Comprehensive quantitative modeling of translation efficiency in a genome-reduced bacterium.

Translation efficiency has been mainly studied by ribosome profiling, which only provides an incomplete picture of translation kinetics. Here, we integrated the absolute quantifications of tRNAs, mRNAs, RNA half-lives, proteins, and protein half-lives with ribosome densities and derived the initiation and elongation rates for 475 genes (67% of all genes), 73 with high precision, in the bacterium Mycoplasma pneumoniae (Mpn). We found that, although the initiation rate varied over 160-fold among genes, most of the known factors had little impact on translation efficiency. Local codon elongation rates could not be fully explained by the adaptation to tRNA abundances, which varied over 100-fold among tRNA isoacceptors. We provide a comprehensive quantitative view of translation efficiency, which suggests the existence of unidentified mechanisms of translational regulation in Mpn.

Diseño y Validación de Contenido de una Guía de Análisis Funcional para Población con Depresión / Design and Validation of Content of a Guide for Functional Analysis for Population with Depression

Resumen El objetivo de esta investigación fue establecer el diseño y la validez de contenido de una Guía de Práctica Clínica (GPC) de análisis funcional (AF) para población con trastorno depresivo mayor (TDM). Se realizó por medio de una metodología cuantitativa de tipo instrumental, implementando la técnica de validación por jueces expertos, con la participación de seis jueces con experiencia en psicología clínica y cuatro en análisis del comportamiento. Resultado de la evaluación de los jueces, se obtuvo un índice de validez de contenido de 0.85, permitiendo establecer la validez de la GPC de análisis funcional para evaluar el TDM. Se concluye que los procedimientos para realizar AF en TDM corresponden con los referentes teórico-prácticos disponibles y con la tradición del enfoque conductual en psicología.

Abstract The objective of this research was to establish the design and content validity of a Clinical Practice Guideline (CPG) for Functional Analysis (FA) for a population with Major Depressive Disorder (MDD). It was carried out by means of an instrumental quantitative methodology, implementing the validation technique by expert judges, with the participation of six judges with experience in clinical psychology and four in behavior analysis. Result of the evaluation of the judges, a Content Validity Index of 0.85 was obtained, allowing to establish the validity of the Functional Analysis CPG to evaluate the TDM. It is concluded that the procedures to perform FA in TDM correspond with the available theoretical-practical references and with the tradition of the behavioral approach in psychology.

Engineering a genome-reduced bacterium to eliminate Staphylococcus aureus biofilms in vivo.

Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.

Widespread ribosome stalling in a genome-reduced bacterium and the need for translational quality control.

Trans-translation is a ubiquitous bacterial mechanism of ribosome rescue mediated by a transfer-messenger RNA (tmRNA) that adds a degradation tag to the truncated nascent polypeptide. Here, we characterize this quality control system in a genome-reduced bacterium, Mycoplasma pneumoniae (MPN), and perform a comparative analysis of protein quality control components in slow and fast-growing prokaryotes. We show in vivo that in MPN the sole quality control cytoplasmic protease (Lon) degrades efficiently tmRNA-tagged proteins. Analysis of tmRNA-mutants encoding a tag resistant to proteolysis reveals extensive tagging activity under normal growth. Unlike knockout strains, these mutants are viable demonstrating the requirement of tmRNA-mediated ribosome recycling. Chaperone and Lon steady-state levels maintain proteostasis in these mutants suggesting a model in which co-evolution of Lon and their substrates offer simple mechanisms of regulation without specialized degradation machineries. Finally, comparative analysis shows relative increase in Lon/Chaperone levels in slow-growing bacteria suggesting physiological adaptation to growth demand.

Topological Boundary Constraints in Artificial Colloidal Ice.

