Analysis of the chemical evolution of the Galactic disk via dynamical simulations of the open cluster system

For several decades now, open clusters have been used to study the structure and chemical evolution of the disk of our Galaxy. Due to the fact that their ages and metallicities can be determined with relatively good precision, and since they can be observed even at great distances, they are excellent tracers of the variations in the abundance of heavy chemical elements with age and position in the Galactic disk. In the present work we analyze the star formation history and the chemical evolution of the disk of the Galaxy using numerical simulations of the dynamical evolution of the system of open clusters in the Milky Way. Starting from hypotheses on the history of cluster formation and the chemical enrichment of the disk, we model the present properties of the Galactic open cluster system. The comparison of these models with the observations allows us to examine the validity of the assumed hypotheses and to improve our knowledge about the initial conditions of the chemical evolution of the Galactic disk

Chemo-Archaeological Downsizing in a Hierarchical Universe: Impact of a Top Heavy IGIMF

We make use of a semi-analytical model of galaxy formation to investigate the origin of the observed correlation between [a/Fe] abundance ratios and stellar mass in elliptical galaxies. We implement a new galaxy-wide stellar initial mass function (Top Heavy Integrated Galaxy Initial Mass Function, TH-IGIMF) in the semi-analytic model SAG and evaluate its impact on the chemical evolution of galaxies. The SFR-dependence of the slope of the TH-IGIMF is found to be key to reproducing the correct [a/Fe]-stellar mass relation. Massive galaxies reach higher [a/Fe] abundance ratios because they are characterized by more top-heavy IMFs as a result of their higher SFR. As a consequence of our analysis, the value of the minimum embedded star cluster mass and of the slope of the embedded cluster mass function, which are free parameters involved in the TH-IGIMF theory, are found to be as low as 5 solar masses and 2, respectively. A mild downsizing trend is present for galaxies generated assuming either a universal IMF or a variable TH-IGIMF. We find that, regardless of galaxy mass, older galaxies (with formation redshifts > 2) are formed in shorter time-scales (< 2 Gyr), thus achieving larger [a/Fe] values. Hence, the time-scale of galaxy formation alone cannot explain the slope of the [a/Fe]-galaxy mass relation, but is responsible for the big dispersion of [a/Fe] abundance ratios at fixed stellar mass.We further test the hyphothesis of a TH-IGIMF in elliptical galaxies by looking into mass-to-light ratios, and luminosity functions. Models with a TH-IGIMF are also favoured by these constraints. In particular, mass-to-light ratios agree with observed values for massive galaxies while being overpredicted for less massive ones; this overprediction is present regardless of the IMF considered.Comment: 24 pages, 15 figures, 2 tables. (Comments most welcome). Summited to MNRA

Effects of environment on the properties of cluster galaxies via ram pressure stripping

We study the effect of ram pressure stripping (RPS) on the colours, cold gas content and star formation of galaxies in clusters, using a combination of N -Body/SPH simulations of galaxy clusters and a semi-analytic model of galaxy formation that includes the effect of RPS.Facultad de Ciencias Astronómicas y Geofísica

Cluster analysis of behavioural and event-related potentials during a contingent negative variation paradigm in remitting-relapsing and benign forms of multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.</p> <p>Methods</p> <p>We investigated MS patients with RRMS and BMS subtypes using event-related potentials (ERPs) acquired in the context of a Posner visual-spatial cueing paradigm. Specifically, our study aimed to assess ERP brain activity in response preparation (contingent negative variation -CNV) and stimuli processing in MS patients. Latency and amplitude of different ERP components (P1, eN1, N1, P2, N2, P3 and late negativity -LN) as well as behavioural responses (reaction time -RT; correct responses -CRs; and number of errors) were analyzed and then subjected to cluster analysis.</p> <p>Results</p> <p>Both MS groups showed delayed behavioural responses and enhanced latency for long-latency ERP components (P2, N2, P3) as well as relatively preserved ERP amplitude, but BMS patients obtained more important performance deficits (lower CRs and higher RTs) and abnormalities related to the latency (N1, P3) and amplitude of ERPs (eCNV, eN1, LN). However, RRMS patients also demonstrated abnormally high amplitudes related to the preparation performance period of CNV (cCNV) and post-processing phase (LN). Cluster analyses revealed that RRMS patients appear to make up a relatively homogeneous group with moderate deficits mainly related to ERP latencies, whereas BMS patients appear to make up a rather more heterogeneous group with more severe information processing and attentional deficits.</p> <p>Conclusions</p> <p>Our findings are suggestive of a slowing of information processing for MS patients that may be a consequence of demyelination and axonal degeneration, which also seems to occur in MS patients that show little or no progression in the physical severity of the disease over time.</p

