57 research outputs found

    GPI-anchored receptor clusters transiently recruit Lyn and Gα for temporary cluster immobilization and Lyn activation: single-molecule tracking study 1

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    The signaling mechanisms for glycosylphosphatidylinositol-anchored receptors (GPI-ARs) have been investigated by tracking single molecules in living cells. Upon the engagement or colloidal gold–induced cross-linking of CD59 (and other GPI-ARs) at physiological levels, CD59 clusters containing three to nine CD59 molecules were formed, and single molecules of Gαi2 or Lyn (GFP conjugates) exhibited the frequent but transient (133 and 200 ms, respectively) recruitment to CD59 clusters, via both protein–protein and lipid–lipid (raft) interactions. Each CD59 cluster undergoes alternating periods of actin-dependent temporary immobilization (0.57-s lifetime; stimulation-induced temporary arrest of lateral diffusion [STALL], inducing IP3 production) and slow diffusion (1.2 s). STALL of a CD59 cluster was induced right after the recruitment of Gαi2. Because both Gαi2 and Lyn are required for the STALL, and because Lyn is constitutively recruited to CD59 clusters, the STALL of CD59 clusters is likely induced by the Gαi2 binding to, and its subsequent activation of, Lyn within the same CD59 cluster

    Diurnal Variation of Human Sweet Taste Recognition Thresholds Is Correlated With Plasma Leptin Levels

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    OBJECTIVE—It has recently been proposed that the peripheral taste organ is one of the targets for leptin. In lean mice, leptin selectively suppresses gustatory neural and behavioral responses to sweet compounds without affecting responses to other taste stimuli, whereas obese diabetic db/db mice with defects in leptin receptor lack this leptin suppression on sweet taste. Here, we further examined potential links between leptin and sweet taste in humans

    Genetic and Molecular Basis of Individual Differences in Human Umami Taste Perception

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    Umami taste (corresponds to savory in English) is elicited by L-glutamate, typically as its Na salt (monosodium glutamate: MSG), and is one of five basic taste qualities that plays a key role in intake of amino acids. A particular property of umami is the synergistic potentiation of glutamate by purine nucleotide monophosphates (IMP, GMP). A heterodimer of a G protein coupled receptor, TAS1R1 and TAS1R3, is proposed to function as its receptor. However, little is known about genetic variation of TAS1R1 and TAS1R3 and its potential links with individual differences in umami sensitivity. Here we investigated the association between recognition thresholds for umami substances and genetic variations in human TAS1R1 and TAS1R3, and the functions of TAS1R1/TAS1R3 variants using a heterologous expression system. Our study demonstrated that the TAS1R1-372T creates a more sensitive umami receptor than -372A, while TAS1R3-757C creates a less sensitive one than -757R for MSG and MSG plus IMP, and showed a strong correlation between the recognition thresholds and in vitro dose - response relationships. These results in human studies support the propositions that a TAS1R1/TAS1R3 heterodimer acts as an umami receptor, and that genetic variation in this heterodimer directly affects umami taste sensitivity

    The activity of the histone chaperone yeast Asf1 in the assembly and disassembly of histone H3/H4–DNA complexes

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    The deposition of the histones H3/H4 onto DNA to give the tetrasome intermediate and the displacement of H3/H4 from DNA are thought to be the first and the last steps in nucleosome assembly and disassembly, respectively. Anti-silencing function 1 (Asf1) is a chaperone of the H3/H4 dimer that functions in both of these processes. However, little is known about the thermodynamics of chaperone–histone interactions or the direct role of Asf1 in the formation or disassembly of histone–DNA complexes. Here, we show that Saccharomyces cerevisiae Asf1 shields H3/H4 from unfavorable DNA interactions and aids the formation of favorable histone–DNA interactions through the formation of disomes. However, Asf1 was unable to disengage histones from DNA for tetrasomes formed with H3/H4 and strong nucleosome positioning DNA sequences or tetrasomes weakened by mutant (H3K56Q/H4) histones or non-positioning DNA sequences. Furthermore, Asf1 did not associate with preformed tetrasomes. These results are consistent with the measured affinity of Asf1 for H3/H4 dimers of 2.5 nM, which is weaker than the association of H3/H4 for DNA. These studies support a mechanism by which Asf1 aids H3/H4 deposition onto DNA but suggest that additional factors or post-translational modifications are required for Asf1 to remove H3/H4 from tetrasome intermediates in chromatin

    The Rare Earth Elements: demand, global resources, and challenges for resourcing future generations

