bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of T-Cell Receptor-Induced Actin Remodeling and Relocalization of Lck Are Evolutionarily Conserved Activities of Lentiviral Nef Proteins
Authors: Rudolph Jochen M. , Eickel Nina , Haller Claudia , Schindler Michael , Fackler Oliver T. 
Published: September 2009

ABSTRACT
Nef, an important pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), elevates virus replication in vivo. Among other activities, Nef affects T-cell receptor (TCR) signaling via several mechanisms. For HIV-1 Nef these include alteration of the organization and function of the immunological synapse (IS) such as relocalization of the Lck kinase, as well as early inhibition of TCR/CD3 complex (TCR-CD3)-mediated actin rearrangements and tyrosine phosphorylation. Although most SIV and HIV-2 Nef alleles (group 2) potently downregulate cell surface TCR-CD3, this activity was lost in the viral lineage that gave rise to HIV-1 and its SIV counterparts (group 1). To address the contribution of TCR-CD3 downregulation to Nef effects on TCR signal initiation, we compared the activities of 18 group 1 and group 2 Nef proteins, as well as SIV Nef mutants with defects in TCR-CD3 downmodulation. We found that alteration of Lck's subcellular localization is largely conserved and occurs independently of actin remodeling inhibition or TCR-CD3 downregulation. Surprisingly, Nef proteins of both groups also strongly reduced TCR-induced actin remodeling and tyrosine phosphorylation on TCR-stimulatory surfaces and TCR-CD3 downmodulation competence by group 2 Nef proteins only slightly elevated these effects. Furthermore, Nef proteins from HIV-1 and SIV reduced conjugation between infected primary human T lymphocytes and Raji B cells and potently prevented F-actin polarization at the IS independently of their ability to downmodulate TCR-CD3. These results establish alterations of early TCR signaling events at the IS, including F-actin remodeling and relocalization of Lck, as evolutionary conserved activities of highly divergent lentiviral Nef proteins.
Mouse Mammary Tumor Virus p75 and p110 CUX1 Transgenic Mice Develop Mammary Tumors of Various Histologic Types
Authors: Cadieux Chantal , Kedinger Valérie , Yao Lu , Vadnais Charles , Drossos Maria , Paquet Marilène , Nepveu Alain 
Published: September 2009

Abstract
The p75 and p110 isoforms of the CUX1 homeodomain protein are overexpressed in breast tumors and cancer cell lines. To assess and compare the ability of these short CUX1 isoforms in driving mammary tumor development, we used site-specific transgenesis into the Hprt locus to generate transgenic mice expressing p75 or p110 CUX1 under the control of the mouse mammary tumor virus-long terminal repeat. We report that mammary tumors developed after a long latency period, and although various histopathologies were observed, the proportion of adenosquamous carcinomas was significantly higher in p75 CUX1 than in p110 CUX1 transgenic mice. Metastasis to the lung was observed in three p75 CUX1 transgenic mice. Comparisons between tumors and adjacent normal mammary glands revealed that transgenes were overexpressed in most but not all tumors, yet in all cases tested, CUX1 DNA binding was increased, suggesting that both higher expression and changes in post-translational modifications can contribute to stimulate transgene activity. Interestingly, higher expression of erbB2 mRNA was seen in most tumors, not only solid carcinomas but also adenosquamous carcinomas, whereas higher expression of various Wnt genes and activation of the β-catenin pathway was observed primarily in adenosquamous carcinomas. Activation of erbB2 expression appeared to represent a cooperating event that occurred independently of CUX1. In contrast, chromatin immunoprecipitation, short hairpin RNA–mediated knockdown, and reporter assays established that CUX1 is involved in the transcriptional regulation of several Wnt genes. Together, these results support the notion that oncogenic activity of CUX1 can facilitate the establishment of a Wnt/β-catenin autocrine loop. [Cancer Res 2009;69(18):7188–97]
Down-regulation of Suppressor of Cytokine Signaling-3 Causes Prostate Cancer Cell Death through Activation of the Extrinsic and Intrinsic Apoptosis Pathways
Authors: Puhr Martin , Santer Frédéric R. , Neuwirt Hannes , Susani Martin , Nemeth Jeffrey A. , Hobisch Alfred , Kenner Lukas , Culig Zoran 
Published: September 2009

