Conservante para flor ornamental cortada

Referencia OEPM: P200000402.-- Fecha de solicitud: 21/02/2000.-- Titulares: Universidad Politécnica de Valencia (UPV), Consejo Superior de Investigaciones Científicas (CSIC).La invención consiste en un conservante para flor ornamental cortada, diseñado como una mezcla de compuestos a base de azúcar comercial, ácido cítrico, citrato de sodio, germicida, inhibidor de la síntesis de etileno y humectante, que se prepara para disolver en un litro de agua y mantener en él los claveles cortados. De esta forma la vida comercial útil de la flor cortada se verá considerablemente incrementada. La principal ventaja que presenta esta composición sobre las ya existentes en el mercado es su mayor efectividad, retardando la senescencia o envejecimiento de la flor cortada y el no contener compuestos que puedan ser contaminantes para el medio ambiente o nocivos para la salud humana o de animales.Peer reviewe

Sex as a prognostic factor for mortality in critically ill adults with sepsis: a systematic review and meta-analysis.

Objective To assess the role of sex as an independent prognostic factor for mortality in patients with sepsis admitted to intensive care units (ICUs). Design Systematic review and meta-analysis. Data sources MEDLINE, Embase, Web of Science, ClinicalTrials. gov and the WHO Clinical Trials Registry from inception to 17 July 2020. Study selection Studies evaluating independent associations between sex and mortality in critically ill adults with sepsis controlling for at least one of five core covariate domains prespecified following a literature search and consensus among experts. Data extraction and synthesis Two authors independently extracted and assessed the risk of bias using Quality In Prognosis Studies tool. Meta-analysis was performed by pooling adjusted estimates. The Grades of Recommendations, Assessment, Development and Evaluation approach was used to rate the certainty of evidence. Results From 14 304 records, 13 studies (80 520 participants) were included. Meta-analysis did not find sex-based differences in all-cause hospital mortality (OR 1.02, 95% CI 0.79 to 1.32; very low-certainty evidence) and all-cause ICU mortality (OR 1.19, 95% CI 0.79 to 1.78; very low-certainty evidence). However, females presented higher 28-day all-cause mortality (OR 1.18, 95% CI 1.05 to 1.32; very low-certainty evidence) and lower 1-year all-cause mortality (OR 0.83, 95% CI 0.68 to 0.98; low-certainty evidence). There was a moderate risk of bias in the domain adjustment for other prognostic factors in six studies, and the certainty of evidence was further affected by inconsistency and imprecision. Conclusion The prognostic independent effect of sex on all-cause hospital mortality, 28-day all-cause mortality and all-cause ICU mortality for critically ill adults with sepsis was uncertain. Female sex may be associated with decreased 1-year all-cause mortality.post-print1281 K

Constitutive phosphorylation of serine 29 as a critical regulator of TRPM8 channel function

Resumen del trabajo presentado al VIII Congreso Red Española de Canales Iónicos, celebrado en Alicante del 24 al 27 de mayo de 2022.The main molecular entity involved in innocuous cold detection in mammals is TRPM8. This polymodal TRP channel is activated by cold, cooling compounds such as menthol, voltage, and rises in osmolality. Basal kinase activity phosphorylates TRPM8 and modulates its function under resting conditions. However, which specific residues, how this post-translational modification modulates TRPM8 activity, and its influence on cold sensing are still poorly understood. We identified four serine residues within the N-terminal domain constitutively phosphorylated in the mouse ortholog by mass spectrometry. TRPM8 function was assessed by Ca2+-imaging and patch-clamp recordings, revealing that treatment with staurosporine, a kinase inhibitor, increased cold- and mentholevoked responses of the channel. S29A mutation is sufficient to enhance TRPM8 activity, suggesting that phosphorylation of this residue is a critical molecular determinant of this negative regulation. Biophysical and TIRF-based analysis revealed a dual mechanism in the potentiated responses of unphosphorylated TRPM8: an increase in the number of active channels at the plasma membrane and a shift in the voltage activation curve towards more negative potentials. Notably, basal kinase activity downregulates TRPM8 function at cold thermoreceptor neurons, an observation accounted for by mathematical modeling. Overall, our findings suggest that cold temperature detection could be rapidly and reversibly fine-tuned by controlling the TRPM8 basal phosphorylation state, a mechanism that acts as a dynamic molecular brake of this thermo-TRP channel function in primary sensory neurons.Supported by Grants Millennium Nucleus for the Study of Pain (MiNuSPain) (RM, MP), Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD) (RM, MP), DICYT VRIDeI-USACH 022143PP (MP, RM) and by VRIDeI-USACH 021843MM (RM).Peer reviewe

La lección del Nunca Más. Una aproximación interdisciplinar al contenido y alcance jurídico internacional de la obligación estatal de garantizar la no repetición a través de la educación en memoria. Informe Final

