Evaluación del riesgo de inundación a múltiples componentes en la costa del Maresme

The coast is one of the areas most affected by natural hazards, with floods being the most frequent and significant of these in terms of their induced impacts, so any management scheme requires their evaluation. In coastal areas, flooding is a hazard associated with different processes acting at different scales: coastal storms, flash floods and sea level rise (SLR). To address the problem as a whole, this study presents a methodology to undertake a preliminary integrated risk assessment of the magnitude of each flood component, taking into account their scope (extension of the affected area) and their temporal scale. The risk is quantified using specific indicators to assess the hazard magnitude (for each component) and the consequences. This allows for a robust comparison of the spatial risk distribution along the coast in order to identify both the most at-risk areas and the most influential risk components. This methodology is applied to a stretch of coastline (Maresme, Catalonia) representative of the Spanish Mediterranean coast. The results obtained characterise this coastline as an area with a relatively low overall risk, although some hotspots are identified as having high-risk values. Resumen: La costa es una de las zonas más sometidas a riesgos naturales, siendo la inundación uno de los más frecuentes e importantes en términos de daños inducidos, por lo que cualquier esquema de gestión requiere evaluación. La inundación en zonas costeras es una amenaza natural asociada a diferentes procesos que actúan a distintas escalas: tormentas costeras, riadas y subida del nivel del mar (SNM). Para abarcar la totalidad del problema, este trabajo propone una metodología para la evaluación preliminar del riesgo integrado de inundación costera a una escala regional que permite evaluar la magnitud de cada componente teniendo en cuenta su alcance (extensión de la zona afectada) y su escala temporal. El riesgo se cuantifica en función de unos indicadores específicos que valoran la magnitud de la amenaza para cada componente y las consecuencias. Esto permite comparar robustamente la distribución espacial del riesgo a lo largo de la costa, para identificar tanto zonas de mayor riesgo como las componentes que más contribuyen al mismo. Aplicamos esta metodología a un tramo de costa característica del Mediterráneo español (Maresme, Cataluña). Los resultados permiten caracterizar esta costa como un área con un riesgo global relativamente bajo, pero algunos puntos singulares con riesgo alto

Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

Down syndrome (DS) is a complex genetic syndrome characterized by intellectual disability, dysmorphism and variable additional physiological traits. Current research progress has begun to decipher the neural mechanisms underlying cognitive impairment, leading to new therapeutic perspectives. Pentylenetetrazol (PTZ) has recently been found to have positive effects on learning and memory capacities of a DS mouse model and is foreseen to treat DS patients. But PTZ is also known to be a convulsant drug at higher dose and DS persons are more prone to epileptic seizures than the general population. This raises concerns over what long-term effects of treatment might be in the DS population. The cause of increased propensity for epilepsy in the DS population and which Hsa21 gene(s) are implicated remain unknown. Among Hsa21 candidate genes in epilepsy, CSTB, coding for the cystein protease inhibitor cystatin B, is involved in progressive myoclonus epilepsy and ataxia in both mice and human. Thus we aim to evaluate the effect of an increase in Cstb gene dosage on spontaneous epileptic activity and susceptibility to PTZ-induced seizure. To this end we generated a new mouse model trisomic for Cstb by homologous recombination. We verified that increasing copy number of Cstb from Trisomy (Ts) to Tetrasomy (Tt) was driving overexpression of the gene in the brain, we checked transgenic animals for presence of locomotor activity and electroencephalogram (EEG) abnormalities characteristic of myoclonic epilepsy and we tested if those animals were prone to PTZ-induced seizure. Overall, the results of the analysis shows that an increase in Cstb does not induce any spontaneous epileptic activity and neither increase or decrease the propensity of Ts and Tt mice to myoclonic seizures suggesting that Ctsb dosage should not interfere with PTZ-treatment

Gene-Expression Profiling Suggests Impaired Signaling via the Interferon Pathway in Cstb(-/-) Microglia

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1, OMIM254800) is an autosomal recessive neurodegenerative disorder characterized by stimulus-sensitive and action-activated myoclonus, tonic-clonic epileptic seizures, and ataxia. Loss-of-function mutations in the gene encoding the cysteine protease inhibitor cystatin B (CSTB) underlie EPM1. The deficiency of CSTB in mice (Cstb(-/-) mice) generates a phenotype resembling the symptoms of EPM1 patients and is accompanied by microglial activation at two weeks of age and an upregulation of immune system-associated genes in the cerebellum at one month of age. To shed light on molecular pathways and processes linked to CSTB deficiency in microglia we characterized the transcriptome of cultured Cstb(-/-) mouse microglia using microarray hybridization and RNA sequencing (RNA-seq). The gene expression profiles obtained with these two techniques were in good accordance and not polarized to either pro- or anti-inflammatory status. In Cstb(-/-) microglia, altogether 184 genes were differentially expressed. Of these, 33 genes were identified by both methods. Several interferon-regulated genes were weaker expressed in Cstb(-/-) microglia compared to control. This was confirmed by quantitative real-time PCR of the transcripts Irf7 and Stat1. Subsequently, we explored the biological context of CSTB deficiency in microglia more deeply by functional enrichment and canonical pathway analysis. This uncovered a potential role for CSTB in chemotaxis, antigen-presentation, and in immune-and defense response-associated processes by altering JAK-STAT pathway signaling. These data support and expand the previously suggested involvement of inflammatory processes to the disease pathogenesis of EPM1 and connect CSTB deficiency in microglia to altered expression of interferon-regulated genes.Peer reviewe

