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Quality early care and education (ECE) presents an unparalleled opportunity to avert disadvantage and promote children's development. Mealtimes are essential daily routines, yet are often overlooked in research on ECE quality. This paper crystallises a composite case study of ECE mealtimes in highly disadvantaged communities by combining Departing Radically in Academic Writing (DRAW) methodology with parent surveys, scorings of educator‐child interactions (inCLASS), and field notes. Poverty is perpetuated in these centres: children do not have enough food, and educator‐dictated feeding practices restrict children's opportunities to exercise their agency and learn. Systemic policy action is needed to address poverty in ECE. [ABSTRACT FROM AUTHOR]

Technology-dependent patients require interventions (eg, tracheostomies, gastrostomy tubes, or total parenteral nutrition) to survive. Such patients are commonly "turfed" between general services or from subspecialty to general services within the hospital. This case commentary proposes several explanations for why technologydependent patients are particularly susceptible to turfing, including clinicians' lack of familiarity with managing patients' technology, bias and ableism, and quality-of-life quandaries. It also addresses ways to combat turfing of technology-dependent patients and proposes educational strategies for managing common problems in the care of technology-dependent patients. [ABSTRACT FROM AUTHOR]

Sleep disorders are prevalent in children with Down Syndrome (DS). However, sleep treatment is not always readily accessed by this group. This study aims to understand families' experiences of having a child with DS and sleep difficulties, and in particular, their healthcare experiences, with the goal of informing practice improvements. We conducted semi-structured interviews with 34 parents (fathers n = 4 and mothers n = 30) with open-ended questions about parents' experiences of sleep, family dynamics, and healthcare. We operationalized a reflexive Thematic Analysis. Parents normalized their experiences of having a child with DS and sleep problems. Parents acknowledged that sleep disruption has adverse and pervasive impacts on their wellbeing and family dynamics, but also found this difficult to identify as a health problem. They accepted sleep difficulties as a regular part of bringing up any child, particularly one with a disability. When they did seek treatment for their child's sleep difficulties, parents often reported encountering insensitive and inadequate care and described that, at times, healthcare professionals also normalized children's sleep difficulties, resulting in sub-optimal treatment. This included at times failure to refer to tertiary sleep medicine services when required. Parents' and healthcare professionals' normalization of sleeping difficulties denies that they are both deleterious and modifiable. Practice implications include raising healthcare professionals' awareness of the importance of proactively addressing sleep, with sensitivity to families' normalization strategies, recognizing that families may require prompting to report concerns. [ABSTRACT FROM AUTHOR]

Families of children with Down syndrome experience complex lives and needs, yet the few existing studies on these families are written in conventional academic prose that is not optimal for knowledge translation beyond academia, particularly for busy healthcare professionals. In this paper, we Depart Radically in Academic Writing (DRAW) (Mackinlay, 2022) and present data poetry and two case studies that draw upon semi-structured interviews with mothers, fathers, and siblings, who were interviewed separately about their experiences of having a child/sibling with Down syndrome. We introduce our interdisciplinary team that includes academics and clinicians to contextualise our focus on research translation. We demonstrate that writing with creative criticality (i.e. 'DRAWing') contributes an embodied and affective understanding of research participants' stories, which is largely lacking in the academic literature on families of children with Down syndrome and the sociology of health and illness field more broadly. Moreover, DRAWing can impact audiences emotionally as well as intellectually (Richardson, 2003, p. 924), which has important knowledge translation implications for both healthcare professionals and these families. DRAWing can capture healthcare professionals' attention, prompting them to critically reflect on their practices and opportunities for improving care and treatment for these families. [ABSTRACT FROM AUTHOR]

