The chromosomal association/dissociation of the chromatin insulator protein Cp190 of Drosophila melanogaster is mediated by the BTB/POZ domain and two acidic regions

<p>Abstract</p> <p>Background</p> <p>Chromatin insulators or boundary elements are a class of functional elements in the eukaryotic genome. They regulate gene transcription by interfering with promoter-enhancer communication. The Cp190 protein of <it>Drosophila </it><it>melanogaster </it>is essential to the function of at least three-types of chromatin insulator complexes organized by Su(Hw), CTCF and BEAF32.</p> <p>Results</p> <p>We mapped functional regions of Cp190 in vivo and identified three domains that are essential for the insulator function and for the viability of flies: the BTB/POZ domain, an aspartic acid-rich (D-rich) region and a C-terminal glutamic acid-rich (E-rich) region. Other domains including the centrosomal targeting domain and the zinc fingers are dispensable. The N-terminal CP190BTB-D fragment containing the BTB/POZ domain and the D-rich region is sufficient to mediate association with all three types of insulator complexes. The fragment however is not sufficient for insulator activity or viability. The Cp190 and CP190BTB-D are regulated differently in cells treated with heat-shock. The Cp190 dissociated from chromosomes during heat-shock, indicating that dissociation of Cp190 with chromosomes can be regulated. In contrast, the CP190BTB-D fragment didn't dissociate from chromosomes in the same heat-shocked condition, suggesting that the deleted C-terminal regions have a role in regulating the dissociation of Cp190 with chromosomes.</p> <p>Conclusions</p> <p>The N-terminal fragment of Cp190 containing the BTB/POZ domain and the D-rich region mediates association of Cp190 with all three types of insulator complexes and that the E-rich region of Cp190 is required for dissociation of Cp190 from chromosomes during heat-shock. The heat-shock-induced dissociation is strong evidence indicating that dissociation of the essential insulator protein Cp190 from chromosomes is regulated. Our results provide a mechanism through which activities of an insulator can be modulated by internal and external cues.</p

Coding culture: challenges and recommendations for comparative cultural databases

Considerable progress in explaining cultural evolutionary dynamics has been made by applying rigorous models from the natural sciences to historical and ethnographic information collected and accessed using novel digital platforms. Initial results have clarified several long-standing debates in cultural evolutionary studies, such as population origins, the role of religion in the evolution of complex societies and the factors that shape global patterns of language diversity. However, future progress requires recognition of the unique challenges posed by cultural data. To address these challenges, standards for data collection, organisation and analysis must be improved and widely adopted. Here, we describe some major challenges to progress in the construction of large comparative databases of cultural history, including recognising the critical role of theory, selecting appropriate units of analysis, data gathering and sampling strategies, winning expert buy-in, achieving reliability and reproducibility in coding, and ensuring interoperability and sustainability of the resulting databases. We conclude by proposing a set of practical guidelines to meet these challenges

Ages of onset of DSM-III anxiety disorders

The Diagnostic and Statistical Manual (DSM-III) contains little specific information pertaining to the ages of onset of anxiety disorders. Such information is of clinical and research value in understanding the natural history of mental illnesses, in determining which of several possible etiologies for a given diagnosis may be relevant for a particular patient, and in testing theories of psychopathology or pathophysiology. Age-of-onset data is presented for 423 psychiatric outpatients seen at a University Hospital--based anxiety disorders program. All adult anxiety disorders are represented except posttraumatic stress disorder. The relevance of this information is discussed in terms of past research on ages of onset of the anxiety disorders, and in its bearing on the psychiatric diagnosis of these conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25743/1/0000303.pd

A pilot randomised controlled trial of community-led ANtipsychotic Drug REduction for adults with learning disabilities

