Comparative genomic analysis of the zebra finch degradome provides new insights into evolution of proteases in birds and mammals

<p>Abstract</p> <p>Background</p> <p>The degradome -the complete repertoire of proteases in an organism- is involved in multiple key biological and pathological processes. Previous studies in several organisms have yielded sets of curated protease sequences which may be used to characterize the degradome in a novel genome by similarity. Differences between degradomes can then be related to physiological traits of the species under study. Therefore, the sequencing of the zebra finch genome allows the comparison between the degradomes of mammals and birds and may help to understand the biological peculiarities of the zebra finch.</p> <p>Results</p> <p>A set of curated protease sequences from humans and chicken was used to predict the sequences of 460 protease and protease-like genes in the zebra finch genome. This analysis revealed important differences in the evolution of mammalian and bird degradomes, including genomic expansions and deletions of caspases, cytotoxic proteases, kallikreins, matrix metalloproteases, and trypsin-like proteases. Furthermore, we found several zebra finch-specific features, such as duplications in <it>CASP3 </it>and <it>BACE</it>, and a large genomic expansion of acrosin.</p> <p>Conclusions</p> <p>We have compared the degradomes of zebra finch, chicken and several mammalian species, with the finding of multiple differences which illustrate the evolution of the protease complement of these organisms. Detailed analysis of these changes in zebra finch proteases has shown that they are mainly related to immunological, developmental, reproductive and neural functions.</p

Dificultades en el aprendizaje del concepto de probabilidad clásica en estudiantes de octavo grado

En este estudio se identifican y se analizan las dificultades que presentan los estudiantes del grado octavo, cuando aprenden lo relacionado con la probabilidad clásica en cuanto a referentes históricos-culturales que han influido en el desarrollo de la probabilidad. A partir de estos referentes teóricos se diseña y aplica una tarea contextualizada a partir de la cual se analizan los resultados obtenidos se determinan las dificultades que se presentan y posteriormente se plantean las conclusiones y se proponen posibles soluciones a las problemáticas encontradas

Squalene stimulates a key innate immune cell to foster wound healing and tissue repair

Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro- and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF-α and NF-κB in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing

Evolution of nutritional biochemical parameters in hemodialysis patients during a one-year follow-up period

La elevada supervivencia actual del paciente en hemodiálisis (52% hasta 5 años), ha hecho que se pongan de manifiesto complicaciones crónicas como la elevada prevalencia de malnutrición en los enfermos, así como la importancia de la situación nutricional en la morbi-mortalidad que presentan. La causa de desnutrición proteico-calórica es multifactorial, aunque procesos de inflamación crónica asociada a la técnica de diálisis cobran cada vez más relevancia. Se han evaluado las variaciones de distintos parámetros bioquímicos nutricionales (proteínas totales, albúmina plasmática, transferrina y colesterol total) de 73 pacientes en hemodiálisis durante un año de seguimiento. La edad media de los pacientes era de 53,3 ± 18,69 años, con 43 varones y 30 mujeres. El tiempo en programa de hemodiálisis ha sido de 43 ± 33 meses, con una duración media de la sesión de 246 ± 24 minutos y dosis media de hemodiálisis administrada de 1,37 ± 0,27 (KT/V) (Daurgidas 2ª generación). Se ha observado un descenso en todos los parámetros bioquímicos evaluados, con diferencias estadísticamente significativas: Proteínas totales (p < 0,001), albúmina (p < 0,00001), colesterol total (p < 0,05) y transferrina (p < 0,01). La evolución de los parámetros bioquímicos nutricionales evaluados mostró un importante deterioro nutricional de los pacientes estables con el tratamiento.Current high survival in hemodialysis patients (52% at 5 years) have made the chronic manifestations to emerge such as the high hyponutrition prevalence of these patients, as well as the importance of the nutritional status in their morbimortality. The reason for protein-caloric hyponutrition is multifactorial, although chronic inflammatory conditions associated to the dialysis technique are becoming more and more relevant. The variations in several nutritional biochemical parameters (total proteins, plasma albumin, transferrin, and total cholesterol) have been assessed in 73 hemodialysis patients for one year. The mean age of the patients was 53.3 ± 18.69 years (43 males and 30 females). The average on hemodialysis program was 43 ± 33 months, with a mean session duration of 246 ± 24 minutes, and mean hemodialysis dose administered of 1.37 ± 0.27 (KT/V) (second generation Daurgidas). A decrease in all the biochemical parameters assessed has been observed, with statistically significant differences: total proteins (p < 0.001), albumin (p < 0.00001), total cholesterol (p < 0.05), and transferrin (p < 0.01). The evolution of the nutritional biochemical parameters assessed showed an important nutritional deterioration of the patients remaining stable with the therapy