In early childhood education and care policy, there are two dominant discourses: 'investment and outcomes' and 'children's rights'. There is little research on how these discourses play out in educators' accounts. In this article, the authors examine the case of discourse pertaining to children's relaxation in early childhood education and care. They demonstrate that Australian relaxation policy for children in early childhood education and care constructs children as passive and incompetent subjects. Some educators reproduce early childhood education and care policy tensions by vacillating between investment-outcomes and children's rights discourse in their accounts, while other educators deviate from the policy constructions and adopt children's rights discourse. [ABSTRACT FROM AUTHOR]

Qualitative researchers can discard data that are unsaturated or unrelated to research questions, but what do we do when these data affect us, or 'haunt' us, 'long after collecting "it"' (Taylor 2013, 691)? In this paper, we draw upon Sara Ahmed to guide our engagement with 'discarded data': young children's gendered accounts of violence that unexpectedly arose during interviews about rest-time and relaxation in childcare. We show what it feels like to be affected by children's accounts throughout the non-linear and zig-zagged 'data analysis' processes. Applying Ahmed's conceptualisation of power as 'directionality', we critique the power of qualitative research conventions to define our focus as researchers and pay attention to what children raise: how they are directed towards gendered futures. We find that, in children's accounts of violence, boys have more agency than girls as they participate in – and respond to – violence. [ABSTRACT FROM AUTHOR]

This paper critically explores the working culture of legal aid lawyers and develops a novel 'Shared Orientation' model to better understand contemporary legal aid work and its workers. Set within a context of changing professional identities, a shrinking industry and financial constraints, the paper draws on ethnographic and interview data conducted with a high-street firm, multiple courtrooms and a law centre. It examines the emerging relevance and applicability of this new conceptual lens, refocusing the gaze on working life in fissured legal workplaces. It is argued that the 'Shared Orientation' model upholds multiple functions. Firstly, it captures the cultural heterogeneity of the legal aid profession, across civil-criminal and solicitor-barrister remits alike. Secondly, the model functions as a form of cohesive coping mechanism in response to the changing professional identity of the legal aid lawyers. Moreover, the 'Shared Orientation' offers unity as a way of functioning in an otherwise fragmented profession through its preservation of working culture ideals. [ABSTRACT FROM AUTHOR]

Background: As 'disease detectives' and directors of public health programs, field epidemiologists play essential roles in protecting public health. Although ethical issues receive considerable attention in medical and research settings, less is known about ethical challenges faced by field epidemiologists in public health programs. Similarly, little is known about moral distress among field epidemiologists, i.e., situations in which they are constrained from acting on what they know to be morally right. Moral distress is strongly associated with empathy fatigue, burnout, reduced job retention, and disengagement. To better understand ethics training needs for field epidemiologists, in February 2019, members of TEPHIConnect, an online and mobile networking platform for Field Epidemiology Training Program (FETP) alumni, were invited to participate in an anonymous survey about ethical challenges and moral distress.Results: Among 126 respondents from 54 countries, leading causes of ethical dilemmas included inadequate informed consent (61%), inequitable allocation of resources (49%), and conflicts of interest (43%). These occur primarily in settings of disease outbreaks (60%); research (55%); and public health programs at the state, province, or national level (45%) or community level (43%). Work-related moral distress was reported by 91% of respondents, including 26% who experience it "frequently" or "almost always." Field epidemiologists working in low- and low-middle income countries were more likely to report moral distress "frequently" or "almost always" than those in higher-income countries (33.0% vs 9.1%, P = 0.006). The most common perceived contributors to moral distress included excessive stress and work demands (30%) and inadequate support from leaders (25%).Conclusions: Field epidemiologists face significant work-related ethical challenges, which are endemic to public health and political systems. A substantial proportion of field epidemiologists also experience some degree of moral distress, often in association with these challenges. These findings indicate an unmet need among field epidemiologists for support in navigating ethical challenges, as well as for resources to address the human and professional consequences of moral distress. [ABSTRACT FROM AUTHOR]

