Phylogeographic and genome-wide investigations of Vietnam ethnic groups reveal signatures of complex historical demographic movements.

The territory of present-day Vietnam was the cradle of one of the world's earliest civilizations, and one of the first world regions to develop agriculture. We analyzed the mitochondrial DNA (mtDNA) complete control region of six ethnic groups and the mitogenomes from Vietnamese in The 1000 Genomes Project (1000G). Genome-wide data from 1000G (~55k SNPs) were also investigated to explore different demographic scenarios.

Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor.

Serum stimulation of mammalian cells induces, via the MAPK pathway, the nuclear protein DUSP5 (dual-specificity phosphatase 5), which specifically interacts with and inactivates the ERK1/2 MAP kinases. However, molecular mechanisms underlying DUSP5 induction are not well known. Here, we found that the DUSP5 mRNA induction depends on a transcriptional regulation by the MAPK pathway, without any modification of the mRNA stability.

[The United Nations conventions on the rights of persons with disabilities: which strategies for protection at work?].

More than 15% of the world's population lives with some form of moderate or severe disabilities, a growing percentage due to aging population as well as to the global increase of chronic diseases. The United Nations approved, in December 2006, the "Convention on the Rights of Persons with Disabilities" which dealt with the theme "work and employment". It prohibited discrimination on the grounds of disability with regard to health and safety at work, ensuring safe and healthy working conditions including protection from harassment.

Typing short amplicon binary polymorphisms: supplementary SNP and Indel genetic information in the analysis of highly degraded skeletal remains.

Two sets of short amplicon binary markers (SABs): 50 single nucleotide polymorphisms (SNPs) and 38 insertion/deletion polymorphisms (Indels) were used to genotype bones of 35 years "post-mortem". Typing results of these binary markers were compared with those obtained for standard commercial STR and mini-STR DNA typing kits. We observed SAB marker performance to be better compared with conventional STR and mini-STR genotyping in degraded bone sample analysis.

The impact of modern migrations on present-day multi-ethnic Argentina as recorded on the mitochondrial DNA genome.

Background: The genetic background of Argentineans is a mosaic of different continental ancestries. From colonial to present times, the genetic contribution of Europeans and sub-Saharan Africans has superposed to or replaced the indigenous genetic 'stratum'. A sample of 384 individuals representing different Argentinean provinces was collected and genotyped for the first and the second mitochondrial DNA (mtDNA) hypervariable regions, and selectively genotyped for mtDNA SNPs.

Indirect participation of Hsp90 in the regulation of the cyclin E turnover.

Cyclin E is the Cdk2-regulatory subunit required for the initiation of DNA replication at the G1/S transition. It accumulates in late G1 phase and gets rapidly degraded by the ubiquitin/proteasome pathway during S phase. The degradation of cyclin E is a consequence of its phosphorylation and subsequent isomerization by the peptidyl-prolyl isomerase Pin1.

Antiproliferative and apoptotic activities of tosylcyclonovobiocic acids as potent heat shock protein 90 inhibitors in human cancer cells.

We evaluated whether inhibition of heat shock protein 90 (hsp90) function by novobiocin derivatives could induce the degradation of signal transducers that drive cancer cell growth and thereby promote apoptosis. Removal of the noviose moiety in novobiocin and introduction of a tosyl substituent at C-4 or C-7 coumarin nucleus provided derivatives 4TCNA and 7TCNA which compared favourably with novobiocin in MCF-7 breast cancer cells. Here we extend the antiproliferative and apoptotic properties of these analogues to a panel of cancer cell lines.

Reversal of glucocorticoids-dependent proopiomelanocortin gene inhibition by leukemia inhibitory factor.

We previously have described molecular mechanisms converging at the Nur response element-signal transducer and activator of transcription (STAT) composite site responsible for synergistic activation of the proopiomelanocortin (POMC) gene promoter by leukemia inhibitory factor (LIF) and CRH. In this study, we asked how glucocorticoids (GC), the physiological negative regulators of POMC gene expression, modulate this synergism. In the corticotroph cell line AtT-20, the response of the wild-type promoter to LIF+CRH was barely inhibited by GC, whereas a distal promoter subregion (-414/-293) encompassing the Nur response element-STAT site and devoid of the negative GC-responsive element located in the proximal domain, displayed a cooperative response to LIF+dexamethasone (DEX) and LIF+CRH+DEX treatments.

Reduced hemodynamic responses to physical and mental stress under low-dose rilmenidine in healthy subjects.

