Rapid, efficient auxin-inducible protein degradation in Candida pathogens.

A variety of inducible protein degradation (IPD) systems have been developed as powerful tools for protein functional characterization. IPD systems provide a convenient mechanism for rapid inactivation of almost any target protein of interest. Auxin-inducible degradation (AID) is one of the most common IPD systems and has been established in diverse eukaryotic research model organisms. Thus far, IPD tools have not been developed for use in pathogenic fungal species. Here, we demonstrate that the original AID and the second generation, AID2, systems work efficiently and rapidly in the human pathogenic yeasts, Candida albicans and Candida glabrata. We developed a collection of plasmids that support AID system use in laboratory strains of these pathogens. These systems can induce >95% degradation of target proteins within minutes. In the case of AID2, maximal degradation was achieved at low nanomolar concentrations of the synthetic auxin analog 5-adamantyl-indole-3-acetic acid. Auxin-induced target degradation successfully phenocopied gene deletions in both species. The system should be readily adaptable to other fungal species and to clinical pathogen strains. Our results define the AID system as a powerful and convenient functional genomics tool for protein characterization in fungal pathogens. IMPORTANCE Life-threatening fungal infections are an escalating human health problem, complicated by limited treatment options and the evolution of drug resistant pathogen strains. Identification of new targets for therapeutics to combat invasive fungal infections, including those caused by Candida species, is an urgent need. In this report, we establish and validate an inducible protein degradation methodology in Candida albicans and Candida glabrata that provides a new tool for protein functional characterization in these, and likely other, fungal pathogen species. We expect this tool will ultimately be useful for the identification and characterization of promising drug targets and factors involved in virulence and drug resistance.

Rapid, efficient auxin-inducible protein degradation in Candida pathogens.

A variety of inducible protein degradation (IPD) systems have been developed as powerful tools for protein functional characterization. IPD systems provide a convenient mechanism for rapid inactivation of almost any target protein of interest. Auxin-inducible degradation (AID) is one of the most common IPD systems and has been established in diverse eukaryotic research model organisms. Thus far, IPD tools have not been developed for use in pathogenic fungal species. Here, we demonstrate that the original AID and the second generation AID2 systems work efficiently and rapidly in the human pathogenic yeasts Candida albicans and Candida glabrata . We developed a collection of plasmids that support AID system use in laboratory strains of these pathogens. These systems can induce >95% degradation of target proteins within minutes. In the case of AID2, maximal degradation was achieved at low nanomolar concentrations of the synthetic auxin analog 5-adamantyl-indole-3-acetic acid (5-Ad-IAA). Auxin-induced target degradation successfully phenocopied gene deletions in both species. The system should be readily adaptable to other fungal species and to clinical pathogen strains. Our results define the AID system as a powerful and convenient functional genomics tool for protein characterization in fungal pathogens.

Análisis de la evolución del conocimiento preventivo y su práctica entre la población de Colombia hacia la enfermedad por Coronavirus (Covid-19)

La presente investigación muestra la evolución que ha presentado el conocimiento y práctica de las recomendaciones dadas por la Organización Mundial de la Salud para la prevención de la Covid-19 en comparación al estudio realizado por Rivera-Diaz et al. Se encuetaron 478 personas, los resultados mostraron que un alto porcentaje conoce y pone en práctica las recomendaciones de la OMS indistintamente del sexo del individuo. Además, el estudio evidencia la problemática relacionada con el consumo de sustancias o medicamentos para la prevención de la Covid-19, que pueden poner en serios riesgos la salud de quien los consume; de otro lado, el uso de plantas medicinales también demuestra ser una práctica muy común en la población.

SUMMARY This research shows the evolution that has been presented by the knowledge and practice by part of the people of the recommendations given by the World Health Organization for the prevention of Covid-19 compared to the study carried out by Rivera-Diaz et al. 478 people were surveyed, the results showed that a high percentage knows and puts into practice the WHO recommendations regardless of the sex of the individual. In addition, the study shows the problems related to the consumption of substances and / or medications for the prevention of Covid-19, which can put the health of those who consume them at serious risk; on the other hand, the use of medicinal plants also proves to be a very common practice in the population.

