ORCID Profile
0000-0003-0445-8812
Current Organisation
Australian National University
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Geology | Igneous and Metamorphic Petrology | Igneous And Metamorphic Petrology | Mineralogy and Crystallography | Inorganic Geochemistry | Mineralogy And Crystallography | Exploration Geochemistry | Geology | Geodynamics | Geochronology | Resource geoscience | Mineralogy and crystallography | Exploration geochemistry | Geochemistry not elsewhere classified |
Expanding Knowledge in the Earth Sciences | Earth sciences | Conserving Collections and Movable Cultural Heritage | First Stage Treatment of Ores and Minerals not elsewhere classified | Expanding Knowledge in Engineering | Precious (Noble) Metal Ore Exploration | Titanium Minerals, Zircon, and Rare Earth Metal Ore (e.g. Monazite) Exploration | Diamond Exploration
Publisher: Geological Society of America
Date: 2013
DOI: 10.1130/G33488.1
Publisher: Springer Science and Business Media LLC
Date: 2012
DOI: 10.1186/AR4096
Publisher: Springer Science and Business Media LLC
Date: 28-01-2021
DOI: 10.1007/S00410-020-01768-Z
Abstract: The pressure dependence of the exchange of Cr between clinopyroxene and garnet in peridotite is applicable as a geobarometer for mantle-derived Cr-diopside xenocrysts and xenoliths. The most widely used calibration (Nimis and Taylor Contrib Miner Petrol 139: 541–554, 2000 herein NT00) performs well at pressures below 4.5 GPa, but has been shown to consistently underestimate pressures above 4.5 GPa. We have experimentally re-examined this exchange reaction over an extended pressure, temperature, and compositional range using multi-anvil, belt, and piston cylinder apparatuses. Twenty-nine experiments were completed between 3–7 GPa, and 1100–1400 °C in a variety of compositionally complex lherzolitic systems. These experiments are used in conjunction with several published experimental datasets to present a modified calibration of the widely-used NT00 Cr-in-clinopyroxene (Cr-in-cpx) single crystal geobarometer. Our updated calibration calculates P (GPa) as a function of T (K), CaCr Tschermak activity in clinopyroxene $$\\left( {a_{{{\\text{CaCrTs}}}}^{{{\\text{cpx}}}} } \\right)$$ a CaCrTs cpx , and Cr/(Cr + Al) (Cr#) in clinopyroxene. Rearranging experimental results into a 2 n polynomial using multiple linear regression found the following expression for pressure: $$P\\left( {{\\text{GPa}}} \\right) = 11.03 + \\left( { - T{ }\\left( {\\text{K}} \\right){\\text{ ln}}(a_{{{\\text{CaCrTs}}}}^{{{\\text{cpx}}}} ) \\times 0.001088{ }} \\right) + \\left( {1.526 \\times {\\text{ln}}\\left( {\\frac{{{\\text{Cr}}\\#^{{{\\text{cpx}}}} }}{{T{ }\\left( {\\text{K}} \\right)}}} \\right)} \\right){ }$$ P GPa = 11.03 + - T K ln ( a CaCrTs cpx ) × 0.001088 + 1.526 × ln Cr # cpx T K where $${\\text{Cr}}\\#^{{{\\text{cpx}}}} = \\left( {\\frac{{{\\text{Cr}}}}{{{\\text{Cr}} + {\\text{Al}}}}} \\right)$$ Cr # cpx = Cr Cr + Al , $$a_{{{\\text{CaCrTs}}}}^{{{\\text{cpx}}}} = {\\text{Cr}} - 0.81 \\cdot {\\text{Cr}}\\#^{{{\\text{cpx}}}} \\cdot \\left( {{\\text{Na}} + {\\text{K}}} \\right),$$ a CaCrTs cpx = Cr - 0.81 · Cr # cpx · Na + K , with all mineral components calculated assuming six oxygen anions per formula unit in clinopyroxene. Temperature (K) may be calculated through a variety of geothermometers, however, we recommend the NT00 single crystal, enstatite-in-clinopyroxene (en-in-cpx) geothermometer. The pressure uncertainty of our updated calibration has been propagated by incorporating all analytical and experimental uncertainties. We have found that pressure estimates below 4 GPa, between 4–6 GPa and above 6 GPa have associated uncertainties of 0.31, 0.35, and 0.41 GPa, respectively. Pressures calculated using our calibration of the Cr-in-cpx geobarometer are in good agreement between 2–7 GPa, and 900–1400 °C with those estimated from widely-used two-phase geobarometers based on the solubility of alumina in orthopyroxene coexisting with garnet. Application of our updated calibration to suites of well-equilibrated garnet lherzolite and garnet pyroxenite xenoliths and xenocrysts from the Diavik-Ekati kimberlite and the Argyle l roite pipes confirm the accuracy and precision of our modified geobarometer, and show that PT estimates using our revised geobarometer result in systematically steeper paleogeotherms and higher estimates of the lithosphere‒asthenosphere boundary compared with the original NT00 calibration.
Publisher: Elsevier BV
Date: 11-2009
Publisher: American Society of Hematology
Date: 25-05-2017
DOI: 10.1182/BLOOD-2016-10-746909
Abstract: Prolonged inhibition of CXCR4/CXCL12 signaling results in exceptional mobilization along with an expansion of the BM HSPC pool. Reversible inhibition of the CXCR4/CXCL12 axis may represent a novel strategy to restore damaged BM.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.BIOMATERIALS.2015.04.057
Abstract: Advances in tissue-engineering have resulted in a versatile tool-box to specifically design a tailored microenvironment for hematopoietic stem cells (HSCs) in order to study diseases that develop within this setting. However, most current in vivo models fail to recapitulate the biological processes seen in humans. Here we describe a highly reproducible method to engineer humanized bone constructs that are able to recapitulate the morphological features and biological functions of the HSC niches. Ectopic implantation of biodegradable composite scaffolds cultured for 4 weeks with human mesenchymal progenitor cells and loaded with rhBMP-7 resulted in the development of a chimeric bone organ including a large number of human mesenchymal cells which were shown to be metabolically active and capable of establishing a humanized microenvironment supportive of the homing and maintenance of human HSCs. A syngeneic mouse-to-mouse transplantation assay was used to prove the functionality of the tissue-engineered ossicles. We predict that the ability to tissue engineer a morphologically intact and functional large-volume bone organ with a humanized bone marrow compartment will help to further elucidate physiological or pathological interactions between human HSCs and their native niches.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2017
DOI: 10.1007/S11914-017-0384-X
Abstract: Mounting evidence supporting the critical contribution of macrophages, in particular osteal macrophages, to bone regeneration is reviewed. We specifically examine the potential role of macrophages in the basic multicellular units coordinating lifelong bone regeneration via remodelling and bone regeneration in response to injury. We review and discuss the distinctions between macrophage and osteoclast contributions to bone homeostasis, particularly the dichotomous role of the colony-stimulating factor 1-colony-stimulating factor 1 receptor axis. The impact of inflammation associated with aging and other hallmarks of aging, including senescence, on macrophage function is addressed in the context of osteoporosis and delayed fracture repair. Resident macrophages versus recruited macrophage contributions to fracture healing are also discussed. We identify some of the remaining knowledge gaps that will need to be closed in order to maximise benefits from therapeutically modulating or mimicking the function of macrophages to improve bone health and regeneration over a lifetime.
Publisher: Geological Society of America
Date: 2007
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.AJPATH.2014.08.017
Abstract: The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine femoral fracture model [internally fixed using a flexible plate (MouseFix)] was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80(+)Mac-2(+)) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80(+)Mac-2(neg)), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2022
DOI: 10.1038/S43247-022-00630-3
Abstract: The thick mantle lithosphere beneath cratons consists of strongly reduced rocks that have reacted with oxidized melts. These low-silica, incipient melts are rich in CO 2 and H 2 O and react with surrounding rocks forming an enriched zone at the base of the lithosphere, which is the source region for many diamonds. Here, we reproduce these reactions in novel experiments in which oxidised, hydrous carbonate-rich melts are reacted with reduced, depleted peridotite at 5 GPa pressure. Results explain several key features of the mantle s le in kimberlites as products of a single process, namely the formation of diamonds, phlogopite and alkali- hibole bearing rocks, iron-rich dunites, and garnets and clinopyroxenes with pyroxenitic compositions. Initially, redox freezing occurs where melts meet the reduced peridotite, depositing diamonds and associated garnet and clinopyroxenes. The spreading reaction front leaves behind Fe-rich dunite, and crystallizing phlogopite and hibole when the melt solidifies at the reaction front.
