66 research outputs found

    The CBRB regulon: Promoter dissection reveals novel insights into the CbrAB expression network in Pseudomonas putida

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    CbrAB is a high ranked global regulatory system exclusive of the Pseudomonads that responds to carbon limiting conditions. It has become necessary to define the particular regulon of CbrB and discriminate it from the downstream cascades through other regulatory components. We have performed in vivo binding analysis of CbrB in P. putida and determined that it directly controls the expression of at least 61 genes; 20% involved in regulatory functions, including the previously identified CrcZ and CrcY small regulatory RNAs. The remaining are porines or transporters (20%), metabolic enzymes (16%), activities related to protein translation (5%) and orfs of uncharacterised function (38%). Amongst the later, we have selected the operon PP2810-13 to make an exhaustive analysis of the CbrB binding sequences, together with those of crcZ and crcY. We describe the implication of three independent non-palindromic subsites with a variable spacing in three different targets; CrcZ, CrcY and operon PP2810-13 in the CbrAB activation. CbrB is a quite peculiar σN—depen-dent activator since it is barely dependent on phosphorylation for transcriptional activation. With the depiction of the precise contacts of CbrB with the DNA, the analysis of the multi-merisation status and its dependence on other factors such as RpoN o IHF, we propose a model of transcriptional activation.Ministerio de Economía y Competitividad BIO2014-57545-

    La incidencia del contexto en los discursos

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    Este volumen recoge diversos trabajos que abordan el estudio de la influencia del contexto en los discursos desde diversas perspectivas (sociolingüística, biolingüística, lingüística clínica, etc.) y en diferentes ámbitos comunicativos (conversación afásica, comunicación publicitaria, comunicación virtual, etc.)This book includes several works where the incidence of context into discourse is analyzed from diferent points of view (sociolinguistics, biolinguistics, clinical linguistics, …) and in diferents communicative frames (aphasic conversation, advertising communication, cybernetic communication, …

    Matrix Metalloproteinase-9 Expression Is Associated with the Absence of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients

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    Triple-negative breast cancer (TNBC) is particularly challenging due to the weak or absent response to therapeutics and its poor prognosis. The effectiveness of neoadjuvant chemotherapy (NAC) response is strongly influenced by changes in elements of the tumor microenvironment (TME). This work aimed to characterize the residual TME composition in 96 TNBC patients using immunohistochemistry and in situ hybridization techniques and evaluate its prognostic implications for partial responders vs. non-responders. Compared with non-responders, partial responders containing higher levels of CD83+ mature dendritic cells, FOXP3+ regulatory T cells, and IL-15 expression but lower CD138+ cell concentration exhibited better OS and RFS. However, along with tumor diameter and positive nodal status at diagnosis, matrix metalloproteinase-9 (MMP-9) expression in the residual TME was identified as an independent factor associated with the impaired response to NAC. This study yields new insights into the key components of the residual tumor bed, such as MMP-9, which is strictly associated with the lack of a pathological response to NAC. This knowledge might help early identification of TNBC patients less likely to respond to NAC and allow the establishment of new therapeutic targets

    Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response

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    Simple Summary Triple-negative breast cancer (TNBC) is currently in the clinical research spotlight because of the tumor's aggressive and invasive nature and the scarcity of therapeutic targets. Despite recent advances in identifying reliable prognostic biomarkers in the tumor microenvironment (TME), rigorous evaluation of their predictive capacity remains challenging. We describe the immune cellular and genetic profile of the residual tumor of TNBC that does not achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). A high concentration of lymphocytes and dendritic cells, as well as genetic TME markers such as MUC-1 and CXCL13 in the residual tumor, are valuable prognostic factors of survival and relapse in TNBC patients. From a clinical health perspective, a thorough understanding of the composition of the TME and its prognostic implications might yield relevant immunological information and reveal key predictive biomarkers. This could ultimately help substantially improve the outcomes of residual cancer-burdened TNBC patients after NAC. With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling

    Validez e invarianza factorial de una medida breve de Satisfacción con la Vida Familiar

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    RESUMEN Se examinó la estructura factorial, la confiabilidad, la validez convergente y discriminante, y la invarianza factorial por sexo, de la Satisfaction with Family Life Scale (SWFLS). Los participantes fueron 804 estudiantes de primaria y secundaria de escuelas privadas de Lima, con un promedio de edad de 13.5 años (DE = 1.6). Los resultados confirman la estructura unidimensional de la escala (χ2 = 3.49, df = 5, p = 0.63; χ2/df = 0.69; GFI = 0.998; CFI = 1; NFI = 0.998; RMSEA = 0 [IC90% 0, 0.038] y SRMR = 0.007), la invarianza factorial por sexo y una consistencia interna adecuada (α = 0.84; ω = 0.84; H = 0.85). Se obtuvieron evidencias satisfactorias de validez convergente y discriminante de las SWFLS con medidas de funcionalidad familiar, bienestar subjetivo y depresión. En conclusión, la SWFLS presenta excelentes propiedades psicométricas para medir la satisfacción con la vida familiar en escolares limeños. Palabras clave análisis factorial confirmatorio; invarianza factorial; satisfacción con la vida familiar; escolares peruanos. ABSTRACT We examined the factor structure, reliability, convergent and discriminant validity, and factorial invariance by sex of the Satisfaction with Family Life Scale (SWFLS). The participants were 804 primary and secondary students from private schools in Lima, with an average age of 13.5 years (SD = 1.6). The results confirm the one-dimensional structure of the scale (χ2 = 3.49, df = 5, p = 0.63, χ2/df = 0.69, GFI = 0.998, CFI = 1, NFI = 0.998, RMSEA = 0 [IC90% 0, 0.038], and SRMR = 0.007), factorial invariance by sex and adequate internal consistency (α = 0.84; ω = 0.84; H = 0.85). Satisfactory evidence of convergent and discriminant validity of the SWFLS was obtained with measures of family functionality, subjective well-being and depression. In conclusion, the SWFLS presents excellent psychometric properties to measure satisfaction with family life in Lima schoolchildren. Keywords confirmatory factor analysis; factorial invariance; satisfaction with family life; Peruvian schoolchildren

