CCCTC-binding factor locks premature IgH germline transcription and restrains class switch recombination

In response to antigenic stimulation B cells undergo class switch recombination (CSR) at the immunoglobulin heavy chain (IgH) to replace the primary IgM/IgD isotypes by IgG, IgE, or IgA. CSR is initiated by activation-induced cytidine deaminase (AID) through the deamination of cytosine residues at the switch (S) regions of IgH. B cell stimulation promotes germline transcription (GLT) of specific S regions, a necessary event prior to CSR because it facilitates AID access to S regions. Here, we show that CCCTC-binding factor (CTCF)-deficient mice are severely impaired in the generation of germinal center B cells and plasma cells after immunization in vivo, most likely due to impaired cell survival. Importantly, we find that CTCF-deficient B cells have an increased rate of CSR under various stimulation conditions in vitro. This effect is not secondary to altered cell proliferation or AID expression in CTCF-deficient cells. Instead, we find that CTCF-deficient B cells harbor an increased mutation frequency at switch regions, probably reflecting an increased accessibility of AID to IgH in the absence of CTCF. Moreover, CTCF deficiency triggers premature GLT of S regions in naïve B cells. Our results indicate that CTCF restricts CSR by enforcing GLT silencing and limiting AID access to IgH

CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation

In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reaction in vivo, whereas in vitro the requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation

Planificación y evaluación del Trabajo de Fin de Grado:el caso del Grado en Información y Documentación de la universidad Carlos III de Madrid

In the framework of the European Higher Education Area, the Undergraduate Dissertation is a subject on the official curriculum for the bachelor's degrees that can be earned in Spanish universities, Carlos III University of Madrid among them. It consists of an individual dissertation in which students apply the knowledge, skills and competencies acquired throughout their 4-year courses to a problem specific to the discipline associated with the degree to which they aspire. Planning, conducting and evaluating the work involved in the dissertation call for ad hoc tools that must be designed to accurately appraise the command of specific competencies associated with the degree sought by the student. The present paper introduces three such tools developed for the Bachelor's Degree in Information and Documentation offered at Carlos III University since 2008-09: a guidance manual, a preview system and an evaluation rubric. The guidance manual provides students with clear and precise instructions on how to undertake their study. The preview system affords a consistent, clear procedure for all students and for suitable monitoring of their progress at specified intervals. The evaluation rubric is a consistent and objective marking tool for juries. The three enable students and staff to suitably monitor progress and for professors to consistently and objectively evaluate all students in accordance with the duly weighted categories into which the competencies associated with the bachelor's degree in Information and Documentation are grouped.El Trabajo Fin de Grado (TFG) es, en el marco del Espacio Europeo de Educación Superior (EEES), y en particular en los estudios de Grado que oferta la Universidad Carlos III de Madrid, una asignatura más dentro del plan de estudios. Consiste en la realización de un trabajo de carácter individual, en el que el alumno demuestra los conocimientos, habilidades y competencias adquiridos durante sus estudios a un problema específico del ámbito de la titulación. La planificación, desarrollo y evaluación de esta asignatura supone diseñar instrumentos ad hoc que permitan valorar adecuadamente la adquisición de las competencias específicas ligadas al título de Grado al que opta el alumno. A tal efecto, en este trabajo, se presentan tres herramientas concretas que se han elaborado para el título de Grado en Información y Documentación que se imparte en la Universidad Carlos III de Madrid desde el curso 2008-09: un manual de orientación, un plan de avances y una rúbrica o matriz de evaluación. El primero de ellos, el manual de orientación, ofrece al estudiante una guía clara y precisa de cómo elaborar el trabajo. El segundo, el plan de avances, ha permitido desarrollar un procedimiento claro y unitario para todos los estudiantes y realizar un seguimiento adecuado de los avances de los alumnos con plazos temporales determinados. El tercero, la rúbrica o matriz de evaluación, ha facilitado una herramienta coherente y objetiva de calificación para los tribunales que los evalúan. Todas ellas permiten, tanto a los profesores como a los alumnos, realizar un seguimiento adecuado de los trabajos y una evaluación coherente y objetiva para todos ellos de las 16 competencias asociadas al TFG en el Grado en Información y Documentación con la correspondiente ponderación de sus indicadores

