Compared patterns of arm regeneration in different taxa of armed echinoderms

Regeneration is a post-embryonic developmental process common in Metazoa, although it tends to be less widespread in the more complex-bodied phyla. An exception to this rule are echinoderms, which are known for phylum-wide and extremely advanced regenerative abilities, being able to regrow all appendages, and often large parts of the central body and viscera (CANDIA CARNEVALI, 2006). Armed echinoderms (Crinoidea, Asteroidea, and Ophiuroidea) are especially practical models as their arms are easy to amputate, and their proximo-distal extension provides a useful reference point to describe the regenerative processes. Samples of four species from these taxa \u2013 the crinoid Antedon mediterranea, the asteroids Echinaster sepositus and Coscinasterias tenuispina, and the ophiuroid Amphipholis squamata \u2013 were subjected to arm amputation to study the progression of arm regeneration from a morphological point of view by means of different microscopy analyses. Particular attention was given to the \u201caxial structures\u201d, defined as the continuous elements running along the proximo-distal axis of each arm, namely the radial water canal, the radial nerve cord, and the arm coelom, as they are believed to be fundamental for the re-organization of the regenerating arm. The comparison highlighted commonalities and differences of arm regeneration in the different taxa. Distal structures, represented in crinoids by the apical blastema and in asteroids and ophiuroids by the terminal ossicle and tube foot, form very quickly, whereas the proximal region develops later, in proximal-to-distal direction. This is in accordance with previously published models of echinoderm regeneration (MOOI et al., 2005; BEN KHADRA et al., 2018). These similarities suggest that the mechanism of regeneration has ancient origins and is extremely conserved through echinoderm evolution. Within the proximal region, the axial structures themselves develop earlier than the nearby discrete structures (e.g. ossicles and tube feet), and seem to have a crucial role in their organization, providing material and possible signalling molecules for the growing tissue. The cellular component of the nerve grows before any other structure, including its own fibres, thus confirming a primary role of the nervous system in the whole process. Molecular analyses must be combined to morphology data to improve our understanding of similarities and differences of the regenerative process as it occurs in the different echinoderm taxa, as well as in different animal phyla, and to identify related processes in both regeneration-competent and non-competent species. References Ben Khadra Y, Sugni M, Ferrario C, Bonasoro F, Oliveri P, Martinez P, Candia Carnevali MD. 2018. Regeneration in Stellate Echinoderms: Crinoidea, Asteroidea and Ophiuroidea. M. Kloc, J. Z. Kubiak (eds.) Marine Organisms as Model Systems in Biology and Medicine. \ua9Springer International Publishing AG, part of Springer Nature 2018. Chapter 14 Candia Carnevali MD. 2006. Regeneration in Echinoderms: repair, regrowth, cloning. Invertebrate Survival Journal, 3 (1): 64-76 Mooi R, David B, Wray GA. 2005. Arrays in rays: terminal addition in echinoderms and its correlation with gene expression. Evolution & Development, 7 (6): 542-55

A new rating system for hydrogeological risk management along railway infrastructures in Prealpine zone (northern Italy)

AbstractRailway infrastructures in mountain areas often develop along hillslopes affected by geomorphological and hydrogeological processes which might lead hazardous events. Therefore, specific tools for risk analysis and management are required. This paper develops a new rating system (Railway Hydrogeological Management System, RHMS), based on a heuristic method which considers the susceptibility to different types of slope instabilities, as well as the peculiar features affecting the railway vulnerability. The proposed method introduces an iterative approach for the risk assessment, based on the definition of acceptability thresholds for the residual risk. The application of this method to a test area pointed out its feasibility, as well as its operational capability to identify the critical sections of the infrastructure, in which protection or mitigation measures are needed in order to reduce the risk

Quando o movimento tece o Estado: as ações públicas em Sergipe na construção de uma agricultura do plantar, colher e comer sem agredir a natureza.

bitstream/item/206763/1/Diogo.pd

The new calcium antagonist lercanidipine and its enantiomers affect major processes of atherogenesis in vitro: is calcium entry involved?

