Serious criminal offending and mental disorder - Case linkage study

Background A relationship exists between mental disorder and offending behaviours but the nature and extent of the association remains in doubt. Method Those convicted in the higher courts of Victoria between 1993 and 1995 had their pyschiatric history explored by case linkage to a register listing virtually all contacts with the public psychiatric services. Results Prior psychiatric contact was found in 25% or offenders, but the personality disorder and substance misuse accounted for much of this relationship. Schizophrenia and affective disorders were also over-represented, particularly those with coexisting substance misuse. Conclusions The increased offending in schizophrenia and affective illness is modest and may often be mediated by coexisting substance misuse. The risk of a serious crime being committed by someone with a major mental illness is small and does not justify subjecting them, as a group, to either increased institutional containment or greater coercion.

Optical properties of metallic films for vertical-cavity optoelectronic devices

We present models for the optical functions of 11 metals used as mirrors and contacts in optoelectronic and optical devices: noble metals (Ag, Au, Cu), aluminum, beryllium, and transition metals (Cr, Ni, Pd, Pt, Ti, W). We used two simple phenomenological models, the Lorentz-Drude (LD) and the Brendel-Bormann (BB), to interpret both the free-electron and the interband parts of the dielectric response of metals in a wide spectral range from 0.1 to 6 eV. Our results show that the BE model was needed to describe appropriately the interband absorption in noble metals, while for Al, Be, and the transition metals both models exhibit good agreement with the experimental data. A comparison with measurements on surface normal structures confirmed that the reflectance and the phase change on reflection from semiconductor-metal interfaces (including the case of metallic multilayers) can be accurately described by use of the proposed models for the optical functions of metallic films and the matrix method for multilayer calculations. (C) 1998 Optical Society of America.

Effects of interventions in health care settings on physical activity or cardiorespiratory fitness

Introduction: This paper reviews studies of physical activity interventions in health care settings to determine effects on physical activity and/or fitness and characteristics of successful interventions. Methods: Studies testing interventions to promote physical activity in health care settings for primary prevention (patients without disease) and secondary prevention (patients with cardiovascular disease [CVD]) were identified by computerized search methods and reference lists of reviews and articles. Inclusion criteria included assignment to intervention and control groups, physical activity or cardiorespiratory fitness outcome measures, and, for the secondary prevention studies, measurement 12 or more months after randomization. The number of studies with statistically significant effects was determined overall as well as for studies testing interventions with various characteristics. Results: Twelve studies of primary prevention were identified, seven of which were randomized. Three of four randomized studies with short-term measurement (4 weeks to 3 months after randomization), and two of five randomized studies with long-term measurement (6 months after randomization) achieved significant effects on physical activity. Twenty-four randomized studies of CVD secondary prevention were identified; 13 achieved significant effects on activity and/or fitness at twelve or more months. Studies with measurement at two time points showed decaying effects over time, particularly if the intervention were discontinued. Successful interventions contained multiple contacts, behavioral approaches, supervised exercise, provision of equipment, and/or continuing intervention. Many studies had methodologic problems such as low follow-up rates. Conclusion: Interventions in health care settings can increase physical activity for both primary and secondary prevention. Long-term effects are more likely with continuing intervention and multiple intervention components such as supervised exercise, provision of equipment, and behavioral approaches. Recommendations for additional research are given.

Involvement of the N-finger in the self-association of GATA-1

Zinc fingers are recognized as small protein domains that bind to specific DNA sequences. Recently however, zinc fingers from a number of proteins, in particular the GATA family of transcription factors, have also been implicated in specific protein-protein interactions. The erythroid protein GATA-1 contains two zinc fingers: the C-finger, which is sufficient for sequence-specific DNA-binding, and the N-finger, which appears both to modulate DNA-binding and to interact with other transcription factors. We have expressed and purified the N-finger domain and investigated its involvement in the self-association of GATA-1. We demonstrate that this domain does not homodimerize but instead makes intermolecular contacts with the C-finger, suggesting that GATA dimers are maintained by reciprocal N-finger-C-finger contacts. Deletion analysis identifies a 25-residue region, C-terminal to the core N-finger domain, that is sufficient for interaction with intact GATA-1. A similar subdomain exists C-terminal to the C-finger, and we show that self-association is substantially reduced when both subdomains are disrupted by mutation. Moreover, mutations that impair GATA-1 self-association also interfere with its ability to activate transcription in transfection studies.

