undergraduates from three dental schools in Australia. Methods: An online survey collected demographic information on gender and age, the program registered for, year and place of study. The level of support for an internship was gauged using a five-point scale. Open-ended questions on the concerns, advantages and disadvantages of an internship concluded the survey. All students in the participating universities were invited to participate via email. Results: There were 445 responses. Forty per cent of students were supportive of an internship scheme. The level of support differed by gender, age, relationship status, having a previous tertiary qualification and year of study. Males, older participants, those with children and those with previous qualifications were less supportive. The main concerns related to issues around choice, family commitments, location of internship placements and salary levels. Conclusion: Support for an internship scheme for dental graduates elicited a divided opinion amongst dental students. Many issues around financing and logistics have to be addressed before any such scheme could be implemented in Australia: there is a need to consult with dental graduates and promote the benefits to the student body.
The effect of eccentric and concentric calf muscle training on Achilles tendon stiffness
Authors: Morrissey Dylan , Roskilly Anna , Twycross-Lewis Richard , Isinkaye Tomide , Screen Hazel , Woledge Roger , Bader Dan 
Published: October 2010

Objective: To compare in vivo effects of eccentric and concentric calf muscle training on Achilles tendon stiffness, in subjects without tendinopathy. Methods: Thirty-eight recreational athletes completed 6 weeks eccentric (6 males, 13 females, 21.6 ± 2.2 years) or concentric training (8 males, 11 females, 21.1 ± 2.0 years). Achilles tendon stiffness, tendon modulus and single-leg jump height were measured before and after intervention. Exercise adherence was recorded using a diary. Results: All data are reported as mean ± SD. Groups were matched for height and weight but the eccentric training group were more active at baseline ( P < 0.05). Tendon stiffness was higher in the eccentrically trained group at baseline compared to the concentrically trained group (20.9 ± 7.3 N/mm v 13.38 ± 4.66 N/mm; P = 0.001) and decreased significantly after eccentric training (to 17.2 ( ± 5.9) N/mm ( P = 0.035)). There was no stiffness change in the concentric group ( P = 0.405). Stiffness modulus showed similar changes to stiffness. An inverse correlation was found between initial, and subsequent, reduction in stiffness (r = −0.66). Jump height did not change and no correlation between stiffness change and adherence was observed in either group ( r = 0.01). Conclusions: Six weeks of eccentric training can alter Achilles tendon stiffness while a matched concentric programme shows no similar effects. Studies in patients with Achilles tendinopathy are warranted.
Influence of magnetic knee wraps on joint proprioception in individuals with osteoarthritis: a randomized controlled pilot trial
Authors: Chen Chung-Yao , Fu Tieh-Cheng , Hu Ching-Fang , Hsu Chih-Chin , Chen Chia-Ling , Chen Chih-Kuang 
Published: October 2010

Objective: To determine the effects of magnetic knee wraps (MKWs) on joint position sense (JPS) in individuals with mild-to-moderate knee osteoarthritis. Design: Randomized, double-blind, placebo-controlled pilot trial. Setting: Rehabilitation clinic of a tertiary hospital. Subjects: Fifty volunteers with mild-to-moderate knee osteoarthritis participated and 33 (66%) completed the trial; only one (2%) withdrew due to study-related adverse effects. Interventions: Knee wraps with a static magnetic field (35 mT) were compared with control knee wraps for 12 weeks. Main measures: The main outcome measure was JPS at first, fourth, and twelfth week while applying of the knee wrap, quantified as the ability to replicate target knee joint angles. The secondary outcome was the Comprehensive Osteoarthritis Test (COAT) total score. Results: In the intention-to-treat analysis with an alpha-level of 0.05, 12-week application of the MKWs did not significantly reduce the mean absolute error (MAE) of JPS ( n = 18; P = 0.627); contrarily, the MAE was found to decrease significantly after wearing the sham MKWs ( n = 20; P = 0.01). The COAT total score gradually improved in both groups ( P < 0.05). When comparing the improvement of MAE and COAT total score at each follow-up between two groups, no significant differences were found; the maximal difference in the improvement of MAE between two groups was noted at week 12 (mean difference: 1.2°; 95% confidence interval −0.4 to 2.9; P = 0.144). In the per-protocol analysis, the study group showed better improvement in the COAT total score at week 12 ( P = 0.033). Conclusion: The 35-mT MKWs could not significantly influence knee JPS in individuals with mild-to-moderate knee osteoarthritis.
Is the Incredible Years programme effective for children with neuro-developmental disorders and for families with Social Services involvement in the “real world” of community CAMHS?
Authors: Kleve Liv , Crimlisk Sue , Shoebridge Philip , Greenwood Rosemary , Baker Bethan , Mead Ben 
Published: October 2010