Although many coho salmon (Oncorhynchus kisutch) caught in recreational fisheries are harvested, a substantial number of salmon are released after capture. Mortality rates of coho salmon released from recreational fisheries are largely unknown in the marine environment. This two-year study investigated factors associated with post-release mortality and travel rate of coho salmon in a marine recreational fishery in British Columbia, Canada. Adult coho salmon were recreationally angled in the marine environment, affixed with acoustic tags, and tracked during their return migration to natal spawning streams using a network of acoustic receivers. We found post-release mortality to the first point of detection (∼50 km from release) was 31.5% (95% CI: 26.1 – 37.4%; n = 279). Scale loss, eye damage, bleeding, and smaller body size of coho salmon were associated with increased odds of mortality. Scale loss and smaller body size were also associated with slower migration rate post-release. Air exposure up to five minutes was not found to be a driving factor in mortality or travel rate. These fishing-related injuries can cause immediate physiological and behavioural disturbances, increase vulnerability to predation, infection, and disease, and delay migration as the fish recovers. Smaller coho salmon may also be less capable of overcoming capture stress. Our study highlights the importance of quantifying mortality of wild fish in their natural environment, and we suggest that small changes to fishing practices (e.g., smaller hook sizes, less handling, etc.) could make large differences in release survival thus encouraging a more sustainable recreational fishery. [ABSTRACT FROM AUTHOR]

The international quality-improvement agenda for Early Childhood Education (ECE) directs attention to maximising children's learning experiences. Yet routines, and particularly those relating to sleep-rest provision, are not well conceptualised as learning opportunities. Often children who no longer sleep in the daytime are required to lie down without alternative activity. Educator discourse frames these practices as 'teaching self-regulation', yet these experiences afford little opportunity for child-directed learning, and both observational and cortisol studies suggest the potential for negative learning experiences. Prior studies have examined children's emotional response and identified sleep-rest time as disliked, but have not examined children's accounts of learning. In this study, we analyse accounts of learning from 54 children (mean age = 56 months). Collectively, the children identified three learnings. Most children learned that adults regulate sleep-rest opportunities through instruction, reward, punishment and priveledge. Some children reported learning coping strategies including imagination and subversion. A rare few identitfied learning to self-regulate. The findings identify a discrepancy between policy aspiration and educator intent, that foreground self-regulation and the de facto lessons children draw from their sleep-rest experiences. Our findings identify standard sleep-rest provision as sub-optimal and the imperative to view care routines, such as sleep-rest, as opportunities for learning. [ABSTRACT FROM AUTHOR]

Researchers and policy‐makers are increasingly concerned with children's well‐being in Early Childhood Education and Care (ECEC) and Outside School Hours Care (OSHC) settings. Recent research identifies the value of using qualitative methods to understand children's experiences of well‐being in ECEC/OSHC, but there remain few such studies. This article presents findings from a child‐centric qualitative study with Australian children of nurses and police, which sought to understand their experiences of well‐being in ECEC/OSHC. Children's experiences of well‐being were shaped by parental relationships, how informed they were about the rationale for their care arrangements and the degree of age‐appropriate autonomy they experienced. [ABSTRACT FROM AUTHOR]

Selectively removing fish based on particular traits, such as body size, may shift trait abundance in the remaining population, resulting in a phenomenon called fisheries-induced evolution. Recently, there is growing interest in evaluating the effects of fisheries-induced evolution on fish behaviour. Aquatic protected areas (APAs) have been designated in some habitats in efforts to prohibit harvesting and maintain natural ranges of phenotypic variation for impacted species. Here, we attempted to test whether APAs that prohibit all forms of fishing have an evolutionary influence on adult largemouth bass (Micropterus salmoides) behaviour by investigating the relationship between capture method and behavioural type. Fish, caught via active (angling) and passive (hoop net) capture techniques in both protected (70+ year old APAs in eastern Ontario) and adjacent nonprotected areas, were subjected to standard tests of boldness (refuge emergence, general activity, and flight-initiation-distance). A behavioural syndrome characterized by consistent within-individual variation and correlation of boldness behaviours (activity and refuge emergence) was present. Our results provide evidence that APAs may promote behavioural diversification and protect traits selectively targeted by recreational angling. [ABSTRACT FROM AUTHOR]

