CfrA, a novel carbon flow regulator, adapts carbon metabolism to nitrogen deficiency in cyanobacteria

Cyanobacteria unable to fix atmospheric nitrogen have evolved sophisticated adaptations to survive to long periods of nitrogen starvation. These genetic programs are still largely unknown—as evidenced by the many proteins whose expression is regulated in response to nitrogen availability, but which belong to unknown or hypothetical categories. In Synechocystis sp. PCC 6803, the global nitrogen regulator NtcA activates the expression of the sll0944 gene upon nitrogen deprivation. This gene encodes a protein that is highly conserved in cyanobacteria, but of unknown function. Based on the results described herein, we named the product of sll0944 carbon flow regulator A (CfrA). We analyzed the phenotypes of strains containing different levels of CfrA, including a knock-out strain (DcfrA), and two strains overexpressing CfrA from either the constitutive Ptrc promoter (Ptrc-cfrA) or the arsenite-inducible promoter ParsB (Pars-cfrA). Our results show that the amount of CfrA determines the accumulation of glycogen, and affects the synthesis of protein and photosynthetic pigments as well as amino acid pools. Strains with high levels of CfrA present high levels of glycogen and a decrease in photosynthetic pigments and protein content when nitrogen is available. Possible interactions between CfrA and the pyruvate dehydrogenase complex or PII protein have been revealed. The phenotype associated with CfrA overexpression is also observed in PII-deficient strains; however, it is lethal in this genetic background. Taken together, our results indicate a role for CfrA in the adaptation of carbon flux during acclimation to nitrogen deficiency

Relación entre las horas de sueño y la frecuencia de consumo de alimentos en niños y niñas en Andalucía en 2015

Introducción: La frecuencia de consumo de alimentos y bebidas en los niños depende de diferentes patrones de comportamiento. Objetivos:Evaluar el efecto de la duración del sueño de los niños sobre la frecuencia de consumo de alimentos, y describir las frecuencias de consumo según su estado ponderal y el nivel de educación familiar. Método: Se estudiaron 2721 niños y niñas de 6 a 9 años del Estudio ALADINO 2015 en Andalucía. Se recogieron el número de horas de sueño y la frecuencia semanal de consumo de 24 grupos de alimentos. Se calculó el estado ponderal mediante el índice de masa corporal, con los estándares de crecimiento de la OMS, se recogió el nivel educativo de los padres y madres. Las frecuencias medias de consumo de alimentos se calcularon según la duración del sueño (mayor o menor que la media diaria). Se ajustaron modelos de regresión logística para evaluar las asociaciones independientes de las horas de sueño sobre las frecuencias de consumo de alimentos (variables resultado), ajustando por edad, sexo, nivel de educación de los padres, estado ponderal y disponibilidad de medios de ocio pasivo en la habitación. Resultados: Dormir suficiente número de horas se asocia con mayor probabilidad de consumir fruta (OR:1,23;IC95%:1,06-1,42) y verdura (OR:1,19;IC95%:1,01-1,40), y menor probabilidad de consumir refrescos azucarados (OR:0,80;IC95%:0,67-0,97), zumos con azúcar (OR:0,79;IC95%:0,64-0,99), snacks salados (OR:0,46;IC95%:0,33-0,65), chocolates o caramelos (OR:0,71;IC95%:0,55-0,92), y galletas y bollos (OR:0,70;IC95%:0,58-0,84). El consumo de frutas y verduras medio semanal es mayor en niños sin sobrepeso y en hijos de padres con mayor nivel educativo. Conclusiones: Una duración de sueño adecuada está asociada con mayor consumo de frutas y verduras, y menos alimentos con alta densidad de energía. Mejorar la higiene del sueño es fundamental para mejorar los hábitos alimentarios, y especialmente en niños con sobrepeso, y de menor nivel educativoUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

The SADDEN DEATH Study: Results from a Pilot Study in Non-ICU COVID-19 Spanish Patients

