Second-Generation Prisoners and the Transmission of Domestic Violence.

Adult inmates who experienced the incarceration of a parent, known as "second-generation prisoners," experience unique challenges and are at heightened risk for experiencing other adversities throughout the life span. Our study investigated one specific, and previously unexplored, type of adversity--domestic violence--within a sample of 293 incarcerated adults. We examined the relation between generation status (first- or second-generation prisoners), childhood exposure to domestic violence, and participation in adult relationship violence prior to incarceration. Results indicate that prisoners who had been exposed to domestic violence in childhood were more likely to engage in intimate partner violence resulting in inflicted and received injury. Relative to first-generation prisoners, second-generation prisoners reported more childhood domestic violence exposure and were more likely to have been injured by a relationship partner. However, this relation between second-generation status and injury victimization was mediated by domestic violence exposure. These results support an intergenerational pattern of domestic violence and suggest that second-generation prisoners are a unique population worthy of future investigation and mental health intervention.

Carbaboranes as pharmacophores: similarities and differences between aspirin and asborin.

In medicinal chemistry carbaboranes have been used almost exclusively as boron carriers for boron neutron capture therapy (BNCT). Recent developments extended the carrier approach and use carbaboranes as scaffolds for radiodiagnostic or therapeutic agents. Most recent studies, however, focus on carbaboranes as modern hydrophobic pharmacophores. This research employs preferably meta- and para-carbaborane, because these isomers are extremely hydrophobic and very stable. In this paper we therefore investigated the pharmacophoric behavior of the ortho isomer as putative phenyl mimetic by comparing aspirin to asborin, its ortho-carbaborane analogue. Special emphasis is placed on the impact of the cluster properties on the pharmacological profile. Subjects under study are the mode of cyclooxygenase (COX) inhibition, stability, and toxicity. The straightforward syntheses of the corresponding nido compounds as well as their contribution to the pharmacology of the closo precursors will be highlighted. Finally, proof will be given that the ortho-carbaborane core of asborin merits the designation "pharmacophore" by definition and is a multifunctional group rather than just a hydrophobic, bulky spectator.

A gold(I) phosphine complex containing a naphthalimide ligand functions as a TrxR inhibiting antiproliferative agent and angiogenesis inhibitor.

The novel luminescent gold(I) complex [N-(N',N'-dimethylaminoethyl)-1,8-naphthalimide-4-sulfide](triethylphosphine)gold(I) was prepared and investigated for its primary biological properties. Cell culture experiments revealed strong antiproliferative effects and induction of apoptosis via mitochondrial pathways. Biodistribution studies by fluorescence microscopy and atomic absorption spectroscopy showed the uptake into cell organelles, an accumulation in the nuclei of tumor cells, and a homogeneous distribution in zebrafish embryos. In vivo monitoring of vascularisation in developing zebrafish embryos revealed a significant anti-angiogenic potency of the complex. Mechanistic experiments indicated that the inhibition of thioredoxin reductase (based on the covalent binding of a gold triethylphosphine fragment) might be involved in the pharmacodynamic behavior of this novel gold species.

Characterisation of cisplatin coordination sites in cellular Escherichia coli DNA-binding proteins by combined biphasic liquid chromatography and ESI tandem mass spectrometry.

Combined multidimensional liquid chromatography and electrospray ionisation tandem mass spectrometry was employed to analyse platinated tryptic peptides from Escherichia coli cells treated with the anticancer drug cis-[PtCl2(NH3)2] at pH 7.0. Prerequisites for the LC/LC/MS/MS analysis of protein targets that are fulfilled by cisplatin are (a) that the original protein binding sites have a high kinetic stability over the range 2.3 < pH < 8.5, and (b) that the metal fragment remains coordinated to a significant number of b+ and y+ peptide ions under MS/MS fragmentation conditions. Matching the MS/MS spectra of the platinated tryptic peptides to sequences of proteins in the E. coli database enabled the identification of 31 protein targets for cisplatin. Whereas six of these are high-abundance enzymes and ribosomal proteins in E. coli cells, five low-abundance DNA-binding proteins were also identified as specific targets. These include the DNA mismatch repair protein mutS, the DNA helicase II (uvrD) and topoisomerase I (top1). Two efflux proteins (acrD, mdtA), the redox regulator thioredoxin 1 (thiO) and the external filament-like type-1 fimbrial protein A chain (fimA1) were also characterised as specific cisplatin-binding proteins. Kinetically favoured carboxylate (D, E) and hydroxy (S, T, Y) O atoms were identified as the Pt coordination sites in 18 proteins and methionyl S atoms in 9 proteins.

Characterisation of cisplatin binding sites in human serum proteins using hyphenated multidimensional liquid chromatography and ESI tandem mass spectrometry.

Cisplatin binding sites in human serum proteins have been characterised by using combined multidimensional liquid chromatography and ESI tandem mass spectrometry (MudPIT). Following incubation periods of 3 h for cisplatin-blood serum mixtures and subsequent trypsin digestion, MS-MS spectra were recorded for individual peptides that had been separated by SCX and RP liquid chromatography. Matching of the MS-MS spectra to theoretical sequences that were generated for human proteins in the SWISS-PROT database led to the identification of specific binding sites in human serum albumin (HSA), serotransferrin (Trfe) and other abundant serum proteins (A2mg, A1at, Apoa1, Apoa2). The cisplatin coordination sites in HSA and Trfe were confirmed by independent MudPIT studies on cisplatin reaction mixtures with the individual proteins. A total of five specific binding sites were identified for HSA, including the cysteine residue C34, two methionine sites (M329, M548) and the tyrosine and aspartate O-donor sites Y150 (or Y148) and D375 (or E376). Methionine-256 was established as a cisplatin coordination site for Trfe in addition to the O-donor sites E265, Y314, E385 and T457. Inspection of the protein structures indicates that the preferred residues belong either to peripheral alpha helices or to flexible loops within the protein-binding pockets. O-donor residues dominate as cisplatin binding sites for other abundant serum proteins.

Identification of (eta6-arene)ruthenium(II) protein binding sites in E. coli cells by combined multidimensional liquid chromatography and ESI tandem mass spectrometry: specific binding of [(eta6-p-cymene)RuCl2 (DMSO)] to stress-regulated proteins and to helicases.

An automated multidimensional protein identification technology, which combines biphasic liquid chromatography with electrospray ionisation tandem mass spectrometry (MS/MS), was employed to analyse tryptic peptides from Escherichia coli cells treated with the antiproliferation agent [(eta(6)-p-cymene)RuCl(2)(DMSO)], where DMSO is dimethyl sulfoxide. MS/MS spectra were recorded for molecular ions generated by neutral loss of p-cymene from intensive peptide ions coordinated by the (eta(6)-p-cymene)Ru(II) fragment. Matching of the MS/MS spectra of the ruthenated peptides to spectra of proteins in the E. coli database enabled the identification of five protein targets for [(eta(6)-p-cymene)RuCl(2)(DMSO)]. One of these is the constitutive cold-shock protein cspC, which regulates the expression of genes encoding stress-response proteins, and three of the other targets, ppiD, osmY and sucC, are proteins of the latter type. The DNA damage-inducible helicase dinG was likewise established as a protein target. Aspartate carboxylate functions were identified as the probable Ru binding sites in cspC, ppiD and dinG, and threonine and lysine side chains in osmY and sucC, respectively.