Transcription controls growth, cell kinetics and cholesterol supply to sustain ACTH responses

Chronic ACTH exposure is associated with adrenal hypertrophy and steroidogenesis. The underlying molecular processes in mice have been analysed by microarray, histological and immunohistochemical techniques. Synacthen infused for 2 weeks markedly increased adrenal mass and plasma corticosterone levels. Microarray analysis found greater than 2-fold changes in expression of 928 genes (P < 0.001; 397 up, 531 down). These clustered in pathways involved in signalling, sterol/lipid metabolism, cell proliferation/hypertrophy and apoptosis. Signalling genes included some implicated in adrenal adenomas but also upregulated genes associated with cyclic AMP and downregulated genes associated with aldosterone synthesis. Sterol metabolism genes were those promoting cholesterol supply (Scarb1, Sqle, Apoa1) and disposal (Cyp27a1, Cyp7b1). Oil red O staining showed lipid depletion consistent with reduced expression of genes involved in lipid synthesis. Genes involved in steroidogenesis (Star, Cyp11a1, Cyp11b1) were modestly affected (P < 0.05; <1.3-fold). Increased Ki67, Ccna2, Ccnb2 and Tk1 expression complemented immunohistochemical evidence of a 3-fold change in cell proliferation. Growth arrest genes, Cdkn1a and Cdkn1c, which are known to be active in hypertrophied cells, were increased >4-fold and cross-sectional area of fasciculata cells was 2-fold greater. In contrast, genes associated with apoptosis (eg Casp12, Clu,) were downregulated and apoptotic cells (Tunel staining) were fewer (P < 0.001) and more widely distributed throughout the cortex. In summary, long-term steroidogenesis with ACTH excess is sustained by genes controlling cholesterol supply and adrenal mass. ACTH effects on adrenal morphology and genes controlling cell hypertrophy, proliferation and apoptosis suggest the involvement of different cell types and separate molecular pathways

An index to track the ecological effects of drought development and recovery on riverine invertebrate communities

© 2017 Elsevier Ltd In rivers, the ecological effects of drought typically result in gradual adjustments of invertebrate community structure and functioning, punctuated by sudden changes as key habitats, such as wetted channel margins, become dewatered and dry. This paper outlines the development and application of a new index (Drought Effect of Habitat Loss on Invertebrates – DEHLI) to quantify the effects of drought on instream macroinvertebrate communities by assigning weights to taxa on the basis of their likely association with key stages of channel drying. Two case studies are presented, in which the DEHLI index illustrates the ecological development of drought conditions and subsequent recovery. These examples demonstrate persistent drought effects months or several years after river flows recovered. Results derived using DEHLI are compared with an established macroinvertebrate flow velocity-reactive index (Lotic-invertebrate Index for Flow Evaluation – LIFE score) and demonstrates its greater sensitivity to drought conditions. Data from a number of rivers in south east England were used to calibrate a statistical model, which was then used to examine the response of DEHLI and LIFE to a hypothetical multi-year drought. This demonstrated a difference in response between sampling seasons, with the spring model indicating a lagged response due to delayed recolonisation and the autumn model differentiating habitat loss and flow velocity-driven responses. The application of DEHLI and the principles which underlie it allow the effects of drought on instream habitats and invertebrates associated with short or long term weather patterns to be monitored, whilst also allowing the identification of specific locations where intervention via river restoration, or revision of existing abstraction licensing, may be required to increase resilience to the effect of anthropogenic activities exacerbated by climate change

Understanding Middle Neolithic food and farming in and around the Stonehenge World Heritage Site: an integrated approach

Little synthesis of evidence for Middle Neolithic food and farming in Wiltshire, particularly in and around the Stonehenge World Heritage Site (WHS) has been possible, until now, due to a paucity of assemblages. The excavation of a cluster of five Middle Neolithic pits and an inhumation burial at West Amesbury Farm (WAF) has prompted a review of our understanding of pit sites of this period from the county. Bioarchaeological assemblages are used to investigate evidence for the consumption of animal and plant-based foods, and for agricultural and pastoral farming. For the first time Middle Neolithic zooarchaeological evidence, including strontium isotope data, is considered alongside archaeobotanical data, and radiocarbon dating. The absence of cultivated plants from WAF and contemporary sites in the county is consistent with the hypothesis that the reduction in cereal cultivation and greater reliance of wild plants witnessed in the later part of the Neolithic in southern England began in the Middle Neolithic. The zooarchaeological evidence from the same sites demonstrates that the shift away from cereal cultivation may be concurrent with, rather than earlier than, an increase in the relative proportion of deposited pig bones relative to cattle. Both cattle and pigs deposited in pits at WAF have strontium and sulphur isotope values consistent with the local biosphere, and therefore were potentially raised in the area. Zooarchaeological data from WAF compliments that from human dental calculus and lipid residues in associated Peterborough Ware pottery that local cattle husbandry included exploitation of dairy. It also highlights the presence of consistent food preparation methods between pits as seen through butchery practice. The faunal and archaeobotanical remains from contemporary pit deposits suggest that similar farming and subsistence strategies can be proposed across the county, though with some inter-site variation in deposition. Together these excavated pit sites are likely to represent only a sample of those present in the area. Application of a similar integrated approach to material from other Middle Neolithic pits holds potential for better understanding of food and farming in this previously neglected period