Background: Over the past few years parenting has become the focus for political attention in an attempt to tackle high levels of disruptive and anti-social behaviour. The Incredible Years (IY) programme (Webster-Stratton, 1999) is one of the parenting training packages that has been identified as a treatment of choice. There are, however, few studies available to demonstrate the clinical relevance in real world Child and Adolescent Mental Health Services (CAMHS) and even less knowledge about how children affected by a neuro-developmental disorder and families involved with Social Services can benefit. Method: The BASIC IY videotape parent training programme was used for consecutive groups of parents across two neighbouring CAMH services ( n = 128). Data were collected before and after intervention using the Eyberg Behaviour Checklist (Eyberg & Ross, 1978) and a number of Visual Analogue Scales. The effectiveness of the group was compared to that of other studies and the outcomes for two sub-groups — children with a neuro-developmental disorder and families with Social Services involvement — were evaluated. Results: Statistically significantly post-intervention scores were found for all groups showing moderate to large effect sizes. Conclusions: The results are comparable to other effectiveness studies (e.g., Gardner, Barton, & Klimes, 2006; Scott, 2005). They also show that the IY is equally effective for children diagnosed with a neuro-developmental disorder and for families with multiple and complex needs.
Diagnosis of Osteoarthritis by Cartilage Surface Smoothness Quantified Automatically from Knee MRI
Authors: Tummala Sudhakar , Bay-Jensen Anne-Christine , Karsdal Morten A. , Dam Erik B. 
Published: October 2010

Objective: We investigated whether surface smoothness of articular cartilage in the medial tibiofemoral compartment quantified from magnetic resonance imaging (MRI) could be appropriate as a diagnostic marker of osteoarthritis (OA). Method: At baseline, 159 community-based subjects aged 21 to 81 with normal or OA-affected knees were recruited to provide a broad range of OA states. Smoothness was quantified using an automatic framework from low-field MRI in the tibial, femoral, and femoral subcompartments. Diagnostic ability of smoothness was evaluated by comparison with conventional OA markers, specifically cartilage volume from MRI, joint space width (JSW) from radiographs, and pain scores. Results: A total of 140 subjects concluded the 21-month study. Cartilage smoothness provided diagnostic ability in all compartments ( P < 0.0001). The diagnostic smoothness markers performed at least similar to JSW and were superior to volume markers (e.g., the AUC for femoral smoothness of 0.80 was higher than the 0.57 for volume, P < 0.0001, and marginally higher than 0.73 for JSW, P = 0.25). The smoothness markers allowed diagnostic detection of pain presence ( P < 0.05) and showed some correlation with pain severity (e.g., r = −0.32). The longitudinal change in smoothness was correlated with cartilage loss ( r up to 0.60, P < 0.0001 in all compartments). Conclusions: This study demonstrated the potential of cartilage smoothness markers for diagnosis of moderate radiographic OA. Furthermore, correlations between smoothness and pain values and smoothness loss and cartilage loss supported a link to progression of OA. Thereby, smoothness markers may allow detection and monitoring of OA-supplemented currently accepted markers.
Angiostatic and chemotactic activities of the CXC chemokine CXCL4L1 (platelet factor-4 variant) are mediated by CXCR3
Authors: Struyf Sofie , Salogni Laura , Burdick Marie D. , Vandercappellen Jo , Gouwy Mieke , Noppen Sam , Proost Paul , Opdenakker Ghislain , Parmentier Marc , Gerard Craig , Sozzani Silvano , Strieter Robert M. , Van Damme Jo 
Published: October 2010

AbstractWe investigated possible cellular receptors for the human CXC chemokine platelet factor-4 variant/CXCL4L1, a potent inhibitor of angiogenesis. We found that CXCL4L1 has lower affinity for heparin and chondroitin sulfate-E than platelet factor-4 (CXCL4) and showed that CXCL10 and CXCL4L1 could displace each other on microvascular endothelial cells. Labeled CXCL4L1 also bound to CXCR3A- and CXCR3B-transfectants and was displaced by CXCL4L1, CXCL4, and CXCL10. The CXCL4L1 anti-angiogenic activity was blocked by anti-CXCR3 antibodies (Abs) in the Matrigel and cornea micropocket assays. CXCL4L1 application in CXCR3−/− or in wild-type mice treated with neutralizing anti-CXCR3 Abs, resulted in reduced inhibitory activity of CXCL4L1 on tumor growth and vascularization of Lewis lung carcinoma. Furthermore, CXCL4L1 and CXCL4 chemoattracted activated T cells, human natural killer cells, and human immature dendritic cells (DCs). Migration of DCs toward CXCL4 and CXCL4L1 was desensitized by preincubation with CXCL10 and CXCL11, inhibited by pertussis toxin, and neutralized by anti-CXCR3 Abs. Chemotaxis of T cells, natural killer cells, and DCs is likely to contribute to the antitumoral action. However, the in vivo data indicate that the angiostatic property of CXCL4L1 is equally important in retarding tumor growth. Thus, both CXCR3A and CXCR3B are implicated in the chemotactic and vascular effects of CXCL4L1.
Myeloperoxidase attracts neutrophils by physical forces
Authors: Klinke Anna , Nussbaum Claudia , Kubala Lukas , Friedrichs Kai , Rudolph Tanja K. , Rudolph Volker , Paust Hans-Joachim , Schröder Christine , Benten Daniel , Lau Denise , Szocs Katalin , Furtmüller Paul G. , Heeringa Peter , Sydow Karsten , Duchstein Hans-Jürgen , Ehmke Heimo , Schumacher Udo , Meinertz Thomas , Sperandio Markus , Baldus Stephan 
Published: October 2010

