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Exposure to agents that interfere with the formation and movement of the mitotic spindle apparatus and cause abnormalities in chromosome number result in a greater risk of cancer. Yet the exact molecular mechanisms involved in mediating transcriptional responses to cadmium remain unresolved. Cadmium has been shown to elevate intracellular calcium levels, which could activate multiple signaling cascades. Here we report the functional analysis of two cadmium responsive genes in the nematode Caenorhabditis elegans, numr-1 and numr-2, whose expression, in part, is regulated by alterations in intracellular calcium ([Ca2+]i) levels. In the absence of metal, constitutive expression of numr1/-2 is developmentally regulated with maximal expression in intestinal cells during the L1 larval stage and minimal expression in adults. When adult nematodes are exposed to metal, numr-1/-2 expression increases dramatically in intestinal cells. Taken together, our data suggests that cadmium affects intracellular calcium levels, which may ultimately regulate the transcriptional response of cadmium inducible genes. These results offer insights into the effect of cadmium exposure on calcium homeostasis and signaling pathways. Understanding how the surface physiochemical properties of nanomaterials dictate biocompatibility and potential toxicity is a central challenge in the emerging field of nanotoxicology. In this work, experimental results were employed to develop a generalized linear model to predict the probability of developmental toxicity in zebrafish embryos 24 hours post-fertilization. The experiment consisted of exposing zebrafish embryos to eight different concentrations of gold nanoparticles, with three different core sizes and four different surface modifications with chemical ligands. The toxicity model was statistically developed using physical and structural characteristics of the gold nanoparticles, including nine different chemical property descriptors as predictor variables. Manganese ions are known to form tight complexes with phosphate in vitro, and we have investigated the effects of intracellular phosphate on manganese using the bakers yeast S. Phosphate accumulation and metabolism in Saccharomyces cerevisiae is regulated by the cyclin dependent kinase Pho85 and the cyclin Pho80. When phosphate is abundant, they negatively regulate the transcription of phosphate uptake and metabolism genes. Cells with a genetic deletion of pho80 accumulate increased amounts of multiple species of phosphate. The pho80 genetic deletion strain also accumulates increased levels of manganese when exposed to high manganese and is very sensitive to manganese toxicity. The reduction in manganese sensitivity is dependent on the N-terminal UbL ("ubiquitin-like") domain of Rad23p that interacts with the proteasome. We conclude that manganese toxicity in cells that hyperaccumulate phosphate involves protein turnover effects of the proteosome. Additionally, in animals we observed a dose dependent clear-cut stimulation of sclerostin levels in osteocytes and osteoblasts. We have also identified a putative Smad repressor element in the promoter for sclerostin. Therefore, we investigated the effects of lead on Smad phosphorylation and found a strong blockage of the kinase responsible for its phosphorylation. We hypothesize that lead depresses bone formation through an up regulation of sclerostin and that this regulation is mediated, in part, by blocking Smad activation. The significance of this research lies in the possibility of treating patients with anti sclerostin therapies for the prevention of lead-induced osteoporosis. This finding may provide more understanding of arsenic induced angiogenesis and its promotion of bladder tumor progression. Environmental and Occupational Health Sciences, University Of Washington Arsenic (As) is a well-known environmental toxicant and carcinogen as well as an effective chemotherapeutic agent. The underlying mechanism of this dual capability, however, is not fully understood. Millions of people worldwide are exposed to arsenic (As) via drinking water, various foods, and industrial and mining sites.

