Naturally Occurring Deletion Mutants of the Pig-Specific, Intestinal Crypt Epithelial Cell Protein CLCA4b without Apparent Phenotype.

The human CLCA4 (chloride channel regulator, calcium-activated) modulates the intestinal phenotype of cystic fibrosis (CF) patients via an as yet unknown pathway. With the generation of new porcine CF models, species-specific differences between human modifiers of CF and their porcine orthologs are considered critical for the translation of experimental data. Specifically, the porcine ortholog to the human CF modulator gene CLCA4 has recently been shown to be duplicated into two separate genes, CLCA4a and CLCA4b. Here, we characterize the duplication product, CLCA4b, in terms of its genomic structure, tissue and cellular expression patterns as well as its in vitro electrophysiological properties. The CLCA4b gene is a pig-specific duplication product of the CLCA4 ancestor and its protein is exclusively expressed in small and large intestinal crypt epithelial cells, a niche specifically occupied by no other porcine CLCA family member. Surprisingly, a unique deleterious mutation of the CLCA4b gene is spread among modern and ancient breeds in the pig population, but this mutation did not result in an apparent phenotype in homozygously affected animals. Electrophysiologically, neither the products of the wild type nor of the mutated CLCA4b genes were able to evoke a calcium-activated anion conductance, a consensus feature of other CLCA proteins. The apparently pig-specific duplication of the CLCA4 gene with unique expression of the CLCA4b protein variant in intestinal crypt epithelial cells where the porcine CFTR is also present raises the question of whether it may modulate the porcine CF phenotype. Moreover, the naturally occurring null variant of CLCA4b will be valuable for the understanding of CLCA protein function and their relevance in modulating the CF phenotype

‘Gobbling drops’: the jetting–dripping transition in flows of polymer solutions

This paper discusses the breakup of capillary jets of dilute polymer solutions and the dynamics associated with the transition from dripping to jetting. High-speed digital video imaging reveals a new scenario of transition and breakup via periodic growth and detachment of large terminal drops. The underlying mechanism is discussed and a basic theory for the mechanism of breakup is also presented. The dynamics of the terminal drop growth and trajectory prove to be governed primarily by mass and momentum balances involving capillary, gravity and inertial forces, whilst the drop detachment event is controlled by the kinetics of the thinning process in the viscoelastic ligaments that connect the drops. This thinning process of the ligaments that are subjected to a constant axial force is driven by surface tension and resisted by the viscoelasticity of the dissolved polymeric molecules. Analysis of this transition provides a new experimental method to probe the rheological properties of solutions when minute concentrations of macromolecules have been added.Schlumberger FoundationMIT Class of 1951 Fellowship Fun

Thermal fission rate around super-normal phase transition

Using Langer's $Im F$ method, we discuss the temperature dependence of nuclear fission width in the presence of dissipative environments. We introduce a low cut-off frequency to the spectral density of the environmental oscillators in order to mimic the pairing gap. It is shown that the decay width rapidly decreases at the critical temperature, where the phase transition from super to normal fluids takes place. Relation to the recently observed threshold for the dissipative fission is discussed.Comment: 12 pages, Latex, Submitted to Physical Review C for publication, 3 Postscript figures are available by request from [email protected]

Concept Maps as Tools for Assessing Students\u27 Epistemologies of Science

The use of concept maps as instruments for assessing preservice teachers’ epistemologies of science (their ideas of the nature of scientific knowledge) was evaluated in this study. Twenty-three preservice elementary teachers’ responses to the Views of the Nature Of Science (VNOS) questionnaire were compared to concept maps created in response to the general probe, “What is science?” While VNOS responses allowed a richer analysis of the content and quality of the participants’ epistemologies, the concept maps provided information about structural changes of participants’ epistemologies as well as how those epistemologies relate to their overall conceptions of science as a field of study. Both instruments also revealed important connections between NOS tenets, which were more numerous on the concept maps but more informative on the VNOS, and between NOS tenets and pedagogical issues. Implications for assessment of students’ epistemologies of science in classrooms are discussed

Digital strategies to a local cultural tourism development: Project e-Carnide

Digital humanities and smart economy strategies are being seen as an important link between tourism and cultural heritage, as they may contribute to differentiate the audiences and to provide different approaches. Carnide is a peripheral neighbourhood of Lisbon with an elderly population, visible traces of rurality, and strong cultural and religious traditions. The academic project e-Carnide concerns its tangible and intangible cultural heritage and the data dissemination through a website and a mobile app, with textual and visual information. The project aims to analyse the impact of technological solutions on cultural tourism development in a sub-region, involving interdisciplinary research in heritage, history of art, ethnography, design communication and software engineering and the collaboration between the university and local residents in a dynamic and innovative way. Framed by a theoretical approach about the role of smart economy for the cultural tourism development in peripheral areas, this paper focuses on a case study, dealing with documents, interviews and observations, in order to understand how the e-Carnide project evolves. The study comprises an analysis about the strengths, weaknesses, opportunities and threats (SWOT analysis) of the project in view to realize its social and cultural implications and to appreciate how it can be applied in other similar and enlarged projects. Results of the research indicates that the new technological strategies can promote the involvement of the population in the knowledge of its own heritage as a factor of cultural and creative tourism development centred on an authentic and immersive experience of the places

Cross-species oncogenomics offers insight into human muscle-invasive bladder cancer

Background In humans, muscle-invasive bladder cancer (MIBC) is highly aggressive and associated with a poor prognosis. With a high mutation load and large number of altered genes, strategies to delineate key driver events are necessary. Dogs and cats develop urothelial carcinoma (UC) with histological and clinical similarities to human MIBC. Cattle that graze on bracken fern also develop UC, associated with exposure to the carcinogen ptaquiloside. These species may represent relevant animal models of spontaneous and carcinogen-induced UC that can provide insight into human MIBC. Results Whole-exome sequencing of domestic canine (n = 87) and feline (n = 23) UC, and comparative analysis with human MIBC reveals a lower mutation rate in animal cases and the absence of APOBEC mutational signatures. A convergence of driver genes (ARID1A, KDM6A, TP53, FAT1, and NRAS) is discovered, along with common focally amplified and deleted genes involved in regulation of the cell cycle and chromatin remodelling. We identify mismatch repair deficiency in a subset of canine and feline UCs with biallelic inactivation of MSH2. Bovine UC (n = 8) is distinctly different; we identify novel mutational signatures which are recapitulated in vitro in human urinary bladder UC cells treated with bracken fern extracts or purified ptaquiloside. Conclusion Canine and feline urinary bladder UC represent relevant models of MIBC in humans, and cross-species analysis can identify evolutionarily conserved driver genes. We characterize mutational signatures in bovine UC associated with bracken fern and ptaquiloside exposure, a human-linked cancer exposure. Our work demonstrates the relevance of cross-species comparative analysis in understanding both human and animal UC