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A characteristic feature of many autoimmune diseases like systemic lupus erythematodes (SLE) is the development of autoantibodies against various cytoplasmatic or nuclear antigens. The mechanisms l...

Chondrules are igneous spherical objects preserved in chondritic meteorites and believed to have formed during transient heating events in the solar protoplanetary disk. Chondrules present in the metal-rich CB chondrites show unusual chemical and petrologic features not observed in other chondrite groups, implying a markedly distinct formation mechanism. Here, we report high-precision Mg-isotope data for 10 skeletal olivine chondrules from the Hammadah al Hamra 237 (HH237) chondrite to probe the formation history of CB chondrules. The 27 Al/ 24 Mg ratios of individual chondrules are positively correlated to their stable Mg-isotope composition (μ 25 Mg), indicating that the correlated variability was imparted by a volatility-controlled process (evaporation/condensation). The mass-independent 26 Mg composition (μ 26 Mg*) of chondrules is consistent with single stage formation from an initially homogeneous magnesium reservoir if the observed μ 25 Mg variability was generated by non-ideal Rayleigh- type evaporative fractionation characterized by a β value of 0.5142, in agreement with experimental work. The magnitude of the mass-dependent fractionation (∼300 ppm) is significantly lower than that suggested by the increase in 27 Al/ 24 Mg values, indicating substantial suppression of isotopic fractionation during evaporative loss of Mg, possibly due to evaporation at high Mg partial pressure. Thus, the Mg-isotope data of skeletal chondrules from HH237 are consistent with their origin as melts produced in the impact-generated plume of colliding planetesimals. The inferred μ 26 Mg* value of −3.87 ± 0.93 ppm for the CB parent body is significantly lower than the bulk solar system value of 4.5 ± 1.1 ppm inferred from CI chondrites, suggesting that CB chondrites accreted material comprising an early formed 26 Al-free component.

Background and Objectives A distinctive feature of cell activation and apoptotic cell death is the formation of MCVs. MCVs have previously been identified as mediators of cell-to-cell communication and are recognised as carriers of microRNA. An impaired clearance of apoptotic debris has been observed in SLE patients. This is caused by an increased rate of apoptosis and by a defect in phagocytic-cell clearance. We investigated differences in the microRNA content of MCVs released by activated and apoptotic lymphoblasts from normal healthy donors (NHDs) and SLE patients. MicroRNA content of lymphoblasts and MCVs and the effect of MCV uptake into monocytes were analysed. Materials and Methods Activated lymphoblasts, UV-B irradiated lymphoblasts and corresponding MCVs of NHDs and SLE patients were compared in an Agilent microRNA array and validated by qPCR MiR-155 expression was determined by qPCR in monocytes with engulfed autologous UV-MCVs. Western blot was performed to investigate the expression of the miR-155 target protein Tab-2. Results MiR-155, miR-155*, miR-34b and miR-99a were significantly less expressed in UV-lymphoblasts compared to non-irradiated lymphoblasts. The effect was even more pronounced in staurosporine-treated lymphoblasts. In contrast, the expression of miR-34a increased after UV-B irradiation but decreased under staurosporine treatment. The comparison of viable and apoptotic MCVs showed a decrease of miR-155* in apoptotic MCVs. In UV-MCVs, the miR-99a level was higher compared to viable MCVs. MiR-155 was not altered in MCVs after apoptosis induction. MiR-34a was expressed at higher levels in viable SLE lymphoblasts and MCVs compared to NHDs. In contrast, miR-34b expression was decreased in UV-lymphoblasts and UV-MCVs of SLE patients. In functional assays we could demonstrate higher miR-155 levels and consecutively decreased target protein levels in monocytes after engulfment of autologous UV-MCVs. Conclusions Our data show an unequal distribution of the content of different microRNAs within apoptotic cells and cell derived MCV. This suggests a directional transport rather than a random distribution. Thus, cells can regulate their microRNA as well as the microRNA content within released MCV. We could show that microRNA and protein expression changes in phagocytes after UV-MCV engulfment. Thus, our results suggest that MCVs could serve as a transport vehicle for microRNAs to mediate cell-cell communication and influence intracellular processes in the phagocyte. Disturbances of this system could contribute to the pathogenesis of SLE.

The existence of correlated nucleosynthetic heterogeneities in solar system reservoirs is now well demonstrated for numerous nuclides. However, it has proven difficult to discriminate between the two disparate processes that can explain such correlated variability: incomplete mixing of presolar material or secondary processing of a well-mixed disk. Using stepwise acid-leaching of the Ivuna CI-chondrite, we show that unlike other nuclides such as 54Cr and 50Ti, Sr-isotope variability is the result of a carrier depleted in 84Sr. The carrier is most likely presolar SiC, which is known to have both high Sr-concentrations relative to solar abundances and extremely depleted 84Sr compositions. Thus, variability in 84Sr in meteorites and their components can be attributed to varying contributions from presolar SiC. The observed 84Sr excesses in calcium-aluminum refractory inclusions (CAIs) suggest their formation from an SiC-free gaseous reservoir, whereas the 84Sr depletions present in differentiated meteorites require their formation from material with an increased concentration of SiC relative to CI chondrites. The presence of a positive correlation between 84Sr and 54Cr, despite being hosted in carriers of negative and positive anomalies, respectively, is not compatible with incomplete mixing of presolar material but instead suggests that the solar system's nucleosynthetic heterogeneity reflects selective thermal processing of dust. Based on vaporization experiments of SiC under nebular conditions, the lack of SiC material in the CAI-forming gas inferred from our data requires that the duration of thermal processing of dust resulting in the vaporization of CAI precursors was extremely short-lived, possibly lasting only hours to days.