We live in an era of abundant data. This has necessitated the development of new and innovative statistical algorithms to get the most from experimental data. For example, faster algorithms make practical the analysis of larger genomic data sets, allowing us to extend the utility of cutting-edge statistical methods. We present a randomised algorithm that accelerates the clustering of time series data using the Bayesian Hierarchical Clustering (BHC) statistical method. BHC is a general method for clustering any discretely sampled time series data. In this paper we focus on a particular application to microarray gene expression data. We define and analyse the randomised algorithm, before presenting results on both synthetic and real biological data sets. We show that the randomised algorithm leads to substantial gains in speed with minimal loss in clustering quality. The randomised time series BHC algorithm is available as part of the R package BHC, which is available for download from Bioconductor (version 2.10 and above) via http://bioconductor.org/packages/2.10/bioc/html/BHC.html. We have also made available a set of R scripts which can be used to reproduce the analyses carried out in this paper. These are available from the following URL. https://sites.google.com/site/randomisedbhc/. [ABSTRACT FROM AUTHOR]

Background: Exercise-based therapy is known to enhance motor recovery after stroke but the most appropriate amount, i.e. the dose, of therapy is unknown. To determine the strength of current evidence for provision of a higher dose of the same types of exercise-based therapy to enhance motor recovery after stroke. Methods: An electronic search of: MEDLINE, EMBASE, CINHAL, AMED, and CENTRAL was undertaken. Two independent reviewers selected studies using predetermined inclusion criteria: randomised or quasi randomised controlled trials with or without blinding of assessors; adults, 18+ years, with a clinical diagnosis of stroke; experimental and control group interventions identical except for dose; exercise-based interventions investigated; and outcome measures of motor impairment, movement control or functional activity. Two reviewers independently extracted outcome and follow-up data. Effect sizes and 95% confidence intervals were interpreted with reference to risk of bias in included studies. Results: 9 papers reporting 7 studies were included. Only 3 of the 7 included studies had all design elements assessed as low risk of bias. Intensity of the control intervention ranged from a mean of 9 to 28 hours over a maximum of 20 weeks. Experimental groups received between 14 and 92 hours of therapy over a maximum of 20 weeks. The included studies were heterogeneous with respect to types of therapy, outcome measures and time-points for outcome and follow-up. Consequently, most effect sizes relate to one study only. Single study effect sizes suggest a trend for better recovery with increased dose at the end of therapy but this trend was less evident at follow-up Meta-analysis was possible at outcome for: hand-grip strength, -10.1 [-19.1,-1.2] (2 studies, 97 participants); Action Research Arm Test (ARAT), 0.1 [-5.7,6.0] (3 studies, 126 participants); and comfortable walking speed, 0.3 [0.1,0.5] (2 studies, 58 participants). At follow-up, between 12 and 26 weeks after start of therapy, meta-analysis findings were: Motricity Arm, 10.7 [1.7,19.8] (2 studies, 83 participants); ARAT, 2.2 [-6.0,10.4] (2 studies, 83 participants); Rivermead Mobility, 1.0 [-0.6, 2.5] (2 studies, 83 participants); and comfortable walking speed, 0.2 [0.0,0.4] (2 studies, 60 participants). Conclusions: Current evidence provides some, but limited, support for the hypothesis that a higher dose of the same type of exercised-based therapy enhances motor recovery after stroke. Prospective dose-finding studies are required. [ABSTRACT FROM AUTHOR]

Abstract: A major challenge in systems biology is the ability to model complex regulatory interactions, such as gene regulatory networks, and a number of computational approaches have been developed over recent years to address this challenge. This paper reviews a number of these approaches, with a focus on probabilistic graphical models and the integration of diverse data sets, such as gene expression and transcription factor binding site location and activity. [Copyright &y& Elsevier]

