Mode d’action moléculaire de la toxine anti-tumorale : PS1Aa2 du bacille de Thuringe

Les parasporines sont des toxines Cry du bacille de Thuringe actives contre des cellules tumorales. Ce travail montre que la parasporine PS1Aa2 (Cry31Aa2) forme des pores dans des membranes artificielles, comme de nombreuses toxines Cry. Ceux-ci ont plusieurs niveaux de conductance dont les plus fréquents étaient de 11, 16 et 21 pS dans une solution de 150 mM KCl. Nos résultats de microspectrofluorométrie avec la sonde Fura-2 montrent que la présence de la PS1Aa2 peut produire des augmentations du calcium intracellulaire, la plupart du temps sous la forme d’oscillations calciques et parfois des augmentations soutenues. Ces réponses ont été observées en présence et en absence de calcium extracellulaire, dans les lignées tumorales HeLa et HepG2 et dans la lignée non tumorale HEK 293. Bien que quelques études aient montré que le calcium semble intervenir dans leur mode d’action, de telles oscillations calciques n’ont jamais été décrites auparavant pour des toxines Cry. Les expériences ont dû être faites à des concentrations beaucoup plus élevées de toxine que prévues sur la base des résultats publiés de cytotoxicité. Malgré la présence des fragments identifiés auparavant comme actifs, sa faible efficacité semble liée à la présence d’ADN dans les préparations qui entraîne la précipitation de la protéine. Les travaux futurs sur cette toxine seraient donc grandement facilités par une amélioration de sa méthode de préparation.

Diferencia venoarterial de PCO2 como predictor de disfunción miocárdica en pacientes pediátricos con sepsis severa y choque séptico

El objetivo de este estudio, es determinar la capacidad de la diferencia venoarterial de de pCO2, como predictor de disfunción miocárdica en pacientes pediátricos con sepsis severa y choque séptico en la Unidad de Cuidado Intensivo Pediátrico de la Fundación Cardio Infantil. El documento eviado corresponde a un informe parcial de un estudio en curso en la Fundación CardioInfantil.

Imaginarios sociales de las organizaciones sobre el desarrollo humano desde la perspectiva de la complejidad

Este trabajo investigativo surge a partir de la indagación que primero se realizó con los coordinadores, gerentes y directores de 16 organizaciones empresariales de Bogotá, para determinar los imaginarios que se tienen en torno a las organizaciones y su desarrollo humano y social desde el punto de vista de la teoría de la complejidad. A partir de esta indagación en los grupos focales se plantean unos conceptos propuestos desde la experiencia y la construcción cultural que posee cada uno de los integrantes. El trabajo tiene los siguientes apartes: en la primera parte en el marco teórico se profundiza en torno a la organización desde las representaciones sociales, el papel de los imaginarios, el proceso del desarrollo humano y social, desde el marco de la complejidad y concluye con la ilustración de los resultados matriciales, que nos permiten observar cómo son percibidas las diferentes dimensiones del ser humano y su desarrollo social en las organizaciones con elementos constitutivos de la teoría de la complejidad

La Ense??anza Secundaria en la Historia de la Educaci??n en Espa??a

Son casi 300 los trabajos espec??ficos sobre la historia de la ense??anza secundaria en Espa??a que se rese??an, la mayor??a dedicados a la ense??anza secundaria p??blica e insertadas en un marco local, publicados por lo esencial tras la fecha de 1982. Las fuentes sobre las que se apoyan estos estudios son relativamente numerosas y asequibles, bien en los archivos, bien en las bibliotecas. El conjunto de estos trabajos llevados a cabo, en general meramente descriptivos o por lo menos de tipo ??nicamente positivista, permite disponer ya de una base s??lida para una visi??n promenorizada y compleja del conjunto de la ense??anza, secundaria espa??ola en la ??poca contempor??nea, permitiendo legar a la etapa siguiente, un enfoque interpretativo y comparado a veces intentado.

Conocimientos de los estudiantes de 16 a 18 años sobre el sistema reproductor humano.

