Application of chelating weak base resin Dowex M4195 to the recovery of uranium from mixed sulfate/chloride media

The use of untreated seawater or bore water in uranium mineral processing circuits may represent a cheaper and more sustainable water resource for Australia’s mining operations. Using present technologies, the increased salinity from these water sources results in decreased uranium extraction and increased extraction of impurities. There is incentive to overcome these challenges, either through new technologies, or repurposing existing technologies. The ion exchange behaviour of U from sulfate media on the weakly basic chelating resin Dowex M4195 (bis-picolylamine functionality) and the effect of competing chloride and impurity metal ions (Th, Fe, Al, Cu, Ni) has been studied. Experiments to determine acid, and sulfate media behaviour, and extraction thermodynamics including the effect of increasing chloride concentration upon extraction behaviour were carried out. Dowex M4195 was found to have pK1 and pK2 values at 4.13 ± 0.04 and 2.1 ± 0.1 determined at 1.0 M NaCl. Dowex M4195 shows affinity for U(VI) over Fe3+ and Al3+ in sulfuric acid media with a U(VI) pH50 a full pH unit below that of Fe3+ at 0.17 and 1.82 respectively. With increasing chloride concentrations U and Th extraction is suppressed but Fe extraction increases. At the highest chloride concentrations explored Fe is preferentially extracted over U, and Th is not extracted at all. As chloride concentration increases the extraction of U passes through a minimum (40%) before increasing to around 60% for 4.0 M chloride at pH 1.80. Al3+ is not extracted by M4195 under any conditions explored. Dowex M4195 does show high selectivity for Cu and Ni over everything else

Enhancement of mouse hematopoietic stem/progenitor cell function via transient gene delivery using integration-deficient lentiviral vectors

Integration-deficient lentiviruses (IdLVs) deliver genes effectively to tissues but are lost rapidly from dividing cells. This property can be harnessed to express transgenes transiently to manipulate cell biology. Here, we demonstrate the utility of short-term gene expression to improve functional potency of hematopoietic stem and progenitor cells (HSPCs) during transplantation by delivering HOXB4 and Angptl3 using IdLVs to enhance the engraftment of HSPCs. Constitutive overexpression of either of these genes is likely to be undesirable, but the transient nature of IdLVs reduces this risk and those associated with unsolicited gene expression in daughter cells. Transient expression led to increased multilineage hematopoietic engraftment in in vivo competitive repopulation assays without the side effects reported in constitutive overexpression models. Adult stem cell fate has not been programmed previously using IdLVs, but we demonstrate that these transient gene expression tools can produce clinically relevant alterations or be applied to investigate basic biology

Inhibition of Overactive Transforming Growth Factor–β Signaling by Prostacyclin Analogs in Pulmonary Arterial Hypertension

YesHeterozygous loss of function mutations in the type II bone morphogenetic protein receptor (BMPR-II), a member of the transforming growth factor (TGF-β) receptor family, underlie the majority of familial cases of pulmonary arterial hypertension (PAH). The TGF-β1 pathway is activated in PAH and inhibitors of TGF-β1 signaling prevent the development and progression of PAH in experimental models. However, the effect of currently utilized therapies on the TGF-β pathway is not known. Prostacyclin analogues remain the first line of treatment for clinical PAH. We hypothesized that these agents effectively decrease the activity of the TGF-β1 pathway. Beraprost sodium (BPS), a prostacyclin analogue selectively inhibits proliferation in a dose-dependent manner in mouse primary pulmonary arterial smooth muscle cells (PASMCs) harbouring a pathogenic BMPR2 nonsense mutation in both the presence and absence of TGF-β1 stimulation. This study demonstrates that this agent inhibits TGF-β1–induced SMAD-dependent and -independent signaling via a PKA dependent pathway by reducing the phosphorylation of SMADs 2 and 3 and p38MAPK proteins. Finally, in a monocrotaline (MCT)-induced rat model of PAH, which is associated with increased TGF-β signaling, this study confirms that treprostinil (TPS), a stable prostacyclin analogue, inhibits the TGF-β pathway by reducing SMAD3 phosphorylation. Taken together, these data suggest that prostacyclin analogues inhibit dysregulated TGF-β signaling in vitro and in vivo and reduce BMPR-II-mediated proliferation defects in mutant mice PASMCs.The authors acknowledge financial support from the British Heart Foundation, United Kingdom (Programme Grant 1-2004-357 to R.C.T. and N.W.M.), a Heptagon Life Science Proof of Concept Fund (grants KCL24 and KCL25 to M.T.N. and R.C.T., respectively), and the Great Britain Sasakawa Foundation (grant B70 to M.T.N.

