27 research outputs found

    Activation-induced cytidine deaminase targets SUV4-20-mediated histone H4K20 trimethylation to class-switch recombination sites

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    Activation-induced cytidine deaminase (AID) triggers antibody diversification in B cells by catalysing deamination and subsequently mutating immunoglobulin (Ig) genes. Association of AID with RNA Pol II and occurrence of epigenetic changes during Ig gene diversification suggest participation of AID in epigenetic regulation. AID is mutated in hyper-IgM type 2 (HIGM2) syndrome. Here, we investigated the potential role of AID in the acquisition of epigenetic changes. We discovered that AID binding to the IgH locus promotes an increase in H4K20me3. In 293F cells, we demonstrate interaction between co-transfected AID and the three SUV4-20 histone H4K20 methyltransferases, and that SUV4-20H1.2, bound to the IgH switch (S) mu site, is replaced by SUV4-20H2 upon AID binding. Analysis of HIGM2 mutants shows that the AID truncated form W68X is impaired to interact with SUV4-20H1.2 and SUV4-20H2 and is unable to bind and target H4K20me3 to the Smu site. We finally show in mouse primary B cells undergoing class-switch recombination (CSR) that AID deficiency associates with decreased H4K20me3 levels at the Smu site. Our results provide a novel link between SUV4-20 enzymes and CSR and offer a new aspect of the interplay between AID and histone modifications in setting the epigenetic status of CSR sites

    Humoral and Cellular Immune Responses After a 3-dose Course of mRNA-1273 COVID-19 Vaccine in Kidney Transplant Recipients: A Prospective Cohort Study.

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    In kidney transplant recipients, there is discordance between the development of cellular and humoral response after vaccination against SARS-CoV-2. We sought to determine the interplay between the 2 arms of adaptive immunity in a 3-dose course of mRNA-1273 100 μg vaccine. Methods: Humoral (IgG/IgM) and cellular (N- and S-ELISpot) responses were studied in 117 kidney and 12 kidney-pancreas transplant recipients at the following time points: before the first dose, 14 d after the second dose' and before and after the third dose, with a median of 203 and 232 d after the start of the vaccination cycle, respectively. Results: After the second dose, 26.7% of naive cases experienced seroconversion. Before the third dose and in the absence of COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion occurred in 80.0% of patients. Naive patients who had at any time point a detectable positivity for S-ELISpot were 75.2% of the population, whereas patients who maintained S-ELISpot positivity throughout the study were 34.3%. S-ELISpot positivity at 42 d was associated with final seroconversion (odds ratio' 3.14; 95% confidence interval' 1.10-8.96; P = 0.032). Final IgG titer was significantly higher in patients with constant S-ELISpot positivity (P < 0.001). Conclusions: A substantial proportion of kidney transplant recipients developed late seroconversion after 2 doses. Cellular immunity was associated with the development of a stronger humoral respons

    Extinction risk of Mesoamerican crop wild relatives

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    Ensuring food security is one of the world's most critical issues as agricultural systems are already being impacted by global change. Crop wild relatives (CWR)—wild plants related to crops—possess genetic variability that can help adapt agriculture to a changing environment and sustainably increase crop yields to meet the food security challenge. Here we report the results of an extinction risk assessment of 224 wild relatives of some of the world's most important crops (i.e. chilli pepper, maize, common bean, avocado, cotton, potato, squash, vanilla and husk tomato) in Mesoamerica—an area of global significance as a centre of crop origin, domestication and of high CWR diversity. We show that 35% of the selected CWR taxa are threatened with extinction according to The International Union for Conservation of Nature (IUCN) Red List demonstrates that these valuable genetic resources are under high anthropogenic threat. The dominant threat processes are land use change for agriculture and farming, invasive and other problematic species (e.g. pests, genetically modified organisms) and use of biological resources, including overcollection and logging. The most significant drivers of extinction relate to smallholder agriculture—given its high incidence and ongoing shifts from traditional agriculture to modern practices (e.g. use of herbicides)—smallholder ranching and housing and urban development and introduced genetic material. There is an urgent need to increase knowledge and research around different aspects of CWR. Policies that support in situ and ex situ conservation of CWR and promote sustainable agriculture are pivotal to secure these resources for the benefit of current and future generations

    Obtención y caracterización química de líneas celulares de Rosmarinus officinalis L.