Atherosclerosis results from multiple factors and involves several mechanisms, including endothelial monocyte and smooth muscle cell (SMC) changes, cholesterol accumulation, plaque rupture and thromboembolism. Calcium ions play a role in the initial and chronic development of atherosclerotic lesions. Several studies in experimental animal models have demonstrated the potential direct antiatherosclerotic effects of calcium antagonists. In this study the antiatherogenic activity of lercanidipine, a new lipophilic, second-generation calcium antagonist, was investigated. Lercanidipine and its enantiomers inhibited the replication and migration of arterial myocytes in concentrations ranging from 10 to 50 microM. The antiproliferative effect of lercanidipine was dose dependent, with a potency similar to that of lacidipine and nifedipine, and was unrelated to the stereoselectivity of enantiomers to bind L-type calcium channels. Lercanidipine and its enantiomers (25 microM) decreased the serum-induced elevation of [Ca2+]i in SMC, with the (S)-enantiomer (69% inhibition) being 2.4-fold more active than the (R)-counterpart (29% inhibition). The studies performed with enantiomers of lercanidipine suggest that the observed effects are not related to the blockade of voltage-dependent Ca2+ channels and confirm, at least in vitro, the pharmacological potential of the compound to influence negatively the process of atherogenesis

In vitro inhibitory effect of lercanidipine on cholesterol accumulation and matrix metalloproteinases secretion by macrophages

Plaque rupture and thromboembolism play a major role in atherosclerotic acute syndrome. Experimental studies have demonstrated the potential direct anti-atherosclerotic effects of calcium antagonists. We investigated the in vitro effect of lercanidipine (REC 15/2375), a third-generation, highly lipophilic calcium antagonist on cholesterol metabolism and matrix metalloproteinases secretion in macrophages, two functions that predispose plaques to rupture. Lercanidipine (10 126\u201310 125 M) inhibited cholesterol esterification in macrophagesand reduced cellular free and esterified cholesterol accumulation from acetylated LDL (63%, 62% of control P < 0.05, respectively). In addition, lercanidipine inhibited the release of metalloproteinases in the extracellular medium (50% and 95% inhibition at 10 125 M for MMP-9 and MMP-2, respectively). Experiments performed with lercanidipine enantiomers or other dihydropyridine derivatives, endowed with different lipophilicity and affinity for calcium channels, indicated that the above effects could be related to the lipophilic, but not to the calcium channel blocking properties of these molecules. When cells, after exposure to the drug, were allowed to equilibrate, lercanidipine inhibitory action could be observed at initial concentrations as low as 10 129 M, which is the actual concentration range observed in plasma in clinical settings. In conclusion, our data indicate that lercanidipine may exert potent anti-atherosclerotic effects by inhibiting macrophage functions involved in plaque stability

ABCA1 and HDL3 are required to modulate smooth muscle cells phenotypic switch after cholesterol loading

Aim. Arterial smooth muscle cells (SMCs) may accumulate cholesterol and modify their phenotypic behavior becoming foam cells. We aimed to characterize the role of HDL3 and the ATP binding cassette transporter ABCA1 in this process. Methods. We evaluated the cholesterol-induced phenotypic changes in SMCs isolated from wild type (WT) and ABCA1 knock out (KO) mice and how HDL3 affects these changes. Results. Cholesterol loading downregulates the expression of ACTA2 (SMC-marker), and increases the expression of Mac-2, SRB1, ABCG1 and ABCA1 (macrophage-related genes). HDL3 normalizes ACTA2 expression and reduces the expression of macrophage-related genes in WT cells. Interestingly, the effect of HDL3 is completely lost in ABCA1 KO cells. Concordantly, ABCA1 knock-down by siRNA completely abolishes the rescue effect by HDL3 in WT SMC. The presence of HDL3 does not differently affect cholesterol accumulation in WT or ABCA1 KO cells and stimulates phospholipids removal only in WT cells. Cholesterol loading reduces the expression of myocardin, the key SMC transcriptional coactivator (-55%, p<0.01 vs control) in both cell types, while increases the expression of KLF4 (a transcriptional factor which represses the expression of myocardin) in WT cells (+240%, p<0.01 vs control). HDL3 normalizes myocardin and KLF4 levels in WT cells while it does not have any effect in ABCA1 KO cells. Similar results are obtained on miR-143/145, which positively regulate myocardin. Conclusions. HDL3 modulates the miR143/145-myocardin-KLF4 axis and prevents the cholesterol-induced phenotypic changes in SMC, but only in the presence of a functional ABCA1

