2,465 research outputs found
Time varying term premia and risK: The case of the spanish interbank money market.
En este trabajo se examinan algunos procedimientos estĂĄndar utilizados para evaluar la importancia del riesgo en la explicaciĂłn del comportamiento de las primas por plazo dentro de la estructura temporal de tipos de interĂŠs. Se ponen de manifiesto sus limitaciones y se propone un procedimiento alternativo basado en la utilizaciĂłn de modelos VARMA. Este procedimiento se ilustra con una evaluaciĂłn de la importancia del riesgo, medido como en Luce (1980), en el comportamiento de dos importantes primas por plazo dentro del mercado interbancario espaĂąol
Molecular Mechanisms Involved in the Acquisition of Resistance to Treatment of Colon Cancer Cells
Cancer cells are remarkably resilient to therapies aimed at their elimination. The exploration of pathways that sustain cancer cells and that allow cancer cells to become resistant has revealed new avenues for chemotherapeutic development, as well as rational approaches to combination therapies based on existing treatment options. Several signaling pathways, such as Wnt, phosphoinositide 3-kinase (PI3K), and Ras-Raf-MEK, constitute integrated networks that work together to maintain cellular homeostasis under basal conditions and to drive cell-mass accumulation and cell cycle progression in the presence of appropriate mitogenic stimuli. During cancer development, these pathways are corrupted in malignant cells to maintain viability and proliferative activity under environmentally stressful conditions such as limited growth factors, oxygen, and nutrients that drive normal cells into quiescence or death. Importantly, dysfunction within any one of these pathways results in compensatory responses from the other networks. Thus, biological research is gradually shifting toward more general approaches that target entire pathways rather than isolated components and integrate those pathways into biological networks
Phytotoxic and dissuasive activity of Chihuahua desert plants
With the purpose of finding plant compounds with the potential use as herbicides and insecticides, a research was realized with the objective of evaluate the phytotoxic and dissuasive activity of four Chihuahua desert plants. The phytotoxic activity evaluation was tested on Lactuca sativa and Lolium perenne, while the dissuasive activity was realized on three species of phytophagous insects: Myzus persicae, Rhopalosiphum padi and Spodoptera littoralis. Raw extracts were used, the solvents hexane, methanol and ethanol of different plantsâ organs (root, steam, leaf and flower) of four species: Fouquieria splendens (ocotillo), Larrea tridentate (governor), Astragalus mollissimus (wild grass) and Pachycereus pecten-aboriginum (echo), by the establishment of in vitro bioassays at a concentration of 10 mg/ml extract/solvent. In the toxicity bioassay, the percentage of germination, root and leaf length were measured. The results showed that the leaf extract of L. tridentata had phytotoxic activity for L. sativa, while for L. perenne the phytotoxicity was observed within the ocotillo, governor and echo extracts. In the dissuasive bioassay, each treatment had 20 repetitions with 10 adult insects per repetition. The methanolic extracts of F. splendens leaf and root, ethanolic extract of A. mollisimus sheet and the ethanolic extract of P. pecten-aboriginum stems showed moderate dissuasive response of feeding against M. persicae, presenting a settlement inhibition index of 53.53, 54.35, 60.00 and 48.84% respectively. Nevertheless, the results indicated that none of the 10 extracts tested on S. littoralis showed significant dissuasive properties for this Lepidoptera, while for R. padi all the tested extracts presented dissuasive properties. The treatments of the four vegetable species evaluated showed defensive or dissuasive properties of moderate to strong feeding against the insects M. persicae and R. padi, presenting interesting potential for being used as insecticides, while the tested extracts that presented phytotoxicity for both lettuce and ryegrass present possibilities for the realization of herbicides
O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells
