Wilson disease protein, ATP7B maintains copper homeostasis in the liver. ATP7B traffics from trans-Golgi network to endolysosomes to export excess copper. Regulation of ATP7B trafficking to and fro endolysosomes is not well understood. We investigated the fate of ATP7B, post-copper export. At high copper ATP7B traffics primarily to acidic, active hydrolase (Cathepsin-B) positive endolysosomes and upon subsequent copper chelation, returns to trans-Golgi network. At high copper, ATP7B co-localizes with endolysosomal markers and with core member of retromer complex, VPS35. Knocking down VPS35 did not abrogate copper export function of ATP7B or its copper-responsive anterograde trafficking to vesicles; rather upon subsequent copper chelation, ATP7B failed to relocalize to TGN that was rescued by overexpressing wtVPS35. Overexpressing mutants of retromer complex associated proteins, Rab7 and COMMD1 yielded similar non-recycling phenotype of ATP7B. At high copper, VPS35 and ATP7B are juxtaposed on the same endolysosome and form a large complex that is stabilized by in-vivo photoamino acid labeling and UV-crosslinking. We demonstrate that retromer regulates endolysosome to TGN trafficking of copper transporter ATP7B and it is dependent upon intracellular copper.
Currently, research on terbium has gained a momentum owing to its four short-lived radioisotopes, 149Tb, 152Tb, 155Tb, and 161Tb, all of which can be considered in one or another field of nuclear medicine. The members of this emerging quadruplet family have appealing nuclear characteristics and have the potential to do justice to the proposed theory of theranostics nuclear medicine, which amalgamates therapeutic and diagnostic radioisotopes together. The main challenge for in vivo use of these radioisotopes is to produce them in sufficient quantity. This review discusses that, at present, neither light charged particle nor the heavy ion (HI) activation are suitable for large-scale production of neutron deficient terbium nuclides. Three technological factors like (i) enrichment of stable isotopes to a considerable level, (ii) non-availability of higher energies in commercial cyclotrons, and (iii) non-availability of the isotope separation technique coupled with commercial accelerators limit the large scale production of terbium radionuclides by light charged particle activation. If in future, the technology can overcome these hurdles, then the light charged particle activation of enriched targets would produce a high amount of useful terbium radionuclides. On the other hand, to date, the spallation reaction coupled with an online isotope separator has been found suitable for such a requirement, which has been adopted by the CERN MEDICIS programme. The therapeutic 161Tb radionuclide can be produced in a reactor by neutron bombardment on enriched 160Gd target to produce 161Gd which subsequently decays to 161Tb. The radiochemical separation is mandatory even if the ISOL technique is used to obtain high radioisotopic purity of the desired radioisotope.
Endophytic microbes isolated from plants growing in contaminated habitats possess specialized properties that help their host detoxify the contaminant/s. The possibility of using microbe-assisted phytoremediation for the clean-up of Arsenic (As) contaminated soils of the Ganga-Brahmaputra delta of India, was explored using As-tolerant endophytic microbes from an As-tolerant plant Lantana camara collected from the contaminated site and an intermediate As-accumulator plant Solanum nigrum. Endophytes from L. camara established within S. nigrum as a surrogate host. The microbes most effectively improved plant growth besides increasing bioaccumulation and root-to-shoot transport of As when applied as a consortium. Better phosphate nutrition, photosynthetic performance, and elevated glutathione levels were observed in consortium-treated plants particularly under As-stress. The consortium maintained heightened ROS levels in the plant without any deleterious effect and concomitantly boosted distinct antioxidant defense mechanisms in the shoot and root of As-treated plants. Increased consortium-mediated As(V) to As(III) conversion appeared to be a crucial step in As-detoxification/translocation. Four aquaporins were differentially regulated by the endophytes and/or As. The most interesting finding was the strong upregulation of an MRP transporter in the root by the As + endophytes, which suggested a major alteration of As-detoxification/accumulation pattern upon endophyte treatment that improved As-phytoremediation.
Integration of palaeobotanical (spores, pollen, phytoliths and non-pollen palynomorphs) and organic geochemical proxies, such as stable isotopes of organic carbon (δ13C) and n-alkanes, for studying the evolution and palaeoenvironmental conditions of an archaeological site are rare in India. The evolution of a protohistoric-historic site at Erenda, situated in the eastern coastal region of India, has been studied by using multiple palaeobotanical and organic geochemical proxies assisted with AMS radiocarbon dates. The excavated site lies above Late Pleistocene–Early Holocene Sijua Formation. The absence of anthropogenic evidence in the Sijua Formation likely indicates inhabitable conditions in nearshore/estuarine marshy conditions. The earliest human settlements at the excavation site begin during the first millennium BCE after the initiation of habitable conditions along the coast. The presence of fungal spores and the dominance of C4 phytolith morphotypes indicate prevailing warm and humid climatic conditions and proximity to a freshwater body. The δ13C signature and n-alkane composition indicate the use of C4 grass for the construction of the mud and clay-built huts. The settlers most likely used to consume wild or domestic variety of rice, as evidenced by the presence of bilobate scooped morphotypes. The site was partly abandoned, covered with C3 and C4 vegetation and used as a dumping ground after 663 ± 92 BCE. This implies that people continued to live in the area but possibly moved to a nearby site while using the excavated site as refuse.
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