Structural and functional studies of a family of Dictyostelium discoideum developmentally regulated, prestalk genes coding for small proteins

Includes additional file: Structure and chromosomal location of Dictyostelium genes similar to sigN1. In this table the DictyBase database accession number, chromosomal location and exon/intron structure of the genes similar to sigN1 is indicated together with the size of the encoded proteins and their percentage of similarity to SigN1.[Background] The social amoeba Dictyostelium discoideum executes a multicellular development program upon starvation. This morphogenetic process requires the differential regulation of a large number of genes and is coordinated by extracellular signals. The MADS-box transcription factor SrfA is required for several stages of development, including slug migration and spore terminal differentiation.[Results] Subtractive hybridization allowed the isolation of a gene, sigN (SrfA-induced gene N), that was dependent on the transcription factor SrfA for expression at the slug stage of development. Homology searches detected the existence of a large family of sigN-related genes in the Dictyostelium discoideum genome. The 13 most similar genes are grouped in two regions of chromosome 2 and have been named Group1 and Group2 sigN genes. The putative encoded proteins are 87–89 amino acids long. All these genes have a similar structure, composed of a first exon containing a 13 nucleotides long open reading frame and a second exon comprising the remaining of the putative coding region. The expression of these genes is induced at10 hours of development. Analyses of their promoter regions indicate that these genes are expressed in the prestalk region of developing structures. The addition of antibodies raised against SigN Group 2 proteins induced disintegration of multi-cellular structures at the mound stage of development.[Conclusion] A large family of genes coding for small proteins has been identified in D. discoideum. Two groups of very similar genes from this family have been shown to be specifically expressed in prestalk cells during development. Functional studies using antibodies raised against Group 2 SigN proteins indicate that these genes could play a role during multicellular development.This work was supported by grants from the Spanish Ministerio de Educación y Ciencia, Dirección General de Investigación (BMC2002-01501 and BFU2005-00138).Peer reviewe

Thyroid lobectomy in patients with differentiated thyroid cancer: an analysis of the clinical outcomes in a nationwide multicenter study

Cirugía de tiroides; Lobectomía; Recurrencia del tumorCirurgia de tiroides; Lobectomia; Recurrència del tumorThyroid surgery; Lobectomy; Tumor recurrenceBackground: Total thyroidectomy is the standard initial surgery for differentiated thyroid carcinoma (DTC), but the extent of the thyroidectomy remains controversial. Thyroid lobectomy (TL) has been widely used in eastern countries; however, its use has not been generalized in western countries, including Spain. Our aims were to analyse the clinical outcome of a multicentre nation-wide cohort of DTC patients treated by TL and to assess the proportion of patients who required completion of the thyroidectomy and who presented disease recurrence. Methods: We retrospectively analyzed patients who underwent TL for DTC and were followed-up for ≥12 months. We collected demographic, clinical, and histopathological data. Dynamic risk stratification (DRS) was performed at 12 months and at last visit. Results: One hundred and sixty-four patients (128 women, mean age 50.8 years, median follow-up 45.4 months) from 9 hospitals were included. There were 158 cases of papillary and 6 of follicular thyroid carcinoma (FTC). Remission of the disease (excellent response) was shown in 71.6% of the patients at 12 months and in 74.4% at the end of follow-up. At that time, there were 34 patients (20.7%) with indeterminate response, 6 (3.7%) with biochemical incomplete response, and 2 (1.2%) with structural incomplete response. Completion of the thyroidectomy was necessary in 8 patients (4.9%), but only 3 of them (1.8%) had disease recurrence. Conclusions: These results, obtained in real clinical practice, suggest that TL is a safe operative option for selected patients with DTC and that the intensity of the treatment must be tailored according to the presurgical tumor-associated risk, in line with a personalized medicine

Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication

<div><p>Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.</p></div

Occupational exposure to endocrine-disrupting chemicals and other parental risk factors in hypospadias and cryptorchidism development: a case–control study

