Does a Gatekeeper Suicide Prevention Program Work in a School Setting? Evaluating Training Outcome and Moderators of Effectiveness

The current study sought to evaluate the suicide prevention gatekeeper training program QPR (Question, Persuade, and Refer) among school personnel using a non-equivalent control group design. Substantial gains were demonstrated from pre- to post-test for attitudes, knowledge, and beliefs regarding suicide and suicide prevention. Exploratory analyses revealed the possible moderating effects of age, professional role, prior training, and recent contact with suicidal youth on QPR participants’ general knowledge, questioning, attitudes toward suicide and suicide prevention, QPR quiz scores, and self-efficacy. The need for replication using a more rigorous experimental design in the context of strong community collaboration is discussed

Germline-encoded neutralization of a Staphylococcus aureus virulence factor by the human antibody repertoire.

Staphylococcus aureus is both an important pathogen and a human commensal. To explore this ambivalent relationship between host and microbe, we analysed the memory humoral response against IsdB, a protein involved in iron acquisition, in four healthy donors. Here we show that in all donors a heavily biased use of two immunoglobulin heavy chain germlines generated high affinity (pM) antibodies that neutralize the two IsdB NEAT domains, IGHV4-39 for NEAT1 and IGHV1-69 for NEAT2. In contrast to the typical antibody/antigen interactions, the binding is primarily driven by the germline-encoded hydrophobic CDRH-2 motifs of IGHV1-69 and IGHV4-39, with a binding mechanism nearly identical for each antibody derived from different donors. Our results suggest that IGHV1-69 and IGHV4-39, while part of the adaptive immune system, may have evolved under selection pressure to encode a binding motif innately capable of recognizing and neutralizing a structurally conserved protein domain involved in pathogen iron acquisition

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Short-Term Effectiveness of a Suicide Prevention Gatekeeper Training Program in a College Setting with Residence Life Advisers

Although the college years prove to be a vulnerable time for students and a critical period for suicide prevention, few school-based prevention strategies have been empirically evaluated. The current study examined the short-term effects of QPR (Question, Persuade, and Refer), a gatekeeper training program that teaches how to recognize warning signs, question suicidal intent, listen to problems, and refer for help. The 122 residence advisers (RAs) who were trained in QPR demonstrated significant post-training gains across a variety of domains relevant to suicide and suicide prevention, with the 60 completing the follow-up assessment showing sustained knowledge and appraisals into the following semester. Although these gains were generally more substantial for RAs trained in QPR, 86 controls who completed both baseline and follow-up assessments also demonstrated changes in appraisals relevant to suicide and suicide prevention, despite having not received QPR training. The need for replication, policy implications, and suggestions for a multifaceted approach to suicide prevention within the college setting are discussed

Development of a single-gene, signature-tag-based approach in combination with alanine mutagenesis to identify listeriolysin O residues critical for the in vivo survival of Listeria monocytogenes.

Listeriolysin O (LLO) is a pore-forming toxin of the cholesterol-dependent cytolysin (CDC) family and a primary virulence factor of the intracellular pathogen Listeria monocytogenes. LLO mediates rupture of phagosomal membranes, thereby releasing bacteria into the growth-permissive host cell cytosol. Several unique features of LLO allow its activity to be precisely regulated in order to facilitate phagosomal escape, intracellular growth, and cell-to-cell spread. To improve our understanding of the multifaceted contribution of LLO to the pathogenesis of L. monocytogenes, we developed a screen that combined saturation mutagenesis and signature tags, termed in vivo analysis by saturation mutagenesis and signature tags (IVASS). We generated a library of LLO mutant strains, each harboring a single amino acid substitution and a signature tag, by using the previously described pPL2 integration vector. The signature tags acted as molecular barcodes, enabling high-throughput, parallel analysis of 40 mutants in a single animal and identification of attenuated mutants by negative selection. Using the IVASS technique we were able to screen over 90% of the 505 amino acids present in LLO and identified 60 attenuated mutants. Of these, 39 LLO residues were previously uncharacterized and potentially revealed novel functions of the toxin during infection. The mutants that were subsequently analyzed in vivo each conferred a 2- to 4-orders of magnitude loss in virulence compared to wild type, thereby validating the screening methods. Phenotypic analysis of the LLO mutant library using common in vitro techniques suggested that the functional contributions of some residues could only have been revealed through in vivo analysis