A presente investigação mostra a evolução que tem apresentado o conhecimento e prática das recomendações da Organização Mundial da Saúden para a prevenção do Covid-19 em comparação com o estudo realizado por Rivera-Diaz et ai. 478 pessoas foram entrevistadas, os resultados mostraram que uma alta porcentagem conhece e coloca em prática as recomendações da OMS, independentemente da sexo do indivíduo. Além disso, o estudo destaca o problema relacionado à consumo de substâncias ou medicamentos para a prevenção da Covid-19, que podem colocar em sério risco a saúde de quem os consome; Por outro lado, o uso de As plantas medicinais também se revelam uma prática muito comum na população.

Unpacking Peer Conversations in a Virtual Communitiy for Diabetes Self-Management Education and Support: Behavior Science and Linguistics Perspective.

Diabetes is a chronic disease that can be effectively managed and controlled using strategies such as self-management education and ongoing support. Virtual environments offer innovative and realistic settings where patients can achieve self-management education and obtain ongoing self-management support from peers and healthcare professionals. Transcribed real-time conversations in an innovative virtual community were analyzed using qualitative and linguistic analysis. These virtual interactions were manually coded to identify embedded behavior change techniques and linguistic features. Results showed 13 behavior change techniques were manifested. Further, language differences were observed between behavior change techniques and social support types. Our research can provide valuable insights into the design of effective digital health interventions that maximize sustained use of virtual environments, subsequently impacting self-management of chronic conditions such as diabetes.

Eng2, a new player involved in feedback loop regulation of Cdc42 activity in fission yeast.

Cell polarity and morphogenesis are regulated by the small GTPase Cdc42. Even though major advances have been done in the field during the last years, the molecular details leading to its activation in particular cellular contexts are not completely understood. In fission yeast, the ß(1,3)-glucanase Eng2 is a "moonlighting protein" with a dual function, acting as a hydrolase during spore dehiscence, and as component of the endocytic machinery in vegetative cells. Here, we report that Eng2 plays a role in Cdc42 activation during polarized growth through its interaction with the scaffold protein Scd2, which brings Cdc42 together with its guanine nucleotide exchange factor (GEF) Scd1. eng2Δ mutant cells have defects in activation of the bipolar growth (NETO), remaining monopolar during all the cell cycle. In the absence of Eng2 the accumulation of Scd1 and Scd2 at the poles is reduced, the levels of Cdc42 activation decrease, and the Cdc42 oscillatory behavior, associated with bipolar growth in wild type cells, is altered. Furthermore, overexpression of Eng2 partially rescues the growth and polarity defects of a cdc42-L160S mutant. Altogether, our work unveils a new factor regulating the activity of Cdc42, which could potentially link the polarity and endocytic machineries.

Exchanges in a Virtual Environment for Diabetes Self-Management Education and Support: Social Network Analysis.

BACKGROUND: Diabetes remains a major health problem in the United States, affecting an estimated 10.5% of the population. Diabetes self-management interventions improve diabetes knowledge, self-management behaviors, and clinical outcomes. Widespread internet connectivity facilitates the use of eHealth interventions, which positively impacts knowledge, social support, and clinical and behavioral outcomes. In particular, diabetes interventions based on virtual environments have the potential to improve diabetes self-efficacy and support, while being highly feasible and usable. However, little is known about the patterns of social interactions and support taking place within type 2 diabetes-specific virtual communities. OBJECTIVE: The objective of this study was to examine social support exchanges from a type 2 diabetes self-management education and support intervention that was delivered via a virtual environment. METHODS: Data comprised virtual environment-mediated synchronous interactions among participants and between participants and providers from an intervention for type 2 diabetes self-management education and support. Network data derived from such social interactions were used to create networks to analyze patterns of social support exchange with the lens of social network analysis. Additionally, network correlations were used to explore associations between social support networks. RESULTS: The findings revealed structural differences between support networks, as well as key network characteristics of supportive interactions facilitated by the intervention. Emotional and appraisal support networks are the larger, most centralized, and most active networks, suggesting that virtual communities can be good sources for these types of support. In addition, appraisal and instrumental support networks are more connected, suggesting that members of virtual communities are more likely to engage in larger group interactions where these types of support can be exchanged. Lastly, network correlations suggest that participants who exchange emotional support are likely to exchange appraisal or instrumental support, and participants who exchange appraisal support are likely to exchange instrumental support. CONCLUSIONS: Social interaction patterns from disease-specific virtual environments can be studied using a social network analysis approach to better understand the exchange of social support. Network data can provide valuable insights into the design of novel and effective eHealth interventions given the unique opportunity virtual environments have facilitating realistic environments that are effective and sustainable, where social interactions can be leveraged to achieve diverse health goals.

