Integrated modelling of cost-effective siting and operation of flow-control infrastructure for river ecosystem conservation

Wetland and floodplain ecosystems along many regulated rivers are highly stressed, primarily due to a lack of environmental flows of appropriate magnitude, frequency, duration, and timing to support ecological functions. In the absence of increased environmental flows, the ecological health of river ecosystems can be enhanced by the operation of existing and new flow-control infrastructure (weirs and regulators) to return more natural environmental flow regimes to specific areas. However, determining the optimal investment and operation strategies over time is a complex task due to several factors including the multiple environmental values attached to wetlands, spatial and temporal heterogeneity and dependencies, nonlinearity, and time-dependent decisions. This makes for a very large number of decision variables over a long planning horizon. The focus of this paper is the development of a nonlinear integer programming model that accommodates these complexities. The mathematical objective aims to return the natural flow regime of key components of river ecosystems in terms of flood timing, flood duration, and interflood period. We applied a 2-stage recursive heuristic using tabu search to solve the model and tested it on the entire South Australian River Murray floodplain. We conclude that modern meta-heuristics can be used to solve the very complex nonlinear problems with spatial and temporal dependencies typical of environmental flow allocation in regulated river ecosystems. The model has been used to inform the investment in, and operation of, flow-control infrastructure in the South Australian River Murray.<br /

Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins

In the pharmaceutical industry, improving the early detection of drug-induced hepatotoxicity is essential as it is one of the most important reasons for attrition of candidate drugs during the later stages of drug development. The first objective of this study was to better characterize different cellular models (i.e., HepG2, HepaRG cells, and fresh primary human hepatocytes) at the gene expression level and analyze their metabolic cytochrome P450 capabilities. The cellular models were exposed to three different CYP450 inducers; beta-naphthoflavone (BNF), phenobarbital (PB), and rifampicin (RIF). HepG2 cells responded very weakly to the different inducers at the gene expression level, and this translated generally into low CYP450 activities in the induced cells compared with the control cells. On the contrary, HepaRG cells and the three human donors were inducible after exposure to BNF, PB, and RIF according to gene expression responses and CYP450 activities. Consequently, HepaRG cells could be used in screening as a substitute and/or in complement to primary hepatocytes for CYP induction studies. The second objective was to investigate the predictivity of the different cellular models to detect hepatotoxins (16 hepatotoxic and 5 nonhepatotoxic compounds). Specificity was 100% with the different cellular models tested. Cryopreserved human hepatocytes gave the highest sensitivity, ranging from 31% to 44% (depending on the donor), followed by lower sensitivity (13%) for HepaRG and HepG2 cells (6.3%). Overall, none of the models under study gave desirable sensitivities (80–100%). Consequently, a high metabolic capacity and CYP inducibility in cell lines does not necessarily correlate with a high sensitivity for the detection of hepatotoxic drugs. Further investigations are necessary to compare different cellular models and determine those that are best suited for the detection of hepatotoxic compounds

Climate Change, Coral Reef Ecosystems, and Management Options for Marine Protected Areas

Marine protected areas (MPAs) provide place-based management of marine ecosystems through various degrees and types of protective actions. Habitats such as coral reefs are especially susceptible to degradation resulting from climate change, as evidenced by mass bleaching events over the past two decades. Marine ecosystems are being altered by direct effects of climate change including ocean warming, ocean acidification, rising sea level, changing circulation patterns, increasing severity of storms, and changing freshwater influxes. As impacts of climate change strengthen they may exacerbate effects of existing stressors and require new or modified management approaches; MPA networks are generally accepted as an improvement over individual MPAs to address multiple threats to the marine environment. While MPA networks are considered a potentially effective management approach for conserving marine biodiversity, they should be established in conjunction with other management strategies, such as fisheries regulations and reductions of nutrients and other forms of land-based pollution. Information about interactions between climate change and more “traditional” stressors is limited. MPA managers are faced with high levels of uncertainty about likely outcomes of management actions because climate change impacts have strong interactions with existing stressors, such as land-based sources of pollution, overfishing and destructive fishing practices, invasive species, and diseases. Management options include ameliorating existing stressors, protecting potentially resilient areas, developing networks of MPAs, and integrating climate change into MPA planning, management, and evaluation

p53 expression and apoptosis in melanomas of dogs and cats.