This paper takes an international perspective on the marketing of alcohol to young people by examining case studies of the marketing of alcohol in the UK and Poland. It is suggested that marketing is a powerful mechanism for attracting young consumers. The alcohol industry is an innovative industry able to use a wide variety of marketing tools to achieve success in the market-place. It is important to recognise that the marketing activities of the industry are becoming increasingly transnational and that policy response has to be equally transnational. [ABSTRACT FROM AUTHOR]

Background: Preventive chemotherapy (PC) is a central strategy for control and elimination of neglected tropical diseases (NTDs). Increased emphasis has been given to "integration" of NTD programs within health systems and coadministration of NTD drugs offers significant programmatic benefits. Guidance from the World Health Organization (WHO) reflects current evidence for safe drug coadministration and highlights measures to prevent choking of young children during PC. Methodology: To understand how coadministration of NTD drugs might affect PC safety, we reviewed literature on choking risk in young children and safety of coadministered NTD drugs. To understand current practices of drug coadministration, we surveyed 15 NTD program managers and implementing partners. Principal findings: In high-income countries, choking on medication is an infrequent cause of death in young children. In low-resource settings, data are limited, but age-appropriate drug formulations are less available. During PC, fatal choking, although infrequent, occurs primarily in young children; forcing them to swallow tablets appears to be the major risk factor. The WHO currently recommends 6 drugs and 5 possible drug combinations for use in PC. Of 105 nations endemic for the 5 PC-NTDs, 72 (68.6%) are co-endemic for 2 or more diseases and could benefit from drug coadministration during PC. All 15 survey respondents reported coadministering medications during PC. Reported responses to a child refusing to take medicine included: not forcing the child to do so (60.0%), encouraging the child (46.7%), bringing the child back later (26.7%), offering powder for oral suspension (POS) for azithromycin (13.3%), and having parents or community members intervene to calm the child (6.7%). Conclusions: Coadministration of NTD drugs during PC appears to be increasingly common. Safety of coadministered PC drugs requires attention to choking prevention, use of approved drug combinations, and increased access to age-appropriate drug formulations. [ABSTRACT FROM AUTHOR]

• Young children have sensory-rich conceptualisations and experiences of relaxation. • Children's relaxation accounts contrast from the dominant medicalised discourses. • Children must be afforded agency to choose where, when, and how they relax. • Carers and educators should consult with children about relaxation preferences. Relaxation is constructed as a health issue, often as a counter to stress. Such constructions serve to medicalise relaxation as a physiological or psychological treatment for stressful experiences. Yet, children's experiences and understandings of relaxation are not well documented and may differ from these prevailing adult conceptualisations. Situated within the sociology of childhood paradigm, this study investigated: How do young children attending childcare experience relaxation? Informed by a child-centric methodology, in 2018, we conducted drawing-prompted group interviews with 46 child participants aged three to five years old recruited from six childcare services in Brisbane, Australia. Children were asked about what it means to relax and what they did to relax. We found that children clearly articulated their relaxation experiences and conceptualised relaxation as sensory-rich experiences that centred on feelings of cosiness, comfortableness, and air temperature. Places and play were key to shaping children's relaxation experiences: common places for relaxation were in nature or at home, and various types of play were central. Recommendations for improving care practices include engaging children in conversations about their relaxation preferences, and affording children agency to choose experiences that are relaxing when in childcare settings. [ABSTRACT FROM AUTHOR]

The influence of alcohol advertising on young people continues to be the subject of much debate. This paper presents a review of the literature showing that, while many econometric studies suggest little effect, more focused consumer studies, especially recent ones with sophisticated designs, do show clear links between advertising and behaviour. Furthermore, these effects have to be viewed in combination with the possible impact of other marketing activities such as price promotions, distribution, point of sale activity and new product development. Here, the evidence base is less well developed, but there are indications of effects. It must be acknowledged that categorical statements of cause and effect are always difficult in the social sciences; marketing is a complex phenomenon involving the active participation of consumers as well as marketers and more research is needed on its cumulative impact. Nonetheless, the literature presents an increasingly compelling picture that alcohol marketing is having an effect on young people's drinking. [ABSTRACT FROM AUTHOR]

