Optimizing periodicity and polymodality in noise-induced genetic oscillators

Many cellular functions are based on the rhythmic organization of biological processes into self-repeating cascades of events. Some of these periodic processes, such as the cell cycles of several species, exhibit conspicuous irregularities in the form of period skippings, which lead to polymodal distributions of cycle lengths. A recently proposed mechanism that accounts for this quantized behavior is the stabilization of a Hopf-unstable state by molecular noise. Here we investigate the effect of varying noise in a model system, namely an excitable activator-repressor genetic circuit, that displays this noise-induced stabilization effect. Our results show that an optimal noise level enhances the regularity (coherence) of the cycles, in a form of coherence resonance. Similar noise levels also optimize the multimodal nature of the cycle lengths. Together, these results illustrate how molecular noise within a minimal gene regulatory motif confers robust generation of polymodal patterns of periodicity.Comment: 9 pages, 6 figure

Univariate parametric survival analysis using GS-distributions.

The GS-distribution is a family of distributions that provide an accurate representation of any unimodal univariate continuous distribution. In this contribution we explore the utility of this family as a general model in survival analysis. We show that the survival function based on the GS-distribution is able to provide a model for univariate survival data and that appropriate estimates can be obtained. We develop some hypotheses tests that can be used for checking the underlying survival model and for comparing the survival of different groups.Peer Reviewe

La mortalidad por cáncer en las comarcas de cataluña (1983–1989)

ResumenObjectivosComparar la mortalidad intercomarcal de Cataluña para algunos de los tumores malignos más frecuentes.MetodologíaSe han analizado los datos globales y de cinco localizaciones tumorales específicas relativos a la mortalidad por cáncer de un período de siete años (1983-1989). Se han obtenido las tasas brutas de mortalidad y las específicas para cada localización analizada. La comparación intercomarcal se ha realizado ajustando las tasas por edad mediante el método directo, tomando como referencia la población de Cataluña de 1986. Se han calculado las razones comparativas de mortalidad (RCM) de cada comarca respecto a Cataluña.ResultadosLa mortalidad global por cáncer es más alta en la comarca del Barcelonés para los hombres y en la de Osona para las mujeres. La RCM de los hombres del Barcelonés es la más alta para el cáncer de tráquea, bronquios y pulmón; la de la comarca del Solsonés es la más alta para el cáncer de estómago, y la de la Cerdanya es la más alta para el cáncer de colon y recto. Entre las mujeres, la RCM más alta para el cáncer de tráquea, bronquios y pulmón la presenta la comarca del Montsiá, para el cáncer de mama la del Baix Empordá y para el cáncer de estómago la del Alt Urgell.ConclusionesEl análisis comparativo de la mortalidad por cáncer, por comarcas y por sexos, permite observar importantes diferencias en la manifestación del fenómeno, lo cual puede orientar de manera más específica las políticas de control del cáncer y de investigación a desarrollar en cada territorio.SummaryObjectivesTo compare mortality among counties (comarques) in Catalonia, Spain for the most frequent malignant tumors.MethodsOverall mortality data and for five specific tumor sites were analyzed for a five-year period (1983-1989). Crude and site-specific mortality rates were computed. The comparison between counties was adjusted for the 1986 population of Catalonia using the direct method. Comparative mortality ratios (CMR) were obtained for each county with respect to Catalonia.ResultsOverall cancer mortality was higher in the Barcelonés for men and in Osona form women. The CMR for men in the Barcelonés was the highest for cancer of the trachea, bronchi and lungs; the CMR in Solsonés was the highest for stomach cancer, while in Cerdanya it was the highest for colorectal cancer. Among women, the highest CMR for cancer of the trachea, bronchi and lungs was in Montsiá, whereas for breast cancer it was Baix Empordá, and Alt Urgell for stomach cancer.ConclusionsComparative analyses of cancer mortality by county in Catalonia and sex underscores differences in its distribution, allowing the orientation of cancer control policies and research to be developed in each geographical area

Percepción del estado de salud en varones y mujeres en las últimas etapas de la vida

