Chronic administration of the angiotensin type 2 receptor agonist C21 improves insulin sensitivity in C57BL/6 mice

The renin–angiotensin system modulates insulin action. Angiotensin type 1 receptor exerts a deleterious effect, whereas the angiotensin type 2 receptor (AT2R) appears to have beneficial effects providing protection against insulin resistance and type 2 diabetes. To further explore the role of the AT2R on insulin action and glucose homeostasis, in this study we administered C57Bl/6 mice with the synthetic agonist of the AT2R C21 for 12 weeks (1 mg/kg per day; ip). Vehicle-treated animals were used as control. Metabolic parameters, glucose, and insulin tolerance, in vivo insulin signaling in main insulin-target tissues as well as adipose tissue levels of adiponectin, and TNF-α were assessed. C21-treated animals displayed decreased glycemia together with unaltered insulinemia, increased insulin sensitivity, and increased glucose tolerance compared to nontreated controls. This was accompanied by a significant decrease in adipocytes size in epididymal adipose tissue and significant increases in both adiponectin and UCP-1 expression in this tissue. C21-treated mice showed an increase in both basal Akt and ERK1/2 phosphorylation levels in the liver, and increased insulin-stimulated Akt activation in adipose tissue. This positive modulation of insulin action induced by C21 appeared not to involve the insulin receptor. In C21-treated mice, adipose tissue and skeletal muscle became unresponsive to insulin in terms of ERK1/2 phosphorylation levels. Present data show that chronic pharmacological activation of AT2R with C21 increases insulin sensitivity in mice and indicate that the AT2R has a physiological role in the conservation of insulin action.Fil: Quiroga, Diego Tomás. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Muñoz, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Gil, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Pffeifer, Marlies. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Toblli, Jorge Eduardo. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Steckelings, Ulrike M.. Southern Denmark University; DinamarcaFil: Giani, Jorge Fernando. Cedars Sinai Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Dominici, Fernando Pablo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin

A detailed exploration of intermolecular interactions in 4-(4-dimethylaminobenzylideneamino)-N-(5-methyl-3-isoxazolyl) benzenesulfonamide and related Schiff bases: Crystal structure, spectral studies, DFT methods, Pixel energies and Hirshfeld surface analysis

The Schiff base of the title has been synthesized and its crystal structure determined by single-crystal X-ray diffraction. The compound was characterized by IR, Raman, 1H NMR, 13C NMR and electronic absorption spectra. DFT calculations provide the quantumchemical basis for the observed molecular conformation. A study of intermolecular interactions of the title compound is comparedwith seven other closely related structures and reveals that molecules in most of the compounds are linked by a cooperative effect of strong and weak hydrogen bonds, C\\H…π, and π…π stacking interactions, and also lp…π contacts. Lattice energy calculations indicate that the dispersion component is the major contribution, with the coulombic term playing a significant role in the total energy. Interaction energies for molecular pairs involving N\\H···N bonds indicate a dominant contribution to packing stabilization coming from coulomb component. Hirshfeld surfaces and 2D–fingerprint plots allowed us to visualize different intermolecular contacts and its relative contributions to total surface in each compound. The analysis of electrostatic potential (ESP) maps correlates well with the computed energies providing evidences on the dominant electrostatic nature of N\\H···N and N\\H···O interactions.Instituto de Física La Plat

Persistence of tree relicts in the Spanish Central System through the Holocene

Persistence of relict tree species in Mediterranean environments is becoming increasingly unlikely in view of ongoing and future global change. The variability in the Holocene climate and more recent anthropogenic impacts have driven many populations to fragmentation and isolation, and even to extinction. However, some have persisted to the present day. The understanding of their evolution requires long-term studies, in which pollen analysis is a key approach both for formulating hypotheses and supporting results from other disciplines. Mountain ranges have played and still play an essential role as both glacial and interglacial refugia during the Quaternary. The Spanish Central System harbors an exceptional diversity due to its geographical location and complex topography. Some cold-adapted species have survived here with significant proportions of their southernmost populations, often displaying striking adaptations to their changing environments. This work contains a comprehensive review of the palynological investigations conducted in the Spanish Central System, and reveals the distribution of genera such as Taxus, Betula, Fagus, Carpinus and Tilia throughout the Holocene. We also highlight the scarcity of well-dated and high-resolution works, which may contribute to a better understanding of their recent and future evolution.This paper is part of the research carried our within the project "Dinámicas socio-ecológicas, resiliencia y vulnerabilidad en un paisaje de montaña: el Sistema Central (9000 cal. BC-1850 cal. AD) " (R&D National Plan of the Spanish Government, HAR2013-43701-P)

Aportes de la clínica forense para conceptuar en materia probatoria sobre el riesgo para la vida en el delito de tentativa de homicidio en Colombia

The establishment of attempted murder requires the judicial inquiry to provide different evidences. Forensic technical report of nonfatal injuries at the request of the authorities can provide valuable medical concepts on the magnitude, location and severity of the injuries. So far, there has been no objective evidence built from medical science for the assessment of the likelihood of a fatal injury. In this article, we review the forensic and medical-legal concepts, which allow providing percentages of probability of fatal injury from world-renowned medical scales.El establecimiento del tipo penal de tentativa de homicidio exige a la investigación judicial aportar diferentes elementos probatorios. En este sentido, el informe técnico médico-legal de lesiones no fatales, realizado a solicitud de las autoridades, puede aportar valiosos conceptos médicos sobre la gravedad de las mismas, su localización y severidad. Sin embargo, hasta el momento no se han incorporado elementos determinantemente objetivos a partir de la ciencia médica forense para la valoración de la probabilidad que tenga una lesión para causar la muerte. En este artículo se revisan conceptos médico-legales y médicos en el contexto jurídico, que permitirían aportar una ponderación más estructurada de la probabilidad de causar la muerte de una lesión, fundamentalmente a partir de escalas médicas mundialmente reconocidas

Seed storage conditions change the germination pattern of clonal growth plants in Mediterranean salt marshes.

