A bioinformatic analysis of genes involved in stress responses in Arabidopsis thaliana

Hyaloperonospora arabidopsidis is an obligate biotrophic oomycete shown to cause downy mildew in Arabidopsis thaliana. The main focus of this project is examining plant stress response and the strategies employed by H. arabidopsidis to infect Arabidopsis and evade plant stress responses. Two regions of the H. arabidopsidis genome containing genes expressed in planta during infection were bioinformatically annotated. The results indicated the genes were involved in regulatory processes associated with the pathogenicity of H. arabidopsidis but not a direct role in pathogenicity. H. arabidopsidis infects its host by secreting effector proteins into the cytoplasm and apoplastic space of the host. The secretome of H. arabidopsidis was analysed to identify classes of cysteine rich apoplastic effectors. This identified 15 candidate elicitin (ELI) and elicitin-like (ELL) sequences, three Kazal-like serine protease inhibitors and four candidates similar to the protein sequences of Ppats 14 and 24, expressed during infection. A second set of aims was to identify potential signalling networks up activated during plant defence responses to infection by H. arabidopsidis using a new model developed by Beal et al (Beal, Falciani et al. 2005) to eventually engineer transcriptional networks. Unfortunately this failed due to problems with the experiment. However, it was still possible to identify signalling networks from a second microarray time course experimental data set centred on signalling networks up regulated in response to the onset of senescence, as they share overlapping signalling pathways. The modelling methodology was used to model the anthocyanin biosynthesis pathway. The model predicted the presence of AtMYB15 as a positive regulator of anthocyanin biosynthesis along with AtMYB90. Research carried out by Nichola Warner (Warner 2008) suggested that AtMYB90 was not essential for anthocyanin biosynthesis during senescence based on by comparing the phenotype of the MYB90 knock out, IM28, with the wild type (WT) Col-0 using a time course microarray. Models of networks of transcriptional regulation of the anthocyanin biosynthesis pathway for IM28 and WT implicate AtMYB29 as a positive regulator of anthocyanin biosynthesis

A bioinformatic analysis of genes involved in stress responses in Arabidopsis thaliana

Hyaloperonospora arabidopsidis is an obligate biotrophic oomycete shown to cause downy mildew in Arabidopsis thaliana. The main focus of this project is examining plant stress response and the strategies employed by H. arabidopsidis to infect Arabidopsis and evade plant stress responses. Two regions of the H. arabidopsidis genome containing genes expressed in planta during infection were bioinformatically annotated. The results indicated the genes were involved in regulatory processes associated with the pathogenicity of H. arabidopsidis but not a direct role in pathogenicity. H. arabidopsidis infects its host by secreting effector proteins into the cytoplasm and apoplastic space of the host. The secretome of H. arabidopsidis was analysed to identify classes of cysteine rich apoplastic effectors. This identified 15 candidate elicitin (ELI) and elicitin-like (ELL) sequences, three Kazal-like serine protease inhibitors and four candidates similar to the protein sequences of Ppats 14 and 24, expressed during infection. A second set of aims was to identify potential signalling networks up activated during plant defence responses to infection by H. arabidopsidis using a new model developed by Beal et al (Beal, Falciani et al. 2005) to eventually engineer transcriptional networks. Unfortunately this failed due to problems with the experiment. However, it was still possible to identify signalling networks from a second microarray time course experimental data set centred on signalling networks up regulated in response to the onset of senescence, as they share overlapping signalling pathways. The modelling methodology was used to model the anthocyanin biosynthesis pathway. The model predicted the presence of AtMYB15 as a positive regulator of anthocyanin biosynthesis along with AtMYB90. Research carried out by Nichola Warner (Warner 2008) suggested that AtMYB90 was not essential for anthocyanin biosynthesis during senescence based on by comparing the phenotype of the MYB90 knock out, IM28, with the wild type (WT) Col-0 using a time course microarray. Models of networks of transcriptional regulation of the anthocyanin biosynthesis pathway for IM28 and WT implicate AtMYB29 as a positive regulator of anthocyanin biosynthesis.EThOS - Electronic Theses Online ServiceBiotechnology and Biological Sciences Research Council (Great Britain) (BBSRC)GBUnited Kingdo

