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

InQuiry: A Participatory Approach for Understanding Stakeholder Perceptions

This article addresses two important and elusive issues for funded projects: quantifiable measures and deep understandings of participant perceptions. It describes the development of the InQuiry evaluation tool, which combines Q methodology (factor analysis process to quantify perceptions) with a qualitative participatory approach. InQuiry generates both quantified metrics of what participants believe about a given topic and also a rich narrative of why participants think the way they do. These data yield metrics for understanding fidelity, outcomes, and impacts. Beginning with the history of a program funded by the W.K. Kellogg Foundation, this article also illustrates the tool’s usefulness. The Seattle Community Learning Exchange, an example of InQuiry in action from beginning to end, explored how members of a diverse community perceived peacemaking and healing within the community and implemented peacemaking circles by building capacity and shifting perceptions

The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

Oxygen is essential for the survival of all living beings. A balanced oxygen environment is required since both lower and higher than the required oxygen levels can be detrimental to the cells (Figure 1). The oxygen state of a tissue results fr om the relative contributions of oxygen consumption and delivery. Different organs in the body exist under different oxygen environments, depending on the location and function of the cells in an organ. Most healthy organs reside in 3-6% oxygen [1] while conditions lower than 3% oxygen are described as hypoxia. Cells also survive in hypoxic environments during normal development [2]. However, hypoxia is mostly detrimental to the cells by disrupting the oxygen homeostasis

Kant's concept of the good

This dissertation asks what Kant means when he talks about the good, and what role this concept plays in his ethical theory. It is divided into three chapters. The first examines the context in which this question was first asked, namely in a review of Kant’s ‘Groundwork’ by H. A. Pistorius. I analyse this review and Kant’s direct response to it in his ‘Critique of Practical Reason’, where he clarifies that the good is the “necessary object of the faculty of desire” and that it can only be determined “after and by means of” the moral law. I argue that traditional law-first and good-first readings of these passages both fail, and that instead we should prefer Stephen Engstrom’s reading which takes the food as an a priori concept of practical reason, whose content is determined by the moral law. The remaining chapters investigate this view, and specifically the strong guise of the good thesis to which it commits Kant. In the second I clarify the guise of the good and the specific version of it to which Engstrom’s view is committed, which is one that holds all willing to aim at satisfying a condition of universal validity. I argue that self-conceit and despondency are two notions from Kant’s psychology which provide a model for how non-moral willing can aim at universal validity. In the third chapter, I use this general framework to try and explain specific cases of non-moral willing. Ii find that the framework can adequately explain away diabolical willing as mere evil willing. It can also deal with frailty, though this requires departure from Engstrom’s and Reath’s views and the introduction of ‘persistent illusion’. It has the same trouble dealing with listlessness that all Kantian views do. I conclude that Engstrom’s view of the good is viable

Development of Scientific Writing Skills Through Activities Embedded into Biochemistry and Molecular Biology Laboratory Courses

Scientific writing skills are important for a career in science and need to be developed. Rather than design courses solely focused on writing, we embedded writing activities into two bioscience laboratory courses at third year undergraduate level, where students wrote about their own data. Students completed writing exercises during breaks in experimental procedures and received feedback during the session. These activities focused on data presentation, data analysis and writing results and discussion paragraphs. These exercises provided a model to assist students in writing the remainder of the report. We probed student opinions regarding scientific writing and the exercises by anonymous pre- and post-course surveys using both closed and open questions. Confidence towards scientific writing and performing simple writing tasks significantly improved after experiencing the writing activities in the first course. Students related that undertaking writing activities in more than one class helped to further improve their writing skills. Independent assessors, with no knowledge of when the reports were written, evaluated reports that originated from the same course held in years before and after writing activities were incorporated. There was a significant improvement in scientific writing quality that correlated with the increase in students’ self-efficacy towards performing various writing tasks

Mutant p53 tunes the NRF2-dependent antioxidant response to support survival of cancer cells

NRF2 (NFE2L2) is one of the main regulators of the antioxidant response of the cell. Here we show that in cancer cells NRF2 targets are selectively upregulated or repressed through a mutant p53-dependent mechanism. Mechanistically, mutant p53 interacts with NRF2, increases its nuclear presence and resides with NRF2 on selected ARE containing gene promoters activating the transcription of a specific set of genes while leading to the transcriptional repression of others. We show that thioredoxin (TXN) is a mutant p53-activated NRF2 target with pro-survival and pro-migratory functions in breast cancer cells under oxidative stress, while heme oxygenase 1 (HMOX1) is a mutant p53-repressed target displaying opposite effects. A gene signature of NRF2 targets activated by mutant p53 shows a significant association with bad overall prognosis and with mutant p53 status in breast cancer patients. Concomitant inhibition of thioredoxin system with Auranofin and of mutant p53 with APR-246 synergizes in killing cancer cells expressing p53 gain-of-function mutants

Au(I) N-heterocyclic carbenes from bisimidazolium amphiphiles: synthesis, cytotoxicity and incorporation onto gold nanoparticles

A gold(I) N-heterocyclic carbene 4 from a bis-imidazolium-amphiphile was synthesized and characterized. The cytotoxicity against HT-29 colon carcinoma and MDA-MB-231 breast adenocarcinoma cells was assessed for the NHC complex 4, the imidazolium salt precursor 2, and its methyl analogue 3, indicating that compounds 2–4 are promising cytotoxic agents. Furthermore, the ability of these compounds to be associated with gold nanoparticles was also explored, in order to develop an anticancer drug delivery system. The free ligands displayed more activity when compared with the ligands immobilized on the gold nanoparticles. The synthesized gold particles incorporating the bis-imidazolium salts either 2 or 3 showed monodisperse spherical shape with sizes of approximately 5 nm

Penalty Dynamic Programming Algorithm for Dim Targets Detection in Sensor Systems

In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations

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 GI₅₀ 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