8 páginas, 4 tablas, 8 figuras.The effect of salinity level and extended exposure to different salinity and flooding conditions on germination patterns of three saltmarsh clonal growth plants (Juncus subulatus, Scirpus litoralis, and S. maritimus) was studied. Seed exposure to extended flooding and saline conditions significantly affected the outcome of the germination process in a different, though predictable, way for each species, after favorable conditions for germination were restored. Tolerance of the germination process was related to the average salinity level measured during the growth/germination season at sites where established individuals of each species dominated the species cover. No relationship was found between salinity tolerance of the germination process and seed response to extended exposure to flooding and salinity conditions. The salinity response was significantly related to the conditions prevailing in the habitats of the respective species during the unfavorable (nongrowth/nongermination) season. Our results indicate that changes in salinity and hydrology while seeds are dormant affect the outcome of the seed-bank response, even when conditions at germination are identical. Because these environmental-history-dependent responses differentially affect seed germination, seedling density, and probably sexual recruitment in the studied and related species, these influences should be considered for wetland restoration and managementFinancial support from the Spanish Ministry of the Environment (MMA, project 05/99) and the Junta de Andalucía (research group 4086)enabled us to carry out the present work.Peer reviewe

Seed storage conditions change the germination pattern of clonal growth plants in Mediterranean salt marshes.

8 páginas, 4 tablas, 8 figuras.The effect of salinity level and extended exposure to different salinity and flooding conditions on germination patterns of three saltmarsh clonal growth plants (Juncus subulatus, Scirpus litoralis, and S. maritimus) was studied. Seed exposure to extended flooding and saline conditions significantly affected the outcome of the germination process in a different, though predictable, way for each species, after favorable conditions for germination were restored. Tolerance of the germination process was related to the average salinity level measured during the growth/germination season at sites where established individuals of each species dominated the species cover. No relationship was found between salinity tolerance of the germination process and seed response to extended exposure to flooding and salinity conditions. The salinity response was significantly related to the conditions prevailing in the habitats of the respective species during the unfavorable (nongrowth/nongermination) season. Our results indicate that changes in salinity and hydrology while seeds are dormant affect the outcome of the seed-bank response, even when conditions at germination are identical. Because these environmental-history-dependent responses differentially affect seed germination, seedling density, and probably sexual recruitment in the studied and related species, these influences should be considered for wetland restoration and managementFinancial support from the Spanish Ministry of the Environment (MMA, project 05/99) and the Junta de Andalucía (research group 4086)enabled us to carry out the present work.Peer reviewe

Mutations in TRIM63 cause an autosomal-recessive form of hypertrophic cardiomyopathy

Objective: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. TRIM63 has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in TRIM63 and the development of HCM. Methods: TRIM63 was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls. Results: Sixteen index cases with rare homozygous or compound heterozygous variants in TRIM63 (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%). Conclusion: TRIM63 appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe

Doñana. Acta vertebrata. vol 24(1/2)

Alimentación de la lagartija colilarga Psammodromus algirus (L) (Sauria, Lacertidae), en el litoral de Huelva (SO EspañaLa alimentación de Myotis myotis Borkh, 1791 (Chiroptera, Vespertilionidae) en la cuenca del rio Guadix (sureste de España)Distribución y selección de hábitat de la garduña (Martes foina, Erxleben, 1777) en Vizcaya y Sierra Salvada (Burgos).Nuevo modelo de trampa para reducir el impacto de la pesca de cangrejos sobre los vertebrados en las marismas del GuadalquiviThe functions of song and the spatial pattern of song production in the rufous bush chat (Cercotrichas galactotes)Migración e invernada de las lavanderas cascadena Motacilla cinerea y blanca M. alba en la Penínula Ibérica e Islas BalearesAbundancia y reproducción de Glis glis (Linnaeus, 1766) (Rodentia, Gliridae) en el Pirineo occidental.Estatus de residencia, categorización trófica y abundancia de aves en el zoológico de La Plata, ArgentinaAvifauna reproductora y estructura del hábitat en la campiña y sierras Subbéticas de JaénDispersión de semillas de retama (Retama sphaerocarpa (L.) Boiss por el conejo (Oryctolagus cuniculus L.) en el centro de EspañaGuía para la identificación de restos óseos pertenecientes a algunos peces comunes en las aguas continentales de la Península Ibérica para el estudio de la dieta de depredadores ictiófagosDistribución y abundancia del corzo (Capreolus capreolus L. 1758) en la provincia de JaénAlimentación de las larvas de anuros en ambientes temporales del sistema del rio Paraná, Argentina.Mauremys leprosa como presa de Lutra lutraNota sobre la alimentación del lince ibérico en el Parque Natural de la Sierra de Andújar (Sierra Morena oriental)Presencia de Echinococcus granulosus (Cestoda) en un lobo ibérico (Canis lupusLa orientación de los nidos de paseriformes estepariosComparación de la dieta obtenida a partir de muestras estomacales y fecales del Tuco-tuco, Ctenomys mendocinus, en dos poblaciones de la precordillera de los Andes, ArgentinaEstructura genética y distribución de la variabilidad enzimática en poblaciones naturales de estornino negro (Sturnus unicolor)Estimación de la disponibilidad trófica para el quebrantahuesos (Gypaetus barbatus) en Cataluña (NE España) e implicaciones sobre su conservaciónPeer reviewe