Publisher: Springer Science and Business Media LLC
Date: 04-12-2018
Publisher: Elsevier BV
Date: 05-2000
Publisher: Springer Science and Business Media LLC
Date: 11-12-2011
DOI: 10.1007/S12015-011-9336-5
Abstract: Mesenchymal stem cells (MSC) from fetal-placental tissues have translational advantages over their adult counterparts, and have variably been reported to express pluripotency markers. OCT-4 expression in fetal-placental MSC has been documented in some studies, paradoxically without tumourogenicity in vivo. It is possible that OCT-4 expression is insufficient to induce true "stemness", but this issue is important for the translational safety of fetal-derived MSC. To clarify this, we undertook a systematic literature review on OCT-4 in fetal or adnexal MSC to show that most studies report OCT-4 message or protein expression, but no study provides definitive evidence of true OCT-4A expression. Discrepant findings were attributable not to different culture conditions, tissue sources, or gestational ages but instead to techniques used. In assessing OCT-4 as a pluripotency marker, we highlight the challenges in detecting the correct OCT-4 isoform (OCT-4A) associated with pluripotency. Although specific detection of OCT-4A mRNA is achievable, it appears unlikely that any antibody can reliably distinguish between OCT-4A and the pseudogene OCT-4B. Finally, using five robust techniques we demonstrate that fetal derived-MSC do not express OCT-4A (or by default OCT-4B). Reports suggesting OCT-4 expression in fetal-derived MSC warrant reassessment, paying attention to gene and protein isoforms, pseudogenes, and antibody choice as well as primer design. Critical examination of the OCT-4 literature leads us to suggest that OCT-4 expression in fetal MSC may be a case of "The Emperor's New Clothes" with early reports of (false) positive expression lified in subsequent studies without critical attention to emerging refinements in knowledge and methodology.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.BIOMATERIALS.2017.10.033
Abstract: Osteal macrophages (osteomacs) contribute to bone homeostasis and regeneration. To further distinguish their functions from osteoclasts, which share many markers and growth factor requirements, we developed a rapid, enzyme-free osteomac enrichment protocol that permitted characterization of minimally manipulated osteomacs by flow cytometry. Osteomacs differ from osteoclasts in expression of Siglec1 (CD169). This distinction was confirmed using the CD169-diphtheria toxin (DT) receptor (DTR) knock-in model. DT treatment of naïve CD169-DTR mice resulted in selective and striking loss of osteomacs, whilst osteoclasts and trabecular bone area were unaffected. Consistent with a previously-reported trophic interaction, osteomac loss was accompanied by a concomitant and proportionately striking reduction in osteoblasts. The impact of CD169
Publisher: The American Association of Immunologists
Date: 12-2020
Abstract: The proliferation, differentiation, and survival of cells of the mononuclear phagocyte system (MPS progenitors, monocytes, macrophages, and classical dendritic cells) are controlled by signals from the M-CSF receptor (CSF1R). Cells of the MPS lineage have been identified using numerous surface markers and transgenic reporters, but none is both universal and lineage restricted. In this article, we report the development and characterization of a CSF1R reporter mouse. A FusionRed (FRed) cassette was inserted in-frame with the C terminus of CSF1R, separated by a T2A-cleavable linker. The insertion had no effect of CSF1R expression or function. CSF1R-FRed was expressed in monocytes and macrophages and absent from granulocytes and lymphocytes. In bone marrow, CSF1R-FRed was absent in lineage-negative hematopoietic stem cells, arguing against a direct role for CSF1R in myeloid lineage commitment. It was highly expressed in marrow monocytes and common myeloid progenitors but significantly lower in granulocyte-macrophage progenitors. In sections of bone marrow, CSF1R-FRed was also detected in osteoclasts, CD169+ resident macrophages, and, consistent with previous mRNA analysis, in megakaryocytes. In lymphoid tissues, CSF1R-FRed highlighted erse MPS populations, including classical dendritic cells. Whole mount imaging of nonlymphoid tissues in mice with combined CSF1R-FRed/Csf1r-EGFP confirmed the restriction of CSF1R expression to MPS cells. The two markers highlight the remarkable abundance and regular distribution of tissue MPS cells, including novel macrophage populations within tendon and skeletal muscle and underlying the mesothelial/serosal/capsular surfaces of every major organ. The CSF1R-FRed mouse provides a novel reporter with exquisite specificity for cells of the MPS.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 07-2014
DOI: 10.1016/J.EXPHEM.2014.03.009
Abstract: Similarly to other tissues, the bone marrow contains subsets of resident tissue macrophages, which are essential to maintain bone formation, functional hematopoietic stem cell (HSC) niches, and erythropoiesis. Pharmacologic doses of granulocyte colony-stimulating factor (G-CSF) mobilize HSC in part by interfering with the HSC niche-supportive function of BM resident macrophages. Because bone marrow macrophages are key to both maintenance of HSC within their niche and erythropoiesis, we investigated the effect of mobilizing doses of G-CSF on erythropoiesis in mice. We now report that G-CSF blocks medullar erythropoiesis by depleting the erythroid island macrophages we identified as co-expressing F4/80, vascular cell adhesion molecule-1, CD169, Ly-6G, and the ER-HR3 erythroid island macrophage antigen. Both broad macrophage depletion, achieved by injecting clodronate-loaded liposomes, and selective depletion of CD169(+) macrophages, also concomitantly depleted F4/80(+)VCAM-1(+)CD169(+)ER-HR3(+)Ly-6G(+) erythroid island macrophages and blocked erythropoiesis. This more precise phenotypic definition of erythroid island macrophages will enable studies on their biology and function in normal settings and on diseases associated with anemia. Finally, this study further illustrates that macrophages are a potent relay of innate immunity and inflammation on bone, hematopoietic, and erythropoietic maintenance. Agents that affect these macrophages, such as G-CSF, are likely to affect these three processes concomitantly.
Publisher: Elsevier BV
Date: 04-2008
Publisher: Elsevier BV
Date: 06-2015
Publisher: Elsevier BV
Date: 03-2014
Publisher: Springer Science and Business Media LLC
Date: 04-2022
DOI: 10.1007/S00410-022-01905-W
Abstract: Devolatilization of subducting lithologies liberates COH-fluids. These may become partially sequestered in peridotites in the slab and the overlying forearc mantle, affecting the cycling of volatiles and fluid mobile elements in subduction zones. Here we assess the magnitudes, timescales and mechanism of channelized injection of COH-fluids doped with $${\\mathrm{Ca}}_{\\mathrm{aq}}^{2+}$$ Ca aq 2 + , $${\\mathrm{Sr}}_{\\mathrm{aq}}^{2+}$$ Sr aq 2 + and $${\\mathrm{Ba}}_{\\mathrm{aq}}^{2+}$$ Ba aq 2 + into the dry forearc mantle by performing piston cylinder experiments between 1–2.5 GPa and 600–700 °C. Cylindrical cores of natural spinel-bearing harzburgites were used as starting materials. Based on mineral assemblage and composition three reaction zones are distinguishable from the rim towards the core of primary olivine and orthopyroxene grains. Zone 1 contains carbonates + quartz ± kyanite and zone 2 contains carbonates + talc ± chlorite. Olivine is further replaced in zone 3 by either antigorite + magnesite or magnesite + talc within or above antigorite stability, respectively. Orthopyroxene is replaced in zone 3 by talc + chlorite. Mineral assemblages and the compositions of secondary minerals depend on fluid composition and the replaced primary silicate. The extent of alteration depends on fluid CO 2 content and fluid/rock-ratio, and is further promoted by fluid permeable reaction zones and reaction driven cracking. Our results show that COH-fluid induced metasomatism of the forearc mantle is self-perpetuating and efficient at sequestering $${\\mathrm{Ca}}_{\\mathrm{aq}}^{2+}$$ Ca aq 2 + , $${\\mathrm{Sr}}_{\\mathrm{aq}}^{2+}$$ Sr aq 2 + , $${\\mathrm{Ba}}_{\\mathrm{aq}}^{2+}$$ Ba aq 2 + and CO 2aq into newly formed carbonates. This process is fast with 90% of the available C sequestered and nearly 50% of the initial minerals altered at 650 °C, 2 GPa within 55 h. The dissolution of primary silicates under high COH-fluid/rock-ratios, as in channelized fluid flow, enriches SiO 2aq in the fluid, while CO 2aq is sequestered into carbonates. In an open system, the remaining CO 2 -depleted, Si-enriched aqueous fluid may cause Si-metasomatism in the forearc further away from the injection of the COH-fluid into peridotite.
Publisher: European Cells and Materials
Date: 17-03-2021
DOI: 10.22203/ECM.V041A22
Abstract: Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or duration. A comparison of healed C57BL/6 and Rag1−/− femora by µCT and ex vivo torsion testing showed no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions.