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These achievements must be contrasted to medicine 5113 v effective 0.25mcg calcitriol elections symptoms 7 days post iui cheap calcitriol 0.25 mcg online, often in the very same countries (Kenya) or regions (West Africa) where other medicine 4211 v cheap calcitriol 0.25mcg without prescription, non-open elections have resulted in ongoing violence and rejection of the democratic process or outcomes treatment xeroderma pigmentosum purchase calcitriol 0.25mcg on line. Another fascinating case was how open data could be used effectively by the government to influence and change citizen behaviour163. However, the City of Cape Town also took the unprecedented step of releasing micro-data about individual consumption patterns to the extent that monthly updated water consumption patterns at the individual homeowner/plot level was released and rendered graphically on a zoomable, high-resolution map interface. This approach, sailing quite close to 163 Interestingly, this is not a type of impact effect evident in any of the theoretical Open Data impact models. Again, like with open election data, the specific contribution of opening up data cannot be disentangled from other initiatives, including the perhaps exaggerated scare tactics approach, drastic financial tariffs, physical interventions (drop in pipe pressure, installation of cut-off valves), etc. But the fact remains that opening up data contributed towards a world-celebrated previously unheard-of change in water consumption behaviour in an urban crisis situation which is sadly likely to occur in many other cities. Focus needs to be on the entire open data ecosystem, including intermediaries A crucial finding is that open data in Africa needs a vibrant, dynamic, open and multi-tier data ecosystem if the datasets are expected to make a real impact. But the democratizing of information technologies and communication platforms has opened up opportunities among a large and diverse set of intermediaries to explore and combine relevant data sources, sometimes with private or leaked data. The role of open data intermediaries is crucial and has been insufficiently recognised in the African context. In more mature democracies with deep resources, transparent communication infrastructure and a highly educated population, and, often, a long history and entrenched culture of citizen engagement if not activism, a deep ecosystem of data stakeholders can be taken for granted. For open data to make a bigger impact in Africa, the ecosystem needs to be strengthened more. Although activism, social entrepreneurship and community spirit are thriving, data analysis skills and resource pools are shallow and dispersed; institutional structures and support are often fragile, and democratic processes or legal protections may be insufficiently entrenched. In practice, much of the impact is created at the grass-roots level, by a diverse set of small players. Complicating this even further, as put so succinctly by one interviewee: whereas at policy or macro level, it is easy to focus on one particular goal such as poverty, on the ground, all problems are intermixed. This means that a different type of intervention or support mechanism is required to improve the impact of open data initiatives: support needs to be more agile, less formalised, easier to access, smallgrained, allowing for more failures. Our research also showed the success of engaging and building the capacity of collectives that bridge the needs of the underserved with the actors that can address them (macro level). Setting as a priority the support for open data intermediaries (meso level) can bring much more capillarity to program outcomes (in effect widely extending the overall network) and would move the program further in the direction of the demand-side, as was raised earlier. The meso level ­ data journalists, open data advocates, hacktivists, open data local organizations and grassroots networks, technology organizations, grassroots organizations ­ provide a much-needed bridge between the macro level ­ policy-makers, decision-makers, regulatory bodies, global "for development" networks, national statistics offices ­ and the micro level, where needs are accurately diagnosed, and solutions are to be applied. They also provide a tight tissue of formal and informal networks with high levels of trust, enabling the quick spread of instruments and knowledge, or of shared diagnosis that can benefit from higher level (up to global) approaches. Not only did they play a crucial role in the open elections, but they continue to play a key role in promoting government transparency, advocacy of marginalised communities and building stronger democratic structures. This is taking place in an environment where there are often strong political pressures, lack of resources to the media sector as a whole due to declining revenue streams, and against a public tendency of wanting to see more polemic or dramatic news stories i. A few talented, dedicated and idealistic journalists (and their supporting editors and media houses) have to be applauded ­ and more concretely supported164. Sadly, the academic sector in most of Africa is under-resourced with funding to higher education institutions constantly under threat, emphasis on teaching rather than research, ongoing academic brain drain and lack of dedicated research funding. Nevertheless, postgraduate research students and academics should take an intellectual leadership role in open data. Not only by doing research around local open data initiatives, but chiefly so by making more and better use of various open data sets to produce socially relevant and visible research. In addition, the African research community must also start acting as a provider of open data by opening up its research data sets, given that good primary research data in Africa is already in short supply ­ although initially most use of open research data could realistically only be expected within its own ranks. The role of open data is not only vital for research purposes, but also in training a capable cadre of data analysts for professional careers in government and the private sector. Initiatives, where open data sets are used in data analytics courses, will provide the necessary key skills to enable African economies to partake in the fourth industrial revolution. The efforts of a few journalists and other courageous individuals have undoubtedly halted South Africa almost guaranteed slide into another 10 years of wholesale corruption which would have led to an almost certain destruction of the economy if not the entire democratic fibre of its society. However, this report also makes some additional recommendations, aimed at various decision makers and policy setters in the open data ecosystem. Better data will make for better decisions and better lives" Makhtar Diop, Vice President, Africa Region, World Bank (Beegle, 2016, p.

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