Introduction: The worldwide pandemic, coronavirus disease 2019 (COVID-19) is a novel infection with serious clinical manifestations, including death. Our aim is to describe the first non-ICU Spanish deceased series with COVID-19, comparing specifically between unexpected and expected deaths. Methods: In this single-centre study, all deceased inpatients with laboratory-confirmed COVID-19 who had died from March 4 to April 16, 2020 were consecutively included. Demographic, clinical, treatment, and laboratory data, were analyzed and compared between groups. Factors associated with unexpected death were identified by multivariable logistic regression methods. Results: In total, 324 deceased patients were included. Median age was 82 years (IQR 76–87); 55.9% males. The most common cardiovascular risk factors were hypertension (78.4%), hyperlipidemia (57.7%), and diabetes (34.3%). Other common comorbidities were chronic kidney disease (40.1%), chronic pulmonary disease (30.3%), active cancer (13%), and immunosuppression (13%). The Confusion, BUN, Respiratory Rate, Systolic BP and age ≥65 (CURB-65) score at admission was >2 in 40.7% of patients. During hospitalization, 77.8% of patients received antivirals, 43.3% systemic corticosteroids, and 22.2% full anticoagulation. The rate of bacterial co-infection was 5.5%, and 105 (32.4%) patients had an increased level of troponin I. The median time from initiation of therapy to death was 5 days (IQR 3.0–8.0). In 45 patients (13.9%), the death was exclusively attributed to COVID-19, and in 254 patients (78.4%), both COVID-19 and the clinical status before admission contributed to death. Progressive respiratory failure was the most frequent cause of death (92.0%). Twenty-five patients (7.7%) had an unexpected death. Factors independently associated with unexpected death were male sex, chronic kidney disease, insulin-treated diabetes, and functional independence. Conclusions: This case series provides in-depth characterization of hospitalized non-ICU COVID-19 patients who died in Madrid. Male sex, insulin-treated diabetes, chronic kidney disease, and independency for activities of daily living are predictors of unexpected death

With flowers to La Atkins

Photobook, Flowers, Gardens, Vegetables, Plants, World Photobook Day, International Photobook Day, 2021Anna Atkins nos regaló un fotolibro de algas, maravillosamente azules, que son como flores del mundo subacuático. Este año, para celebrar el Día Internacional del Fotolibro 2021, os proponemos hacer un fotolibro colectivo que será como un ramo de flores para Anna. Se trata de hacer fotos a flores, hierbas, plantas, hierbajos, suculentas, cactus... Las fotos nos van a permitir poner en el ramo lo que más nos guste sin preocuparnos de los problemas que nos daría una pieza floral fresca. Podéis sacar la foto a una flor o planta viva, vuestra o de un jardín público o del campo Podéis fotografiar algo de un herbario o una flor prensada que guardabais dentro de un libro Podéis fotografiar una foto de una flor Podéis sacarle una foto a una flor de plástico Podéis fotografiar un dibujo o una pintura (con motivos florales o vegetales, claro) Podéis fotografiar una planta carnívora (en ayunas o haciendo la digestión) Podéis fotografiar flores del mal o del "buenri" Siempre que sea vegetal y/o floral entrará en este libro ramo para Anna. ¡Queremos tanto a Anna! Vamos a mandarle flores como para una boda, como para un fiestón, como para una diva de la ópera que no conoce las alergias y le cabe de todo en el camerino, como para la primavera que está comenzando en el Cono Sur. Organizan: Biblioteca de la Facultad de Bellas Artes de la UCM Photobook Club MadridFac. de Bellas Artesunpu

CfrA, a Novel Carbon Flow Regulator, Adapts Carbon Metabolism to Nitrogen Deficiency in Cyanobacteria