Background: Early childhood education and care (ECEC) services have the potential to influence or disrupt sleep patterns given that ECEC attendance coincides with the normative transition towards napping cessation. Objective: In light of the evidence that sleep patterns in early childhood are foundational to lifelong health, this study investigated parent–educator communication about children's 24-h sleep cycles. Communication is critical in ensuring regularity and responsiveness to children's sleep behaviours, yet knowledge about if and how this happens is limited. We sought to address this gap. Method: This study draws upon survey data, both numeric and text, from 116 parents and 39 educators across 25 ECEC services in Brisbane, Australia. The type and regularity of communication strategies between ECEC educators and parents were analysed to establish frequency and demographic patterning. Qualitative analyses investigated the content of sleep-related communication between educators and parents. Results: Most educators and parents reported discussing children's sleep through in-person communication at pick-up and drop-off times. Qualitative analysis of the content of parent–educator communication identified three key themes: sleep quantity, quality and practices. Communication focused primarily on the quantity of children's sleep while attending ECEC settings, and communication about sleep quality and home practices were less frequent. Educators communicated more sleep-related information with parents than parents did with educators. Conclusions: This study highlights the need for frequent, bi-directional parent–educator communication. Providing practices which support regularity of sleep across home and ECEC settings and responding to the developmental transition toward napping cessation promotes children's sleep health. [ABSTRACT FROM AUTHOR]

The mobility and agency of the unemployed have rarely been examined together in welfare administration. Mobility research has much to offer the (im)mobility of low-skilled and unemployed workers. The article begins by critically examining dominant public discourse and policy reforms that stigmatise the assumed immobility of the unemployed. Drawing on empirical data from in-depth interviews with people on income support payments in Australia, it then offers a critical view on the mobility decision-making processes of these job-seekers. Building on previous research concerning the politics of mobility, it shows that structural inequalities impact mobility choices, making relocation difficult for many job-seekers. At the same time, it highlights the localised mobility that job search now involves, complicating orthodox associations between mobility and power – as well as assumptions that job-seekers are immobile. [ABSTRACT FROM AUTHOR]

Wildlife are exposed to neurotoxic mercury at locations distant from anthropogenic emission sources because of long-range atmospheric transport of this metal. In this study, mercury bioaccumulation in insectivorous bat species (Mammalia: Chiroptera) was investigated on a broad geographic scale in Canada. Fur was analyzed (n = 1178) for total mercury from 43 locations spanning 20° latitude and 77° longitude. Total mercury and methylmercury concentrations in fur were positively correlated with concentrations in internal tissues (brain, liver, kidney) for a small subset (n = 21) of little brown bats ( Myotis lucifugus ) and big brown bats ( Eptesicus fuscus ), validating the use of fur to indicate internal mercury exposure. Brain methylmercury concentrations were approximately 10% of total mercury concentrations in fur. Three bat species were mainly collected (little brown bats, big brown bats, and northern long-eared bats [ M. septentrionalis ]), with little brown bats having lower total mercury concentrations in their fur than the other two species at sites where both species were sampled. On average, juvenile bats had lower total mercury concentrations than adults but no differences were found between males and females of a species. Combining our dataset with previously published data for eastern Canada, median total mercury concentrations in fur of little brown bats ranged from 0.88–12.78 μg/g among 11 provinces and territories. Highest concentrations were found in eastern Canada where bats are most endangered from introduced disease. Model estimates of atmospheric mercury deposition indicated that eastern Canada was exposed to greater mercury deposition than central and western sites. Further, mean total mercury concentrations in fur of adult little brown bats were positively correlated with site-specific estimates of atmospheric mercury deposition. This study provides the largest geographic coverage of mercury measurements in bats to date and indicates that atmospheric mercury deposition is important in determining spatial patterns of mercury accumulation in a mammalian species. [ABSTRACT FROM AUTHOR]

