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

Ictal propagation of high frequency activity is recapitulated in interictal recordings: effective connectivity of epileptogenic networks recorded with intracranial EEG

Seizures are increasingly understood to arise from epileptogenic networks across which ictal activity is propagated and sustained. In patients undergoing invasive monitoring for epilepsy surgery, high frequency oscillations have been observed within the seizure onset zone during both ictal and interictal intervals. We hypothesized that the patterns by which high frequency activity is propagated would help elucidate epileptogenic networks and thereby identify network nodes relevant for surgical planning. Intracranial EEG recordings were analyzed with a multivariate autoregressive modeling technique (short-time direct directed transfer function--SdDTF), based on the concept of Granger causality, to estimate the directionality and intensity of propagation of high frequency activity (70-175 Hz) during ictal and interictal recordings. These analyses revealed prominent divergence and convergence of high frequency activity propagation at sites identified by epileptologists as part of the ictal onset zone. In contrast, relatively little propagation of this activity was observed among the other analyzed sites. This pattern was observed in both subdural and depth electrode recordings of patients with focal ictal onset, but not in patients with a widely distributed ictal onset. In patients with focal ictal onsets, the patterns of propagation recorded during pre-ictal (up to 5 min immediately preceding ictal onset) and interictal (more than 24h before and after seizures) intervals were very similar to those recorded during seizures. The ability to characterize epileptogenic networks from interictal recordings could have important clinical implications for epilepsy surgery planning by reducing the need for prolonged invasive monitoring to record spontaneous seizures

Establishing LA VIDA: A Community-Based Partnership to Prevent Intimate Violence against Latina Women

LA VIDA—the Southwest Detroit Partnership to Prevent Intimate Violence Against Latina Women— evolved in response to community concern about the problem of intimate partner violence (IPV) and the lack of culturally competent preventive and support services for Latino women and men in southwest Detroit. Since 1997, diverse organizations have mobilized as a community-academic partnership to ensure the availability, accessibility, and utilization of IPV services. This article describes and analyzes the evolution of LA VIDA within a community-based participatory research framework using a case study approach that draws on multiple data sources including group and individual interviews and field notes. The challenges and lessons learned in addressing a complex multifaceted problem such as IPV in an ethnic minority community are highlighted in an examination of the process of mobilizing diverse organizations, conducting community diagnosis and needs assessment activities, establishing goals and objectives within a social ecological framework, and integrating evaluation during the development phase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66991/2/10.1177_109019819902600606.pd

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

Short-Term Hurricane Impacts on a Neotropical Community of Marked Birds and Implications for Early-Stage Community Resilience

Populations in fragmented ecosystems risk extirpation through natural disasters, which must be endured rather than avoided. Managing communities for resilience is thus critical, but details are sketchy about the capacity for resilience and its associated properties in vertebrate communities. We studied short-term resilience in a community of individually marked birds, following this community through the catastrophic destruction of its forest habitat by Hurricane Iris in Belize, Central America. We sampled for 58 d immediately before the storm, 28 d beginning 11 d after Hurricane Iris, and for 69 d approximately one year later. Our data showed that the initial capacity for resilience was strong. Many banded individuals remained after the storm, although lower post-hurricane recapture rates revealed increased turnover among individuals. Changes occurred in community dynamics and in abundances among species and guilds. Survivors and immigrants both were critical components of resilience, but in a heterogeneous, species-specific manner. Delayed effects, including higher fat storage and increased species losses, were evident one year later

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

Self-balancing control strategy for a battery based H-bridge multilevel inverter

This paper presents a novel control strategy for isolated multilevel inverters. This converter has been chosen due to the autonomy of each full bridge. Other advantage is the feasibility of handling the power by cell when there are changes in the batteries state of charge (SOC). In order to take advantage of these benefits, a control strategy has been developed. The main goal of the proposed solution is to change the power produced by each inverter in function of SOC, guaranteeing a proper regulation of the overall power, without affecting the parameters of quality of the output voltage like harmonic distortion and amplitude. The designed solution was tested by power sources variations, finding the control strategy appropriate to accomplish the objective, to modify the power produced by each full bridge in function of SOC without changing overall power of the system and keeping the output voltage constant