Publisher: American Geophysical Union (AGU)
Date: 10-2023
DOI: 10.1029/2023GC011120
Publisher: Elsevier BV
Date: 04-2009
Publisher: Mineralogical Society of America
Date: 10-2021
DOI: 10.2138/GSELEMENTS.17.5.315
Abstract: Carbonatites are the most silica-poor magmas known and are amongst Earth’s most enigmatic igneous rocks. They crystallise to rocks dominated by the carbonate minerals calcite and dolomite. We review models for carbonatite petrogenesis, including direct partial melting of mantle lithologies, exsolution from silica-undersaturated alkali silicate melts, or direct fractionation of carbonated silicate melts to carbonate-rich residual melts. We also briefly discuss carbonatite–mantle wall-rock reactions and other processes at mid-to upper crustal depths, including fenitisation, overprinting by carbohydrothermal fluids, and reaction between carbonatite melt and crustal lithologies.
Publisher: Elsevier BV
Date: 09-2019
Publisher: Wiley
Date: 19-11-2015
DOI: 10.1002/JBMR.2735
Publisher: Oxford University Press (OUP)
Date: 24-09-2014
Publisher: Geological Society of London
Date: 2009
Publisher: Springer Science and Business Media LLC
Date: 23-01-2012
DOI: 10.1038/LEU.2012.17
Abstract: The CXCR4 antagonist AMD3100 is progressively replacing cyclophosphamide (CYP) as adjuvant to granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) for autologous transplants in patients who failed prior mobilization with G-CSF alone. It has recently emerged that G-CSF mediates HSC mobilization and inhibits bone formation via specific bone marrow (BM) macrophages. We compared the effect of these three mobilizing agents on BM macrophages, bone formation, osteoblasts, HSC niches and HSC reconstitution potential. Both G-CSF and CYP suppressed niche-supportive macrophages and osteoblasts, and inhibited expression of endosteal cytokines resulting in major impairment of HSC reconstitution potential remaining in the mobilized BM. In sharp contrast, although AMD3100 was effective at mobilizing HSC, it did not suppress osteoblasts, endosteal cytokine expression or reconstitution potential of HSC remaining in the mobilized BM. In conclusion, although G-CSF, CYP and AMD3100 efficiently mobilize HSC into the blood, their effects on HSC niches and bone formation are distinct with both G-CSF and CYP targeting HSC niche function and bone formation, whereas AMD3100 directly targets HSC without altering niche function or bone formation.
Publisher: Wiley
Date: 26-03-2015
DOI: 10.1002/PATH.4519
Abstract: Neurological heterotopic ossification (NHO) is the abnormal formation of bone in soft tissues as a consequence of spinal cord or traumatic brain injury. NHO causes pain, ankyloses, vascular and nerve compression and delays rehabilitation in this high-morbidity patient group. The pathological mechanisms leading to NHO remain unknown and consequently there are no therapeutic options to prevent or reduce NHO. Genetically modified mouse models of rare genetic forms of heterotopic ossification (HO) exist, but their relevance to NHO is questionable. Consequently, we developed the first model of spinal cord injury (SCI)-induced NHO in genetically unmodified mice. Formation of NHO, measured by micro-computed tomography, required the combination of both SCI and localized muscular inflammation. Our NHO model faithfully reproduced many clinical features of NHO in SCI patients and both human and mouse NHO tissues contained macrophages. Muscle-derived mesenchymal progenitors underwent osteoblast differentiation in vitro in response to serum from NHO mice without additional exogenous osteogenic stimuli. Substance P was identified as a candidate NHO systemic neuropeptide, as it was significantly elevated in the serum of NHO patients. However, antagonism of substance P receptor in our NHO model only modestly reduced the volume of NHO. In contrast, ablation of phagocytic macrophages with clodronate-loaded liposomes reduced the size of NHO by 90%, supporting the conclusion that NHO is highly dependent on inflammation and phagocytic macrophages in soft tissues. Overall, we have developed the first clinically relevant model of NHO and demonstrated that a combined insult of neurological injury and soft tissue inflammation drives NHO pathophysiology.
Publisher: Springer Science and Business Media LLC
Date: 24-06-2014
DOI: 10.1007/S00125-014-3291-Z
Abstract: The AGEs and the receptor for AGEs (RAGE) are known contributors to diabetic complications. RAGE also has a physiological role in innate and adaptive immunity and is expressed on immune cells. The aim of this study was to determine whether deletion of RAGE from bone-marrow-derived cells influences the pathogenesis of experimental diabetic nephropathy. Groups (n = 8/group) of lethally irradiated 8 week old wild-type (WT) mice were reconstituted with bone marrow from WT (WT → WT) or RAGE-deficient (RG) mice (RG → WT). Diabetes was induced using multiple low doses of streptozotocin after 8 weeks of bone marrow reconstitution and mice were followed for a further 24 weeks. Compared with diabetic WT mice reconstituted with WT bone marrow, diabetic WT mice reconstituted with RG bone marrow had lower urinary albumin excretion and podocyte loss, more normal creatinine clearance and less tubulo-interstitial injury and fibrosis. However, glomerular collagen IV deposition, glomerulosclerosis and cortical levels of TGF-β were not different among diabetic mouse groups. The renal tubulo-interstitium of diabetic RG → WT mice also contained fewer infiltrating CD68(+) macrophages that were activated. Diabetic RG → WT mice had lower renal cortical concentrations of CC chemokine ligand 2 (CCL2), macrophage inhibitory factor (MIF) and IL-6 than diabetic WT → WT mice. Renal cortical RAGE ligands S100 calgranulin (S100A)8/9 and AGEs, but not high mobility box protein B-1 (HMGB-1) were also decreased in diabetic RG → WT compared with diabetic WT → WT mice. In vitro, bone-marrow-derived macrophages from WT but not RG mice stimulated collagen IV production in cultured proximal tubule cells. These studies suggest that RAGE expression on haemopoietically derived immune cells contributes to the functional changes seen in diabetic nephropathy by promoting macrophage infiltration and renal tubulo-interstitial damage.
Publisher: Elsevier BV
Date: 30-05-2009
Publisher: Elsevier BV
Date: 04-2018
Publisher: Oxford University Press (OUP)
Date: 11-10-2007
Publisher: Springer Science and Business Media LLC
Date: 06-01-2021
DOI: 10.1186/S13045-020-00997-W
Abstract: Prior chemotherapy and/or underlying morbidity commonly leads to poor mobilisation of hematopoietic stem cells (HSC) for transplantation in cancer patients. Increasing the number of available HSC prior to mobilisation is a potential strategy to overcome this deficiency. Resident bone marrow (BM) macrophages are essential for maintenance of niches that support HSC and enable engraftment in transplant recipients. Here we examined potential of donor treatment with modified recombinant colony-stimulating factor 1 (CSF1) to influence the HSC niche and expand the HSC pool for autologous transplantation. We administered an acute treatment regimen of CSF1 Fc fusion protein (CSF1-Fc, daily injection for 4 consecutive days) to naive C57Bl/6 mice. Treatment impacts on macrophage and HSC number, HSC function and overall hematopoiesis were assessed at both the predicted peak drug action and during post-treatment recovery. A serial treatment strategy using CSF1-Fc followed by granulocyte colony-stimulating factor (G-CSF) was used to interrogate HSC mobilisation impacts. Outcomes were assessed by in situ imaging and ex vivo standard and imaging flow cytometry with functional validation by colony formation and competitive transplantation assay. CSF1-Fc treatment caused a transient expansion of monocyte-macrophage cells within BM and spleen at the expense of BM B lymphopoiesis and hematopoietic stem and progenitor cell (HSPC) homeostasis. During the recovery phase after cessation of CSF1-Fc treatment, normalisation of hematopoiesis was accompanied by an increase in the total available HSPC pool. Multiple approaches confirmed that CD48 − CD150 + HSC do not express the CSF1 receptor, ruling out direct action of CSF1-Fc on these cells. In the spleen, increased HSC was associated with expression of the BM HSC niche macrophage marker CD169 in red pulp macrophages, suggesting elevated spleen engraftment with CD48 − CD150 + HSC was secondary to CSF1-Fc macrophage impacts. Competitive transplant assays demonstrated that pre-treatment of donors with CSF1-Fc increased the number and reconstitution potential of HSPC in blood following a HSC mobilising regimen of G-CSF treatment. These results indicate that CSF1-Fc conditioning could represent a therapeutic strategy to overcome poor HSC mobilisation and subsequently improve HSC transplantation outcomes.
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B510719A
Publisher: Springer Science and Business Media LLC
Date: 07-2000
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-05-2007
DOI: 10.1126/SCIENCE.