&lt;p&gt;Twenty-seven melanocytic tumours from 20 dogs and four cats were examined for p53 expression and apoptosis. They included tumours that were histologically classified as benign (BM), primary malignant (PMM) and metastatic malignant melanomas (MMM). For all cases clinical follow-up was available. p53 expression was examined immunohistochemically using different monoclonal and polyclonal antibodies. Apoptosis was detected using the TUNEL technique. The tissue sections were analysed using a quantitative image analysing system. A p53 index (p53I) and an apoptotic index (AI) were determined. p53 over-expression was found infrequently in these canine and feline melanocytic tumours. Apoptosis was observed in some of the malignant tumours. In one feline case of malignant melanoma, p53 accumulation together with apoptosis was seen in three metastases but not in the primary tumour. p53I and AI were not significantly correlated with survival. These results are similar to those reported for human cutaneous melanomas.&lt;/p&gt;</p

PCNA and Ki67 proliferation markers as criteria for prediction of clinical behaviour of melanocytic tumours in cats and dogs.

&lt;p&gt;Melanocytic tumours in domestic animals vary from benign to highly malignant. Diagnosis and prognosis are mainly based on the somewhat uncertain interpretation of cytological signs of malignancy in histological sections. The purpose of the present retrospective study was to compare the accuracy of prognosis based on the classical morphological criteria with that provided by quantitative computerized analysis of proliferation-associated antigens. Twenty-seven melanocytic tumours (20 canine and seven feline) from 24 animals (20 dogs and four cats) were examined. These comprised eight tumours histologically classified as benign melanoma (BM) (seven canine, one feline), 16 classified as primary malignant melanoma (PMM) (13 canine, three feline) and three classified as metastatic melanoma (MMM) (three feline). Tumour size, predominant histological cell type, invasive growth and clinical outcome were recorded for each case. In addition, the proliferation (phase) index and growth fraction were measured, after bleaching, by means of quantitative image analysis of tissue sections immunolabelled for proliferating cell nuclear antigen (PCNA) and MIB-1 (Ki67). Lesions classified histologically as benign or malignant, differed significantly (Copyright P&lt;0.001) in respect of Ki67 and PCNA positivity. No such difference could be shown between PMM and MMM. High growth fraction (measured by the Ki67 positive cells) and macroscopic invasive growth were associated with decreased survival time (P=0.027 and P=0.024, respectively). Moreover, the established cytological classification also proved to be associated with the survival time (P&lt;0.001). The results suggest that Ki67 is a potentially important prognostic factor in melanomas of the cat and dog. Other criteria, including tumour size, predominant cell type and intensity of PCNA expression, were not of significant prognostic value (P&gt;0.05).&lt;/p&gt;</p

Proliferation, DNA ploidy, p53 overexpression and nuclear DNA fragmentation in six equine melanocytic tumours.

&lt;p&gt;Melanocytic tumours are a well-known clinical and pathological entity in horses, but further phenotypic characterization of these tumours is lacking. Six melanocytic tumours from five horses (two metastatic and four benign) were examined by Ki67, PCNA and p53 immunostaining, DNA nick end labelling (Tunel) and Feulgen staining. The stainings were evaluated using quantitative image analysis. The resulting parameters of growth fraction (Ki67), S-phase index (PCNA), p53 index, apoptotic index, DNA index, nuclear diameter, ploidy balance, proliferation index (Feulgen) and hyperploidy were analysed. The metastatic melanomas showed overexpression of p53 in a large portion of the cells. Apoptosis was also found in the metastatic melanomas. No differences were found in growth fraction, S-phase index (PCNA) nor in DNA configuration between the metastatic and the benign tumours. No immunohistochemical evidence of mutant p53 could be found in the tumours. In conclusion, melanocytic tumours in horses seem to have different phenotypic characteristics in comparison with melanocytic tumours in dogs, cats and humans, especially with respect to proliferative activity of the benign tumours. Therefore, markers put forward in these other species for predicting the clinical behaviour of the melanomas seem to be of no value in the horse. Moreover, quantitative DNA changes or p53 mutations do not seem to be involved in tumourogenesis in these cases.&lt;/p&gt;</p