209 research outputs found

    Roles of the Bloom's syndrome helicase in the maintenance of genome stability

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    The RecQ family of DNA helicases is highly conserved in evolution from bacteria to humans. Of the five known human RecQ family members, three (BLM, WRN and RECQ4, which cause Bloom's syndrome, Werner's syndrome and Rothmund-Thomson syndrome respectively) are mutated in distinct clinical disorders associated with cancer predisposition and/or premature aging. BLM forms part of a multienzyme complex including topoisomerase IIIalpha, replication protein A and a newly identified factor called BLAP75. Together, these proteins play a role in the resolution of DNA structures that arise during the process of homologous recombination repair. In the absence of BLM, cells show genomic instability and a high incidence of sister-chromatid exchanges. In addition to a DNA structure-specific helicase activity, BLM also catalyses Holliday-junction branch migration and the annealing of complementary single-stranded DNA molecules

    Effect of psychiatry liaison with general practitioners on depression severity in recently hospitalised cardiac patients: a randomised controlled trial

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    The document attached has been archived with permission from the editor of the Medical Journal of Australia (26 April 2007). An external link to the publisher’s copy is included.Objective: To evaluate the effect on depressive symptoms in cardiac patients of patient-specific advice to general practitioners regarding management of comorbid depression. Design and setting: A randomised controlled trial in four general hospitals in Adelaide, South Australia. Participants: Patients (n = 669) admitted to cardiology units for a range of cardiovascular conditions who were screened and assessed as being depressed according to the Center for Epidemiological Studies Depression Scale (CES-D). Intervention: Inpatient psychiatric review, followed by telephone case conferencing between specialist hospital staff and GPs to provide patient-specific information about the patient’s depression and its management, educational material, and ongoing clinical support. Main outcome measures: Level of depression severity at 12 months posthospitalisation. Results: On the basis of intention to treat, intervention patients had lower rates of moderate to severe depression (CES-D ≄ 27) after 12 months (25% v 35%, relative risk, 0.72; 95% CI, 0.54–0.96, number needed to treat for benefit, 11). The intervention was most effective in preventing progression from mild depression to moderate to severe depression. The multidisciplinary telephone case conferencing was difficult to implement and, in a post hoc analysis, brief phone advice from a psychiatrist was found to be effective. Conclusions: Screening hospitalised cardiac patients for depression and providing targeted advice to their GPs reduces depression severity 12 months after hospitalisation.Geoff Schrader, Frida Cheok, Ann-Louise Hordacre, Julie Marker and Victoria Wad

    Depression after cardiac hospitalisation: the identifying depression as a comorbid condition (IDACC) study

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    Copyright © 2005 Royal Australian College of General Practitioners Copyright to Australian Family Physician. Reproduced with permission. Permission to reproduce must be sought from the publisher, The Royal Australian College of General Practitioners.Background: The Identifying Depression as a Comorbid Condition (IDACC) study aimed to identify depressive symptoms in hospitalised cardiac patients and support management of depression in general practice. Objective: This post hoc analysis of the IDACC trial examines the effectiveness and practicality of different forms of communication between hospital psychiatric services and general practitioners. Methods: We randomised 669 cardiac inpatients with depressive symptoms, identified with the Center for Epidemiological Studies Depression Scale (CES-D), to an intervention or usual care control group. Individual depression scores and depression management guidelines were sent to GPs of all intervention patients. Where possible, psychiatric advice was provided to the GP either by multidisciplinary enhanced primary care case conference or one-to-one telephone advice. Results: Multidisciplinary case conferences were implemented for only 24% of intervention patients. General practitioners received individual telephone advice in 40% of cases, and 36% received written information only. The psychiatrist telephone advice resulted in a significant reduction in the proportion of patients with moderate to severe depression 12 months after cardiac hospitalisation (19% vs. 35%). Discussion: Screening, combined with psychiatrist telephone advice to GPs, was simple to organise and effective in reducing depression severity after cardiac admission.Victoria Wade, Frida Cheok, Geoff Schrader, Ann-Louise Hordacre and Julie Marke

    Depression after cardiac hospitalisation: the identifying depression as a comorbid condition (IDACC) study

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    Copyright © 2005 Royal Australian College of General Practitioners Copyright to Australian Family Physician. Reproduced with permission. Permission to reproduce must be sought from the publisher, The Royal Australian College of General Practitioners.Background: The Identifying Depression as a Comorbid Condition (IDACC) study aimed to identify depressive symptoms in hospitalised cardiac patients and support management of depression in general practice. Objective: This post hoc analysis of the IDACC trial examines the effectiveness and practicality of different forms of communication between hospital psychiatric services and general practitioners. Methods: We randomised 669 cardiac inpatients with depressive symptoms, identified with the Center for Epidemiological Studies Depression Scale (CES-D), to an intervention or usual care control group. Individual depression scores and depression management guidelines were sent to GPs of all intervention patients. Where possible, psychiatric advice was provided to the GP either by multidisciplinary enhanced primary care case conference or one-to-one telephone advice. Results: Multidisciplinary case conferences were implemented for only 24% of intervention patients. General practitioners received individual telephone advice in 40% of cases, and 36% received written information only. The psychiatrist telephone advice resulted in a significant reduction in the proportion of patients with moderate to severe depression 12 months after cardiac hospitalisation (19% vs. 35%). Discussion: Screening, combined with psychiatrist telephone advice to GPs, was simple to organise and effective in reducing depression severity after cardiac admission.Victoria Wade, Frida Cheok, Geoff Schrader, Ann-Louise Hordacre and Julie Marke

