Magmatic Cu-Ni-PGE-Au sulfide mineralisation in alkaline igneous systems: An example from the Sron Garbh intrusion, Tyndrum, Scotland

Magmatic sulfide deposits typically occur in ultramafic-mafic systems, however, mineralisation can occur in more intermediate and alkaline magmas. Sron Garbh is an appinite-diorite intrusion emplaced into Dalradian metasediments in the Tyndrum area of Scotland that hosts magmatic Cu-Ni-PGE-Au sulfide mineralisation in the appinitic portion. It is thus an example of magmatic sulfide mineralisation hosted by alkaline rocks, and is the most significantly mineralised appinitic intrusion known in the British Isles. The intrusion is irregularly shaped, with an appinite rim, comprising amphibole cumulates classed as vogesites. The central portion of the intrusion is comprised of unmineralised, but pyrite-bearing, diorites. Both appinites and diorites have similar trace element geochemistry that suggests the diorite is a more fractionated differentiate of the appinite from a common source that can be classed with the high Ba-Sr intrusions of the Scottish Caledonides. Mineralisation is present as a disseminated, primary chalcopyrite-pyrite-PGM assemblage and a blebby, pyrite-chalcopyrite assemblage with significant Co-As-rich pyrite. Both assemblages contain minor millerite and Ni-Co-As-sulfides. The mineralisation is Cu-, PPGE-, and Au-rich and IPGE-poor and the platinum group mineral assemblage is overwhelmingly dominated by Pd minerals; however, the bulk rock Pt/Pd ratio is around 0.8. Laser ablation analysis of the sulfides reveals that pyrite and the Ni-Co-sulfides are the primary host for Pt, which is present in solid solution in concentrations of up to 22 ppm in pyrite. Good correlations between all base and precious metals indicate very little hydrothermal remobilisation of metals despite some evidence of secondary pyrite and PGM. Sulfur isotope data indicate some crustal S in the magmatic sulfide assemblages. The source of this is unlikely to have been the local quartzites, but S-rich Dalradian sediments present at depth. The generation of magmatic Cu-Ni-PGE-Au mineralisation at Sron Garbh can be attributed to post-collisional slab drop off that allowed hydrous, low-degree partial melting to take place that produced a Cu-PPGE-Au-enriched melt, which ascended through the crust, assimilating crustal S from the Dalradian sediments. The presence of a number of PGE-enriched sulfide occurrences in appinitic intrusions across the Scottish Caledonides indicates that the region contains certain features that make it more prospective than other alkaline provinces worldwide, which may be linked the post-Caledonian slab drop off event. We propose that the incongruent melting of pre-existing magmatic sulfides or ‘refertilised’ mantle in low-degree partial melts can produce characteristically fractionated, Cu-PPGE-Au-semi metal bearing, hydrous, alkali melts, which, if they undergo sulfide saturation, have the potential to produce alkaline-hosted magmatic sulfide deposits

Amnion Epithelial Cells as a Candidate Therapy for Acute and Chronic Lung Injury

Acute and chronic lung injury represents a major and growing global burden of disease. For many of these lung diseases, the damage is irreparable, exhausting the host's ability to regenerate new lung, and current therapies are simply supportive rather than restorative. Cell-based therapies offer the promise of tissue regeneration for many organs. In this paper, we examine the potential application of amnion epithelial cells, derived from the term placenta, to lung regeneration. We discuss their unique properties of plasticity and immunomodulation, reviewing the experimental evidence that amnion epithelial cells can prevent and repair lung injury, offering the potential to be applied to both neonatal, childhood, and adult lung disease. It is amazing to suggest that the placenta may offer renewed life after birth as well as securing new life before

Undecalcified Bone Preparation for Histology, Histomorphometry and Fluorochrome Analysis

