Unique functions of specialised cells such as those of the immune and haemostasis systems, skin, blood vessels, lung, and bone require specialised compartments, collectively referred to as ...lysosome-related organelles (LROs), that share features of endosomes and lysosomes. LROs harbour unique morphological features and cell type-specific contents, and most if not all undergo regulated secretion for diverse functions. Ongoing research, largely driven by analyses of inherited diseases and their model systems, is unravelling the mechanisms involved in LRO generation, maturation, transport and secretion. A molecular understanding of these features will provide targets and markers that can be exploited for diagnosis and therapy of a myriad of diseases.
A global review on agpaitic rocks Marks, Michael A.W.; Markl, Gregor
Earth-science reviews,
October 2017, 2017-10-00, Volume:
173
Journal Article
Peer reviewed
Open access
Peralkaline igneous rocks are defined by a molar (Na+K)/Al ratio>1 and are subdivided into miaskitic and agpaitic varieties depending on their mineralogy. In the more common miaskitic types, rare ...earth elements (REEs) and high field strength elements (HFSEs) are largely stored in zircon and titanite, while agpaitic varieties contain a wealth of mostly halogen-bearing Na-Ca-HFSE minerals instead. Among those, minerals of the eudialyte, rinkite, and wöhlerite groups are the most common ones. The present review on the geological and mineralogical information available on agpaitic rocks provides a summary of the fluid inclusion record of miaskitic and agpaitic rocks as fluids play a key role in the evolution of peralkaline rocks.
Magmas that crystallize peralkaline rocks are generally believed to originate from low-degree partial melting of geochemically enriched mantle lithologies, combined with prolonged differentiation processes at shallow crustal levels. Agpaitic and hyperagpaitic rocks (the latter containing appreciable amounts of water-soluble minerals) represent the most evolved stages of peralkaline systems. They form either parts of plutonic to subvolcanic composite magmatic complexes, which consist of several agpaitic and/or miaskitic intrusive units, or they occur as sills, laccoliths, domes, dykes, or even as lavas. However, as agpaitic rocks are notably rare compared to miaskitic rocks (about 100 vs. several thousand occurrences worldwide), their formation requires special conditions that are not generally met during the evolution of peralkaline rocks. Despite their rarity, agpaitic and hyperagpaitic rocks form important deposits of critical metals such as REE, Zr, Nb, and U and are interesting targets for otherwise rare elements such as F, Be, Sn, Zn, and Ga.
The relative timing when magmas reach their agpaitic stage is highly variable. Magmatic–agpaitic assemblages can form only if early-magmatic crystallization conditions were reduced enough (low fO2) to enable subsequent Fe enrichment, an increase in peralkalinity, retention of halogens, and extreme enrichment of HFSEs in the evolving magmas, as only these contribute to the direct crystallization of agpaitic minerals. Late-magmatic interstitial agpaitic assemblages indicate that the required enrichment levels of the above-mentioned constituents were reached only during the final differentiation stages of magmas. Hydrothermal agpaitic assemblages precipitate from highly saline brines released from peralkaline magmas and are capable of transporting HFSEs. All three varieties of agpaitic assemblages occur in plutonic, subvolcanic, and volcanic rocks. Although many modern and detailed studies have dealt with plutonic–subvolcanic agpaitic rocks, most volcanic occurrences are insufficiently studied, mainly because of difficult outcrop or logistic situations. However, especially the volcanic examples raise questions on the details of why and how degassing of halogens at such shallow emplacement levels is sufficiently prevented to precipitate halogen-bearing agpaitic assemblages. Thus, a thorough geochemical and petrological investigation of such localities is desired.
The presently valid definitions of agpaitic and miaskitic rocks are not appropriate, and therefore, alternative definitions are suggested. Similarly, the frequently used classification scheme for nepheline syenites must be abandoned as it is inconsistent and excludes very similar mineral assemblages observed in other partly even quartz-bearing rock types. Variable processes may produce sequences of mineral assemblages that belong to different groups of this classification. Therefore, we suggest that rather than dividing agpaitic rocks into specific subgroups, careful textural studies that distinguish early-magmatic, late-magmatic, and hydrothermal phase assemblages are warranted. This is the only way to understand the effect of various physicochemical parameters (such as P, T, fO2, aSiO2, aH2O, peralkalinity, and the activity of other compounds including halogens) during different evolutionary stages of these mineralogically and texturally diverse rocks.
Cargo sorting to intraluminal vesicles (ILVs) of multivesicular endosomes is required for lysosome-related organelle (LRO) biogenesis. PMEL—a component of melanocyte LROs (melanosomes)—is sorted to ...ILVs in an ESCRT-independent manner, where it is proteolytically processed and assembled into functional amyloid fibrils during melanosome maturation. Here we show that the tetraspanin CD63 directly participates in ESCRT-independent sorting of the PMEL luminal domain, but not of traditional ESCRT-dependent cargoes, to ILVs. Inactivating CD63 in cell culture or in mice impairs amyloidogenesis and downstream melanosome morphogenesis. Whereas CD63 is required for normal PMEL luminal domain sorting, the disposal of the remaining PMEL transmembrane fragment requires functional ESCRTs but not CD63. In the absence of CD63, the PMEL luminal domain follows this fragment and is targeted for ESCRT-dependent degradation. Our data thus reveal a tight interplay regulated by CD63 between two distinct endosomal ILV sorting processes for a single cargo during LRO biogenesis.