Abstract
Suppressor of cytokine signaling-3 (SOCS-3) acts as a negative feedback regulator of the Janus-activated kinase/signal transducers and activators of transcription factors signaling pathway and plays an important role in the development and progression of various cancers. To better understand the role of SOCS-3 in prostate cancer, SOCS-3 expression was down-regulated in DU-145, LNCaP-IL-6+, and PC3 cells by consecutive SOCS-3 small interfering RNA transfections. SOCS-3 mRNA and protein expression as measured by quantitative reverse transcription-PCR and Western blot, respectively, were decreased by ∼70% to 80% compared with controls. We observed a significant decrease in cell proliferation and viability in all SOCS-3–positive cell lines but not in the parental LNCaP cell line, which is SOCS-3 negative. In this study, we show that down-regulation of SOCS-3 leads to an increased cell death in prostate cancer cell lines. We found a considerable increase in the activation of the proapoptotic caspase-3/caspase-7, caspase-8, and caspase-9. A significant up-regulation of cleaved poly(ADP-ribose) polymerase and inhibition of Bcl-2 expression was observed in all SOCS-3–positive cell lines. Overexpression of Bcl-2 could rescue cells with decreased SOCS-3 levels from going into apoptosis. Tissue microarray data prove that SOCS-3 is highly expressed in castration-refractory tumor samples. In conclusion, we show that SOCS-3 is an important protein in the survival machinery in prostate cancer and is overexpressed in castration-resistant tumors. SOCS-3 knockdown results in an increase of cell death via activation of the extrinsic and intrinsic apoptosis pathways. [Cancer Res 2009;69(18):7375–84]
Lower concentrations of thrombin-antithrombin complex (TAT) correlate to higher recanalisation rates among ischaemic stroke patients treated with t-PA
Authors: Fernandez-Cadenas Israel , Mendioroz Maite , Munuera Josep , Alvarez-Sabin José , Rovira Alex , Quiroga Adoracion , Corbeto Natalia , Rubiera Marta , Delgado Pilar , Rosell Anna , Ribó Marc , Molina Carlos A. , Montaner Joan 
Published: September 2009

SummaryAn elevated concentration of the thrombin-antithrombin complex (TAT) has been associated with high mortality rates and poor outcome in ischaemic stroke patients treated with tissue plasminogen activator (t-PA). Moreover, antithrombin drugs have been tested in combination with t-PA in the acute phase of ischaemic stroke to increase treatment efficacy. We aimed to study whether poor outcome associated with TAT among ischaemic stroke patients treated with t-PA could be due to the effects of this complex on recanalisation rates of the middle cerebral artery (MCA) and on haemorrhagic transformation. The TAT levels of 89 patients having a proximal MCA occlusion were measured by ELISA, and the patients were then treated with t-PA. Complete recanalisation was diagnosed by transcranial Doppler (TCD) at 1, 2 and 6 hours post-t-PA infusion and haemorrhagic transformation was identified by computed tomography (CT). Lower levels of TAT were associated with better recanalisation rates at all time-points (1 hour: OR = 24.8 95% CI 1.4–434.8, p = 0.028;2 hours:OR = 6.3 95% CI 1.5–27, p = 0.014; 6 hours: OR = 6.4 95% CI 1.5–26.5, p = 0.011) after adjustment for stroke risk factors. However, no correlation was found between TAT concentration and haemorrhagic transformation. The elevated mortality rates previously observed in patients with high levels of TAT might have been due to revascularisation resistance. Low levels of TAT are not associated with an increase in haemorrhagic complications after t-PA, indicating that the combination of thrombin blockers and t-PA could be a safe and effective treatment for ischaemic stroke in the future.
Utility of 96-well plate aggregometry and measurement of thrombi adhesion to determine aspirin and clopidogrel effectiveness
Authors: Armstrong Paul C. J. , Dhanji Al-Rehan , Truss Nicola J. , Zain Zetty N. M. , Tucker Arthur T. , Mitchell Jane A. , Warner Timothy D. 
Published: September 2009