Publisher: Wiley
Date: 15-11-2017
DOI: 10.1038/ICB.2016.74
Abstract: Better understanding of bone growth and regeneration mechanisms within periosteal tissues will improve understanding of bone physiology and pathology. Macrophage contributions to bone biology and repair have been established but specific investigation of periosteal macrophages has not been undertaken. We used an immunohistochemistry approach to characterize macrophages in growing murine bone and within activated periosteum induced in a mouse model of bone injury. Osteal tissue macrophages (osteomacs) and resident macrophages were distributed throughout resting periosteum. In tissues collected from 4-week-old mice, osteomacs were observed intimately associated with sites of periosteal diaphyseal and metaphyseal bone dynamics associated with normal growth. This included F4/80
Publisher: Elsevier BV
Date: 10-1999
Publisher: Springer Science and Business Media LLC
Date: 30-05-2017
Publisher: The Company of Biologists
Date: 04-2022
DOI: 10.1242/DMM.049387
Abstract: Resident and recruited macrophages control the development and proliferation of the liver. We have previously shown in multiple species that treatment with a macrophage colony stimulating factor (CSF1)-Fc fusion protein initiated hepatocyte proliferation and promoted repair in models of acute hepatic injury in mice. Here, we investigated the impact of CSF1-Fc on resolution of advanced fibrosis and liver regeneration, using a non-resolving toxin-induced model of chronic liver injury and fibrosis in C57BL/6J mice. Co-administration of CSF1-Fc with exposure to thioacetamide (TAA) exacerbated inflammation consistent with monocyte contributions to initiation of pathology. After removal of TAA, either acute or chronic CSF1-Fc treatment promoted liver growth, prevented progression and promoted resolution of fibrosis. Acute CSF1-Fc treatment was also anti-fibrotic and pro-regenerative in a model of partial hepatectomy in mice with established fibrosis. The beneficial impacts of CSF1-Fc treatment were associated with monocyte-macrophage recruitment and increased expression of remodelling enzymes and growth factors. These studies indicate that CSF1-dependent macrophages contribute to both initiation and resolution of fibrotic injury and that CSF1-Fc has therapeutic potential in human liver disease.
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.EXPHEM.2021.07.001
Abstract: The bone marrow (BM) contains a mosaic of niches specialized in supporting different maturity stages of hematopoietic stem and progenitor cells such as hematopoietic stem cells and myeloid, lymphoid, and erythroid progenitors. Recent advances in BM imaging and conditional gene knockout mice have revealed that niches are a complex network of cells of mesenchymal, endothelial, neuronal, and hematopoietic origins, together with local physicochemical parameters. Within these complex structures, phagocytes, such as neutrophils, macrophages, and dendritic cells, all of which are of hematopoietic origin, have been found to be important in regulating several niches in the BM, including hematopoietic stem cell niches, erythropoietic niches, and niches involved in endosteal bone formation. There is also increasing evidence that these macrophages have an important role in adapting hematopoiesis, erythropoiesis, and bone formation in response to inflammatory stressors and play a key part in maintaining the integrity and function of these. Likewise, there is also accumulating evidence that subsets of monocytes, macrophages, and other phagocytes contribute to the progression and response to treatment of several lymphoid malignancies such as multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma, as well as lymphoblastic leukemia, and may also play a role in myelodysplastic syndrome and myeloproliferative neoplasms associated with Noonan syndrome and aplastic anemia. In this review, the potential functions of macrophages and other phagocytes in normal and pathologic niches are discussed, as are the challenges in studying BM and other tissue-resident macrophages at the molecular level.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Elsevier BV
Date: 04-2017
Publisher: Elsevier BV
Date: 06-2017
Publisher: Elsevier BV
Date: 07-2004
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.JMBBM.2019.04.030
Abstract: Macroscopic mechanical properties of porous PHBV bone TE scaffolds have been well studied. However, their mechanical behavior at microscopic level has yet to be explored. In this study, the micro-mechanical behavior of a PHBV bone scaffold under compression was investigated using a numerical method that combines micro-computed tomography (μ-CT) and finite element analysis (FEA). It was found that the use of a linear-elastic model resulted in an overestimation of the stiffness of the scaffold, whereas a more realistic estimation of the scaffold's deformation behavior was obtained by utilizing a bilinear material model. The onset of plastic deformation occurred in the very early stage of loading resulting in significantly reduced stiffness of the scaffold. The non-uniform and arbitrary microstructure of the scaffold led to a heterogeneous stress distribution within the porous construct, which was subjected to a mixture of compressive and tensile stresses. Nevertheless, the resultant stress contours showed that the scaffold experienced primarily elastic deformation when it was loaded up to 0.003 strain, while localized plastic deformation occurred at sharp corners and necked regions of the micro-struts. The scaffold expanded slightly in the horizontal direction as it was compressed and the change in geometries of pores within the scaffold was insignificant. The proposed method provides a valuable tool to study the localized mechanical behavior of bone scaffolds in micrometer scale with arbitrary porous architecture. This approach could prove highly useful for guiding the fabrication of scaffolds that have anatomy specific mechanical properties and porous architecture.
Publisher: Elsevier BV
Date: 09-2000
Publisher: Oxford University Press (OUP)
Date: 20-05-2010
Publisher: Springer Science and Business Media LLC
Date: 12-09-2013
DOI: 10.1038/LEU.2013.266
Publisher: Elsevier BV
Date: 04-2017
Publisher: Elsevier BV
Date: 10-2016
Publisher: European Association of Geochemistry
Date: 2017
Publisher: Springer Science and Business Media LLC
Date: 2004
Publisher: American Geophysical Union (AGU)
Date: 11-2022
DOI: 10.1029/2022GC010558
Abstract: To improve the understanding of the formation and evolution of the sub‐continental lithospheric mantle (SCLM) underlying the South Australian Craton we have conducted a detailed petrological study on ,000 mantle xenocrysts from 13 kimberlites emplaced across the craton. Pressure ( P ) and temperature ( T ) estimates on Cr diopside and garnet have been coupled with their chemical concentrations to constrain lithospheric thickness and chemo‐lithostratigraphy. We show that lithospheric thickness is greatest beneath the Gawler Craton, whereas thinner lithosphere occurs beneath the Adelaide Fold Belt. Mineral compositions highlight two litho‐chemical domains within the shallow and deep SCLM that are separated by a mid‐lithosphere discontinuity (MLD). The shallow SCLM (60–130 km) comprises low Cr 2 O 3 lherzolite and wehrlite. Shallow SCLM xenocrysts record depleted and refertilized compositions enriched in light rare earth elements related to metasomatism by kimberlite or related melts. The mid‐lithosphere (130–160 km) is depleted in garnet and Cr diopside which may relate to a layer of pargasite lherzolite. The deep SCLM ( km) comprises high Cr 2 O 3 lherzolite with elevated TiO 2 and FeO. We interpret the litho‐chemical stratification of the SCLM to reflect a multi‐stage top‐down growth. The shallow SCLM reflects an amalgamation of Precambrian cratonic nuclei characterized by heterogeneity in geochemical enrichment and depletion. Interaction of the shallow SCLM with mantle plumes accreted melts along the paleo‐lithosphere‐asthenosphere boundary, which now occurs as a MLD. The deep SCLM represents depleted mantle residue formed during mantle plume impingement and thickened during orogenesis. This domain has been metasomatized and refertilized by high‐T melts from the asthenosphere.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2020
DOI: 10.1038/S41598-020-63518-2
Abstract: Diamond formation in the Earth has been extensively discussed in recent years on the basis of geochemical analysis of natural materials, high-pressure experimental studies, or theoretical aspects. Here, we demonstrate experimentally for the first time, the spontaneous crystallization of diamond from CH 4 -rich fluids at pressure, temperature and redox conditions approximating those of the deeper parts of the cratonic lithospheric mantle (5–7 GPa) without using diamond seed crystals or carbides. In these experiments the fluid phase is nearly pure methane, even though the oxygen fugacity was significantly above metal saturation. We propose several previously unidentified mechanisms that may promote diamond formation under such conditions and which may also have implications for the origin of sublithospheric diamonds. These include the hydroxylation of silicate minerals like olivine and pyroxene, H 2 incorporation into these phases and the “etching” of graphite by H 2 and CH 4 and reprecipitation as diamond. This study also serves as a demonstration of our new high-pressure experimental technique for obtaining reduced fluids, which is not only relevant for diamond synthesis, but also for investigating the metasomatic origins of diamond in the upper mantle, which has further implications for the deep carbon cycle.
