Chemical fluxes from time series sampling of the Irrawaddy and Salween Rivers, Myanmar

The Irrawaddy and Salween rivers in Myanmar deliver water fluxes to the ocean equal to ~ 70% of the Ganges–Brahmaputra river system. Together these systems are thought to deliver about half the dissolved load from the tectonically active Himalayan–Tibetan orogen. Previously very little data was available on the dissolved load and isotopic compositions of these major rivers. Here we present time series data of 171 samples collected fortnightly at intervals throughout 2004 to 2007 from the Irrawaddy and Salween at locations near both the river mouths, the up-stream Irrawaddy at Myitkyina, the Chindwin, a major tributary of the Irrawaddy and a set of 28 small tributaries which rise in the flood plain of the Irrawaddy between Yangon and Mandalay. The samples have been analysed for major cation, anion and 87Sr/86Sr ratios. The new data indicates that the Irrawaddy has an annual average Na concentration only a third of the widely quoted single previously published analysis. The Irrawaddy and Salween drain about 0.5% of global continental area and deliver about 3.3% of the global silicate-derived dissolved Ca + Mg fluxes and 2.6% of the global Sr riverine fluxes to the oceans. This compares with Ganges and Brahmaputra which deliver about 3.4% of the global silicate-derived dissolved Ca + Mg fluxes and 3.2% of the global Sr riverine fluxes to the oceans from about 1.1% of global continental area. The discharge-weighted mean 87Sr/86Sr ratio of the Irrawaddy is 0.71024 and the Salween 0.71466. The chemistry of the Salween and the Irrawaddy waters reflects their different bedrock geology. The catchment of the Salween extends across the Shan Plateau in Myanmar through the Eastern syntaxis of the Himalayas and into Tibet. The Irrawaddy flows over the Cretaceous and Tertiary magmatic and metamorphic rocks exposed along the western margin of the Shan Plateau and the Cretaceous to Neogene Indo-Burma ranges. The 87Sr/86Sr compositions of the Salween and Upper Irrawaddy (between 0.7128 and 0.7176) are significantly higher than the downstream Irrawaddy (0.7095 to 0.7108) and the Chindwin (0.7082 to 0.7095). The Irrawaddy and the Chindwin exhibit lower 87Sr/86Sr and Na/Ca ratios during and immediately post-monsoon, interpreted to reflect higher weathering of carbonate at high flow. The Salween exhibits higher 87Sr/86Sr ratios but lower Na/Ca ratios during the monsoon, interpreted to reflect higher inputs from the upper parts of the catchment in the Himalayas.The research was funded by the UK Natural Environmental Research Council grant NE/C513850/1.This is the final published version. It first appeared at: http://www.sciencedirect.com/science/article/pii/S0009254115000510#

TCTP protects from apoptotic cell death by antagonizing bax function

International audienceTranslationally controlled tumor protein (TCTP) is a potential target for cancer therapy. It functions as a growth regulating protein implicated in the TSC1-TSC2 -mTOR pathway or a guanine nucleotide dissociation inhibitor for the elongation factors EF1A and EF1Bbeta. Accumulating evidence indicates that TCTP also functions as an antiapoptotic protein, through a hitherto unknown mechanism. In keeping with this, we show here that loss of tctp expression in mice leads to increased spontaneous apoptosis during embryogenesis and causes lethality between E6.5 and E9.5. To gain further mechanistic insights into this apoptotic function, we solved and refined the crystal structure of human TCTP at 2.0 A resolution. We found a structural similarity between the H2-H3 helices of TCTP and the H5-H6 helices of Bax, which have been previously implicated in regulating the mitochondrial membrane permeability during apoptosis. By site-directed mutagenesis we establish the relevance of the H2-H3 helices in TCTP's antiapoptotic function. Finally, we show that TCTP antagonizes apoptosis by inserting into the mitochondrial membrane and inhibiting Bax dimerization. Together, these data therefore further confirm the antiapoptotic role of TCTP in vivo and provide new mechanistic insights into this key function of TCTP

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The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein. TCTP is able to interact with a large number of other proteins and is therefore involved in many core cell biological processes, predominantly in the response to cellular stresses, such as oxidative stress, heat shock, genotoxic stress, imbalance of ion metabolism as well as other conditions. Mechanistically, TCTP acts as an anti-apoptotic protein, and it is involved in DNA-damage repair and in cellular autophagy. Thus, broadly speaking, TCTP can be considered a cytoprotective protein. In addition, TCTP facilitates cell division through stabilising the mitotic spindle and cell growth through modulating growth signalling pathways and through its interaction with the proteosynthetic machinery of the cell. Due to its activities, both as an anti-apoptotic protein and in promoting cell growth and division, TCTP is also essential in the early development of both animals and plants. Apart from its involvement in various biological processes at the cellular level, TCTP can also act as an extracellular protein and as such has been involved in modulating whole-body defence processes, namely in the mammalian immune system. Extracellular TCTP, typically in its dimerised form, is able to induce the release of cytokines and other signalling molecules from various types of immune cells. There are also several examples, where TCTP was shown to be involved in antiviral/antibacterial defence in lower animals. In plants, the protein appears to have a protective effect against phytotoxic stresses, such as flooding, draught, too high or low temperature, salt stress or exposure to heavy metals. The finding for the latter stress condition is corroborated by earlier reports that TCTP levels are considerably up-regulated upon exposure of earthworms to high levels of heavy metals. Given the involvement of TCTP in many biological processes aimed at maintaining cellular or whole-body homeostasis, it is not surprising that dysregulation of TCTP levels may promote a range of disease processes, foremost cancer. Indeed a large body of evidence now supports a role of TCTP in at least the most predominant types of human cancers. Typically, this can be ascribed to both the anti-apoptotic activity of the protein and to its function in promoting cell growth and division. However, TCTP also appears to be involved in the later stages of cancer progression, such as invasion and metastasis. Hence, high TCTP levels in tumour tissues are often associated with a poor patient outcome. Due to its multiple roles in cancer progression, TCTP has been proposed as a potential target for the development of new anti-cancer strategies in recent pilot studies. Apart from its role in cancer, TCTP dysregulation has been reported to contribute to certain processes in the development of diabetes, as well as in diseases associated with the cardiovascular system. Since cellular TCTP levels are highly regulated, e.g. in response to cell stress or to growth signalling, and because deregulation of this protein contributes to many disease processes, a detailed understanding of regulatory processes that impinge on TCTP levels is required. The last section of this chapter summarises our current knowledge on the mechanisms that may be involved in the regulation of TC