Key residues characteristic of GATA N-fingers are recognized by FOG

Protein-protein interactions play significant roles in the control of gene expression. These interactions often occur between small, discrete domains within different transcription factors. In particular, zinc fingers, usually regarded as DNA-binding domains, are now also known to be involved in mediating contacts between proteins. We have investigated the interaction between the erythroid transcription factor GATA-1 and its partner, the 9 zinc finger protein, FOG (Friend of GATA). We demonstrate that this interaction represents a genuine finger-finger contact, which is dependent on zinc coordinating residues within each protein. We map the contact domains to the core of the N-terminal zinc finger of GATA-1 and the 6th zinc finger of FOG. Using a scanning substitution strategy we identify key residues within the GATA-1 N-finger which are required for FOG binding. These residues are conserved in the N-fingers of all GATA proteins known to bind FOG, but are not found in the respective C-fingers, This observation may, therefore, account for the particular specificity of FOG for N-fingers, Interestingly, the key N-finger residues are seen to form a contiguous surface, when mapped onto the structure of the N-finger of GATA-1.

Bonding effects and the crystal structures of (NH4)(2)[Cu(H2O)(6)](SO4)(2) and its (H2O)-O-18 substituted form at 9.5 K

The crystal structures of the Tutton salts (NH4)(2)[Cu(H2O)(6)](SO4)(2), diammonium hexaaquacopper disulfate, formed with normal water and isotopically substituted (H2O)-O-18, have been determined by X-ray diffraction at 9.5 K and are very similar, with Cu-O(7) the longest of the Cu-O bonds of the Jahn-Teller distorted octahedral [Cu(H2O)(6)](2+) complex. It is known that structural differences accompany deuteration of (NH4)(2)[Cu(H2O)(6)](SO4)(2), the most dramatic of which is a switch to Cu-O(8) as the longest such bond. The present result suggests that the structural differences are associated with hydrogen-bonding effects rather than with increased mass of the water ligands affecting the Jahn-Teller coupling. The Jahn-Teller distortions and hydrogen-bonding contacts in the compounds are compared with those reported for other Tutton salts at ambient and high pressure.

Suicidal ideation and suicide attempts as predictors of mental health service use

Objective: To examine the extent to which suicidal ideation and suicide attempts are predictive of service use. Design and setting: The National Survey of Mental Health and Wellbeing considered service utilisation in relation to self-reported mental health problems. Service utilisation was inquired of in relation to hospital-based care (including both specialist mental health and general care settings), as well as consultations with a range of health professionals (both specialist and non-specialist mental health professionals, including psychiatrists, psychologists and general practitioners) on an outpatient basis. Participants: Secondary analysis of self-report data from 10 641 randomly selected Australian adults who participated in the National Survey of Mental Health and Wellbeing in 1997. The key predictor variables were reported suicidal ideation and suicide attempts over the past 12 months. Main outcome measures: Use of services for mental health problems (past 12 months). Results: When considered in isolation, individuals reporting suicidal ideation were more likely to make use of at least one type of service for mental health problems than non-suicidal individuals (OR, 17.3; 95% Cl, 13.2-22.6), and individuals reporting suicide attempts were even more likely to do so (OR, 32.3; 95% CI, 9.0-115.4). In the case of suicidal ideation, this effect remained significant after controlling for a range of potential confounders. For suicide attempts, the effect of mental health service use was no longer significant after other variables were taken into account. Conclusions: Suicidal individuals are likely to make use of services, and a high proportion of suicides may be preventable through appropriate healthcare system responses.

Choking deaths: the role of antipsychotic medication

Background An increased risk of choking associated with antipsychotic medication has been repeatedly postulated. Aims To examine this association in a large number of cases of choking deaths. Method Cases of individuals who had died because of choking were linked with a case register recording contacts with public mental health services. The actual and expected rates of psychiatric disorder and the presence of psychotropic medication in post-mortem blood samples were compared. Results The 70 people who had choked to death were over 20 times more likely to have been treated previously for schizophrenia. They were also more likely to have had a prior organic psychiatric syndrome. The risk for those receiving thioridazine or lithium was. respectively, 92 times and 30 times greater than expected. Other antipsychotic and psychotropic drugs were not over-represented. Conclusions The increased risk of death in people with schizophrenia may be a combination of inherent predispositions and the use of specific antipsychotic drugs. The increased risk of choking in those with organic psychiatric syndromes is consistent with the consequences of compromised neurological competence. Declaration of interest None.