Resistance of hyperhomocysteinemia in renal patients to treatment with supra-physiological doses of parenteral folic acid

Los pacientes en hemodiálisis presentan un aumento de homocisteína plasmática (Hcy), debido a la alteración en la metilación causada por la uremia y déficit de los cofactores necesarios (vitamina B, ácido fólico). Esto se correlaciona con un mayor desarrollo de la enfermedad vascular prematura. El tratamiento, no está consensuado, siendo escasa la respuesta a la administración oral de dosis convencionales de ácido fólico. En este trabajo valoramos la respuesta de la hiperhomocisteinemia de 73 pacientes en programa de hemodiálisis periódica tras la administración de 50 mg de ácido folínico parenteral durante 18 meses. La homocisteína plasmática de los pacientes en el momento de inicio del estudio presentaba unos valores medios de 22,67 (μmol/l). Durante el primer año de suplementación mantuvieron el valor medio de 20 μmol/l. A partir del primer año de tratamiento, y hasta finalizar los 18 meses de observación, los niveles medios de homocisteína fueron de 19,58 μmol/l. Aunque con el tiempo de tratamiento encontramos una clara tendencia al descenso de sus valores plasmáticos, no existieron diferencias estadísticamente significativas. Los valores de homocisteína no se normalizaron en ninguno de los pacientes tratados.Hemodialysis patients present an increase in plasma homocysteine (Hcy) due to methylation impairment caused by uremia and the deficiency of the co-factors needed (vitamin B, folic acid). This correlates with a more common development of premature vascular disease. There is no consensus on the therapy, with a poor response to oral administration of conventional doses of folic acid. In this work, we assessed the response of hyperhomocysteinemia in 73 regular hemodialysis patients after the administration of 50 mg of parenteral folinic acid for 18 months. Plasma homocysteine of the patients at the time of the study beginning presented mean values of 22.67 (μmol/L). During the first year of supplementation the mean value was kept at 20 μmol/L. From the first year to the end of the 18-months observation period the mean homocysteine levels were 19.58 μmol/L. Although we found a clear trend towards a decrease in plasma homocysteine levels during the treatment period, there were no significant differences. Homocysteine levels did not come back to normal in none of the patients treated

Ecosystem services of tropical dry forests : insights from longterm ecological and social research on the Pacific coast of Mexico

In the search for an integrated understanding of the relationships among productive activities, human well-being, and ecosystem functioning, we evaluated the services delivered by a tropical dry forest (TDF) ecosystem in the Chamela Region, on the Pacific Coast of Mexico. We synthesized information gathered for the past two decades as part of a long-term ecosystem research study and included social data collected in the past four years using the Millennium Ecosystem Assessment (MA) conceptual framework as a guide. Here we identify the four nested spatial scales at which information has been obtained and emphasize one of them through a basin conceptual model. We then articulate the biophysical and socio-economic constraints and drivers determining the delivery of ecosystem services in the Region. We describe the nine most important services, the stakeholders who benefit from those services, and their degree of awareness of such services. We characterize spatial and temporal patterns of the services&rsquo; delivery as well as trade-offs among services and stakeholders. Finally, we contrast three alternative future scenarios on the delivery of ecosystem services and human well-being. Biophysical and socioeconomic features of the study site strongly influence human&minus;ecosystem interactions, the ecosystem services delivered, the possible future trajectories of the ecosystem, and the effect on human well-being. We discuss future research approaches that will set the basis for an integrated understanding of human&minus;ecosystem interactions and for constructing sustainable management strategies for the TDF.<br /

Miniatures from domestic contexts in Iron age Iberia

This article reviews a set of miniatures from domestic contexts in Iron Age eastern Iberia, and interprets them in terms of their role in forging social personae. After an introduction to the historical case under consideration, the miniatures are described in terms of their typology and their contexts of provenance are outlined. Though not abundant, they tend to occur in central places in the landscape; specifically, they are often found in houses of the powerful. The vast majority are miniatures of pottery and tools, though some miniature weapons are recorded. We contend that these objects were used as a means of enculturation and for the learning of values and norms. It is no coincidence that they emerge in the archaeological record of Iron Age Iberia at the same time as the rise of a social structure based on hereditary power

