Negative feedback and transcriptional overshooting in a regulatory network for horizontal gene transfer

Horizontal gene transfer (HGT) is a major force driving bacterial evolution. Because of their ability to cross inter-species barriers, bacterial plasmids are essential agents for HGT. This ability, however, poses specific requisites on plasmid physiology, in particular the need to overcome a multilevel selection process with opposing demands. We analyzed the transcriptional network of plasmid R388, one of the most promiscuous plasmids in Proteobacteria. Transcriptional analysis by fluorescence expression profiling and quantitative PCR revealed a regulatory network controlled by six transcriptional repressors. The regulatory network relied on strong promoters, which were tightly repressed in negative feedback loops. Computational simulations and theoretical analysis indicated that this architecture would show a transcriptional burst after plasmid conjugation, linking the magnitude of the feedback gain with the intensity of the transcriptional burst. Experimental analysis showed that transcriptional overshooting occurred when the plasmid invaded a new population of susceptible cells. We propose that transcriptional overshooting allows genome rebooting after horizontal gene transfer, and might have an adaptive role in overcoming the opposing demands of multilevel selection

Amoebicidal activity of cationic carbosilane dendrons derived with 4-phenylbutyric acid against Acanthamoeba griffini and Acanthamoeba polyphaga trophozoites and cysts

Amoebae from the genus Acanthamoeba are important pathogens responsible for severe illnesses in humans such as Acanthamoeba keratitis and granulomatous amoebic encephalitis. In the last few decades, AK diagnoses have steadily increased. Most patients suffering from AK were contact lens users and the infection was related to poor hygiene. However, therapy is not yet well established, and treatments may last for several months due to resistance. Moreover, these treatments have been described to generate cytotoxicity. Therefore, there is an urgent need to develop new therapeutic strategies against AK. In this study, the amoebicidal activity of different generation cationic carbosilane dendrons derived with 4-phenylbutyric acid was demonstrated against Acanthamoeba polyphaga and Acanthamoeba griffini trophozoites and cysts. In addition, the combination of chlorhexidine digluconate and the most effective dendron (ArCO(2)G(2)(SNMe3I)(4)) showed an in vitro effect against Acanthamoeba trophozoites and cysts, reducing the minimal trophozoite amoebicidal concentration as well as concentrations with cysticidal activity.Ministerio de Economía y CompetitividadUniversidad de AlcaláComunidad de Madri

Assessment of the sensitivity and specificity of serological (IFAT) and molecular (direct PCR) techniques for diagnosis of leishmaniasis in lagomorphs using a Bayesian approach

Leishmaniasis, caused by Leishmania infantum, is a vector-borne zoonotic disease that is endemic to the Mediterranean basin. The potential of rabbits and hares to serve as competent reservoirs for the disease has recently been demonstrated, although assessment of the importance of their role on disease dynamics is hampered by the absence of quantitative knowledge on the accuracy of diagnostic techniques in these species. A Bayesian latent-class model was used here to estimate the sensitivity and specificity of the Immuno-fluorescence antibody test (IFAT) in serum and a Leishmania-nested PCR (Ln-PCR) in skin for samples collected from 217 rabbits and 70 hares from two different populations in the region of Madrid, Spain. A two-population model, assuming conditional independence between test results and incorporating prior information on the performance of the tests in other animal species obtained from the literature, was used. Two alternative cut-off values were assumed for the interpretation of the IFAT results: 1/50 for conservative and 1/25 for sensitive interpretation. Results suggest that sensitivity and specificity of the IFAT were around 70–80%, whereas the Ln-PCR was highly specific (96%) but had a limited sensitivity (28.9% applying the conservative interpretation and 21.3% with the sensitive one). Prevalence was higher in the rabbit population (50.5% and 72.6%, for the conservative and sensitive interpretation, respectively) than in hares (6.7% and 13.2%). Our results demonstrate that the IFAT may be a useful screening tool for diagnosis of leishmaniasis in rabbits and hares. These results will help to design and implement surveillance programmes in wild species, with the ultimate objective of early detecting and preventing incursions of the disease into domestic and human populations

Mediterranean lifestyle index and 24-h systolic blood pressure and heart rate in community-dwelling older adults

