Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis Is Associated With Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM

OBJECTIVE: Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability. APPROACH AND RESULTS: Muscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitation-sequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation. CONCLUSIONS: We identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation

Aspetti epidemiologici della calcolosi di calcio in Italia: distribuzione dei fenotipi intermedi nella popolazione italiana

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Fire Responses to the 2010 and 2015/2016 Amazonian Droughts

Extreme droughts in Amazonia cause anomalous increase in fire occurrence, disrupting the stability of environmental, social, and economic systems. Thus, understanding how droughts affect fire patterns in this region is essential for anticipating and planning actions for remediation of possible impacts. Focused on the Brazilian Amazon biome, we investigated fire responses to the 2010 and 2015/2016 Amazonian droughts using remote sensing data. Our results revealed that the 2015/2016 drought surpassed the 2010 drought in intensity and extent. During the 2010 drought, we found a maximum area of 846,800 km2 (24% of the Brazilian Amazon biome) with significant (p ≤ 0.05) rainfall decrease in the first trimester, while during the 2015/2016 the maximum area reached 1,702,800 km2 (47% of the Brazilian Amazon biome) in the last trimester of 2015. On the other hand, the 2010 drought had a maximum area of 840,400 km2 (23% of the Brazilian Amazon biome) with significant (p ≤ 0.05) land surface temperature increase in the first trimester, while during the 2015/2016 drought the maximum area was 2,188,800 km2 (61% of the Brazilian Amazon biome) in the last trimester of 2015. Unlike the 2010 drought, during the 2015/2016 drought, significant positive anomalies of active fire and CO2 emissions occurred mainly during the wet season, between October 2015 and March 2016. During the 2010 drought, positive active fire anomalies resulted from the simultaneous increase of burned forest, non-forest vegetation and productive lands. During the 2015/2016 drought, however, this increase was dominated by burned forests. The two analyzed droughts emitted together 0.47 Pg CO2, with 0.23 Pg CO2 in 2010, 0.15 Pg CO2 in 2015 and 0.09 Pg CO2 in 2016, which represented, respectively, 209%, 136%, 82% of annual Brazil’s national target for reducing carbon emissions from deforestation by 2017 (approximately 0.11 Pg CO2 year-1 from 2006 to 2017). Finally, we anticipate that the increase of fires during the droughts showed here may intensify and can become more frequent in Amazonia due to changes in climatic variability if no regulations on fire use are implemented

Phenotypic Modulation of Smooth Muscle Cells in Atherosclerosis is Associated with Downregulation of LMOD1, SYNPO2, PDLIM7, PLN, and SYNM

Objective-Key augmented processes in atherosclerosis have been identified, whereas less is known about downregulated pathways. Here, we applied a systems biology approach to examine suppressed molecular signatures, with the hypothesis that they may provide insight into mechanisms contributing to plaque stability. Approach and Results-Muscle contraction, muscle development, and actin cytoskeleton were the most downregulated pathways (false discovery rate=6.99e-21, 1.66e-6, 2.54e-10, respectively) in microarrays from human carotid plaques (n=177) versus healthy arteries (n=15). In addition to typical smooth muscle cell (SMC) markers, these pathways also encompassed cytoskeleton-related genes previously not associated with atherosclerosis. SYNPO2, SYNM, LMOD1, PDLIM7, and PLN expression positively correlated to typical SMC markers in plaques (Pearson r>0.6, P0.8, P<0.0001). By immunohistochemistry, the proteins were expressed in SMCs in normal vessels, but largely absent in human plaques and intimal hyperplasia. Subcellularly, most proteins localized to the cytoskeleton in cultured SMCs and were regulated by active enhancer histone modification H3K27ac by chromatin immunoprecipitationsequencing. Functionally, the genes were downregulated by PDGFB (platelet-derived growth factor beta) and IFNg (interferron gamma), exposure to shear flow stress, and oxLDL (oxidized low-density lipoprotein) loading. Genetic variants in PDLIM7, PLN, and SYNPO2 loci associated with progression of carotid intima-media thickness in high-risk subjects without symptoms of cardiovascular disease (n=3378). By eQTL (expression quantitative trait locus), rs11746443 also associated with PDLIM7 expression in plaques. Mechanistically, silencing of PDLIM7 in vitro led to downregulation of SMC markers and disruption of the actin cytoskeleton, decreased cell spreading, and increased proliferation. Conclusions-We identified a panel of genes that reflect the altered phenotype of SMCs in vascular disease and could be early sensitive markers of SMC dedifferentiation

PID controlling approach based on FBG array measurements for laser ablation of pancreatic tissues

In this paper, we propose a temperature-based proportional–integral–derivative (PID) controlling algorithm using highly dense fiber Bragg grating (FBG) arrays for laser ablation (LA) of ex vivo pancreatic tissues. Custom-made highly dense FBG arrays with a spatial resolution of 1.2 mm were fabricated with the femtosecond point-by-point writing technology and optimized for LA applications. In order to obtain proper PID gain values, finite element method-based iterative simulation of different PID gains was performed. Then, the proposed algorithm, with numerically derived PID gains, was experimentally validated. In the experiments, the point temperature was controlled at different distances from the laser fiber tip (6.0 mm, 7.2 mm, 8.4 mm, and 10.8 mm). The obtained results report robust controlling and correlation between controlled distance and the resulting area of ablation. The results of the work encourage further investigation of FBG array application for LA control

Update on the genetics of nephrolithiasis

Genetic studies of calcium kidney stones evidenced the possible involvement of calcium-sensing receptor gene, vitamin D receptor gene and bicarbonate-sensitive adenylate cyclase gene, but it is uncertain which specific polymorphisms could be responsible. Thus, further studies are required to better assess the involvement of these or other genes and the interactions between different genes and between genes and environment. In addition to research in humans, the study of different strains of knock-out mice let us include the gene of phosphate reabsorption carrier NPT2, caveolin-1, protein NHERF-1, osteopontin and Tamm-Horsfall protein among the possible determinants. Further steps in the knowledge of calcium stone causes may be done using the instruments that the modern biotechnology and bioinformatics have made available to the researchers