Structural basis for the homotypic fusion of chlamydial inclusions by the SNARE-like protein IncA.

Many intracellular bacteria, including Chlamydia, establish a parasitic membrane-bound organelle inside the host cell that is essential for the bacteria\u27s survival. Chlamydia trachomatis forms inclusions that are decorated with poorly characterized membrane proteins known as Incs. The prototypical Inc, called IncA, enhances Chlamydia pathogenicity by promoting the homotypic fusion of inclusions and shares structural and functional similarity to eukaryotic SNAREs. Here, we present the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion during infection

The VVV near-IR galaxy catalogue in a Northern part of the Galactic disc

The automated identification of extragalactic objects in large surveys provides reliable and reproducible samples of galaxies in less time than procedures involving human interaction. However, regions near the Galactic disc are more challenging due to the dust extinction. We present the methodology for the automatic classification of galaxies and non-galaxies at low Galactic latitude regions using both images and, photometric and morphological near-IR data from the VVVX survey. Using the VVV-NIRGC, we analyse by statistical methods the most relevant features for galaxy identification. This catalogue was used to train a CNN with image data and an XGBoost model with both photometric and morphological data and then to generate a dataset of extragalactic candidates. This allows us to derive probability catalogues used to analyse the completeness and purity as a function of the configuration parameters and to explore the best combinations of the models. As a test case, we apply this methodology to the Northern disc region of the VVVX survey, obtaining 172,396 extragalatic candidates with probabilities of being galaxies. We analyse the performance of our methodology in the VVV disc, reaching an F1-score of 0.67, a 65 per cent purity and a 69 per cent completeness. We present the VVV-NIR Galaxy Catalogue: Northern part of the Galactic disc comprising 1,003 new galaxies, with probabilities greater than 0.6 for either model, with visual inspection and with only 2 previously identified galaxies. In the future, we intend to apply this methodology to other areas of the VVVX survey.Comment: 12 pages, 14 figures, accepted in MNRA

Prolonged exposure for the treatment of Spanish-speaking Puerto Ricans with posttraumatic stress disorder: a feasibility study

<p>Abstract</p> <p>Background</p> <p>Most of the empirical studies that support the efficacy of prolonged exposure (PE) for treating posttraumatic stress disorder (PTSD) have been conducted on white mainstream English-speaking populations. Although high PTSD rates have been reported for Puerto Ricans, the appropriateness of PE for this population remains unclear. The purpose of this study was to examine the feasibility of providing PE to Spanish speaking Puerto Ricans with PTSD. Particular attention was also focused on identifying challenges faced by clinicians with limited experience in PE. This information is relevant to help inform practice implications for training Spanish-speaking clinicians in PE.</p> <p>Results</p> <p>Fourteen patients with PTSD were randomly assigned to receive PE (n = 7) or usual care (UC) (n = 7). PE therapy consisted of 15 weekly sessions focused on gradually confronting and emotionally processing distressing trauma-related memories and reminders. Five patients completed PE treatment; all patients attended the 15 sessions available to them. In UC, patients received mental health services available within the health care setting where they were recruited. They also had the option of self-referring to a mental health provider outside the study setting. The Clinician-Administered PTSD Scale (CAPS) was administered at baseline, mid-treatment, and post-treatment to assess PTSD symptom severity. Treatment completers in the PE group demonstrated significantly greater reductions in PTSD symptoms than the UC group. Forty percent of the PE patients showed clinically meaningful reductions in PTSD symptoms from pre- to post-treatment.</p> <p>Conclusions</p> <p>PE appears to be viable for treating Puerto Rican Spanish-speaking patients with PTSD. This therapy had good patient acceptability and led to improvements in PTSD symptoms. Attention to the clinicians' training process contributed strongly to helping them overcome the challenges posed by the intervention and increased their acceptance of PE.</p

Natural Disaster and Risk of Psychiatric Disorders in Puerto Rican Children

We examined the persistence of psychiatric disorders at approximately 18 and 30 months after a hurricane among a random sample of the child and adolescent population (4–17 years) of Puerto Rico. Data were obtained from caretaker-child dyads (N = 1,886) through in person interviews with primary caretakers (all children) and youth (11–17 years) using the Diagnostic Interview Schedule for Children IV in Spanish. Logistic regressions, controlling for sociodemographic variables, were used to study the relation between disaster exposure and internalizing, externalizing, or any disorder. Children’s disaster-related distress manifested as internalizing disorders, rather than as externalizing disorders at 18 months post-disaster. At 30 months, there was no longer a significant difference in rates of disorder between hurricane-exposed and non-exposed youth. Results were similar across age ranges. Rates of specific internalizing disorders between exposed and unexposed children are provided. Research and clinical implications are discussed

