135 research outputs found

    Integrated Modelling Frameworks for Environmental Assessment and Decision Support

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    As argued in Chapter 1, modern management of environmental resources defines problems from a holistic and integrated perspective, thereby imposing strong requirements on Environmental Decision Support Systems (EDSSs) and Integrated Assessment Tools (IATs). These systems and tools tend to be increasingly complex in terms of software architecture and computational power in order to cope with the type of problems they must solve. For instance, the discipline of Integrated Assessment (IA) needs tools that arc able to span a wide range of disciplines, from socio-economics to ecology to hydrology. Such tools must support a wide range of methodologies and techniques like agent-based modeling, Bayesian decision networks, optimization, multicriteria analyses and visualization tools, to name a few

    Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic fibrosis airway epithelial cells

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    Š 2018 Sutanto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene can reduce function of the CFTR ion channel activity and impair cellular chloride secretion. The gold standard method to assess CFTR function of ion transport using the Ussing chamber requires a high number of airway epithelial cells grown at air-liquid interface, limiting the application of this method for high throughput screening of potential therapeutic compounds in primary airway epithelial cells (pAECs) featuring less common CFTR mutations. This study assessed an alternative approach, using a small scale halide assay that can be adapted for a personalized high throughput setting to analyze CFTR function of pAEC. Methods Pediatric pAECs derived from children with CF (pAEC CF ) were established and expanded as monolayer cultures, before seeding into 96-well plates for the halide assay. Cells were then transduced with an adenoviral construct containing yellow fluorescent protein (eYFP) reporter gene, alone or in combination with either wild-type CFTR (WT-CFTR) or p.Phe508-del CFTR. Four days post transduction, cells were stimulated with forskolin and genistein, and assessed for quenching of the eYFP signal following injection of iodide solution into the assay media. Results Data showed that pAEC CF can express eYFP at high efficiency following transduction with the eYFP construct. The halide assay was able to discriminate functional restoration of CFTR in pAEC CF treated with either WT-CFTR construct or the positive controls syntaxin 8 and B-cell receptor-associated protein 31 shRNAs. Significance The current study demonstrates that the halide assay can be adapted for pediatric pAEC CF to evaluate restoration of CFTR function. With the ongoing development of small molecules to modulate the folding and/or activity of various mutated CFTR proteins, this halide assay presents a small-scale personalized screening platform that could assess therapeutic potential of molecules across a broad range of CFTR mutations

    Spatial analysis of biomineralization associated gene expression from the mantle organ of the pearl oyster Pinctada maxima

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    Background: Biomineralization is a process encompassing all mineral containing tissues produced within an organism. One of the most dynamic examples of this process is the formation of the mollusk shell, comprising a variety of crystal phases and microstructures. The organic component incorporated within the shell is said to dictate this architecture. However general understanding of how this process is achieved remains ambiguous. The mantle is a conserved organ involved in shell formation throughout molluscs. Specifically the mantle is thought to be responsible for secreting the protein component of the shell. This study employs molecular approaches to determine the spatial expression of genes within the mantle tissue to further the elucidation of the shell biomineralization. Results: A microarray platform was custom generated (PmaxArray 1.0) from the pearl oyster Pinctada maxima. PmaxArray 1.0 consists of 4992 expressed sequence tags (ESTs) originating from mantle tissue. This microarray was used to analyze the spatial expression of ESTs throughout the mantle organ. The mantle was dissected into five discrete regions and analyzed for differential gene expression with PmaxArray 1.0. Over 2000 ESTs were determined to be differentially expressed among the tissue sections, identifying five major expression regions. In situ hybridization validated and further localized the expression for a subset of these ESTs. Comparative sequence similarity analysis of these ESTs revealed a number of the transcripts were novel while others showed significant sequence similarities to previously characterized shell related genes

    A Fragment of the LG3 Peptide of Endorepellin Is Present in the Urine of Physically Active Mining Workers: A Potential Marker of Physical Activity

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    Biomarker analysis has been implemented in sports research in an attempt to monitor the effects of exertion and fatigue in athletes. This study proposed that while such biomarkers may be useful for monitoring injury risk in workers, proteomic approaches might also be utilised to identify novel exertion or injury markers. We found that urinary urea and cortisol levels were significantly elevated in mining workers following a 12 hour overnight shift. These levels failed to return to baseline over 24 h in the more active maintenance crew compared to truck drivers (operators) suggesting a lack of recovery between shifts. Use of a SELDI-TOF MS approach to detect novel exertion or injury markers revealed a spectral feature which was associated with workers in both work categories who were engaged in higher levels of physical activity. This feature was identified as the LG3 peptide, a C-terminal fragment of the anti-angiogenic/anti-tumourigenic protein endorepellin. This finding suggests that urinary LG3 peptide may be a biomarker of physical activity. It is also possible that the activity mediated release of LG3/endorepellin into the circulation may represent a biological mechanism for the known inverse association between physical activity and cancer risk/survival

    Production and perception of situationally variable alarm calls in wild tufted capuchin monkeys (Cebus apella nigritus)

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    Many mammalian and avian species produce conspicuous vocalizations upon encountering a predator, but vary their calling based on risk urgency and/or predator type. Calls falling into the latter category are termed “functionally referential” if they also elicit predator-appropriate reactions in listeners. Functionally referential alarm calling has been well documented in a number of Old World monkeys and lemurs, but evidence among Neotropical primates is limited. This study investigates the alarm call system of tufted capuchin monkeys (Cebus apella nigritus) by examining responses to predator and snake decoys encountered at various distances (reflecting differences in risk urgency). Observations in natural situations were conducted to determine if predator-associated calls were given in additional contexts. Results indicate the use of three call types. “Barks” are elicited exclusively by aerial threats, but the call most commonly given to terrestrial threats (the “hiccup”) is given in nonpredatory contexts. The rate in which this latter call is produced reflects risk urgency. Playbacks of these two call types indicate that each elicits appropriate antipredator behaviors. The third call type, the “peep,” seems to be specific to terrestrial threats, but it is unknown if the call elicits predator-specific responses. “Barks” are thus functionally referential aerial predator calls, while “hiccups” are better seen as generalized disturbance calls which reflect risk urgency. Further evidence is needed to draw conclusions regarding the “peep.” These results add to the evidence that functionally referential aerial predator alarm calls are ubiquitous in primates, but that noncatarrhine primates use generalized disturbance calls in response to terrestrial threats
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