Glucanases and Chitinases.

In many yeast and fungi, ß-(1,3)-glucan and chitin are essential components of the cell wall, an important structure that surrounds cells and which is responsible for their mechanical protection and necessary for maintaining the cellular shape. In addition, the cell wall is a dynamic structure that needs to be remodelled along with the different phases of the fungal life cycle or in response to extracellular stimuli. Since ß-(1,3)-glucan and chitin perform a central structural role in the assembly of the cell wall, it has been postulated that ß-(1,3)-glucanases and chitinases should perform an important function in cell wall softening and remodelling. This review focusses on fungal glucanases and chitinases and their role during fungal morphogenesis.

Author Correction: Signalling through the yeast MAPK Cell Wall Integrity pathway controls P-body assembly upon cell wall stress.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A new toolkit for gene tagging in Candida albicans containing recyclable markers.

Gene manipulation and epitope tagging are essential tools for understanding the molecular function of specific genes. The opportunistic human pathogen Candida albicans is a diploid fungus that utilizes a non-canonical genetic code. Since selection markers available in this organism are scarce, several tools based on recyclable markers have been developed for gene disruption, such as the Clox system. This system relies on the Cre recombinase, which recycles selection markers flanked by loxP sites with high efficiency, facilitating single marker or multi-marker recycling. However, PCR-based modules for epitope tagging, such the pFA-modules, mainly use limited non-recyclable auxotrophic markers. To solve this problem, we have used a Gibson assembly strategy to construct a set of new plasmids where the auxotrophic markers of the pFA vectors were swapped with five recyclable marker modules of the Clox system, enhancing the versatility of the pFA plasmids. This new toolkit, named pFA-Clox, is composed of 36 new vectors for gene disruption and epitope tagging (GFP, 3xGFP, mCherry, 3xHA, 5xmyc and TAP). These plasmids contain the dominant NAT1 marker, as well as URA3, HIS1 and ARG4 cassettes, thereby permitting functional analysis of laboratory strains as well as clinical isolates of C. albicans. In summary, we have adapted the Clox system to the pFA-backbone vectors. Thus, the set of primers used for the amplification of previously published pFA modules can also be utilized in this new pFA-Clox system. Therefore, this new toolkit harbors the advantages of both systems, allowing accelerated gene modification strategies that could reduce time and costs in strain construction for C. albicans.

Signalling through the yeast MAPK Cell Wall Integrity pathway controls P-body assembly upon cell wall stress.

Post-transcriptional control of mRNA is a key event in the regulation of gene expression. From yeast to human cells, P-bodies are cytoplasmic RNA-protein aggregates that play an essential role in this process, particularly under stress conditions. In this work, we show that in the model yeast Saccharomyces cerevisiae cell wall stress induces the formation of these structures. This effect is dependent on multiple elements in the Cell Wall Integrity (CWI) MAPK signalling pathway, a signal transduction cascade responsible for the maintenance of cell integrity under adverse environmental conditions. Remarkably, P-body assembly requires the catalytic activity of the MAPK of the pathway, Slt2/Mpk1. In accordance with the control exerted by this signalling pathway, the timing of P-body formation is similar to that of the activation of the CWI pathway. Noticeably, mRNAs whose expression is regulated by this pathway localize in P-bodies after the cell is exposed to stress following a temporal pattern coincident with CWI pathway activation. Moreover, when these mRNAs are overexpressed in a mutant background unable to form visible P-bodies, the cells show hypersensitivity to agents that interfere with cell wall integrity, supporting that they play a role in the mRNA lifecycle under stress conditions.