SummaryAspirin and clopidogrel are key anti-thrombotic therapies. Results from platelet reactivity testing during therapy, have been shown to correlate with future events and would allow for the optimisation of therapy. However, there is little agreement among current tests and there remains a clear clinical need for a universal standardised test. It was the objective of this study to explore the potential of 96-well plate aggregometry as a definitive clinical test of platelet reactivity with respect to aspirin and clopidogrel.A small non-blinded trial of 16 healthy male volunteers assigned to seven days of aspirin (75mg/day) or clopidogrel (75mg/day) therapy. Blood was collected before and on day 7 of treatment. Platelet aggregation was measured using a 96-well plate based aggregation method, and thrombi adhesion measured by colourimetric assay. Platelet agonists used were ADP (0.1–30µM), arachidonic acid (0.03–1.3mM), collagen (0.1–30µg/ml), adrenaline (0.001–100µM), ristocetin (0.2–3mg/ ml),TRAP6 amide (0.130µM) and U46619 (0.130µM). Concentration response curves were constructed to each agonist under the various conditions and used to extract data such as log EC50, Hill slope, and area under the curve. These demonstrated low intraand inter-assay variability and strong discrimination of drug effects.This study demonstrates the ability of the 96-well plate based aggregation and adhesion method to detect and differentiate between stable aspirin and clopidogrel treatment in healthy volunteers.Moreover,this assay marries the ability to test subjects or patients using a range of platelet agonists with more rapidity and ease than the current gold standard platelet assay, traditional light transmission aggregometry, making it a serious alternative assay for use in clinical settings.
C-reactive protein and venous thromboembolism
Authors: Lutsey Pamela L. , Astor Brad C. , Cushman Mary , Folsom Aaron R. 
Published: September 2009

SummaryThe role of inflammation in the causation of venous thromboembolism (VTE) is uncertain. In 10,505 participants of the Atherosclerosis Risk in Communities (ARIC) Study, we assessed the association of the systemic inflammation marker, elevated C-reactive protein (CRP), with incidence of VTE (n=221) over a median of 8.3 years of follow-up. Adjusted for age, race, and sex, the hazard ratios of VTE across quintiles of CRP were 1.0, 1.61, 1.16, 1.56, and 2.31 (p for trend p<0.0007). For CRP above the upper 10 percentile (≥8.55 mg/L), compared with the lowest 90% of CRP values, the hazard ratio of VTE was 2.07 (95% CI 1.47, 2.94). Further adjustment for baseline hormone replacement therapy, diabetes, and body mass index attenuated the hazard ratios only slightly. For example, the adjusted hazard ratio of VTE was 1.76 (95% CI 1.23, 2.52) for CRP above versus below the 90th percentile. In conclusion, this prospective, populationbased study suggests elevated CRP is independently associated with increased risk of VTE.
Food Sovereignty – An Appropriate Approach to Ensure the Right to Food?
Authors: Haugen Hans Morten 
Published: September 2009

AbstractThe article reviews the food sovereignty concept, comparing it with the legally recognised human right to food. It is found that there are certain elements of Article 11(2) of the International Covenant on Economic, Social and Cultural Rights which have not been properly emphasised in the context of food trade and new technologies in food production. The article argues in favour of strengthening the right to food approach when faced with these challenges. While acknowledging the mobilising potential that the concept food sovereignty has among civil society actors, it is nevertheless argued that the right to food is both more precise, has stronger support among states, and is on a much higher level with regard to legally binding obligations compared to the food sovereignty concept.
Judicial Review of UN Sanctions by the European Court of Justice
Authors: Lavranos Nikolaos 
Published: September 2009