ResumenObjetivoAnalizar las diferencias en la percepción del estado de salud de los varones y mujeres en las últimas etapas de la vida y explorar su relación con variables sociodemográficas y de salud.MétodosDatos procedentes de la Encuesta de Salud de Cataluña de 1994, de 1.459 varones y 1.993 mujeres de 60 y más años. Se realizó un análisis de la autovaloración del estado de salud según la edad, el sexo, la clase social, la declaración de enfermedades crónicas y la discapacidades y se aplicó un modelo de análisis multivariable de regresión logística teniendo en cuenta el diseño muestral.ResultadosEl 57,3% de las mujeres de 60 y más años declaraba no tener buena salud, frente al 43,6% de los varones. También fue superior la proporción de mujeres que padecía una o más discapacidades (41,2%) respecto a los varones (28,7%), así como la de enfermedades crónicas, el 92,2% de las mujeres y el 85,6% de los varones. En el modelo de regresión logística multivariable continúa manteniéndose una percepción de mala salud superior en las mujeres y aparecen como factores explicativos el número de enfermedades crónicas, padecer discapacidades y pertenecer a las clases sociales más desfavorecidas. La edad en interacción con las enfermedades crónicas amortigua el efecto de éstas en la valoración del estado de salud.ConclusionesEntre la población anciana, la percepción de mala salud fue superior en las mujeres incluso ajustando por otras variables explicativas significativas (clase social, edad, discapacidades y enfermedades crónicas). Padecer enfermedades crónicas y/o discapacidades constituyen los factores explicativos más importantes en la percepción del estado de salud. El impacto del padecimiento de enfermedades crónicas en relación con la percepción de mala salud disminuye a medida que los grupos son de mayor edad.SummaryObjectivesTo analyze the differences in health self-perception between men and women in the later stages of life and to assess their association with sociodemographic and health variables.MethodsData on 1,459 men and 1,993 women aged 60 or older from the 1994 Catalan Health Survey, were collected and an analysis of health self-perception according to age, gender, social class, reporting of chronic disease and handicaps was performed. Multivariate logistic regression analysis was used, taking into account the survey design.ResultsOf the women aged 60 and older, 57.3% reported poor health compared with 43.6% of men of the same age. The proportion of women with one or more handicaps was also greater (41.2%) than that of the men (28.7%), as was the case with chronic disease (92.2% inwomen and 85.6% in men). The multivariate model also revealed that health self-peerception was poorer among women than among men. Other explanatory factors were the number of chronic diseases, having handicaps, and being a member of a lower social class. Age interacted with the number of chronic diseases to mitigate the effect of chronic diseases on perceived health status.ConclusionsIn the elderly population, poor health self-perception was greater among women, even when other significant explanatory variable (social class, age, handicaps and chronic disease) were adjusted for. The most important explanatory factors in health self-perception were having chronic disease and/or handicaps. The impact of chronic disease on poor health self-perception decreased in older age groups

Análisis del infrarregistro de la mortalidad perinatal y sus factores asociados en una región sanitaria de Cataluña

ResumenObjetivosEvaluar la magnitud del infrarregistro de las muertes perinatales de la Región Sanitaria «Centre» (RSC) (Cataluña). Estimar las tasas de mortalidad reales y analizar los factores asociados al infrarregistro.MétodosEstudio observacional retrospectivo del infrarregistro de la mortalidad perinatal durante el período 1991–1992 en la RSC. Mediante una recogida activa se han identificado las muertes perinatales de peso igual o superior a 500 gr o de 22 semanas o más, ocurridas en los hospitales del RSC, comparándolas, mediante un apareamiento informático, con las muertes perinatales del registro oficial de mortalidad. Las variables de apareamiento utilizadas han sido: nombre y apellidos del recién nacido, sexo, municipio y fecha de la defunción. Se ha aplicado el análisis de regresión logística para detectar los factores asociados al infrarregistro.ResultadosLa mortalidad perinatal en la RSC en el período 1991–92 se ha infraestimado en un 34% (IC 95%: 26%–42%). La mayor parte de las muertes no declaradas corresponde a muertes fetales y/o recién nacidos de muy bajo peso o de gran prematuridad que mueren a las pocas horas de vida. Durante el fin de semana el infrarregistro es unas cuatro veces mayor. Una vez recogida, la tasa de mortalidad perinatal en la RSC para los años 1991–1992 pasa de 6,3 por 1.000 nacimientos a 9,6 por 1.000 nacimientos.ConclusionesPara disponer de una información precisa de las necesidades de salud de las mujeres en edad fértil y de los recién nacidos de la RSC, y de cada uno de sus sectores, debe mejorarse la declaración de las muertes perinatales.SummaryObjectivesTo assess the degree of undereporting of perinatal deaths in the «Centre» Region (CR) during 1991 and 1992.MethodsObservational retrospective study of the undereporting of perinatal deaths in the CR during 1991 and 1992. Perinatal deaths above 499 grams or 21 weeks of gestation which occurred in the hospitals of the CR were identified by reviewing hospital records, and then compared through linkage with perinatal deaths recorded in vital statistics. The following variables were used for the matching: name and surname, sex, county and date of death. Logistic regression was used to identify factors associated with undereporting.ResultsThe degree of undereporting of perinatal deaths in the CR during 1991–1992 was 34% [95% CI: (26%–42%)]. Most undereported perinatal deaths corresponded to fetal deaths, or very low birthweight or preterm livebirths that died shortly after birth. Over the weekend, undereporting increases by four-fold. The official perinatal mortality rate for the CR, 6.3 per 1,000 births, increased to 9.6 per 1,000 births, after taking into account undereporting.ConclusionsIn order to have valid information of the health needs of mothers and newborns reporting of perinatal deaths must be improved

