De la cosmologie à la formation des galaxies : que nous apprennent les grandes structures de l'Univers ?

This thesis by publication is devoted to the theoretical understanding of the large-scale structure of the Universe and its role in the context of cosmology and galaxy formation. The birth and evolution of galaxies occur within the large cosmic highways drawn by the cosmic web and the natural question which arises is whether galaxies retain a memory of the large-scale cosmic flows from which they emerge. To address this key question, we will first show that in cosmological simulations, the spin of galaxies and the direction of their host filament are correlated in a mass-dependent way. This signal will be shown to be qualitatively understood in the context of hierarchical structure formation. An analytic model which explicitly takes into account the anisotropy of the cosmic web will complement this qualitative understanding by reproducing the measured correlations. Those ideas are important to understand the evolution of galaxy morphology but also to understand the intrinsic alignments of galaxies that contaminate cosmological probes like cosmic shear experiments. We will in particular measure this contamination directly from a state-of-the-art hydrodynamical simulation. In a second part, we will address the question of how to efficiently use large-scale structure data to probe the cosmological model describing our Universe by measuring its topology and geometry and using perturbation theory in the weakly and even mildly non-linear regime. The major contribution of this work is to analytically study the effect of redshift space distortions and non-linear collapse of structures on the topology, geometry and statistics of the cosmic density field.Dans cette thèse sur articles, nous nous intéressons aux grandes structures de l’Univers et à leur rôle fondamental pour la cosmologie et la formation des galaxies. Les galaxies naissent et grandissent au sein des filaments de la toile cosmique soulevant la question de l’impact de ces filaments sur les propriétés galactiques telles que la morphologie. Pour étudier cette question fondamentale, nous allons dans un premier temps montrer que dans les simulations numériques de l’Univers, le spin des galaxies est fortement lié à la direction de leur filament hôte avec un comportement qui dépend de leur masse. Ces corrélations spin-filament seront expliquées qualitativement dans le contexte de la formation hiérarchique des structures cosmologiques. Un modèle analytique tenant compte de l’anisotropie de la toile cosmique complètera ce tableau en reproduisant les corrélations observées. Ces idées sont importantes pour comprendre la morphologie des galaxies mais aussi les alignements intrinsèques qui peuvent certaines sondes cosmologiques basées sur la mesure de l’astigmatisme cosmique. Nous allons en particulier mesurer cette contamination dans une simulation hydrodynamique. Dans la seconde partie de ce manuscrit, nous nous poserons la question de comment extraire efficacement de l’information de la toile cosmique en mesurant sa topologie et sa géométrie et en utilisant la théorie perturbative dans un régime quasi-linéaire, la pierre angulaire de ce travail reposant sur l’étude analytique de l’impact de l’effondrement non-linéaire des structures et des distorsions en espace des redshifts sur la statistique du champ de densité cosmique

LH-21, a CB1 antagonist, reduces hepatotoxic damage produced by paracetamol overdose in a mice model.

Drug-induced liver injury (DILI) is one of the main causes of hepatic acute failure. Paracetamol can cause it when is ingested in excessive doses, leading to the depletion of the antioxidant mechanisms of the hepatocytes and a series of processes that conclude with cell death. One of the altered metabolic pathways is the endocannabinoid system (ECS), which has become a very interesting target to alleviate these events due to its involvement in inflammatory processes. For this reason, the triazole-derived compound LH-21, a cannabinoid receptor Cb1 antagonist, was used for the treatment of DILI in 8-week-old male C57BL/6 mice. In the present study, fasting mice were subjected to an oral overdose of paracetamol (300 mg/kg) and treated 2 hours later with 3 mg/kg of LH-21. After 24 hours, the animals were sacrificed and the livers were collected to determine the hepatic levels of metabolites related to antioxidant mechanisms, the expression of proteins involved in the generation of cellular damage and the transcription grade of the different components of the ECS. The observed results showed that LH-21 treatment raises GSH levels and total antioxidant capacity, in addition to reducing malondialdehyde values. Furthermore, the phosphorylation degree of Jnk and Stat3, as well as the activation status of Casp3, diminished. Regarding the ECS, the expression of Ppara, Cnr1, Cnr2 and Gpr55 did return to normal levels. This suggests that LH-21 effectively blocks the Cb1 activity, allowing the correct function of Ppar-α that promotes a cellular anti-inflammatory state and the relief of the symptoms produced by DILI. These results exhibit a promising perspective for the prevention or treatment of some toxic effects of paracetamol overdose with LH-21. Nevertheless, these findings are a first step to continue studying the involvement of the ECS in this type of liver disease and investigating the effectiveness of this Cb1 antagonist against the pathophysiology of DILI.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Environmental Enrichment, Age, and PPARα Interact to Regulate Proliferation in Neurogenic Niches

