47 research outputs found
Recommended from our members
Food System Transformation: Integrating a Political-Economy and Social-Ecological Approach to Regime Shifts.
Sustainably achieving the goal of global food security is one of the greatest challenges of the 21st century. The current food system is failing to meet the needs of people, and at the same time, is having far-reaching impacts on the environment and undermining human well-being in other important ways. It is increasingly apparent that a deep transformation in the way we produce and consume food is needed in order to ensure a more just and sustainable future. This paper uses the concept of regime shifts to understand key drivers and innovations underlying past disruptions in the food system and to explore how they may help us think about desirable future changes and how we might leverage them. We combine two perspectives on regime shifts-one derived from natural sciences and the other from social sciences-to propose an interpretation of food regimes that draws on innovation theory. We use this conceptualization to discuss three examples of innovations that we argue helped enable critical regime shifts in the global food system in the past: the Haber-Bosch process of nitrogen fixation, the rise of the supermarket, and the call for more transparency in the food system to reconnect consumers with their food. This paper concludes with an exploration of why this combination of conceptual understandings is important across the Global North/ Global South divide, and proposes a new sustainability regime where transformative change is spearheaded by a variety of social-ecological innovations
Genomic organisation and alternative splicing of mouse and human thioredoxin reductase 1 genes
BACKGROUND: Thioredoxin reductase (TR) is a redox active protein involved in many cellular processes as part of the thioredoxin system. Presently there are three recognised forms of mammalian thioredoxin reductase designated as TR1, TR3 and TGR, that represent the cytosolic, mitochondrial and novel forms respectively. In this study we elucidated the genomic organisation of the mouse (Txnrd1) and human thioredoxin reductase 1 genes (TXNRD1) through library screening, restriction mapping and database mining. RESULTS: The human TXNRD1 gene spans 100 kb of genomic DNA organised into 16 exons and the mouse Txnrd1 gene has a similar exon/intron arrangement. We also analysed the alternative splicing patterns displayed by the mouse and human thioredoxin reductase 1 genes and mapped the different mRNA isoforms with respect to genomic organisation. These isoforms differ at the 5' end and encode putative proteins of different molecular mass. Genomic DNA sequences upstream of mouse exon 1 were compared to the human promoter to identify conserved elements. CONCLUSIONS: The human and mouse thioredoxin reductase 1 gene organisation is highly conserved and both genes exhibit alternative splicing at the 5' end. The mouse and human promoters share some conserved sequences
The NRF2-mediated oxidative stress response pathway is associated with tumor cell resistance to arsenic trioxide across the NCI-60 panel
<p>Abstract</p> <p>Background</p> <p>Drinking water contaminated with inorganic arsenic is associated with increased risk for different types of cancer. Paradoxically, arsenic trioxide can also be used to induce remission in patients with acute promyelocytic leukemia (APL) with a success rate of approximately 80%. A comprehensive study examining the mechanisms and potential signaling pathways contributing to the anti-tumor properties of arsenic trioxide has not been carried out.</p> <p>Methods</p> <p>Here we applied a systems biology approach to identify gene biomarkers that underlie tumor cell responses to arsenic-induced cytotoxicity. The baseline gene expression levels of 14,500 well characterized human genes were associated with the GI<sub>50</sub> data of the NCI-60 tumor cell line panel from the developmental therapeutics program (DTP) database. Selected biomarkers were tested <it>in vitro</it> for the ability to influence tumor susceptibility to arsenic trioxide.</p> <p>Results</p> <p>A significant association was found between the baseline expression levels of 209 human genes and the sensitivity of the tumor cell line panel upon exposure to arsenic trioxide. These genes were overlayed onto protein-protein network maps to identify transcriptional networks that modulate tumor cell responses to arsenic trioxide. The analysis revealed a significant enrichment for the oxidative stress response pathway mediated by nuclear factor erythroid 2-related factor 2 (NRF2) with high expression in arsenic resistant tumor cell lines. The role of the NRF2 pathway in protecting cells against arsenic-induced cell killing was validated in tumor cells using shRNA-mediated knock-down.</p> <p>Conclusions</p> <p>In this study, we show that the expression level of genes in the NRF2 pathway serve as potential gene biomarkers of tumor cell responses to arsenic trioxide. Importantly, we demonstrate that tumor cells that are deficient for NRF2 display increased sensitivity to arsenic trioxide. The results of our study will be useful in understanding the mechanism of arsenic-induced cytotoxicity in cells, as well as the increased applicability of arsenic trioxide as a chemotherapeutic agent in cancer treatment.</p
Modification of the Boyden chamber to improve uniformity of cell invasion of matrigel-coated membranes
The ability of cells to invade basement membranes is critical to a number of important biological processes, such as cell metastasis, embryo implantation and early development, and inflammation. Several in vitro invasion assays have been developed so that the invasiveness of cells can be measured.These assays are also used to monitor the altered cell response to stimuli or inhibitors, such as in the evaluation of potential inhibitors of metastasis and other chemotherapeutic drugs. One of the most rapid assays is performed in a modified blind-well Boyden chamber(1,4) containing a filter coated with Matrigel, which is a commercially available reconstituted basement ex-tract from the Engelbreth-Holm-Swarmmurine sarcoma (Becton Dickinson,Franklin Lakes, NJ, USA). The Matrigel acts as a barrier on the surface of a porous filter, separating cells in one compartment from a chemo attractant in another compartment..