El impacto demográfico y económico del envejecimiento de la población de la cc.aa. de Euskadi

El principal objetivo de este trabajo ha sido determinar el impacto del coste total de las pensiones del País Vasco a pagar hacia el futuro. Para ello hemos recabado información del colectivo de Euskadi, y además de haber analizado su evolución respecto a algunos elementos demográficos, también hemos obtenido la información estadística necesaria para la elaboración del tanto central de mortalidad (para cada año de edad y año de calendario). Con los datos obtenidos se ha procedido a realizar un análisis de sensibilidad comparando los resultados que se obtienen al aplicar la tabla de mortalidad propia, creada a partir del tanto central de mortalidad (mx), con la tabla PASEM-2010 y la PERM/F-2000, de uso frecuente en las transacciones de seguros. En relación a los datos más destacados en este trabajo, se aprecia que hay una gran similitud, entre los resultados obtenidos respecto a los costes de las pensiones de jubilación, aplicando la tabla que se ha elaborado a partir de las estadísticas de defunciones y población especificas del País Vasco, y la PERM/F-2000, 2000. Por otro lado, se observan grandes desviaciones en los costes de las pensiones reduciéndose en el caso de la tabla PASEM-2010 o aumentando en el caso de PERM/F-2000, 2010, respecto al resto tablas utilizadas.

Subcutaneous fat composition of youthful and mature Canadian beef: emphasis on individual conjugated linoleic acid and trans-18:1 isomers

[EN]A comprehensive evaluation of the fatty acid composition of subcutaneous adipose tissue from beef cattle produced in western Canada was undertaken to determine if the current Canadian grading system is able to distinguish classes of animals with value added potential due to their fatty acid composition. Grades included youthful Canadian Yield Grade 1 A/AA beef, under (YUTM) and over (YOTM) 30 mo of age and the four mature grades (D1, D2, D2 and D4). Subcutaneous fat between the 12th and 13th ribs over the longissimus muscle was obtained from 18_21 animals per grade. Fatty acids were analyzed using a combination of silver-ion HPLC and GC with a highly polar 100 m column. There were no differences in total trans-18:1 content amongst grades, but adipose tissue from grade D1, D2 and D4 had more 11t-18:1 than YUTM (PB0.05), whereas adipose tissue from YUTM carcasses had more 10t-18:1 than all other grades (PB0.05). Adipose tissue from YUTM carcasses also had less total CLA (PB0.05) than the D grades, mainly due to a lower level of 9c,11t-CLA, but they had slightly more 7t,9c-CLA and 10t,12c-CLA (PB0.05). Adipose tissue from YOTM and D grades contained more n-3 fatty acids relative to YUTM (0.56% vs. 0.29%; PB0.05) and lower n-6:n-3 ratios (PB0.05). Overall, older animals (YOTM and D grades) had adipose tissue compositions with higher levels of fatty acids with reported health benefits. Taken together, these higher levels may provide opportunities for value added marketing if regulatory authorities allow claims for their enrichment based on demonstrated health benefits. Higher concentrations of beneficial fatty acids, however, need to be considered within the context of the complete fatty acid profile and it would be important to demonstrate their advantages in the presence of relatively high levels of saturated fatty acids.

Papel de las GTPasas de la familia rho en la señalización mediada por el receptor P2X7

El objetivo de este proyecto es estudiar la señalización del receptor P2X7 en respuesta a ATP en macrófagos J774A.1 y en células CHO K1. Para ello, se subclonó el gen que codifica para la proteína P2X7 en el vector PMT2 HA AA. Este plásmido fue transfectado a células CHO K1, J774.A1 y HEK 293T para distintas pruebas como la movilización de calcio intracelular para comprobar si ambos tipos celulares muestran la misma señal, y además se miró la expresión de este receptor y si su activación mediada por ATP se traduce en la activación de proteínas de la familia Rho. Se ha visto que las J774A.1 expresan funcionalmente el receptor P2X7, mientras que las CHO K1 muestran una respuesta funcional diferente que no se corresponde con la clásica señalización del P2X7 asociado a la apertura del canal y posterior poro. Además, al expresar el receptor en celúlas HEK 293T, se ha visto de una manera indirecta, midiendo la fosforilación de PAK, que la ruta de rac se regula de forma positiva cuando se activa el receptor P2X7 en macrófagos.

La cooperación al desarrollo de las Comunidades Autónomas del Estado español: relevancia, alcance y aportación específica

318 p.

Ikas-Komunitateak: solasaldi dialogiko literarioak eta irakur-laguna, Etxebarriko Kukullaga eskolan.