Conceptualmente, el proyecto giró en torno a las garantías de no repetición, es decir: medidas orientadas a evitar futuros incumplimientos del Derecho internacional, de muy diversa naturaleza, pues virtualmente pueden consistir en cualquier cosa (siempre que no resulte abusiva), aunque las más habituales en la práctica internacional son la adopción/derogación/reforma de legislación o de medidas administrativas y las medidas de carácter institucional (relativas a la existencia, organización o funcionamiento de órganos del Estado). Cuando un Estado incumple una obligación internacional –y, por tanto, comete un hecho internacionalmente ilícito–, la principal consecuencia que surge para él es la obligación de reparar, en cualquier de sus tres formas –restitución (o, en su caso, compensación por equivalencia), indemnización o satisfacción (reparación moral)–. Además, en circunstancias excepcionales, tendría también la obligación de ofrecer garantías de no repetición1. Esas “circunstancias excepcionales” vienen en esencia delimitadas por la existencia de violaciones graves de normas imperativas de Derecho internacional, como ocurre cuando se lesionan de manera flagrante o sistemática derechos humanos fundamentales, prácticas que a su vez están tipificadas como crímenes internacionales (genocidio o crímenes contra la humanidad). Por tanto, cuando en el interior de un Estado se cometen atrocidades de esa naturaleza, bien por parte de las propias autoridades estatales, bien por parte de actores no estatales cuyo comportamiento no ha sido prevenido o reprimido por el Estado, surgiría para este la obligación de ofrecer garantías de no repetición

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Development of a T7 Phage Display Library to Detect Sarcoidosis and Tuberculosis by a Panel of Novel Antigens

Sarcoidosis is a granulomatous inflammatory disease, diagnosed through tissue biopsy of involved organs in the absence of other causes such as tuberculosis (TB). No specific serologic test is available to diagnose and differentiate sarcoidosis from TB. Using a high throughput method, we developed a T7 phage display cDNA library derived from mRNA isolated from bronchoalveolar lavage (BAL) cells and leukocytes of sarcoidosis patients. This complex cDNA library was biopanned to obtain 1152 potential sarcoidosis antigens and a microarray was constructed to immunoscreen two different sets of sera from healthy controls and sarcoidosis. Meta-analysis identified 259 discriminating sarcoidosis antigens, and multivariate analysis identified 32 antigens with a sensitivity of 89% and a specificity of 83% to classify sarcoidosis from healthy controls. Additionally, interrogating the same microarray platform with sera from subjects with TB, we identified 50 clones that distinguish between TB, sarcoidosis and healthy controls. The top 10 sarcoidosis and TB specific clones were sequenced and homologies were searched in the public database revealing unique epitopes and mimotopes in each group. Here, we show for the first time that immunoscreenings of a library derived from sarcoidosis tissue differentiates between sarcoidosis and tuberculosis antigens. These novel biomarkers can improve diagnosis of sarcoidosis and TB, and may aid to develop or evaluate a TB vaccine

Understanding the mechanisms of chilling injury in bell pepper fruits using the proteomic approach

In order to advance in the understanding of CI in pepper fruits, the cell ultrastructure alterations induced by CI and the physiological and metabolic changes have been studied along with the proteomic study. When stored at low temperatures bell pepper (Capsicum annuum) fruits exhibited visual CI symptoms and important alterations within the cell ultrastructure, since peroxisomes and starch grains were not detected and the structure of the chloroplast was seriously damaged in chilled tissues. Physiological and metabolic disorders were also observed in chilled fruits, such as higher ethylene production, increased MDA content, changes in sugar and organic acids and enzymatic activities. The comparative proteomic analysis between control and chilled fruits reveals that the main alterations induced by CI in bell pepper fruits are linked to redox homeostasis and carbohydrate metabolism. Thus, protein abundance in the ascorbate-glutathione cycle is altered and catalase is down-regulated. Key proteins from glycolysis, Calvin cycle and Krebs cycle are also inhibited in chilled fruits. Enolase and GAPDH are revealed as proteins that may play a key role in the development of chilling injury. This study also provides the first evidence at the protein level that cytosolic MDH is involved in abiotic stress. © 2012 Elsevier B.V.P.S.B. and I.E. were supported by a postdoctoral position from the JAE-Doc program of the National Research Council (CSIC). This work was supported by the Spanish Ministry of Science and Innovation (MICINN) [grants AGL2007-60447 and PIE2009-40I080], and by the Council of Science and Technology from the Region of Murcia (Spain) (Fundación SENECA) [grant 04553/GERM/06].Peer Reviewe

Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis

BACKGROUND: Autoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V. METHODS: In this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1α. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype. RESULTS: We identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis. CONCLUSIONS: MNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis