Non-fatal suicidal behaviour, depression and poverty among young men living in low-resource communities in South Africa.

BACKGROUND: Suicide is a serious public health problem in low- and middle-income countries. Understanding the context- and gender-specific risk factors for non-fatal suicidal behaviour is the cornerstone of evidence-based public health interventions to reduce suicide. Poverty and symptoms of depression are well established risk factors for suicidal behaviour. However, little is understood about how proximal economic factors (such as losing one's job, or food insecurity) may confound the effects of symptoms of depression to increase the risk of non-fatal suicidal behaviour in vulnerable populations, such as young men living under conditions of endemic poverty. The aim of this study was to explore the extent to which a wide range of poverty-related variables account for non-fatal suicidal behaviour independent of, or in addition to, symptoms of depression among young men living in low-resource communities in South Africa (SA). METHODS: Data were collected from a clustered sample of 647 young men living in low-resource communities in the Western Cape province of SA. Multivariate regressions were used to identify the associations between poverty-related measures, symptoms of depression, and past-month prevalence of non-fatal suicidal behaviour. RESULTS: Non-fatal suicidal behaviour in the last month was reported by 47 (6.13%) participants: suicidal ideation (n = 43; 5.97%); suicide plan (n = 5; 0.77%); suicide attempt (n = 4; 0.62%), and deliberate self-harm without intent to die (n = 4; 0.62%). Past-month prevalence of non-fatal suicidal behaviour was significantly associated with particular dimensions of poverty (living in a home without a toilet on the premises, having previously been fired, and food insecurity), but not with other dimensions of poverty (such as prolonged unemployment and low levels of income). However, symptoms of depression were a more significant predictor of non-fatal suicidal behaviour than any measure of poverty (aOR=1.093, 95% CI=1.058-1.129, p < .000). CONCLUSIONS: Depressive symptoms are more strongly associated with non-fatal suicidal behaviour than a range of proximal and distal economic factors among young men living under conditions of endemic poverty in South Africa. This has important public health implications and highlights the importance of increasing young men's access to psychiatric services and targeting depression as an integral component of suicide prevention in low resource communities.

Diffuse scattering resulting from macromolecular frustration.

Distinctive diffuse scattering in the form of diffuse rings around Bragg positions has been observed in the diffraction patterns of a crystal of the N-terminal fragment of the Gag protein from Feline Foamy Virus. It is shown that these are caused by geometric frustration as molecules try to pack on the triangular b-c mesh of the space group P6(1)22. In order to explain the strong diffuse scattering it is necessary for the crystal to contain occupational disorder such that each unit cell contains one or other of two different molecular arrangements, A and B. The frustration arises because the nearest-neighbour packing prefers neighbouring cells to be AB or BA, which cannot be achieved on all three sides of a triangle simultaneously. To explain the observation that reciprocal sections hk5n, where n = integer, contain only Bragg peaks it is necessary that A and B are identical molecular arrangements differing only by a translation of 0.2c. The implications of the disorder for solving the structure of the protein by conventional techniques as well as the possibility of using the diffuse scattering for this purpose are discussed.

Structural analysis of the GH43 enzyme Xsa43E from Butyrivibrio proteoclasticus.

The rumen of dairy cattle can be thought of as a large, stable fermentation vat and as such it houses a large and diverse community of microorganisms. The bacterium Butyrivibrio proteoclasticus is a representative of a significant component of this microbial community. It is a xylan-degrading organism whose genome encodes a large number of open reading frames annotated as fibre-degrading enzymes. This suite of enzymes is essential for the organism to utilize the plant material within the rumen as a fuel source, facilitating its survival in this competitive environment. Xsa43E, a GH43 enzyme from B. proteoclasticus, has been structurally and functionally characterized. Here, the structure of selenomethionine-derived Xsa43E determined to 1.3 Šresolution using single-wavelength anomalous diffraction is reported. Xsa43E possesses the characteristic five-bladed ß-propeller domain seen in all GH43 enzymes. GH43 enzymes can have a range of functions, and the functional characterization of Xsa43E shows it to be an arabinofuranosidase capable of cleaving arabinose side chains from short segments of xylan. Full functional and structural characterization of xylan-degrading enzymes will aid in creating an enzyme cocktail that can be used to completely degrade plant material into simple sugars. These molecules have a range of applications as starting materials for many industrial processes, including renewable alternatives to fossil fuels.