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    Resumen del trabajo presentado a las III Jornadas Científicas CIAL Fórum, celebradas del 22 al 23 de noviembre de 2018 en el Instituto de Investigación en Ciencias de la Alimentación (CIAL).El romero (Rosmarinus officinalis L.) es una planta utilizada en la industria alimentaria, cosmética y farmacéutica que produce compuestos con actividad antioxidante, antibacteriana y antiinflamatoria. En estudios de análisis químico se han identificado como compuestos mayoritarios al ácido carnósico, carnosol y ácido rosmarínico. En cultivos in vitro de romero se acumulan moléculas sintetizadas por la planta silvestre. El objetivo de este trabajo fue analizar el perfil químico de tres líneas celulares de Rosmarinus officinalis L. Se establecieron cultivos de células desdiferenciadas a partir de explantes de hoja en medio Murashige y Skoog (MS) adicionado con sacarosa (30 g/L), fitagel (3 g/L), ácido 2,4-diclorofenoxiacético (1.5 mg/L) y 6-bencilaminopurina (2.0 mg/L). Se analizó el proceso de desdiferenciación celular mediante análisis digital de imágenes con el software ImageJ® y se seleccionaron las líneas celulares. La extracción de los compuestos de romero por maceración se llevó a cabo con etanol absoluto. Los extractos de las líneas celulares se analizaron mediante cromatografía en capa fina (TLC), cromatografía en capa fina de alta resolución (HPTLC), cromatografía de gases acoplada a espectrometría de masas (GC-MS) y cromatografía de líquidos acoplada a espectrometría de masas en tándem (UHPLC-MS/MS). Los resultados permiten identificar tres etapas durante el proceso de desdiferenciación en explantes de romero, definidas como: adaptación del tejido al medio de cultivo, inducción al proceso de desdiferenciación celular y duplicación de células desdiferenciadas. Se logró obtener tres líneas celulares denominadas RoG (línea celular verde), RoY (línea celular amarilla), RoW (línea celular blanca). Se observaron diferencias en el perfil químico de las tres líneas celulares mediante TLC y HPTLC y se identificaron los compuestos de cada línea mediante GC-MS y UHPLC-MS/MS.A la SIP-IPN por el soporte financiero (SIP 20180804). Araceli Urquiza-López agradece al CONACyT por la beca otorgada y al CIAL por su acogida.Peer reviewe

    Optical Fiber Sensor For Pressure Based On Multimode Interference As Sensitive Element

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    The experimental results of applications on a novel intrinsic fiber optic pressure sensor based on multimode interference are presented. The sensitive element consists in a SM-MM-SM (MMI) fiber structure embedded in a membrane. © 2010 Optical Society of America

    The quest quality, 1935-1985

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    C CA reprint 2/86; Paper presented at the series of seminars on development of concrete- 50 years and onwards London, Edinburgh and Cardiff (GB)Available from British Library Document Supply Centre- DSC:87/15170(Quest) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

    COMPORTAMIENTO A FRACTURA DE FILMS DE NANOCOMPUESTOS DE UN COPOLÍMERO EVOH

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    Se analizó el comportamiento a fractura de films de nanocompuestos de un copolímero EVOH con diferentes porcentajes en peso de dos tipos de arcillas montmorillonitas. Los nanocompuestos fueron obtenidos a través de un proceso de extrusión de doble husillo. Mediante una extrusora calandra, se obtuvieron los diferentes films con un espesor de aproximadamente 300μm. El estudio morfológico se llevó a cabo mediante difracción de rayos X y microscopia electrónica de transmisión (MET) observando rasgos de intercalación con algunos porcentajes. El análisis fractográfico se realizó por microscopia electrónica de barrido (MEB). El comportamiento mecánico se analizó mediante ensayos de tracción y el de fractura mediante la técnica de trabajo esencial de fractura (EWF). Se encontraron variaciones importantes en la tenacidad de los compuestos en función del tipo y porcentaje de arcilla que se relacionan con las morfologías resultantes.Peer Reviewe