Activation of the sympathetic nervous system plays a major role in the pathogenesis and prognosis of cardiovascular diseases. Rilmenidine is an I(1)-imidazoline receptor agonist that reduces blood pressure by modulation of central sympathetic activity, but the effects of low-dose rilmenidine on the hemodynamic responses to physiological maneuvers that increase adrenergic drive is not known. To assess the effects of low-dose rilmenidine on the hemodynamic responses to stress, 32 healthy subjects (20-56 years old) underwent acute physical exercise (n = 15, individualized ramp protocol on treadmill) and mental stress (n = 17, word color Stroop and mental arithmetics tests) two hours after the oral administration of 0.

Synergistic signaling by corticotropin-releasing hormone and leukemia inhibitory factor bridged by phosphorylated 3',5'-cyclic adenosine monophosphate response element binding protein at the Nur response element (NurRE)-signal transducers and activators of transcription (STAT) element of the proopiomelanocortin promoter.

Leukemia inhibitory factor (LIF) cooperates with CRH at the pituitary level to induce POMC gene transcription, resulting in activation of the pituitary-adrenal axis. However, the underlying molecular mechanisms remain elusive. Here, we show that the NurRE-signal transducers and activators of transcription (STAT) composite element of the POMC promoter was the predominant target of the LIF-CRH synergy.

Protective effects of centrally acting sympathomodulatory drugs on myocardial ischemia induced by sympathetic overactivity in rabbits.

It is recognized that an imbalance of the autonomic nervous system is involved in the genesis of ventricular arrhythmia and sudden death during myocardial ischemia. In the present study we investigated the effects of clonidine and rilmenidine, two centrally acting sympathomodulatory drugs, on an experimental model of centrally induced sympathetic hyperactivity in pentobarbital-anesthetized New Zealand albino rabbits of either sex (2-3 kg, N = 89). We also compared the effects of clonidine and rilmenidine with those of propranolol, a beta-blocker, known to induce protective cardiovascular effects in patients with ischemic heart disease.

Different mechanisms for leukemia inhibitory factor-dependent activation of two proopiomelanocortin promoter regions.

To better understand how leukemia inhibitory factor (LIF) activates proopiomelanocortin (POMC) gene transcription in pituitary corticotrophs, time-course studies of the induction of POMC promoter activity and specific tyrosine phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 were performed. It was found that both phosphorylation of STAT1 and -3 and activation of the promoter activity rapidly and transiently take place within minutes and 2-6 h, respectively, in favor of a direct effect of the LIF pathway on POMC promoter. Activated STAT1 and -3 form homo-/heterodimers able to bind the Sis-inducible element.

The N-terminal adenosine triphosphate binding domain of Hsp90 is necessary and sufficient for interaction with estrogen receptor.

To understand how the molecular chaperone Hsp90 participates in conformational maturation of the estrogen receptor (ER), we analyzed the interaction of immobilized purified avian Hsp90 with mammalian cytosolic ER. Hsp90 was either immunoadsorbed to BF4 antibody-Sepharose or GST-Hsp90 fusion protein (GST.90) was adsorbed to glutathione-Sepharose.

Binding of ATP to heat shock protein 90: evidence for an ATP-binding site in the C-terminal domain.

The presence of a nucleotide binding site on hsp90 was very controversial until x-ray structure of the hsp90 N-terminal domain, showing a nonconventional nucleotide binding site, appeared. A recent study suggested that the hsp90 C-terminal domain also binds ATP (Marcu, M. G.

Cardiovascular effects of chronic ifenprodil in a model of central sympathetic stimulation.

In the present study we investigated the effects of a long-term treatment (14 days) with ifenprodil on the excitatory haemodynamic responses induced by central pharmacological stimulation in anaesthetised rabbits. The intracerebroventricular injection of L-glutamate (3 mg/kg) induced important rises in dP/dtmax (32.9%), mean arterial pressure (42.

Dimerization and N-terminal domain proximity underlie the function of the molecular chaperone heat shock protein 90.

Heat shock protein (hsp)90 functions in a complex chaperoning pathway where its activity is modulated by ATP and by interaction with several co-chaperones. One co-chaperone, p23, binds selectively to the ATP-bound state of hsp90. However, the isolated ATP-binding domain of hsp90 does not bind p23.

The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone.

Heat shock protein 90 (Hsp90), one of the most abundant chaperones in eukaryotes, participates in folding and stabilization of signal-transducing molecules including steroid hormone receptors and protein kinases. The amino terminus of Hsp90 contains a non-conventional nucleotide-binding site, related to the ATP-binding motif of bacterial DNA gyrase. The anti-tumor agents geldanamycin and radicicol bind specifically at this site and induce destabilization of Hsp90-dependent client proteins.