A study of some fundamental physicochemical variables on the morphology of mesoporous silica nanoparticles MCM-41 type

[EN] All variables affecting the morphology of mesoporous silica nanoparticles (MSN) should be carefully analyzed in order to truly tailored design their mesoporous structure according to their final use. Although complete control on MCM-41 synthesis has been already claimed, reproducibility and repeatability of results remain a big issue due to the lack of information reported in literature. Stirring rate, reaction volume, and system configuration (i.e., opened or closed reactor) are three variables that are usually omitted, making the comparison of product characteristics difficult. Specifically, the rate of solvent evaporation is seldom disclosed, and its influence has not been previously analyzed. These variables were systematically studied in this work, and they were proven to have a fundamental impact on final particle morphology. Hence, a high degree of circularity (C = 0.97) and monodispersed particle size distributions were only achieved when a stirring speed of 500 rpm and a reaction scale of 500 mL were used in a partially opened system, for a 2 h reaction at 80 degrees C. Well-shaped spherical mesoporous silica nanoparticles with a diameter of 95 nm, a pore size of 2.8 nm, and a total surface area of 954 m(2) g(-1) were obtained. Final characteristics made this product suitable to be used in biomedicine and nanopharmaceutics, especially for the design of drug delivery systems.This study was funded partially by Departamento Administrativo de Ciencia Tecnología e Innovación–COLCIENCIAS (recipient, Angela A. Beltrán-Osuna); Ministerio de Economía y Competitividad, MINECO, research number MAT2016-76039-C4-1-R (Recipient, José L. Gómez-Ribelles); and Universidad Nacional de Colombia, grant number DIB201010021438 (Recipient, Jairo E. Perilla).Beltrán-Osuna, A.; Gómez Ribelles, JL.; Perilla-Perilla, JE. (2017). 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Exploring the Conformational Transitions of Biomolecular Systems Using a Simple Two-State Anisotropic Network Model

Biomolecular conformational transitions are essential to biological functions. Most experimental methods report on the long-lived functional states of biomolecules, but information about the transition pathways between these stable states is generally scarce. Such transitions involve short-lived conformational states that are difficult to detect experimentally. For this reason, computational methods are needed to produce plausible hypothetical transition pathways that can then be probed experimentally. Here we propose a simple and computationally efficient method, called ANMPathway, for constructing a physically reasonable pathway between two endpoints of a conformational transition. We adopt a coarse-grained representation of the protein and construct a two-state potential by combining two elastic network models (ENMs) representative of the experimental structures resolved for the endpoints. The two-state potential has a cusp hypersurface in the configuration space where the energies from both the ENMs are equal. We first search for the minimum energy structure on the cusp hypersurface and then treat it as the transition state. The continuous pathway is subsequently constructed by following the steepest descent energy minimization trajectories starting from the transition state on each side of the cusp hypersurface. Application to several systems of broad biological interest such as adenylate kinase, ATP-driven calcium pump SERCA, leucine transporter and glutamate transporter shows that ANMPathway yields results in good agreement with those from other similar methods and with data obtained from all-atom molecular dynamics simulations, in support of the utility of this simple and efficient approach. Notably the method provides experimentally testable predictions, including the formation of non-native contacts during the transition which we were able to detect in two of the systems we studied. An open-access web server has been created to deliver ANMPathway results. © 2014 Das et al

Structural insight into the formation of lipoprotein-β-barrel complexes

The β-barrel assembly machinery (BAM) inserts outer membrane β-barrel proteins (OMPs) in the outer membrane of Gram-negative bacteria. In Enterobacteriacea, BAM also mediates export of the stress sensor lipoprotein RcsF to the cell surface by assembling RcsF–OMP complexes. Here, we report the crystal structure of the key BAM component BamA in complex with RcsF. BamA adopts an inward-open conformation, with the lateral gate to the membrane closed. RcsF is lodged deep within the lumen of the BamA barrel, binding regions proposed to undergo outward and lateral opening during OMP insertion. On the basis of our structural and biochemical data, we propose a push-and-pull model for RcsF export following conformational cycling of BamA, and provide a mechanistic explanation for how RcsF uses its interaction with BamA to detect envelope stress. Our data also suggest that the flux of incoming OMP substrates is involved in the control of BAM activity