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  • 1
    Language: English
    In: Science (New York, N.Y.), 20 January 2012, Vol.335(6066), pp.332-5
    Description: Infections with Shiga toxin (STx)-producing bacteria cause more than a million deaths each year and have no definitive treatment. To exert its cytotoxic effect, STx invades cells through retrograde membrane trafficking, escaping the lysosomal degradative pathway. We found that the widely available metal manganese (Mn(2+)) blocked endosome-to-Golgi trafficking of STx and caused its degradation in lysosomes. Mn(2+) targeted the cycling Golgi protein GPP130, which STx bound in control cells during sorting into Golgi-directed endosomal tubules that bypass lysosomes. In tissue culture cells, treatment with Mn(2+) yielded a protection factor of 3800 against STx-induced cell death. Furthermore, mice injected with nontoxic doses of Mn(2+) were completely resistant to a lethal STx challenge. Thus, Mn(2+) may represent a low-cost therapeutic agent for the treatment of STx infections.
    Keywords: Endosomes -- Metabolism ; Lysosomes -- Metabolism ; Manganese -- Pharmacology ; Shiga Toxin 1 -- Metabolism ; Shiga Toxins -- Metabolism
    ISSN: 00368075
    E-ISSN: 1095-9203
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  • 2
    In: Nature, 2012, Vol.486(7401), p.101
    Description: The isotopes super(129)Xe, produced from the radioactive decay of extinct super(129)I, and super(136)Xe, produced from extinct super(244)Pu and extant super(238)U, have provided important constraints on early mantle outgassing and volatile loss from Earth. The low ratios of radiogenic to non-radiogenic xenon ( super(129)Xe/ super(130)Xe) in ocean island basalts (OIBs) compared with mid-ocean-ridge basalts (MORBs) have been used as evidence for the existence of a relatively undegassed primitive deep-mantle reservoir. However, the low super(129)Xe/ super(130)Xe ratios in OIBs have also been attributed to mixing between subducted atmospheric Xe and MORB Xe, which obviates the need for a less degassed deep-mantle reservoir. Here I present new noble gas (He, Ne, Ar, Xe) measurements from an Icelandic OIB that reveal differences in elemental abundances and super(20)Ne/ super(22)Ne ratios between the Iceland mantle plume and the MORB source. These observations show that the lower super(129)Xe/ super(130)Xe ratios in OIBs are due to a lower I/Xe ratio in the OIB mantle source and cannot be explained solely by mixing atmospheric Xe with MORB-type Xe. Because super(129)I became extinct about 100 million years after the formation of the Solar System, OIB and MORB mantle sources must have differentiated by 4.45 billion years ago and subsequent mixing must have been limited. The Iceland plume source also has a higher proportion of Pu- to U-derived fission Xe, requiring the plume source to be less degassed than MORBs, a conclusion that is independent of noble gas concentrations and the partitioning behaviour of the noble gases with respect to their radiogenic parents. Overall, these results show that Earth's mantle accreted volatiles from at least two separate sources and that neither the Moon-forming impact nor 4.45 billion years of mantle convection has erased the signature of Earth's heterogeneous accretion and early differentiation.
    Keywords: Plumes ; Ane, Atlantic, Iceland ; Convection ; Air Pollution;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 3
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 11 January 2011, Vol.108(2), pp.858-63
    Description: P-type ATPases transport a wide array of ions, regulate diverse cellular processes, and are implicated in a number of human diseases. However, mechanisms that increase ion transport by these ubiquitous proteins are not known. SPCA1 is a P-type pump that transports Mn(2+) from the cytosol into the Golgi. We developed an intra-Golgi Mn(2+) sensor and used it to screen for mutations introduced in SPCA1, on the basis of its predicted structure, which could increase its Mn(2+) pumping activity. Remarkably, a point mutation (Q747A) predicted to increase the size of its ion permeation cavity enhanced the sensor response and a compensatory mutation restoring the cavity to its original size abolished this effect. In vivo and in vitro Mn(2+) transport assays confirmed the hyperactivity of SPCA1-Q747A. Furthermore, increasing Golgi Mn(2+) transport by expression of SPCA1-Q747A increased cell viability upon Mn(2+) exposure, supporting the therapeutic potential of increased Mn(2+) uptake by the Golgi in the management of Mn(2+)-induced neurotoxicity.
    Keywords: Mutation ; Adenosine Triphosphatases -- Chemistry ; Calcium-Transporting Atpases -- Genetics ; Golgi Apparatus -- Metabolism ; Manganese -- Chemistry ; Proton-Translocating Atpases -- Chemistry
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 4
    Language: English
    In: Journal of Hydrology, Jan 4, 2012, Vol.412-413, p.14(20)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jhydrol.2011.06.005 Byline: Biswajit Mukhopadhyay Keywords: Perennial snow and ice covers; Climate change; Water availability model; Upper Indus Basin; Himalaya; Karakoram Abstract: a* A monthly river flow model of Upper Indus Basin with MODIS derived snow covered areas. a* Perennial snow/ice covers within the Upper Indus Basin has decreased in recent years. a* Decrease in perennial snow/ice covers has dual effects on river flow characteristics. a* Decrease in discharge rates during the peak melting season (June-August). a* Shift of peak discharge period from July/August to late spring/early summer (May/June). Author Affiliation: Water Infrastructure Program, Jacobs Engineering Group, Inc., 7950 Elmbrook Drive, Dallas, Texas 75247-4951, USA
    Keywords: Hydrology -- Analysis ; Hydrology -- Models
    ISSN: 0022-1694
    Source: Cengage Learning, Inc.