Levels and sources of hydrocarbons in the Patos Lagoon estuary and Cassino Beach mud bank (South Atlantic, Brazil): evidence of transference between environments

This study assessed the concentrations and sources of natural and anthropogenic aliphatic (AHs) and polycyclic aromatic hydrocarbons (PAHs) in superficial sediments collected along the Patos Lagoon estuary and in sediment cores obtained from the Cassino Beach mud bank. Levels and distribution of n-alkanes indicate terrestrial sources, overlapping with a low amount of petrogenic hydrocarbons (heavy oils). Unresolved complex mixture (UCM) was observed in all samples. On the other hand, the distribution of PAHs in the sediments showed a predominance of pyrolytic over petrogenic sources. In general, hydrocarbons (HCs) contamination in the Patos Lagoon estuary and its adjacent coastal area can be considered low, except for sites near urban or industrial effluents, where moderate to high levels of contamination were found. Concentrations of hydrocarbons were homogeneous throughout the sediment cores, suggesting that mixing processes may have occurred along the layers or that HCs inputs to the mud banks were uniform during the studied deposition period. In addition, the levels and profile of HCs in the coastal sediments were similar to those observed in the estuary. Moreover, the frequent remobilization of sediments from the mud bank towards Cassino beach does not seem to pose any threats to the local biota or beach users since the levels of contamination were relatively low and below the threshold limits of sediment quality guideline

Presión arterial : ¿esfigmomanómetro manual o digital?

El presente es un estudio prospectivo y comparativo entre la medición de la presión arterial obtenida de manera manual con esfigmomanómetro aneroide y la obtenida mediante monitor automático. El desarrollo de la práctica se realizó sobre un grupo de 100 pacientes hospitalizados en el servicio de Neurocirugía y Otorrinolaringología del Consorcio Hospital General de Valencia durante el primer trimestre del año 2007, mediante mediciones secuenciales y efectuadas por el mismo observador con ambos aparatos bien calibrados. Se observó mediante el método de correlación bivariada de Pearson que no existen diferencias estadísticamente significativas entre las presiones tomadas por ambos aparatos determinando así la fiabilidad del aparato automático utilizado en esta sala para el registro de la tensión arterial.This is a prospective and comparative work between arterial pressure obtained through manual measurement with aneroid sphygmomanometer and the arterial pressure obtained through automatic monitor. The practice was carried out in a group of 100 inpatients in the Neurosurgery and Otolaryngology Service in the Consortium of the General Hospital of Valencia during the first term of 2007. The development of this hospital training was made on each individual through sequential measurements and executed by the same observer with both well-calibrated machines. It was observed that through the method of Pearson's bivaried correlation there are not statistically significant differences between the pressures taken by both machines. As regards this fact, both automatic machines of arterial pressure register are [email protected] [email protected]

Porous carbons-derived from vegetal biomass in the synthesis of quinoxalines. Mechanistic insights.

We report herein for the first-time acid biomass-derived carbons from vegetal biomass, with high developed porosity, prepared through the integrating method comprising pyrolysis and surface phosphonation, able to efficiently catalyze the synthesis of quinoxalines from 1,2-diamines and -hydroxi ketones, under aerobic conditions. The obtained results indicate that the type and number of acid sites drive the reaction in terms of conversion and selectivity. Furthermore, our experimental and theoretical observations suggest that the preferred reaction pathway for this transformation, in the presence of the investigated acid carbon catalysts, involves cascade reactions including imination reaction between reactants, successive imine-enamine and ceto-enol tautomerisms, heterocyclization followed by dehydration, and aromatization. While the acid sites seem to be a relevant role in each reaction step, the system formed by activated carbon and molecular oxygen could be behind the last oxidative reaction to give quinoxalines.pre-print615 K

Ventilatory threshold prediction by spectral analysis of heart rate variability in incremental maximal tests

