Guidelines for the use of cell lines in biomedical research

Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise

Irreversible Effects of Ivermectin on Adult Parasites in Onchocerciasis Patients in the Onchocerciasis Control Programme in West Africa

Ivermectin is an effective drug for the treatment of human onchocerciasis, a disease caused by the parasitic filarial nematode Onchocerca volvulus. When humans are treated, the microfilariae normally found in the skin are rapidly and very nearly completely eliminated. Nonetheless, after a delay, microfilariae gradually reappear in the skin. This study is concerned with the causes of this delay. Hypotheses are tested by comparing the results of model calculations with skin microfilaria counts collected from 114 patients during a trial of five annual treatments in the focus area of Asubende, Ghana. The results obtained strongly suggest that annual treatment with ivermectin causes an irreversible decline in microfilariae production of ∼30%/treatment. This result has important implications for public health strategies designed to eliminate onchocerciasis as a significant health hazar

Measuring regional creative capacity: A literature review for rural-specific approaches

Recent theories on regional creative capacity often focus on urban regions without taking into account rural regions. In addition, the application of such analyses to rural regions may lead to misrepresentation or misunderstanding of rural creative capacity. Against this background, the aim of the present study is to integrate the existing literature on different components of creative capacity, namely, knowledge, innovation, entrepreneurship and networks, in order to build a more comprehensive framework for rural creative capacity and its evaluation. In the light of the perspective from the empirical literature review on the evaluation of creative capacity in rural regions, various empirical measurements seem to misrepresent or underestimate the creative capacity of rural regions. Therefore, there is a clear need to use the locality in relation to its dynamics, i.e. tacit knowledge, cultural heritage and social and physical environment as the main and basic measurement unit for creative capacity analysis. 2010 Taylor & Francis

Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition

p300 is a transcriptional cofactor and prototype histone acetyltransferase involved in regulating multiple cellular processes. We generated p300 deficient (p300−) cells from the colon carcinoma cell line HCT116 by gene targeting. Comparison of epithelial and mesenchymal proteins in p300− with parental HCT116 cells showed that a number of genes involved in cell and extracellular matrix interactions, typical of ‘epithelial to mesenchyme transition' were differentially regulated at both the RNA and protein level. p300− cells were found to have aggressive ‘cancer' phenotypes, with loss of cell–cell adhesion, defects in cell–matrix adhesion and increased migration through collagen and matrigel. Although migration was shown to be metalloproteinase mediated, these cells actually showed a downregulation or no change in the level of key metalloproteinases, indicating that changes in cellular adhesion properties can be critical for cellular mobility

Whose Sense of Place? A Political Ecology of Amenity Development

Using a political ecology framework, this chapter examines the ways in which sense of place and amenity migration contribute to alternative residential development, which relies on uneven use of conservation subdivision features in the American West. Using case studies from Central Oregon, this chapter demonstrates how senses of place and developer decision-making are tied to wider political economic changes. It highlights the roles that amenity migrants and developers, two groups that are sometimes identical, play in landscape transformations that simultaneously draw on a particular sense of place and commodify landscapes in new ways

Genome-Wide Analyses of Nkx2-1 Binding to Transcriptional Target Genes Uncover Novel Regulatory Patterns Conserved in Lung Development and Tumors

The homeodomain transcription factor Nkx2-1 is essential for normal lung development and homeostasis. In lung tumors, it is considered a lineage survival oncogene and prognostic factor depending on its expression levels. The target genes directly bound by Nkx2-1, that could be the primary effectors of its functions in the different cellular contexts where it is expressed, are mostly unknown. In embryonic day 11.5 (E11.5) mouse lung, epithelial cells expressing Nkx2-1 are predominantly expanding, and in E19.5 prenatal lungs, Nkx2-1-expressing cells are predominantly differentiating in preparation for birth. To evaluate Nkx2-1 regulated networks in these two cell contexts, we analyzed genome-wide binding of Nkx2-1 to DNA regulatory regions by chromatin immunoprecipitation followed by tiling array analysis, and intersected these data to expression data sets. We further determined expression patterns of Nkx2-1 developmental target genes in human lung tumors and correlated their expression levels to that of endogenous NKX2-1. In these studies we uncovered differential Nkx2-1 regulated networks in early and late lung development, and a direct function of Nkx2-1 in regulation of the cell cycle by controlling the expression of proliferation-related genes. New targets, validated in Nkx2-1 shRNA transduced cell lines, include E2f3, Cyclin B1, Cyclin B2, and c-Met. Expression levels of Nkx2-1 direct target genes identified in mouse development significantly correlate or anti-correlate to the levels of endogenous NKX2-1 in a dosage-dependent manner in multiple human lung tumor expression data sets, supporting alternative roles for Nkx2-1 as a transcriptional activator or repressor, and direct regulator of cell cycle progression in development and tumors

Catheter ablation for AF improves global thrombotic profile and enhances fibrinolysis

© The Author(s) 2017. This article is an open access publication. The final authenticated version is available online at: https://doi.org/10.1007/s11239-017-1548-3Patients with atrial fibrillation (AF) are at increased risk of thrombotic events despite oral anticoagulation (OAC). Radiofrequency catheter ablation (RFCA) can restore and maintain sinus rhythm (SR) in patients with AF. To assess whether RFCA improves thrombotic status. 80 patients (71% male, 64 ± 12y) with recently diagnosed AF, on OAC and scheduled to undergo RFCA or DC cardioversion (DCCV) were recruited. Thrombotic status was assessed using the point-of-care global thrombosis test (GTT), before, and 4-6 weeks after DCCV and 3 months after RFCA. The GTT first measures the time taken for occlusive thrombus formation (occlusion time, OT), while the second phase of the test measures the time taken to spontaneously dissolve this clot through endogenous thrombolysis (lysis time, LT). 3 months after RFCA, there was a significant reduction in LT (1994s [1560; 2475] vs. 1477s [1015; 1878]) in those who maintained SR, but not in those who reverted to AF. At follow-up, LT was longer in those in AF compared to those in SR (AF 2966s [2038; 3879] vs. SR 1477s [1015; 1878]). RFCA resulted in no change in OT value, irrespective of rhythm outcome. Similarly, there was no change in OT or LT in response to DCCV, irrespective of whether SR was restored. Successful restoration and maintenance of SR following RFCA of AF is associated with improved global thrombotic status with enhanced fibrinolysis. Larger studies are required to confirm these early results and investigate whether improved thrombotic status translates into fewer thromboembolic events.Peer reviewedFinal Published versio

Disaggregate economic base multipliers in small communities

Economic base analysis is frequently used to describe employment profiles and to predict project-related impacts in small communities. Considerable evidence suggests, however, that economic base multipliers should be estimated from survey data and not from shortcut methods. In this paper two competing versions of the economic base model are developed and then these two models are estimated by use of the Arizona community data set. In both cases, marginal multiplier estimates, controlled for transfer payments, are generated for ten individual sectors in five different types of communities. Results from these two disaggregate economic base models are assessed and then compared with results provided earlier by more aggregate models. The better of these two new models closely resembles the popular input - output model.