Evidence of Resistance to Cry34/35Ab1 Corn by Western Corn Rootworm (Coleoptera: Chrysomelidae): Root Injury in the Field and Larval Survival in Plant-Based Bioassays

Western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), is a serious pest of corn in the United States, and recent management of western corn rootworm has included planting of Bt corn. Beginning in 2009, western corn rootworm populations with resistance to Cry3Bb1 corn and mCry3A corn were found in Iowa and elsewhere. To date, western corn rootworm populations have remained susceptible to corn producing Bt toxin Cry34/35Ab1. In this study, we used single-plant bioassays to test field populations of western corn rootworm for resistance to Cry34/35Ab1 corn, Cry3Bb1 corn, and mCry3A corn. Bioassays included nine rootworm populations collected from fields where severe injury to Bt corn had been observed and six control populations that had never been exposed to Bt corn. We found incomplete resistance to Cry34/35Ab1 corn among field populations collected from fields where severe injury to corn producing Cry34/35Ab1, either singly or as a pyramid, had been observed. Additionally, resistance to Cry3Bb1 corn and mCry3A corn was found among the majority of populations tested. These first cases of resistance to Cry34/35Ab1 corn, and the presence of resistance to multiple Bt toxins by western corn rootworm, highlight the potential vulnerability of Bt corn to the evolution of resistance by western corn rootworm. The use of more diversified management practices, in addition to insect resistance management, likely will be essential to sustain the viability of Bt corn for management of western corn rootworm

Genome Majority Vote Improves Gene Predictions

Recent studies have noted extensive inconsistencies in gene start sites among orthologous genes in related microbial genomes. Here we provide the first documented evidence that imposing gene start consistency improves the accuracy of gene start-site prediction. We applied an algorithm using a genome majority vote (GMV) scheme to increase the consistency of gene starts among orthologs. We used a set of validated Escherichia coli genes as a standard to quantify accuracy. Results showed that the GMV algorithm can correct hundreds of gene prediction errors in sets of five or ten genomes while introducing few errors. Using a conservative calculation, we project that GMV would resolve many inconsistencies and errors in publicly available microbial gene maps. Our simple and logical solution provides a notable advance toward accurate gene maps

Challenges of diabetes prevention in the real world : results and lessons from the Melbourne diabetes prevention study

OBJECTIVE: To assess effectiveness and implementability of the public health programme Life! Taking action on diabetes in Australian people at risk of developing type 2 diabetes. RESEARCH DESIGN AND METHODS: Melbourne Diabetes Prevention Study (MDPS) was a unique study assessing effectiveness of Life! that used a randomized controlled trial design. Intervention participants with AUSDRISK score &ge;15 received 1 individual and 5 structured 90 min group sessions. Controls received usual care. Outcome measures were obtained for all participants at baseline and 12 months and, additionally, for intervention participants at 3 months. Per protocol set (PPS) and intention to treat (ITT) analyses were performed. RESULTS: PPS analyses were considered more informative from our study. In PPS analyses, intervention participants significantly improved in weight (-1.13 kg, p=0.016), waist circumference (-1.35 cm, p=0.044), systolic (-5.2 mm Hg, p=0.028) and diastolic blood pressure (-3.2 mm Hg, p=0.030) compared with controls. Based on observed weight change, estimated risk of developing diabetes reduced by 9.6% in the intervention and increased by 3.3% in control participants. Absolute 5-year cardiovascular disease (CVD) risk reduced significantly for intervention participants by 0.97 percentage points from 9.35% (10.4% relative risk reduction). In control participants, the risk increased by 0.11 percentage points (1.3% relative risk increase). The net effect for the change in CVD risk was -1.08 percentage points of absolute risk (p=0.013). CONCLUSIONS: MDPS effectively reduced the risk of diabetes and CVD, but the intervention effect on weight and waist reduction was modest due to the challenges in recruiting high-risk individuals and the abbreviated intervention

The need for illness

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45466/1/11089_2005_Article_BF01845887.pd