175 research outputs found
Implementación de un algoritmo de morfogénesis para el diseño de disipadores de calor
Este artĂculo presenta el resultado de un trabajo de investigaciĂłn que pretende realizar el diseño de un disipador de calor, optimizado para las proporciones del empaquetado para transistores TO-220, por medio de un algoritmo de morfogĂ©nesis realizado en Matlab. Este algoritmo toma como base la lĂłgica de los sistemas Lindenmayer con el fin de crear formas en dos dimensiones para ser optimizadas a travĂ©s de un algoritmo genĂ©tico. Posteriormente se evidencian los diversos comportamientos de dichas formas en cuanto a la disipaciĂłn de calor, por medio de simulaciones tĂ©rmicas en el toobox PDEtool de Matlab
SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150
SPROUTY-2 (SPRY2) is a modulator of tyrosine kinase receptor signaling with
receptor- and cell type-dependent inhibitory or enhancing effects. Studies on the action
of SPRY2 in major cancers are conflicting and its role remains unclear. Here we have
dissected SPRY2 action in human colon cancer. Global transcriptomic analyses show
that SPRY2 downregulates genes encoding tight junction proteins such as claudin-7 and
occludin and other cell-to-cell and cell-to-matrix adhesion molecules in human SW480-
ADH colon carcinoma cells. Moreover, SPRY2 represses LLGLL2/HUGL2,
PATJ1/INADL and ST14, main regulators of the polarized epithelial phenotype, and
ESRP1, an epithelial-to-mesenchymal transition (EMT) inhibitor. A key action of
SPRY2 is the upregulation of the major EMT inducer ZEB1, as these effects are
reversed by ZEB1 knock-down by means of RNA interference. Consistently, we found
an inverse correlation between the expression level of claudin-7 and those of SPRY2
and ZEB1 in human colon tumors. Mechanistically, ZEB1 upregulation by SPRY2
results from the combined induction of ETS1 transcription factor and the repression of
microRNAs (miR-200 family, miR-150) that target ZEB1 RNA. Moreover, SPRY2
increased AKT activation by epidermal growth factor (EGF) whereas AKT and also Src
inhibition reduced the induction of ZEB1. Altogether, these data suggest that AKT and
Src are implicated in SPRY2 action. Collectively, these results show a tumorigenic role
of SPRY2 in colon cancer that is based on the dysregulation of tight junction and
epithelial polarity master genes via upregulation of ZEB1. The dissection of the
mechanism of action of SPRY2 in colon cancer cells is important to understand the
upregulation of this gene in a subset of patients with this neoplasia that have poor
prognosis.This study was supported by the Ministerio de
EconomĂa y Competitividad of Spain and Fondo Europeo de Desarrollo Regional
(FEDER) (grant SAF2013-43468-R to A.M., SAF2011-29530 to F.X.R.); FEDERInstituto
de Salud Carlos III (RD12/0036/0021 to A.M. and J.M.R., RD12/0036/0034 to
F.X.R., RD12/0036/0016 to M.S., RD12/0036/0012 to H.G.P., RD06/0020/0003,
PS09/00562 and PI13/00703 to J.M.R.); Comunidad de Madrid (S2010/BMD-2344
Colomics2 to A.M.); FundaciĂłn CientĂfica de la AsociaciĂłn Española contra el CĂĄncer
(to J.M.R.); U.S. Department of Defense (CA093471 and CA110602 to E.H.); National
Institutes of Health/National Cancer Institute (1R01CA155234-01 to E.H.); National
Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin
Diseases (1R21AR062239-01 to E.H.); and the Melanoma Research Alliance (to E. H.)
Near barrier scattering of 8He on 208Pb
The exotic nucleus 8He is investigated by means of the measurement of the angular distributions of the elastic channel and the 6He and 4He fragment yields produced in the collision with a 208Pb target at two energies around the Coulomb barrier, 16 and 22 MeV. The experiment was performed at the GANIL-SPIRAL facility, with the aim of extracting information about the structure of 8He and the relevant reaction mechanisms. In this contribution, details of the experimental setup and preliminary data on elastic cross sections are reporte
Epigenetic loss of RNA-methyltransferase NSUN5 in glioma targets ribosomes to drive a stress adaptive translational program
Altres ajuts: This work was supported by the Obra Social "La Caixa" (to M. Esteller).Tumors have aberrant proteomes that often do not match their corresponding transcriptome profiles. One possible cause of this discrepancy is the existence of aberrant RNA modification landscapes in the so-called epitranscriptome. Here, we report that human glioma cells undergo DNA methylation-associated epigenetic silencing of NSUN5, a candidate RNA methyltransferase for 5-methylcytosine. In this setting, NSUN5 exhibits tumor-suppressor characteristics in vivo glioma models. We also found that NSUN5 loss generates an unmethylated status at the C3782 position of 28S rRNA that drives an overall depletion of protein synthesis, and leads to the emergence of an adaptive translational program for survival under conditions of cellular stress. Interestingly, NSUN5 epigenetic inactivation also renders these gliomas sensitive to bioactivatable substrates of the stress-related enzyme NQO1. Most importantly, NSUN5 epigenetic inactivation is a hallmark of glioma patients with long-term survival for this otherwise devastating disease
HisAK70: Progress towards a vaccine against different forms of leishmaniosis
Background: Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd. Methods: Here, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL. Results: HisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100 % inhibition of parasite visceralization in the CL model. Conclusions: The results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (AGL2010-17394 and AGL2013-44100R) and PLATESA (P2013/ABI-2906) from the Comunidad de Madrid (Spain).Peer Reviewe
Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study
Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders
Salinity tolerance mechanisms in glycophytes: An overview with the central focus on rice plants
Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic
This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic
TRY plant trait database â enhanced coverage and open access
Plant traitsâthe morphological, anatomical, physiological, biochemical and phenological characteristics of plantsâdetermine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of traitâbased plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traitsâalmost complete coverage for âplant growth formâ. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and traitâenvironmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives
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