Publisher: Springer Science and Business Media LLC
Date: 05-2017
DOI: 10.1038/NATURE22054
Abstract: Mantle plumes are buoyant upwellings of hot rock that transport heat from Earth's core to its surface, generating anomalous regions of volcanism that are not directly associated with plate tectonic processes. The best-studied ex le is the Hawaiian-Emperor chain, but the emergence of two sub-parallel volcanic tracks along this chain, Loa and Kea, and the systematic geochemical differences between them have remained unexplained. Here we argue that the emergence of these tracks coincides with the appearance of other double volcanic tracks on the Pacific plate and a recent azimuthal change in the motion of the plate. We propose a three-part model that explains the evolution of Hawaiian double-track volcanism: first, mantle flow beneath the rapidly moving Pacific plate strongly tilts the Hawaiian plume and leads to lateral separation between high- and low-pressure melt source regions second, the recent azimuthal change in Pacific plate motion exposes high- and low-pressure melt products as geographically distinct volcanoes, explaining the simultaneous emergence of double-track volcanism across the Pacific and finally, secondary pyroxenite, which is formed as eclogite melt reacts with peridotite, dominates the low-pressure melt region beneath Loa-track volcanism, yielding the systematic geochemical differences observed between Loa- and Kea-type lavas. Our results imply that the formation of double-track volcanism is transitory and can be used to identify and place temporal bounds on plate-motion changes.
Publisher: Elsevier BV
Date: 07-2000
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 06-2014
Publisher: Springer Science and Business Media LLC
Date: 12-2013
Publisher: Springer Science and Business Media LLC
Date: 27-07-2022
DOI: 10.1007/S00410-022-01944-3
Abstract: The reliability of eight Fe–Mg exchange geothermobarometers for garnet-bearing peridotites, pyroxenites and eclogites has been examined using a database comprised of more than 300 published peridotite, pyroxenite and eclogite experiments conducted from 10 to 70 kbar and 850 to 1650 $$^\\circ{\\rm C}$$ ∘ C . We have tested Fe–Mg exchange geothermometers suitable for a range of mantle lithologies, including websterite, harzburgite, wehrlite and eclogite. All geothermometers maintained an average difference in experimental and calculated temperature (T) $$\\left( {\\Delta {\\text{T}} = {\\text{T}}_{{\\exp - { }}} {\\text{T}}_{{{\\text{calc}}}} } \\right)$$ Δ T = T exp - T calc of less than $$\\pm$$ ± 50 °C with a standard deviation of $$\\Delta {\\text{T}}$$ Δ T between $$\\pm$$ ± 50 to 150 °C. Most geothermometers performed well across a narrow range in ln $${\\text{Kd}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{A}} - {\\text{B}}}}$$ Kd Fe - Mg A - B (where $${\\text{Kd}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{A}} - {\\text{B}}}} =$$ Kd Fe - Mg A - B = $$\\frac{{\\left( {{\\text{Fe}}_{{\\text{A}}} \\times {\\text{Mg}}_{{\\text{B}}} } \\right)}}{{({\\text{Fe}}_{{\\text{B}}} \\times {\\text{Mg}}_{{\\text{A}}} )}}$$ Fe A × Mg B ( Fe B × Mg A ) ), however, systematic overestimation and underestimation of T were observed outside of the optimal range of $${\\text{lnKd}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{A}} - {\\text{B}}}}$$ lnKd Fe - Mg A - B . Increases in experimental pressure (P) adversely affected several geothermometers, particularly those calibrated empirically using natural s les. All previously published calibrations of the garnet-clinopyroxene geothermometer were unable to reliably reproduce the experimental T for both peridotite and eclogite experimental compositions, which hinders their confident application to natural datasets. To improve the state of mantle geothermobarometry we have used our experimental database to recalibrate the (1) garnet-clinopyroxene Fe–Mg exchange geothermometer, and (2) garnet-orthopyroxene Fe–Mg exchange geothermometer. Each geothermometer has been recalibrated across an extended P, T, and compositional range. The inclusion of eclogitic experiments in the calibration for the garnet-clinopyroxene geothermometer permits application to both eclogitic and peridotitic yroxenitic assemblages equilibrated under a wide range of PT conditions in the upper mantle. Using multiple linear regression to solve for lnKd, we found the following expressions best reproduced the experimental T (℃) of our dataset: $${\\text{T}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{grt}} - {\\text{cpx}}}} { (}^{ \\circ } {\\text{C)}} = { }\\frac{3356.34}{{\\left( {\\left( { - 0.008 \\times {\\text{P }}\\left( {{\\text{kbar}}} \\right)} \\right) + \\left( {0.259 \\times {\\text{X}}_{{{\\text{Ca}}}}^{{{\\text{grt}}}} } \\right) + \\left( {0.914 \\times {\\text{X}}_{{{\\text{Mg}}}}^{{{\\text{grt}}}} } \\right) + \\left( { - 0.159 \\times {\\text{Jd}}^{{{\\text{cpx}}}} } \\right) + \\left( {{\\text{ln}}\\left( {{\\text{ Kd}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{grt}} - {\\text{cpx}}}} } \\right) + 1.265} \\right)} \\right)}} - 273{ }$$ T Fe - Mg grt - cpx ( ∘ C) = 3356.34 - 0.008 × P kbar + 0.259 × X Ca grt + 0.914 × X Mg grt + - 0.159 × Jd cpx + ln Kd Fe - Mg grt - cpx + 1.265 - 273 $${\\text{T}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{grt}} - {\\text{opx}}}} { (}^{ \\circ } {\\text{C)}} = { }\\frac{1851.85}{{\\left( {\\left( { - 0.007 \\times {\\text{P }}\\left( {{\\text{kbar}}} \\right)} \\right) + \\left( { - 1.83 \\times {\\text{X}}_{{{\\text{Ca}}}}^{{{\\text{grt}}}} } \\right) + \\left( {{\\text{ln}}\\left( {{\\text{ Kd}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{grt}} - {\\text{cpx}}}} } \\right) + 1.08} \\right)} \\right)}} - 273$$ T Fe - Mg grt - opx ( ∘ C) = 1851.85 - 0.007 × P kbar + - 1.83 × X Ca grt + ln Kd Fe - Mg grt - cpx + 1.08 - 273 . where, $${\\text{X}}_{{{\\text{Ca}}}}^{{{\\text{grt}}}} =$$ X Ca grt = $$\\frac{{{\\text{Ca}}}}{{\\left( {{\\text{Ca}} + {\\text{Fe}} + {\\text{Mg}}} \\right)}}$$ Ca Ca + Fe + Mg , $${\\text{Kd}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{grt}} - {\\text{opx}}}} =$$ Kd Fe - Mg grt - opx = $$\\frac{{\\left( {{\\text{Fe}}_{{{\\text{grt}}}} \\times {\\text{Mg}}_{{{\\text{opx}}}} } \\right)}}{{({\\text{Fe}}_{{{\\text{opx}}}} \\times {\\text{Mg}}_{{{\\text{grt}}}} )}} , {\\text{X}}_{{{\\text{Mg}}}}^{{{\\text{grt}}}} =$$ Fe grt × Mg opx ( Fe opx × Mg grt ) , X Mg grt = $$\\frac{{{\\text{Mg}}}}{{\\left( {{\\text{Ca}} + {\\text{Fe}} + {\\text{Mg}}} \\right)}}$$ Mg Ca + Fe + Mg , $${\\text{Jd}}^{{{\\text{cpx}}}} = {\\text{Na}} - {\\text{Cr}} - 2 \\times {\\text{Ti}}$$ Jd cpx = Na - Cr - 2 × Ti , $${\\text{Kd}}_{{{\\text{Fe}} - {\\text{Mg}}}}^{{{\\text{grt}} - {\\text{cpx}}}} =$$ Kd Fe - Mg grt - cpx = $$\\frac{{\\left( {{\\text{Fe}}_{{{\\text{grt}}}} \\times {\\text{Mg}}_{{{\\text{cpx}}}} } \\right)}}{{({\\text{Fe}}_{{{\\text{cpx}}}} \\times {\\text{Mg}}_{{{\\text{grt}}}} )}},$$ Fe grt × Mg cpx ( Fe cpx × Mg grt ) , with all elements calculated on the basis of 12 oxygen anions in garnet and 6 oxygen anions in clino- and orthopyroxene. Fe 2+ = total Fe. Our updated calibrations resolve several issues with earlier calibrations, including a poor performance at elevated P and compositional limitations. An improvement in precision and accuracy has been demonstrated through application to the experimental calibration dataset, a second independent set of published experimental data, and to natural peridotites, pyroxenites and eclogites from on and off craton settings. Iterative PT estimates on natural datasets calculated using our updated calibrations compare well with estimates from widely used calibrations such as the Taylor (1998) two-pyroxene solvus geothermometer. We anticipate that this contribution will provide an important reference for the reliability of mantle geothermometers and that our updated calibrations will be used in future studies on peridotite, pyroxenite and eclogite inclusions in diamond and mantle-derived xenoliths.