    Squalus acanthias, spiny dogfish

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    While there are reported subpopulations of Squalus acanthias (Linnaeus, 1758) elsewhere in the world, the North Pacific subpopulation is now considered a separate species, Squalus suckleyi (Girard, 1854) (see Ebert et al. 2010). Further taxonomic studies on this genus are required, including in relation to Mediterranean and Black Sea subpopulations. In Europe, three subpopulations are inferred to occur.Fil: Finucci, B.. National Institute of Water and Atmospheric Research; Nueva ZelandaFil: Cheok, J.. University Fraser Simon; CanadåFil: Chiaramonte, Gustavo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia". Estación Hidrobiológica de Puerto Quequén (sede Quequén); ArgentinaFil: Cotton, C. F.. Florida State University; Estados UnidosFil: Dulvy, N. K.. University Fraser Simon; CanadåFil: Kulka, D. W.. No especifíca; ArgentinaFil: Neat, F. C.. No especifíca; ArgentinaFil: Pacoureau, N.. University Fraser Simon; CanadåFil: Rigby, C. L.. James Cook University; AustraliaFil: Tanaka, S.. No especifíca; ArgentinaFil: Walker, T. I.. University of Melbourne; Australi

    Mechanistic mathematical modelling of mercaptopurine effects on cell cycle of human acute lymphoblastic leukaemia cells

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    The antimetabolite mercaptopurine (MP) is widely used to treat childhood acute lymphoblastic leukaemia (ALL). To study the dynamics of MP on the cell cycle, we incubated human T-cell leukaemia cell lines (Molt-4 sensitive and resistant subline and P12 resistant) with 10 ΌM MP and measured total cell count, cell cycle distribution, percent viable, percent apoptotic, and percent dead cells serially over 72 h. We developed a mathematical model of the cell cycle dynamics after treatment with MP and used it to show that the Molt-4 sensitive controls had a significantly higher rate of cells entering apoptosis (2.7-fold, P<0.00001) relative to the resistant cell lines. Additionally, when treated with MP, the sensitive cell line showed a significant increase in the rate at which cells enter apoptosis compared to its controls (2.4-fold, P<0.00001). Of note, the resistant cell lines had a higher rate of antimetabolite incorporation into the DNA of viable cells (>1.4-fold, P<0.01). Lastly, in contrast to the other cell lines, the Molt-4 resistant subline continued to cycle, though at a rate slower relative to its control, rather than proceed to apoptosis. This led to a larger S-phase block in the Molt-4 resistant cell line, but not a higher rate of cell death. Gene expression of apoptosis, cell cycle, and repair genes were consistent with mechanistic dynamics described by the model. In summary, the mathematical model provides a quantitative assessment to compare the cell cycle effects of MP in cells with varying degrees of MP resistance

    Direct comparisons of logging and agroforestry influence on tropical mammals in Sarawak, Borneo

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    Tropical regions are undergoing rapid land use change, with major implications for global biodiversity. Selective logging and agroforestry are particularly widespread across tropical forests, often occurring in close proximity. But while a number of studies have addressed their impacts separately, few have directly compared how they influence forest vertebrates. Here, we assessed the occurrence of medium- to large-bodied mammals in logged forest, unlogged forest, and agroforestry areas in three study areas in interior Sarawak, Malaysian Borneo. We detected 34 species across 99 camera trap locations and used multi-species occupancy models to estimate species-specific occurrence while accounting for imperfect detectability, spatial autocorrelation, natural habitat heterogeneity, and metrics of site accessibility (distance to human infrastructure) as proxies for potential hunting pressure. We found that species occurrences were unaffected by the distance to the nearest road or village and only responded to elevation and the distance to the nearest river in a single species each. Detection rates tended to vary with micro-habitat characteristics such as the size of tree stumps and the prevalence of trees and rattan palms, which are often not considered in camera-based occupancy studies. Occurrence rates of five species varied across habitat types but were not detectably lower in agroforestry sites than in unlogged forest for any species. Our results indicate that without unsustainable hunting, agroforestry and logged forest provide usable habitat for some, though not all, rainforest mammals. We also suggest that camera trap studies may benefit from the incorporation of fine-scale habitat information into detectability estimation

    DNA resection in eukaryotes: deciding how to fix the break

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    DNA double-strand breaks are repaired by different mechanisms, including homologous recombination and nonhomologous end-joining. DNA-end resection, the first step in recombination, is a key step that contributes to the choice of DSB repair. Resection, an evolutionarily conserved process that generates single-stranded DNA, is linked to checkpoint activation and is critical for survival. Failure to regulate and execute this process results in defective recombination and can contribute to human disease. Here, I review recent findings on the mechanisms of resection in eukaryotes, from yeast to vertebrates, provide insights into the regulatory strategies that control it, and highlight the consequences of both its impairment and its deregulation
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