bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lentiviral Nef Proteins Utilize PAK2-Mediated Deregulation of Cofilin as a General Strategy To Interfere with Actin Remodeling
Authors: Stolp Bettina , Abraham Libin , Rudolph Jochen M. , Fackler Oliver T. 
Published: February 2010

ABSTRACT

Nef is an accessory protein and pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) which elevates virus replication
in vivo
. We recently described for HIV type 1
SF2
(HIV-1
SF2
) the potent interference of Nef with T-lymphocyte chemotaxis via its association with the cellular kinase PAK2. Mechanistic analysis revealed that this interaction results in deregulation of the actin-severing factor cofilin and thus blocks the chemokine-mediated actin remodeling required for cell motility. However, the efficiency of PAK2 association is highly variable among Nef proteins from different lentiviruses, prompting us to evaluate the conservation of this actin-remodeling/cofilin-deregulating mechanism. Based on the analysis of a total of 17 HIV-1, HIV-2, and SIV Nef proteins, we report here that inhibition of chemokine-induced actin remodeling as well as inactivation of cofilin are strongly conserved activities of lentiviral Nef proteins. Of note, even for Nef variants that display only marginal PAK2 association
in vitro
, these activities require the integrity of a PAK2 recruitment motif and the presence of endogenous PAK2. Thus, reduced
in vitro
affinity to PAK2 does not indicate limited functionality of Nef-PAK2 complexes in intact HIV-1 host cells. These results establish hijacking of PAK2 for deregulation of cofilin and inhibition of triggered actin remodeling as a highly conserved function of lentiviral Nef proteins, supporting the notion that PAK2 association may be critical for Nef's activity
in vivo
.
Proviruses Selected for High and Stable Expression of Transduced Genes Accumulate in Broadly Transcribed Genome Areas
Authors: Plachý Jiří , Kotáb Jan , Divina Petr , Reinišová Markéta , Šenigl Filip , Hejnar Jiří 
Published: February 2010

ABSTRACT

Retroviruses and retrovirus-derived vectors integrate nonrandomly into the genomes of host cells with specific preferences for transcribed genes, gene-rich regions, and CpG islands. However, the genomic features that influence the transcriptional activities of integrated retroviruses or retroviral vectors are poorly understood. We report here the cloning and characterization of avian sarcoma virus integration sites from chicken tumors. Growing progressively, dependent on high and stable expression of the transduced v-
src
oncogene, these tumors represent clonal expansions of cells bearing transcriptionally active replication-defective proviruses. Therefore, integration sites in our study distinguished genomic loci favorable for the expression of integrated retroviruses and gene transfer vectors. Analysis of integration sites from avian sarcoma virus-induced tumors showed strikingly nonrandom distribution, with proviruses found prevalently within or close to transcription units, particularly in genes broadly expressed in multiple tissues but not in tissue-specifically expressed genes. We infer that proviruses integrated in these genomic areas efficiently avoid transcriptional silencing and remain active for a long time during the growth of tumors. Defining the differences between unselected retroviral integration sites and sites selected for long-terminal-repeat-driven gene expression is relevant for retrovirus-mediated gene transfer and has ramifications for gene therapy.
Regulation of ICP0-Null Mutant Herpes Simplex Virus Type 1 Infection by ND10 Components ATRX and hDaxx
Authors: Lukashchuk Vera , Everett Roger D. 
Published: February 2010