Background Data suggest that approximately 50,000 adults with learning disabilities (LDs) in England and Wales are currently prescribed antipsychotic medication. Illness in this population is common, including significant rates of challenging behaviour and mental illness, but there is particular concern over the use of antipsychotics prescribed for reasons other than the treatment of psychosis. Control of challenging behaviour is the primary reason why such medications are prescribed despite the absence of good evidence for any therapeutic effect for this purpose. Objectives To assess the feasibility of recruitment and retention and to explore non-efficacy-based barriers to a blinded antipsychotic medication withdrawal programme for adults with LDs without psychosis compared with treatment as usual. A secondary objective was to compare trial arms regarding clinical outcomes. Design A two-arm individually randomised double-blind placebo-controlled drug reduction trial. Setting Recruitment was through community learning disability teams (CLDTs) in south Wales and south-west England. Participants Adults with LDs who are prescribed risperidone for treatment of challenging behaviour with no known current psychosis or previous recurrence of psychosis following prior drug reduction. Intervention A double-blind drug reduction programme leading to full withdrawal within 6 months. Treatment in the intervention group was gradually reduced over a 6-month period and then maintained at the same level for a further 3 months, still under blind conditions. In the control group, the baseline level of medication was maintained throughout the 9-month period. The blind was broken at 9 months, following final data collection. Main outcome measures Feasibility outcomes were (1) the number and proportion of general practices/CLDTs that progressed from initial approach to recruitment of participants and (2) the number and proportion of recruited participants who progressed through the various stages of the study. Trial arms were also compared regarding clinical outcomes, the Modified Overt Aggression Scale, the Aberrant Behaviour Checklist, the Psychiatric Assessment Schedule for Adults with Developmental Disability checklist, the Antipsychotic Side-effect Checklist, the Dyskinesia Identification System Condensed User Scale, the Client Service Receipt Inventory, use of other interventions to manage challenging behaviour, use of as-required (pro re nata) medication and level of psychotropic medication use. Results Of the 22 participants randomised (intervention, n = 11; control, n = 11), 13 (59%) achieved progression through all four stages of reduction. Follow-up data at 6 and 9 months were obtained for 17 participants (intervention, n = 10; and control, n = 7; 77% of those randomised). There were no clinically important changes in participants’ levels of aggression or challenging behaviour at the end of the study. There were no expedited safety reports. Four adverse events and one serious adverse event were reported during the trial. Limitations Recruitment was challenging, which was largely a result of difficulty in identifying appropriate persons to consent and carer concerns regarding re-emergence of challenging behaviour. Reduced recruitment meant that the full trial became an exploratory pilot study. Conclusions The results indicate that drug reduction is possible and safe. However, concerns about taking part were probably exacerbated by limited availability of alternative (behavioural) interventions to manage behaviour; therefore, focused support and alternative interventions are required. The results of the qualitative study provide important insights into the experiences of people taking part in drug reduction studies that should influence future trial development. Future work We recommend that further work focuses on support for practitioners, carers and patients in reducing antipsychotic medication. Trial registration Current Controlled Trials ISRCTN38126962

Non-pharmacological interventions for adults with intellectual disabilities and depression

Background: Although high rates of depression symptoms are reported in adults with intellectual disabilities (IDs), there is a lack of knowledge about non-pharmacological treatment options for depression in this population. The first research question of this paper is: Which non-pharmacological interventions have been studied in adults with ID and depression? The second research question is: What were the results of these non-pharmacological interventions?. Method: Systematic review of the literature with an electronic search in six databases has been completed with hand searches. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines have been followed. Selected studies met predefined inclusion criteria. Results: Literature search resulted in 4267 papers of which 15 met the inclusion criteria. Five different types of non-pharmacological interventions have been studied: cognitive behavioural therapy, behavioural therapy, exercise intervention, social problem-solving skills programme and bright light therapy. Conclusion: There are only a few studies of good quality evaluating non-pharmacological interventions for adults with ID and depression. Some of these studies, especially studies on cognitive behavioural therapy, show good results in decreasing depressive symptoms. High-quality randomised controlled trials evaluating non-pharmacological

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Emerging themes to support ambitious UK marine biodiversity conservation