The 2.0 angstrom crystal structure of a pocilloporin at pH 3.5: The structural basis for the linkage between color transition and halide binding

The pocilloporin Rtms5 and an engineered variant Rtms5(H146S) undergo distinct color transitions (from blue to red to yellow to colorless) in a pH-dependent manner. pK(a) values of 4.1 and 3.2 were determined for the blue (absorption lambda(max), 590 nm) to yellow (absorption lambda(max), similar to 453 nm) transitions of Rtms5 and Rtms5H(146). The pK(a) for the blue-yellow transition of Rtms5H(146S) increased by 1.4 U in the presence of 0.1 M KI, whereas the pK(a) for the same transition of Rtms5 was relatively insensitive to added halides. To understand the structural basis for these observations, we have determined to 2.0 A resolution the crystal structure of a yellow form of Rtms5(H146S) at pH 3.5 in the presence of iodide. Iodide was found occupying a pocket in the structure with a pH of 3.5, forming van der Waals contacts with the tyrosyl moiety of the chromophore. Elsewhere, it was determined that this pocket is occupied by a water molecule in the Rtms5(H141S) structure (pH 8.0) and by the side chain of histidine 146 in the wild-type Rtms5 structure. Collectively, our data provide an explanation for the observed linkage between color transitions for Rtms5(H146S) and binding to halides.

Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A

We describe the mechanism of ribonuclease inhibition by ribonuclease inhibitor, a protein built of leucine-rich repeats, based on the crystal structure of the complex between the inhibitor and ribonuclease A. The structure was determined by molecular replacement and refined to an R(cryst) of 19.4% at 2.5 Angstrom resolution. Ribonuclease A binds to the concave region of the inhibitor protein comprising its parallel beta-sheet and loops. The inhibitor covers the ribonuclease active site and directly contacts several active-site residues. The inhibitor only partially mimics the RNase-nucleotide interaction and does not utilize the pi phosphate-binding pocket of ribonuclease A, where a sulfate ion remains bound. The 2550 Angstrom(2) of accessible surface area buried upon complex formation may be one of the major contributors to the extremely tight association (K-i = 5.9 x 10(-14) M). The interaction is predominantly electrostatic; there is a high chemical complementarity with 18 putative hydrogen bonds and salt links, but the shape complementarity is lower than in most other protein-protein complexes. Ribonuclease inhibitor changes its conformation upon complex formation; the conformational change is unusual in that it is a plastic reorganization of the entire structure without any obvious hinge and reflects the conformational flexibility of the structure of the inhibitor. There is a good agreement between the crystal structure and other biochemical studies of the interaction. The structure suggests that the conformational flexibility of RI and an unusually large contact area that compensates for a lower degree of complementarity may be the principal reasons for the ability of RI to potently inhibit diverse ribonucleases. However, the inhibition is lost with amphibian ribonucleases that have substituted most residues corresponding to inhibitor-binding residues in RNase A, and with bovine seminal ribonuclease that prevents inhibitor binding by forming a dimer. (C) 1996 Academic Press Limited

Giant protein kinases: Domain interactions and structural basis of autoregulation

The myosin-associated giant protein kinases twitchin and titin are composed predominantly of fibronectin- and immunoglobulin-like modules, We report the crystal structures of two autoinhibited twitchin kinase fragments, one from Aplysia and a larger fragment from Caenorhabditis elegans containing an additional C-terminal immunoglobulin-like domain, The structure of the longer fragment shoes that the immunoglobulin domain contacts the protein kinase domain on the opposite side from the catalytic cleft, laterally exposing potential myosin binding residues, Together, the structures reveal the cooperative interactions between the autoregulatory region and the residues from the catalytic domain involved in protein substrate binding, ATP binding, catalysis and the activation loop, and explain the differences between the observed autoinhibitory mechanism and the one found in the structure of calmodulin-dependent kinase I.

Reorganization of terminator DNA upon binding replication terminator protein: Implications for the functional replication fork arrest complex

Termination of DNA replication in Bacillus subtilis involves the polar arrest of replication forks by a specific complex formed between the replication terminator protein (RTP) and DNA terminator sites. While determination of the crystal structure of RTP has facilitated our understanding of how a single RTP dimer interacts with terminator DNA, additional information is required in order to understand the assembly of a functional fork arrest complex, which requires an interaction between two RTP dimers and the terminator site. In this study, we show that the conformation of the major B. subtilis DNA terminator, Terl, becomes considerably distorted upon binding RTP. Binding of the first dimer of RTP to the B site of Terl causes the DNA to become slightly unwound and bent by similar to 40 degrees. Binding of a second dimer of RTP to the A site causes the bend angle to increase to similar to 60 degrees. We have used this new data to construct two plausible models that might explain how the ternary terminator complex can block DNA replication in a polar manner, in the first model, polarity of action is a consequence of the two RTP-DNA half-sites having different conformations. These different conformations result from different RTP-DNA contacts at each half-site (due to the intrinsic asymmetry at the terminator DNA), as well as interactions (direct or indirect) between the RTP dimers on the DNA. In the second model, polar fork arrest activity is a consequence of the different affinities of RTP for the A and B sites of the terminator DNA, modulated significantly by direct or indirect interactions between the RTP dimers.