The dataset describes : phenotypic changes induced by cholesterol loading in smooth muscle cells isolated from the aortae of C57BL/6 mice

The data presented in this article is related to the research article entitled \u201cABCA1 and HDL3 are Required to Modulate Smooth Muscle Cells Phenotypic Switch after Cholesterol Loading\u201d (Castiglioni et al.) [1]. This data describes the characterization of the phenotypic changes induced by cholesterol loading in smooth muscle cells (SMCs) isolated from the aortae of C57BL/6 mice. Upon cholesterol loading, there is a significant and concentration-dependent decrease in the expression of Acta2 and a parallel increase in Mac-2, and ATP binding cassette (ABC) transporters Abca1 and Abcg1. Cholesterol incubation causes the transformation of SMCs into foam cells with a 3-fold increase in cellular total cholesterol content and a 2.5-fold stimulation of the activity of the esterifying enzyme Acyl-CoA:cholesterol acyltransferase (ACAT). The addition of the same amount of cholesterol, either dissolved in ethanol or as lipoprotein cholesterol (AcLDL or native LDL) only slightly induces the activity of the enzyme ACAT, and does not cause the accumulation of lipid droplets into SMCs. We describe also the knock down of ABCA1 expression by siRNA treatment in mouse smooth muscle cells

ExoS/ChvI two-component signal-transduction system activated in the absence of bacterial phosphatidylcholine

Sinorhizobium meliloti contains the negatively charged phosphatidylglycerol and cardiolipin as well as the zwitterionic phosphatidylethanolamine (PE) and phosphatidylcholine (PC) as major membrane phospholipids. In previous studies we had isolated S. meliloti mutants that lack PE or PC. Although mutants deficient in PE are able to form nitrogen-fixing nodules on alfalfa host plants, mutants lacking PC cannot sustain development of any nodules on host roots. Transcript profiles of mutants unable to form PE or PC are distinct; they differ from each other and they are different from the wild type profile. For example, a PC-deficient mutant of S. meliloti shows an increase of transcripts that encode enzymes required for succinoglycan biosynthesis and a decrease of transcripts required for flagellum formation. Indeed, a PC-deficient mutant is unable to swim and overproduces succinoglycan. Some suppressor mutants, that regain swimming and form normal levels of succinoglycan, are altered in the ExoS sensor. Our findings suggest that the lack of PC in the sinorhizobial membrane activates the ExoS/ChvI two-component regulatory system. ExoS/ChvI constitute a molecular switch in S. meliloti for changing from a free-living to a symbiotic life style. The periplasmic repressor protein ExoR controls ExoS/ChvI function and it is thought that proteolytic ExoR degradation would relieve repression of ExoS/ChvI thereby switching on this system. However, as ExoR levels are similar in wild type, PC-deficient mutant and suppressor mutants, we propose that lack of PC in the bacterial membrane provokes directly a conformational change of the ExoS sensor and thereby activation of the ExoS/ChvI two-component system.Fil: Geiger, Otto. Universidad Nacional Autónoma de México; MéxicoFil: Sohlenkamp, Christian. Universidad Nacional Autónoma de México; MéxicoFil: Vera-Cruz, Diana. Universidad Nacional Autónoma de México; MéxicoFil: Medeot, Daniela Beatriz. Universidad Nacional Autónoma de México; México. Universidad Nacional de Rio Cuarto. Facultad de Cs.exactas Fisicoquimicas y Naturales. Instituto de Biotecnologia Ambiental y Salud. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Cordoba. Instituto de Biotecnologia Ambiental y Salud.; ArgentinaFil: Martínez-Aguilar, Lourdes. Universidad Nacional Autónoma de México; MéxicoFil: Sahonero-Canavesi, Diana X.. Universidad Nacional Autónoma de México; MéxicoFil: Weidner, Stefan. Universitaet Biehlefeld; AlemaniaFil: Pühler, Alfred. Universitaet Biehlefeld; AlemaniaFil: López Lara, Isabel M.. Universidad Nacional Autónoma de México; Méxic

HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages

Macrophages secrete matrix metalloproteinases (MMPs) that may weaken the fibrous cap of atherosclerotic plaque, predisposing its fissuration. The 92- kDa gelatinase B (MMP-9) has been identified in abdominal aortic aneurysms and in atherosclerotic tissues. Fluvastatin, through the inhibition of the isoprenoid pathway, inhibits major processes of atherogenesis in experimental models (smooth muscle cell migration and proliferation and cholesterol accumulation in macrophages). We studied the effect of fluvastatin on the activity of MMP-9 in mouse and human macrophages in culture. Conditioned media of cells treated for 24 hours with fluvastatin were analyzed by gelatin zymography. In mouse macrophages, fluvastatin (5 to 100 \u3bcmol/L) significantly inhibited in a dose-dependent manner MMP-9 activity from 20% to 40% versus control. The drug, at a concentration as low as 5 \u3bcmol/L, inhibited MMP-9 activity ( 4330%) in human monocyte-derived macrophages as well. Phorbol esters (TPA, 50 ng/mL) stimulated MMP-9 activity by 50%, and fluvastatin inhibited this enhanced activity up to 50% in both mouse and human macrophages. The above results on the secretion of MMP-9 were confirmed by Western blotting and ELISA. The inhibitory effect of fluvastatin was overcome by the simultaneous addition of exogenous mevalonate (100 \u3bcmol/L), a precursor of isoprenoids. Fluvastatin's effect was fully reversible, and the drug did not cause any cellular toxicity. The statin did not block directly the in vitro activation of the secreted protease. Similar data were obtained with simvastatin. Altogether, our data indicate an inhibition of MMP-9 secretion by the drug. This effect is mediated by the inhibition of synthesis of mevalonate, a precursor of numerous derivatives essential for several cellular functions

IL28B gene polymorphism rs12979860, but not rs8099917, contributes to the occurrence of chronic HCV infection in uruguayan patients

Background: Host single-nucleotide polymorphisms (SNPs) near the interleukin 28B (IL28B) locus are associated with sustained virological response to antiviral therapy and with spontaneous Hepatitis C Virus (HCV) clearance. Prevalence of these SNPs varies depending on ethnicity. The impact of IL28B SNPs in HCV-infected patients is currently unknown in Uruguay. Therefore, the aim of this study was to evaluate and compare the distribution of polymorphisms in the IL28B gene (rs12979860 and rs8099917) among HCV-infected patients and healthy individuals in Uruguay and thus assess their possible association with the establishment of HCV infection. Methods: DNA was recovered from 92 non-infected individuals and 78 HCV-infected patients and SNPs were determined by RFLP and allelic discrimination by real-time PCR. Results: The distribution of rs12979860 genotypes for the infected population was 29.5%-CC, 47.4%-CT and 23.1%-TT and for the control group 45.7,% 42.4% and 11.9,% respectively. Prevalence in both infected and uninfected individuals is similar to that reported in other countries with admixed populations. The distribution of rs8099917 genotypes for the infected population was 57.7%-TT, 27.2%-TG and 14.1%-GG and for the control group 60.9,% 33.7% and 5.4,% respectively. The comparison of rs12979860 genotype distribution between the two populations evidenced a higher prevalence of the favourable genotype (CC) in the uninfected control group (p < 0.05). Additionally, results generated using logistic regression analysis show that individuals carrying rs12979860-TT or CT genotypes have a higher likelihood of developing chronic hepatitis upon infection with HCV, when compared to CC carriers, considering rs8099917 genotype as constant. Conclusion: Patients with HCV infection have a statistically significant lower prevalence of the favourable rs12979860 genotype when compared to uninfected individuals; therefore we can establish that only IL28B rs12979860-CT and TT genotypes seem to contribute to the occurrence of chronic HCV infection in the cohort of Uruguayan population studied. Considering that a trend towards a higher frequency of "good" response genotypes was observed in responder patients, we believe that IL28B rs12979860 genotyping could be a useful tool for predicting different therapies outcome, including in the DAA era