Ventilatory thresholds (VT1 and VT2) are useful in many fields of medicine and sports. Nevertheless, their measurement is cumbersome and needs trained personnel. This work proposes an alternative method to predict VT1, VT2 and maximum loads in incremental maximal tests based on heart rate variability (HRV) analysis. Twelve competitive male cyclists executed an incremental exhaustive test. During the test, RR time series and gas concentrations were recorded. After artifact correction the power spectrum was estimated in a sliding window, and central frequency (CF) and bandwidth that contains half the total power (BW) were computed. An automatic algorithm recognized the loads where CF and BW undergo a significant change. These loads were used as inputs in linear regression models to predict VT1, VT2 and maximum loads. The errors of the predictions are similar to the load resolution.Postprint (published version

Evaluación del cribado y la efectividad de una intervención breve en bebedores de riesgo atendidos en consultas de atención primaria

ObjetivosEvaluar el cribado y la efectividad de una intervención breve antialcohólica, el grado de aceptación y la evolución de los parámetros biológicos asociados con el consumo de alcohol tras la intervención.DiseñoEstudio prospectivo longitudinal de intervención de 1 año de duración.EmplazamientoCinco consultas de atención primaria urbanas.ParticipantesDe una muestra aleatoria de 681 sujetos de ambos sexos y de edad de 18-65 años, se seleccionó a 78 bebedores de riesgo. Los que cumplían criterios de exclusión (n=10), no aceptaban participar (n=24) y presentaban sospecha de síndrome de dependencia alcohólica (n=11) no participaron en el estudio.IntervencionesSe ofrecía un breve consejo antialcohólico apoyado con soporte escrito, y se realizaba un seguimiento a los 2 y 12 meses mediante la cuantificación del consumo de alcohol y un control analítico.Mediciones principalesSe estimó la prevalencia de bebedores de riesgo, el grado de aceptación a participar en el estudio, la disminución del consumo de alcohol y de bebedores de riesgo a los 2 y 12 meses, y la evolución de los parámetros analíticos tras la intervención.ResultadosLa prevalencia de bebedores de riesgo fue del 11,5% (intervalo de confianza [IC] del 95%, 8,3-14,7%). El grado de aceptación a participar en el estudio fue del 64,7%. Se observó un decremento significativo (p<0,05) en el consumo de alcohol a los 2 y 12 meses, así como una disminución de los bebedores de riesgo, que a los 2 meses fue del 57,6% (IC del 95%, 50,3-64,9%; p=0,01) y a los 12 meses del 42,4% (IC del 95%, 35,9-48,9%; p=0,003). Asimismo, se produjeron disminuciones significativas en las concentraciones de GGT, VCM, colesterol y triglicéridos.ConclusionesSe observa una baja prevalencia de bebedores de riesgo sin sospecha de síndrome de dependencia alcohólica en nuestro medio, así como una elevada efectividad del consejo breve antialcohol y del grado de aceptación a participar en el estudio. Se apreció una disminución de las concentraciones de GGT, VCM, colesterol y triglicéridos tras la intervención.AimsTo evaluate the screening, the effectiveness of an antialcoholic brief intervention for risk drinkers, the acceptation level to participate in this study, and the analytical parameters evolution associated to the alcohol consumption after of the intervention.DesignLongitudinal prospective intervention study of 1 year of duration.Setting5 urban primary care physician's practices.ParticipantsOf an aleatory pattern of 681 patients, men and women of 18-65 years old, were selected 78 risk drinkers. Patients with exclusion criteria (n=10), didn’t wanted to participate (n=24) and had suspicion of alcoholic dependence syndrome (ADS) (n=11), didn’t participated in this intervention.InterventionsWere offered antialcoholic brief counselling with written supporter and were followed with alcohol consumption rate and analytical control at 2 and 12 months.Main measuresWas estimated the prevalence of risk drinkers, the acceptation level to participate in this study, alcohol consumption and risk drinkers decreased at 2 and 12 months, analytical parameters evolution after of the intervention.ResultsPrevalence of risk drinkers: 11.5% (95% confidence interval [CI], 8.3%-14.7%). Acceptation level to participate in this study: 64.7%. Significative alcohol consumption decreased at 2 and 12 months (P<.05). Risk drinkers decreased: at 2 months were 57.6% (95% CI, 50.3%-64.9%; P=.01) and at 12 months were 42.4% (95% CI; 35.9%-48.9%) (P=.003). GGT, MCV, cholesterol, and triglycerides significative decreased.ConclusionsLow prevalence of risk drinkers without suspicion of ADS in our setting; high effectiveness of antialcoholic brief counselling and high acceptation level to participate in this study; reduction of the GGT, MCV, cholesterol, and triglycerides after of the intervention