Peroxisome proliferator-activated receptor alpha (PPARα) ligands have been shown to modulate recovery after brain insults such as ischemia and irradiation by enhancing neurogenesis. In the present study, we investigated the effect of the genetic deletion of PPARα receptors on the proliferative rate of neural precursor cells (NPC) in the adult brain. The study was performed in aged Pparα −/− mice exposed to nutritional (treats) and environmental (games) enrichments for 20 days. We performed immunohistochemical analyses of cells containing the replicating cell DNA marker 5-bromo-2′ -deoxyuridine (BrdU+) and the immature neuronal marker doublecortin (Dcx+) in the main neurogenic zones of the adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ), and/or hypothalamus. Results indicated a reduction in the number of BrdU+ cells in the neurogenic zones analyzed as well as Dcx+ cells in the SGZ during aging (2, 6, and 18 months). Pparα deficiency alleviated the age-related reduction of NPC proliferation (BrdU+ cells) in the SVZ of the 18-months-old mice. While no genotype effect on NPC proliferation was detected in the SGZ during aging, an accentuated reduction in the number of Dcx+ cells was observed in the SGZ of the 6-months-old Pparα −/− mice. Exposing the 18-months-old mice to nutritional and environmental enrichments reversed the Pparα −/−-induced impairment of NPC proliferation in the neurogenic zones analyzed. The enriched environment did not modify the number of SGZ Dcx+ cells in the 18 months old Pparα −/− mice. These results identify PPARα receptors as a potential target to counteract the naturally observed decline in adult NPC proliferation associated with aging and impoverished environments.Grant sponsor: 7th Framework Programme of European Union. Grant number: HEALTH-F2-2008-223713, REPROBESITY to FR. Grant sponsor: Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), UEERDF. Grant numbers: PI13/02261 to FR. and CP12/03109 to JS. Grant sponsor: Red de Trastornos Adictivos, ISCIII, MINECO. Grant number: RD12/0028/0001 to FR. Grant sponsor: Plan Nacional Sobre Drogas, Ministerio de Sanidad y Consumo. Grant number: PNSD2010/143 and PNSD2015/047 to JS. Grant sponsor: Fundació La Marató de TV3. Grant number: 386/C/2011. Grant sponsor: Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE/ERDF. Grant numbers: PI45403 and CTS-8221 to FR. Grant sponsor: Consejería de Salud, Junta de Andalucía, UE/ERDF. Grant number: SAS111224 to FR. JS, FP and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII (grant numbers: CP12/03109, CP14/00212 and CP14/00173, respectively

Análisis económico de la evolución de un agrosistema de manejo agroecológico en etapa de consolidación

Los agrosistemas de manejo agroecológico suelen ser reconocidos por su contribución hacia la sustentabilidad desde las dimensiones Ambiental y Social, mas suele señalarse como un desafío el mejorar su contribución desde la dimensión Económica. En este trabajo se describe la evaluación económica de un agrosistema fruti hortícola de manejo agroecológico en etapa de consolidación, en dos años sucesivos. Para ello se midieron las variables Eficiencia, Productividad y Seguridad a través de una serie de indicadores. Como principales resultados se observa que la familia cumple sus objetivos, que son la autosuficiencia alimentaria y la generación de excedentes, en ese orden prioritario. También se observó que, en el camino de la consolidación, los indicadores económicos han mejorado de un año al otro, lo que puede señalar una tendencia positiva.Agroecological management agricultural systems are often recognized for their contribution to sustainability from environmental and social dimensions, most often noted as a challenge to improve its contribution from the Economic dimension. In this paper the economic evaluation of horticultural farms with agroecological management in a consolidation phase, in two successive years is described. To do the Efficiency, Productivity and Safety variables were measured through a series of indicators. The main results shows that the family fulfills its objectives, which are food self-sufficiency and generating surpluses, in that order of priority. It was also noted that in the way of consolidation, economic indicators have improved from one year to another, which may indicate a positive trend.Eje: A1: Sistemas de producción de base agroecológicaFacultad de Ciencias Agrarias y Forestale

Anti-hyperglycemic and antioxidant effect of fucoidan extract from Lessonia trabeculata in alloxan-induced diabetes rats

The objective of this research was to evaluate a nutritional strategy based on the consumption of a fucoidan extract from brown algae Lessonia trabeculata to control oxidative stress in experimental alloxan-induced insulin-dependent diabetes mellitus rats. Over 30 days, 75, 100, and 125 mg kg−1 of body weight of fucoidan doses were administered and both positive and negative control (n = 5 per group). Serum, liver, pancreas, and kidney biochemical indicators of oxidative stress improvement were evaluated. Measures included lipid peroxidation, superoxide dismutase and catalase activity, and antioxidant activity by assessment of free radical scavenging power and histopathological changes. The results showed an increase in the activity of antioxidant enzymes while reducing oxidative damage (lipid peroxidation index) in serum (p ≤ 0.05) and tissues (p ≤ 0.05). Further, no liver necrosis was observed in treated groups, unlike the Type 1 diabetes positive control group that presented mild necrosis and moderate congestion. In the pancreas, treated rats presented mild oedema, while the positive control group showed moderate oedema. A significant protective effect against oxidative stress caused by alloxan-induced diabetes was found in this model, therefore it can be concluded that fucoidan extracted from the Lessonia trabeculata algae could be considered a good functional compound for the control of oxidative stress in diabetic patients. Because diabetes is such a widespread public health issue, developing fucoidan-based products could be a natural way to improve patients' quality of life.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Funding for open access charge: Universidad de Málaga / CBUA This work was supported by grants from the following institutions: L.T.L-G., E.V.A.S., L.A.A-M. and J.A.C-P. are supported by Project “Desarrollo e Implementación de Procesos Tecnológicos de Validación Analítica y Bioactiva para fucoidano de algas pardas como suplementos nutricionales para humanos”, Convenio N°143-PNICP-PIAP-2015, INNOVATE-PERU. J.D. hold a “Miguel Servet” (CP21/00021) research contract from the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (ISCIII) co-funded by European Social Fund (ESF), “Investing in your future”, Gobierno de España

