Two-long terminal repeat (LTR) DNA circles are a substrate for HIV-1 integrase.

Integration of the HIV-1 DNA into the host genome is essential for viral replication and is catalyzed by the retroviral integrase. To date, the only substrate described to be involved in this critical reaction is the linear viral DNA produced in reverse transcription. However, during HIV-1 infection, two-long terminal repeat DNA circles (2-LTRcs) are also generated through the ligation of the viral DNA ends by the host cell's nonhomologous DNA end-joining pathway.

Category-Specific Visual Recognition and Aging from the PACE Theory Perspective: Evidence for a Presemantic Deficit in Aging Object Recognition.

Unlabelled: Background/Study Context: The objective of this study was to investigate the object recognition deficit in aging. Age-related declines were examined from the presemantic account of category effects (PACE) theory perspective (Gerlach, 2009, Cognition, 111, 281-301). This view assumes that the structural similarity/dissimilarity inherent in living and nonliving objects, respectively, can account for a wide range of category-specific effects.

The MAP3K ZAK, a novel modulator of ERK-dependent migration, is upregulated in colorectal cancer.

Often described as a mediator of cell cycle arrest or as a pro-apoptotic factor in stressful conditions, the MAP3K ZAK (Sterile alpha motif and leucine zipper-containing kinase) has also been proven to positively regulate epidermal growth factor receptor (EGFR) and WNT signaling pathways, cancer cell proliferation and cellular neoplastic transformation. Here, we show that both isoforms of ZAK, ZAK-α and ZAK-β are key factors in cancer cell migration. While ZAK depletion reduced cell motility of HeLa and HCT116 cells, its overexpression triggered the activation of all three mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK) and p38, as well as an increase in cell motion.

DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity.

Retroviral integrases (INs) catalyse the integration of the reverse transcribed viral DNA into the host cell genome. This process is selective, and chromatin has been proposed to be a major factor regulating this step in the viral life cycle. However, the precise underlying mechanisms are still under investigation.

ST1926, an orally active synthetic retinoid, induces apoptosis in chronic myeloid leukemia cells and prolongs survival in a murine model.

The tyrosine kinase inhibitor, imatinib, is the first line of treatment for chronic myeloid leukemia (CML) patients. Unfortunately, patients develop resistance and relapse due to bcr-abl point mutations and the persistence of leukemia initiating cells (LIC). Retinoids regulate vital biological processes such as cellular proliferation, apoptosis, and differentiation, in particular of hematopoietic progenitor cells.

Large-scale imatinib dose-concentration-effect study in CML patients under routine care conditions.

This observational study analyzed imatinib pharmacokinetics and response in 2478 chronic myeloid leukemia (CML) patients. Data were obtained through centralized therapeutic drug monitoring (TDM) at median treatment duration of ≥ 2 years. First, individual initial trough concentrations under 400mg/day imatinib starting dose were estimated.

Management of upper respiratory tract infections by different medical practices, including homeopathy, and consumption of antibiotics in primary care: the EPI3 cohort study in France 2007-2008.

Background: Prescribing of antibiotics for upper respiratory tract infections (URTI) varies substantially in primary care.

Objectives: To describe and compare antibiotic and antipyretic/anti-inflammatory drugs use, URTI symptoms' resolution and occurrence of potentially-associated infections in patients seeking care from general practitioners (GPs) who exclusively prescribe conventional medications (GP-CM), regularly prescribe homeopathy within a mixed practice (GP-Mx), or are certified homeopathic GPs (GP-Ho).

Method: The EPI3 survey was a nationwide population-based study of a representative sample of 825 GPs and their patients in France (2007-2008).

Contextual and behavioral influences on uncertainty in obsessive-compulsive disorder.

Introduction: Behavioral adaptation generally follows the contextual changes arising from the consequences (rewards and punishments) of an action. According to the reciprocal determinism model, there is a mutual influence between external context, cognitive processes and behavior. The maladaptive behaviors observed in obsessive-compulsive disorder (OCD) have been hypothesized to result from the disruption of the interactions between these three entities.

Evaluation of antiproliferative and anti-inflammatory activities of methanol extract and its fractions from the Mediterranean sponge.

Background: Without doubt, natural products have been, and still are, the cornerstone of the health care armamentarium. Of all natural sources, the marine environment is clearly the last great frontier for pharmaceutical and medical research.

Methods: This work progresses in the direction of identifying component(s) from the Mediterranean sponge, Spongia officinalis with pharmacological activities.

Two-dimensional blue native/SDS gel electrophoresis of multiprotein complexes.

The two-dimensional blue native/sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D BN/SDS-PAGE) is a method of choice for the investigation of protein complexes. This highly resolvent separation method is unique in that it facilitates the identification of many protein complexes simultaneously. Because of its simplicity and suitability, the 2D BN/SDS-PAGE can be now applied to a wide range of organisms, including bacteria, viruses, yeasts, animals, and plants.

Rapid nanoscale quantitative analysis of plant sphingolipid long-chain bases by GC-MS.

In eukaryotic organisms, sphingolipids are major structural lipids of biological membranes and perform additional essential functions as signalling molecules. While long-chain bases (LCB), the common precursor to all sphingolipid classes, is represented by only one major molecular species in animals and fungi, up to nine LCB have been found in plants. In the absence of genuine plant sphingolipid references required for proper quantification, we have reinvestigated and optimized a protocol destined to the quantification of total plant LCB that relies on the use of gas chromatography-mass spectrometry (GC-MS).

Contemporary body armor: technical data, injuries, and limits.

