Stable Isotopes of Platinum: Measurement and Application to Constraining the Formation and Differentiation of Earth

<p>A wide range of novel, non-traditional, stable isotope systems have been developed over the last decade, largely as a result of the advent of multiple-collector inductively coupled plasma mass spectrometry (MC-ICPMS), and continue to provide valuable new insights in the earth, environmental and planetary sciences. The platinum (Pt) stable isotope system represents a potentially powerful but, as yet, unexplored addition to this suite of stable isotope tracers. Pt has six naturally occurring isotopes, and can exist in a range of oxidation states. The geochemical behaviour of Pt coupled with the relatively large mass difference (ca. 2%) between the abundant heavy and light isotopes and its variable oxidation states leads to potential applications in tracing a range of natural processes. In particular, the strong elemental partitioning of Pt between metals and silicates makes the Pt stable isotope system uniquely suited to tracing processes of Earth’s accretion and differentiation. This study aims to develop new techniques for measurement of Pt stable isotopes in geological samples, and to apply these to terrestrial and meteorite samples to attempt to resolve outstanding questions relating to Earth’s early evolution. A technique was developed for measurement of Pt stable isotope ratios using multiple collector inductively coupled plasma mass spectrometry (MCICPMS), employing a ¹⁹⁶Pt–¹⁹⁸Pt double-spike to correct for instrumental mass fractionation. Results are reported in terms of δ¹⁹⁸Pt, which represents the per mil difference in the ¹⁹⁸Pt/¹⁹⁴Pt ratio from the IRMM-010 Pt isotope standard. A range of analytical tests were conducted and show that this approach has a reproducibility of ca. ±0.04 %∘ on δ¹⁹⁸Pt (i.e., ±0.01%∘ amu⁻¹) for Pt solution standards, and is insensitive to minor amounts of matrix that may be retained after chemical purification of Pt. Measurements of Pt solution standards conducted using two different MC-ICPMS instruments showed resolvable variations, which suggest that natural fractionations exist that exceed the reproducibility of the technique. Techniques were also developed for dissolution of natural samples and chemical separation of Pt. Geological standards were digested using a nickel sulphide fire assay technique, which pre-concentrates the highly siderophile elements in a NiS bead that is readily dissolved in acid. This was followed by chemical separation of Pt from digested samples using anion exchange chemical techniques. Elution curves were constructed for a range of synthetic rock matrices. These tests show that Pt separation is achieved with >90% Pt yield and ca. 95% purity. Analytical tests show that this level of Pt separation is sufficient for accurate determination of Pt stable isotope ratios by double-spike MC-ICPMS. These techniques were then applied to 11 international geological standard reference materials representing mantle peridotites, igneous samples, and Pt ore materials. The reproducibility in natural samples was determined by processing multiple replicate digestions of a standard reference material, and was shown to be ca. ±0.08%∘ (2 sd). Pt stable isotope data for the full set of reference materials have a range of δ¹⁹⁸Pt values with offsets of up to 0.40%∘ from the IRMM-010 standard, which are readily resolved with this technique. Mantle samples yielded the lightest (most negative) isotopic compositions of the terrestrial standards, with igneous and Pt ore samples defining a continuous trend towards zero, which is consistent with the IRMM-010 standard being derived from a Pt ore. These results demonstrate the potential of the Pt isotope system as a tracer in geochemical systems. The techniques developed above were then applied to investigate an outstanding problem relating to Earth’s accretion and differentiation. Highly siderophile elements (HSE) are strongly partitioned into the cores of terrestrial planets during core formation, and the abundances of HSE in Earth’s mantle compared with primitive meteorites have provided key constraints on models of Earth’s early evolution. Two leading models to explain the HSE abundances in the silicate Earth involve either a late-veneer of chondritic material that was added after core formation or core formation in a deep magma ocean. The platinum (Pt) stable isotope system represents a novel tool for investigating these processes. Using the techniques developed above, Pt stable isotope ratios were measured in a range of meteorite samples, including enstatite, ordinary and carbonaceous chondrites, primitive achondrites, achondrites and iron meteorites, as well as additional terrestrial mantle xenolith samples. Our data set reveals that the Pt stable isotopic composition of Earth’s mantle overlaps with all of the chondrite groups. Primitive achondrite and ureilite samples revealed the heaviest compositions of all meteorite groups. These data suggest that metal–silicate differentiation produces an isotopic fractionation for Pt, with heavy isotopes being preferentially retained in the silicate phase. Thus, Earth’s mantle is expected to have been significantly enriched in the heavy isotopes of Pt during core formation, even if metal–silicate differentiation took place in a magma ocean. The absence of a large fractionation between chondrites, representing the composition of the undifferentiated Earth, and the mantle suggests that the signature of core formation in the mantle has been subsequently overprinted. Considering the overlap between the Pt stable isotopic compositions of the mantle and chondrites, the most likely means for overprinting the composition of the mantle is by addition of a chondritic late-veneer. Mixing calculations show that addition of 0.5% of Earth’s mass by a late-veneer of chondritic material would be sufficient to overprint highly fractionated Pt stable isotope signatures resulting from core-formation.</p>