The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer. However, the role played by this modification in the establishment of CSC phenotype has been poorly studied so far and remains unclear. In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype. We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1â10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture. We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition. Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions
Fault kinematics in northern Central America and coupling along the subduction interface of the Cocos Plate, from GPS data in Chiapas (Mexico), Guatemala and El Salvador
International audienceNew GPS measurements in Chiapas (Mexico), Guatemala and El Salvador are used to constrain the fault kinematics in the North America (NA), Caribbean (CA) and Cocos (CO) plates triple junction area. The regional GPS velocity field is first analysed in terms of strain partitioning across the major volcano-tectonic structures, using elastic half-space modelling, then inverted through a block model. We show the dominant role of the Motagua Fault with respect to the Polochic Fault in the accommodation of the present-day deformation associated with the NA and CA relative motion. The NA/CA motion decreases from 18-22 mm yrâ1 in eastern Guatemala to 14-20 mm yrâ1 in central Guatemala (assuming a uniform locking depth of 14-28 km), down to a few millimetres per year in western Guatemala. As a consequence, the western tip of the CA Plate deforms internally, with â9 mm yrâ1 of east-west extension (â5 mm yrâ1 across the Guatemala city graben alone). Up to 15 mm yrâ1 of dextral motion can be accommodated across the volcanic arc in El Salvador and southeastern Guatemala. The arc seems to mark the northern boundary of an independent forearc sliver (AR), pinned to the NA plate. The inversion of the velocity field shows that a four-block (NA, CA, CO and AR) model, that combines relative block rotations with elastic deformation at the block boundaries, can account for most of the GPS observations and constrain the overall kinematics of the active structures. This regional modelling also evidences lateral variations of coupling at the CO subduction interface, with a fairly high-coupling (â0.6) offshore Chiapas and low-coupling (â0.25) offshore Guatemala and El Salvador
Microbiota diversity in nonalcoholic fatty liver disease and in drug-induced liver injury
The gut microbiota could play a significant role in the progression of nonalcoholic fatty liver disease (NAFLD); however, its relevance in drug-induced liver injury (DILI) remains unexplored. Since the two hepatic disorders may share damage pathways, we analysed the metagenomic profile of the gut microbiota in NAFLD, with or without significant liver fibrosis, and in DILI, and we identified the main associated bacterial metabolic pathways. In the NAFLD group, we found a decrease in Alistipes, Barnesiella, Eisenbergiella, Flavonifractor, Fusicatenibacter, Gemminger, Intestinimonas, Oscillibacter, Parasutterella, Saccharoferementans and Subdoligranulum abundances compared with those in both the DILI and control groups. Additionally, we detected an increase in Enterobacter, Klebsiella, Sarcina and Turicibacter abundances in NAFLD, with significant liver fibrosis, compared with those in NAFLD with no/mild liver fibrosis. The DILI group exhibited a lower microbial bacterial richness than the control group, and lower abundances of Acetobacteroides, Blautia, Caloramator, Coprococcus, Flavobacterium, Lachnospira, Natronincola, Oscillospira, Pseudobutyrivibrio, Shuttleworthia, Themicanus and Turicibacter compared with those in the NAFLD and control groups. We found seven bacterial metabolic pathways that were impaired only in DILI, most of which were associated with metabolic biosynthesis. In the NAFLD group, most of the differences in the bacterial metabolic pathways found in relation to those in the DILI and control groups were related to fatty acid and lipid biosynthesis. In conclusion, we identified a distinct bacterial profile with specific bacterial metabolic pathways for each type of liver disorder studied. These differences can provide further insight into the physiopathology and development of NAFLD and DILI.This work was supported in part by a grant from the Instituto de Salud Carlos III (Spain) (PI18/01804, PI19/00883, PI21/01248), from the ConsejerĂa de EconomĂa, Conocimiento, Empresas y Universidad (Junta de AndalucĂa, Spain) (PI18âRTâ3364, UMA18-FEDERJA-194), and from the ConsejerĂa de Salud (Junta de AndalucĂa, Spain) (PI-0285â2016). This study has been co-funded by FEDER funds (âA way to make Europeâ) (âAndalucĂa se mueve con Europaâ). CRD is supported by a grant from the ConsejerĂa de TransformaciĂłn EconĂłmica, Industria, Conocimiento y Universidades de Junta de AndalucĂa (Spain) (DOC_01610). FMR is supported by a grant from the ISCIII (Spain) (FI19/00189). AC is supported by a grant from the ISCIII (Spain) (IFI18/00047). EGF is supported by the Nicolas Monardes program from the ConsejerĂa de Salud de AndalucĂa (Spain) (C-0031â2016). Funding for open access charge: Universidad de MĂĄlaga / CBUA (Spain)