Undecalcified bone histology demonstrates the micro-architecture of bone. It shows both the mineralised and cellular components of bone, which provides vital information on bone turnover or bone formation and resorption. This has tremendous importance in a variety of clinical and research applications. It yields beautiful images1 and allows for techniques such as fluorochrome assessment and histomorphometry2. Fluorochrome analysis is a technique where fluorescent dyes that bind to calcium are injected at a particular time point, which allows for quantification of the amount of mineralisation at that given time. Histomorphometry is a process of bone quantification at the microscopic level

A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored

The Beneficial Effects of Melatonin Administration Following Hypoxia-Ischemia in Preterm Fetal Sheep

Melatonin (MLT) is an endogenous hormone that controls circadian cycle. MLT has additional important properties that make it appealing as a neuroprotective agent—it is a potent anti-oxidant, with anti-apoptotic and anti-inflammatory properties. MLT is safe for administration during pregnancy or to the newborn after birth, and can reduce white matter brain injury under conditions of chronic fetal hypoxia. Accordingly, in the current study, we examined whether an intermediate dose of MLT could restore white matter brain development when administered after an acute hypoxic ischemic (HI) insult in preterm fetal sheep. Fifteen fetal sheep at 95–98 days gestation were instrumented with femoral artery and vein catheters, and a silastic cuff placed around the umbilical cord. At 102 days gestation, the cuff was inflated, causing complete umbilical cord occlusion for 25 min in 10 fetuses, to induce acute severe HI. Five HI fetuses received intravenous MLT for 24 h beginning at 2 h after HI. The remaining five fetuses were administered saline alone. Ten days after HI, the fetal brain was collected from each animal and white and gray matter neuropathology assessed. HI caused a significant increase in apoptotic cell death (TUNEL+), activated microglia (Iba-1+), and oxidative stress (8-OHdG+) within the subventricular and subcortical white matter. HI reduced the total number of oligodendrocytes and CNPase+ myelin density. MLT administration following HI decreased apoptosis, inflammation and oxidative stress within the white matter. MLT had intermediate benefits for the developing white matter: it increased oligodendrocyte cell number within the periventricular white matter only, and improved CNPase+ myelin density within the subcortical but not the striatal white matter. MLT administration following HI was also associated with improved neuronal survival within the cortex. Neuropathology in preterm infants is complex and mediated by multiple mechanisms, including inflammation, oxidative stress and apoptotic pathways. Treatment with MLT presents a safe approach to neuroprotective therapy in preterm infants but appears to have brain region-specific benefits within the white matter

Umbilical Cord Blood Cells for Perinatal Brain Injury: The Right Cells at the Right Time?

Cerebral palsy (CP) is the most common cause of physical disability in children. CP currently has no cure and there are only few interventions to prevent the development of disability. There are four principal complications of pregnancy or birth that can damage the developing brain and lead to CP: preterm birth, fetal growth restriction, infection during pregnancy and severe hypoxia-ischemia at birth. Umbilical cord blood (UCB) cells are a very promising therapy for the treatment of CP. While UCB therapy for juveniles with CP is currently being assessed in clinical trials, very little is known about their mechanisms of action or which cells found in umbilical cord blood protect against and/or repair brain injury. In this chapter, we first explore the complications that can lead to perinatal brain injury. We then discuss the different cell types found in UCB and the specific properties that make each of them individually attractive therapeutic candidates for treatment of perinatal brain injury. While UCB holds much promise as a therapy for CP, it is imperative that more research is conducted to understand how the different cell types found in UCB can protect against brain injury in order to design more effective and targeted therapies

Impact of oxygen levels on human hematopoietic stem and progenitor cell expansion

