A variety of simple cysteine-containing lipopeptides, with sequences modeled on those found in naturally occurring S-acylated proteins, undergo spontaneous S-acylation in phospholipid vesicles at physiological pH when either long-chain acyl-CoAs or other S-acylated peptides are added as acyl donors. Fluorescent or radiolabeled lipopeptides with the sequence myristoyl-GCX- (X = G, L, R, T, or V), a motif found to undergo S-acylation in several intracellular regulatory proteins, and the prenylated peptide -SCRC(farnesyl)-OMe, modeled on the carboxyl terminus of p21H-ras, were all found to be suitable acyl acceptors for such uncatalyzed S-acyl transfer reactions at physiological pH. Acylation of these cysteinyl-containing lipopeptides to high stoichiometry was observed, on time scales ranging from a few hours to a few tens of minutes, in vesicles containing relatively low concentrations (< or = mol %) and only a modest molar excess (2.5:1) of the acyl donor species. No evidence was obtained for acyl transfer to peptide serine or threonine hydroxyl groups under the same conditions. These observations may have significant implications both for the design of in vitro studies of the S-acylation of membrane-associated proteins and for our understanding of the mechanisms of S-acylation of these species in vivo.
This preliminary pilot study suggests that providing a relationship-based intervention to street-involved youth may offer promise to strengthen social relationships and to mitigate overwhelming hopelessness and despair.
The Li-Fraumeni Syndrome (LFS) is a rare, dominantly inherited syndrome that features high risk of cancers in childhood and early adulthood. Aected families tend to develop bone and soft tissue sarcomas, breast cancers, brain tumors, leukemias, and adrenocortical carcinomas. In some kindreds, the genetic abnormality associated with this cancer phenotype is a heterozygous germline mutation in the p53 tumor suppressor gene. Recently, we identi®ed one patient who presented in early childhood with multiple primary cancers and who harbored three germline p53 alterations (R156H and R267Q on the maternal allele and R290H on the paternal allele). To classify the biologic eects of these alterations, functional properties of each of the p53 mutants were examined using in vitro assays of cellular growth suppression and transcriptional activation. Each amino acid substitution conferred partial or complete loss of wild-type p53 function, but the child completed normal embryonic development. This observation has not been previously reported in a human, but is consistent with observations of normal embryogenesis in p53-de®cient mice.
Purpose
The purpose of this paper is to evaluate the effectiveness of the dialectical behavior therapy (DBT) training which was provided to community agency staff (N=18) implementing DBT in the community with street-involved youth.
Design/methodology/approach
Staff participated in a multi-component approach to training which consisted of webinars, online training, self-study manuals, and ongoing peer consultation. To evaluate assess the effectiveness of the training, questionnaires assessing evaluating DBT skills knowledge, behavioral anticipation and confidence, and DBT skills use, were completed at baseline, immediately post-training, four to six months post-training, and 12-16 months post-training. Additionally, the mental health outcomes for youth receiving the DBT intervention are reported to support the effectiveness of the training outcomes.
Findings
Results demonstrate that the DBT skills, knowledge, and confidence of community agency staff improved significantly from pre to post-training and that knowledge and confidence were sustained over time. Additionally, the training was clinically effective as demonstrated by the significant improvement in mental health outcomes for street-involved youth participating in the intervention.
Practical implications
Findings suggest that this evidence-based intervention can be taught to a range of staff working in community service agencies providing care to street-involved youth and that the intervention can be delivered effectively.
Originality/value
These findings help to close the knowledge-practice gap between evidence-based treatment (EBT) research and practice while promoting the implementation of EBT in the community to enhance positive youth outcomes.
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