Interferon gamma responses to proteome-determined specific recombinant proteins: Potential as diagnostic markers for ovine Johne’s disease

Johne’s disease (JD), or paratuberculosis is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). There may be a long subclinical phase with no signs of clinical disease. Diagnosis of JD is problematic and no test can reliably detect sub-clinical disease. Th1 responses to Map are believed to be activated first with a later switch to Th2 responses and progression to clinical disease. Detection of a cell-mediated response, indicated by interferon gamma (IFN-) produced in response to mycobacterial antigens, may give an early indication of infection. Crude extracts of Map (PPDj) have been used to detect the cell-mediated response, but more specific, quantifiable antigens would improve the test. Thirty Map-specific proteins were screened for their ability to raise a cell-mediated response in subclinically infected sheep. Four proteins were selected and tested using blood from subclinical animals and controls from a JD-free flock. Three proteins elicited IFN- levels which were higher in the subclinical group than in the control group, two were statistically significant. Thus these proteins have the ability to discriminate groups of infected and uninfected animals and may have use in diagnosis of JD

High-resolution temporal profiling of transcripts during Arabidopsis leaf senescence reveals a distinct chronology of processes and regulation

Leaf senescence is an essential developmental process that impacts dramatically on crop yields and involves altered regulation of thousands of genes and many metabolic and signaling pathways, resulting in major changes in the leaf. The regulation of senescence is complex, and although senescence regulatory genes have been characterized, there is little information on how these function in the global control of the process. We used microarray analysis to obtain a highresolution time-course profile of gene expression during development of a single leaf over a 3-week period to senescence. A complex experimental design approach and a combination of methods were used to extract high-quality replicated data and to identify differentially expressed genes. The multiple time points enable the use of highly informative clustering to reveal distinct time points at which signaling and metabolic pathways change. Analysis of motif enrichment, as well as comparison of transcription factor (TF) families showing altered expression over the time course, identify clear groups of TFs active at different stages of leaf development and senescence. These data enable connection of metabolic processes, signaling pathways, and specific TF activity, which will underpin the development of network models to elucidate the process of senescence

Components, impacts and costs of dementia home support: a research programme including the DESCANT RCT