Hsp90 chaperone activity requires the full-length protein and interaction among its multiple domains.

Hsp90 is an abundant and ubiquitous protein involved in a diverse array of cellular processes. Mechanistically we understand little of the apparently complex interactions of this molecular chaperone. Recently, progress has been made in assigning some of the known functions of hsp90, such as nucleotide binding and peptide binding, to particular domains within the protein.

[Functional interaction of HSP90 with steroid receptors].

Hsp90 (Heat Shock Protein 90) is a component of the inactive and metastable hetero-oligomeric structure of steroid receptors. Recent data on Hsp90 structure and function as a stress protein and dedicated molecular chaperone are here reviewed with a particular focus on Hsp90 chaperone cycle interfering with steroid receptor action. The dual role of Hsp90 as a positive and negative modulator of steroid receptor function is considered along the activation-desactivation process of the receptors.

Presence of an aromatase inhibitor, possibly heat shock protein 90, in dominant follicles of cattle.

In cattle, it has been suggested that follicular fluid has direct modulatory effects on follicular growth and maturation. In the first part of this study, an in vitro test using aromatase activity of follicular wall fragments as an end point was validated for cattle follicles and was used to test whether follicular fluid (from dominant or non-dominant follicles) modulates aromatase activity. Fluid from dominant follicles at a concentration of 24 or 12% (obtained during the luteal and follicular phases, respectively) significantly inhibited aromatase activity.

Delimitation of two regions in the 90-kDa heat shock protein (Hsp90) able to interact with the glucocorticosteroid receptor (GR).

The role of the 90-kDa heat shock protein (Hsp90) as a chaperone and its regulatory functions for cellular proteins such as the glucocorticosteroid receptor (GR) depends on the direct interaction of the Hsp90 with the corresponding protein as part of a multiprotein complex. The search for the amino acid sequence(s) in Hsp90 involved in interaction with the human GR has been carried out by mutational deletion analysis in whole cells, studying the effects of interaction on the nucleocytoplasmic distributions of transiently expressed Hsp90 and GR derivatives in COS-7 cells. Using a recently developed confocal microscopic immunofluorescence method that allows quantification of the nucleocytoplasmic ratios of the proteins in individual cells and statistical comparison of cell populations, two subregions of the Hsp90 molecule have been defined that allow interaction with GR (residues 206-291 and 446-581).

The molecular chaperone Hsp90 can negatively regulate the activity of a glucocorticosteroid-dependent promoter.

Hsp90, a molecular chaperone required for the functioning of glucocorticosteroid receptor (GR), ensures, by direct interaction, the conformational competence of the steroid-binding pocket. In addition to having this positive function, Hsp90 maintains steroid receptors in an inactive form in the absence of hormone. However, neither the participation of Hsp90 once the pathway has been activated by the ligand nor the importance of increased Hsp90 levels in determining the amplitude of the response has ever been assessed directly.

Heat-induced oligomerization of the molecular chaperone Hsp90. Inhibition by ATP and geldanamycin and activation by transition metal oxyanions.

It has been previously reported that heat shock protein 90 (Hsp90) oligomerizes at high temperatures and displays concomitantly a novel chaperone activity (Yonehara, M., Minami, Y., Kawata, Y.

Luciferase activity and synthesis of Hsp70 and Hsp90 are insensitive to 50Hz electromagnetic fields.

The activity of luciferase expressed in transfected 34i cells has been monitored under 50Hz EMF and heat shock. While heat shock decreased the luciferase activity, short exposure to EMFs did not, the luciferase expressed in cells exposed to EMFs at 300-3000 microT showing the same activity as that of control cells. To further analyse whether EMF and thermal stress display similar effects, the relative rate of Hsp90 and Hsp70 synthesis was investigated.

Quantification of the nucleocytoplasmic distribution of wild type and modified proteins using confocal microscopy: interaction between 90-kDa heat shock protein (Hsp90 alpha) and glucocorticosteroid receptor (GR).

The investigation of molecular interactions in whole cells by immunofluorescence was developed recently, based on the targeting of the protein partners to different cellular compartments and analysis of the modifications in their subcellular distribution resulting from their interaction. This paper describes the adaptation of the confocal microscopy to the quantification of the partitioning of transiently coexpressed proteins between nucleus and cytoplasm. We defined a nucleocytoplasmic ratio R, corresponding to the difference between nuclear and cytoplasmic fluorescence intensities divided by their sum (N - C/N + C), which does not refer to absolute fluorescence intensities.