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An understanding of the metabolic determinants of postexercise appetite regulation would facilitate development of adjunctive therapeutics to suppress compensatory eating behaviours and improve the efficacy of exercise as a weight-loss treatment. Metabolic responses to acute exercise are, however, dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite regulation across nutritional states. In this randomized crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% of maximal oxygen uptake); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at predefined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones glucagon-like peptide 1 (carbohydrate, 16.8 pmol/L; exercise, 7.4 pmol/L), ghrelin (carbohydrate, -48.8 pmol/L; exercise: -22.7 pmol/L) and glucagon (carbohydrate, 9.8 ng/L; exercise, 8.2 ng/L) that were linked to the generation of distinct plasma 1 H nuclear magnetic resonance metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in postexercise appetite regulation. KEY POINTS: Carbohydrate and exercise independently influence key appetite-regulating hormones. Temporal changes in postexercise appetite are linked to acetate, lactate and peptide YY. Postexercise energy intake is associated with glucagon-like peptide 1 and succinate levels., (© 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Reduced protein intake, through dilution with carbohydrate, extends lifespan and improves mid-life metabolic health in animal models. However, with transition to industrialised food systems, reduced dietary protein is associated with poor health outcomes in humans. Here we systematically interrogate the impact of carbohydrate quality in diets with varying carbohydrate and protein content. Studying 700 male mice on 33 isocaloric diets, we find that the type of carbohydrate and its digestibility profoundly shape the behavioural and physiological responses to protein dilution, modulate nutrient processing in the liver and alter the gut microbiota. Low (10%)-protein, high (70%)-carbohydrate diets promote the healthiest metabolic outcomes when carbohydrate comprises resistant starch (RS), yet the worst outcomes were with a 50:50 mixture of monosaccharides fructose and glucose. Our findings could explain the disparity between healthy, high-carbohydrate diets and the obesogenic impact of protein dilution by glucose-fructose mixtures associated with highly processed diets.

Background: We conducted a cluster randomized trial of a workplace mental health intervention in an Australian police department. The intervention was co-designed and co-implemented with the police department. Intervention elements included tailored mental health literacy training for all members of participating police stations, and a leadership development and coaching program for station leaders. This study presents the results of a mixed-methods implementation evaluation of the trial., Methods: Descriptive quantitative analyses characterized the extent of participation in intervention activities, complemented by a qualitative descriptive analysis of transcripts of 60 semistructured interviews with 53 persons and research team field notes., Results: Participation rates in the multicomponent leadership development activities were highly variable, ranging from <10% to approximately 60% across stations. Approximately 50% of leaders and <50% of troops completed the mental health literacy training component of the intervention. Barriers to implementation included rostering challenges, high staff turnover and changes, competing work commitments, staff shortages, limited internal personnel resources to deliver the mental health literacy training, organizational cynicism, confidentiality concerns, and limited communication about the intervention by station command or station champions. Facilitators of participation were also identified, including perceived need for and benefits of the intervention, engagement at various levels, the research team's ability to create buy-in and manage stakeholder relationships, and the use of external, credible leadership development coaches., Conclusions: Implementation fell far short of expectations. The identified barriers and facilitators should be considered in the design and implementation of similar workplace mental health interventions., (© 2020 Wiley Periodicals LLC.)