Low-dose statin treatment increases prostate cancer aggressiveness
Altres ajuts: NM-M was supported by the Spanish Association Against Cancer (AECC), AECC JP Vizcaya. VT is supported by FundaciĂłn Vasca de InnovaciĂłn e InvestigaciĂłn Sanitarias, BIOEF (BIO15/CA/052), the department of health of the Basque Government (2016111109) and the 2016 grant of the AECC (Junta provincial de Bizkaia). LA, AA-A and LV-J were supported by the Basque Government of education. The work of A.C. is supported by the RamĂłn y Cajal award, the Basque Department of Industry, Tourism and Trade (Etortek) and the department of education (IKERTALDE IT1106-16), FERO VIII Fellowship, the BBVA foundation, Severo Ochoa. Excellence Accreditation SEV-2016-0644) and the European Research Council (Starting Grant 336343; Proof of Concept 754627). The participation of AC, VT, NM-M, SF and AZ as part of CIBERONC was co-funded with FEDER funds.Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that in vivo simvastatin administration alone increases prostate cancer aggressiveness. In vitro cell line systems supported the notion that this phenomenon occurs, at least in part, through the direct action on cancer cells of low doses of statins, in range of what is observed in human plasma. In sum, our results reveal a prostate cancer experimental system where statins exhibit an undesirable effect, and warrant further research to address the relevance and implications of this observation in human prostate cancer
Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma
Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and tumor progression processes has been described in-depth, little is known about the regulation of chimeric fusion-gene expression. Here, we demonstrate that the active nuclear HDAC6 in EWS modulates the acetylation status of specificity protein 1 (SP1), consequently regulating the SP1/P300 activator complex binding to EWSR1 and EWSR1-FLI1 promoters. Selective inhibition of HDAC6 impairs binding of the activator complex SP1/P300, thereby inducing EWSR1-FLI1 downregulation and significantly reducing its oncogenic functions. In addition, sensitivity of EWS cell lines to HDAC6 inhibition is higher than other tumor or non-tumor cell lines. High expression of HDAC6 in primary EWS tumor samples from patients correlates with a poor prognosis in two independent series accounting 279 patients. Notably, a combination treatment of a selective HDAC6 and doxorubicin (a DNA damage agent used as a standard therapy of EWS patients) dramatically inhibits tumor growth in two EWS murine xenograft models. These results could
lead to suitable and promising therapeutic alternatives for patients with EWS.Research in the E.D.A. lab is supported by AsociaciĂłn EspaĂąola Contra el CĂĄncer (AECC), the Ministry of Science of Spain-FEDER (CIBERONC, PI1700464, PI2000003, RD06/0020/0059)S. D.G.D. and L.H.P. are supported by CIBERONC (CB16/12/00361). D.G.D., M.J.R. and L.H.P. are PhD researchers funded by the ConsejerĂa de Salud, Junta de AndalucĂa (PI-0197-2016, ECAI F2-0012-2018 and PI-0013-2018, respectively).Peer reviewe
Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV
A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay
channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7
TeV is presented. The data were collected at the LHC, with the CMS detector,
and correspond to an integrated luminosity of 4.6 inverse femtobarns. No
significant excess is observed above the background expectation, and upper
limits are set on the Higgs boson production cross section. The presence of the
standard model Higgs boson with a mass in the 270-440 GeV range is excluded at
95% confidence level.Comment: Submitted to JHE
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