    Examining the immune signatures of SARS-CoV-2 infection in pregnancy and the impact on neurodevelopment: Protocol of the SIGNATURE longitudinal study.

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    The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders. Based on the hypothesis that neuroinflammation during early stages of life is associated with neurodevelopmental disorders and confers a greater risk of developing neuropsychiatric disorders, we propose a cohort study of SARS-CoV-2-infected pregnant women and their newborns. The main objective of SIGNATURE project is to explore how the presence of prenatal SARS-CoV-2 infection and other non-infectious stressors generates an abnormal inflammatory activity in the newborn. The cohort of women during the COVID-19 pandemic will be psychological and biological monitored during their pregnancy, delivery, childbirth and postpartum. The biological information of the umbilical cord (foetus blood) and peripheral blood from the mother will be obtained after childbirth. These samples and the clinical characterisation of the cohort of mothers and newborns, are tremendously valuable at this time. This is a protocol report and no analyses have been conducted yet, being currently at, our study is in the recruitment process step. At the time of this publication, we have identified 1,060 SARS-CoV-2 infected mothers and all have already given birth. From the total of identified mothers, we have recruited 537 SARS-COV-2 infected women and all of them have completed the mental health assessment during pregnancy. We have collected biological samples from 119 mothers and babies. Additionally, we have recruited 390 non-infected pregnant women

    Vulnerable marine ecosystems and biological features of Gazul mud volcano (Gulf of Cádiz): A contribution towards a potential "Gulf of Cádiz" EBSA

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    The Gulf of Cádiz (GoC) represents an area of socioeconomic and scientific importance for oceanographic, geological and biological processes. An interesting feature of the GoC is the presence of a large amount of mud volcanoes (MVs) and diapirs that display different seepage, seabed types, oceanographic settings and biological communities. Detailed exploration of some MVs is still needed for detecting Vulnerable Marine ecosystems (VMEs) that seem to be rare in other areas of the GoC, improving the current knowledge on its biodiversity and ecological attributes. During different expeditions (MEDWAVES-ATLAS, INDEMARES-CHICA 0610 & 0412 and ISUNEPCA 0616) carried out in different years, biological samples and videos were obtained in Gazul MV (Spanish Margin of the GoC). The study of those samples and videos has revealed the presence of several ecologically important VMEs (e.g. 3 species of reef framework-forming corals, coral gardens including solitary scleractinians, gorgonians and antipatharians, as well as deep-sea sponge aggregations and chemosynthesis-related structures) and a large number of species occurring in this MV, including new records for the European margin, threatened species and non-previously described species. The combination of different environmental and anthropogenic factors allowed the present-day persistence of these VMEs in the GoC. Some of Gazul MV biological and ecological attributes fit several criteria of the Convention on Biological Diversity for EBSA description (e.g. 1,3,4,6) that, together with those of other areas of the GoC, may contribute to the future potential nomination of an EBSA in this area of the NE Atlantic

    Estudio cycEVA: casos y controles para la estimación de la efectividad de la vacuna antigripal en España, 2008-2013

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    Fundamentos: Desde 2008-09 la efectividad de la vacuna (EV) antigripal en España se estima con el estudio de casos y controles para la evaluación de la EV antigripal (cycEVA), componente español de la red europea (Influenza-Monitoring Vaccine Effectiveness (I-MOVE). El objetivo es describir la evolución del estudio cycEVA durante las cinco temporadas del período 2008/09– 2012/13. Métodos: Se analizaron los siguientes indicadores: 1) participación de los médicos/pediatras centinela (MP); 2) población y periodo de estudio, 3) calidad de los datos y 4) difusión de los resultados mediantes publicaciones. Se calculó el porcentaje anual de cambio constante de los indicadores analizándose su tendencia mediante el test de Cochran-Armitage. Resultados: El número de MP participantes aumentó de 164 en 2008-09 hasta 246 en ediciones posteriores. El porcentaje de médicos que reclutaron al menos un paciente experimentó un cambio anual significativo (PCA) del 15,33%. El porcentaje de pacientes reclutados incluidos en el análisis aumen- tó del 77% en 2008-09 a más del 95% en las siguientes ediciones (PCA=5,91%). El porcentaje de casos y controles participantes en cycEVA sobre el total de pacientes que contribuyeron al estudio europeo I-MOVE osciló entre el 23% en la edición piloto y 30% en la temporada 2011-12. Los resultados finales se difundieron en revistas científicas con un factor de impacto situado en el cuartil 2 y en 2010-11 y 2011-12 se publicaron resultados preliminares en revistas con un factor de impacto situado en el cuartil 1 (97 citas). Conclusiones: La experiencia del estudio cycEVA se reflejó en una mejora en la oportunidad e impacto de sus resultados, cruciales para orientar las recomendaciones anuales de vacunación antigripal
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