Determinación del comportamiento térmico de un invernadero espacial colombiano mediante dinámica de fluidos computacional / Determination of the thermal behavior of a colombian spatial greenhouse through computational fluid dynamics

RESUMEN En Colombia, la producción de flores se lleva a cabo en invernaderos de diferentes tipos y formas geométricas, pero con la una característica común de usar ventilación natural, para control de clima. En la actualidad, el conocimiento sobre el desempeño climático de estas estructuras es escaso. El objetivo del trabajo consistió en evaluar el comportamiento térmico de un invernadero espacial en condiciones de clima diurno y nocturno. La evaluación realizada, mediante modelado computacional, empleó la dinámica de fluidos computacional (CFD, en idioma inglés), aplicada a un invernadero dedicado a la producción de clavel (Dianthus caryophyllus), bajo las condiciones meteorológicas de la Sabana de Bogotá (Colombia). Este enfoque metodológico permitió obtener los patrones de distribución térmica en el interior del invernadero, encontrando que, para las condiciones meteorológicas evaluadas, el invernadero genera unas condiciones térmicas inadecuadas para el desarrollo del cultivo. La validación del modelo CFD, se realizó comparando los resultados de las simulaciones y las temperaturas registradas en el prototipo real del invernadero, obteniendo un grado de ajuste adecuado entre los valores simulados y medidos.

ABSTRACT In Colombia, flower production takes place in greenhouses of different types and geometric shapes, but with the common feature of using natural ventilation for climate control. At present the knowledge on the climatic performance of these structures is scarce. The aim of this work was to evaluate the thermal behavior of a greenhouse under day and night climate conditions. The evaluation made by computational modeling used the computational fluid dynamics (CFD) approach applied to a greenhouse dedicated to the production of carnation (Dianthus caryophyllus) and exposed to the weather conditions of the Sabana de Bogotá (Colombia). This methodological approach allowed us to obtain the thermal distribution patterns inside the greenhouse, finding that for the meteorological conditions evaluated, the greenhouse generates inadequate thermal conditions for the development of the crop. The validation of the CFD model was carried out by comparing the results of the simulations and the temperatures recorded in the real prototype of the greenhouse, obtaining an adequate degree of adjustment between the simulated and measured values.

The anillin-related Int1 protein and the Sep7 septin collaborate to maintain cellular ploidy in Candida albicans.

Variation in cell ploidy is a common feature of Candida albicans clinical isolates that are resistant to the antifungal drug fluconazole. Here, we report that the anillin-related protein Int1 interacts with septins for coupling cytokinesis with nuclear segregation. Loss of Int1 results in a rapid disassembly of duplicated septin rings from the bud neck at the onset of actomyosin ring contraction. Strikingly, this has no major impact on cytokinesis and septum formation. However, Int1 genetically interacts with the Sep7 septin, maintaining the diffusion barrier at the bud neck and guarantying a faithful nuclear segregation. Indeed, int1ΔΔ sep7ΔΔ mutant cells, in contrast to int1ΔΔ cdc10ΔΔ, undergo a premature activation of mitotic exit prior to the alignment of the mitotic spindle with the division axis, producing large multinucleated cells. Some of these multinucleated cells arise from trimeras similar to those observed upon fluconazole exposure. Finally, the defects in nuclear segregation could be in part due to the inability to maintain the Lte1 mitotic exit activator at the cortex of the daughter cell. These results suggest that Int1 and Sep7 play a role in maintaining genome stability by acting as a diffusion barrier for Lte1.

Effects of a Community Population Health Initiative on Blood Pressure Control in Latinos.

Background Hypertension remains one of the most important, modifiable cardiovascular risk factors. Yet, the largest minority ethnic group (Hispanics/Latinos) often have different health outcomes and behavior, making hypertension management more difficult. We explored the effects of an American Heart Association-sponsored population health intervention aimed at modifying behavior of Latinos living in Texas. Methods and Results We enrolled 8071 patients, and 5714 (65.7%) completed the 90-day program (58.5 years ±11.7; 59% female) from July 2016 to June 2018. Navigators identified patients with risk factors; initial and final blood pressure ( BP ) readings were performed in the physician's office; and interim home measurements were recorded telephonically. The intervention incorporated home BP monitoring, fitness and nutritional counseling, and regular follow-up. Primary outcomes were change in systolic BP and health-related quality of life. Using a univariate paired-samples pre-post design, we found an average 5.5% (7.6-mm Hg) improvement in systolic BP (139.1 versus 131.5, t=10.32, P<0.001). Quality of life measured by the European quality of life 5-dimension visual analog scale improved from 0.79 to 0.82 (t=31.03, P<0.001). After multivariate regression analyses, improvements in quality of life and overall body mass index were significantly associated with reductions in systolic BP . Conclusions A noninvasive, population health initiative that encourages routine engagement in patients' own BP control was associated with improvements in systolic BP and quality of life for this largely Latino community.

