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Nonsuicidal self-injury (NSSI) is a major public health concern. Web-based personalized feedback interventions (PFIs) may be a cost-effective and efficient way to treat NSSI. In order to develop a PFI, it is imperative to assess descriptive and injunctive norms. The current study examines descriptive and injunctive norms of NSSI within college students and adults in the community, comparing how perceived norms may differ for those who do or do not engage in NSSI. Study 1 calculated percentages of NSSI behavior within the student sample. Study 2 then examined perceived descriptive and injunctive norms between those with and without history of NSSI in both samples. Study 1 indicated that 19% of undergraduate students had histories of NSSI. Additionally, there was a general tendency to overestimate the percentage of people who engage in NSSI and the number of times a typical person engages in NSSI. Finally, those who engaged in NSSI believed that most people do not understand why individuals engage in NSSI; comparatively, the majority of people without history of NSSI still indicated that they understand why others would engage in NSSI. These research findings may be utilized in a PFI to reduce shame and NSSI behavior. [ABSTRACT FROM AUTHOR]

Background:Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy.Methods:We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy.Results:We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å2) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively.Conclusion:We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Previous attempts to isolate auxotrophic mutants of Anacystis nidulans produced only a limited range of phenotypes. The frequency of recovery of auxotrophic mutants has been quantified following different mutagenic and selective treatments, and their yield has been improved by using (1) a complete medium, (2) additional mutagens, (3) multiple cycles of penicillin enrichment and (4) altered pre-enrichment starvation conditions. These modified induction and selection conditions permitted the isolation of mutants defective in nitrate reductase, nitrite reductase or malate dehydrogenase, unable to reduce sulphate, or deficient in the synthesis of biotin, thiamine, paminobenzoate, serine, glutamate, adenine or uracil. [ABSTRACT FROM AUTHOR]

Genes encoding the mosquitocidal binary toxin of Bacillus sphaericus 2362 were introduced into Synechococcus PCC6301, a cyanobacterium that can tolerate a number of potential variations in the mosquito breeding environment, and can serve as a food source for mosquito larvae. The toxin genes, preceded by a Synechococcus rbcL promoter, were located on a mobilizable Escherichia coli Synechococcus shuttle vector, which was introduced into Synechococcus PCC6301 at frequencies of 10−5–10−7 exconjugants/recipient, depending on the selective conditions used. Recombinant Synechococcus exhibited significant toxicity against 2-day-old and 6-day-old Culex quinquefasciatus larvae, the concentration required to kill 50 % of larvae (LC50) being 2.1 × 105 and 1.3 × 105 cells/ml respectively. Mosquitocidal activity decreased tenfold after 20 generations of non-selective growth. [ABSTRACT FROM AUTHOR]