Healthy marine ecosystems provide a wide range of resources and services that support life on Earth and contribute to human wellbeing. Marine Protected Areas (MPAs) are accepted as an important tool for the restoration and maintenance of marine ecosystem structure, function, health and ecosystem integrity through the conservation of significant species, habitats, or entire ecosystems. In recent years there has been a rapid expansion in the area of ocean designated as an MPA. Despite this progress in spatial protection targets and the progressive knowledge of the essential interdependence between the human and the ocean system, marine biodiversity continues to decline, placing in jeopardy the range of ecosystem services benefits humans rely on. There is a need to address this shortcoming. Ambitious marine conservation:• Requires a shift from managing individual marine features within MPAs to whole-sites to enable repair and renewal of marine systems;• Reflects an ambition for sustainable livelihoods by fully integrating fisheries management with conservation (Ecosystem Based Fisheries Management) as the two are critically interdependent;• Establishes a world class and cost effective ecological and socio-economic monitoring and evaluation framework that includes the use of controls and sentinel sites to improve sustainability in marine management; and• Challenges policy makers and practitioners to be progressive by integrating MPAs into the wider seascape as critical functional components rather than a competing interest and move beyond MPAs as the only tool to underpin the benefits derived from marine ecosystems by identifying other effective area-based conservation measures (OECMs) to establish synergies with wider governance frameworks

The restructuring of market socialism: the contribution of an 'agency' theoretical perspective

Most discussions of the development of market socialism in China adopt an ‘institutional approach’ in which socio-economic and political organizations are described as a complex set of arrangements determined by the policies and role of the Communist Party. Such institutions are often seen to be little more than passive forces responding to the imperatives and stipulations of the Party. However the character and continuing development of market socialism is far more complex than this. It is made up of inter-acting forces that are the outcome of the purposive actions of economic agents that, although created and nurtured by the Party, create tensions within the socio-economic structure and thereby shape the direction of societal change. It is these that constitute many of the defining characteristics of market socialism. There is, the tensions between the imperatives of an emerging market economy and the political imperatives of the Party. But there are others that are determined by the goals and values of a diversity of agents within both the state-owned and privately-owned sectors of the economy. For an understanding of these, we argue in this paper for the need to adopt an ‘agency approach’; that is, one that focuses upon the key roles of actors and agencies, in shaping institutional arrangements of the sort that constitute present-day market socialism. This, we argue, does not displace an ‘institutional’ theoretical perspective but compliments it thereby offers a more complete insight into the generic character of a socio-economic structure; in this case, Chinese market socialism

National and firm-level drivers of the devolution of HRM decision making to line managers

Multinational companies must understand the influences on responsibility for managing people so that they can manage talent consistently thus ensuring that it is transferable across locations. We examine the impact of firm and national level characteristics on the devolution of HRM decision making to line managers. Our analysis draws on data from 2335 indigenous organizations in 21 countries. At the firm level, we found that where the HR function has higher power, devolution is less likely. At the national level, devolution of decision making to line management is more likely in societies with more stringent employment laws and lower power distance

Living at home after emergency hospital admission:prospective cohort study in older adults with and without cognitive spectrum disorder

Background: Cognitive spectrum disorders (CSDs) are common in hospitalised older adults and associated with adverse outcomes. Their association with the maintenance of independent living has not been established. The aim was to establish the role of CSDs on the likelihood of living at home 30 days after discharge or being newly admitted to a care home. Methods: A prospective cohort study with routine data linkage was conducted based on admissions data from the acute medical unit of a district general hospital in Scotland. 5570 people aged ≥ 65 years admitted from a private residence who survived to discharge and received the Older Persons Routine Acute Assessment (OPRAA) during an incident emergency medical admission were included. The outcome measures were living at home, defined as a private residential address, 30 days after discharge and new care home admission at hospital discharge. Outcomes were ascertained through linkage to routine data sources. Results: Of the 5570 individuals admitted from a private residence who survived to discharge, those without a CSD were more likely to be living at home at 30 days than those with a CSD (93.4% versus 81.7%; difference 11.7%, 95%CI 9.7–13.8%). New discharge to a care home affected 236 (4.2%) of the cohort, 181 (76.7%) of whom had a CSD. Logistic regression modelling identified that all four CSD categories were associated with a reduced likelihood of living at home and an increased likelihood of discharge to a care home. Those with delirium superimposed on dementia were the least likely to be living at home (OR 0.25), followed by those with dementia (OR 0.43), then unspecified cognitive impairment (OR 0.55) and finally delirium (OR 0.57). Conclusions: Individuals with a CSD are at significantly increased risk of not returning home after hospitalisation, and those with CSDs account for the majority of new admissions to care homes on discharge. Individuals with delirium superimposed on dementia are the most affected. We need to understand how to configure and deliver healthcare services to enable older people to remain as independent as possible for as long as possible and to ensure transitions of care are managed supportively