The solution structure of C1-T1, a two-domain proteinase inhibitor derived from a circular precursor protein from Nicotiana alata

A two-domain portion of the proteinase inhibitor precursor from Nicotiana alata (NaProPI) has been expressed and its structure determined by NMR spectroscopy. NaProPI contains six almost identical 53 amino acid repeats that fold into six highly similar domains; however, the sequence repeats do nut coincide with the structural domains. Five of the structural domains comprise the C-terminal portion of one repeat and the N-terminal portion of the next. The sixth domain contains the C-terminal portion of the sixth repeat and the N-terminal portion of the first repeat. Disulphide bonds link these C and N-terminal fragments to generate the clasped-bracelet fold of NaProPI. The three-dimensional structure of NaProPI is not known, but it is conceivable that adjacent domains in NaProPI interact to generate the circular bracelet with the N and C termini in close enough proximity to facilitate formation of the disulphide bonds that form the clasp The expressed protein, examined in the current study, comprises residues 25-135 of NaProPI and encompasses the first two contiguous structural domains, namely the chymotrypsin inhibitor C1 and the trypsin inhibitor T1, joined by a five-residue linker, and is referred to as C1-T1. The tertiary structure of each domain in C1-T1 is identical to that found in the isolated inhibitors. However, no nuclear Overhauser effect contacts are observed between the two domains and the five-residue linker adopts an extended conformation. The absence of interactions between the domains indicates that adjacent domains do not specifically interact to drive the circularisation of NaProPI. These results are in agreement with recent data which describe similar PI precursors from other members of the Solanaceae having two, three, or four repeats. The lack of strong interdomain association is likely to be important for the function of individual inhibitors by ensuring that there is no masking of reactive sites upon release from the precursor. (C) 2001 Academic Press.

Articulatory dysfunction in multiple sclerosis: An electropalatographic study

Dysfunction of the articulatory subsystem (i.c.. the lips, tongue, and jaw) has bccn identified as a major contributor to the reduction in speech intelligibility experienced by a high proportion of people with multiple sclerosis (MS). In particular. consonant imprecision has been reported to be the articulatory deficit that contributes most to variations in overall intelligibility of MS speakers. Electropalatography(EPG) IS an instrurncntal technique that visually documents the location and timing of tongue-topalatc contacts during speech. Although such a technique would be valuablc in objectively assessing the articulatory disturbances exhibited by individuals with dysarthria ia motor speech disorder) associated with MS, to-date no such study ha< been reported. The aim of the present study was to use EPG to assess tongue-to-palate contact patterns and articulatory timing in patients with dysarthria associated with MS. A dysarthric participant with a diagnosis of definite MS was fitted with an acrylic EPG palate (Reading EPG.?) and asked to read aloud a list of single syllable words which contained lingual consonants in the word-initial position and in consonant clusters. Each mord was repeated five times. The EPG palate was specifically moulded to tit the participant's hard palate and contained 62 electrodes that detected the tongue contacts. A non-neurologically impaired participant matched for age and sex servcd as a control. The results of the study revealed that the tongue-to-palate contacts produced by the participant with MS varied from those produced by the control in a number of ways in regard to spatial configurations and timing characteristics exhibited. The rcsults arc discussed in relation to the neuropathophysiological effects of MS on speech production. The potcntial use of EPG in programs for treating speech disorders associated with MS will be highlightcd.

Dynamin-dependent endocytosis is necessary for convergent-extension movements in Xenopus animal cap explants

Cadherin cell-cell adhesion molecules are important determinants of morphogenesis and tissue patterning. C-cadherin plays a key role in the cell-upon-cell movements seen during Xenopus gastrulation. In particular, regulated changes in C-cadherin adhesion critically influence convergence-extension movements, thereby determining organization of the body plan. It is also predicted that remodelling of cadherin adhesive contacts is important for such cell-on-cell movements to occur. The recent demonstration that Epithelial (E-) cadherin is capable of undergoing endocytic trafficking to and from the cell surface presents a potential mechanism for rapid remodelling of such adhesive contacts. To test the potential role for C-cadherin endocytosis during convergence-extension, we expressed in early Xenopus embryos a dominantly-inhibitory mutant of the GTPase, dynamin, a key regulator of clathrin-mediated endocytosis. We report that this dynamin mutant significantly blocked the elongation of animal cap explants in response to activin, accompanied by inhibition of C-cadherin endocytosis. We propose that dynamin-dependent endocytosis of C-cadherin plays an important role in remodelling adhesive contacts during convergence-extension movements in the early Xenopus embryo.