El desarrollo de la profesionalidad docente mediante redes

Desde 2001, un grupo de profesores representantes de distintos centros de educación secundaria del área de Barcelona, se han articulado en red coordinados por el Grupo Observatori d'Oportunitats Educatives de la Universidad Autònoma de Barcelona. El eje del trabajo en red en este período se centró en el análisis de la intervención educativa que reciben los alumnos con dificultades académicas y sociales. El propósito central de esta comunicación es presentar una validación del trabajo realizado durante este período de tiempo, a partir de las consideraciones de los profesores participantes en dicha red. En este sentido, la referencia de la reflexión al contexto social, administrativo y político de la Educción en Catalunya es un factor esencial para comprender aquella validación en todo su sentido

Novel Human/Non-Human Primate Cross-Reactive Anti-Transferrin Receptor Nanobodies for Brain Delivery of Biologics

The blood-brain barrier (BBB), while being the gatekeeper of the central nervous system (CNS), is a bottleneck for the treatment of neurological diseases. Unfortunately, most of the biologicals do not reach their brain targets in sufficient quantities. The antibody targeting of receptor-mediated transcytosis (RMT) receptors is an exploited mechanism that increases brain permeability. We previously discovered an anti-human transferrin receptor (TfR) nanobody that could efficiently deliver a therapeutic moiety across the BBB. Despite the high homology between human and cynomolgus TfR, the nanobody was unable to bind the non-human primate receptor. Here we report the discovery of two nanobodies that were able to bind human and cynomolgus TfR, making these nanobodies more clinically relevant. Whereas nanobody BBB00515 bound cynomolgus TfR with 18 times more affinity than it did human TfR, nanobody BBB00533 bound human and cynomolgus TfR with similar affinities. When fused with an anti-beta-site amyloid precursor protein cleaving enzyme (BACE1) antibody (1A11AM), each of the nanobodies was able to increase its brain permeability after peripheral injection. A 40% reduction of brain Aβ1–40 levels could be observed in mice injected with anti-TfR/BACE1 bispecific antibodies when compared to vehicle-injected mice. In summary, we found two nanobodies that could bind both human and cynomolgus TfR with the potential to be used clinically to increase the brain permeability of therapeutic biologicals

Taxon Appearance From Extraction and Amplification Steps Demonstrates the Value of Multiple Controls in Tick Microbiota Analysis

Background: The development of high-throughput sequencing technologies has substantially improved analysis of bacterial community diversity, composition, and functions. Over the last decade, high-throughput sequencing has been used extensively to identify the diversity and composition of tick microbial communities. However, a growing number of studies are warning about the impact of contamination brought along the different steps of the analytical process, from DNA extraction to amplification. In low biomass samples, e.g., individual tick samples, these contaminants may represent a large part of the obtained sequences, and thus generate considerable errors in downstream analyses and in the interpretation of results. Most studies of tick microbiota either do not mention the inclusion of controls during the DNA extraction or amplification steps, or consider the lack of an electrophoresis signal as an absence of contamination. In this context, we aimed to assess the proportion of contaminant sequences resulting from these steps. We analyzed the microbiota of individual Ixodes ricinus ticks by including several categories of controls throughout the analytical process: homogenization, DNA extraction, and DNA amplification. Results: Controls yielded a significant number of sequences (1, 126–13, 198 mean sequences, depending on the control category). Some operational taxonomic units (OTUs) detected in these controls belong to genera reported in previous tick microbiota studies. In this study, these OTUs accounted for 50.9% of the total number of sequences in our samples, and were considered contaminants. Contamination levels (i.e., the percentage of sequences belonging to OTUs identified as contaminants) varied with tick instar and sex: 76.3% of nymphs and 75% of males demonstrated contamination over 50%, while most females (65.7%) had rates lower than 20%. Contamination mainly corresponded to OTUs detected in homogenization and extraction reagent controls, highlighting the importance of carefully controlling these steps. Conclusion: Here, we showed that contaminant OTUs from sample laboratory processing steps can represent more than half the total sequence yield in sequencing runs, and lead to unreliable results when characterizing tick microbial communities. We thus strongly advise the routine use of negative controls in tick microbiota studies, and more generally in studies involving low biomass samples

El desarrollo de la profesionalidad docente mediante redes

Desde 2001, un grupo de profesores representantes de distintos centros de educación secundaria del área de Barcelona, se han articulado en red coordinados por el Grupo Observatori d'Oportunitats Educatives de la Universidad Autònoma de Barcelona. El eje del trabajo en red en este período se centró en el análisis de la intervención educativa que reciben los alumnos con dificultades académicas y sociales. El propósito central de esta comunicación es presentar una validación del trabajo realizado durante este período de tiempo, a partir de las consideraciones de los profesores participantes en dicha red. En este sentido, la referencia de la reflexión al contexto social, administrativo y político de la Educción en Catalunya es un factor esencial para comprender aquella validación en todo su sentido