Peroxynitrite activates the NLRP3 inflammasome cascade in SOD1(G93A) mouse model of amyotrophic lateral sclerosis

Neuroinflammation, characterized by the appearance of reactive microglial and astroglial cells, is one of the several pathogenic mechanisms of amyotrophic lateral sclerosis (ALS), a fast-progressing and fatal neurodegenerative disease. Cerebrospinal fluid and spinal cord of ALS patients and SOD1 mutant mice show high concentrations of IL-1β. This interleukin, expressed as an inactive precursor, undergoes a proteolytic maturation by caspase1, whose activation, in turn, depends on inflammasomes. Whether and how inflammasome is activated in ALS models is still to be clarified. The mechanism of inflammasome activation was studied in murine microglial cells overexpressing hSOD1(G93A) and verified in the spinal cord of hSOD1(G93A) mice. Murine microglial hSOD1(G93A) cells express all the inflammasome components and LPS activates caspase1 leading to an increase in the secretion of IL-1β. By activating NF-κB, LPS increases ROS and NO levels that spontaneously react to form peroxynitrite, thus leading to protein nitration. Reduction in peroxynitrite levels results in a decrease in caspase1 activity. Protein nitration and caspase1 activity are concomitantly increased in the spinal cord of pre-symptomatic SOD1(G93A) mice. Oxidative/nitrosative stress induces peroxynitrite formation that may be a key trigger of caspase1/inflammasome activation. Peroxynitrite formation may play a critical role in inflammasome activation and might be exploited as potential therapeutic target for ALS

Robotic versus laparoscopic approach in colonic resections for cancer and Benign diseases. Systematic review and meta-analysis

Objectives The aim of this systematic review and meta-Analysis is to compare robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of intraoperative and postoperative outcomes. Materials and Methods A systematic literature search was performed to retrieve comparative studies of robotic and laparoscopic colectomy. The databases searched were PubMed, Embase and the Cochrane Central Register of Controlled Trials from January 2000 to October 2014. The Odds ratio, Risk difference and Mean difference were used as the summary statistics. Results A total of 12 studies, which included a total of 4,148 patients who had undergone robotic or laparoscopic colectomy, were included and analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage (MD-0.51, P = 0.003) and the length of hospital stay (MD-0.68, P = 0.01) were significantly shorter after RC. Additionally, the intraoperative blood loss (MD-16.82, P<0.00001) was significantly less in RC. There was also a significantly lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and wound infections (RD-0.02, P = 0.03) after RC. No differences in the postoperative ileus, in the anastomotic leak, or in the conversion to open surgery rate and in the number of harvested lymph nodes outcomes were found between the approaches. Conclusions The present meta-Analysis, mainly based on observational studies, suggests that RC is more time-consuming and expensive than laparoscopy but that it results in faster recovery of bowel function, a shorter hospital stay, less blood loss and lower rates of both overall postoperative complications and wound infections. Copyright: © 2015 Trastulli et al.OBJECTIVES: The aim of this systematic review and meta-analysis is to compare robotic colectomy (RC) with laparoscopic colectomy (LC) in terms of intraoperative and postoperative outcomes. MATERIALS AND METHODS: A systematic literature search was performed to retrieve comparative studies of robotic and laparoscopic colectomy. The databases searched were PubMed, Embase and the Cochrane Central Register of Controlled Trials from January 2000 to October 2014. The Odds ratio, Risk difference and Mean difference were used as the summary statistics. RESULTS: A total of 12 studies, which included a total of 4,148 patients who had undergone robotic or laparoscopic colectomy, were included and analyzed. RC demonstrated a longer operative time (MD 41.52, P<0.00001) and higher cost (MD 2.42, P<0.00001) than did LC. The time to first flatus passage (MD -0.51, P = 0.003) and the length of hospital stay (MD -0.68, P = 0.01) were significantly shorter after RC. Additionally, the intraoperative blood loss (MD -16.82, P<0.00001) was significantly less in RC. There was also a significantly lower incidence of overall postoperative complications (OR 0.74, P = 0.02) and wound infections (RD -0.02, P = 0.03) after RC. No differences in the postoperative ileus, in the anastomotic leak, or in the conversion to open surgery rate and in the number of harvested lymph nodes outcomes were found between the approaches. CONCLUSIONS: The present meta-analysis, mainly based on observational studies, suggests that RC is more time-consuming and expensive than laparoscopy but that it results in faster recovery of bowel function, a shorter hospital stay, less blood loss and lower rates of both overall postoperative complications and wound infections

Development of an international scale of socio-economic position based on household assets.