Opposite functions of Ki and Ha ras genes in the regulation of redox signals

Ras p21 signaling is involved in multiple aspects of growth, differentiation, and stress response [1-2]. There is evidence pointing to superoxides as relays of pas signaling messages. Chemicals with antioxidant activity suppress pas-induced DNA synthesis. The inhibition of pas significantly reduces the production of superoxides by the NADPH-oxidase complex [3]. Kirsten and Harvey are nonallelic Ras cellular genes that share a high degree of structural and functional homology. The sequences of Ki- and Ha-Ras proteins are almost identical. They diverge only in the 20-amino acid hypervariable domain at the COOH termini. To date, their functions remain indistinguishable [4]. We show that Ki- and Ha-Ras genes differently regulate the redox state of the cell, Ha-Ras-expressing cells produce high levels of reactive oxygen species (ROS) by inducing the NADPH-oxidase system. Ki-Ras, on the other hand, stimulates the scavenging of ROS by activating posttranscriptionally the mitochondrial antioxidant enzyme, Mn-superoxide dismutase (Mn-SOD), via an ERK1/2-dependent pathway. Glutamic acid substitution of the four lysine residues in the polybasic stretch at the COOH terminus of Ki-Ras completely abolishes the activation of Mn-SOD, although it does not inhibit ERK1/2-induced transcription. In contrast, an alanine substitution of the cysteine of the CAAX box has very little effect on Mn-SOD activity but eliminates ERK1/2-dependent transcription

Opposing functions of Ki- and Ha-Ras genes in the regulation of redox signals.

Ras p21 signaling is involved in multiple aspects of growth, differentiation, and stress response [1-2]. There is evidence pointing to superoxides as relays of pas signaling messages. Chemicals with antioxidant activity suppress pas-induced DNA synthesis. The inhibition of pas significantly reduces the production of superoxides by the NADPH-oxidase complex [3]. Kirsten and Harvey are nonallelic Ras cellular genes that share a high degree of structural and functional homology. The sequences of Ki- and Ha-Ras proteins are almost identical. They diverge only in the 20-amino acid hypervariable domain at the COOH termini. To date, their functions remain indistinguishable [4]. We show that Ki- and Ha-Ras genes differently regulate the redox state of the cell, Ha-Ras-expressing cells produce high levels of reactive oxygen species (ROS) by inducing the NADPH-oxidase system. Ki-Ras, on the other hand, stimulates the scavenging of ROS by activating posttranscriptionally the mitochondrial antioxidant enzyme, Mn-superoxide dismutase (Mn-SOD), via an ERK1/2-dependent pathway. Glutamic acid substitution of the four lysine residues in the polybasic stretch at the COOH terminus of Ki-Ras completely abolishes the activation of Mn-SOD, although it does not inhibit ERK1/2-induced transcription. In contrast, an alanine substitution of the cysteine of the CAAX box has very little effect on Mn-SOD activity but eliminates ERK1/2-dependent transcription

Metabolomics-assisted discovery of a new anticancer GLS-1 inhibitor chemotype from a nortopsentin-inspired library: From phenotype screening to target identification

The enzyme glutaminase-1 (GLS-1) has shown a clear and coherent implication in the progression and exacerbation of different aggressive tumors such as glioblastoma, hepatocarcinoma, pancreas, bone, and triple-negative breast cancer. Few chemotypes are currently available as selective GLS-1 inhibitors, and still, fewer of them are at the clinical stage. In the present paper, starting from a naturally-inspired antitumor compound library, metabolomics has been used to putatively identify the molecular mechanism underlying biological activity. GLS-1 was identified as a potential target. Biochemical analysis confirmed the hypothesis leading to the identification of a new hit compound acting as a GLS-1 selective inhibitor (IC50 = 3.96 ± 1.05 μM), compared to the GLS-2 isoform (IC50 = 12.90 ± 0.87 μM), with remarkable antitumor potency over different aggressive tumor cell lines. Molecular modelling studies revealed new insight into the drug-target interaction providing robust SAR clues for the rational hit-to-lead development. The approach undertaken underlines the wide potential of metabolomics applied to drug discovery, particularly in target identification and hit discovery following phenotype screening