Aim of the study: Endocrine-disrupting chemicals (EDCs) are exogenous agents that are capable of altering the endocrine system functions, including the regulation of developmental processes. The aim of this study was to investigate the association between EDC exposure and other parental factors in the etiology of hypospadias and cryptorchidism. Methods: A case–control study was conducted. Cases (n = 210) were infants aged between 6 months and 14 years diagnosed with hypospadias or cryptorchidism who attended the authors' hospital over a period of 18 months, and controls (n = 210) were infants within the same range of age and without any urological disorders who attended the outpatient clinic of the same hospital during the same time period. Their selection was independent of exposures. Data on parental occupational exposure to EDCs and other sociodemographic variables were collected through face-to-face interviews and systematically for both cases and controls. Crude and adjusted odds ratios (ORs) were estimated to control for confounding with their 95% confidence interval (CI) by means of logistic regressions. Specifically, three final models of a dichotomous outcome were constructed: one for cryptorchidism, one for hypospadias, and the third considering both malformations together. The Hosmer-Lemeshow test was used to assess the goodness of fit of the models. Their discriminatory accuracy (DA) was ascertained by estimating their areas under the receiver operating characteristic curves area under the curve (AUC) along with their 95% CI. Results: Associations were found between advanced maternal age (OR adjusted = 1.82; 95% CI: 1.14–2.92), mother's consumption of anti-abortives (OR = 5.40; 95% CI: 1.40–38.5) and other drugs (OR = 2.02; 95% CI: 1.31–3.16) during pregnancy, maternal and paternal occupational exposure to EDCs (OR = 4.08; 95% CI: 2.03–8.96 and OR = 3.90; 95% CI: 2.41–6.48, respectively), fathers smoking (OR = 2.0; 95% CI: 1.33–2.99), and fathers with urological disorders (OR = 2.31; 95% CI: 1.15–4.90). Maternal and paternal high educational level could be protective of cryptorchidism (OR = 0.47; 95% CI: 0.28–0.76 and OR = 0.63; 95% CI: 0.42–0.93, respectively). The DA of the models for the whole sample (AUC = 0.75; 95% CI: 0.70–0.79) for cryptorchidism (AUC = 0.76; 95% CI: 0.71–0.82) and for hypospadias (AUC = 0.75; 95% CI: 0.69–0.81) was moderately high. Conclusions: Advanced age, some parental occupational exposure to EDCs, some drug consumption, smoking, and the father's history of urological disorders may increase risk and predict the developments of these malformations. Studies with higher samples sizes are needed to assess associations between individual EDC occupational exposures and drugs and these malformations. [Table presented

Composites de hidroxiapatita con matrices biodegradables

Mucho se ha publicado sobre el empleo de la hídroxíapatita (HAP) como un sustituto del hueso en diferentes áreas de la medicina Desde hace algunos años, se viene criticando el uso de este sistema debido a la capacidad de migración de las partí­culas de HAP del sitio del implante. Su posible estabilización se viene investigando y se han desarrollado métodos para lograrlo. Se prepararon composites de hídroxíapatita con quitosana (CHI) y ácido acrílico (AA) con el objetivo de obtener sistemas biodegradables con características osteoconductoras. Se estudió la influencia de dife­rentes factores: método de preparación, contenido de HAP y la concentración de CID sobre la cinética de fotopolimerización de estos composites bajo irradación con luz visible. Como sistema de iniciación se empleó el par canforquinona-alcohol N,N­dirnetilaminobencílico, ambos al 1 % en peso con respecto al AA. Se encontró que el método de preparación influye sobre las propiedades fisico-quínúcas y cinéticas de los composites. Por ejemplo, para los sistemas preparados sobre la base de geles de AA y CHl previamente hinchada con agua, se observan menores velocidades de polimeriza­ción (R,) que para los composites obtenidos a partir de los llamados geles inversos, donde el AA se pone previamente en contacto con la CHI (antes de la formación de su gel con agua)

Determining the Role of Fe-Doping on Promoting the Thermochemical Energy Storage Performance of (Mn1-xFex)(3)O-4 Spinels