Este trabajo es una primera reseña de un proyecto completo dedicado a investigar las concepciones sobre el aparato reproductor que poseen los estudiantes argentinos de esducación post-obligatoria. Se muestra sólo la parte diagnóstica inicial y su respectivo análisis, aunque el proyecto engloba posteriormente el diseño y planificación de unidades didácticas para el desarrollo y construcción de conceptos clave de la temática, y también la elaboración de instrumentos acordes de evaluación . El diagnóstico fue realizado en dos escuelas privadas: una ubicada en la ciudad de Buenos Aires con alumnos de clase media y media-baja. En ella se trabajó con ocho estudiantes del último curso de educación secundaria (17-18 años). La otra institución es una escuela con matrícula mayoritariamente perteneciente a clase alta ubicada en la provincia de Buenos Aires, en la que se trabajó con un grupo de dieciséis estudiantes del penúltimo año (segundo año del polimodal, 16-17 años)El instrumento de diagnóstico utilizado sugería a los estudiantes que realizaran un esquema del aparato reproductor de su sexo y otro del sexo opuesto, y que colocaran las referencias correspondientes a los órganos y estructuras que conocían. Luego se les pedía que respondieran a un cuestionario sobre el origen de esos conocimientos, el papel de la escuela en la adquisición de esos conocimientos, cuáles son los conocimientos que consideran no poseen y cómo evaluarían los conocimientos que poseen. Los resultados evidenciaron que los esquemas realizados presentaban confusiones y errores en relación con la estructura y ubicación de los distintos órganos, y en algunos casos con su función. En el primer grupo se reconoce como fuente de estos conocimientos fundamentalmente a los amigos y la familia, relegando la escuela; el segundo grupo reconoce mayoritariamente a la familia como fuente de conocimiento y en segundo lugar la escuela. Coinciden ambos grupos en la consideración de los conocimientos que les faltan en especial de la anticoncepción y las enfermedades. Los estudiantes del primer grupo se muestran fuertemente críticos : saben poco y mal. Esta primera fase de la investigación invita a la reflexión sobre los contenidos que han de abordarse respecto a la educación sexual en los alumnos que van a finalizar estudios secundarios superiores en Argentina y a su tratamiento didáctico .

Estimates of global multicomponent aerosol optical depth and direct radiative perturbation in the Laboratoire de Météorologie Dynamique general circulation model

The global cycle of multicomponent aerosols including sulfate, black carbon (BC),organic matter (OM), mineral dust, and sea salt is simulated in the Laboratoire de Me´te´orologie Dynamique general circulation model (LMDZT GCM). The seasonal open biomass burning emissions for simulation years 2000–2001 are scaled from climatological emissions in proportion to satellite detected fire counts. The emissions of dust and sea salt are parameterized online in the model. The comparison of model-predicted monthly mean aerosol optical depth (AOD) at 500 nm with Aerosol Robotic Network (AERONET) shows good agreement with a correlation coefficient of 0.57(N = 1324) and 76% of data points falling within a factor of 2 deviation. The correlation coefficient for daily mean values drops to 0.49 (N = 23,680). The absorption AOD (ta at 670 nm) estimated in the model is poorly correlated with measurements (r = 0.27, N = 349). It is biased low by 24% as compared to AERONET. The model reproduces the prominent features in the monthly mean AOD retrievals from Moderate Resolution Imaging Spectroradiometer (MODIS). The agreement between the model and MODIS is better over source and outflow regions (i.e., within a factor of 2).There is an underestimation of the model by up to a factor of 3 to 5 over some remote oceans. The largest contribution to global annual average AOD (0.12 at 550 nm) is from sulfate (0.043 or 35%), followed by sea salt (0.027 or 23%), dust (0.026 or 22%),OM (0.021 or 17%), and BC (0.004 or 3%). The atmospheric aerosol absorption is predominantly contributed by BC and is about 3% of the total AOD. The globally and annually averaged shortwave (SW) direct aerosol radiative perturbation (DARP) in clear-sky conditions is �2.17 Wm�2 and is about a factor of 2 larger than in all-sky conditions (�1.04 Wm�2). The net DARP (SW + LW) by all aerosols is �1.46 and �0.59 Wm�2 in clear- and all-sky conditions, respectively. Use of realistic, less absorbing in SW, optical properties for dust results in negative forcing over the dust-dominated regions.