ABSTRACT
Herpes simplex virus type 1 (HSV-1) immediate-early gene product ICP0 activates lytic infection and relieves cell-mediated repression of viral gene expression. This repression is conferred by preexisting cellular proteins and is commonly referred to as intrinsic antiviral resistance or intrinsic defense. PML and Sp100, two core components of nuclear substructures known as ND10 or PML nuclear bodies, contribute to intrinsic resistance, but it is clear that other proteins must also be involved. We have tested the hypothesis that additional ND10 factors, particularly those that are involved in chromatin remodeling, may have roles in intrinsic resistance against HSV-1 infection. The two ND10 component proteins investigated in this report are ATRX and hDaxx, which are known to interact with each other and comprise components of a repressive chromatin-remodeling complex. We generated stable cell lines in which endogenous ATRX or hDaxx expression is severely suppressed by RNA interference. We found increases in both gene expression and plaque formation induced by ICP0-null mutant HSV-1 in both ATRX- and hDaxx-depleted cells. Reconstitution of wild-type hDaxx expression reversed the effects of hDaxx depletion, but reconstitution with a mutant form of hDaxx unable to interact with ATRX did not. Our results suggest that ATRX and hDaxx act as a complex that contributes to intrinsic antiviral resistance to HSV-1 infection, which is counteracted by ICP0.
Is the Extra-territorial Application of the Human Rights Act Really Justified?
Authors: Farrant James 
Published: February 2010

AbstractThe question of whether the Human Rights Act can apply outside the UK has exercised English appellate courts in a number of recent cases. The European Court of Human Rights in Strasbourg has also dealt with the question of extra-territoriality in respect of the European Convention on Human Rights, most notably in the case of Bankovic v Belgium. This article considers whether, as a matter of strict construction, there can be extra-territorial application of the Act and/or the Convention. It goes on to consider some particular circumstances where extra-territorial application has been found, and attempts to set down some principles governing when the courts ought to apply the Act or Convention outside the territory of a High Contracting Party. The article concludes that the existing jurisprudence both at Strasbourg and in the UK strikes a sensible balance between the Convention's regional character and the need to ensure States Parties are accountable for their conduct abroad. This article applauds the Strasbourg and UK courts' importation of relevant principles of public international law in determining the scope and applicability of the rights protected by the Convention.
Pattern of acute induction ofHomer1agene is preserved after chronic treatment with first- and second-generation antipsychotics: effect of short-term drug discontinuation and comparison with Homer1a-interacting genes
Authors: Iasevoli Felice , Ambesi-Impiombato Alberto , Fiore Germano , Panariello Fabio , Muscettola Giovanni , de Bartolomeis Andrea 
Published: February 2010

Homer1a is a glutamate-related gene whose expression is induced by antipsychotics acutely (i.e. 90 min after treatment). Acute Homer1a expression is preserved after prolonged antipsychotic treatments, while the effects of short-term discontinuation after chronic antipsychotic treatment have not yet been assessed. Here, we studied early and long-term effects on gene expression by antipsychotics for Homer1a and other components of glutamatergic synapses.In the first paradigm, we evaluated Homer1a acute expression by single administration of antipsychotics (haloperidol 0.8 mg/kg, ziprasidone 10 and 4 mg/kg, clozapine 15 mg/kg). Haloperidol and ziprasidone induced Homer1a in the striatum. Induction by ziprasidone was dose-dependent. These results suggest that acute Homer1a expression correlates with dopaminergic affinity and motor side effects of antipsychotics. In the second paradigm, we studied antipsychotic-mediated long-term changes in Homer1a and glutamate-related genes. Rats were treated (21 days) with haloperidol 0.8 mg/kg, ziprasidone 4 mg/kg, or vehicle, and then sacrificed at 90 min (early time-point) or 24 h (delayed time-point) after last injection. Gene expression at these two time-points was compared. Homer1a preserved its pattern of expression at the early but not at the delayed time-point. Significant changes were also observed for PSD-95. The results suggest that Homer1a preserves its expression profile after chronic antipsychotics.
Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease
Authors: Zahn Roland C. , Rett Melisa D. , Li Ming , Tang Haili , Korioth-Schmitz Birgit , Balachandran Harikrishnan , White Robert , Pryputniewicz Sarah , Letvin Norman L. , Kaur Amitinder , Montefiori David C. , Carville Angela , Hirsch Vanessa M. , Allan Jonathan S. , Schmitz Jörn E. 
Published: February 2010