We examined whether job security improvements were associated with improvements in mental health in a large, nationally representative panel study in Australia. We used both within-person fixed effects (FE) and random effects (RE) regression to analyze data from 14 annual waves covering the calendar period of 2002-2015 (19,169 persons; 106,942 observations). Mental Health Inventory-5 scores were modeled in relation to self-reported job security (categorical, quintiles), adjusting for age, year, education, and job change in the past year. Both FE and RE models showed stepwise improvements in Mental Health Inventory-5 scores with improving job security, with stronger exposure-outcome relationships in the RE models and for men compared with women. The RE coefficients for improvements in job security in men were 2.06 (95% confidence interval (CI): 1.67, 2.46) for 1 quintile, steadily increasing for 2- (3.94 (95% CI: 3.54, 4.34)), 3- (5.82 (95% CI: 5.40, 6.24)), and 4-quintile (7.18 (95% CI: 6.71, 7.64)) improvements. The FE model for men produced slightly smaller coefficients, reaching a maximum of 5.55 (95% CI: 5.06, 6.05). This analysis, with improved causal inference over previous observational research, showed that improving job security is strongly associated with decreasing depression and anxiety symptoms. Policy and practice intervention to improve job security could benefit population mental health., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The effects of poor-quality work (high job demands, low job control, job insecurity, and effort-reward imbalance) are harmful to health but it isn't clear whether exposure to these psychosocial work stressors over time translates into increased risk of mortality., Objective: We investigated the effect of time-varying psychosocial work stressors on mortality using data from a longitudinal cohort of working Australians by examining association between job control, job demands, job insecurity, unfair pay overtime and all-cause mortality. We examined whether gender modified these relationships., Methods: Over 20,000 participants from the Household Income and Labour Dynamics in Australia survey with self-reported repeated exposure measures were followed for 15 years. Survival analysis models with baseline hazard specified by the Weibull distribution were used to examine the association between psychosocial work stressors over time and mortality., Results: Low job control (HR=1.39; 95% CI: 1.06-1.83) and job insecurity (1.36; 1.06-1.74) were associated with increased risk of mortality. High job demands (1.01; 0.75-1.34) and effort-reward unfairness (1.20; 0.90-1.59) were not associated with mortality. The effect of job insecurity was attenuated (1.20; 0.93-1.54) after controlling for sociodemographic and health risk factors. Male participants exposed to low job control and job insecurity had an 81% and 39% increase risk of mortality, respectively., Conclusions: Long-term exposure to low job control and low job security is associated with increased risk of all-cause mortality. Effects were largely restricted to males and persisted after adjustments for sociodemographic and health characteristics. The lack of effects observed for females may have been due to the small number of deaths in females. Awareness of implications of the adverse effects of psychosocial work stressors on health and mortality in workplaces, and interventions to improve job control and job security could contribute to better health and wellbeing, reducing the effect of psychosocial work stressors on mortality., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: There is no review on the effect of work-related stressors on mental health of young workers. We systematically reviewed epidemiological evidence on this relationship., Methods: The review searched eight databases: Embase, PubMed, Web of Science, Cinahl, Cochrane Library, Informit, PsycINFO, and Scopus from their respective start dates until May 2017. Studies that have examined a mental health outcome in relation to a work-related stressor as exposure in young workers were included. The review was reported based on the PRISMA statement., Results: Three cross-sectional studies and six longitudinal cohort studies were included. Cross-sectional evidence showed that adverse work conditions including working overtime, job boredom, low skill variety, low autonomy, high job insecurity, and lack of reward were associated with poor mental health of young workers. Longitudinal evidence showed that high job demands, low job control, effort-reward imbalance, and low work support (men only) were associated with poor mental health. There was evidence on the contemporaneous relationship between two or more adverse work conditions and poor mental health., Conclusions: Although more research (particularly high-quality longitudinal studies) is warranted in this area, our review indicates that work-related stressors have a negative impact on the mental health of young workers. The current review suggests that workplace interventions and policy are required to improve the quality of work for young workers.

Objectives Psychosocial work stressors are common exposures affecting the working population, and there is good evidence that they have adverse health consequences. There is some evidence that they may impact on mortality, but this has not been systematically examined. We performed a systematic review, including risk of bias, and meta-analyses of observational studies to examine the association between psychosocial work stressors and all-cause mortality and death due to coronary heart disease (CHD). Methods Electronic databases were searched to identify studies and information on study characteristics and outcomes extracted in accordance with PRISMA guidelines. Risk estimates of outcomes associated with psychosocial work stressors: specifically, all-cause mortality, and death due to CHD were pooled using inverse variance weighted random effects meta-analysis. Results We identified 45 eligible cohort studies, of which 32 were included in the quantitative analyses of psychosocial work stressors and mortality. Low job control was associated with an increased risk of all-cause mortality [hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.07-1.37, minimally-adjusted; HR 1.05, 95% CI 1.01-1.10, multivariable-adjusted; HR 1.03, 95% CI 1.00-1.06 exclusion of low quality studies and multivariable-adjusted] and CHD mortality [HR 1.50, 95% CI 1.42-1.58, minimally-adjusted; HR 1.23, 95% CI 1.17-1.30, multivariable-adjusted; HR 1.19, 95% CI 1.01-1.40, exclusion of low quality studies and multivariable-adjusted]. Conclusions Workers with low job control are at increased risk of all-cause and CHD mortality compared to workers with high job control. Policy and practice interventions to improve job control could contribute to reductions in all-cause and CHD mortality.