Specifc foods, nutrients, dietary patterns, and physical activity are associated with lower blood pressure (BP) and heart rate (HR), but little is known about the joint efect of lifestyle factors captured in a multidimensional score. We assessed the association of a validated Mediterranean-lifestyle (MEDLIFE) index with 24-h-ambulatory BP and HR in everyday life among community-living older adults. Data were taken from 2,184 individuals (51% females, mean age: 71.4 years) from the SeniorsENRICA-2 cohort. The MEDLIFE index consisted of 29 items arranged in three blocks: 1) Food consumption; 2) Dietary habits; and 3) Physical activity, rest, and conviviality. A higher MEDLIFE score (0–29 points) represented a better Mediterranean lifestyle adherence. 24-h-ambulatory BP and HR were obtained with validated oscillometric devices. Analyses were performed with linear regression adjusted for the main confounders. The MEDLIFEhighest quintile (vs Q1) was associated with lower nighttime systolic BP (SBP) (-3.17 mmHg [95% CI: -5.25, -1.08]; p-trend=0.011), greater nocturnal-SBP fall (1.67% [0.51, 2.83]; p-trend=0.052), and lower HR (-2.04 bpm [daytime], -2.33 bpm [nighttime], and -1.93 bpm [24-h]; all p-trend<0.001). Results were similar for each of the three blocks of MEDLIFE and by hypertension status (yes/no). Among older adults, higher adherence to MEDLIFE was associated with lower nighttime SBP, greater nocturnal-SBP fall, and lower HR in their everyday life. These results suggest a synergistic BP-related protection from the components of the Mediterranean lifestyle. Future studies should determine whether these results replicate in older adults from other Mediterranean and non-Mediterranean countriesThis work was supported by FIS grants 19/319, 20/00896, and 22/1164 from the Carlos III Health Institute, the Secretary of R+D+I, and the European Regional Development Fund/European Social Fund; and by International; REACT EU Program. Comunidad de Madrid and European Regional Development Fund (ERDF), European Union: FACINGLCOVID-CM project, Comunidad de Madrid and European Regional Development Fund (ERDF), European Union. MSP holds a Ramón y Cajal contract (RYC2018–025069-I) from the Spanish Ministry of Science, Innovation and Universitie

Explicando la impresión lejos de los talleres de la UAM

3er Coloquio Fortalecimiento de los Colectivos de Docencia.Se consideran las limitantes y ventajas en la impartición de las UEAS: Tecnología para el Diseño Gráfico II. Introducción a las Artes Gráficas y Tecnología para el Diseño Gráfico IV. Preprensa y DTP. Se trabajo en la búsqueda de actividades que permitieran un aprendizaje significativo, las estrategias de enseñanza-aprendizaje han requerido de un gran esfuerzo y creatividad. Fue útil reflexionar en la utilidad de lo que se ha estado haciendo por mucho tiempo y como se podría modificar; se observó que algunas actividades y temas se pueden simplificar mucho, incluso eliminarlos o combinarlos y generar actividades diferentes desde una nueva perspectiva

Consideraciones en torno a un modelo semipresencial para la UEA de medios impresos

3er Coloquio Fortalecimiento de los Colectivos de Docencia.Tomando en consideración las experiencias derivadas del trabajo en el Programa Emergente de Educación Remota (PEER), los integrantes del subcolectivo de medios impresos, queremos compartir algunas consideraciones y estrategias que surgen de la reflexión en torno a la posibilidad que se tiene de un regreso a las aulas, específicamente para las UEAS de tipo teórico-práctico correspondientes a nuestro colectivo tomando en consideración la posible implementación de un modelo semipresencial

Aproximación al significado léxico con primitivos y moléculas: trabajo experimental (I)

Documento de trabajo que recoge trece informes realizados por estudiantes del Grado de Lengua Española y sus Literaturas durante el curso 2017/18, que recoge los datos, su análisis y discusión de diversos trabajos experimentales en los que se intenta una aproximación al significado léxico de algunas palabras mediante primitivos y moléculas. Este trabajo se inserta en el Proyecto de Innovación "Piensapalabras" (2017/18, nº 125)

Beta cell functionality and hepatic insulin resistance are major contributors to type 2 diabetes remission and starting pharmacological therapy: from CORDIOPREV randomized controlled trial