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► ESCRT-independent sorting of PMEL to intraluminal vesicles depends on CD63 ► CD63 depletion inhibits formation of PMEL-derived amyloid fibers in vitro and in vivo ► PMEL C-terminal fragment is degraded in an ESCRT-dependent manner ► PMEL becomes sensitive to ESCRT-dependent degradation in CD63-depleted cells
Synopsis
Melanins, the main pigments of the skin and hair in mammals, are synthesized within membrane-bound organelles of melanocytes called melanosomes. Melanosome structure and function are ...determined by a cohort of resident transmembrane proteins, many of which are expressed only in pigment cells and localize specifically to melanosomes. Defects in the genes that encode melanosome-specific proteins or components of the machinery required for their transport in and out of melanosomes underlie various forms of ocular or oculocutaneous albinism, characterized by hypopigmentation of the hair, skin, and eyes and by visual impairment. We review major components of melanosomes, including the enzymes that catalyze steps in melanin synthesis from tyrosine precursors, solute transporters that allow these enzymes to function, and structural proteins that underlie melanosome shape and melanin deposition. We then review the molecular mechanisms by which these components are biosynthetically delivered to newly forming melanosomes—many of which are shared by other cell types that generate cell type-specific lysosome-related organelles. We also highlight unanswered questions that need to be addressed by future investigation.
Melanosomes are tissue-specific lysosome-related organelles of pigment cells in which melanins are synthesized and stored. Analyses of the trafficking and fate of melanosomal components are beginning ...to reveal how melanosomes are formed through novel pathways from early endosomal intermediates. These studies unveil generalized structural and functional modifications of the endosomal system in specialized cells, and provide unexpected insights into the biogenesis of multivesicular bodies and how compartmentalization regulates protein refolding. Moreover, genetic disorders that affect the biogenesis of melanosomes and other lysosome-related organelles have shed light onto the molecular machinery that controls specialized endosomal sorting events.
Lysosome‐related organelles (LROs) comprise a diverse group of cell type‐specific, membrane‐bound subcellular organelles that derive at least in part from the endolysosomal system but that have ...unique contents, morphologies and functions to support specific physiological roles. They include: melanosomes that provide pigment to our eyes and skin; alpha and dense granules in platelets, and lytic granules in cytotoxic T cells and natural killer cells, which release effectors to regulate hemostasis and immunity; and distinct classes of lamellar bodies in lung epithelial cells and keratinocytes that support lung plasticity and skin lubrication. The formation, maturation and/or secretion of subsets of LROs are dysfunctional or entirely absent in a number of hereditary syndromic disorders, including in particular the Hermansky‐Pudlak syndromes. This review provides a comprehensive overview of LROs in humans and model organisms and presents our current understanding of how the products of genes that are defective in heritable diseases impact their formation, motility and ultimate secretion.
Lysosome‐related organelles (LROs) are cell type‐specific subcellular structures that derive from both the secretory and endolysosomal pathways and that play key roles in numerous physiological systems, in most cases following stimulus‐dependent secretion of their contents. The biogenesis and/or secretion of LRO subsets are disrupted in hereditary syndromic disorders such as the Hermansky‐Pudlak syndromes and familial hemophagocytic lymphohistiocytosis. We comprehensively review LROs in humans and model organisms and the mechanisms by which products of disease genes regulate their formation, motility and ultimate secretion.
The 2060 Ma old Palabora Carbonatite Complex (PCC), South Africa, comprises diverse REE mineral assemblages formed during different stages and reflects an outstanding instance to understand the ...evolution of a carbonatite-related REE mineralization from orthomagmatic to late-magmatic stages and their secondary post-magmatic overprint. The 10 rare earth element minerals monazite, REE-F-carbonates (bastnasite, parisite, synchysite), ancylite, britholite, cordylite, fergusonite, REE-Ti-betafite, and anzaite are texturally described and related to the evolutionary stages of the PCC. The identification of the latter five REE minerals during this study represents their first described occurrences in the PCC as well as in a carbonatite complex in South Africa.The variable REE mineral assemblages reflect a multi-stage origin: (1) fergusonite and REE-Ti-betafite occur as inclusions in primary magnetite. Bastnasite is enclosed in primary calcite and dolomite. These three REE minerals are interpreted as orthomagmatic crystallization products. (2) The most common REE minerals are monazite replacing primary apatite, and britholite texturally related to the serpentinization of forsterite or the replacement of forsterite by chondrodite. Textural relationships suggest that these two REE-minerals precipitated from internally derived late-magmatic to hydrothermal fluids. Their presence seems to be locally controlled by favorable chemical conditions (e.g., presence of precursor minerals that contributed the necessary anions and/or cations for their formation). (3) Late-stage (post-magmatic) REE minerals include ancylite and cordylite replacing primary magmatic REE-Sr-carbonates, anzaite associated with the dissolution of ilmenite, and secondary REE-F-carbonates. The formation of these post-magmatic REE minerals depends on the local availability of a fluid, whose composition is at least partly controlled by the dissolution of primary minerals (e.g., REE-fluorocarbonates).This multi-stage REE mineralization reflects the interplay of magmatic differentiation, destabilization of early magmatic minerals during subsequent evolutionary stages of the carbonatitic system, and late-stage fluid-induced remobilization and re-/precipitation of precursor REE minerals. Based on our findings, the Palabora Carbonatite Complex experienced at least two successive stages of intense fluid-rock interaction.