AbstractOne of the most puzzling observations in HIV research is the lack of pathogenicity in most nonhuman primate species that are natural hosts of simian immunodeficiency virus (SIV) infection. Despite this, natural hosts experience a level of viremia similar to humans infected with HIV or macaques infected with SIV. To determine the role of adaptive immune responses in viral containment and lack of disease, we delayed the generation of cellular and humoral immune responses by administering anti-CD8– and anti-CD20 lymphocyte–depleting antibodies to sabaeus African green monkeys (Chlorocebus sabaeus) before challenge with SIVsab9315BR. In vivo lymphocyte depletion during primary infection resulted in a brief elevation of viremia but not in disease. Based on the magnitude and timing of SIV-specific CD8+ T-cell responses in the lymphocyte-depleted animals, CD8+ T-cell responses appear to contribute to viral containment in natural hosts. We found no evidence for a contribution of humoral immune responses in viral containment. These studies indicate that natural hosts have developed mechanisms in addition to classic adaptive immune responses to cope with this lentiviral infection. Thus, adaptive immune responses in natural hosts appear to be less critical for viral containment than in HIV infection.
A means to an end: ubiquitination of Mpl
Authors: Tong Wei 
Published: February 2010

Abstract
In this issue of Blood, Saur and colleagues report that ubiquitin-mediated degradation of the Mpl receptor constrains Tpo-mediated cell proliferation, highlighting the importance of the E3 ubiquitin ligase c-Cbl in rapid down-regulation of Tpo/Mpl signaling.
Fungal Secretome Database: Integrated platform for annotation of fungal secretomes
Authors: Choi Jaeyoung , Park Jongsun , Kim Donghan , Jung Kyongyong , Kang Seogchan , Lee Yong-Hwan 
Published: February 2010

Abstract

Background
Fungi secrete various proteins that have diverse functions. Prediction of secretory proteins using only one program is unsatisfactory. To enhance prediction accuracy, we constructed Fungal Secretome Database (FSD).

Description
A three-layer hierarchical identification rule based on nine prediction programs was used to identify putative secretory proteins in 158 fungal/oomycete genomes (208,883 proteins, 15.21% of the total proteome). The presence of putative effectors containing known host targeting signals such as RXLX [EDQ] and RXLR was investigated, presenting the degree of bias along with the species. The FSD's user-friendly interface provides summaries of prediction results and diverse web-based analysis functions through Favorite, a personalized repository.

Conclusions
The FSD can serve as an integrated platform supporting researches on secretory proteins in the fungal kingdom. All data and functions described in this study can be accessed on the FSD web site at http://fsd.snu.ac.kr/.
Mapping main, epistatic and sex-specific QTL for body composition in a chicken population divergently selected for low or high growth rate
Authors: Ankra-Badu Georgina A , Shriner Daniel , Le Bihan-Duval Elisabeth , Mignon-Grasteau Sandrine , Pitel Frédérique , Beaumont Catherine , Duclos Michel J , Simon Jean , Porter Tom E , Vignal Alain , Cogburn Larry A , Allison David B , Yi Nengjun , Aggrey Samuel E 
Published: February 2010

Abstract

Background
Delineating the genetic basis of body composition is important to agriculture and medicine. In addition, the incorporation of gene-gene interactions in the statistical model provides further insight into the genetic factors that underlie body composition traits. We used Bayesian model selection to comprehensively map main, epistatic and sex-specific QTL in an F2 reciprocal intercross between two chicken lines divergently selected for high or low growth rate.

Results
We identified 17 QTL with main effects across 13 chromosomes and several sex-specific and sex-antagonistic QTL for breast meat yield, thigh + drumstick yield and abdominal fatness. Different sets of QTL were found for both breast muscles [Pectoralis (P) major and P. minor], which suggests that they could be controlled by different regulatory mechanisms. Significant interactions of QTL by sex allowed detection of sex-specific and sex-antagonistic QTL for body composition and abdominal fat. We found several female-specific P. major QTL and sex-antagonistic P. minor and abdominal fatness QTL. Also, several QTL on different chromosomes interact with each other to affect body composition and abdominal fatness.

