Unraveling the genetics of transformed splenic marginal zone lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; MutationLeucemia linfocítica crónica de células B; Linfoma de células B grandes difuso; MutaciónLeucèmia limfocítica crònica de cèl·lules B; Limfoma de cèl·lules B grans difús; MutacióThe genetic mechanisms associated with splenic marginal zone lymphoma (SMZL) transformation are not well defined. We studied 41 patients with SMZL that eventually underwent large B-cell lymphoma transformation. Tumor material was obtained either only at diagnosis (9 patients), at diagnosis and transformation (18 patients), and only at transformation (14 patients). Samples were categorized in 2 groups: (1) at diagnosis (SMZL, n = 27 samples), and (2) at transformation (SMZL-T, n = 32 samples). Using copy number arrays and a next-generation sequencing custom panel, we identified that the main genomic alterations in SMZL-T involved TNFAIP3, KMT2D, TP53, ARID1A, KLF2, 1q gains, and losses of 9p21.3 (CDKN2A/B) and 7q31-q32. Compared with SMZL, SMZL-T had higher genomic complexity, and higher incidence of TNFAIP3 and TP53 alterations, 9p21.3 (CDKN2A/B) losses, and 6p gains. SMZL and SMZL-T clones arose by divergent evolution from a common altered precursor cell that acquired different genetic alterations in virtually all evaluable cases (92%, 12 of 13 cases). Using whole-genome sequencing of diagnostic and transformation samples in 1 patient, we observed that the SMZL-T sample carried more genomic aberrations than the diagnostic sample, identified a translocation t(14;19)(q32;q13) present in both samples, and detected a focal B2M deletion due to chromothripsis acquired at transformation. Survival analysis showed that KLF2 mutations, complex karyotype, and International Prognostic Index score at transformation were predictive of a shorter survival from transformation (P = .001; P = .042; and P = .007; respectively). In summary, SMZL-T are characterized by higher genomic complexity than SMZL, and characteristic genomic alterations that could represent key players in the transformation event.This study was supported by Fundacion Asociación Española Contra el Cancer (AECC)/Centro de Investigación Biomédica en Red de Cancer (CIBERONC): PROYE18020BEA (S.B.), fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III “Cofinanciado por la Union Europea ´ and Fondos FEDER: European Regional Development Fund “Una manera de hacer Europa”: PI17/ 01061 (S.B.), PI19/00887 (A.L.-G. and E.G.), INT20/00050 (A.L.- G.), MaratO TV3-Cancer/201904-30 (S.B.), Generalitat de Catalunya Suport Grups de Recerca AGAUR (2021-SGR-01293 [S.B.] and 2021-SGR-01172 [E.C.]), and Ministerio de Ciencia e Innovacion (PID2021-123054OB-I00 [E.C.]). C.L. is supported by postdoctoral Beatriu de Pinos grant, Secretaria d´Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya and by Marie Sklodowska-Curie COFUND program from H2020 (2018-BP-00055). E.C. is an Academia Researcher of the "Institucio Catalana de Recerca i Estudis Avançats" of the Generalitat de Catalunya. This work was mainly developed at the Centre Esther Koplowitz (CEK), Barcelona, Spain

Validación por SRM de marcadores de la actividad TGF-β en CSF de pacientes con glioma

Comunicaciones a congreso

Arqueologia dels centres productors de manufactures al Comtat de Manresa (Segles X-XII): els jaciments de monistrol de gaià i cal ticó. (Gaià-castellnou de Bages)

Amb aquesta aportació pretenem exposar els avenços experimentats en els darrers anys des del grup de recerca Ocorde en terres de la Catalunya Central, tot donant continuïtat a unes primeres dades publicades en les anteriors jornades d'arqueologia (Folch et ali, 2012)2. Llavors fèiem conèixer els resultats acumulats en diversos projectes de prospecció i excavació desenvolupats al llarg d'una quinzena d'anys i que, a nivell geogràfic, se circumscrivien especialment a l'àrea del nord del Bages i el Baix Berguedà. Ara, però, la nostra intenció és centrar-nos en els dos jaciments on hem mantingut activitat durant els darrers temps, Monistrol de Gaià i Cal Ticó. La seva exposició i tractament conjunts es justifiquen, més enllà de la seva proximitat geogràfica, per la seva natura d'establiments caracteritzats principalment per l'existència d'una activitat específica de producció de manufactures que s'insereix en un context històric i cronològic prou precís, que es correspon amb els primers temps comtals (segles X-XII) i la imposició de senyories

