miR-20a represses endothelial cell migration by targeting MKK3 and inhibiting p38 MAP kinase activation in response to VEGF.

Endothelial cell migration induced in response to vascular endothelial growth factor (VEGF) is a crucial step of angiogenesis and it depends on the activation of the p38 MAP-kinase pathway downstream of VEGFR2. In this study, we investigated the role of microRNAs (miRNAs) in regulating these processes. We found that the VEGF-induced p38 activation and cell migration are modulated by overexpression of Argonaute 2, a key protein in the functioning of miRNAs.

Quantitative prediction of vasopressin secretion using a computational population model of rat magnocellular neurons.

The goal of this study was to create a realistic and quantitative simulation of vasopressin (AVP) secretion under iso-osmotic and short-term challenged plasma osmolality. The relationship between AVP concentration ([AVP]) and plasma osmolality was computed using a sophisticated and integrated model that chronologically simulates (1) the overall firing rate of the hypothalamus' magnocellular neuronal (MCN) population, (2) the propagation of the spike activity down the axons, (3) the fatigue and facilitation mechanisms of AVP release at the axon terminals and (4) the [AVP] pharmacodynamics based on the trains of AVP release. This global simulation predicted that the differential MCN sensitivity to dynorphin would be the most critical mechanism underlying the individual variability of MCN firing behaviors (silence, irregular, phasic and continuous firing patterns).

The Werner syndrome gene product (WRN): a repressor of hypoxia-inducible factor-1 activity.

Werner syndrome (WS) is a rare autosomal disease characterized by the premature onset of several age-associated pathologies. The protein defective in WS patients (WRN) is a helicase/exonuclease involved in DNA repair, replication, transcription and telomere maintenance. Hypoxia-inducible factor-1 (HIF-1) is a decisive element for the transcriptional regulation of genes essential for adaptation to low oxygen conditions.

Integrin signaling in cancer cell survival and chemoresistance.

Resistance to apoptosis and chemotherapy is a hallmark of cancer cells, and it is a critical factor in cancer recurrence and patient relapse. Extracellular matrix (ECM) via its receptors, the integrins, has emerged as a major pathway contributing to cancer cell survival and resistance to chemotherapy. Several studies over the last decade have demonstrated that ECM/integrin signaling provides a survival advantage to various cancer cell types against numerous chemotherapeutic drugs and against antibody therapy.

Bovine sperm raft membrane associated Glioma Pathogenesis-Related 1-like protein 1 (GliPr1L1) is modified during the epididymal transit and is potentially involved in sperm binding to the zona pellucida.

Glioma pathogenesis-related 1-like protein1 (GliPr1L1) was identified by liquid chromatography-tandem mass spectrometry analyses of proteins associated to bovine sperm lipid raft membrane domains. This protein belongs to the CAP superfamily including cysteine-rich secretory proteins, Antigen 5 and pathogenesis-related 1 protein. PCR analysis revealed that GliPr1L1 is expressed in testis and, at a much lower level, all along the epididymis.

Comparison of risk factors for human metapneumovirus and respiratory syncytial virus disease severity in young children.

Background: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are leading pediatric pathogens. However, risk factors for severe hMPV disease remain unknown. We comparatively assessed environmental, host, and viral determinants for severe hMPV and RSV infections.

Role of microRNAs in controlling gene expression in different segments of the human epididymis.

Background: The molecular mechanisms implicated in regionalized gene expression in the human epididymis have not yet been fully elucidated. Interestingly, more than 200 microRNAs (miRNAs) have been identified in the human epididymis and could be involved in the regulation of mRNA stability and post-transcriptional expression in this organ.

Methods: Using a miRNA microarray approach, we investigated the correlation between miRNA signatures and gene expression profiles found in three distinct regions (caput, corpus and cauda) of human epididymides from 3 donors.

Long-term local area employment rates as predictors of individual mortality and morbidity: a prospective study in England, spanning more than two decades.