In order to assess whether previous hepatic IR (Hepatic-IR fasting) and beta-cell functionality could modulate type 2 diabetes remission and the need for starting glucose- lowering treatment, newly-diagnosed type 2 diabetes participants who had never received glucose-lowering treatment (190 out of 1002) from the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (a prospective, randomized and controlled clinical trial), were randomized to consume a Mediterranean or a low-fat diet. Type 2 diabetes remission was defined according to the American Diabetes Association recommendation for levels of HbA1c, fasting plasma glucose and 2h plasma glucose after oral glucose tolerance test, and having maintained them for at least 2 consecutive years. Patients were classified according to the median of Hepatic-IR fasting and beta-cell functionality, measured as the disposition index (DI) at baseline. Cox proportional hazards regression determined the potential for Hepatic-IR fasting and DI indexes as predictors of diabetes remission and the probability of starting pharmacological treatment after a 5-year follow-up. Low-Hepatic-IR fasting or high-DI patients had a higher probability of diabetes remission than high-Hepatic-IR fasting or low-DI subjects (HR:1.79; 95% CI 1.06_3.05; and HR:2.66; 95% CI 1.60_4.43, respectively) after a dietary intervention with no pharmacological treatment and no weight loss. The combination of low- Hepatic-IR fasting and high-DI presented the highest probability of remission (HR:4.63; 95% CI 2.00_10.70). Among patients maintaining diabetes, those with high- Hepatic-IR fasting and low-DI showed the highest risk of starting glucose-lowerin

Could radiotherapy effectiveness be enhanced by electromagnetic field treatment?

One of the main goals in radiobiology research is to enhance radiotherapy effectiveness without provoking any increase in toxicity. In this context, it has been proposed that electromagnetic fields (EMFs), known to be modulators of proliferation rate, enhancers of apoptosis and inductors of genotoxicity, might control tumor recruitment and, thus, provide therapeutic benefits. Scientific evidence shows that the effects of ionizing radiation on cellular compartments and functions are strengthened by EMF. Although little is known about the potential role of EMFs in radiotherapy (RT), the radiosensitizing effect of EMFs described in the literature could support their use to improve radiation effectiveness. Thus, we hypothesized that EMF exposure might enhance the ionizing radiation effect on tumor cells, improving the effects of RT. The aim of this paper is to review reports of the effects of EMFs in biological systems and their potential therapeutic benefits in radiotherapy.This study was supported by the Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (PI08/0728, Fondos FEDER) to M.I. Núñez. F. Artacho-Cordón is supported by the Spanish Ministry of Science and Education (AP2012-2524). A grant from the Fundación Benéfica San Francisco Javier y Santa Cándida, University of Granada, to S. Ríos-Arrabal greatly aided this work. This research was also funded by the San Cecilio University Hospital, Granada

Pregnancy Outcomes and SARS-CoV-2 Infection: The Spanish Obstetric Emergency Group Study

Pregnant women who are infected with SARS-CoV-2 are at an increased risk of adverse perinatal outcomes. With this study, we aimed to better understand the relationship between maternal infection and perinatal outcomes, especially preterm births, and the underlying medical and interventionist factors. This was a prospective observational study carried out in 78 centers (Spanish Obstetric Emergency Group) with a cohort of 1347 SARS-CoV-2 PCR-positive pregnant women registered consecutively between 26 February and 5 November 2020, and a concurrent sample of PCR-negative mothers. The patients' information was collected from their medical records, and the association of SARS-CoV-2 and perinatal outcomes was evaluated by univariable and multivariate analyses. The data from 1347 SARS-CoV-2-positive pregnancies were compared with those from 1607 SARS-CoV-2-negative pregnancies. Differences were observed between both groups in premature rupture of membranes (15.5% vs. 11.1%, p < 0.001); venous thrombotic events (1.5% vs. 0.2%, p < 0.001); and severe pre-eclampsia incidence (40.6 vs. 15.6%, p = 0.001), which could have been overestimated in the infected cohort due to the shared analytical signs between this hypertensive disorder and COVID-19. In addition, more preterm deliveries were observed in infected patients (11.1% vs. 5.8%, p < 0.001) mainly due to an increase in iatrogenic preterm births. The prematurity in SARS-CoV-2-affected pregnancies results from a predisposition to end the pregnancy because of maternal disease (pneumonia and pre-eclampsia, with or without COVID-19 symptoms)