AbstractRecruitment of polymorphonuclear neutrophils (PMNs) remains a paramount prerequisite in innate immune defense and a critical cofounder in inflammatory vascular disease. Neutrophil recruitment comprises a cascade of concerted events allowing for capture, adhesion and extravasation of the leukocyte. Whereas PMN rolling, binding, and diapedesis are well characterized, receptor-mediated processes, mechanisms attenuating the electrostatic repulsion between the negatively charged glycocalyx of leukocyte and endothelium remain poorly understood. We provide evidence for myeloperoxidase (MPO), an abundant PMN-derived heme protein, facilitating PMN recruitment by its positive surface charge. In vitro, MPO evoked highly directed PMN motility, which was solely dependent on electrostatic interactions with the leukocyte's surface. In vivo, PMN recruitment was shown to be MPO-dependent in a model of hepatic ischemia and reperfusion, upon intraportal delivery of MPO and in the cremaster muscle exposed to local inflammation or to intraarterial MPO application. Given MPO's affinity to both the endothelial and the leukocyte's surface, MPO evolves as a mediator of PMN recruitment because of its positive surface charge. This electrostatic MPO effect not only displays a so far unrecognized, catalysis-independent function of the enzyme, but also highlights a principal mechanism of PMN attraction driven by physical forces.
How I treat superficial venous thrombosis
Authors: Kitchens Craig S. 
Published: October 2010

Abstract
Thrombosis of superficial veins has long been regarded as a benign disorder. If patients with a clinical diagnosis of superficial venous thrombosis (SVT) are thoroughly evaluated, the degree and extent of thrombosis in patients with SVT are characteristically underestimated (∼ 75% of the time) and such patients have coexistence (∼ 25% of the time) of, and/or rapid progression (∼ 10% of the time) to, systemic venous thromboembolism (VTE). Pulmonary embolism (PE; ∼ 25% of the time) and death (∼ 1% of the time) occur. Contributory risk factors for SVT are the same for VTE. Treatment of patients' SVT with parenteral anticoagulants appears to be both efficacious and certainly safe. I regard most patients with a clinical diagnosis of SVT the same as those with VTEs. Systemic anticoagulant therapy of patients with a clinical diagnosis of SVT obviates extensive imaging and laboratory workup and may be cost effective while encompassing treatment of any unknown concomitant thromboses with only low risk for hemorrhage. This decision is especially clear in those patients with known hypercoagulability. Patients without clinical risk factors are at lower risk to develop VTE complications and might be those who can be simply observed.
Vascular bed–specific regulation of the von Willebrand factor promoter in the heart and skeletal muscle
Authors: Liu Ju , Yuan Lei , Molema Grietje , Regan Erzsébet , Janes Lauren , Beeler David , Spokes Katherine C. , Okada Yoshiaki , Minami Takashi , Oettgen Peter , Aird William C. 
Published: October 2010

AbstractA region of the human von Willebrand factor (VWF) gene between −2812 and the end of the first intron (termed vWF2) was previously shown to direct expression in the endothelium of capillaries and a subset of larger blood vessels in the heart and skeletal muscle. Here, our goal was to delineate the DNA sequences responsible for this effect. A series of constructs containing deletions or mutations of vWF2 coupled to LacZ were targeted to the Hprt locus of mice, and the resulting animals were analyzed for reporter gene expression. The findings demonstrate that DNA sequences between −843 and −620 are necessary for expression in capillary but not large vessel endothelium in heart and skeletal muscle. Further, expression of VWF in capillaries and larger vessels of both tissues required the presence of a native or heterologous intron. In vitro assays implicated a role for ERG-binding ETS motif at −56 in mediating basal expression of VWF. In Hprt-targeted mice, mutation of the ETS consensus motif resulted in loss of LacZ expression in the endothelium of the heart and skeletal muscle. Together, these data indicate that distinct DNA modules regulate vascular bed–specific expression of VWF.