Background: Although long-term trends in local labour market conditions are likely to influence health, few studies have assessed whether this is so. This paper examines whether (1) trends in local employment rates have relevance for mortality and morbidity outcomes in England and (2) trends are stronger predictors of these outcomes than employment rates measured at one point in time.

Methods: Using latent class growth models, local areas were classified into eight groups following distinct trends in employment rates between 1981 and 2008.

PARP1 parylation promotes silent locus transmission in the nucleolus: the suspicion confirmed.

Parylation modulates various processes, including transcription. In this issue of Molecular Cell, Guetg et al. (2012) show that, in the nucleolus, PARP1-mediated parylation of TIP5 promotes the silencing of rDNA chromatin during replication, uncovering the mechanism by which PARP1 ensures that silent rDNA regions are properly inherited.

Signaling pathways mediating the neuroprotective effects of sex steroids and SERMs in Parkinson's disease.

Studies with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson's disease have shown the ability of 17β-estradiol to protect the nigrostriatal dopaminergic system. This paper reviews the signaling pathways mediating the neuroprotective effect of 17β-estradiol against MPTP-induced toxicity. The mechanisms of 17β-estradiol action implicate activation of signaling pathways such as the phosphatidylinositol-3 kinase/Akt and the mitogen-activated protein kinase pathways.

Sex and temporally-dependent effects of methamphetamine toxicity on dopamine markers and signaling pathways.

Methamphetamine induces a greater neurodegenerative effect in male versus female mice. In order to investigate this sex difference we studied the involvement of Akt and extracellular signal-regulated kinase (ERK1/2) in methamphetamine toxicity as a function of time post-treatment (30 min, 1 and 3 days). Methamphetamine-induced decreases in dopamine concentrations and dopamine transporter (DAT) specific binding in the medial striatum were similar in female and male mice when evaluated 1 day post-methamphetamine (40 mg/kg).

LRRK2 in Transcription and Translation Regulation: Relevance for Parkinson's Disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the selective loss of dopaminergic neurons and the presence of Lewy bodies. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of both familial and sporadic PD. One critical question is how PD-associated LRRK2 mutations cause neurodegeneration.

MicroRNAs in Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder and is the most common form of dementia in the elderly. Accumulating evidence in AD research suggests that alterations in the microRNA (miRNA) network could contribute to risk for the disease. miRNAs are conserved small non-coding RNAs that control gene expression at the posttranscriptional level and are essential for neuronal function and survival.

Genetic polymorphisms and drug susceptibility in four isolates of Leishmania tropica obtained from Canadian soldiers returning from Afghanistan.

Background: Cutaneous leishmaniasis (CL) is a vector-borne parasitic disease characterized by the presence of one or more lesions on the skin that usually heal spontaneously after a few months. Most cases of CL worldwide occur in Southwest Asia, Africa and South America, and a number of cases have been reported among troops deployed to Afghanistan. No vaccines are available against this disease, and its treatment relies on chemotherapy.

Rapid filtration separation-based sample preparation method for Bacillus spores in powdery and environmental matrices.

Authorities frequently need to analyze suspicious powders and other samples for biothreat agents in order to assess environmental safety. Numerous nucleic acid detection technologies have been developed to detect and identify biowarfare agents in a timely fashion. The extraction of microbial nucleic acids from a wide variety of powdery and environmental samples to obtain a quality level adequate for these technologies still remains a technical challenge.

Infectious Disease Management through Point-of-Care Personalized Medicine Molecular Diagnostic Technologies.

Infectious disease management essentially consists in identifying the microbial cause(s) of an infection, initiating if necessary antimicrobial therapy against microbes, and controlling host reactions to infection. In clinical microbiology, the turnaround time of the diagnostic cycle (>24 hours) often leads to unnecessary suffering and deaths; approaches to relieve this burden include rapid diagnostic procedures and more efficient transmission or interpretation of molecular microbiology results. Although rapid nucleic acid-based diagnostic testing has demonstrated that it can impact on the transmission of hospital-acquired infections, we believe that such life-saving procedures should be performed closer to the patient, in dedicated 24/7 laboratories of healthcare institutions, or ideally at point of care.