Rol, situación laboral y prospectiva de especialistas en Medicina Familiar en Colombia, 2017 / Role, employment status and prospective for Graduate Family Medicine Physicians in Colombia, 2017 / Papel, situação trabalhista e prospectiva. Especialistas de medicina familiar na Colômbia, 2017

Introducción.Se reconoce que el médico familiar es el especialista ideal en la puerta de entrada a un sistema de salud que se orienta hacia la atención primaria en salud. Los especialistas en medicina familiar en Colombia están preocupados por el desempleo y por la falta de oportunidades con un pago adecuado para los especialistas que salen al mercado laboral. Metodología. Se hizo una encuesta de 20 preguntas mediante la plataforma Google Forms, dirigida a especialistas en Medicina Familiar. Resultados. Respondieron 281 (38 %) de los médicos familiares. Se encontró un desempleo del 9 %. De los que ejercen la especialidad en nuestro país, 9,6 % tienen títulos convalidados y 90,4 % de universidades colombianas. Los 256 empleados cumplen más de un rol: 34 % tiene actividades administrativas y 75 % ofrece apoyo directo a médicos generales. Otras funciones incluyen: consulta como médicos de cabecera (32 %), docencia (31 %), participación en programas especiales como los de enfermedades crónicas (27 %) y atención en urgencias (14 %). Conclusión. Es importante que los especialistas en Medicina Familiar discutan los diferentes roles que tienen dentro del sistema y planteen su postura ante las partes interesadas, como el Ministerio de Salud y Protección Social, los entes territoriales, las empresas promotoras de salud (EPS) e instituciones prestadoras de salud (IPS), con el fin de posicionarse adecuadamente en la implementación del modelo integral de atención en salud.

Overview:The family physician is the ideal professional in a health system geared towards Primary Care Health. In Colombia however, there is an increasing concern regarding employment and lack of professional opportunities with commensurate pay of Family Medicine Physicians. Methodology: A survey containing 20 questions was conducted with graduate family medicine physicians through Google Forms. Results: 281, 38% of Family Medicine Physicians answered the survey. The unemployment rate was 9%. 9.6% of Family Medicine Physicians working in Colombia have certified degrees. 90.4% of such qualifications are from Colombian universities. Out of the professionals who answered the survey, 256 family physicians performed more than one duty: 34% perform administrative duties; 75% work in tandem with general practitioners; 32% act as primary care physicians and 14% work in Emergency rooms. Conclusions: It is important that family physicians discuss the various roles they perform within the Colombian health system thus bridge building with local health authorities as a way to acknowledge their roles through the implementation of the comprehensive model for health services.

Introdução. Se reconhece que o médico familiar é o especialista ideal para a atenção na entrada do sistema de saúde, direcionado à atenção primaria em Saúde. No entanto, uma preocupação dos especialistas em medicina familiar no país é o desemprego, subemprego e falta de oportunidades de trabalho. Metodologia. Foi realizada uma enquete com 20 perguntas através de Google Forms, dirigida a especialistas em medicina familiar. Resultados. Responderam 281 (38%) dos médicos familiares, entre eles o desemprego foi de 9%. 9,6% tem títulos convalidados e 90% são formados em universidades colombianas. Entre os 256 empregados há diversas funções: 34% tem funções administrativas, 75% oferecem apoio a médicos gerais, 32% são médicos de consulta, 31% são docentes, 27% participa de programas especiais como de doenças crónicas e 14% atende urgências. Conclusão. É importante que os especialistas desta área refletam sobre seu papel no sistema de saúde e consigam defender e posicionar sua especialidade na implementação do Modelo Integral de Atenção em Saúde (MIAS), com o Ministério de Saúde e Proteção Social, entidades territoriais, empresas promotoras de saúde e instituições prestadoras de serviços