Oxygen levels are an important variable during the in vitro culture of stem cells. There has been increasing interest in the use of low oxygen to maximize proliferation and, in some cases, effect differentiation of stem cell populations. It is generally assumed that the defined pO2 in the incubator reflects the pO2 to which the stem cells are being exposed. However, we demonstrate that the pO2 experienced by cells in static culture can change dramatically during the course of culture as cell numbers increase and as the oxygen utilization by cells exceeds the diffusion of oxygen through the media. Dynamic culture (whereby the cell culture plate is in constant motion) largely eliminates this effect, and a combination of low ambient oxygen and dynamic culture results in a fourfold increase in reconstituting capacity of human hematopoietic stem cells compared with those cultured in static culture at ambient oxygen tension. Cells cultured dynamically at 5% oxygen exhibited the best expansion: 30-fold increase by flow cytometry, 120-fold increase by colony assay, and 11% of human CD45 engraftment in the bone marrow of NOD/SCID mice. To our knowledge, this is the first study to compare individual and combined effects of oxygen and static or dynamic culture on hematopoietic ex vivo expansion. Understanding and controlling the effective oxygen tension experienced by cells may be important in clinical stem cell expansion systems, and these results may have relevance to the interpretation of low oxygen culture studies

Human Umbilical Cord Therapy Improves Long-Term Behavioral Outcomes Following Neonatal Hypoxic Ischemic Brain Injury

Background: Hypoxic ischemic (HI) insult in term babies at labor or birth can cause long-term neurodevelopmental disorders, including cerebral palsy (CP). The current standard treatment for term infants with hypoxic ischemic encephalopathy (HIE) is hypothermia. Because hypothermia is only partially effective, novel therapies are required to improve outcomes further. Human umbilical cord blood cells (UCB) are a rich source of stem and progenitor cells making them a potential treatment for neonatal HI brain injury. Recent clinical trials have shown that UCB therapy is a safe and efficacious treatment for confirmed cerebral palsy. In this study, we assessed whether early administration of UCB to the neonate could improve long-term behavioral outcomes and promote brain repair following neonatal HI brain injury.Methods: HI brain injury was induced in postnatal day (PND) 7 rat pups via permanent ligation of the left carotid artery, followed by a 90 min hypoxic challenge. UCB was administered intraperitoneally on PND 8. Behavioral tests, including negative geotaxis, forelimb preference and open field test, were performed on PND 14, 30, and 50, following brains were collected for assessment of neuropathology.Results: Neonatal HI resulted in decreased brain weight, cerebral tissue loss and apoptosis in the somatosensory cortex, as well as compromised behavioral outcomes. UCB administration following HI improved short and long-term behavioral outcomes but did not reduce long-term histological evidence of brain injury compared to HI alone. In addition, UCB following HI increased microglia activation in the somatosensory cortex compared to HI alone.Conclusion: Administration of a single dose of UCB cells 24 h after HI injury improves behavior, however, a single dose of cells does not modulate pathological evidence of long-term brain injury

Mineral-scale variation in the trace metal and sulfur isotope composition of pyrite: implications for metal and sulfur sources in mafic VMS deposits

The link between metal enrichment and the addition of a magmatic volatile phase in volcanogenic massive sulfide deposits and actively forming seafloor massive sulfide deposits remains poorly characterized. This is especially true when considering how metal, sulfur and fluid flux change with time. In this study, we combine in situ sulfur isotope (δ34S; n = 31) measurements with trace metal chemistry of pyrite (n = 143) from the Mala VMS deposit, Troodos, Cyprus. The aim of our study is to assess the links between volatile influx and metal enrichment and establish how, or indeed if, this is preserved at the scale of individual mineral grains. We classify pyrite based on texture into colloform, granular, disseminated and massive varieties. The trace metal content of different pyrite textures is highly variable and relates to fluid temperature and secondary reworking that are influenced by the location of the sample within the mound. The sulfur isotope composition of pyrite at Mala ranges from − 17.1 to 7.5‰ (n = 31), with a range of − 10.9 to 2.5‰ within a single pyrite crystal. This variation is attributed to changes in the relative proportion of sulfur sourced from (i) SO2 disproportionation, (ii) thermochemical sulfate reduction, (iii) the leaching of igneous sulfur/sulfide and (iv) bacterial sulfate reduction. Our data shows that there is no correlation between δ34S values and the concentration of volatile elements (Te, Se) and Au in pyrite at Mala indicating that remobilization of trace metals occurred within the mound