    Chronic consumption of avocado seed (Persea americana) promotes a negative energy balance and body weight reduction in high-fat diet exposed mice: Implications for functional foods

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    Obesity is the main challenge for public health systems. Functional foods have emerged as an alternative to the ineffectiveness of pharmacological therapies. However, it is necessary to investigate to find sources of raw material for its preparation. The aim of this work was to evaluate the functional effects of residual avocado seed in diet-induced obese mice. Animals were fed a high-fat diet supplemented with avocado seed (1.25%) for 6 weeks. Body weight, food intake, satiety, physical activity, and energy expenditure-involved gene expression were measured. Supplementation with avocado seed led to reduced body weight, delayed satiety, increased physical activity, and induced Dio2 and Adrb1 expression in hypothalamus and white adipose tissue, respectively. No changes in markers of hepatic injury were observed. In conclusion, avocado seed exerts functional effects on obese mice, by promoting energy expenditure, without toxicity effects, making it possible to use this by-product in the development of functional foods

    The early-life exposome modulates the effect of polymorphic inversions on DNA methylation

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    Polymorphic genomic inversions are chromosomal variants with intrinsic variability that play important roles in evolution, environmental adaptation, and complex traits. We investigated the DNA methylation patterns of three common human inversions, at 8p23.1, 16p11.2, and 17q21.31 in 1,009 blood samples from children from the Human Early Life Exposome (HELIX) project and in 39 prenatal heart tissue samples. We found inversion-state specific methylation patterns within and nearby flanking each inversion region in both datasets. Additionally, numerous inversion-exposure interactions on methylation levels were identified from early-life exposome data comprising 64 exposures. For instance, children homozygous at inv-8p23.1 and higher meat intake were more susceptible to TDH hypermethylation (P = 3.8 × 10-22); being the inversion, exposure, and gene known risk factors for adult obesity. Inv-8p23.1 associated hypermethylation of GATA4 was also detected across numerous exposures. Our data suggests that the pleiotropic influence of inversions during development and lifetime could be substantially mediated by allele-specific methylation patterns which can be modulated by the exposome.The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no 308333 (HELIX project), and the H2020-EU.3.1.2.—Preventing Disease Programme under grant agreement no 874583 (ATHLETE project). The HELIX genotyping was supported by the projects PI17/01225 and PI17/01935, funded by the Instituto de Salud Carlos III and cofunded by European Union (ERDF, “A way to make Europe”) and the Centro Nacional de Genotipado-CEGEN (PRB2-ISCIII). BiB received core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1). INMA-SAB data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV.2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers, EU FP7-HEALTH-2009- single stage CHICOS, EU FP7 ENV.2008.1.2.1.6. Proposal No 226285 ENRIECO, EU FP7-HEALTH-2012 Proposal No 308333 HELIX). This research has received funding from the Spanish Ministry of Education, Innovation and Universities, the National Agency for Research and the Fund for Regional Development (RTI2018-100789-B-I00), MaratóTV3 (2015–3230), the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023 (CEX2018-000806-S) and Maria de Maeztu (MDM-2014-0370)” Programs, and support from the Generalitat de Catalunya through the CERCA and Consolidated Research Group (2017SGR01974) Programs. NC and JU are supported by Spanish regional program PERIS (Ref.: SLT017/20/000061 and SLT017/20/000119, respectively), granted by Departament de Salut de la Generalitat de Cataluny
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