Experiencias en la formación de médicos familiares en la modalidad a distancia y virtual: una posibilidad para el sistema de salud colombiano / Experiencies in training family physicians through both virtual and distance-learning modes: a possibility for Colombia ́s health system / Experiências na formação de médicos familiares à distância e virtual: uma possibilidade para o sistema de saúde colombiano

Introducción. Mediante la Resolución 429 de 2016, Colombia adoptó el modelo de Atención Primaria en Salud como una política de atención integral en salud. Los médicos familiares son un elemento fundamental para su desarrollo. Para 2014, se estimó que en Colombia había poco más de 1,2 médicos familiares por 100.000 habitantes y solo siete programas de formación de posgrado presencial en todo el país, concentrados en las ciudades más desarrolladas. Por este motivo, el Ministerio de Educación y el Ministerio de Salud y Protección Social buscan incrementar la formación de especialistas en Medicina Familiar. Brasil, India, México, Paraguay y Sudan, entre otros países, exploraron la educación virtual y a distancia como una opción de formación médica para esta especialidad. Por lo anterior, los investigadores se preguntaron si las características que permitieron el desarrollo de estas experiencias en otros países podrían servir para orientar la creación de un programa similar en Colombia. Objetivo. Hacer una descripción detallada de las características que permitieron el desarrollo de experiencias de formación a distancia y virtual para médicos familiares en el mundo y, a partir de su análisis, encontrar bases que puedan servir para el desarrollo de un programa similar en Colombia. Metodología. Se trata de un estudio cualitativo, hermenéutico, basado en la recopilación y el análisis documentales. La búsqueda se hizo en Pub-med, ProQuest, Embase, Lilacs, Bireme, Springer Link, PlosOne y World Library of Science, utilizando los términos "distance learning", "family practice", "e-learning", "education B-learning", "ICT learning", "computer-assisted instruction", "educación a distancia", "educación virtual", y "medicina familiar y comunitaria". Resultados. Se seleccionaron 71 artículos de 23 países. Se señalaron las características comunes en los programas de educación virtual y a distancia, mediante una matriz de fortalezas, oportunidades, debilidades y amenazas, y se reseñaron los rasgos políticos, económicos, sociales, y tecnológicos del contexto colombiano que pudieren favorecer o no el desarrollo de un programa similar. Conclusiones. La educación de posgrado a distancia para médicos familiares ha sido posible en diferentes países. En Colombia, deben desarrollarse ajustes políticos, económicos, tecnológicos y legales para que un programa de estas características tenga un impacto significativo en el desarrollo de la especialidad.

Overview: Through Resolution 429 promulgated in 2016, Colombia adopts Primary Care model as comprehensive health service policy and family physicians have been essential for such model adoption. According to different sources, in 2014 there was an estimated 1.2 family physicians per 100.000 in-habitants and only 7 Family Medicine postgraduate programs throughout the country. Consequently, Colombia ́s National Health Ministry sought to increase training of Family Physicians. Countries such as Brazil, India, México, Paraguay y Sudan looked into virtual and distance- learning strategies as options for family physicians training. This led researchers to inquire whether such education options could allow the implementation of similar experiences in ColombiaObjective: Conducting a thorough description of features involved in the development of distance-learning and virtual education strategies for family physician training worldwide. Such description aimed as a means to develop a similar program in Colombia. Methodology: Qualitative-hermeneutic study based on data collection and analysis. Search was conducted through the following web search engines: PubMed, ProQuest, Embase, Lilacs, Bireme, Springer Link, Plos One and World library Of Science. Search terms included: "distance learning", "family practice", "e-learning", "education B-learning", "ICT learning", "computer-assisted instruction", " distance-learning education", "on -line education" and "family and community medicine." Results: 71 articles from 23 countries around the world were selected. Commonalities amongst on line education and distance-learning programs were drawn through the use of SWOT analysis that included social, political, economic and technological contextual features that may favor or hinder the development of a similar program in Colombian Conclusions: Graduate distance learning for Family Physicians has been successful in various countries. Colombia ought to implement political, economic, technological and legal adjustments to allow for the development of such an educational program and its significant impact for this medical specialty.