BackgroundOver half of people with dementia live at home. We know little about what home support could be clinically effective or cost-effective in enabling them to live well.ObjectivesWe aimed to (1) review evidence for components of home support, identify their presence in the literature and in services in England, and develop an appropriate economic model; (2) develop and test a practical memory support package in early-stage dementia, test the clinical effectiveness and cost-effectiveness of routine home support in later-stage dementia and design a toolkit based on this evidence; and (3) elicit the preferences of staff, carers and people with dementia for home support inputs and packages, and evaluate the cost-effectiveness of these approaches in early- and later-stage dementia.DesignWe undertook (1) an evidence synthesis, national surveys on the NHS and social care and an economic review; (2) a multicentre pragmatic randomised trial [Dementia Early Stage Cognitive Aids New Trial (DESCANT)] to estimate the clinical effectiveness and cost-effectiveness of providing memory aids and guidance to people with early-stage dementia (the DESCANT intervention), alongside process evaluation and qualitative analysis, an observational study of existing care packages in later-stage dementia along with qualitative analysis, and toolkit development to summarise this evidence; and (3) consultation with experts, staff and carers to explore the balance between informal and paid home support using case vignettes, discrete choice experiments to explore the preferences of people with dementia and carers between home support packages in early- and later-stage dementia, and cost–utility analysis building on trial and observational study.SettingThe national surveys described Community Mental Health Teams, memory clinics and social care services across England. Recruitment to the trial was through memory services in nine NHS trusts in England and one health board in Wales. Recruitment to the observational study was through social services in 17 local authorities in England. Recruitment for the vignette and preference studies was through memory services, community centres and carers’ organisations.ParticipantsPeople aged > 50 years with dementia within 1 year of first attendance at a memory clinic were eligible for the trial. People aged > 60 years with later-stage dementia within 3 months of a review of care needs were eligible for the observational study. We recruited staff, carers and people with dementia for the vignette and preference studies. All participants had to give written informed consent.Main outcome measuresThe trial and observational study used the Bristol Activities of Daily Living Scale as the primary outcome and also measured quality of life, capability, cognition, general psychological health and carers’ sense of competence.MethodsOwing to the heterogeneity of interventions, methods and outcome measures, our evidence and economic reviews both used narrative synthesis. The main source of economic studies was the NHS Economic Evaluation Database. We analysed the trial and observational study by linear mixed models. We analysed the trial by ‘treatment allocated’ and used propensity scores to minimise confounding in the observational study.ResultsOur reviews and surveys identified several home support approaches of potential benefit. In early-stage dementia, the DESCANT trial had 468 randomised participants (234 intervention participants and 234 control participants), with 347 participants analysed. We found no significant effect at the primary end point of 6 months of the DESCANT intervention on any of several participant outcome measures. The primary outcome was the Bristol Activities of Daily Living Scale, for which scores range from 0 to 60, with higher scores showing greater dependence. After adjustment for differences at baseline, the mean difference was 0.38, slightly but not significantly favouring the comparator group receiving treatment as usual. The 95% confidence interval ran from –0.89 to 1.65 (p = 0.56). There was no evidence that more intensive care packages in later-stage dementia were more effective than basic care. However, formal home care appeared to help keep people at home. Staff recommended informal care that cost 88% of formal care, but for informal carers this ratio was only 62%. People with dementia preferred social and recreational activities, and carers preferred respite care and regular home care. The DESCANT intervention is probably not cost-effective in early-stage dementia, and intensive care packages are probably not cost-effective in later-stage dementia. From the perspective of the third sector, intermediate intensity packages were cheaper but less effective. Certain elements may be driving these results, notably reduced use of carers’ groups.LimitationsOur chosen outcome measures may not reflect subtle outcomes valued by people with dementia.ConclusionsSeveral approaches preferred by people with dementia and their carers have potential. However, memory aids aiming to affect daily living activities in early-stage dementia or intensive packages compared with basic care in later-stage dementia were not clinically effective or cost-effective.Future workFurther work needs to identify what people with dementia and their carers prefer and develop more sensitive outcome measures.Study registrationCurrent Controlled Trials ISRCTN12591717. The evidence synthesis is registered as PROSPERO CRD42014008890.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 6. See the NIHR Journals Library website for further project information

Global development and diffusion of outcome evaluation research for interpersonal and self-directed violence prevention from 2007 to 2013: A systematic review

© 2014 The Authors. Published by Elsevier Ltd. Through a global review, we identified gaps in the geographical distribution of violence prevention evidence outcome evaluation studies and the types of violence addressed. Systematic literature searches identified 355 articles published between 2007 and 2013 that evaluated programs to prevent interpersonal or self-directed violence; focused on universal or selected populations; and reported outcomes measuring violence or closely related risk factors. The number of studies identified increased annually from 2008 (n = 37), reaching 64 in 2013. Over half (n = 203) of all studies focused on youth violence yet only one on elder maltreatment. Study characteristics varied by year and violence type. Only 9.3% of all studies had been conducted in LMICs. These studies were less likely than those in high income countries (HICs) to have tested established interventions yet more likely to involve international collaboration. Evaluation studies successfully established in LMIC had often capitalized on other major regional priorities (e.g. HIV). Relationships between violence and social determinants, communicable and non-communicable diseases, and even economic prosperity should be explored as mechanisms to increase the global reach of violence prevention research. Results should inform future research strategies and provide a baseline for measuring progress in developing the violence prevention evidence-base, especially in LMICs

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups

BACKGROUND: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders. METHODS/DESIGN: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress. DISCUSSION: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing

Introduction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67161/2/10.1177_0308275X9301300401.pd