AbstractWith its Kadi-judgment, the European Court of Justice firmly rejected the Kadi/Yusuf-judgments of the Court of First Instance. The Court of Justice made unambiguously clear that Community law, in particular its basic, core fundamental rights values prevail over any international law obligations of the EC and its Member States, including UN Security Council Resolutions and the UN Charter. As a consequence thereof, individuals targeted by UN sanctions must have access to full judicial review in order to be able to ensure the effective protection of their fundamental rights, including procedural rights as guaranteed by the European Convention of Human Rights (ECHR). As a result, the Court of Justice proved that the Community is indeed based on the rule of law and that the fight against terrorism – how important it may be – cannot be used as a justification for completely abrogating European constitutional law values as guaranteed within the Community and its Member States.
The International Criminal Court and the Warrant of Arrest for Sudan's President Al-Bashir: A Crucial Step Towards Challenging Impunity or a Political Decision?
Authors: Ssenyonjo Manisuli 
Published: September 2009

AbstractOn 4 March 2009 the Pre-Trial Chamber I of the International Criminal Court (ICC) held that it was satisfied that there were reasonable grounds to believe that Omar Hassan Ahmad Al Bashir, the president of Sudan, is criminally responsible under Article 25(3)(a) of the Rome Statute as an indirect (co)perpetrator for war crimes and crimes against humanity (but not for genocide). The Chamber issued a warrant for the arrest of Al Bashir making him the third sitting head of state to be charged by an international court following Liberia's Charles Taylor and Yugoslavia's Slobodan Milošević. Since then the ICC has been accused of making a "political decision" and that it is "part of a new mechanism of neo-colonialism". This article examines the ICC's decision against the background of the situation in Darfur. The article concludes that although the ICC decision and warrant cannot be considered political and neo-colonial in nature, the decision and warrant can be criticised as selective. It calls on the ICC to broaden its scope of investigations and for the international community to affirm its support for the ICC and insist that Sudan and other states cooperate fully as required by the United Nations Security Council.
Private International Law Aspects of the Introduction of Same-Sex Marriages in Sweden
Authors: Bogdan Michael 
Published: September 2009

AbstractOn 1 May 2009, Swedish law was amended in order to allow regular marriages between two persons of the same gender. While this reform was relatively simple from the point of view of Swedish family law, it gives rise to a number of questions concerning private international law, mainly because the large majority of foreign countries do not, and within foreseeable future will not, permit such marriages.
A Clinical Comparison of Screw and Suture Fixation of Anterior Cruciate Ligament Tibial Avulsion Fractures
Authors: Seon Jong Keun , Park Sang Jin , Lee Keun Bae , Gadikota Hemanth R. , Kozanek Michal , Oh Luke S. , Hariri Sanaz , Song Eun Kyoo 
Published: September 2009

Background Screw and suture fixations are the most commonly used methods of fixation in treatment of anterior cruciate ligament tibial avulsion fractures. Even though a few biomechanical studies have compared the stability of the 2 fixation techniques, a clinical comparison has not yet been reported. Hypothesis The authors hypothesized that both fixations would be identical in all studied clinical outcome measures at a minimum 2-year follow-up. Study Design Cohort study; Level of evidence, 3. Materials and Methods Thirty-three patients treated with either screw fixation (16 patients) or suture fixation (17 patients) within 1 month of the anterior cruciate ligament tibial avulsion fracture (type II or III) without associated ligamentous injury were included. All patients were evaluated at a minimum 2-year follow-up in terms of Lysholm knee scores and return to preinjury activities. Knee stability was compared based on the Lachman test and stress radiography. Results No significant differences were found between the 2 groups in terms of average Lysholm knee scores (91.7 in the screw group and 92.7 in the suture group, P = .413) at follow-up. All patients except 2 (1 in each group) returned to preinjury activity levels. However, flexion contractures (5° to 10°) were found in 3 patients in the screw group and 2 patients in the suture group without significant intergroup difference. Stabilities based on the Lachman test and instrumented stress radiography were also similar between the 2 groups at follow-up. However, 2 patients in the screw group and 1 in the suture group showed more than 5 mm laxity compared with the contralateral knee on stress radiographs. Conclusion Both the screw and suture fixation techniques for the anterior cruciate ligament tibial avulsion fracture produced relatively good results in terms of functional outcomes and stability without any significant differences. However, some patients in both groups showed residual laxity or flexion contractures.
The Landing Error Scoring System (LESS) Is a Valid and Reliable Clinical Assessment Tool of Jump-Landing Biomechanics
Authors: Padua Darin A. , Marshall Stephen W. , Boling Michelle C. , Thigpen Charles A. , Garrett William E. , Beutler Anthony I. 
Published: September 2009