The effect of boundaries and how these can be used to influence the bulk behavior in geometrically frustrated systems are both long-standing puzzles, often relegated to a secondary role. Here, we use numerical simulations and "proof of concept" experiments to demonstrate that boundaries can be engineered to control the bulk behavior in a colloidal artificial ice. We show that an antiferromagnetic frontier forces the system to rapidly reach the ground state (GS), as opposed to the commonly implemented open or periodic boundary conditions. We also show that strategically placing defects at the corners generates novel bistable states, or topological strings, which result from competing GS regions in the bulk. Our results could be generalized to other frustrated micro- and nanostructures where boundary conditions may be engineered with lithographic techniques.

Determination of the Gene Regulatory Network of a Genome-Reduced Bacterium Highlights Alternative Regulation Independent of Transcription Factors.

Here, we determined the relative importance of different transcriptional mechanisms in the genome-reduced bacterium Mycoplasma pneumoniae, by employing an array of experimental techniques under multiple genetic and environmental perturbations. Of the 143 genes tested (21% of the bacterium's annotated proteins), only 55% showed an altered phenotype, highlighting the robustness of biological systems. We identified nine transcription factors (TFs) and their targets, representing 43% of the genome, and 16 regulators that indirectly affect transcription. Only 20% of transcriptional regulation is mediated by canonical TFs when responding to perturbations. Using a Random Forest, we quantified the non-redundant contribution of different mechanisms such as supercoiling, metabolic control, RNA degradation, and chromosome topology to transcriptional changes. Model-predicted gene changes correlate well with experimental data in 95% of the tested perturbations, explaining up to 70% of the total variance when also considering noise. This analysis highlights the importance of considering non-TF-mediated regulation when engineering bacteria.

Arteritis de células gigantes con compromiso de aorta y grandes vasos / Aortitis and large vessel involvement in giant cell arteritis

La arteritis de células gigantes (ACG) es una vasculitis sistémica de grandes vasos que no solo puede afectar a vasos craneales, si no que cada vez más frecuentemente se ha asociado a compromiso de vasos extracraneales. Este compromiso puede ser asintomático por lo que puede pasar inadvertido al estudio clínico básico y llevar a importantes complicaciones. Se presentan dos casos clínicos de ACG, ambos con aortitis y uno, además, con compromiso de grandes vasos del cayado aórtico y del cuello. Se discuten aspectos fisiopatológicos, clínicos y terapéuticos, con el objetivo de vislumbrar estrategias de abordaje de futuros pacientes con presentaciones similares.

Giant cell arteritis (GCA) is a age related, large vessels systemic vasculitis that not only affect cranial vessels, but is increasingly associated with extracranial vessel involvement. This extracranial involvement can be asymptomatic, so it can go unnoticed after basic clinical and laboratory study and lead to serious complications. We report two cases of GCA, both presenting aortitis and one of them presenting also involvement of aortic arch and of neck large vessels. We discuss physiopathologic, clinic and therapeutic aspects, with the aims of developing management strategies for the future patients with similar manifestations.

Neumatosis intestinal secundaria a esclerosis sistémica: caso clínico / Intestinal pneumatosis secondary to systemic sclerosis: clinical case

Intestinal pneumatosis is a rare complication that can occur in systemic sclerosis (ES), its pathogenesis is not entirely specified and is characterized by the presence of gas in the submucosa wall and / or bowel subserosa. For a 37 year old woman presented with a diagnosis of diffuse variety EN who consults repeatedly by pain, bloating and intermittent episodes of chronic diarrhea associated with weight loss. The imaging study revealed an intestinal pneumatosis and pneumoperitoneum as the source of the picture...

La neumatosis intestinal es una complicación rara que puede presentarse en la Esclerosis Sistémica (ES), su etiopatogenia no está del todo precisada y se caracteriza por presencia de gas en la pared submucosa y/o subserosa del intestino. Se presenta el caso de una mujer de 37 años, con diagnóstico de ES variedad difusa quien consulta en repetidas ocasiones por dolor, distensión abdominal y episodios de diarrea crónica intermitente asociado a disminución de peso. El estudio con imágenes reveló una neumatosis intestinal y neumoperitoneo como origen del cuadro...