Publisher: Springer Science and Business Media LLC
Date: 07-04-2021
DOI: 10.1007/S00410-021-01791-8
Abstract: The temperature-dependent exchange of Ni and Mg between garnet and olivine in mantle peridotite is an important geothermometer for determining temperature variations in the upper mantle and the diamond potential of kimberlites. Existing calibrations of the Ni-in-garnet geothermometer show considerable differences in estimated temperature above and below 1100 °C hindering its confident application. In this study, we present the results from new synthesis experiments conducted on a piston cylinder apparatus at 2.25–4.5 GPa and 1100–1325 °C. Our experimental approach was to equilibrate a Ni-free Cr-pyrope-rich garnet starting mixture made from sintered oxides with natural olivine capsules (Ni olv ≅ 3000 ppm) to produce an experimental charge comprised entirely of peridotitic pyrope garnet with trace abundances of Ni (10–100 s of ppm). Experimental runs products were analysed by wave-length dispersive electron probe microanalysis (EPMA) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). We use the partition coefficient for the distribution of Ni between our garnet experimental charge and the olivine capsule $$\\left( {{\\text{lnD}}_{{{\\text{grt}}/{\\text{olv}}}}^{{{\\text{Ni}}}} \\frac{{{\\text{Ni}}_{{{\\text{grt}}}} }}{{{\\text{Ni}}_{{{\\text{olv}}}} }}} \\right)$$ lnD grt / olv Ni ; Ni grt Ni olv , the Ca mole fraction in garnet ( $${\\mathrm{X}}_{\\mathrm{grt}}^{\\mathrm{Ca}} $$ X grt Ca ; Ca/(Ca + Fe + Mg)), and the Cr mole fraction in garnet ( $${\\mathrm{X}}_{\\mathrm{grt}}^{\\mathrm{Cr}} $$ X grt Cr ; Cr/(Cr + Al)) to develop a new formulation of the Ni-in-garnet geothermometer that performs more reliably on experimental and natural datasets than existing calibrations. Our updated Ni-in-garnet geothermometer is defined here as: $$T \\left(^\\circ{\\rm C} \\right)=\\frac{-8254.568}{\\left(\\left( {\\mathrm{X}}_{\\mathrm{grt}}^{\\mathrm{Ca}} \\times 3.023 \\right)+\\left({\\mathrm{X}}_{\\mathrm{grt}}^{\\mathrm{Cr}} \\times 2.307 \\right)+\\left({\\mathrm{lnD}}_{\\frac{\\mathrm{grt}}{\\mathrm{olv}}}^{\\mathrm{Ni}} - 2.639 \\right)\\right)}-273\\pm 55$$ T ∘ C = - 8254.568 X grt Ca × 3.023 + X grt Cr × 2.307 + lnD grt olv Ni - 2.639 - 273 ± 55 where $${\\mathrm{D}}_{\\mathrm{grt}/\\mathrm{olv}}^{\\mathrm{Ni}}= \\frac{{\\mathrm{Ni}}_{\\mathrm{grt}}}{{\\mathrm{Ni}}_{\\mathrm{olv}}},$$ D grt / olv Ni = Ni grt Ni olv , Ni is in ppm, $${\\mathrm{X}}_{\\mathrm{grt}}^{\\mathrm{Ca}}$$ X grt Ca = Ca/(Ca + Fe + Mg) in garnet, and $${\\mathrm{X}}_{\\mathrm{grt}}^{\\mathrm{Cr}}$$ X grt Cr = Cr/(Cr + Al) in garnet. Our updated Ni-in-garnet geothermometer can be applied to garnet peridotite xenoliths or monomineralic garnet xenocrysts derived from disaggregation of a peridotite source. Our calibration can be used as a single grain geothermometer by assuming an average mantle olivine Ni concentration of 3000 ppm. To maximise the reliability of temperature estimates made from our Ni-in-garnet geothermometer, we provide users with a data quality protocol method which can be applied to all garnet EPMA and LA-ICP-MS analyses prior to Ni-in-garnet geothermometry. The temperature uncertainty of our updated calibration has been rigorously propagated by incorporating all analytical and experimental uncertainties. We have found that our Ni-in-garnet temperature estimates have a maximum associated uncertainty of ± 55 °C. The improved performance of our updated calibration is demonstrated through its application to previously published experimental datasets and on natural, well-characterised garnet peridotite xenoliths from a variety of published datasets, including the diamondiferous Diavik and Ekati kimberlite pipes from the Lac de Gras kimberlite field, Canada. Our new calibration better aligns temperature estimates using the Ni-in-garnet geothermometer with those estimated by the widely used (Nimis and Taylor, Contrib Mineral Petrol 139:541–554, 2000) enstatite-in-clinopyroxene geothermometer, and confirms an improvement in performance of the new calibration relative to existing versions of the Ni-in-garnet geothermometer.
Publisher: Elsevier BV
Date: 2015
Publisher: Elsevier BV
Date: 06-2012
Publisher: Oxford University Press (OUP)
Date: 28-01-2012
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.AJPATH.2017.05.007
Abstract: Multicentric carpal-tarsal osteolysis multicentric osteolysis, nodulosis, and arthropathy and Winchester syndromes, skeletal dysplasias characterized by carpal/tarsal and epiphyseal abnormalities, are caused by mutations in v-maf musculoaponeurotic fibrosarcoma oncogene ortholog B (MAFB), matrix metalloproteinase (MMP) 2, and MMP14, respectively however, the underlying pathophysiology is unclear. Osteoclast-mediated osteolysis has been regarded as the main mechanism, but does not explain the skeletal distribution. We hypothesized that MAFB, MMP-2, and MMP-14 have integral roles in carpal/tarsal and epiphyseal bone development. Normal neonatal mouse forepaws were imaged by micro-computed tomography and examined histologically. Murine forepaw ossification occurred sequentially. Subarticular regions of endochondral ossification showed morphologic and calcification patterns that were distinct from archetypical physeal endochondral ossification. This suggests that two different forms of endochondral ossification occur. The skeletal sites showing the greatest abnormality in the carpal-tarsal osteolysis syndromes are regions of subarticular ossification. Thus, abnormal bone formation in areas of subarticular ossification may explain the site-specific distribution of the carpal-tarsal osteolysis phenotype. MafB, Mmp-2, and Mmp-14 were expressed widely, and tartrate-resistant acid phosphatase staining notably was absent in the subarticular regions of the cartilage anlagen and entheses at a time point most relevant to the human osteolysis syndromes. Thus, abnormal peri-articular skeletal development and modeling, rather than excessive bone resorption, may be the underlying pathophysiology of these skeletal syndromes.
Publisher: American Society of Hematology
Date: 16-08-2018
DOI: 10.1182/BLOOD-2018-01-829663
Abstract: Recipient macrophages persist in hematopoietic tissues and self-repopulate via in situ proliferation after syngeneic transplantation. Targeted depletion of recipient CD169+ macrophages after transplant impaired long-term bone marrow engraftment of hematopoietic stem cells.
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 04-2017
Publisher: Springer Science and Business Media LLC
Date: 17-12-2013
DOI: 10.1038/NCOMMS3921
Abstract: Kimberlites are a volumetrically minor component of the Earth's volcanic record, but are very important as the major commercial source of diamonds and as the deepest s les of the Earth's mantle. They were predominantly emplaced from ≈2,100 Ma to ≈10 ka ago, into ancient, stable regions of continental crust (cratons), but are also known from continental rifts and mobile belts. Kimberlites have been reported from almost all major cratons on all continents except for Antarctica. Here we report the first bona fide Antarctic kimberlite occurrence, from the northern Prince Charles Mountains, emplaced during the reactivation of the Lambert Graben associated with rifting of India from Australia-Antarctica. The s les are texturally, mineralogically and geochemically typical of Group I kimberlites from more classical localities. Their ≈120 Ma ages overlap with those of many kimberlites from other world-wide localities, extending a vast Cretaceous, Gondwanan kimberlite province, for the first time, into Antarctica.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.FORSCIINT.2009.03.018
Abstract: Discrimination of material based on elemental composition was achieved within a compositional data (CoDa) analysis framework in a form appropriate for use in forensic science. The methods were carried out on ex le data from New Zealand nephrite. We have achieved good separation of the in situ outcrops of nephrite from within a well-defined area. The most significant achievement of working within the CoDa analysis framework is that the implications of the constraints on the data are acknowledged and dealt with, not ignored. The full composition was reduced based on collinearity of elements, principal components analysis (PCA) and scalings from a backwards linear discriminant analysis (LDA). Thus, a descriptive subcomposition was used for the final discrimination, using LDA, and proved to be more successful than using the full composition. The classification based on the LDA model showed a mean error rate of 2.9% when validated using a 10 repeat, three-fold cross-validation. The methods presented lend objectivity to the process of interpretation, rather than relying on subjective pattern matching type approaches.