The importance of studying associations between socio-economic position and health has often been highlighted. Previous studies have linked the prevalence and severity of lung disease with national wealth and with socio-economic position within some countries but there has been no systematic evaluation of the association between lung function and poverty at the individual level on a global scale. The BOLD study has collected data on lung function for individuals in a wide range of countries, however a barrier to relating this to personal socio-economic position is the need for a suitable measure to compare individuals within and between countries. In this paper we test a method for assessing socio-economic position based on the scalability of a set of durable assets (Mokken scaling), and compare its usefulness across countries of varying gross national income per capita.Ten out of 15 candidate asset questions included in the questionnaire were found to form a Mokken type scale closely associated with GNI per capita (Spearmans rank rs = 0.91, p = 0.002). The same set of assets conformed to a scale in 7 out of the 8 countries, the remaining country being Saudi Arabia where most respondents owned most of the assets. There was good consistency in the rank ordering of ownership of the assets in the different countries (Cronbachs alpha = 0.96). Scores on the Mokken scale were highly correlated with scores developed using principal component analysis (rs = 0.977).Mokken scaling is a potentially valuable tool for uncovering links between disease and socio-economic position within and between countries. It provides an alternative to currently used methods such as principal component analysis for combining personal asset data to give an indication of individuals relative wealth. Relative strengths of the Mokken scale method were considered to be ease of interpretation, adaptability for comparison with other datasets, and reliability of imputation for even quite large proportions of missing values

Geometric Path Integrals. A Language for Multiscale Biology and Systems Robustness

In this paper we suggest that, under suitable conditions, supervised learning can provide the basis to formulate at the microscopic level quantitative questions on the phenotype structure of multicellular organisms. The problem of explaining the robustness of the phenotype structure is rephrased as a real geometrical problem on a fixed domain. We further suggest a generalization of path integrals that reduces the problem of deciding whether a given molecular network can generate specific phenotypes to a numerical property of a robustness function with complex output, for which we give heuristic justification. Finally, we use our formalism to interpret a pointedly quantitative developmental biology problem on the allowed number of pairs of legs in centipedes

Permeation of CO2 and N2 through glassy poly(dimethyl phenylene) oxide under steady- and presteady-state conditions

Glassy polymers are often used for gas separations because of their high selectivity. Although the dual-mode permeation model correctly fits their sorption and permeation isotherms, its physical interpretation is disputed, and it does not describe permeation far from steady state, a condition expected when separations involve intermittent renewable energy sources. To develop a more comprehensive permeation model, we combine experiment, molecular dynamics, and multiscale reaction–diffusion modeling to characterize the time-dependent permeation of N2 and CO2 through a glassy poly(dimethyl phenylene oxide) membrane, a model system. Simulations of experimental time-dependent permeation data for both gases in the presteady-state and steady-state regimes show that both single- and dual-mode reaction–diffusion models reproduce the experimental observations, and that sorbed gas concentrations lag the external pressure rise. The results point to environment-sensitive diffusion coefficients as a vital characteristic of transport in glassy polymers

Myriapoda at "Reserva Ducke", Central Amazonia/Brazil

Myriapoda contains the four recent classes Chilopoda, Diplopoda, Pauropoda and Symphyla. In total, 159 families, 2166 genera and >15162 species are known world-wide. Twenty-nine families, >93 genera and >401 described species occur in Amazonia. One-fifth of the families presently known in the myriapods are represented in Amazonia. About 3% of all described species live, and at least 9% of the species estimated to exist world-wide in Myriapoda are assumed to live in Amazonia. From the forest reserve 'Reserva Ducke' near Manaus, 22 families, 38 genera and 73 described species are known at present. The Chilopoda represent 5 families, 9 genera, 23 species and one undescribed morphospecies, the Diplopoda 13 families, 18 described genera, 14 species and 19 undescribed morphospecies, the Pauropoda 2 families, 7 genera, 31 species, and the Sympyla 2 families, 4 genera and 5 species. All names are liste

Absence of acquired copy number neutral loss of heterozygosity (CN-LOH) of chromosome 7 in a series of 10 patients with Shwachman-Diamond syndrome

We report that acquired copy number neutral loss of heterozygosity (CN-LOH) of chromosome 7 was not identified in a series of 10 patients with Shwachman\u2013Diamond syndrome (SDS)

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Exclusive neuronal expression of SUCLA2 in the human brain

SUCLA2 encodes the ATP-forming subunit (A-SUCL-) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here we show that immunoreactivity of A-SUCL- in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye. A-SUCL- immunoreactivity co-localized >99% with that of the d subunit of the mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL- antiserum was verified by the absence of labeling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL- immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming subunit (G-SUCL-) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL- immunoreactivity that was however, not upregulated in samples obtained from diabetic versus non-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex

Search for Gravitational Wave Bursts from Soft Gamma Repeaters

We present the results of a LIGO search for short-duration gravitational waves (GWs) associated with Soft Gamma Repeater (SGR) bursts. This is the first search sensitive to neutron star f-modes, usually considered the most efficient GW emitting modes. We find no evidence of GWs associated with any SGR burst in a sample consisting of the 27 Dec. 2004 giant flare from SGR 1806-20 and 190 lesser events from SGR 1806-20 and SGR 1900+14 which occurred during the first year of LIGO's fifth science run. GW strain upper limits and model-dependent GW emission energy upper limits are estimated for individual bursts using a variety of simulated waveforms. The unprecedented sensitivity of the detectors allows us to set the most stringent limits on transient GW amplitudes published to date. We find upper limit estimates on the model-dependent isotropic GW emission energies (at a nominal distance of 10 kpc) between 3x10^45 and 9x10^52 erg depending on waveform type, detector antenna factors and noise characteristics at the time of the burst. These upper limits are within the theoretically predicted range of some SGR models.Comment: 6 pages, 1 Postscript figur