Mass spectrometry-based functional proteomics of poly(ADP-ribose) polymerase-1.

PARP-1 is an abundant nuclear protein that plays an essential role in the regulation of many genome integrity and chromatin-based processes, such as DNA repair, replication or transcriptional regulation. PARP-1 modulates the function of chromatin and nuclear proteins through several poly(ADP-ribose) (pADPr)-dependent pathways. Aside from the clearly established role of PARP-1 in the maintenance of genome stability, PARP-1 also emerged as an important regulator that links chromatin functions with extranuclear compartments.

Influence of mercury exposure on blood pressure, resting heart rate and heart rate variability in French Polynesians: a cross-sectional study.

Background: Populations which diet is rich in seafood are highly exposed to contaminants such as mercury, which could affect cardiovascular risk factors

Objective: To assess the associations between mercury and blood pressure (BP), resting heart rate (HR) and HR variability (HRV) among French Polynesians

Methods: Data were collected among 180 adults (≥ 18 years) and 101 teenagers (12-17 years). HRV was measured using a two-hour ambulatory electrocardiogram (Holter) and BP was measured using a standardized protocol. The association between mercury and HRV and BP parameters was studied using analysis of variance (ANOVA) and analysis of covariance (ANCOVA) RESULTS: Among teenagers, the high frequency (HF) decreased between the 2nd and 3rd tertile (380 vs.

Alzheimer-specific variants in the 3'UTR of Amyloid precursor protein affect microRNA function.

Background: APP expression misregulation can cause genetic Alzheimer's disease (AD). Recent evidences support the hypothesis that polymorphisms located in microRNA (miRNA) target sites could influence the risk of developing neurodegenerative disorders such as Parkinson's disease (PD) and frontotemporal dementia. Recently, a number of single nucleotide polymorphisms (SNPs) located in the 3'UTR of APP have been found in AD patients with family history of dementia.

Impact of mercury exposure on blood pressure and cardiac autonomic activity among Cree adults (James Bay, Quebec, Canada).

Aboriginal populations from Quebec (Canada) are exposed to higher mercury levels than southern regions since these populations consume high quantities of fish. Epidemiological evidence suggests a detrimental impact of mercury on cardiovascular risk factors such as heart rate variability (HRV) and blood pressure (BP). The objective of this study was to assess the impact of mercury exposure on BP, resting heart rate (HR) and HRV among Cree adults.

No evidence of selenosis from a selenium-rich diet in the Brazilian Amazon.

Selenium (Se) is an essential element and a well-known anti-oxidant. In the Lower Tapajós River region of the Brazilian Amazon, biomarkers of Se range from normal to very high. The local traditional diet includes important Se sources such as Brazil nuts, chicken, game meat and certain fish species.

MicroRNAs and Alzheimer's Disease Mouse Models: Current Insights and Future Research Avenues.

Evidence from clinical trials as well as from studies performed in animal models suggest that both amyloid and tau pathologies function in concert with other factors to cause the severe neurodegeneration and dementia in Alzheimer's disease (AD) patients. Accumulating data in the literature suggest that microRNAs (miRNAs) could be such factors. These conserved, small nonprotein-coding RNAs are essential for neuronal function and survival and have been implicated in the regulation of key genes involved in genetic and sporadic AD.

MicroRNA-132 loss is associated with tau exon 10 inclusion in progressive supranuclear palsy.

Tauopathies represent a large class of neurological and movement disorders characterized by abnormal intracellular deposits of the microtubule-associated protein tau. It is now well established that mis-splicing of tau exon 10, causing an imbalance between three-repeat (3R) and four-repeat (4R) tau isoforms, can cause disease; however, the underlying mechanisms affecting tau splicing in neurons remain poorly understood. The small noncoding microRNAs (miRNAs), known for their critical role in posttranscriptional gene expression regulation, are increasingly acknowledged as important regulators of alternative splicing.