Cyanobacteria unable to fix atmospheric nitrogen have evolved sophisticated adaptations to survive to long periods of nitrogen starvation. These genetic programs are still largely unknown¿as evidenced by the many proteins whose expression is regulated in response to nitrogen availability, but which belong to unknown or hypothetical categories. In Synechocystis sp. PCC 6803, the global nitrogen regulator NtcA activates the expression of the sll0944 gene upon nitrogen deprivation. This gene encodes a protein that is highly conserved in cyanobacteria, but of unknown function. Based on the results described herein, we named the product of sll0944 carbon flow regulator A (CfrA). We analyzed the phenotypes of strains containing different levels of CfrA, including a knock-out strain (DcfrA), and two strains overexpressing CfrA from either the constitutive Ptrc promoter (Ptrc-cfrA) or the arsenite-inducible promoter ParsB (Pars-cfrA). Our results show that the amount of CfrA determines the accumulation of glycogen, and affects the synthesis of protein and photosynthetic pigments as well as amino acid pools. Strains with high levels of CfrA present high levels of glycogen and a decrease in photosynthetic pigments and protein content when nitrogen is available. Possible interactions between CfrA and the pyruvate dehydrogenase complex or PII protein have been revealed. The phenotype associated with CfrA overexpression is also observed in PII-deficient strains; however, it is lethal in this genetic background. Taken together, our results indicate a role for CfrA in the adaptation of carbon flux during acclimation to nitrogen deficiency

A sustained activation of PI3K/NF-κB pathway is critical for the survival of chronic lymphocytic leukemia B cells

The progressive rise of mature CD5+ B lymphocytes, despite the low proportion of proliferating cells, has led to the notion that B cell chronic lymphocytic leukemia (B-CLL) is primarily related to defective apoptosis. The microenvironment likely plays a prominent role because the malignant cells progressively accumulate in vivo, whereas they rapidly undergo spontaneous apoptosis when cultured in vitro. To assess microenvironment-mediated survival signals, B-CLL cells were cultured with a murine fibroblast cell line, Ltk−, with and without an agonistic antibody to CD40. Spontaneous apoptosis was associated with the loss of Akt and NF-κB activities. Interactions with fibroblasts sustained a basal level of Akt and NF-κB activities, which was dependent on phosphatidylinositol-3 kinase (PI3K). Constitutive activity of the PI3K pathway in B-CLL cells when cultured with fibroblasts prevented the downregulation of the prosurvival Bcl-2 family protein Bcl-xL and the caspase inhibitor proteins FLIPL and XIAP, and consequently caspase-3 activation and apoptosis. CD40 crosslinking in B-CLL cells did not further prevent murine fibroblasts-mediated apoptosis but induced cell proliferation, which was associated with an increase of Akt and NF-κB activation compared with cells cultured with fibroblasts alone. The PI3K pathway seems to play a pivotal role in B-CLL cell survival and growth.This work was supported by Fundación LAIR, Madrid, Spain

Conociendo mi entorno

El trabajo no ha sido publicadoEl proyecto se ha realizado en el CP Virgen de la V Angustia de Cacabelos (León) durante el curso 2001-2002, participando en él 9 profesores-as y 149 alumnos correspondientes a Educación Infantil, primer ciclo de E. Primaria (segundo nivel), segundo ciclo de E. Primaria (tercer y cuarto niveles), tercer ciclo de E. Primaria (sexto nivel) y el alumnado con necesidades educativas especiales incluidos en los ciclos. Aunque todo el trabajo de investigación ha tocado las diversas áreas de cada ciclo con un marcado carácter globalizador, ha sido en el área de Conocimiento del Medio donde se ha desarrollado de forma más profunda. Los objetivos generales en Educación Infantil son: observar y explorar el entorno inmediato con actitud de curiosidad y cuidado, identificando las características y propiedades más significativas de los elementos que lo forman y algunas de las relaciones que se establecen entre ellos; conocer algunas manifestaciones culturales de nuestro entorno, mostrando actitudes de respeto, interés y participación hacia ellas; proponer actividades al aire libre que permitan conocer y valorar el entorno; representar y evocar aspectos diversos de la realidad y expresarlos mediante las posibilidades que ofrece el juego. Los objetivos en Educación Primaria son: realizar tareas en grupo de forma cooperativa, asumiendo responsabilidades y participando de forma solidaria; valorar la pertenencia a grupos sociales con características y rasgos propios; identificar los principales elementos del entorno natural y social; reconocer en el medio próximo la intervención humana distinguiendo lo positivo de lo negativo; contribuir a crear hábitos de investigación. Para lograr todos estos objetivos primero se presenta el plan de trabajo donde se acuerdan los aspectos que se van a investigar, cómo se va a trabajar, los materiales a utilizar y se preparan las salidas a realizar, seguidamente se producen las salidas para recoger los datos y toda la información necesaria, después se realizan las actividades de aula, donde se organiza y analiza toda la información recogida en las salidas, en este paso es donde se utilizan los libros de consulta para profundizar en determinados aspectos; por último las actividades de síntesis, para completar datos, elaborar esquemas, tablas...Los materiales elaborados han sido: memoria del proyecto; un volumen donde se recoge la fundamentación y el desarrollo del proyecto y 5 cuadernos de actividades por ciclos, uno de E. Infantil, tres de E. Primaria (primer, segundo y tercer ciclo) y otro de alumnos con adaptaciones curriculares. También se ha elaborado una cinta de audio titulada 'We speak about our village' que se llevó a cabo en el área de Inglés. La experiencia ha sido muy enriquecedora a nivel personal y profesional. Las actividades han sido muy gratificantes para alumnos y profesores y los materiales elaborados pueden servir para otros cursos como experiencia práctica a seguir y para continuar estudiando nuestro entorno. .Castilla y LeónES