Stable Isotopes of Platinum: Measurement and Application to Constraining the Formation and Differentiation of Earth

<p>A wide range of novel, non-traditional, stable isotope systems have been developed over the last decade, largely as a result of the advent of multiple-collector inductively coupled plasma mass spectrometry (MC-ICPMS), and continue to provide valuable new insights in the earth, environmental and planetary sciences. The platinum (Pt) stable isotope system represents a potentially powerful but, as yet, unexplored addition to this suite of stable isotope tracers. Pt has six naturally occurring isotopes, and can exist in a range of oxidation states. The geochemical behaviour of Pt coupled with the relatively large mass difference (ca. 2%) between the abundant heavy and light isotopes and its variable oxidation states leads to potential applications in tracing a range of natural processes. In particular, the strong elemental partitioning of Pt between metals and silicates makes the Pt stable isotope system uniquely suited to tracing processes of Earth’s accretion and differentiation. This study aims to develop new techniques for measurement of Pt stable isotopes in geological samples, and to apply these to terrestrial and meteorite samples to attempt to resolve outstanding questions relating to Earth’s early evolution. A technique was developed for measurement of Pt stable isotope ratios using multiple collector inductively coupled plasma mass spectrometry (MCICPMS), employing a ¹⁹⁶Pt–¹⁹⁸Pt double-spike to correct for instrumental mass fractionation. Results are reported in terms of δ¹⁹⁸Pt, which represents the per mil difference in the ¹⁹⁸Pt/¹⁹⁴Pt ratio from the IRMM-010 Pt isotope standard. A range of analytical tests were conducted and show that this approach has a reproducibility of ca. ±0.04 %∘ on δ¹⁹⁸Pt (i.e., ±0.01%∘ amu⁻¹) for Pt solution standards, and is insensitive to minor amounts of matrix that may be retained after chemical purification of Pt. Measurements of Pt solution standards conducted using two different MC-ICPMS instruments showed resolvable variations, which suggest that natural fractionations exist that exceed the reproducibility of the technique. Techniques were also developed for dissolution of natural samples and chemical separation of Pt. Geological standards were digested using a nickel sulphide fire assay technique, which pre-concentrates the highly siderophile elements in a NiS bead that is readily dissolved in acid. This was followed by chemical separation of Pt from digested samples using anion exchange chemical techniques. Elution curves were constructed for a range of synthetic rock matrices. These tests show that Pt separation is achieved with >90% Pt yield and ca. 95% purity. Analytical tests show that this level of Pt separation is sufficient for accurate determination of Pt stable isotope ratios by double-spike MC-ICPMS. These techniques were then applied to 11 international geological standard reference materials representing mantle peridotites, igneous samples, and Pt ore materials. The reproducibility in natural samples was determined by processing multiple replicate digestions of a standard reference material, and was shown to be ca. ±0.08%∘ (2 sd). Pt stable isotope data for the full set of reference materials have a range of δ¹⁹⁸Pt values with offsets of up to 0.40%∘ from the IRMM-010 standard, which are readily resolved with this technique. Mantle samples yielded the lightest (most negative) isotopic compositions of the terrestrial standards, with igneous and Pt ore samples defining a continuous trend towards zero, which is consistent with the IRMM-010 standard being derived from a Pt ore. These results demonstrate the potential of the Pt isotope system as a tracer in geochemical systems. The techniques developed above were then applied to investigate an outstanding problem relating to Earth’s accretion and differentiation. Highly siderophile elements (HSE) are strongly partitioned into the cores of terrestrial planets during core formation, and the abundances of HSE in Earth’s mantle compared with primitive meteorites have provided key constraints on models of Earth’s early evolution. Two leading models to explain the HSE abundances in the silicate Earth involve either a late-veneer of chondritic material that was added after core formation or core formation in a deep magma ocean. The platinum (Pt) stable isotope system represents a novel tool for investigating these processes. Using the techniques developed above, Pt stable isotope ratios were measured in a range of meteorite samples, including enstatite, ordinary and carbonaceous chondrites, primitive achondrites, achondrites and iron meteorites, as well as additional terrestrial mantle xenolith samples. Our data set reveals that the Pt stable isotopic composition of Earth’s mantle overlaps with all of the chondrite groups. Primitive achondrite and ureilite samples revealed the heaviest compositions of all meteorite groups. These data suggest that metal–silicate differentiation produces an isotopic fractionation for Pt, with heavy isotopes being preferentially retained in the silicate phase. Thus, Earth’s mantle is expected to have been significantly enriched in the heavy isotopes of Pt during core formation, even if metal–silicate differentiation took place in a magma ocean. The absence of a large fractionation between chondrites, representing the composition of the undifferentiated Earth, and the mantle suggests that the signature of core formation in the mantle has been subsequently overprinted. Considering the overlap between the Pt stable isotopic compositions of the mantle and chondrites, the most likely means for overprinting the composition of the mantle is by addition of a chondritic late-veneer. Mixing calculations show that addition of 0.5% of Earth’s mass by a late-veneer of chondritic material would be sufficient to overprint highly fractionated Pt stable isotope signatures resulting from core-formation.</p>