Conclusions
The detection of main effects, epistasis and sex-dimorphic QTL suggest complex genetic regulation of somatic growth. An understanding of such regulatory mechanisms is key to mapping specific genes that underlie QTL controlling somatic growth in an avian model.
Leptin receptor (LEPR) SNP polymorphisms in HELLP syndrome patients determined by quantitative real-time PCR and melting curve analysis
Authors: Várkonyi Tibor , Lázár Levente , Molvarec Attila , Than Nándor Gábor , Rigó János , Nagy Bálint 
Published: February 2010

Abstract

Background
Several studies have shown overexpression of leptin in microarray experiments in pre-eclampsia (PE) and in hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. We decided to study four leptin receptor (LEPR) SNP polymorphisms in HELLP syndrome patients by using quantitative real-time PCR and melting curve analysis.

Methods
DNA was isolated from blood samples from 83 normotensive pregnant women and 75 HELLP syndrome patients. Four SNPs, LEPR c.326A>G (K109), LEPR c.668A>G (Q223R), LEPR c.1968G>C (K656N) and LEPR c.3024A>G (S1008) were determined by quantitative real-time PCR and melting curve analysis. Investigators were blinded to clinical outcomes.

Results

LEPR c.326A>G, LEPR c.668A>G, LEPR c.1968G>C and LEPR c.3024A>G allele, genotype and haplotype polymorphisms were not different in HELLP syndrome patients and normotensive healthy pregnants. There were strong linkage disequilibrium (LD) between loci c.326A>G and c.6687A>G (D' = 0.974), and c.668A>G and c.1968G>C (D' = 0.934), and c.326A>G and c.1968G>C (D' = 0.885), and c.1968G>C and c.3024A>G (D' = 1.0). However, linkages of c.3024A>G with c.668A>G (D' = 0.111) and c.326A>G (D' = 0.398) were weak. The Hardy-Weinberg equilibrium was observed for all polymorphisms. However the LEPR c.326A>G AG genotype was twice more frequent and the (AG AG GG AG) haplotype was three times more frequent in HELLP syndrome patients. The introduced quantitative real-time PCR combined with melting curve analysis is a fast and reliable method for the determination of LEPR SNPs.

Conclusion
Although certain LEPR haplotypes are more frequent in HELLP syndrome, we conclude that there is no compelling evidence that the four studied LEPR SNP polymorphisms associated with the development of HELLP syndrome.
Sequential chemotherapy and intensity-modulated radiation therapy in the management of locoregionally advanced nasopharyngeal carcinoma: Experience of 370 consecutive cases
Authors: Lin Shaojun , Lu Jiade Jay , Han Lu , Chen Qisong , Pan Jianji 
Published: February 2010

Abstract

Introduction
To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) after induction chemotherapy, with or without concomitant chemotherapy.

Methods
Between August 2003 and March 2007, 370 patients with locoregionally advanced NPC were treated with IMRT. Presenting stages were stage IIB in 62, stage III in 197, and stage IVA/B in 111 patients. All patients except for 36 patients with cervical lymphadenopathy of 4 cm or less in diameter received 2 cycles of cisplatin-based neoadjuvant chemotherapy. Forty-eight patients received cisplatin-based concurrent chemotherapy as well.

Results
With a median follow-up time of 31 months (range 5 to 61 months), the 3-year local control, regional control, metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) rates were 95%, 97%, 86%, 81% and 89%, respectively. Multivariate analyses revealed that both age (≤ 60 vs. >60) and N-classification are significant prognosticators for OS (P = 0.001, hazard ratio [HR] 2.395, 95% confidence interval [CI] 1.432-4.003; P = 0.012, hazard ratio [HR] 2.614, 95% confidence interval [CI] 1.235-5.533); And N-classification is the only significant predicative factor for MFS (P = 0.002, [HR] 1.99, 95% CI 1.279-3.098). T-classification and concurrent chemotherapy were not significant prognostic factors for local/regional control, MFS, DFS, or OS. Subgroup analysis revealed that concurrent chemotherapy provided no significant benefit to IMRT in locoregionally advanced NPC, but was responsible for higher rates of grade 3 or 4 acute toxicities (50% vs. 29.8%, P < 0.005). No grade 3 or 4 late toxicity including xerostomia was observed. However, two patients treated with IMRT and neoadjuvant but without concurrent and adjuvant chemotherapy died of treatment related complications.