Toxicidad severa asociada a metotrexato: caso clínico / Severe toxicity associated with methotrexate: clinical case

El metotrexato (MTX) es un agente anti folato con actividad antineoplásica e inmunosupresora que ha alcanzado gran aceptación y uso debido a su eficacia en distintos desórdenes reumatológicos. Sin embargo, tiene el potencial para causar complicaciones serias y, a veces, mortales, principalmente hematológicas, hepáticas o pulmonares. Los factores de riesgo para el desarrollo de pancitopenia incluyen edad avanzada, alteración de la función renal, niveles bajos de ácido fólico y uso concomitante de otros fármacos que modifiquen el metabolismo del folato. Presentamos un caso de pancitopenia severa y estomatitis, secundaria a una dosis estándar de MTX, en una paciente de 53 años de edad, con Artritis Reumatoídea (AR) de 10 años de evolución y enfermedad renal crónica en hemodiálisis trisemanal. Es muy importante prestar atención a los factores de riesgo asociados a la aparición de efectos adversos antes de iniciar terapia con MTX en pacientes reumatológicos. Además, los pacientes con MTX deben ser monitorizados durante su tratamiento para identificar efectos adversos hematológicos severos, como la pancitopenia.

Methotrexate (MTX) is an agent for anti-folate with antineoplastic activity and immunosuppressive that has achieved wide acceptance and use due to its efficacy in various rheumatologic disorders. However, it has the potential to cause complications serious and sometimes deadly, primarily hematologic, hepatic or pulmonary. The factors of risk for the development of pancytopenia include advanced age, renal function, low levels of folic acid and concomitant use of other drugs that alter the metabolism of folate. We present a case of severe pancytopenia and stomatitis, secondary to a standard dose of MTX in patient of 53 years, with rheumatoid arthritis (RA) of 10 years of evolution and chronic kidney disease on hemodialysis immediately. It is very important to pay attention to the risk factors associated with the occurrence of adverse effects, before initiating therapy with MTX in rheumatologic patients. In addition MTX patients should be monitored during treatment to identify severe haematological adverse effects such as pancytopenia.

Caracterización clínica, epidemiológica e histopatológica de pacientes con diagnóstico de queratosis actínica / Clinical, epidemiological and histopathological characterization of patients with actinic keratosis

Introducción: en otros países se han descrito ciertos factores relacionados con el desarrollo de queratosis actínica (QA). Objetivo: describir las características clínicas, epidemiológicas e histopatológicas de pacientes institucionales de Medellín, con diagnóstico de QA. Metodología: estudio descriptivo de pacientes con QA. Se aplicó una encuesta estructurada tomando datos demográficos, clínicos y relacionados con el desarrollo de la QA. Resultados: se incluyeron 153 pacientes (58 hombres [37,9%] y 95 mujeres [62,1%]), con edad promedio de 70 años. Tenían 75 años o más 64 pacientes (41,8%). Ciento ocho pacientes (70,6%) refirieron haber tenido un grado alto de exposición solar en la niñez; 76 (49,7%) tenían el antecedente de fumar y 16 de estos (21,1%) aún fumaban; 46 (30,1%) informaron el antecedente de un familiar con cáncer de piel. Setenta y tres (47,7%) realizaban las actividades tanto bajo techo como al aire libre; 80 (52,3%) informaron que se aplicaban protector solar y 37 (24,4%) usaban gorra o sombrero por la época en que fueron encuestados. Predominó el fototipo II (101 pacientes; 66%) y había daño actínico moderado en 76 (49,7%). Cuando hubo un solo patrón histológico predominó el atrófico (12%) y cuando hubo dos, el atróficohiperqueratósico (18,7%). Conclusiones: las características fenotípicas y de exposición de los pacientes con QA estudiados en Medellín (Colombia) son similares a las reportadas en la literatura.