Mn oxides are promising materials for thermochemical heat store, but slow reoxidation of Mn3O4 to Mn2O3 limits efficiency. In contrast, (Mn1-xFex)(3)O-4 oxides show an enhanced transformation rate, but fundamental understanding of the role played by Fe cations is lacking. Here, nanoscale characterization of Fe-doped Mn oxides is performed to elucidate how Fe incorporation influences solid-state transformations. X-ray diffraction reveals the presence of two distinct spinel phases, cubic jacobsite and tetragonal hausmannite for samples with more than 10% of Fe. Chemical mapping exposes wide variation of Fe content between grains, but an even distribution within crystallites. Due to the similarities of spinels structures, high-resolution scanning transmission electron microscopy cannot discriminate unambiguously between them, but Fe-enriched crystallites likely correspond to jacobsite. In situ X-ray absorption spectroscopy confirms that increasing Fe content up to 20% boosts the reoxidation rate, leading to the transformation of Mn2+ in the spinel phase to Mn3+ in bixbyite. Extended X-ray absorption fine structure shows that Fe-O length is larger than Mn-O, but both electron energy loss spectroscopy and X-ray absorption near edge structure indicate that iron is always present as Fe3+ in octahedral sites. These structural modifications may facilitate ionic diffusion during bixbyite formation.The authors thank the financial support from "Ramon Areces" Foundation (project SOLARKITE), Comunidad de Madrid and European Structural Funds (project ACES2030 P2018/EMT-4319), and University of Cadiz and European Structural Funds (project FEDER-UCA18-107139). A.J.C. thanks the financial support by Juan de la Cierva Formacion Program (MICINN), grant FJCI-2017-33967. The authors acknowledge ALBA-CELLS Synchrotron facility for granting beamtime at CLAESS (experiment 2016021666-2) and Electron Microscopy division located in the Servicios Centrales de Investigacion Cientifica y Tecnologica (SC-ICYT) of the University of Cadiz. Assistance of Dr. Laura Simonelli during the XAS measurements in ALBA is fully appreciated

Id2 leaves the chromatin of the E2F4-p130-controlled c-myc promoter during hepatocyte priming for liver regeneration

The Id (inhibitor of DNA binding or inhibitor of differentiation) helix-loop-helix proteins are involved in the regulation of cell growth, differentiation and cancer. The fact that the molecular mechanisms of liver regeneration are not completely understood prompted us to study the fate of Id2 in proliferating liver. Id2 increases in liver regeneration after partial hepatectomy, following the early induction of its gene. Co-immunoprecipitation shows that Id2 forms a complex with E2F4, p130 and mSin3A in quiescent liver and all these components are present at the c-myc promoter as shown using ChIP (chromatin immunoprecipitation). Activation of c-myc during hepatocyte priming (G0-G1 transition) correlates with the dissociation of Id2 and HDAC (histone deacetylase), albeit p130 remains bound at least until 6 h. Moreover, as the G0-G1 transition progresses, Id2 and HDAC again bind the c-myc promoter concomitantly with the repression of this gene. The time course of c-myc binding to the Id2 promoter, as determined by ChIP assays is compatible with a role of the oncoprotein as a transcriptional inducer of Id2 in liver regeneration. Immunohistochemical analysis shows that Id2 also increases in proliferating hepatocytes after bile duct ligation. In this case, the pattern of Id2 presence in the c-myc promoter parallels that found in regenerating liver. Our results may suggest a control role for Id2 in hepatocyte priming, through a p130 dissociation-independent regulation of c-my

Ammonia levels in different kinds of sampling sites in the central Iberian Peninsula

Ponencia presentada en:2nd Iberian Meeting on Aerosol Science and Technology (RICTA 2014) celebrado en Tarragona del 7 al 9 de julio de 2014.Ammonia is the Secondary Inorganic Aerosol (SIC) gaseous precursor which has been studied to a lesser extent in the Madrid Metropolitan Area up to date. A study conducted in the city of Madrid with the aim of characterizing levels of ammonia took place in 2011. These campaigns formed part of a larger study conducted in 6 Spanish cities. A time series of weekly integrated ammonia measurements available at an EMEP rural site (Campisábalos) has been used to obtain information on the ammonia rural background in the region. The results point to traffic and waste treatment plants as the main ammonia sources in Madrid. Relevant seasonal differences have not been observed in the Metropolitan Area. The explanation can be related to the fall in the rural background levels during July 2011, which might conceal urban summer emission increases observed in other cities

Influence of Regulated Deficit Irrigation on Arbequina’s Crop Yield and EVOOs Quality and Sensory Profile

Regulated deficit irrigation in super-high-density (SHD) olive orchards is a well-known strategy to save water and control plant vigor, without decreasing fruit or oil yield. As there is controversial information about its influence on virgin olive oil quality, a trial was conducted in five SHD olive orchards of Arbequina cultivar in different locations of central, east, north and northeast Spain under full irrigation (FI) and regulated deficit irrigation (RDI) treatments. RDI applied during phase II of fruit growing (40% of total needs) saves more than 20% of water on average, without reductions in olive fruit or extra virgin olive oil (EVOO) yield. No threshold of 3.5 MPa of stem water potential was crossed in any case. RDI modified sterols and the fatty acid profile of EVOOs but not phenols, quality parameters, or the sensory profile. Latitude, altitude, and yearly rainfall have a big impact on some compounds such as campesterol, oleuropein, or margaroleic or linolenic acids.info:eu-repo/semantics/publishedVersio