The adrenal medulla modulates mechanical allodynia in a rat model of neuropathic pain

We have investigated whether the stress response mediated by the adrenal medulla in rats subjected to chronic constriction injury of the sciatic nerve (CCI) modulates their nocifensive behavior. Treatment with SK29661 (300 mg/kg; intraperitoneal (I.P.)), a selective inhibitor of phenylethanolamine N-methyltransferase (PNMT) that converts noradrenaline (NA) into adrenaline (A), fully reverted mechanical allodynia in the injured hind paw without affecting mechanical sensitivity in the contralateral paw. The effect was fast and reversible and was associated with a decrease in the A to NA ratio (A/NA) in the adrenal gland and circulating blood, an A/NA that was elevated by CCI. 1,2,3,4-tetrahydroisoquinoline-7-sulfonamide (SKF29661) did not a ect exocytosis evoked by Ca2+ entry as well as major ionic conductances (voltage-gated Na+, Ca2+, and K+ channels, nicotinic acetylcholine receptors) involved in stimulus-secretion coupling in chroma n cells, suggesting that it acted by changing the relative content of the two adrenal catecholamines. Denervation of the adrenal medulla by surgical splanchnectomy attenuated mechanical allodynia in neuropathic animals, hence confirming the involvement of the adrenal medulla in the pathophysiology of the CCI model. Inhibition of PNMT appears to be an effective and probably safe way to modulate adrenal medulla activity and, in turn, to alleviate pain secondary to the injury of a peripheral nerveThis research was funded by the SPANISH MINISTER OF SCIENCE AND INNOVATION, grants BFU2011-26253, BFU2015-70067-REDC to A.R.A., and SAF2016-78892 to A.G.G, and by UNIVERSIDAD COMPLUTENSE DE MADRID, grant PR75/18-21593 to A.R.A

Impact assessment of agricultural inputs into a Mediterranean coastal lagoon (Mar Menor, SE)

The Mar Menor is a coastal lagoon threatened by the development of intensive agriculture in the surrounding areas. Large amounts of pesticides from these areas are discharged into El Albujón, a permanent watercourse flowing into the lagoon. We have used a multi-biomarker approach to assess the biological effects arising in bivalve species affected by agricultural pollution. Biomarkers indicative of neurotoxicity (acetylcholinesterase, AchE), oxidative stress (catalase, CAT; glutathione reductase, GR and lipid peroxidation, LPO), phase II biotransformation of xenobiotics (glutathione S-transferase, GST) and physiological stress (scope for growth, SFG) were measured in clams transplanted to four sites of the lagoon (two reference sites and two sites affected by the dispersion of the effluent of the El Albujón), for exposure periods of 7 and 22 days. The hazards of this effluent were also examined by simultaneously measuring up to 83 contaminants (pesticides, PCBs, PAHs and others) in samples of fresh water from the watercourse mouth and seawater from the deployed sites, as well as the bioaccumulation of organochlorinated compounds and PAHs in the transplanted animals. Biomarker responses showed marked differences between reference and affected sites after 7 and 22 days. However it was only after 22 days that Principal Component Analysis (PCA) of the biomarker responses distinguished between clams deployed in sites affected by the dispersion of the effluent of the watercourse and those from the reference sites. The chemical analysis of water showed high concentrations of pesticides close to El Albujón watercourse mouth, with the greatest input flux corresponding to the organophosphate chlorpyrifos, followed by pendimethalin and naphthalene, and at lower levels acenaphthene, terbuthylazine-desethyl and chlorpyrifos-methyl. In this regard, PCA analysis showed that the biological effects of the mixture of pesticides in caged clams after 22 days were reduced levels of AchE and SFG and increased levels of GR and phase II GST activity. An Integrated Biomarker Response index was calculated from the combination of these biomarkers, proving useful for the assessment of the impact of agricultural pollution in caged clams.Preprint3,761