Background: Suicide rates are higher among unemployed men as well as those employed in male-dominated occupations such as construction. There has been less research on whether these patterns are similar for suicide ideation and attempt. Aims: In a cohort of 13,892 Australian males, this study examined the relationship between employment status and occupational gender ratio on reported thoughts of suicide and suicide attempts. Method: Men reporting suicide ideation or attempts at Wave 1 were removed from the sample. Logistic regression was used to examine Wave 1 employment status and occupational gender ratio and Wave 2 reported suicide ideation and attempts, controlling for confounders (measured in Wave 1). We conducted a sensitivity analysis controlling for mental health status. Results: Those who were unemployed or not in the labor force had elevated rates of suicide ideation (unemployed OR = 1.91, 95% CI [1.30, 2.82], p = .001; not in the labor force OR  = 1.68, 95% CI [1.09, 2.60], p = .020). Those who were not in the labor force had greater odds of attempts ( OR = 2.32, 95% CI [1.05, 5.12], p = .037). There was no association between occupational gender ratio and suicide ideation or attempt. Limitations: We only had single item measures of ideation and attempts. Conclusion: There is a need for further investigation into risk factors for suicide among males, both when they are in and out of employment.

Objective: To assess depression literacy, help-seeking and help-offering to others in members of the police force in the state of Victoria, Australia., Methods: All staff in police stations involved in a cluster randomised controlled trial of an integrated workplace mental health intervention were invited to participate. Survey questions covered sociodemographic and employment information, recognition of depression in a vignette, stigma, treatment beliefs, willingness to assist co-workers with mental health problems, help-giving and help-seeking behaviours, and intentions to seek help. Using the baseline dataset associated with the trial, the paper presents a descriptive analysis of mental health literacy and helping behaviours, comparing police station leaders and lower ranks., Results: Respondents were 806 staff, comprising 618 lower-ranked staff and 188 leaders. Almost 84% of respondents were able to correctly label the problem described in the vignette. Among those who had helped someone with a mental health problem, both lower ranks and leaders most commonly reported 'talking to the person' although leaders were more likely to facilitate professional help. Leaders' willingness to assist the person and confidence in doing so was very high, and over 80% of leaders appropriately rated police psychologists, general practitioners, psychologists, talking to a peer and contacting welfare as helpful. However, among both leaders and lower ranks with mental health problems, the proportion of those unlikely to seek professional help was greater than those who were likely to seek it., Conclusion: Knowledge about evidence-based interventions for depression was lower in this police sample than surveys in the general population, pointing to the need for education and training to improve mental health literacy. Such education should also aim to overcome barriers to professional help-seeking. Interventions that aim to improve mental health literacy and help-seeking behaviour appear to be suitable targets for better protecting police member mental health.

The social gradient for cardiovascular disease (CVD) onset and outcomes is well established. The American Heart Association's Social Determinants of Risk and Outcomes of Cardiovascular Disease Scientific Statement advocates looking beyond breakthroughs in biological science toward a social determinants approach that focuses on socioeconomic position, race and ethnicity, social support, culture and access to medical care, and residential environments to curb the burden of CVD going forward. Indeed, the benefits of this approach are likely to be far reaching, enhancing the positive effects of advances in CVD related to prevention and treatment while reducing health inequities that contribute to CVD onset and outcomes. It is disappointing that the role of gender has been largely neglected despite being a critical determinant of cardiovascular health. It is clear that trajectories and outcomes of CVD differ by biological sex, yet the tendency for sex and gender to be conflated has contributed to the idea that both are constant or fixed with little room for intervention. Rather, as distinct from biological sex, gender is socially produced. Overlaid on biological sex, gender is a broad term that shapes and interacts with one's cognition to guide norms, roles, behaviors, and social relations. It is a fluid construct that varies across time, place, and life stage. Gender can interact with biological sex and, indeed, other social determinants, such as ethnicity and socioeconomic position, to shape cardiovascular health from conception, through early life when health behaviors and risk factors are shaped, into adolescence and adulthood. This article will illustrate how gender shapes the early adoption of health behaviors in childhood, adolescence, and young adulthood by focusing on physical activity, drinking, and smoking behaviors (including the influence of role modeling). We will also discuss the role of gender in psychosocial stress with a focus on trauma from life events (childhood assault and intimate partner violence) and work, home, and financial stresses. We conclude by exploring potential biological pathways, with a focus on autonomic functioning, which may underpin gender as a social determinant of cardiovascular health. Finally, we discuss implications for cardiovascular treatment and awareness campaigns and consider whether gender equality strategies could reduce the burden of CVD for men and women at the population level., (© 2018 American Heart Association, Inc.)