Publisher: Proceedings of the National Academy of Sciences
Date: 31-12-2013
Abstract: SMG1 is a member of the phosphoinositide kinase-like kinase family of proteins that includes ATM, ATR, and DNA-PK, proteins with known roles in DNA damage and cellular stress responses. SMG1 has a well-characterized role in nonsense-mediated decay as well as suggested roles in the DNA damage response, resistance to oxidative stress, regulation of hypoxic responses, and apoptosis. To understand the roles of SMG1 further, we generated a Genetrap Smg1 mouse model. Smg1 homozygous KO mice were early embryonic lethal, but Smg1 heterozygous mice showed a predisposition to a range of cancers, particularly lung and hematopoietic malignancies, as well as development of chronic inflammation. These mice did not display deficiencies in known roles of SMG1, including nonsense-mediated decay. However, they showed elevated basal tissue and serum cytokine levels, indicating low-level inflammation before the development of tumors. Smg1 heterozygous mice also showed evidence of oxidative damage in tissues. These data suggest that the inflammation observed in Smg1 haploinsufficiency contributes to susceptibility to cancer and that Smg1 -deficient animals represent a model of inflammation-enhanced cancer development.
Publisher: Geological Society of America
Date: 08-2013
DOI: 10.1130/G34311.1
Publisher: Geological Society of America
Date: 03-2013
DOI: 10.1130/G33787.1
Publisher: Springer Science and Business Media LLC
Date: 03-12-2015
DOI: 10.1038/NCOMMS9983
Abstract: Multiple myeloma is largely incurable, despite development of therapies that target myeloma cell-intrinsic pathways. Disease relapse is thought to originate from dormant myeloma cells, localized in specialized niches, which resist therapy and repopulate the tumour. However, little is known about the niche, and how it exerts cell-extrinsic control over myeloma cell dormancy and reactivation. In this study, we track in idual myeloma cells by intravital imaging as they colonize the endosteal niche, enter a dormant state and subsequently become activated to form colonies. We demonstrate that dormancy is a reversible state that is switched ‘on’ by engagement with bone-lining cells or osteoblasts, and switched ‘off’ by osteoclasts remodelling the endosteal niche. Dormant myeloma cells are resistant to chemotherapy that targets iding cells. The demonstration that the endosteal niche is pivotal in controlling myeloma cell dormancy highlights the potential for targeting cell-extrinsic mechanisms to overcome cell-intrinsic drug resistance and prevent disease relapse.
Publisher: Springer Science and Business Media LLC
Date: 14-02-2017
DOI: 10.1038/S41598-017-00049-3
Abstract: We present the first oxygen fugacity ( f O 2 ) profile through the cratonic lithospheric mantle under the Panda kimberlite (Ekati Diamond Mine) in the Lac de Gras kimberlite field, central Slave Craton, northern Canada. Combining this data with new and existing data from garnet peridotite xenoliths from an almost coeval kimberlite (A154-N) at the nearby Diavik Diamond Mine demonstrates that the oxygen fugacity of the Slave cratonic mantle varies by several orders of magnitude as a function of depth and over short lateral distances. The lower part of the diamond-bearing Slave lithosphere ( –130 km deep) has been oxidized by up to 4 log units in f O 2 , and this is clearly linked to metasomatic enrichment. Such coupled enrichment and oxidation was likely caused by infiltrating carbonate-bearing, hydrous, silicate melts in the presence of diamond, a process proposed to be critical for “pre-conditioning” deep lithospheric mantle and rendering it suitable for later generation of kimberlites and other SiO 2 -undersaturated magmas.
Publisher: Elsevier BV
Date: 11-2015
Publisher: Rockefeller University Press
Date: 03-03-2021
DOI: 10.1084/JEM.20201452
Abstract: Vincristine is an important component of many regimens used for pediatric and adult malignancies, but it causes a dose-limiting sensorimotor neuropathy for which there is no effective treatment. This study aimed to delineate the neuro-inflammatory mechanisms contributing to the development of mechanical allodynia and gait disturbances in a murine model of vincristine-induced neuropathy, as well as to identify novel treatment approaches. Here, we show that vincristine-induced peripheral neuropathy is driven by activation of the NLRP3 inflammasome and subsequent release of interleukin-1β from macrophages, with mechanical allodynia and gait disturbances significantly reduced in knockout mice lacking NLRP3 signaling pathway components, or after treatment with the NLRP3 inhibitor MCC950. Moreover, treatment with the IL-1 receptor antagonist anakinra prevented the development of vincristine-induced neuropathy without adversely affecting chemotherapy efficacy or tumor progression in patient-derived medulloblastoma xenograph models. These results detail the neuro-inflammatory mechanisms leading to vincristine-induced peripheral neuropathy and suggest that repurposing anakinra may be an effective co-treatment strategy to prevent vincristine-induced peripheral neuropathy.
Publisher: Springer Science and Business Media LLC
Date: 25-02-2022
DOI: 10.1038/S41413-022-00188-Y
Abstract: The cells of origin of neurogenic heterotopic ossifications (NHOs), which develop frequently in the periarticular muscles following spinal cord injuries (SCIs) and traumatic brain injuries, remain unclear because skeletal muscle harbors two progenitor cell populations: satellite cells (SCs), which are myogenic, and fibroadipogenic progenitors (FAPs), which are mesenchymal. Lineage-tracing experiments using the Cre recombinase/LoxP system were performed in two mouse strains with the fluorescent protein ZsGreen specifically expressed in either SCs or FAPs in skeletal muscles under the control of the Pax7 or Prrx1 gene promoter, respectively. These experiments demonstrate that following muscle injury, SCI causes the upregulation of PDGFRα expression on FAPs but not SCs and the failure of SCs to regenerate myofibers in the injured muscle, with reduced apoptosis and continued proliferation of muscle resident FAPs enabling their osteogenic differentiation into NHOs. No cells expressing ZsGreen under the Prrx1 promoter were detected in the blood after injury, suggesting that the cells of origin of NHOs are locally derived from the injured muscle. We validated these findings using human NHO biopsies. PDGFRα + mesenchymal cells isolated from the muscle surrounding NHO biopsies could develop ectopic human bones when transplanted into immunocompromised mice, whereas CD56 + myogenic cells had a much lower potential. Therefore, NHO is a pathology of the injured muscle in which SCI reprograms FAPs to undergo uncontrolled proliferation and differentiation into osteoblasts.
Publisher: Cambridge University Press
Date: 31-10-2019
Publisher: Frontiers Media SA
Date: 07-03-2019
Publisher: Elsevier BV
Date: 2019
Publisher: Geological Society of London
Date: 2008
DOI: 10.1144/SP308.11
Publisher: Oxford University Press (OUP)
Date: 06-05-2013
Publisher: American Society for Clinical Investigation
Date: 02-11-2017
Publisher: Geological Society of America
Date: 28-08-2015
DOI: 10.1130/G37052.1
Publisher: Elsevier BV
Date: 05-2012
Publisher: American Geophysical Union (AGU)
Date: 2006
DOI: 10.1029/2006GL026446
Publisher: Wiley
Date: 27-04-2016
DOI: 10.1002/PATH.4718
Abstract: Skeletal metastases present a major clinical challenge for prostate cancer patient care, inflicting distinctive mixed osteoblastic and osteolytic lesions that cause morbidity and refractory skeletal complications. Macrophages are abundant in bone and bone marrow and can influence both osteoblast and osteoclast function in physiology and pathology. Herein, we examined the role of macrophages in prostate cancer bone lesions, particularly the osteoblastic response. First, macrophage and lymphocyte distributions were qualitatively assessed in patient's prostate cancer skeletal lesions by immunohistochemistry. Second, macrophage functional contributions to prostate tumour growth in bone were explored using an immune-competent mouse model combined with two independent approaches to achieve in vivo macrophage depletion: liposome encapsulated clodronate that depletes phagocytic cells (including macrophages and osteoclasts) and targeted depletion of CD169(+) macrophages using a suicide gene knock-in model. Immunohistochemistry and histomorphometric analysis were performed to quantitatively assess cancer-induced bone changes. In human bone metastasis specimens, CD68(+) macrophages were consistently located within the tumour mass. Osteal macrophages (osteomacs) were associated with pathological woven bone within the metastatic lesions. In contrast, lymphocytes were inconsistently present in prostate cancer skeletal lesions and when detected, had varied distributions. In the immune-competent mouse model, CD169(+) macrophage ablation significantly inhibited prostate cancer-induced woven bone formation, suggesting that CD169(+) macrophages within pathological woven bone are integral to tumour-induced bone formation. In contrast, pan-phagocytic cell, but not targeted CD169(+) macrophage depletion resulted in increased tumour mass, indicating that CD169(-) macrophage subset(s) and/or osteoclasts influenced tumour growth. In summary, these observations indicate a prominent role for macrophages in prostate cancer bone metastasis that may be therapeutically targetable to reduce the negative skeletal impacts of this malignancy, including tumour-induced bone modelling. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Publisher: Geological Society of America
Date: 03-2014
DOI: 10.1130/G35373Y.1
Publisher: Society of Economic Geologists
Date: 2018
DOI: 10.5382/SP.20.05
Publisher: Geological Society of America
Date: 06-2013
DOI: 10.1130/G34119.1
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.EXPHEM.2021.08.011
Abstract: It has recently emerged that tissue-resident macrophages are key regulators of several stem cell niches orchestrating tissue formation during development, as well as postnatally, when they also organize the repair and regeneration of many tissues including the hemopoietic tissue. The fact that macrophages are also master regulators and effectors of innate immunity and inflammation allows them to coordinate hematopoietic response to infections, injuries, and inflammation. After recently reviewing the roles of phagocytes and macrophages in regulating normal and pathologic hematopoietic stem cell niches, we now focus on the key roles of macrophages in regulating erythropoiesis and iron homeostasis. We review herein the recent advances in understanding how macrophages at the center of erythroblastic islands form an erythropoietic niche that controls the terminal differentiation and maturation of erythroblasts into reticulocytes how red pulp macrophages in the spleen control iron recycling and homeostasis how these macrophages coordinate emergency erythropoiesis in response to blood loss, infections, and inflammation and how persistent infections or inflammation can lead to anemia of inflammation via macrophages. Finally, we discuss the technical challenges associated with the molecular characterization of erythroid island macrophages and red pulp macrophages.