POT1 mutations predispose to familial melanoma

Deleterious germline variants in CDKN2A account for around 40% of familial melanoma cases, and rare variants in CDK4, BRCA2, BAP1 and the promoter of TERT have also been linked to the disease. Here we set out to identify new high-penetrance susceptibility genes by sequencing 184 melanoma cases from 105 pedigrees recruited in the UK, The Netherlands and Australia that were negative for variants in known predisposition genes. We identified families where melanoma cosegregates with loss-of-function variants in the protection of telomeres 1 gene (POT1), with a proportion of family members presenting with an early age of onset and multiple primary tumors. We show that these variants either affect POT1 mRNA splicing or alter key residues in the highly conserved oligonucleotide/oligosaccharide-binding (OB) domains of POT1, disrupting protein-telomere binding and leading to increased telomere length. These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres.D.J.A., C.D.R.-E., Z.D., J.Z.L., J.C.T., M.P. and T.M.K. were supported by Cancer Research UK and the Wellcome Trust (WT098051). C.D.R.-E. was also supported by the Consejo Nacional de Ciencia y Tecnología of Mexico. K.A.P. and A.M.D. were supported by Cancer Research UK (grants C1287/A9540 and C8197/A10123) and by the Isaac Newton Trust. N.K.H. was supported by a fellowship from the National Health and Medical Research Council of Australia (NHMRC). L.G.A. was supported by an Australia and New Zealand Banking Group Limited Trustees PhD scholarship. A.L.P. is supported by Cure Cancer Australia. The work was funded in part by the NHMRC and Cancer Council Queensland. The work of N.A.G. was in part supported by the Dutch Cancer Society (UL 2012-5489). M.H., J.A.N.-B. and D.T.B. were supported by Cancer Research UK (programme awards C588/A4994 and C588/A10589 and the Genomics Initiative). C.L.-O., A.J.R. and V.Q. are funded by the Spanish Ministry of Economy and Competitiveness through the Instituto de Salud Carlos III (ISCIII), the Red Temática de Investigación del Cáncer (RTICC) del ISCIII and the Consolider-Ingenio RNAREG Consortium. C.L.-O. is an investigator with the Botín Foundation.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.294

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Accelerated inbreeding depression suggests synergistic epistasis for deleterious mutations in Drosophila melanogaster

Epistasis may have important consequences for a number of issues in quantitative genetics and evolutionary biology. In particular, synergistic epistasis for deleterious alleles is relevant to the mutation load paradox and the evolution of sex and recombination. Some studies have shown evidence of synergistic epistasis for spontaneous or induced deleterious mutations appearing in mutation-accumulation experiments. However, many newly arising mutations may not actually be segregating in natural populations because of the erasing action of natural selection. A demonstration of synergistic epistasis for naturally segregating alleles can be achieved by means of inbreeding depression studies, as deleterious recessive allelic effects are exposed in inbred lines. Nevertheless, evidence of epistasis from these studies is scarce and controversial. In this paper, we report the results of two independent inbreeding experiments carried out with two different populations of Drosophila melanogaster. The results show a consistent accelerated inbreeding depression for fitness, suggesting synergistic epistasis among deleterious alleles. We also performed computer simulations assuming different possible models of epistasis and mutational parameters for fitness, finding some of them to be compatible with the results observed. Our results suggest that synergistic epistasis for deleterious mutations not only occurs among newly arisen spontaneous or induced mutations, but also among segregating alleles in natural populationsWe acknowledge the support by Uvigo Marine Research Centre funded by the “Excellence in Research (INUGA)” Programme from the Regional Council of Culture, Education and Universities, with co-funding from the European Union through the ERDF Operational Programme Galicia 2014-2020. This work was funded by Agencia Estatal de Investigación (AEI) (CGL2016-75904-C2-1-P), Xunta de Galicia (ED431C 2016-037) and Fondos Feder: “Unha maneira de facer Europa.” SD was founded by a predoctoral (FPI) grant from Ministerio de Economía y Competitividad, SpainS