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    The rare earth elements (REE) have attracted much attention in recent years, being viewed as critical metals because of China’s domination of their supply chain. This is despite the fact that REE enrichments are known to exist in a wide range of settings, and have been the subject of much recent exploration. Although the REE are often referred to as a single group, in practice each individual element has a specific set of end-uses, and so demand varies between them. Future demand growth to 2026 is likely to be mainly linked to the use of NdFeB magnets, particularly in hybrid and electric vehicles and wind turbines, and in erbium-doped glass fiber for communications. Supply of lanthanum and cerium is forecast to exceed demand. There are several different types of natural (primary) REE resources, including those formed by high-temperature geological processes (carbonatites, alkaline rocks, vein and skarn deposits) and those formed by low-temperature processes (placers, laterites, bauxites and ion-adsorption clays). In this paper, we consider the balance of the individual REE in each deposit type and how that matches demand, and look at some of the issues associated with developing these deposits. This assessment and overview indicate that while each type of REE deposit has different advantages and disadvantages, light rare earth-enriched ion adsorption types appear to have the best match to future REE needs. Production of REE as by-products from, for example, bauxite or phosphate, is potentially the most rapid way to produce additional REE. There are still significant technical and economic challenges to be overcome to create substantial REE supply chains outside China

    The origin and composition of carbonatite-derived carbonate-bearing fluorapatite deposits

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    Carbonate-bearing fluorapatite rocks occur at over 30 globally distributed carbonatite complexes and represent a substantial potential supply of phosphorus for the fertiliser industry. However, the process(es) involved in forming carbonate-bearing fluorapatite at some carbonatites remain equivocal, with both hydrothermal and weathering mechanisms inferred. In this contribution, we compare the paragenesis and trace element contents of carbonate-bearing fluorapatite rocks from the Kovdor, Sokli, Bukusu, Catalão I and Glenover carbonatites in order to further understand their origin, as well as to comment upon the concentration of elements that may be deleterious to fertiliser production. The paragenesis of apatite from each deposit is broadly equivalent, comprising residual magmatic grains overgrown by several different stages of carbonate-bearing fluorapatite. The first forms epitactic overgrowths on residual magmatic grains, followed by the formation of massive apatite which, in turn, is cross-cut by late euhedral and colloform apatite generations. Compositionally, the paragenetic sequence corresponds to a substantial decrease in the concentration of rare earth elements (REE), Sr, Na and Th, with an increase in U and Cd. The carbonate-bearing fluorapatite exhibits a negative Ce anomaly, attributed to oxic conditions in a surficial environment and, in combination with the textural and compositional commonality, supports a weathering origin for these rocks. Carbonate-bearing fluorapatite has Th contents which are several orders of magnitude lower than magmatic apatite grains, potentially making such apatite a more environmentally attractive feedstock for the fertiliser industry. Uranium and cadmium contents are higher in carbonate-bearing fluorapatite than magmatic carbonatite apatite, but are much lower than most marine phosphorites

    Study on the Critical Metal and Rare Earth Element Occurrences in Sulawesi

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    As the development of modern-high technology application is growing, demands of the constant supply of Scandium (Sc) and rare earth elements (REE) as a new green source of energy is increasing. Meanwhile, source of these elements are limited hence new source of these minerals have to be found. Nowadays, Scandium (Sc) is an important metal for electrolyte of solid oxide fuel cells and the demand is likely to increase in the near future. In addition, REE is an important element in the use of permanent magnets and rechargeable batteries. Exploration on critical metals and rare earth element in Indonesia is still scarce due to lacking of skillful human resource who understand about the occurrences and distribution of these elements. Based on the most update investigation, critical metal particularly Scandium can be found in weathering crust of highly weathered nickelcontained ultramafic rock. Scandium will be concentrated in limonite and saprolite layer, but the volume of enrichment is still unknown. Meanwhile, rare earth element found in granitic rocks particularly in zircon, monazite and xenotime. It has been reported that rare earth ore were extracted from heavily weathered granitic rocks. Sulawesi Island is one of the island where lateritic deposit from heavily weathered ultramafic can be found. The lateritic soil can be potential source of scandium. Meanwhile, granitic rocks cover almost 20% of the island which also potential source of rare earth element. These suggest that Sulawesi Island has a big potential and challenge for critical metal and rare earth element exploration. This manuscript reports the exploration potential and challenge of critical metal and rare earth element in Sulawesi based on geological data
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