Objective: To provide guidance for the organisation and delivery of clinical services and the clinical management of patients who deliberately self-harm, based on scientific evidence supplemented by expert clinical consensus and expressed as recommendations., Method: Articles and information were sourced from search engines including PubMed, EMBASE, MEDLINE and PsycINFO for several systematic reviews, which were supplemented by literature known to the deliberate self-harm working group, and from published systematic reviews and guidelines for deliberate self-harm. Information was reviewed by members of the deliberate self-harm working group, and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to successive consultation and external review involving expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest and expertise in deliberate self-harm., Results: The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for deliberate self-harm provide up-to-date guidance and advice regarding the management of deliberate self-harm patients, which is informed by evidence and clinical experience. The clinical practice guidelines for deliberate self-harm is intended for clinical use and service development by psychiatrists, psychologists, physicians and others with an interest in mental health care., Conclusion: The clinical practice guidelines for deliberate self-harm address self-harm within specific population sub-groups and provide up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus., (© The Royal Australian and New Zealand College of Psychiatrists 2016.)

Objectives: To report age-standardised rates and methods of suicide by health professionals, and to compare these with suicide rates for other occupations., Study Design: Retrospective mortality study., Setting, Participants: All intentional self-harm cases recorded by the National Coronial Information System during the period 2001-2012 were initially included. Cases were excluded if the person was unemployed at the time of death, if their employment status was unknown or occupational information was missing, or if they were under 20 years of age at the time of death. Suicide rates were calculated using Australian Bureau of Statistics population-level data from the 2006 census., Main Outcome Measures: Suicide rates and method of suicide by occupational group., Results: Suicide rates for female health professionals were higher than for women in other occupations (medical practitioners: incidence rate ratio [IRR], 2.52; 95% CI, 1.55-4.09; P < 0.001; nurses and midwives: IRR, 2.65; 95% CI, 2.22-3.15; P < 0.001). Suicide rates for male medical practitioners were not significantly higher than for other occupations, but the suicide rate for male nurses and midwives was significantly higher than for men working outside the health professions (IRR, 1.50; 95% CI 1.12-2.01; P = 0.006). The suicide rate for health professionals with ready access to prescription medications was higher than for those in health professions without such access or in non-health professional occupations. The most frequent method of suicide used by health professionals was self-poisoning., Conclusion: Our results indicate the need for targeted prevention of suicide by health professionals.

This report investigated whether suicide risk by occupational groups differed for males and females. We examined this using a sub-set of articles examined in a recent meta-analysis and stratified by gender. For certain occupational groups, males and females had a similar risk of suicide (the military, community service occupations, managers, and clerical workers). There was some indication of gender differences for other occupations (technicians, plant and machine operators and ship's deck crew, craft and related trades workers, and professionals), although these did not reach statistical significance. These findings highlight the complexity of the relationship between occupation and suicide and suggest the possible role of a range of individual, work-related and social-environmental risk factors that may differ for males and females.