Structure and inhibition of SARS-CoV-1 and SARS-CoV-2 main proteases by oral antiviral compound AG7404

Severe acute respiratory syndrome coronaviruses 1 and 2 (SARS-CoV-1 and SARS-CoV-2) pose a threat to global public health. The 3C-like main protease (Mpro), which presents structural similarity with the active site domain of enterovirus 3C protease, is one of the best-characterized drug targets of these viruses. Here we studied the antiviral activity of the orally bioavailable enterovirus protease inhibitor AG7404 against SARS-CoV-1 and SARS-CoV-2 from a structural, biochemical, and cellular perspective, comparing it with the related molecule rupintrivir (AG7800). Crystallographic structures of AG7404 in complex with SARS-CoV-1 Mpro and SARS-CoV-2 Mpro and of rupintrivir in complex with SARS-CoV-2 Mpro were solved, revealing that all protein residues interacting with the inhibitors are conserved between the two proteins. A detailed analysis of protein-inhibitor interactions indicates that AG7404 has a better fit to the active site of the target protease than rupintrivir. This observation was further confirmed by biochemical FRET assays showing IC50 values of 47 μM and 101 μM for AG7404 and rupintrivir, respectively, in the case of SARS-CoV-2 Mpro. Equivalent IC50 values for SARS-CoV-1 also revealed greater inhibitory capacity of AG7404, with a value of 29 μM vs. 66 μM for rupintrivir. Finally, the antiviral activity of the two inhibitors against SARS-CoV-2 was confirmed in a human cell culture model of SARS-CoV-2 infection, although rupintrivir showed a higher potency and selectivity index in this assay.This study was supported by the Ministry of Science and Innovation of Spain (grant numbers BFU2017-83720-P and PID-2020-120141GB-I00 to MC) and Spanish National Research Council (grant numbers 2020AEPP116 to MC and PIE-RD-COVID-19 ref. E202020E079 to the CNB-CSIC). We acknowledge institutional funding from the Ministry of Science and Innovation of Spain through the Severo Ochoa Award of Excellence (SEV-2015-0500 and CEX2019-000913-S to IRB Barcelona) and Maria de Maeztu Award (MDM-2014-0435 to IBMB-CSIC Structural Biology Unit), and from the Catalan Government's CERCA Programme (grant to IRB Barcelona). This research work was also funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global). AHM was supported by National Agency for Research and Development (ANID)/Scholarship Program POSTDOCTORADO BECAS CHILE/2019–74200135. SMG was supported by an FPI fellowship from the Ministry of Science and Innovation of Spain. AG7404 ((E)-(S)-4-((S)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-pent-4-ynoylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester) was provided by Pfizer under Pure Compound Grant 63236753. With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000913-S