The introduction of firearms in the fifteenth century led to the continuous development of bulletproof personal protection. Due to recent industrial progress and the emergence of a new generation of ballistic fibers in the 1960s, the ability of individual ballistic protections to stop projectiles greatly increased. While protective equipment is able to stop increasingly powerful missiles, deformation during the impact can cause potentially lethal nonpenetrating injuries that are grouped under the generic term of behind armor blunt trauma, and the scope and consequences of these are still unclear.

Molecular characterization of HIV-1 CRF01_AE in Mekong Delta, Vietnam, and impact of T-cell epitope mutations on HLA recognition (ANRS 12159).

Background: To date, 11 HIV-1 subtypes and 48 circulating recombinant forms have been described worldwide. The underlying reason why their distribution is so heterogeneous is not clear. Host genetic factors could partly explain this distribution.

Occupational and residential exposure to electromagnetic fields and risk of brain tumors in adults: a case-control study in Gironde, France.

The etiology of brain tumors remains largely unknown. Among potential risk factors, exposure to electromagnetic fields is suspected. We analyzed the relationship between residential and occupational exposure to electromagnetic field and brain tumors in adults.

Mutation rate switch inside Eurasian mitochondrial haplogroups: impact of selection and consequences for dating settlement in Europe.

R-lineage mitochondrial DNA represents over 90% of the European population and is significantly present all around the planet (North Africa, Asia, Oceania, and America). This lineage played a major role in migration "out of Africa" and colonization in Europe. In order to determine an accurate dating of the R lineage and its sublineages, we analyzed 1173 individuals and complete mtDNA sequences from Mitomap.

Accurate determination of the oxidative phosphorylation affinity for ADP in isolated mitochondria.

Background: Mitochondrial dysfunctions appear strongly implicated in a wide range of pathologies. Therefore, there is a growing need in the determination of the normal and pathological integrated response of oxidative phosphorylation to cellular ATP demand. The present study intends to address this issue by providing a method to investigate mitochondrial oxidative phosphorylation affinity for ADP in isolated mitochondria.

Validation of a specific health-related quality of life instrument in a large cohort of patients with psoriasis: the QualiPso Questionnaire.

The aim of this study was to develop and validate a standardized tool designed to assess health-related quality of life (HRQoL) in a large cohort of French patients with psoriasis, the QualiPso Questionnaire. A draft questionnaire was developed based on a literature review, followed by one-to-one interviews of 50 patients with psoriasis conducted by trained psychologists. The interview transcripts were analysed, after which 56 items were retained and validated in a cohort of 569 patients.

Quantitative analysis of erythropoietin in human plasma by tandem mass spectrometry.

The extended use of protein drugs in therapeutics has created the need for their quantification in human plasma. A methodology using the therapeutic protein itself as internal standard for quantitative analysis by multiple reaction monitoring (MRM) has been designed and applied to epoetin beta, a recombinant human erythropoietin (rhEPO). After depletion of major proteins, plasma samples were desalted and enriched in rhEPO by reversed phase liquid chromatography prior to tryptic cleavage.

Brain tumors and hormonal factors: review of the epidemiological literature.

Background: To date, the etiology of primary tumors of the central nervous system (mainly gliomas and meningiomas) is poorly understood. The role of sex hormones has been suggested, based on clinical, experimental, biological, and epidemiological data.

Objective: To review the epidemiological studies on the relation between hormonal factors and the occurrence of glioma and meningioma, in order to identify new research developments.

Strategy selection and aging: impact of item concreteness in paired-associate task.

The aim of this study was to examine the effect of aging on strategy selection in a paired-associate word task. Twenty-eight younger adults (mean age = 20.68 years) and 28 older adults (mean age = 68.

Effects of antibiotics on Chlamydia trachomatis viability as determined by real-time quantitative PCR.

The objective of this study was to determine the effect of antibiotics on Chlamydia trachomatis viability by using a quantitative real-time PCR assay that measured DNA replication and mRNA transcription of the structural omp1 and omp2 genes, 16S rRNA and the groEL1 gene with and without antibiotics. Ofloxacin, moxifloxacin, azithromycin and doxycycline were tested against the serovar D and L2 reference strains and a derivative mutant resistant to fluoroquinolones, L2-OFXR, obtained by in vitro selection. Using DNA quantification, the antibiotic MIC was calculated when the number of DNA copies was equal to that of the chlamydial inoculum at time zero.

Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares: an observational cohort study.

Introduction: The aim of this study was to determine whether mycophenolate mofetil (MMF) pharmacokinetics (PK) under combined MMF and prednisone remission-maintenance therapy can predict systemic lupus erythematosus (SLE) clinical flares.

Methods: At inclusion, steady-state PK parameters of the MMF active form, mycophenolic acid (MPA), and its glucuronide metabolite (MPAG) were determined for 25 stable SLE patients without renal manifestations. Disease activity was assessed during 6 months of follow-up.

The pharmacogenetics of imanitib.

Imatinib mesylate (IM), a tyrosine kinase inhibitor, is one of the first molecularly targeted therapies to have been used in the clinic. It has proven to be efficient in the treatment of chronic myeloid leukemia and also in other malignancies that involve expression of a tyrosine kinase. However, some patients can develop resistance and others suffer from toxic side effects.

High resolution mapping of OCA2 intragenic rearrangements and identification of a founder effect associated with a deletion in Polish albino patients.

Oculocutaneous albinism type 2 (OCA2) represents about 30% of OCA worldwide. Using quantitative multiplex fluorescent PCR and very high-resolution array-CGH focussed on the OCA2 gene and surrounding regions in 15q12, we identified new rearrangements. Deletion 1, encompassing exons 3-20, was present in three patients (including one in the homozygous state), and Deletion 2 (exons 1-20) was found in one patient (heterozygous state).