551 research outputs found
Garnet: Witness to the Evolution of Destructive Plate Boundaries
Thanks to its unique chemical and mechanical properties, garnet records evidence of rocks\u27 paths through the crust at tectonic plate boundaries. The compositions of garnet and coexisting mineral phases permit metamorphic pressure and temperature to be determined, while garnet\u27s compositional zoning allows the evolution of these parameters to be constrained. But careful study of garnet reveals far more, including the dehydration history of subducted oceanic crust, the depths reached during the earliest stages of continental collision, and the mechanisms driving heat and mass flow as orogens develop. Overall, chemical and textural characterization of garnet can be coupled with thermodynamic, thermoelastic, geochronologic, diffusion, and geodynamic models to constrain the evolution of rocks in a wide variety of settings
Preservation of Garnet Growth Zoning and the Duration of Prograde Metamorphism
Chemically zoned garnet growth and coeval modification of this zoning through diffusion are calculated during prograde metamorphic heating to temperatures of up to 850°C. This permits quantification of how the preservation or elimination of zoning profiles in garnet crystals of a given size is sensitive to the specific burial and heating (P-T) path followed, and the integrated duration spent at high temperature (dT/dt). Slow major element diffusion in garnet at T 30 Myr at amphibolite-grade conditions, but small-scale (tens of micrometres) zoning features will be lost early in the prograde stage unless this is ‘rapid' (5 Myr for rocks reaching c. 600°C). Calculations indicate that preservation of unmodified growth compositions in even relatively large (up to 3 mm diameter) pelitic garnet crystals requires prograde and exhumational events to be <10 Myr for rocks reaching c. 600°C. This timescale can be 5 Myr for garnet in rocks reaching 650°C or hotter. It is likely, therefore, that most natural prograde-zoned crystals record compositions already partially re-equilibrated between the time of crystal growth and of reaching maximum temperature. However, a large T-t window exists within which crystals begin to lose their growth compositions but retain evidence of crystal-scale zoning trends that may still be useful for thermobarometry purposes. The upper limit of this window for 500 μm diameter crystals can be as much as several tens of millions of years of heating to c. 700°C. Absolute re-equilibration timescales can be significantly different for garnet growing in different rock compositions, with examples of a granodiorite and a pelite give
Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition
Inositol phosphates (InsPs) are signaling molecules with multiple roles in cells. In particular Graphic (InsP6) is involved in mRNA export and editing or chromatin remodeling among other events. InsP6 accumulates as mixed salts (phytate) in storage tissues of plants and plays a key role in their physiology. Human diets that are exclusively grain-based provide an excess of InsP6 that, through chelation of metal ions, may have a detrimental effect on human health. Ins(1,3,4,5,6)P5 2-kinase (InsP5 2-kinase or Ipk1) catalyses the synthesis of InsP6 from InsP5 and ATP, and is the only enzyme that transfers a phosphate group to the axial 2-OH of the myo-inositide. We present the first structure for an InsP5 2-kinase in complex with both substrates and products. This enzyme presents a singular structural region for inositide binding that encompasses almost half of the protein. The key residues in substrate binding are identified, with Asp368 being responsible for recognition of the axial 2-OH. This study sheds light on the unique molecular mechanism for the synthesis of the precursor of inositol pyrophosphates
Correlation of Growth and Breakdown of Major and Accessory Minerals in Metapelites from Campolungo, Central Alps
Regionally metamorphosed pelitic rocks at Campolungo, Central Alps, contain biotite, muscovite, garnet, staurolite, kyanite, and quartz, and the minor minerals tourmaline, plagioclase, chlorite, rutile, and ilmenite. Accessory allanite, apatite, monazite, potassium feldspar, xenotime, and zircon have also been identified. The bulk-rock chemical composition is similar to that of shales, and indicates that the protolith was deposited in an active continental margin setting. Element distribution maps, electron microprobe analyses and in situ UV-laser ablation inductively coupled plasma mass spectrometry data document a pronounced zoning in garnet and tourmaline porphyroblasts. Garnet displays a typical bell-shaped MnO zoning profile, with a maximum (∼3 wt %) in the euhedral core. Cores are also rich in Y and heavy rare earth elements (HREE; e.g. 2150 ppm Y). In their broad rim, all garnet crystals display a subhedral annulus (10-15 µm wide), which is distinctly enriched in Ca, Sr, Y, and HREE, and which probably resulted from the breakdown of allanite (at ∼550°C, ∼6·4 kbar). Another characteristic feature of garnet rims is their sinusoidal chondrite-normalized REE pattern, which may represent partial equilibration with a light REE-enriched medium, probably generated through the breakdown of metamorphic allanite. Similar REE patterns are exhibited by a Ca-poor internal zone (inside the annulus), which may represent an earlier partial equilibration following the breakdown of detrital monazite. The large tourmaline crystals exhibit an optically visible three-stage zoning, which comprises: a euhedral core; a continuously zoned inner rim with a prominent euhedral Ca-rich annulus; and an outer rim, which also displays a distinct Ca-rich annulus and is separated from the inner rim by a sutured boundary. This boundary represents a marked chemical discontinuity, characterized for example by a decrease in the Zn concentration from 250 ppm (inner rim) to 20 ppm (outer rim). This change in Zn content reflects staurolite growth, which started after resorption of the inner rim of tourmaline and after a major deformation event. This chemical and textural discontinuity coincides with a marked shift in δ18O, which increases by ∼0·8‰ across the inner rim-outer rim boundary. Our thermodynamic models suggest that resorption of the inner rim of tourmaline may be associated with small amounts (5-7 vol. %) of melt formed at ∼650°C and 8·5 kbar. By using detailed textural observations, major and trace element zoning patterns and thermodynamic data, it was possible to model the metamorphic evolution of these rocks in considerable detail and, specifically, to correlate the growth and breakdown of major and accessory mineral