Introdução. Em 2016 mediante a Resolução 429, a Colômbia adotou o modelo de Atenção primária em Saúde (APS) como uma política de atenção integral em saúde (PAIS), os médicos familiares são um elemento fundamental para seu desenvolvimento. Para 2014 foi estimado no país mais do que 1,2 médicos familiares por cada 100.000 habitantes e somente 7 programas de formação de Pós-Graduação presencial no país todo, concentrados nas principais cidades. Os Ministérios de Educação e de Saúde e proteção Social procuram incrementar a formação de especialistas em Medicina Familiar. Brasil, India, México, Paraguay e Sudán, são entre outros países, exploraram a educação virtual e a distância como uma opção de formação médica para esta especialidade. Pelo anterior, os pesquisadores questionam sobre se as características que permitiram o desenvolvimento dessa experiência nesses países, servem para orientar a criação de um programa semelhante na Colômbia. Objetivo. Descrever detalhadamente as características que permitiram o desenvolvimento de experiências de formação à distância e virtual para médicos familiares no mundo, para buscar alternativas de desenvolvimento de um programa semelhante na Colômbia.Metodologia. estudo qualitativo, hermético, baseado na colheita e análise documental. A busca bibliográfica foi realizada nas bases de dados especializadas (Pubmed, ProQuest, Embase, Lilacs, Bireme, Springer Link, Plos One y World library Of Science) usando os térmos "distance learning", "family practi-ce", "e-learning", "education B-learning", "ICT learning", "computer-assisted instruction", "educación a distancia", "educación virtual" e "medicina familiar y comunitaria". Resultados. Foram selecionados 71 artigos de 23 países para identificar características comuns dos programas de educação virtual e a distância, com fortalezas, oportunidades, fraquezas e ameaças, sendo também resenhados os atributos políticos, econômicos, sociais e tecnológicos do contexto colombiano. Conclusões. A educação de Pós-graduação a distância para médicos familiares tem sido possível em vários países. Na Colômbia podem ser desenvolvidos ajustes para gerar as condições que favoreçam a realização de um programa como esse com alto impacto significativo.

Estudio sobre la lixiviación de cadmio, cromo y plomo de un limpiador lingual en saliva artificial / Study on the leaching of cadmium, chromium and lead from a tongue cleaner onto artificial saliva

Objetivos: Determinar la presencia y concentración de los metales plomo, cadmio y cromo migrados desde el limpiador lingual "Alitest" en saliva artificial, y estimar la exposición oral a estas sustancias. Material y métodos: Diseño pre-experimental y analítico, para cuantificar las sustancias que son liberadas desde el limpiador lingual al contacto con saliva artificial. Los metales fueron analizados por AAS. Se estimaron los valores de exposición por ingesta oral que fueron comparados con valores de ingesta diaria tolerable para cada grupo etario. Resultados: Se cuantificó la migración de cadmio y cromo en concentraciones promedio de 0.008mg/L y 0.437 mg/L, respectivamente. La concentración de plomo estuvo por debajo de los niveles detectables utilizando el método. A partir de estos valores se estimó la ingesta oral para cada grupo etario y se comparó con el valor provisional de ingesta mensual tolerable (PTMI) o Dosis de Referencia (RfD). Conclusiones: Las sustancias se cuantificaron en concentraciones normales, que no excedieron los valores máximos recomendados.

Objectives: To determine the concentration of heavy metals cadmium and chromium leached from the tongue cleaner "Alitest" into artificial saliva and to assess oral exposure of these substances. Material and methods: Analytical pre-experimental design, to determine the amount of those substances released from the tongue cleaner onto artificial saliva and to quantified them by AAS. Assessment of exposure from oral intake values and comparison with the Provisional Tolerable Monthly Intake (PTMI) or Reference Dose (RfD) values. Results: Cadmium and chromium leachated into artificial saliva were quantified in concentrations of 0.008mg/L and 0.437 mg/L, respectively. Lead concentration was under detectable levels using the method. These values were used to estimate the oral intake for each age group and were compared to PTMI or RfD values. Conclusions: The substances were found in normal concentrations, none exceeding the maximum values of PTMI or RfD.