The concentrations of halogens in serpentinised olivine-rich lithologies in the lower oceanic crust (e.g. troctolites and wehrlites) and altered-gabbros, recovered from IODP Hole U1309D on the ...Atlantis Massif of the Mid-Atlantic Ridge, are contrasted. The aims were to evaluate if serpentinisation of lower crustal lithologies could significantly contribute to the volatile budget of oceanic lithosphere and test if serpentinites formed from seawater preserve seawater-like halogen signatures. The olivine-rich lithologies are variably serpentinised by lizardite with minor chrysotile. The maximum concentrations of halogens in the most strongly serpentinised samples are 70 µg/g F, 2,100 µg/g Cl, 9,800 ng/g Br and 8 ng/g I. In comparison, the maxima in interlayered gabbros are 200 µg/g F, 130 µg/g Cl, 400 ng/g Br and 9 ng/g I. The Br/Cl ratios of the altered gabbros are strongly influenced by the presence of amphibole, which preferentially incorporates the smaller halides. The serpentinised lithologies have low F/Cl ratios, due to their strong enrichment in seawater-derived Cl, and they have Br/Cl and I/Cl ratios intermediate of unaltered oceanic crust and seawater-derived fluids. Br/Cl and I/Cl ratios similar to seawater are best preserved in the most Cl-rich samples consistent with these ratios fingerprinting the fluid responsible for serpentinisation. Serpentinites formed from seawater in the lower ocean crust and lithosphere are likely to have low I/Cl ratios. Serpentinsed lithologies in the lower crust (and mantle lithosphere) could, therefore, significantly contribute to halogen subduction helping to explain the range of I/Cl ratios in arc lavas and a proposed decrease of mantle I/Cl over time.
Apatite is ubiquitous in a wide range of magmatic rocks and its F–Cl–Br–S systematics can be used to decipher e.g., mixing processes within a magmatic complex and may give insights into fluid ...un-mixing and degassing processes during the emplacement and cooling of plutonic rocks.
In this study, we analyzed a F-apatite (Durango, Mexico), a Cl-apatite (Ødegården, Norway) and apatites from five plutonic samples from the alkaline Mt. Saint Hilaire Complex (Canada) by means of Electron Microprobe Analysis (EPMA), Laser Ablation ICP-MS (LA-ICP-MS), Secondary Ion Mass Spectrometry (SIMS), pyrohydrolysis combined with ion chromatography, Fourier Transformed Infrared Spectroscopy (FTIR), Instrumental Neutron Activation Analysis (INAA) and Total Reflection X-ray Fluorescence Analysis (TXRF).
The special focus of our study is Br, since the analytical possibilities for this element are especially in the low- to sub-μg/g range restricted and thus, reliable concentration data for Br in rock-forming minerals are scarce. We demonstrate here that TXRF, which is barely used in geosciences so far, is suitable for analyzing the bulk content of Br and Cl as well as of a range of important trace metals (e.g., Sr, Ce, Fe, Mn, As) in apatite simultaneously. The TXRF method combines the advantages of low to very low detection limits (μg/g- to sub-μg/g range), small sample amounts needed (mg range) and a relatively fast and inexpensive analytical procedure. Depending on the As content of apatite, reliable concentration data for Br can be produced with detection limits as low as 0.2
μg/g.
Using the Durango apatite as an internal reference material, SIMS analyses give consistent results with EPMA, INAA and TXRF and allow for detailed insights into the F–Cl–Br–S systematics of apatites. The presented data set reveals significant heterogeneities within and between different apatite grains from a single sample.
► Br concentrations for magmatic minerals are scarce. ► TXRF can be used to analyze the bulk Br content in apatite. ► A Br concentration of around 0.1
μg/g for the Durango apatite is proposed.
Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly ...assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis.
We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days.
Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years SD 13·7, 259 51·3% women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76–3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83–3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0–2) than best medical therapy alone (122 45·9% of 266 vs 46 19·3% of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 16·5% of 266 vs 46 19·3% of 238) or symptomatic intracerebral haemorrhage (14 5·3% of 266 vs eight 3·3% of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12–24 h (common OR 5·86 95% CI 3·14–10·94) than those randomly assigned within 6–12 h (1·76 1·18–2·62; pinteraction=0·0087).
These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6–24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6–24 h time window.
Stryker Neurovascular.
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