Analysis of the expression of metabolic sensors and inflammation mediators in the brain of animals with genetic obesity exposed to adiponectin activator NP1

Drug treatment strategies that interfere with adipokines secreted by adipose tissue, such as adiponectin and leptin, have been recently developed for treating obesity. Adiponectin is able of reducing both, food intake and body weight through both,  its action on the hypothalamus, and concerted actions on glucose and insulin sensitivity, and oxidation of fatty acids in peripheral tissues. Furthermore, in vitro studies have shown that adiponectin attenuates inflammation in endothelial, muscle and macrophage cells. Leptin acts synergistically with adiponectin in the regulation of energy balance, inhibiting food intake, and being its levels regulated in the hypothalamus through the endocannabinoid system and the peptides NPY/AgRP, POMC and orexins. Therefore, the restoration of normal adiponectin levels can be considered a good clinical option for the treatment of obesity. Recently, a new thiazole-derived drug called NP-1 has been described as an adiponectin promoter activator able to promote adiponectin release. We investigated the effects of NP-1 in the hypothalamus of lean (fa/-) and obese (fa/fa) leptin signaling deficient Zucker rats, after a 15-day exposure to vehicle or NP-1 (5 mg/Kg). Brains were removed and frozen and the hypothalamus was dissected out from a coronal section, following the rodent atlas of Paxinos. Protein extraction was performed from the obtained tissue to analyze it by Western Blot, and RNA was isolated to determine gene expression by RT-qPCR. Treatment with NP-1 increased circulating TNFα, which led to weight loss through decreased intake. NP-1 reduced the expression of adiponectin and TNF α receptors in the hypothalamus. It also reduced mRNA expression of intake promoters such as NPY, AGRP and hypocretin-1, and a specific obesity-dependent modulation of POMC. Leptin deficiency-induced obesity was associated with specific insulin resistance preventing NP-1-induced sensitization of insulin signaling (Phosphorylation of IRS1 and PI3K) in lean animals. Finally, NP-1 was able to decrease ERK1/ERk2 and NFkB activation, suggesting reduced inflammation of the hypothalamus. In conclusión, NP-1 modulates feeding through increased TNFα and regulation of hypothalamic neuropeptides without increasing inflammation

Endocrine and Metabolic impact of oral ingestion of a carob-pod derived natural syrup containing D-Pinitol: potential use as a novel sweetener in diabetes

The use of added sugars or non-nutritive sweeteners in processed foods and soft drinks are being blamed for multiple complications associated with obesity and diabetes. High fructose content contributes to obesity and liver steatosis, and excessive consumption of non-nutritive sweeteners can generate gut dysbiosis complicating the metabolic control exerted by the liver. Beyond its evolutionary significance in the selection of foods with a high glucose content as an energy source, the fact is that the consumption of sweets produces a hedonic pleasure in our brain. Then, the challenge stands at: how do we control the use of added sugars while providing a safe, palatable, sweet flavour to foods?. The present work explores an alternative approach, in humans and rodents, for sweetening through the use of a simple carob-pod-derived syrup which contains the inositol D-Pinitol. This inositol is known as an insulin sensitizer in muscle capable of keeping glycaemia while avoiding both unnecessary insulin secretion and the conversion of carbohydrates into fat depots .Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle

Funding: This work was supported by CIBERobn (CB06/03/1008), Ministerio de Economía y Competitividad (MINECO) (PG: BFU2012-33334), Instituto de Salud Carlos III (ISCIII), MINECO, co-funded by UE-ERDF program (JS: CP12/03109), Red de Trastornos Adictivos (FRF: RD12/0028/0001, PG: RD12/0028/0004, JM: RD12/0028/0013), The Basque Country Government (PG: BCG IT764-13), Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE-ERDF (FRF: CTS-8221, JM: CVI-6656), Consejería de Salud, Junta de Andalucía, UE-ERDF (FRF: SAS111224), and University of the Basque Country UPV/EHU (PG: UFI11/41). JS, FJP and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII, UE-ERDF (CP12/03109, CP14/00212, and CP14/00173 respectively)Peer reviewedPublisher PD