Structural basis of the filamin A actin-binding domain interaction with F-actin

Cryo-EM reconstructions were deposited in the Electron Microscopy Data Bank with the following accession numbers: F20-F-actin-FLNaABD, EMD-7833; F20-F-actin-FLNaABD-Q170P, EMD-7832; F20-F-actin-FLNaABD-E254K, EMD-8918; Krios-F-actin-FLNaABD-E254K, EMD-7831. The corresponding FLNaABD-E254K filament model was deposited in the PDB with accession number 6D8C. Source data for F-actin-targeting analyses (Figs. 2c,d,g,h, 3b,c,e,f, 4d,e, 5c,d, and 6a,b) and co-sedimentation assays (Figs. 5g and 6d) are available with the paper online. Other data are available from the corresponding author upon reasonable request. We thank Z. Razinia for generating numerous FLNa constructs, S. Wu for expertise in using the Krios microscope, J. Lees for advice on model refinement, and M. Lemmon for helpful comments in preparing the manuscript. We also thank the Yale Center for Research Computing for guidance and use of the Farnam Cluster, as well as the staff at the YMS Center for Molecular Imaging for the use of the EM Core Facility. This work was funded by grants from the National Institutes of Health (R01-GM068600 (D.A.C.), R01-NS093704 (D.A.C.), R37-GM057247 (C.V.S.), R01-GM110530 (C.V.S.), T32-GM007324, T32-GM008283) and an award from American Heart Association (15PRE25700119 (D.V.I.)).Peer reviewedPostprin

A Community Study of the Psychological Effects of the Omagh Car Bomb on Adults

Background The main aims of the study were to assess psychological morbidity among adults nine months after a car bomb explosion in the town of Omagh, Northern Ireland and to identify predictors of chronic posttraumatic stress disorder symptoms. Method A questionnaire was sent to all adults in households in The Omagh District Council area. The questionnaire comprised established predictors of PTSD (such as pre-trauma personal characteristics, type of exposure, initial emotional response and long-term adverse physical or financial problems), predictors derived from the Ehlers and Clark (2000) cognitive model, a measure of PTSD symptoms and the General Health Questionnaire. Results Among respondents (n = 3131) the highest rates of PTSD symptoms and probable casesness (58.5%) were observed among people who were present in the street when the bomb exploded but elevated rates were also observed in people who subsequently attended the scene (21.8% probable caseness) and among people for whom someone close died (11.9%). People with a near miss (left the scene before the explosion) did not show elevated rates. Exposure to the bombing increased PTSD symptoms to a greater extent than general psychiatric symptoms. Previously established predictors accounted for 42% of the variance in PTSD symptoms among people directly exposed to the bombing. Predictors derived from the cognitive model accounted for 63%. Conclusions High rates of chronic PTSD were observed in individuals exposed to the bombing. Psychological variables that are in principle amenable to treatment were the best predictors of PTSD symptoms. Teams planning treatment interventions for victims of future bombings and other traumas may wish to take these results into account

Exposure to Bioterrorism and Mental Health Response among Staff on Capitol Hill

The October 2001 anthrax attacks heralded a new era of bioterrorism threat in the U.S. At the time, little systematic data on mental health effects were available to guide authorities' response. For this study, which was conducted 7 months after the anthrax attacks, structured diagnostic interviews were conducted with 137 Capitol Hill staff workers, including 56 who had been directly exposed to areas independently determined to have been contaminated. Postdisaster psychopathology was associated with exposure; of those with positive nasal swab tests, PTSD was diagnosed in 27% and any post-anthrax psychiatric disorder in 55%. Fewer than half of those who were prescribed antibiotics completed the entire course, and only one-fourth had flawless antibiotic adherence. Thirty percent of those not exposed believed they had been exposed; 18% of all study participants had symptoms they suspected were symptoms of anthrax infection, and most of them sought medical care. Extrapolation of raw numbers to large future disasters from proportions with incorrect belief in exposure in this limited study indicates a potential for important public health consequences, to the degree that people alter their healthcare behavior based on incorrect exposure beliefs. Incorrect belief in exposure was associated with being very upset, losing trust in health authorities, having concerns about mortality, taking antibiotics, and being male. Those who incorrectly believe they were exposed may warrant concern and potential interventions as well as those exposed. Treatment adherence and maintenance of trust for public health authorities may be areas of special concern, warranting further study to inform authorities in future disasters involving biological, chemical, and radiological agents