COFFEE: A HEALTH FUEL-BLOT POPULAR DRINKING

Now, the days begin with cups of coffee worldwide. Caffeine is the main component of coffee, which is vastly consumed as a psychoactive agent, and in varieties of dietary supplements. Day by day coffee and caffeinated-consumption areas are expanding. Only a single cup of coffee contains thousands of biochemical. Otherwise, during roasting, some of which turn to convert other chemicals moieties. Thus, the coffee is an interesting item to the drug scientists. Upon this jackpot, a number of researches have been done on coffee and its chemical components; in which many postulations are still in contentious and some are unclear to the coffee users. Upon going through the stand-point, this study has been snapshot to sketch a complete overview on coffee and its components. Our finding depicts constituents of coffee to have antioxidant, anti-inflammatory, anti-Alzheimer's disease, anti-Parkinson's disease, and cardioprotective activities. But the anti-cancerous effect of coffee components is not clear yet. In conclusion, coffee, and its constituents are in important in phytopharmacological research.Keywords: Coffee, Coffee components, Health-effect

The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis

The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity

Possible oxidative effects of isotretinoin and modulatory effects of vitamins A and C in Saccharomyces cerevisiae

Isotretinoin (ITN), chemically known as 13-cis-retinoic acid, is a part of the broad group of compounds related to vitamin A. It is particularly employed in the treatment of nodular cystic acne and as an inhibitor of proliferation of neoplastic cells, by exerting a regulatory effect on the cell differentiation. This study aimed at investigating the possible oxidative effects of ITN and modulatory effects of vitamins A and C in mutant and non-mutant Saccharomyces cerevisiae strains. In addition, to reconfirm the oxidative effects, five in vitro antioxidant assays were also prepared taking the alpha-tocopherol analogue, trolox as a standard. In vivo study conducted on S. cerevisiae cells was carried out with ITN 20 μg/ml taking hydrogen peroxide (H2O2) as stressor (STR), whereas ITN 5 to 50 μg/ml was considered for in vitro assays taking similar dose of trolox (TRO). Results show ITN to have oxidative effect in both in vitro and in vivo tests. In conclusion, ITN produced oxidative effects and there may be an hypervitaminosis effect with vitamins A and C, thus insinuation to genetic material.Key words: Assay, isotretinoin, vitamin A, vitamin C, oxidative stress

Trapped in the prison of the mind: notions of climate-induced (im)mobility decision-making and wellbeing from an urban informal settlement in Bangladesh

The concept of Trapped Populations has until date mainly referred to people ‘trapped’ in environmentally high-risk rural areas due to economic constraints. This article attempts to widen our understanding of the concept by investigating climate-induced socio-psychological immobility and its link to Internally Displaced People’s (IDPs) wellbeing in a slum of Dhaka. People migrated here due to environmental changes back on Bhola Island and named the settlement Bhola Slum after their home. In this way, many found themselves ‘immobile’ after having been mobile—unable to move back home, and unable to move to other parts of Dhaka, Bangladesh, or beyond. The analysis incorporates the emotional and psychosocial aspects of the diverse immobility states. Mind and emotion are vital to better understand people’s (im)mobility decision-making and wellbeing status. The study applies an innovative and interdisciplinary methodological approach combining Q-methodology and discourse analysis (DA). This mixed-method illustrates a replicable approach to capture the complex state of climate-induced (im)mobility and its interlinkages to people’s wellbeing. People reported facing non-economic losses due to the move, such as identity, honour, sense of belonging and mental health. These psychosocial processes helped explain why some people ended up ‘trapped’ or immobile. The psychosocial constraints paralysed them mentally, as well as geographically. More empirical evidence on how climate change influences people’s wellbeing and mental health will be important to provide us with insights in how to best support vulnerable people having faced climatic impacts, and build more sustainable climate policy frameworks

PomBase – the scientific resource for fission yeast

The fission yeast Schizosaccharomyces pombe has become well established as a model species for studying conserved cell-level biological processes, especially the mechanics and regulation of cell division. PomBase integrates the S. pombe genome sequence with traditional genetic, molecular and cell biological experimental data as well as the growing body of large datasets generated by emerging high-throughput methods. This chapter provides insight into the curation philosophy and data organization at PomBase, and provides a guide to using PomBase for infrequent visitors and anyone considering exploring S. pombe in their research

Mug20, a novel protein associated with linear elements in fission yeast meiosis

In the fission yeast, Schizosaccharomyces pombe, homologous chromosomes efficiently pair and recombine during meiotic prophase without forming a canonical synaptonemal complex (SC). Instead, it features simpler filamentous structures, the so-called linear elements (LinEs), which bear some resemblance to the axial/lateral element subunits of the SC. LinEs are required for wild-type recombination frequency. Here, we recognized Mug20, the product of a meiotically upregulated gene, as a LinE-associated protein. GFP-tagged Mug20 and anti-Mug20 antibody co-localized completely with Rec10, one of the major constituents of LinEs. In the absence of Mug20, LinEs failed to elongate beyond their initial state of nuclear dots. Foci of recombination protein Rad51 and genetic recombination were reduced. Since meiotic DNA double-strand breaks (DSBs), which initiate recombination, are induced at sites of preformed LinEs, we suggest that reduced recombination is a consequence of incomplete LinE extension. Therefore, we propose that Mug20 is required to extend LinEs from their sites of origin and thereby to increase DSB proficient regions on chromosomes