Conclusion
IMRT following neoadjuvant chemotherapy produced a superb outcome in terms of local control, regional control, MFS, DFS, and OS rates in patients with stage IIB to IVB NPC. Effective treatment strategy is urgently needed for distant control in patients diagnosed with locoregionally advanced NPC.
Antecedents of teenage pregnancy from a 14-year follow-up study using data linkage
Authors: Gaudie Jennifer , Mitrou Francis , Lawrence David , Stanley Fiona J , Silburn Sven R , Zubrick Stephen R 
Published: February 2010

AbstractBackgroundMany western nations continue to have high rates of teenage pregnancies and births, which can result in adverse outcomes for both mother and child. This study identified possible antecedents of teenage pregnancy using linked data from administrative sources to create a 14-year follow-up from a cross-sectional survey.MethodsData were drawn from two sources - the 1993 Western Australian Child Health Survey (WACHS), a population-based representative sample of 2,736 children aged 4 to 16 years (1,374 girls); and administrative data relating to all their subsequent births and hospital admissions. We used weighted population estimates to examine differences between rates for teenage pregnancy, motherhood and abortion. We used Cox proportional hazards regression to model risk for teenage pregnancy.ResultsThere were 155 girls aged less than 20 years at the time of their first recorded pregnancy. Teenage pregnancy was significantly associated with: family type; highest school year completed by primary carer; combined carer income; whether the primary carer was a smoker; and whether the girl herself displayed aggressive and delinquent behaviours. An age-interaction analysis on the association with aggressive and delinquent behaviours found that while girls with aggressive and delinquent behaviours who were older at the time of the survey were at highest risk of teenage pregnancy, there was elevated risk for future teenage pregnancy across all ages.ConclusionsOur findings suggest that interventions to reduce teenage pregnancy rates could be introduced during primary school years, including those that are focused on the prevention and management of aggressive and delinquent behaviour.
Discrepancy between prevalence and perceived effectiveness of treatment methods in myofascial pain syndrome: Results of a cross-sectional, nationwide survey
Authors: Fleckenstein Johannes , Zaps Daniela , Rüger Linda J , Lehmeyer Lukas , Freiberg Florentina , Lang Philip M , Irnich Dominik 
Published: February 2010

Abstract

Background
Myofascial pain is a common dysfunction with a lifetime prevalence affecting up to 85% of the general population. Current guidelines for the management of myofascial pain are not available. In this study we investigated how physicians on the basis of prescription behaviour evaluate the effectiveness of treatment options in their management of myofascial pain.

Methods
We conducted a cross-sectional, nationwide survey with a standardized questionnaire among 332 physicians (79.8% male, 25.6% female, 47.5 ± 9.6 years) experienced in treating patients with myofascial pain. Recruitment of physicians took place at three German meetings of pain therapists, rheumatologists and orthopaedists, respectively. Physicians estimated the prevalence of myofascial pain amongst patients in their practices, stated what treatments they used routinely and then rated the perceived treatment effectiveness on a six-point scale (with 1 being excellent). Data are expressed as mean ± standard deviation.

Results
The estimated overall prevalence of active myofascial trigger points is 46.1 ± 27.4%. Frequently prescribed treatments are analgesics, mainly metamizol/paracetamol (91.6%), non-steroidal anti-inflammatory drugs/coxibs (87.0%) or weak opioids (81.8%), and physical therapies, mainly manual therapy (81.1%), TENS (72.9%) or acupuncture (60.2%). Overall effectiveness ratings for analgesics (2.9 ± 0.7) and physical therapies were moderate (2.5 ± 0.8). Effectiveness ratings of the various treatment options between specialities were widely variant. 54.3% of all physicians characterized the available treatment options as insufficient.

Conclusions
Myofascial pain was estimated a prevalent condition. Despite a variety of commonly prescribed treatments, the moderate effectiveness ratings and the frequent characterizations of the available treatments as insufficient suggest an urgent need for clinical research to establish evidence-based guidelines for the treatment of myofascial pain syndrome.