Social implications of multiple pathology.

The degree of multiple pathology in 184 consecutive patients admitted to a geriatric unit was recorded using the 13 commonest conditions present at the time of admission to provide a standard group of disorders for comparison. All of the conditions were chronic in nature, and 35% of the patients had a combination of four or more of these present. Multiple pathology was associated with poor prognosis in terms of mortality and the need for long-term institutional care. Families, including those who were elderly, continued to support most of the frail elderly people even in the presence of multiple pathology. This emphasizes the social implications of multiple pathology and the need for support and information in the management of long-term disability.

Crystallization and initial crystallographic analysis of the disulfide bond isomerase DsbC in complex with the alpha domain of the electron transporter DsbD.

The protein disulfide bond isomerase DsbC catalyzes the rearrangement of incorrect disulfide bonds during oxidative protein folding in the periplasm of Escherichia coli. The active site cysteines of DsbC are maintained in the active reduced form by the transmembrane electron transporter DsbD. DsbD obtains electrons from the cytoplasm, transports them across the inner membrane, and passes them onto periplasmic substrates, such as DsbC. The electron transport process involves several thiol disulfide exchange reactions between different classes of thiol oxidoreductase. We were able to trap the final electron transport reaction using active site mutants yielding a stable DsbC-DsbDalpha complex. This disulfide cross-linked complex was purified to homogeneity and crystallized. Dehydration of the tetragonal crystals changed the unit cell dimensions from a approximately b = 73 A, c = 267.5 A to a = b = 68.9 A, c = 230.3 A, reducing the cell volume by 23% and the solvent content from 55 to 41%. Crystal dehydration and cryo-cooling improved the diffraction quality of the crystals from 7 to 2.3 A resolution.

DsbC activation by the N-terminal domain of DsbD.

The correct formation of disulfide bonds in the periplasm of Escherichia coli involves Dsb proteins, including two related periplasmic disulfide-bond isomerases, DsbC and DsbG. DsbD is a membrane protein required to maintain the functional oxidation state of DsbC and DsbG. In this work, purified proteins were used to investigate the interaction between DsbD and DsbC. A 131-residue N-terminal fragment of DsbD (DsbDalpha) was expressed and purified and shown to form a functional folded domain. Gel filtration results indicate that DsbDalpha is monomeric. DsbDalpha was shown to interact directly with and to reduce the DsbC dimer, thus increasing the isomerase activity of DsbC. The DsbC-DsbDalpha complex was characterized, and formation of the complex was shown to require the N-terminal dimerization domain of DsbC. These results demonstrate that DsbD interacts directly with full-length DsbC and imply that no other periplasmic components are required to maintain DsbC in the functional reduced state.

Turning a disulfide isomerase into an oxidase: DsbC mutants that imitate DsbA.

There are two distinct pathways for disulfide formation in prokaryotes. The DsbA-DsbB pathway introduces disulfide bonds de novo, while the DsbC-DsbD pathway functions to isomerize disulfides. One of the key questions in disulfide biology is how the isomerase pathway is kept separate from the oxidase pathway in vivo. Cross-talk between these two systems would be mutually destructive. To force communication between these two systems we have selected dsbC mutants that complement a dsbA null mutation. In these mutants, DsbC is present as a monomer as compared with dimeric wild-type DsbC. Based on these findings we rationally designed DsbC mutants in the dimerization domain. All of these mutants are able to rescue the dsbA null phenotype. Rescue depends on the presence of DsbB, the native re-oxidant of DsbA, both in vivo and in vitro. Our results suggest that dimerization acts to protect DsbC's active sites from DsbB-mediated oxidation. These results explain how oxidative and reductive pathways can co-exist in the periplasm of Escherichia coli.