Background Anterior cruciate ligament injuries are common in athletes and have serious sequelae. A valid clinical tool that reliably identifies individuals at an increased risk for ACL injury would be highly useful for screening sports teams, because individuals identified as “high-risk” could then be provided with intensive prevention programs. Hypothesis A clinical screening tool (the Landing Error Scoring System, or LESS) will reliably identify subjects with potentially high-risk biomechanics. Study Design Cohort study (Diagnosis); Level of evidence, 2. Methods A jump-landing-rebound task was used. Off-the-shelf camcorders recorded frontal and sagittal plane views of the subject performing the task. The LESS was scored from replay of this video. Three-dimensional lower extremity kinematics and kinetics were also collected and used as the gold standard against which the validity of the LESS was assessed. Three trials of the jump-landing task were collected for 2691 subjects. Kinematic and kinetic measures were compared across LESS score quartiles using 1-way analysis of variance; LESS quartiles were compared across genders using the chi-square test. The LESS scores from a subset of 50 subjects were rescored to determine intrarater and interrater reliability. Results Subjects with high LESS scores (poor jump-landing technique) displayed significantly different lower extremity kinematics and kinetics compared with subjects with low LESS scores (excellent jump-landing technique). Women had higher (worse) LESS scores than men. Intrarater and interrater reliability of the LESS ranged from good to excellent. Conclusion The LESS is a valid and reliable tool for identifying potentially high-risk movement patterns during a jump-landing task.
Balancing Mechanisms of Distortion to Yield Distortion-free/Shape Stable Composites
Authors: Radford D.W. 
Published: September 2009

The underlying mechanisms of manufacturing distortion in composite components have been suggested to be anisotropy, material property gradients, and part-tool interactions. These mechanisms have been sub-divided into those that result in shape change with changing temperature (thermoelastic) and those that are one-time-only effects (non-thermoelastic), generally related to isothermal cure shrinkage. The responses related to anisotropy and material property gradient mechanisms are predicted to include both thermoelastic and non-thermoelastic contributions; however, stresses imposed on the laminate and the resulting distortion due to part—tool interaction is merely non-thermoelastic in nature. Previous research has suggested that this non-thermoelastic component is critical to generating a composite angle bracket on net-shape tooling that is simultaneously distortion-free and shape-stable with temperature. The current research investigates the degree of tailorability available in both the part—tool interaction and in the thermoelastic response to local corner asymmetry. Autoclave-cured angle brackets were produced with variations in the local stacking sequence in the corner to balance the thermoelastic contributions and with different mold releases to affect the stress transferred from the tool to the part. Two asymmetric stacking sequences are compared to the baseline symmetric laminate. The fraction of the corner radius that is made up of these regions of asymmetry is also adjusted to vary the thermoelastic effect. Mold release variations are investigated to evaluate the effect of changing levels of non-thermoelastic distortion. To measure the response, the curvatures of flat composite laminates are measured using an LVDT-based panel measurement technique, which enables measurement of changing curvature with temperature. The included angle of various composite angle bracket specimens is also measured as a function of temperature, using a laser reflection technique. The results of this testing indicate that tailoring of both non-thermoelastic and thermoelastic components of process-induced distortion can be accomplished. The balancing of the compensation of these effects is shown to result in an angle bracket specimen, which has very little distortion and is much more stable with temperature than the baseline laminate. Further, it is found that the variation in laminate stiffness with changing local laminate stacking sequence plays an important role in the tailoring of the distortion of this geometry. Overall, the results of the research point very clearly to a methodology for the composites engineer to tailor the laminate, and the process, to generate a distortion-free/shape stable angle bracket molded on net-shape tooling.