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  • 5
    Language: English
    In: Tetrahedron Letters, 30 November 2011, Vol.52(48), pp.6431-6438
    Description: A new methodology has been developed towards the room temperature synthesis of novel 2-amino-5-alkylidenethiazol-4-ones from aldehydes, amines and rhodanine in one-pot. A heterogeneous dipolar catalyst has been utilized for this reaction. The unique properties of this catalyst effectively synthesize such compounds at room temperature in contrast to all earlier reports.
    Keywords: 2-Amino-5-Alkylidenethiazol-4-Ones ; Dipolar Catalyst ; Silica-Based Substituted Pyridine ; Carbon-13 CP Mas NMR ; Bet Surface Area Analysis ; Chemistry
    ISSN: 0040-4039
    E-ISSN: 1873-3581
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  • 6
    Language: English
    In: Tetrahedron, 2011, Vol.67(41), pp.7936-7945
    Description: A new methodology has been developed towards the synthesis of novel 2-amino-5-alkylidenethiazol-4-ones from ketones, amines, and rhodanine. This is the first report of the use of ketones in contrast to aldehydes in all the earlier reported procedures. A new heterogeneous dipolar catalyst is designed and synthesized for this reaction. The unique properties of this catalyst facilitate the synthesis of such compounds. These 5-alkylidene rhodanine precursors display wide range of biological activities to possess antiviral, antimicrobial, cardiotonic and anti-inflammatory effects.
    Keywords: 2-Amino-5-Alkylidenethiazol-4-Ones ; Ketones ; Rhodanine ; Amines ; Dipolar Catalyst ; Silica Based Substituted Pyridine ; Chemistry
    ISSN: 0040-4020
    E-ISSN: 1464-5416
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  • 7
    Language: English
    In: Journal of Biological Chemistry, 02/07/2014, Vol.289(6), pp.3825-3825
    Keywords: Chemistry ; Anatomy & Physiology;
    ISSN: 0021-9258
    E-ISSN: 1083-351X
    Source: CrossRef
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  • 8
    Language: English
    In: Journal of Consumer Research, 01 February 2012, Vol.38(5), pp.815-832
    Description: This research presents a comprehensive conceptual model of the dynamics of goal revision over multiple periods. First, based on an integrative literature review, we derive four principles that govern how individuals update their goals over time (monotonicity, diminishing sensitivity, aspiration maximization, and performance satisficing). We then integrate these principles logically as well as mathematically into a goal-discrepancy response function. Next, we advance existing cybernetic models of self-regulation by synthesizing the four principles and the response function into a Test-Operate-Test-Adjust-Loop (TOTAL) model, which captures the dynamics of goal revision in self-regulation. We report four laboratory experiments that demonstrate initial support for the postulates of our model and conclude with a discussion of limitations and future directions.
    Keywords: Goal Setting ; Self Control ; Consumer Behavior ; Models ; Studies ; Market Research ; Experiment/Theoretical Treatment;
    ISSN: 00935301
    E-ISSN: 15375277
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  • 9
    Language: English
    In: Nature, August 2018, Vol.560(7717), pp.223-227
    Description: The long-term exchange of volatile species (such as water, carbon, nitrogen and the noble gases) between deep Earth and surface reservoirs controls the habitability of the Earth's surface. The present-day volatile budget of the mantle reflects the integrated history of outgassing and retention of primordial volatiles delivered to the planet during accretion, volatile species generated by radiogenic ingrowth and volatiles transported into the mantle from surface reservoirs over time. Variations in the distribution of volatiles between deep Earth and surface reservoirs affect the viscosity, cooling rate and convective stress state of the solid Earth. Accordingly, constraints on the flux of surface volatiles transported into the deep Earth improve our understanding of mantle convection and plate tectonics. However, the history of surface volatile regassing into the mantle is not known. Here we use mantle xenon isotope systematics to constrain the age of initiation of volatile regassing into the deep Earth. Given evidence of prolonged evolution of the xenon isotopic composition of the atmosphere, we find that substantial recycling of atmospheric xenon into the deep Earth could not have occurred before 2.5 billion years ago. Xenon concentrations in downwellings remained low relative to ambient convecting mantle concentrations throughout the Archaean era, and the mantle shifted from a net degassing to a net regassing regime after 2.5 billion years ago. Because xenon is carried into the Earth's interior in hydrous mineral phases, our results indicate that downwellings were drier in the Archaean era relative to the present. Progressive drying of the Archean mantle would allow slower convection and decreased heat transport out of the mantle, suggesting non-monotonic thermal evolution of the Earth's interior.
    Keywords: Geochemical Cycles – Observations ; Mantle (Geology) – Chemical Properties ; Mantle (Geology) – Environmental Aspects ; Xenon – Chemical Properties ; Xenon – Environmental Aspects;
    ISSN: 00280836
    E-ISSN: 1476-4687
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  • 10
    Language: English
    In: Nature, November 2018, Vol.563(7732), pp.E28
    Description: In this Letter, owing to a production error, the arrows in the middle panel of Fig. 1 were wrongly coloured and there were some some typos elsewhere. These errors have been corrected online.
    ISSN: 00280836
    E-ISSN: 1476-4687
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