Background: In this paper, we present the protocol for a cluster-randomised trial to evaluate the implementation and effectiveness of a workplace mental health intervention in the state-wide police department of the south-eastern Australian state of Victoria. n. The primary aims of the intervention are to improve psychosocial working conditions and mental health literacy, and secondarily to improve mental health and organisational outcomes., Methods/design: The intervention was designed collaboratively with Victoria Police based on a mixed methods pilot study, and combines multi-session leadership coaching for the senior officers within stations (e.g., Sergeants, Senior Sergeants) with tailored mental health literacy training for lower and upper ranks. Intervention effectiveness will be evaluated using a two-arm cluster-randomised trial design, with 12 police stations randomly assigned to the intervention and 12 to the non-intervention/usual care control condition. Data will be collected from all police members in each station (estimated at >20 per station). Psychosocial working conditions (e.g., supervisory support, job control, job demands), mental health literacy (e.g., knowledge, confidence in assisting someone who may have a mental health problem), and mental health will be assessed using validated measures. Organisational outcomes will include organisational depression disclosure norms, organisational cynicism, and station-level sickness absence rates. The trial will be conducted following CONSORT guidelines. Identifying data will not be collected in order to protect participant privacy and to optimise participation, hence changes in primary and secondary outcomes will be assessed using a two-sample t-test comparing summary measures by arm, with weighting by cluster size., Discussion: This intervention is novel in its integration of stressor-reduction and mental health literacy-enhancing strategies. Effectiveness will be rigorously evaluated, and if positive results are observed, the intervention will be adapted across Victoria Police (total employees ~16,500) as well as possibly in other policing contexts, both nationally and internationally., Trial Registration: Current Controlled Trials: ISRCTN82041334. Registered 24th July, 2014.

Background: Previous research showed an increase in Australian suicide rates during the Global Financial Crisis (GFC). There has been no research investigating whether suicide rates by occupational class changed during the GFC. The aim of this study was to investigate whether the GFC-associated increase in suicide rates in employed Australians may have masked changes by occupational class., Methods: Negative binomial regression models were used to investigate Rate Ratios (RRs) in suicide by occupational class. Years of the GFC (2007, 2008, 2009) were compared to the baseline years 2001-2006., Results: There were widening disparities between a number of the lower class occupations and the highest class occupations during the years 2007, 2008, and 2009 for males, but less evidence of differences for females., Conclusions: Occupational disparities in suicide rates widened over the GFC period. There is a need for programs to be responsive to economic downturns, and to prioritise the occupational groups most affected.

Background: Whether veterinarians have an elevated suicide rate compared with the general population is controversial., Methods: Reported cases of suicide among veterinarians and veterinary nurses in Australia over the period 2001 to 2012 were investigated in a retrospective case-series study., Results: The standardised mortality ratio of veterinarians (n = 18) was 1.92 (95% CI 1.14-3.03) and that of veterinary nurses (n = 7) to the general population was 1.24 (95% CI 0.80-1.85). Overdosing on drugs (pentobarbitone) was the main method of suicide in these occupations., Conclusion: The reasons for veterinary suicides are likely to be multifactorial, including work- and life-related stressors, and individual characteristics. This research highlights the need for targeted suicide prevention and intervention for veterinarians., (© 2015 Australian Veterinary Association.)

Background: There is growing interest in brief contact interventions for self-harm and suicide attempt., Aims: To synthesise the evidence regarding the effectiveness of brief contact interventions for reducing self-harm, suicide attempt and suicide., Method: A systematic review and random-effects meta-analyses were conducted of randomised controlled trials using brief contact interventions (telephone contacts; emergency or crisis cards; and postcard or letter contacts). Several sensitivity analyses were conducted to examine study quality and subgroup effects., Results: We found 14 eligible studies overall, of which 12 were amenable to meta-analyses. For any subsequent episode of self-harm or suicide attempt, there was a non-significant reduction in the overall pooled odds ratio (OR) of 0.87 (95% CI 0.74-1.04, P = 0119) for intervention compared with control. The number of repetitions per person was significantly reduced in intervention v. control (incidence rate ratio IRR = 066, 95% CI 0.54-0.80, P<0001). There was no significant reduction in the odds of suicide in intervention compared with control (OR = 0.58, 95% CI 0.24-1.38)., Conclusions: A non-significant positive effect on repeated self-harm, suicide attempt and suicide and a significant effect on the number of episodes of repeated self-harm or suicide attempts per person (based on only three studies) means that brief contact interventions cannot yet be recommended for widespread clinical implementation. We recommend further assessment of possible benefits in well-designed trials in clinical populations., (Royal College of Psychiatrists.)