[EUS] Egungo informazioaren gizartean, etengabeko aldaketa sakonak jasaten eta sortzen ditugu, halaber gure gizabanako harremanetan ere. Hala ere, hezkuntzak oraindik ez du aldaketa handirik egin, izan ere, nahiko estatikoa izaten jarraitzen du eta bertan ematen diren harremanak zeharo hierarkikoak dira. Honengatik guztiagatik, ikerketa honen xede nagusia, Ikas-Komunitateak eta honen barruan dagoen Etxebarriko KUKULLAGA LHI (Bizkaia) aztertzea izango da. Horrez gain, eskolarekin batera diseinatu dudan proiektua aurkeztuko dut, zeinean Ikas-Komunitateen bi jarduera burutzen diren: irakur-laguna eta solasaldi dialogiko literarioak. Bertan, Lehen Hezkuntzako 6. mailako eta 5 urteko ikasleek parte hartu dute. Aipatzekoa da lortutako emaitzak guztiz baikorrak izan direla eta epe-laburrerako ezarritako helburuak lortu direla. Horrez gain, epe-luzerako helburuak hein handi batean beteko direla aurreikusten da. Beraz, argi dago, zentroetan antolakuntza egoki bat ematen bada, Ikas- Komunitateen proiektuarekiko inplikazioa badago eta komunitatearen kohesioa lortzen bada, hezkuntza sistema hein batean alda daitekeela. Hori gertatuz gero, edozein motatako pertsonak hezkuntza emaitzarik onenak lor ditzake eta baita informazioaren gizarte honetan jarduten ikas dezake ere.

Structure-function analysis of USP1: insights into the role of Ser313 phosphorylation site and the effect of cancer-associated mutations on autocleavage

Background: In complex with its cofactor UAF1, the USP1 deubiquitinase plays an important role in cellular processes related to cancer, including the response to DNA damage. The USP1/UAF1 complex is emerging as a novel target in cancer therapy, but several aspects of its function and regulation remain to be further clarified. These include the role of the serine 313 phosphorylation site, the relative contribution of different USP1 sequence motifs to UAF1 binding, and the potential effect of cancer-associated mutations on USP1 regulation by autocleavage. Methods: We have generated a large set of USP1 structural variants, including a catalytically inactive form (C90S), non-phosphorylatable (S313A) and phosphomimetic (S313D) mutants, deletion mutants lacking potential UAF1 binding sites, a mutant (GG/AA) unable to undergo autocleavage at the well-characterized G670/G671 diglycine motif, and four USP1 mutants identified in tumor samples that cluster around this cleavage site (G667A, L669P, K673T and A676T). Using cell-based assays, we have determined the ability of these mutants to bind UAF1, to reverse DNA damage-induced monoubiquitination of PCNA, and to undergo autocleavage. Results: A non-phosphorylatable S313A mutant of USP1 retained the ability to bind UAF1 and to reverse PCNA ubiquitination in cell-based assays. Regardless of the presence of a phosphomimetic S313D mutation, deletion of USP1 fragment 420-520 disrupted UAF1 binding, as determined using a nuclear relocation assay. The UAF1 binding site in a second UAF1-interacting DUB, USP46, was mapped to a region homologous to USP1(420-520). Regarding USP1 autocleavage, co-expression of the C90S and GG/AA mutants did not result in cleavage, while the cancer-associated mutation L669P was found to reduce cleavage efficiency. Conclusions: USP1 phosphorylation at S313 is not critical for PCNA deubiquitination, neither for binding to UAF1 in a cellular environment. In this context, USP1 amino acid motif 420-520 is necessary and sufficient for UAF1 binding. This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs. On the other hand, our results support the view that USP1 autocleavage may occur in cis, and can be altered by a cancer-associated mutation.

Serological and Genetic Evidence for Altered Complement System Functionality in Systemic Lupus Erythematosus: Findings of the GAPAID Consortium

Systemic lupus erythematosus is a chronic autoimmune disease with multifactorial ethiopathogenesis. The complement system is involved in both the early and late stages of disease development and organ damage. To better understand autoantibody mediated complement consumption we examined ex vivo immune complex formation on autoantigen arrays. We recruited patients with SLE (n = 211), with other systemic autoimmune diseases (n = 65) and non-autoimmune control subjects (n = 149). Standard clinical and laboratory data were collected and serum complement levels were determined. The genotype of SNP rs1143679 in the ITGAM gene was also determined. Ex vivo formation of immune complexes, with respect to IgM, IgG, complement C4 and C3 binding, was examined using a functional immunoassay on autoantigen microarray comprising nucleic acids, proteins and lipids. Complement consumption of nucleic acids increased upon binding of IgM and IgG even when serum complement levels were decreased due to consumption in SLE patients. A negative correlation between serum complement levels and ex vivo complement deposition on nucleic acid autoantigens is demonstrated. On the contrary, complement deposition on tested protein and lipid autoantigens showed positive correlation with C4 levels. Genetic analysis revealed that the non-synonymous variant rs1143679 in complement receptor type 3 is associated with an increased production of anti-dsDNA IgG antibodies. Notwithstanding, homozygous carriers of the previously reported susceptible allele (AA) had lower levels of dsDNA specific IgM among SLE patients. Both the non-synonymous variant rs1143679 and the high ratio of nucleic acid specific IgG/IgM were associated with multiple organ involvement. In summary, secondary complement deficiency in SLE does not impair opsonization of nucleic-acid-containing autoantigens but does affect other antigens and potentially other complement dependent processes. Dysfunction of the receptor recognizing complement opsonized immune complexes promotes the development of class-switched autoantibodies targeting nucleic acids.