Exposure of Kenyan population to aflatoxins in foods with special reference to Nandi and Makueni counties

201

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060

Induction of WNT11 by hypoxia and hypoxia-inducible factor-1α regulates cell proliferation, migration and invasion

Changes in cellular oxygen tension play important roles in physiological processes including development and pathological processes such as tumor promotion. The cellular adaptations to sustained hypoxia are mediated by hypoxia-inducible factors (HIFs) to regulate downstream target gene expression. With hypoxia, the stabilized HIF-α and aryl hydrocarbon receptor nuclear translocator (ARNT, also known as HIF-β) heterodimer bind to hypoxia response elements (HREs) and regulate expression of target genes. Here, we report that WNT11 is induced by hypoxia in many cell types, and that transcription of WNT11 is regulated primarily by HIF-1α. We observed induced WNT11 expression in the hypoxic area of allograft tumors. In addition, in mice bearing orthotopic malignant gliomas, inhibition with bevacizumab of vascular endothelial growth factor, which is an important stimulus for angiogenesis, increased nuclear HIF-1α and HIF-2α, and expression of WNT11. Gain- and loss-of-function approaches revealed that WNT11 stimulates proliferation, migration and invasion of cancer-derived cells, and increases activity of matrix metalloproteinase (MMP)-2 and 9. Since tumor hypoxia has been proposed to increase tumor aggressiveness, these data suggest WNT11 as a possible target for cancer therapies, especially for tumors treated with antiangiogenic therapy

Exposure of Kenyan population to aflatoxins in foods with special reference to Nandi and Makueni counties

201

Sanitary risk observation of hazards at and surrounding rural water sources in Siaya County, Kenya 2018-2019

These data were collected to quantify hazards at water sources, particularly contact between livestock and water sources. In addition, they were collected to assess inter-observer agreement in hazard observations. Sanitary risk inspection is a structured means of observing and recording contamination hazards at and surrounding water sources, which has been promoted as a tool for water safety planning. It is however unclear how far different observers can consistently record hazards at a given water source. Water sources used for drinking, including rainwater systems, surface waters such as streams and dams, wells, boreholes and springs were all surveyed for hazards. Sources were visited twice, once in the wet season and again in the dry season, when the sample of sources visited was expanded. Six surveyors with varying backgrounds independently recorded the hazards they observed at each source, based on a structured observation protocol. Diarrhoeal disease and lack of access to safe water remain significant public health issues in developing countries. There is also growing concern about the potential for disease, including diarrhoeal infections, to be transmitted from livestock to humans. This project addresses the potential drinking-water contamination risks to human health in rural sub-Saharan Africa, where people and livestock often live in close proximity. Preliminary fieldwork will be carried out in rural Kenya, building on an ongoing study that is simultaneously recording human and livestock disease in ten villages. The fieldwork will test different techniques to identify contamination hazards from livestock, alongside water quality testing and recording of diarrhoea in children. These techniques will include the use of GPS collars to track cattle movements, maps of hazardous areas created by the communities themselves, and also checklists for recording signs of livestock hazards at water sources and around water stored in the home. We will look at how feasible it is to record hazards using these techniques. We will also statistically assess whether we find greater water contamination and greater diarrhoea in children where there are more recorded hazards. Since measurement of water contamination used in such areas is based on bacteria found in both livestock and humans, the project will also work on affordable ways of testing for micro-organisms that are specifically found in livestock faeces versus those found in human faeces. If successful, such techniques could be used to investigate the importance of different sources of faecal contamination of drinking-water. This in turn could help manage the safety of rural water sources like wells and rainwater and better protect drinking-water stored in the home from contamination through livestock. Because this complex problem requires a wide range of expertise, during the project we will strength our academic team to include more disciplines, particularly specialists in child health and social sciences. The tools for identifying hazards from livestock will be made widely available at the end of the project and UK expertise in the microbiological laboratory techniques will be shared with Kenyan collaborators. The experience gained will be used to build up contacts and develop a plan and team for a larger-scale study of livestock hazards, water contamination, and diarrhoeal disease risk in several countries.</p

Dkk-1 Inhibits Intestinal Epithelial Cell Migration by Attenuating Directional Polarization of Leading Edge Cells

Wnt signaling pathways regulate proliferation, motility, and survival in a variety of human cell types. Dickkopf-1 (Dkk-1) is a secreted Wnt antagonist that has been proposed to regulate tissue homeostasis in the intestine. In this report, we show that Dkk-1 is secreted by intestinal epithelial cells after wounding and that it inhibits cell migration by attenuating the directional orientation of migrating epithelial cells. Dkk-1 exposure induced mislocalized activation of Cdc42 in migrating cells, which coincided with a displacement of the polarity protein Par6 from the leading edge. Consequently, the relocation of the microtubule organizing center and the Golgi apparatus in the direction of migration was significantly and persistently inhibited in the presence of Dkk-1. Small interfering RNA-induced down-regulation of Dkk-1 confirmed that extracellular exposure to Dkk-1 was required for this effect. Together, these data demonstrate a novel role of Dkk-1 in the regulation of directional polarization of migrating intestinal epithelial cells, which contributes to the effect of Dkk-1 on wound closure in vivo

Fourth report on chicken genes and chromosomes 2022

The chicken continues to hold its position as a leading model organism within many areas of research, as well as a being major source of protein for human consumption. The First Report on Chicken Genes and Chromosomes [Schmid et al., 2000], which was published in 2000, was the brainchild of the late, and sadly missed, Prof Michael Schmid of the University of Würzburg. It was a publication bringing together updates on the latest research and resources in chicken genomics and cytogenetics. The success of this First report led to the subsequent publication of the Second [Schmid et al., 2005] and Third [Schmid et al., 2015] reports proving popular references for the research community. It is now our pleasure to be able to introduce publication of the Fourth report. Being seven years since the last report, this publication captures the many advances that have taken place during that time. This includes presentation of the detailed genomic resources that are now available, largely due to increasing capabilities of sequencing technologies and which herald the pangenomic age, allowing for a much richer and more complete knowledge of the avian genome. Ongoing cytogenetic work also allows for examination of chromosomes, specific elements within chromosomes and the evolutionary history and comparison of karyotypes. We also examine chicken research efforts with a much more ‘global’ outlook with a greater impact on food security and the impact of climate change, and highlight the efforts of international consortia, such as the Chicken Diversity Consortium. We dedicate this Report to Michael