Objective: To examine whether positive mental health (PMH)-a positively focused well-being construct-moderates the job stress-distress relationship., Methods: Longitudinal regression was used to test two waves of matched, population-level data from a sample of older, working Australian adults (n = 3291) to see whether PMH modified the relationship between work stress and later psychological distress., Results: Time 1 work stress was positively associated with distress at both time points. Positive mental health was negatively associated with work stress at both time points. Positive mental health modified the impact of work stress on psychological distress. This effect only occurred for those with the highest levels of PMH., Conclusions: Positive mental health may help protect workers from the effect of workplace stress but only in a small proportion of the population. Therefore, to improve workplace mental health, workplaces need to both prevent stress and promote PMH.

Background: Mental health problems are prevalent and costly in working populations. Workplace interventions to address common mental health problems have evolved relatively independently along three main threads or disciplinary traditions: medicine, public health, and psychology. In this Debate piece, we argue that these three threads need to be integrated to optimise the prevention of mental health problems in working populations., Discussion: To realise the greatest population mental health benefits, workplace mental health intervention needs to comprehensively 1) protect mental health by reducing work-related risk factors for mental health problems; 2) promote mental health by developing the positive aspects of work as well as worker strengths and positive capacities; and 3) address mental health problems among working people regardless of cause. We outline the evidence supporting such an integrated intervention approach and consider the research agenda and policy developments needed to move towards this goal, and propose the notion of integrated workplace mental health literacy., Summary: An integrated approach to workplace mental health combines the strengths of medicine, public health, and psychology, and has the potential to optimise both the prevention and management of mental health problems in the workplace.

Low-frequency stimulation (LFS) is used to induce long-term depression (LTD) and depotentiation at rodent CA3-CA1 hippocampal synapses. The relationship between the efficacy of LFS induction and postnatal age remains to be clearly defined in rat and had not been studied in mouse. The data presented here show that in acute mouse hippocampal slices LFS-induced LTD and depotentiation at CA3-CA1 synapses are: synapse specific; NMDA receptor-dependent; and metabotropic glutamate (mGlu) receptor type I/II independent. Furthermore LFS-induced LTD is highly age-dependent whilst long-term potentiation (LTP) and depotentiation are not. In slices from very young mice (P6-9) LFS induced a robust and stable LTD (-31.1 +/- 5.9%, n = 8, P < 0.01) of CA1 field excitatory post-synaptic potentials (fEPSPs), measured 55-60 min after conditioning. LFS also induced LTD in slices from mice aged P10-13 and P14-17 (-16.0 +/- 3.0%, n = 35, P < 0.001 and -17.9 +/- 5.5%, n = 12, P < 0.01, respectively). However, LTD was not expressed in slices from animals aged P18-21 ( -7.0 +/- 4.1%, n = 16, P > 0.05) or older.

Recently, a new class of soluble inorganic pyrophosphatase (type-C PPase) has been described that is not homologous in amino acid sequence or kinetic properties to the well-studied PPases (types A and B) found in many organisms from bacteria to humans and thought to be essential to the cell. Structural studies of the type-C PPases from Streptococcus gordonii and Bacillus subtilis reveal a homodimeric structure, with each polypeptide folding into two domains joined by a flexible hinge. The active site, formed at the interface between the N and C-terminal domains, binds two manganese ions approximately 3.6 A apart in a conformation resembling binuclear metal centres found in other hydrolytic enzymes. An activated water molecule bridging the two metal ions is likely poised for nucleophilic attack of the substrate. Importantly, the S. gordonii and B. subtilis enzymes have crystallised in strikingly different conformations. In both subunits of the S. gordonii crystal structure (1.5 A resolution) the C-terminal domain is positioned such that the active site is occluded, with a sulphate ion bound in the active site. In contrast, in the B. subtilis structure (3.0 A resolution) the C-terminal domain is rotated by about 90 degrees, leaving the active site wide open and accessible for substrate binding., (Copyright 2001 Academic Press.)