Methodological pluralism in qualitative research: Reflections on a meta-study
A short report is provided of a meta-study of methodological pluralism in qualitative research; that is, of the use of two or more qualitative methods to analyse the same data set. Ten eligible papers were identified and assessed. Their contents are described with respect to theory, methods and findings, and their possible implications discussed in relation to a series of wider debates in qualitative research more generally
A Plug-and-Play Approach for the De Novo Generation of Dually Functionalized Bispecifics
Diseases are multifactorial, with redundancies and synergies between various pathways. However, most of the antibody-based therapeutics on the market interact with only one target, thus limiting their efficacy. The targeting of multiple epitopes could improve the therapeutic index of treatment and counteract mechanisms of resistance. To this effect, a new class of therapeutics has emerged: bispecific antibodies. Bispecific formation using chemical methods is rare and low-yielding and/or requires a large excess of one of the two proteins to avoid homodimerization and heterogeneity. In order for chemically prepared bispecifics to deliver their full potential, high-yielding, modular, and reliable cross-linking technologies are required. Herein, we describe a novel approach not only for the rapid and high-yielding chemical generation of bispecific antibodies from native antibody fragments, but also for the site-specific dual functionalization of the resulting bioconjugates. Based on orthogonal clickable functional groups, this strategy enables the assembly of functionalized bispecifics with controlled loading in a modular and convergent manner
Evaluating the use of Apo-neocarzinostatin as a cell penetrating protein.
Protein-ligand complex neocarzinostatin (NCS) is a small, thermostable protein-ligand complex that is able to deliver its ligand cargo into live mammalian cells where it induces DNA damage. Apo-NCS is able to functionally display complementarity determining regions loops, and has been hypothesised to act as a cell-penetrating protein, which would make it an ideal scaffold for cell targeting, and subsequent intracellular delivery of small-molecule drugs. In order to evaluate apo-NCS as a cell penetrating protein, we have evaluated the efficiency of its internalisation into live HeLa cells using matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry and fluorescence microscopy. Following incubation of cells with apo-NCS, we observed no evidence of internalisation
Sulphur and carbon cycling in the subduction zone mélange
Subduction zones impose an important control on the geochemical cycling between the surficial and internal reservoirs of the Earth. Sulphur and carbon are transferred into Earth’s mantle by subduction of pelagic sediments and altered oceanic lithosphere. Release of oxidizing sulphate- and carbonate-bearing fluids modifies the redox state of the mantle and the chemical budget of subduction zones. Yet, the mechanisms of sulphur and carbon cycling within subduction zones are still unclear, in part because data are typically derived from arc volcanoes where fluid compositions are modified during transport through the mantle wedge. We determined the bulk rock elemental, and sulphur and carbon isotope compositions of exhumed ultramafic and metabasic rocks from Syros, Greece. Comparison of isotopic data with major and trace element compositions indicates seawater alteration and chemical exchange with sediment-derived fluids within the subduction zone channel. We show that small bodies of detached slab material are subject to metasomatic processes during exhumation, in contrast to large sequences of obducted ophiolitic sections that retain their seafloor alteration signatures. In particular, fluids circulating along the plate interface can cause sulphur mobilization during several stages of exhumation within high-pressure rocks. This takes place more pervasively in serpentinites compared to mafic rocks
Hand osteomyelitis in arterial calcification, diabetes mellitus and end-stage renal failure : a comparison of 210 cases over 12Â years
We present 210 patients with hand osteomyelitis in 246 rays over 12 years, including detailed analysis of 29 patients in this cohort with digital artery calcification evident on plain X-ray. Overall 71 patients had diabetes mellitus and/or end-stage renal failure, including 28 of 29 patients with calcification. In the calcification group, 17 patients had ipsilateral arteriovenous fistulae, five had steal syndrome and 15 had digital ulceration or skin necrosis. Compared with 181 controls, patients with calcification had more affected bones, polymicrobial infections, surgical procedures, phalanges and digits amputated and had higher mortality at 1 year (12 of 29) and 5 years (20 of 29), as a result of comorbidities. Absence of calcification in 43 patients with diabetes and/or end-stage renal failure was associated with better outcomes on all the above parameters. Early amputation to maximize disease-free survival may be appropriate for patients with hand osteomyelitis and arterial calcification
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