Shiro, Burt and Phyllis, interviewed by Sam Levine on January 17, 2010: Audio Recording

Some of the themes discussed are: • Occupation—store, The Jefferson Hotel (2, 4-6, 11, 17-18) • Food (2) • Colby—Greek life (3, 7) • Military service (3-4) • Bar Mitzvah (6, 12) • Life in Waterville—Circus (6) • Anti-semitism (10-12) • Occupation—law (8-9) • Occupation—legislature (14) • Jewish education (12) • Synagogue (13) • Civic engagement—United Way (15) • Civic engagement (26-28) • Camp—Modin (18) • College—attendance (19) • Colby—football (20-21, 23, 30)

Shiro, Burt, and Phyllis, interviewed by Sam Levine on January 17, 2010: Transcript

Some of the themes discussed are: • Occupation—store, The Jefferson Hotel (2, 4-6, 11, 17-18) • Food (2) • Colby—Greek life (3, 7) • Military service (3-4) • Bar Mitzvah (6, 12) • Life in Waterville—Circus (6) • Anti-semitism (10-12) • Occupation—law (8-9) • Occupation—legislature (14) • Jewish education (12) • Synagogue (13) • Civic engagement—United Way (15) • Civic engagement (26-28) • Camp—Modin (18) • College—attendance (19) • Colby—football (20-21, 23, 30)

HLA-Bw4-B*57 and Cw*18 alleles are associated with plasma viral load modulation in HIV-1 infected individuals in Salvador, Brazil

Host genetic factors play an important role in mediating resistance to HIV-1 infection and may modify the course of infection. HLA-B alleles (Bw4 epitope; B*27 and B*57) as well as killer cell immunoglobulin-like receptors have been associated with slow progression of HIV-1 infection. OBJECTIVE: To evaluate the association between serological epitopes HLA-Bw4 and HLA-Bw6 and prognostic markers in AIDS. METHODS: 147 HIV-infected individuals in Bahia, Northeast Brazil, were genotyped for HLA class I locus. HLA class I genotyping was performed by hybridization with sequence-specific oligonucleotide probes following amplification of the corresponding HLA-A, HLA-B and HLA-C genes. Statistical analysis was performed using Fisher's exact and ANOVA tests for categorical and continuous variables, respectively. RESULTS: We detected a significant association (χ2 = 4.856; p = 0.018) between the presence of HLA-Bw4 and low levels of viremia. Eighteen out of the 147 HIV-infected individuals presented viremia <1,800 copies/mL and 129 presented viremia > 2,000 copies/mL. Ninety and four percent (17/18) of all individuals with viremia < 1,800 copies/mL carried HLA-Bw4, compared to 67.4% (87/129) of individuals with viremia > 2,000 copies/mL. Additionally, we found a significantly higher frequency of B*57 (OR = 13.94; 95% CI = 4.19-46.38; p < 0.0001) and Cw*18 (OR = 16.15; 95% CI = 3.46-75.43; p < 0.0001) alleles, favoring the group with lower viremia levels, in comparison with those with higher viral load. CONCLUSION: HLA-Bw4-B*57 and Cw*18 alleles are associated with lower level of viral load in HIV-infected Brazilian patients. These findings may help us in understanding the determinants of HIV evolution in Brazilian patients, as well as in providing important information on immune response correlates of protection for such population.

Parâmetros de produção de leite de búfala fermentado por Lactobacillus casei

O leite de búfala foi fermentado por Lactobacillus casei, com diferentes concentrações de açúcar e tempos de fermentação, e estocado durante 30 dias a 5 e 10°C. Avaliaram-se a acidez, o pH e a viabilidade de L. casei nos diferentes tratamentos. O leite fermentado por 18 horas não apresentou os parâmetros requeridos para o produto, enquanto os fermentados por 22 e 24 horas apresentaram acidez e pH adequados. O tempo e a temperatura de estocagem influenciaram esses parâmetros. A viabilidade de L. casei inicial foi maior que 9 log UFC mL^-1 e a final, maior que 8 log UFC mL^-1, com influência da acidez.