Brain inflammation is accompanied by peripheral inflammation in Cstb(-/-) mice, a model for progressive myoclonus epilepsy

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb(-/-)) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb(-/-) mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb(-/-) mice and higher CXCL13 expression in activated microglia in Cstb(-/-) compared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstb(-/-) mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb(-/-)mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.Peer reviewe

Neuroprotective properties of peroxisome proliferator-activated receptor alpha (PPARα) and its lipid ligands

Signalling lipids are known to control a wide array of cellular processes, including cell proliferation, apoptosis, migration, and energy metabolism. Fatty acids and their derivatives, eicosanoids, phosphoinositides, sphingolipids, some cannabinoid-like molecules bind and activate nuclear receptors, including peroxisome proliferator-activated receptors (PPARs). This subfamily of transcription factors comprises three isotypes - PPARα (NR1C1), PPAR β/δ (NR1C2), PPARγ (NR1C3) - which bind to specific DNA response elements, as heterodimers with retinoid X receptors. PPAR activity is modulated by post-translational modifications and cofactors, towards which they show differential affinity. The three PPARs mutually interact, being integrated in a complex system, leading to the concept of a "PPAR triad". Nevertheless, the isotypes also show distinct actions on cellular physiology and partially different tissue, ligand and target gene specificities. In the brain, while the functions of PPARγ and its ligands are being thoroughly investigated, the actual and potential roles of PPARα and β/δ are far from being clarified. PPARα appears especially intriguing, since it is selectively expressed in certain brain areas and neuronal/glial populations, and modulates antioxidant responses, neurotransmission, neuroinflammation, neurogenesis, and glial cell proliferation/differentiation. This receptor and its endogenous ligands, including oleoylethanoloamide (OEA) and palmitoylethanolamide (PEA), are involved in physiological and pathological responses, such as satiety, memory consolidation, and modulation of pain perception. The protective role of PPARα agonists in neurodegenerative diseases and in neuropsychiatric disorders makes manipulation of this pathway highly attractive as therapeutic strategy for neuropathological conditions. In this review, we focus on the pleiotropic functions of PPARα and its lipid ligands in the nervous tissue, devoting special attention to neuroprotection. © 2014 Bentham Science Publishers

Lysosomal involvement in the removal of clofibrate-induced rat liver peroxisomes. A biochemical and morphological analysis

Peroxisomal proliferators induce in rodents hepatic hyperplasia and hypertrophy; the significant increase in the peroxisomal population is accompanied by specific and reversible induction of some peroxisomal enzymes. In suckling rats born from clofibrate-treated mothers, a massive removal of proliferated organelles occurs within 3 days of recovery. In the present paper we examined the early stages of the recovery period in liver of male rats treated with clofibrate for 5 days. The lysosomal involvement in the removal of drug-induced peroxisomes was investigated under physiological conditions, ie in the absence of inhibitors of the autophagic process. Biochemical results indicate that peroxisomal beta-oxidation, but not catalase activity, returns to the control values within the examined period. Total acid phosphatase activity is not affected by clofibrate treatment, but following fractionation on a linear density gradient the lysosomal marker enzyme activity is shifted towards lower density values, particularly at day 1 and 2 of recovery. This class of organelles possibly represents lysosomes involved in active autophagic processes. Acid phosphatase cytochemistry shows an increase of lysosome number at day 1 of recovery. Combination of acid phosphatase cytochemistry either with catalase cytochemistry or with catalase immunogold labelling allows to reveal organelles containing both marker enzymes. These results strongly support the involvement of autophagic processes in the removal of proliferated peroxisomes. ((C) Elsevier, Paris)

Topological location of diamine oxidase in the transverse plane of rabbit liver microsomal membranes.

The transverse topology of diamine oxidase within rabbit liver microsomal membranes was studied by examining the proteolytic digestion of sealed or detergent-permeabilized microsomal vesicles. Trypsin and pronase had no effect on diamine oxidase activity in any incubation conditions tested, while nagarse treatment reduced by 60-70% the enzymic activity of intact microsomes; no further loss of activity was observed in the presence of detergent. These results demonstrate that the active site of diamine oxidase faces the cytoplasmic membrane surface, and suggest that it does not possess or expose on either membrane surfaces bonds susceptible to the proteolytic attack by trypsin or pronase. The possible significance and the biological implications of the results are discussed

Retinoic acid-induced modulation of rat liver transglutaminase and total polyamines in vivo.

The effect of a single intraperitoneal injection of retinoic acid on liver transglutaminase (EC 2.3.2.13) activity and total putrescine, spermidine and spermine was studied. The results demonstrate that: (1) transglutaminase activity is increased over control values as early as 4-6 h after treatment, reaching a maximum (2-fold increase) at 12 h and returning to control values at 36 h; (2) the retinoic acid-induced form of enzyme is the soluble tissue transglutaminase; (3) actinomycin D treatment does not completely inhibit the early (6 h) increase of activity, while suppressing that at 12 h; (4) the immunoassay of the soluble transglutaminase shows that, 6 h after treatment, there is no increase in the protein, whereas at 12 and 24 h a significant increase is observed; (5) putrescine, but not spermidine and spermine, increases (5-7-fold) 6 and 18 h after the retinoic acid treatment. The possibility also that the expression of soluble transglutaminase is modulated in vivo by retinoic acid and the relationship to polyamine levels are discussed