Introduction: Several factors related with the development of actinic keratosis (AK) have been reported in other countries. Objective: To describe the clinical, epidemiological and histopathological characteristics of patients with diagnosis of AK in Medellín, Colombia. Methodology: This was a descriptive study of patients with AK. A structured survey including demographic, clinical and epidemiological information was applied. Results: 153 patients were included (58 men [37.9%] and 95 women [62.1%]) with an average age of 70 years. Sixty four patients (41.8%) were aged 75 years or more. With regard to their personal history, 108 individuals (70.6%) had a high degree of solar exposure during childhood; 76 (49.7%) reported the habit of smoking and 16 out of these (21.1%) still smoked. In 46 (30.1%) there was a family history of skin cancer. Regarding individual habits, 73 (47.7%) carried out both indoor and outdoor activities, 80 (52.3%) reported the use of sunscreen and 37 (24.4%) used hat or cap at the time of the study. Fitzpatrick´s type II phototype predominated (101 patients; 66%) and 76 (49.7%) had moderate actinic damage. The predominant single histologic subtype corresponded to the atrophic type (12%) and the main mixed subtype was the atrophichyperkeratotic subtype (18.7%). Conclusions: Clinical, epidemiological and histopathological features found among two institutional populations with AK in Medellin (Colombia) were similar to those reported in the literature.

Concepto de corrupción y su representación en los estudiantes universitarios / The concept of corruption and its representation among university students

En este trabajo se fundamenta epistemológica y psicológicamente en un modo de conceptuar la corrupción. Se plantea que en la sociedad contemporánea, en particular en países como Argentina, se pueden distinguir dos grandes formas de corrupción que, aunque representan momentos históricos distintos, tienen plena vigencia y, además, una fuerte dinámica de entrelazamiento. Una de esas formas de corrupción es propia de las sociedades de mercado desarrolladas (capitalismo) mientras que la otra es inherente a las sociedades donde priman formas de poder precapitalista. Se considera que una claridad conceptual es decisiva para percibir no sólo la magnitud sino también la cadena causal a que da lugar o en la cual se halla implicado ese fenómeno psico-político. Aquí se presentan y analizan los datos obtenidos en un relevamiento empírico efectuado en septiembre-octubre de 2003 con estudiantes universitarios. El objetivo del mismo era registrar las conceptualizaciones que éstos presentaban acerca de la corrupción y compararlas con las construidas desde nuestro marco teórico. También se analiza la estimación que los entrevistados realizan acerca del grado de vigencia de la corrupción en las instituciones más notorias del país. En este último aspecto, los resultados muestran una ligera variación respecto de los datos obtenidos en las encuestas del año 2001 y 2002. A la par, en la población, se mantiene un nivel de conceptualización y de explicación insuficientemente objetivo de la noción estudiada.

Um estudo preliminar sobre o teatro como espaço de desenvolvimento humano / A preliminary study on theater as a place of human development

Este trabalho partiu da intenção de relacionar o Teatro com a Psicologia sob o enfoque do desenvolvimento humano. Através de uma visão psicológica acerca das características transformadoras que o Teatro apresenta e principalmente, através dos movimentos intra e interpessoais que o permeiam, pretendeu-se encaminhar um estudo preliminar sobre o Teatro como espaço de desenvolvimento humano. Para tanto, foram entrevistadas três pessoas ligadas ativa e afetivamente ao Teatro: um ator, um diretor e um espectador. Foram realizadas entrevistas semi-estruturadas, sendo que o conteúdo das mesmas foi categorizado segundo temas que se apresentaram de modo repetitivo pelos entrevistados. As categorias formadas foram analisadas qualitativamente de acordo com Winnicott - que postula a importância e necessidade, inerentes ao ser humano, de expressar, interagir e criar como condições constituintes de um desenvolvimento psicológico saudável. Os resultados da pesquisa foram divididos entre dois conceitos principais: Teatro-Função e Teatro-Situação, no sentido de se alcançar uma visão mais abrangente e produtiva dos dados. Foi ressaltado que as possibilidades de transformação implícitas no Teatro são, grande parte das vezes, tratadas de maneira consciente pelas pessoas que se vinculam à esta arte. Para o ser humano, expressar e dar novas formas ao que é percebido do mundo interno e do externo compõe um processo de desenvolvimento saudável, e no Teatro as experiências podem ser revividas, representadas e, assim, reelaboradas(AU)