Association between education in EOL care and variability in EOL practice: a survey of ICU physicians

This study investigated the association between physician education in EOL and variability in EOL practice, as well as the differences between beliefs and practices regarding EOL in the ICU. Physicians from 11 ICUs at a university hospital completed a survey presenting a patient in a vegetative state with no family or advance directives. Questions addressed approaches to EOL care, as well physicians' personal, professional and EOL educational characteristics. The response rate was 89%, with 105 questionnaires analyzed. Mean age was 38 +/- A 8 years, with a mean of 14 +/- A 7 years since graduation. Physicians who did not apply do-not-resuscitate (DNR) orders were less likely to have attended EOL classes than those who applied written DNR orders [0/7 vs. 31/47, OR = 0.549 (0.356-0.848), P = 0.001]. Physicians who involved nurses in the decision-making process were more likely to be ICU specialists [17/22 vs. 46/83, OR = 4.1959 (1.271-13.845), P = 0.013] than physicians who made such decisions among themselves or referred to ethical or judicial committees. Physicians who would apply "full code" had less often read about EOL [3/22 vs. 11/20, OR = 0.0939 (0.012-0.710), P = 0.012] and had less interest in discussing EOL [17/22 vs. 20/20, OR = 0.210 (0.122-0.361), P < 0.001], than physicians who would withdraw life-sustaining therapies. Forty-four percent of respondents would not do what they believed was best for their patient, with 98% of them believing a less aggressive attitude preferable. Legal concerns were the leading cause for this dichotomy. Physician education about EOL is associated with variability in EOL decisions in the ICU. Moreover, actual practice may differ from what physicians believe is best for the patient.

Mutation Spectrum in the Large GTPase Dynamin 2, and Genotype-Phenotype Correlation in Autosomal Dominant Centronuclear Myopathy

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT. Hum Mutat 33: 949-959, 2012. (C) 2012 Wiley Periodicals, Inc.

Multilocus sequence analysis and rpoB sequencing of Mycobacterium abscessus (sensu lato) strains

Mycobacterium abscessus, Mycobacterium bolletii, and Mycobacterium massiliense (Mycobacterium abscessus sensu lato) are closely related species that currently are identified by the sequencing of the rpoB gene. However, recent studies show that rpoB sequencing alone is insufficient to discriminate between these species, and some authors have questioned their current taxonomic classification. We studied here a large collection of M. abscessus (sensu lato) strains by partial rpoB sequencing (752 bp) and multilocus sequence analysis (MLSA). The final MLSA scheme developed was based on the partial sequences of eight housekeeping genes: argH, cya, glpK, gnd, murC, pgm, pta, and purH. The strains studied included the three type strains (M. abscessus CIP 104536(T), M. massiliense CIP 108297(T), and M. bolletii CIP 108541(T)) and 120 isolates recovered between 1997 and 2007 in France, Germany, Switzerland, and Brazil. The rpoB phylogenetic tree confirmed the existence of three main clusters, each comprising the type strain of one species. However, divergence values between the M. massiliense and M. bolletii clusters all were below 3% and between the M. abscessus and M. massiliense clusters were from 2.66 to 3.59%. The tree produced using the concatenated MLSA gene sequences (4,071 bp) also showed three main clusters, each comprising the type strain of one species. The M. abscessus cluster had a bootstrap value of 100% and was mostly compact. Bootstrap values for the M. massiliense and M. bolletii branches were much lower (71 and 61%, respectively), with the M. massiliense cluster having a fuzzy aspect. Mean (range) divergence values were 2.17% (1.13 to 2.58%) between the M. abscessus and M. massiliense clusters, 2.37% (1.5 to 2.85%) between the M. abscessus and M. bolletii clusters, and 2.28% (0.86 to 2.68%) between the M. massiliense and M. bolletii clusters. Adding the rpoB sequence to the MLSA-concatenated sequence (total sequence, 4,823 bp) had little effect on the clustering of strains. We found 10/120 (8.3%) isolates for which the concatenated MLSA gene sequence and rpoB sequence were discordant (e.g., M. massiliense MLSA sequence and M. abscessus rpoB sequence), suggesting the intergroup lateral transfers of rpoB. In conclusion, our study strongly supports the recent proposal that M. abscessus, M. massiliense, and M. bolletii should constitute a single species. Our findings also indicate that there has been a horizontal transfer of rpoB sequences between these subgroups, precluding the use of rpoB sequencing alone for the accurate identification of the two proposed M. abscessus subspecies.