The design and synthesis of a novel series of 2,6-disubstituted pyrazine derivatives as CK2 kinase inhibitors is described. Structure-guided optimization of a 5-substituted-3-thiophene carboxylic acid screening hit ( 3a ) led to the development of a lead compound ( 12b ), which shows inhibition in both enzymatic and cellular assays. Subsequent design and hybridization efforts also led to the unexpected identification of analogs with potent PIM kinase activity ( 14f ). [ABSTRACT FROM AUTHOR]

A model is presented describing the gene regulatory network surrounding three similar NAC transcription factors that have roles in Arabidopsis leaf senescence and stress responses. ANAC019, ANAC055 and ANAC072 belong to the same clade of NAC domain genes and have overlapping expression patterns. A combination of promoter DNA/protein interactions identified using yeast 1-hybrid analysis and modelling using gene expression time course data has been applied to predict the regulatory network upstream of these genes. Similarities and divergence in regulation during a variety of stress responses are predicted by different combinations of upstream transcription factors binding and also by the modelling. Mutant analysis with potential upstream genes was used to test and confirm some of the predicted interactions. Gene expression analysis in mutants of ANAC019 and ANAC055 at different times during leaf senescence has revealed a distinctly different role for each of these genes. Yeast 1-hybrid analysis is shown to be a valuable tool that can distinguish clades of binding proteins and be used to test and quantify protein binding to predicted promoter motifs. [ABSTRACT FROM AUTHOR]

Transcriptional reprogramming forms a major part of a plant's response to pathogen infection. Many individual components and pathways operating during plant defense have been identified, but our knowledge of how these different components interact is still rudimentary. We generated a high-resolution time series of gene expression profiles from a single Arabidopsis thaliana leaf during infection by the necrotrophic fungal pathogen Botrytis cinerea. Approximately one-third of the Arabidopsis genome is differentially expressed during the first 48 h after infection, with the majority of changes in gene expression occurring before significant lesion development. We used computational tools to obtain a detailed chronology of the defense response against B. cinerea , highlighting the times at which signaling and metabolic processes change, and identify transcription factor families operating at different times after infection. Motif enrichment and network inference predicted regulatory interactions, and testing of one such prediction identified a role for TGA3 in defense against necrotrophic pathogens. These data provide an unprecedented level of detail about transcriptional changes during a defense response and are suited to systems biology analyses to generate predictive models of the gene regulatory networks mediating the Arabidopsis response to B. cinerea. [ABSTRACT FROM AUTHOR]

Early identification of toxicity associated with new chemical entities is important for reducing compound attrition in late stage drug discovery. Activation of the aryl hydrocarbon receptor (AhR) by xenobiotics is a recognised mechanism of toxicity: the AhR mediates most, if not all, of the serious toxicities caused by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In addition to compounds such as TCDD, the AhR can be activated by compounds with drug-like properties; consequently there is a desire to eliminate AhR activity in candidate drug programs. Endogenous AhR translocates from the cytoplasm to the nucleus in response to prototypical AhR ligands. This trafficking was monitored in mouse Hepa-1 cells, human HepG2 cells and rat primary hepatocytes using an anti-AhR antibody. A confocal imaging plate reader, the InCell® Analyzer 3000, was used to image fixed cells cultured in 96 well plates, and algorithms were used to analyse both population data and individual cell responses. The subsequent induction of the CYP1A1 gene, in the three cell models, was also assessed using quantitative real-time polymerase chain reaction and showed good correlation with the translocation assay. To conclude, we have established robust, automated high throughput assays for the identification of AhR activators in primary hepatocytes and cell lines. [ABSTRACT FROM AUTHOR]

The original version of the article was unfortunately published without displaying the blinded contents. [ABSTRACT FROM AUTHOR]