Publisher: Oxford University Press (OUP)
Date: 27-02-2020
DOI: 10.1093/PETROLOGY/EGAA035
Abstract: High-pressure experiments were performed to investigate the effectiveness, rate and mechanism of carbonation of serpentinites by a carbon-saturated COH fluid at 1·5–2·5 GPa and 375–700 °C. This allows a better understanding of the fate and redistribution of slab-derived carbonic fluids when they react with the partially hydrated mantle within and above the subducting slab under pressure and temperature conditions corresponding to the forearc mantle. Interactions between carbon-saturated CO2–H2O–CH4 fluids and serpentinite were investigated using natural serpentinite cylinders with natural grain sizes and shapes in piston-cylinder experiments. The volatile composition of post-run fluids was quantified by gas chromatography. Solid phases were examined by Raman spectroscopy, electron microscopy and laser ablation inductively coupled plasma mass spectrometry. Textures, porosity and phase abundances of recovered rock cores were visualized and quantified by three-dimensional, high-resolution computed tomography. We find that carbonation of serpentinites is efficient at sequestering CO2 from the interacting fluid into newly formed magnesite. Time-series experiments demonstrate that carbonation is completed within ∼96 h at 2 GPa and 600 °C. With decreasing CO2,aq antigorite is replaced first by magnesite + quartz followed by magnesite + talc + chlorite in distinct, metasomatic fronts. Above antigorite stability magnesite + enstatite + talc + chlorite occur additionally. The formation of fluid-permeable reaction zones enhances the reaction rate and efficiency of carbonation. Carbonation probably occurs via an interface-coupled replacement process, whereby interconnected porosity is present within reaction zones after the experiment. Consequently, carbonation of serpentinites is self-promoting and efficient even if fluid flow is channelized into veins. We conclude that significant amounts of carbonates may accumulate, over time, in the hydrated forearc mantle.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.AJPATH.2013.01.046
Abstract: Previous studies have generated conflicting results regarding the contribution of B cells to bone formation during physiology and repair. Here, we have investigated the role of B cells in osteoblast-mediated intramembranous anabolic bone modeling. Immunohistochemistry for CD45 receptor expression indicated that B cells had no propensity or aversion for endosteal regions or sites of bone modeling and/or remodeling in wild-type mice. In the endocortical diaphyseal region, quantitative immunohistology demonstrated that young wild-type and B-cell deficient mice had similar amounts of osteocalcin(+) osteoblast bone modeling surface. The degree of osteoblast-associated osteomac canopy was also comparable in these mice inferring that bone modeling cellular units were preserved in the absence of B cells. In a tibial injury model, only rare CD45 receptor positive B cells were located within areas of high anabolic activity, including minimal association with osterix(+) osteoblast-lineage committed mesenchymal cells in wild-type mice. Quantitative immunohistology demonstrated that collagen type I matrix deposition and macrophage and osteoclast distribution within the injury site were not compromised by the absence of B cells. Overall, osteoblast distribution during normal growth and bone healing via intramembranous ossification proceeded normally in the absence of B cells. These observations support that in vivo, these lymphoid cells have minimal influence, or at most, make redundant contributions to osteoblast function during anabolic bone modeling via intramembranous mechanisms.
Publisher: Elsevier BV
Date: 08-2018
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.CELREP.2021.110058
Abstract: Mouse hematopoietic tissues contain abundant tissue-resident macrophages that support immunity, hematopoiesis, and bone homeostasis. A systematic strategy to characterize macrophage subsets in mouse bone marrow (BM), spleen, and lymph node unexpectedly reveals that macrophage surface marker staining emanates from membrane-bound subcellular remnants associated with unrelated cells. Intact macrophages are not present within these cell preparations. The macrophage remnant binding profile reflects interactions between macrophages and other cell types in vivo. Depletion of CD169
Publisher: Springer Science and Business Media LLC
Date: 11-04-2007
Publisher: Springer Science and Business Media LLC
Date: 09-01-2016
Publisher: Elsevier BV
Date: 12-2011
Publisher: Elsevier BV
Date: 08-2018
Publisher: Springer Science and Business Media LLC
Date: 28-09-2004
Publisher: Elsevier BV
Date: 11-2010
Publisher: Springer Science and Business Media LLC
Date: 11-01-0007
Publisher: Wiley
Date: 03-08-2021
DOI: 10.1002/JBMR.4413
Abstract: Osteal macrophages (osteomacs) support osteoblast function and promote bone anabolism, but their contribution to osteoporosis has not been explored. Although mouse ovariectomy (OVX) models have been repeatedly used, variation in strain, experimental design and assessment modalities have contributed to no single model being confirmed as comprehensively replicating the full gamut of osteoporosis pathological manifestations. We validated an OVX model in adult C3H/HeJ mice and demonstrated that it presents with human postmenopausal osteoporosis features with reduced bone volume in axial and appendicular bone and bone loss in both trabecular and cortical bone including increased cortical porosity. Bone loss was associated with increased osteoclasts on trabecular and endocortical bone and decreased osteoblasts on trabecular bone. Importantly, this OVX model was characterized by delayed fracture healing. Using this validated model, we demonstrated that osteomacs are increased post‐OVX on both trabecular and endocortical bone. Dual F4/80 (pan‐macrophage marker) and tartrate‐resistant acid phosphatase (TRAP) staining revealed osteomacs frequently located near TRAP + osteoclasts and contained TRAP + intracellular vesicles. Using an in vivo inducible macrophage depletion model that does not simultaneously deplete osteoclasts, we observed that osteomac loss was associated with elevated extracellular TRAP in bone marrow interstitium and increased serum TRAP. Using in vitro high‐resolution confocal imaging of mixed osteoclast‐macrophage cultures on bone substrate, we observed macrophages juxtaposed to osteoclast basolateral functional secretory domains scavenging degraded bone byproducts. These data demonstrate a role for osteomacs in supporting osteoclastic bone resorption through phagocytosis and sequestration of resorption byproducts. Overall, our data expose a novel role for osteomacs in supporting osteoclast function and provide the first evidence of their involvement in osteoporosis pathogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR).
Start Date: 2006
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Funder: Australian Research Council
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Funder: Australian Research Council
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End Date: 2021
Funder: Australian Research Council
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Funder: Australian Research Council
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End Date: 12-2008
Amount: $270,000.00
Funder: Australian Research Council
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End Date: 07-2025
Amount: $413,000.00
Funder: Australian Research Council
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Amount: $121,244.00
Funder: Australian Research Council
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Amount: $270,000.00
Funder: Australian Research Council
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Amount: $330,000.00
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End Date: 01-2014
Amount: $686,400.00
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End Date: 12-2018
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Amount: $5,000,000.00
Funder: Australian Research Council
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