Regulation of Ace2-dependent genes requires components of the PBF complex in Schizosaccharomyces pombe.

The division cycle of unicellular yeasts is completed with the activation of a cell separation program that results in the dissolution of the septum assembled during cytokinesis between the 2 daughter cells, allowing them to become independent entities. Expression of the eng1(+) and agn1(+) genes, encoding the hydrolytic enzymes responsible for septum degradation, is activated at the end of each cell cycle by the transcription factor Ace2. Periodic ace2(+) expression is regulated by the transcriptional complex PBF (PCB Binding Factor), composed of the forkhead-like proteins Sep1 and Fkh2 and the MADS box-like protein Mbx1. In this report, we show that Ace2-dependent genes contain several combinations of motifs for Ace2 and PBF binding in their promoters. Thus, Ace2, Fkh2 and Sep1 were found to bind in vivo to the eng1(+) promoter. Ace2 binding was coincident with maximum level of eng1(+) expression, whereas Fkh2 binding was maximal when mRNA levels were low, supporting the notion that they play opposing roles. In addition, we found that the expression of eng1(+) and agn1(+) was differentially affected by mutations in PBF components. Interestingly, agn1(+) was a major target of Mbx1, since its ectopic expression resulted in the suppression of Mbx1 deletion phenotypes. Our results reveal a complex regulation system through which the transcription factors Ace2, Fkh2, Sep1 and Mbx1 in combination control the expression of the genes involved in separation at the end of the cell division cycle.

A single nucleotide polymorphism uncovers a novel function for the transcription factor Ace2 during Candida albicans hyphal development.

Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages.

Eng2 is a component of a dynamic protein complex required for endocytic uptake in fission yeast.

Eng2 is a glucanase required for spore release, although it is also expressed during vegetative growth, suggesting that it might play other cellular functions. Its homology to the Saccharomyces cerevisiae Acf2 protein, previously shown to promote actin polymerization at endocytic sites in vitro, prompted us to investigate its role in endocytosis. Interestingly, depletion of Eng2 caused profound defects in endocytic uptake, which were not due to the absence of its glucanase activity. Analysis of the dynamics of endocytic proteins by fluorescence microscopy in the eng2Δ strain unveiled a previously undescribed phenotype, in which assembly of the Arp2/3 complex appeared uncoupled from the internalization of the endocytic coat and resulted in a fission defect. Strikingly also, we found that Eng2-GFP dynamics did not match the pattern of other endocytic proteins. Eng2-GFP localized to bright cytosolic spots that moved around the cellular poles and occasionally contacted assembling endocytic patches just before recruitment of Wsp1, the Schizosaccharomyces pombe WASP. Interestingly, Csh3-YFP, a WASP-interacting protein, interacted with Eng2 by co-immunoprecipitation and was recruited to Eng2 in bright cytosolic spots. Altogether, our work defines a novel endocytic functional module, which probably couples the endocytic coat to the actin module.

The NDR/LATS kinase Cbk1 controls the activity of the transcriptional regulator Bcr1 during biofilm formation in Candida albicans.

In nature, many microorganisms form specialized complex, multicellular, surface-attached communities called biofilms. These communities play critical roles in microbial pathogenesis. The fungal pathogen Candida albicans is associated with catheter-based infections due to its ability to establish biofilms. The transcription factor Bcr1 is a master regulator of C. albicans biofilm development, although the full extent of its regulation remains unknown. Here, we report that Bcr1 is a phosphoprotein that physically interacts with the NDR kinase Cbk1 and undergoes Cbk1-dependent phosphorylation. Mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to alanine markedly impaired Bcr1 function during biofilm formation and virulence in a mouse model of disseminated candidiasis. Cells lacking Cbk1, or any of its upstream activators, also had reduced biofilm development. Notably, mutating the two putative Cbk1 phosphoacceptor residues in Bcr1 to glutamate in cbk1Δ cells upregulated the transcription of Bcr1-dependent genes and partially rescued the biofilm defects of a cbk1Δ strain. Therefore, our data uncovered a novel role of the NDR/LATS kinase Cbk1 in the regulation of biofilm development through the control of Bcr1.