Capsid-E2 interactions rescue core assembly in viruses that cannot form cytoplasmic nucleocapsid cores

Alphavirus capsid proteins (CPs) have two domains: the N-terminal domain (NTD) that interacts with the viral RNA, and the C-terminal domain (CTD) that forms CP-CP interactions and interacts with the cytoplasmic domain of the E2 spike protein (cdE2). In this study, we examine how mutations in the CP NTD affect CP CTD interactions with cdE2. We changed the length and/or charge of the NTD of Ross River virus CP and found that changing the charge of the NTD has a greater impact on core and virion assembly than changing the length of the NTD. The NTD CP insertion mutants are unable to form cytoplasmic cores during infection but they do form cores or core-like structures in virions. Our results are consistent with cdE2 having a role in core maturation during virion assembly and rescuing core formation when cytoplasmic cores are not assembled. We go on to find that the isolated cores from some mutant virions are now assembly competent in that they can be disassembled and reassembled back into cores. These results show how the two domains of CP may have distinct yet coordinated roles. IMPORTANCE: Structural viral proteins have multiple roles during entry and assembly. The capsid protein (CP) of alphaviruses has one domain that interacts with the viral genome and another domain that interacts with the E2 spike protein. In this work we determine that the length and/or charge of the CP affects cytoplasmic core formation. However, defects in cytoplasmic core formation can be overcome by E2-CP interactions, thus assembling a core or core-like complex in the virion. In the absence of both cytoplasmic cores and CP-E2 interactions, CP is not even packaged in the released virions, but some infectious particles are still released presumably as RNA packaged in a glycoprotein containing membrane shell. This suggests that the virus has multiple mechanisms in place to ensure the viral genome is surrounded by a capsid core during its lifecycle.

K-80003 Inhibition of Macrophage Apoptosis and Necrotic Core Development in Atherosclerotic Vulnerable Plaques

Purpose Macrophage apoptosis coupled with a defective phagocytic clearance of the apoptotic cells promotes plaque necrosis in advanced atherosclerosis, which causes acute atherothrombotic vascular disease. Nonsteroidal anti-inflammatory drug sulindac derivative K-80003 treatment was previously reported to dramatically attenuate atherosclerotic plaque progression and destabilization. However, the underlying mechanisms are not fully understood. This study aimed to determine the role of K-80003 on macrophage apoptosis and elucidate the underlying mechanism. Methods The mouse model of vulnerable carotid plaque in ApoE−/− mice was developed in vivo. Consequently, mice were randomly grouped into two study groups: the control group and the K-80003 group (30 mg/kg/day). Samples of carotid arteries were collected to determine atherosclerotic necrotic core area, cellular apoptosis, and oxidative stress. The effects of K-80003 on RAW264.7 macrophage apoptosis, oxidative stress, and autophagic flux were also examined in vitro. Results K-80003 significantly suppressed necrotic core formation and inhibited cellular apoptosis of vulnerable plaques. K-80003 can also inhibit 7-ketocholesterol-induced macrophage apoptosis in vitro. Furthermore, K-80003 inhibited intraplaque cellular apoptosis mainly through the suppression of oxidative stress, which is a key cause of advanced lesional macrophage apoptosis. Mechanistically, K-80003 prevented 7-ketocholesterol-induced impairment of autophagic flux in macrophages, evidenced by the decreased LC3II and SQSTM1/p62 expression, GFP-RFP-LC3 cancellation upon K-80003 treatment. Conclusion Inhibition of macrophage apoptosis and necrotic core formation by autophagy-mediated reduction of oxidative stress is one mechanism of the suppression of plaque progression and destabilization by K-80003.