Fake News i la política catalana

La campanya presidencial de Donald Trump als Estats Units va posicionar les fake news en l'àmbit comunicatiu mundial. Aquest reportatge analitzarà la situació d'aquestes notícies falses dins del territori català i la influència en la celebració del referèndum de l'1 d'octubre del 2017 i les eleccions catalanes del 21 de desembre del mateix any. Per poder realitzar el reportatge s'ha entrevistat els responsables de comunicació de diferents partits polítics amb representació al Parlament de Catalunya, els caps d'informatius dels principals mitjans de comunicació de Catalunya, com també periodistes i fact-checkers.La campaña presidencial de Donald Trump en los Estados Unidos posicionó las fake news en el ámbito comunicativo mundial. Este reportaje analizará la situación de estas noticias falsas en el territorio catalán y la influencia en la celebración del referéndum del 1 de octubre y las elecciones catalanas del 21 de diciembre del mismo año. Para realizar el reportaje se ha entrevistado a responsables de comunicación de distintos partidos políticos con representación en el Parlamento de Cataluña, a responsables de informativos de los principales medios de comunicación de Cataluña y también a periodistas y fact-checkers.The concept: fake news appeared first during Donald Trump's presidency campaign and placed the term in the jornalistic world. This longform piece will analyze the situation these kind of news face in the Catalan territory considering the celebration of the 2017's 1st of October referendum and the Catalan elections held that same year. In order to write the piece we have interviewed the communication's team leader of different political parties at the Catalan Parliament and some heads of news programs from the main media outlets in Catalonia, as well as journalists and fact-checkers

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

Variants of the FADS1 FADS2 Gene Cluster, Blood Levels of Polyunsaturated Fatty Acids and Eczema in Children within the First 2 Years of Life

Association of genetic-variants in the FADS1-FADS2-gene-cluster with fatty-acid-composition in blood of adult-populations is well established. We analyze this genetic-association in two children-cohort-studies. In addition, the association between variants in the FADS-gene-cluster and blood-fatty-acid-composition with eczema was studied. Data of two population-based-birth-cohorts in The Netherlands and Germany (KOALA, LISA) were pooled (n = 879) and analyzed by (logistic) regression regarding the mutual influence of single-nucleotide-polymorphisms (SNPs) in the FADS-gene-cluster (rs174545, rs174546, rs174556, rs174561, rs3834458), on polyunsaturated fatty acids (PUFA) in blood and parent-reported eczema until the age of 2 years. All SNPs were highly significantly associated with all PUFAs except for alpha-linolenic-acid and eicosapentaenoic-acid, also after correction for multiple-testing. All tested SNPs showed associations with eczema in the LISA-study, but not in the KOALA-study. None of the PUFAs was significantly associated with eczema neither in the pooled nor in the analyses stratified by study-cohort. PUFA-composition in young children's blood is under strong control of the FADS-gene-cluster. Inconsistent results were found for a link between these genetic-variants with eczema. PUFA in blood was not associated with eczema. Thus the hypothesis of an inflammatory-link between PUFA and eczema by the metabolic-pathway of LC-PUFAs as precursors for inflammatory prostaglandins and leukotrienes could not be confirmed by these data

Complex I-Associated Hydrogen Peroxide Production Is Decreased and Electron Transport Chain Enzyme Activities Are Altered in n-3 Enriched fat-1 Mice

The polyunsaturated nature of n-3 fatty acids makes them prone to oxidative damage. However, it is not clear if n-3 fatty acids are simply a passive site for oxidative attack or if they also modulate mitochondrial reactive oxygen species (ROS) production. The present study used fat-1 transgenic mice, that are capable of synthesizing n-3 fatty acids, to investigate the influence of increases in n-3 fatty acids and resultant decreases in the n-6∶n-3 ratio on liver mitochondrial H2O2 production and electron transport chain (ETC) activity. There was an increase in n-3 fatty acids and a decrease in the n-6∶n-3 ratio in liver mitochondria from the fat-1 compared to control mice. This change was largely due to alterations in the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine, with only a small percentage of fatty acids in cardiolipin being altered in the fat-1 animals. The lipid changes in the fat-1 mice were associated with a decrease (p<0.05) in the activity of ETC complex I and increases (p<0.05) in the activities of complexes III and IV. Mitochondrial H2O2 production with either succinate or succinate/glutamate/malate substrates was also decreased (p<0.05) in the fat-1 mice. This change in H2O2 production was due to a decrease in ROS production from ETC complex I in the fat-1 animals. These results indicate that the fatty acid changes in fat-1 liver mitochondria may at least partially oppose oxidative stress by limiting ROS production from ETC complex I