Nuclear actin modulates cell motility via transcriptional regulation of adhesive and cytoskeletal genes

The actin cytoskeleton is a classic biomechanical mediator of cell migration. While it is known that actin also shuttles in and out of the nucleus, its functions within this compartment remain poorly understood. In this study, we investigated how nuclear actin regulates keratinocyte gene expression and cell behavior. Gene expression profiling of normal HaCaT keratinocytes compared to HaCaTs over-expressing wild-type beta-actin or beta-actin tagged with a nuclear localization sequence (NLS-actin), identified multiple adhesive and cytoskeletal genes, such as MYL9, ITGB1, and VCL, which were significantly down-regulated in keratinocytes with high levels of nuclear actin. In addition, genes associated with transcriptional regulation and apoptosis were up-regulated in cells over expressing NLS-actin. Functionally, accumulation of actin in the nucleus altered cytoskeletal and focal adhesion organization and inhibited cell motility. Exclusion of endogenous actin from the nucleus by knocking down Importin 9 reversed this phenotype and enhanced cell migration. Based on these findings, we conclude that the level of actin in the nucleus is a transcriptional regulator for tuning keratinocyte migration.Peer reviewe

Chemical composition of atmospheric aerosols between Moscow and Vladivostok

International audienceThe TROICA-9 expedition (Trans-Siberian Observations Into the Chemistry of the Atmosphere) was carried out at the Trans-Siberian railway between Moscow and Vladivostok in October 2005. Measurements of aerosol physical and chemical properties were made from an observatory carriage connected to a passenger train. Black carbon (BC) concentrations in fine particles (PM2.5, aerodynamic diameter ?, NO3?, SO42?, Na+, NH4+, K+, Ca2+, Mg2+, oxalate and methane sulphonate) were measured continuously by using an on-line system with a 15-min time resolution. In addition, particle volume size distributions were determined for particles in the diameter range 3?850 nm using a 10-min. time resolution. The continuous measurements were completed with 24-h. PM2.5 filter samples which were stored in a refrigerator and later analyzed in chemical laboratory. The analyses included mass concentrations of PM2.5, ions, monosaccharide anhydrides (levoglucosan, galactosan and mannosan) and trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sb, V and Zn). The mass concentrations of PM2.5 varied in the range of 4.3?34.8 ?g m?3 with an average of 21.6 ?g m?3. Fine particle mass consisted mainly of BC (average 27.6%), SO42? (13.0%), NH4+ (4.1%), and NO3? (1.4%). One of the major constituents was obviously also organic carbon which was not determined. The contribution of BC was high compared with other studies made in Europe and Asia. High concentrations of ions, BC and particle volume were observed between Moscow and roughly 4000 km east of it, as well as close to Vladivostok, primarily due to local anthropogenic sources. In the natural background area between 4000 and 7200 km distance from Moscow, observed concentrations were low, even though there were local particle sources, such as forest fires, that increased occasionally concentrations. The measurements indicated that during forest fire episodes, most of the aerosol mass consisted of organic particulate matter. Concentrations of biomass burning tracers levoglucosan, oxalate and potassium were elevated close to the forest fire areas observed by the MODIS satellite. The polluted air masses from Asia seem to have significant influences on the concentration levels of fine particles over south-eastern Russia

Using a moving measurement platform for determining the chemical composition of atmospheric aerosols between Moscow and Vladivostok

