Clinical Persistence of Chlamydia trachomatis Sexually Transmitted Strains Involves Novel Mutations in the Functional αββα Tetramer of the Tryptophan Synthase Operon.

Clinical persistence of Chlamydia trachomatis (Ct) sexually transmitted infections (STIs) is a major public health concern. In vitro persistence is known to develop through interferon gamma (IFN-γ) induction of indoleamine 2,3-dioxygenase (IDO), which catabolizes tryptophan, an essential amino acid for Ct replication. The organism can recover from persistence by synthesizing tryptophan from indole, a substrate for the enzyme tryptophan synthase. The majority of Ct strains, except for reference strain B/TW-5/OT, contain an operon comprised of α and β subunits that encode TrpA and TrpB, respectively, and form a functional αββα tetramer. However, trpA mutations in ocular Ct strains, which are responsible for the blinding eye disease known as trachoma, abrogate tryptophan synthesis from indole. We examined serial urogenital samples from a woman who had recurrent Ct infections over 4 years despite antibiotic treatment. The Ct isolates from each infection episode were genome sequenced and analyzed for phenotypic, structural, and functional characteristics. All isolates contained identical mutations in trpA and developed aberrant bodies within intracellular inclusions, visualized by transmission electron microscopy, even when supplemented with indole following IFN-γ treatment. Each isolate displayed an altered αββα structure, could not synthesize tryptophan from indole, and had significantly lower trpBA expression but higher intracellular tryptophan levels compared with those of reference Ct strain F/IC-Cal3. Our data indicate that emergent mutations in the tryptophan operon, which were previously thought to be restricted only to ocular Ct strains, likely resulted in in vivo persistence in the described patient and represents a novel host-pathogen adaptive strategy for survival.IMPORTANCE Chlamydia trachomatis (Ct) is the most common sexually transmitted bacterium with more than 131 million cases occurring annually worldwide. Ct infections are often asymptomatic, persisting for many years despite treatment. In vitro recovery from persistence occurs when indole is utilized by the organism's tryptophan synthase to synthesize tryptophan, an essential amino acid for replication. Ocular but not urogenital Ct strains contain mutations in the synthase that abrogate tryptophan synthesis. Here, we discovered that the genomes of serial isolates from a woman with recurrent, treated Ct STIs over many years were identical with a novel synthase mutation. This likely allowed long-term in vivo persistence where active infection resumed only when tryptophan became available. Our findings indicate an emerging adaptive host-pathogen evolutionary strategy for survival in the urogenital tract that will prompt the field to further explore chlamydial persistence, evaluate the genetics of mutant Ct strains and fitness within the host, and their implications for disease pathogenesis

Proyecto para la utilización de la fibra de abacá en la elaboración de muebles artesanales en la ciudad de santo domingo para su consumo en la ciudad de Guayaquil

El desarrollo del presente proyecto, constituye la creación de una empresa que se dedique a la fabricación de muebles de fibra de abacá para el consumo interno. En virtud de que en el Ecuador se produce la fibra y sólo se la exporta, se ha observado la necesidad de crear un producto con ésta fibra, con lo cual se le daría un valor agregado a la misma. El proyecto presenta, en primera instancia un análisis de la situación actual del mercado nacional de muebles, este análisis se lo desarrolló para poder determinar si era o no conveniente la entrada de la empresa a este nuevo mercado. Siguiendo con el estudio tenemos un análisis de mercado, en el cual se analizaron, los diferentes segmentos de mercado, y se determinó cuidadosamente el mercado objetivo, a través de la realización de la respectiva encuesta. El capítulo dos abarca el estudio técnico del proyecto para la fabricación de muebles de fibra de abacá. Se destacan tres principales áreas de análisis siendo éstos; proceso de elaboración, insumos y maquinaria requerida para la fabricación. Dentro del estudio de los procesos se define la existencia de métodos a nivel internacional para llevar a cabo la producción de los muebles de fibra. Por parte del estudio de insumos, se describe a la materia prima además se explica la tecnología requerida para la producción, la necesidad de obtener mano de obra calificada, así como los posibles proveedores. Para finalizar el estudio de insumos se presentan ideas de subproductos a realizar con la fibra. Para el estudio de la maquinaria requerida se presenta una lista de los equipos a considerar para la elaboración, acompañado de una explicación detallada de la localización escogida para ubicar la planta

A real-time proximity querying algorithm for haptic-based molecular docking

Intermolecular binding underlies every metabolic and regulatory processes of the cell, and the therapeutic and pharmacological properties of drugs. Molecular docking systems model and simulate these interactions in silico and allow us to study the binding process. Haptic-based docking provides an immersive virtual docking environment where the user can interact with and guide the molecules to their binding pose. Moreover, it allows human perception, intuition and knowledge to assist and accelerate the docking process, and reduces incorrect binding poses. Crucial for interactive docking is the real-time calculation of interaction forces. For smooth and accurate haptic exploration and manipulation, force-feedback cues have to be updated at a rate of 1 kHz. Hence, force calculations must be performed within 1ms. To achieve this, modern haptic-based docking approaches often utilize pre-computed force grids and linear interpolation. However, such grids are time-consuming to pre-compute (especially for large molecules), memory hungry, can induce rough force transitions at cell boundaries and cannot be applied to flexible docking. Here we propose an efficient proximity querying method for computing intermolecular forces in real time. Our motivation is the eventual development of a haptic-based docking solution that can model molecular flexibility. Uniquely in a haptics application we use octrees to decompose the 3D search space in order to identify the set of interacting atoms within a cut-off distance. Force calculations are then performed on this set in real time. The implementation constructs the trees dynamically, and computes the interaction forces of large molecular structures (i.e. consisting of thousands of atoms) within haptic refresh rates. We have implemented this method in an immersive, haptic-based, rigid-body, molecular docking application called Haptimol_RD. The user can use the haptic device to orientate the molecules in space, sense the interaction forces on the device, and guide the molecules to their binding pose. Haptimol_RD is designed to run on consumer level hardware, i.e. there is no need for specialized/proprietary hardware

Age and trust as moderators in the relation between procedural justice and turnover: a large-scale longitudinal study

Item does not contain fulltextThe current study investigated the moderating roles of age and trust in the relation of procedural justice with turnover. It was expected that the relation between procedural justice and turnover was weaker for older workers and those with high prior trust in their leader. Older workers are better at regulating their emotions, and focus more on positive aspects of their relationships with others, and therefore react less intensely to unfair treatment. Moreover, people with high trust are more likely to attribute unfair treatment to circumstances instead of deliberate intention than people with low trust. Finally, we expected a three-way interaction between age, trust, and procedural justice in relation to turnover, where older workers with high trust would have less strong reactions than younger workers and older workers with low trust. Results from a three-wave longitudinal survey among 1,597 Dutch employees indeed revealed significant interactions between trust and procedural justice in relation to turnover. Furthermore, the three-way interaction was significant, with negative relations for younger workers, but a non-significant relation was found for older workers with low trust. Contrary to expectations, negative relations were found between procedural justice and turnover for older workers with high trust