The transcription factors Egr1 and Egr2 have opposing influences on adipocyte differentiation.

The zinc finger-containing transcription factors Egr1 (Krox24) and Egr2 (Krox20) have been implicated in the proliferation and differentiation of many cell types. Egr2 has earlier been shown to play a positive role in adipocyte differentiation, but the function of Egr1 in this context is unknown. We compared the roles of Egr1 and Egr2 in the differentiation of murine 3T3-L1 adipocytes. Egr1 protein was rapidly induced after addition of differentiation cocktail, whereas Egr2 protein initially remained low before increasing on days 1 and 2, concomitant with the disappearance of Egr1. In marked contrast to the effects of Egr2, differentiation was inhibited by ectopic expression of Egr1 and potentiated by knockdown of Egr1. The pro-adipogenic effects of Egr1 knockdown were particularly notable when isobutylmethylxanthine (IBMX) was omitted from the differentiation medium. However, knockdown of Egr1 did not affect CCAAT/enhancer binding protein (C/EBP)beta protein expression or phosphorylation of CREB Ser133. Further, Egr1 did not directly affect the activity of promoters for the master adipogenic transcription factors, C/EBPalpha or peroxisome proliferator-activated receptor-gamma2, as assessed in luciferase reporter assays. These data indicate that Egr1 and Egr2 exert opposing influences on adipocyte differentiation and that the careful regulation of both is required for maintaining appropriate levels of adipogenesis. Further, the pro-differentiation effects of IBMX involve suppression of the inhibitory influence of Egr1

Care planning for consumers on community treatment orders: an integrative literature review

Background Case management is the established model for care provision in mental health and is delivered within current care philosophies of person-centred and recovery-oriented care. The fact that people with a mental illness may be forced to receive care and treatment in the community poses challenges for clinicians aiming to engage in approaches that promote shared decision-making and self-determination. This review sought to gain an in-depth understanding of stakeholders’ perspectives and experiences of care planning for consumers’ on CTOs. Methods An integrative review method allowed for inclusion of a broad range of studies from diverse empirical sources. Systematic searches were conducted across six databases. Following appraisal, findings from included papers were coded into groups and presented against a framework of case management. Results Forty-eight papers were included in the review. Empirical studies came from seven countries, with the majority reporting on qualitative methods. Many similarities were reported across studies. Positive gains from CTOs were usually associated with the nature of support received, highlighting the importance of the therapeutic relationship in care planning. Key gaps in care planning included a lack of connection between CTO, treatment and consumer goals and lack of implementation of focussed interventions. Conclusions Current case management processes could be better utilised for consumers on CTOs, with exploration of how this could be achieved warranted. Workers need to be sensitive to the ‘control and care’ dynamic in the care planning relationship, with person-centred approaches requiring core and advanced practitioner and communication skills, including empathy and trust

The Importance of Tree Size and Fecundity for Wind Dispersal of Big-Leaf Mahogany

Seed dispersal by wind is a critical yet poorly understood process in tropical forest trees. How tree size and fecundity affect this process at the population level remains largely unknown because of insufficient replication across adults. We measured seed dispersal by the endangered neotropical timber species big-leaf mahogany (Swietenia macrophylla King, Meliaceae) in the Brazilian Amazon at 25 relatively isolated trees using multiple 1-m wide belt transects extended 100 m downwind. Tree diameter and fecundity correlated positively with increased seed shadow extent; but in combination large, high fecundity trees contributed disproportionately to longer-distance dispersal events (>60 m). Among three empirical models fitted to seed density vs. distance in one dimension, the Student-t (2Dt) generally fit best (compared to the negative exponential and inverse power). When seedfall downwind was modelled in two dimensions using a normalised sample, it peaked furthest downwind (c. 25 m) for large, high-fecundity trees; with the inverse Gaussian and Weibull functions providing comparable fits that were slightly better than the lognormal. Although most seeds fell within 30 m of parent trees, relatively few juveniles were found within this distance, resulting in juvenile-to-seed ratios peaking at c. 35–45 m. Using the 2Dt model fits to predict seed densities downwind, coupled with known fecundity data for 2000–2009, we evaluated potential Swietenia regeneration near adults (≤30 m dispersal) and beyond 30 m. Mean seed arrival into canopy gaps >30 m downwind was more than 3× greater for large, high fecundity trees than small, high-fecundity trees. Tree seed production did not necessarily scale up proportionately with diameter, and was not consistent across years, and this resulting intraspecific variation can have important consequences for local patterns of dispersal in forests. Our results have important implications for management and conservation of big-leaf mahogany populations, and may apply to other threatened wind-dispersed Meliaceae trees

The Natural Product Domain Seeker NaPDoS: A Phylogeny Based Bioinformatic Tool to Classify Secondary Metabolite Gene Diversity

New bioinformatic tools are needed to analyze the growing volume of DNA sequence data. This is especially true in the case of secondary metabolite biosynthesis, where the highly repetitive nature of the associated genes creates major challenges for accurate sequence assembly and analysis. Here we introduce the web tool Natural Product Domain Seeker (NaPDoS), which provides an automated method to assess the secondary metabolite biosynthetic gene diversity and novelty of strains or environments. NaPDoS analyses are based on the phylogenetic relationships of sequence tags derived from polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes, respectively. The sequence tags correspond to PKS-derived ketosynthase domains and NRPS-derived condensation domains and are compared to an internal database of experimentally characterized biosynthetic genes. NaPDoS provides a rapid mechanism to extract and classify ketosynthase and condensation domains from PCR products, genomes, and metagenomic datasets. Close database matches provide a mechanism to infer the generalized structures of secondary metabolites while new phylogenetic lineages provide targets for the discovery of new enzyme architectures or mechanisms of secondary metabolite assembly. Here we outline the main features of NaPDoS and test it on four draft genome sequences and two metagenomic datasets. The results provide a rapid method to assess secondary metabolite biosynthetic gene diversity and richness in organisms or environments and a mechanism to identify genes that may be associated with uncharacterized biochemistry

Recommendations for the design of laboratory studies on non-target arthropods for risk assessment of genetically engineered plants

This paper provides recommendations on experimental design for early-tier laboratory studies used in risk assessments to evaluate potential adverse impacts of arthropod-resistant genetically engineered (GE) plants on non-target arthropods (NTAs). While we rely heavily on the currently used proteins from Bacillus thuringiensis (Bt) in this discussion, the concepts apply to other arthropod-active proteins. A risk may exist if the newly acquired trait of the GE plant has adverse effects on NTAs when they are exposed to the arthropod-active protein. Typically, the risk assessment follows a tiered approach that starts with laboratory studies under worst-case exposure conditions; such studies have a high ability to detect adverse effects on non-target species. Clear guidance on how such data are produced in laboratory studies assists the product developers and risk assessors. The studies should be reproducible and test clearly defined risk hypotheses. These properties contribute to the robustness of, and confidence in, environmental risk assessments for GE plants. Data from NTA studies, collected during the analysis phase of an environmental risk assessment, are critical to the outcome of the assessment and ultimately the decision taken by regulatory authorities on the release of a GE plant. Confidence in the results of early-tier laboratory studies is a precondition for the acceptance of data across regulatory jurisdictions and should encourage agencies to share useful information and thus avoid redundant testing

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700