The TROICA-9 expedition (Trans-Siberian Observations Into the Chemistry of the Atmosphere) was carried out at the Trans-Siberian railway between Moscow and Vladivostok in October 2005. Measurements of aerosol physical and chemical properties were made from an observatory carriage connected to a passenger train. Black carbon (BC) concentrations in fine particles (PM<sub>2.5</sub>, aerodynamic diameter <2.5 μm) were measured with an aethalometer using a five-minute time resolution. Concentrations of inorganic ions and some organic compounds (Cl<sup>−</sup>, NO<sub>3</sub><sup>−</sup>, SO<sub>4</sub><sup>2−</sup>, Na<sup>+</sup>, NH<sub>4</sub><sup>+</sup>, K<sup>+</sup>, Ca<sup>2+</sup>, Mg<sup>2+</sup>, oxalate and methane sulphonate) were measured continuously by using an on-line system with a 15-min time resolution. In addition, particle volume size distributions were determined for particles in the diameter range 3–850 nm using a 10-min time resolution. The continuous measurements were completed with 24-h PM<sub>2.5</sub> filter samples stored in a refrigerator and analyzed later in a chemical laboratory. The analyses included the mass concentrations of PM<sub>2.5</sub>, ions, monosaccharide anhydrides (levoglucosan, galactosan and mannosan) and trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sb, V and Zn). The mass concentrations of PM<sub>2.5</sub> varied in the range of 4.3–34.8 μg m<sup>−3</sup> with an average of 21.6 μg m<sup>−3</sup>. Fine particle mass consisted mainly of BC (average 27.6%), SO<sub>4</sub><sup>2−</sup> (13.0%), NH<sub>4</sub><sup>+</sup> (4.1%) and NO<sub>3</sub><sup>−</sup> (1.4%). One of the major constituents was obviously organic carbon which was not determined. The contribution of BC was high compared with other studies made in Europe and Asia. High concentrations of ions, BC and particle volume were observed between Moscow and roughly 4000 km east of it, as well as close to Vladivostok, primarily due to local anthropogenic sources. In the natural background area between 4000 and 7200 km away from Moscow, observed concentrations were low, even though local particle sources, such as forest fires, occasionally increased concentrations. During the measured forest fire episodes, most of the aerosol mass appeared to consist of organic particulate matter. Concentrations of the biomass burning tracers levoglucosan, oxalate and potassium were elevated close to the forest fire areas observed by the MODIS satellite. The polluted air masses from Asia seem to have significant influences on the concentration levels of fine particles over south-eastern Russia

Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With “Western or Eastern Environments/Lifestyles”

Purpose: We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. Methods: This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. Results: The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. Conclusion: Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments

SILAC-based proteomic quantification of chemoattractant-induced cytoskeleton dynamics on a second to minute timescale

Cytoskeletal dynamics during cell behaviours ranging from endocytosis and exocytosis to cell division and movement is controlled by a complex network of signalling pathways, the full details of which are as yet unresolved. Here we show that SILAC-based proteomic methods can be used to characterize the rapid chemoattractant-induced dynamic changes in the actin–myosin cytoskeleton and regulatory elements on a proteome-wide scale with a second to minute timescale resolution. This approach provides novel insights in the ensemble kinetics of key cytoskeletal constituents and association of known and novel identified binding proteins. We validate the proteomic data by detailed microscopy-based analysis of in vivo translocation dynamics for key signalling factors. This rapid large-scale proteomic approach may be applied to other situations where highly dynamic changes in complex cellular compartments are expected to play a key role

Health-related quality of life change in patients treated at a multidisciplinary pain clinic

Background Multidisciplinary pain management (MPM) is a generally accepted method for treating chronic pain, but heterogeneous outcome measures provide only limited conclusions concerning its effectiveness. Therefore, further studies on the effectiveness of MPM are needed to identify subgroups of patients who benefit, or do not benefit, from these interventions. Our aim was to analyse health-related quality of life (HRQoL) changes after MPM and to identify factors associated with treatment outcomes. Methods We carried out a real world observational follow-up study of chronic pain patients referred to a tertiary multidisciplinary outpatient pain clinic to describe, using the validated HRQoL instrument 15D, the HRQoL change after MPM and to identify factors associated with this change. 1,043 patients responded to the 15D HRQoL questionnaire at baseline and 12 months after the start of treatment. Background data were collected from the pre-admission questionnaire of the pain clinic. Results Fifty-three percent of the patients reported a clinically important improvement and, of these, 81% had a major improvement. Thirty-five percent reported a clinically important deterioration, and 12% had no change in HRQoL. Binary logistic regression analysis revealed that major improvement was positively associated with shorter duration of pain (Peer reviewe

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively

Depression: An Important Comorbidity With Metabolic Syndrome in a General Population

OBJECTIVE—There is a recognized association among depression, diabetes, and cardiovascular disease. The aim of this study was to examine in a sample representative of the general population whether depression, anxiety, and psychological distress are associated with metabolic syndrome and its components