We present a new technique for the precise determination of platinum (Pt) stable isotope ratios by multiple-collector inductively coupled plasma mass spectrometry (MC-ICPMS) using two different Pt double-spikes (192Pt–198Pt and 196Pt–198Pt). Results are expressed relative to the IRMM-010 Pt isotope standard as the parts per million difference in 198Pt/194PtPt ratios (μ198Pt). Repeated measurements of the IRMM-010 Pt standard in two different laboratories, consuming ca. 40–85 ng of Pt, show that a long-term external reproducibility for μ192Pt of ≤40 ppm (2 sd; equivalent to ≤10 ppm u−1, where u is the unified atomic mass unit) can be obtained on Pt stable isotope ratios with either double-spike. Elemental doping tests reveal that double-spike corrected Pt stable isotope ratios are insensitive to the presence of relatively high (up to 10%) levels of matrix elements, although the 192Pt–198Pt double-spike is affected by an isobaric interference on 192Pt from 192Os. The 196Pt–198Pt double-spike does not use 192Pt in the double-spike inversion and is unaffected by Os contamination, and is our recommended double-spike for use with natural samples. As part of this study, we re-determined the natural Pt isotopic composition of IRMM-010 by MC-ICPMS using external element (Pb) doping to correct for instrumental mass bias and have identified relative Pt isotope differences of up to 10% from the reference values for this standard. The new isotopic composition of the IRMM-010 standard (190Pt = 0.01289%, 192Pt = 0.7938%, 194Pt = 32.81%, 195Pt = 33.79%, 196Pt = 25.29% and 198Pt = 7.308%) results in a redefined Pt atomic weight of 195.08395 ± 0.00068. Using our technique we have measured small, reproducible and statistically significant offsets in Pt stable isotope ratios between different Pt element standards and the IRMM-010 standard, which potentially indicates that natural Pt stable isotope fractionations exist that are larger than the reproducibility of our technique.

The precision of the 26Al–26Mg system—one of the most widely used chronometers for constraining the relative timing of events in the early solar system—is presently limited by methods for the determination of 27Al/24Mg ratios, which have seen little improvement in the last decade. We present a novel method for the measurement of 27Al/24Mg ratios in unpurified sample solutions by multiple-collector inductively coupled plasma mass spectrometry. Because Al is monoisotopic we use a modified isotope dilution approach that employs a mixed spike containing isotopically enriched 25Mg and natural 27Al in an accurately known ratio. In order to determine the spike to sample ratio for Al, measurements of spiked aliquots are bracketed by unspiked aliquots, which negates the impact of elemental bias. Unlike conventional isotope dilution, samples do not require chromatographic separation prior to analysis, which both saves time and minimises the risk of contamination of other samples with spike (which is added immediately prior to analysis). Repeat measurements of the BHVO-2, BCR-2, and BIR-1 international rock standards, as well as a gravimetrically prepared Al–Mg reference solution, indicate that our method is both accurate and reproducible to 0.2%. This 4- to 10-fold improvement over previous methods translates directly to an equal gain in the resolution of the 26Al–26Mg chronometer. The approach presented here could, in principle, be applied to other monoisotopic elements such as the Mn–Cr system. Based on multiple measurements of a ∼2.7 gram piece of the Ivuna CI chondrite, we present a new estimate for the 27Al/24Mg ratio of this meteorite of 0.09781 ± 0.00029.

Asteroid 4 Vesta has long been postulated as the source for the howardite-eucrite-diogenite (HED) achondrite meteorites. Here we show that Al-free diogenite meteorites record variability in the mass-independent abundance of 26Mg (26Mg*) that is correlated with their mineral chemistry. This suggests that these meteorites captured the Mg-isotopic evolution of a large-scale differentiating magma body with increasing 27Al/24Mg during the lifespan of the short-lived 26Al nuclide (t 1/2 ~ 730,000 yr). Thus, diogenites and eucrites represent crystallization products of a large-scale magma ocean associated with the differentiation and magmatic evolution of the HED parent body. The 26Mg* composition of the most primitive diogenites requires onset of the magma ocean crystallization within 0.6–0.4 + 0.5 Myr of solar system formation. Moreover, 26Mg* variations among diogenites and eucrites imply that near complete solidification of the HED parent body occurred within the following 2-3 Myr. Thermal models predict that such rapid cooling and magma ocean crystallization could only occur on small asteroids (

With a half-life of 0.73 Myr, the 26Al-to-26Mg decay system is the most widely used short-lived chronometer for understanding the formation and earliest evolution of the solar protoplanetary disk. However, the validity of 26Al-26Mg ages of meteorites and their components relies on the critical assumption that the canonical 26Al/27Al ratio of ~5 × 10–5 recorded by the oldest dated solids, calcium-aluminium-rich inclusions (CAIs), represents the initial abundance of 26Al for the solar system as a whole. Here, we report high-precision Mg-isotope measurements of inner solar system solids, asteroids, and planets demonstrating the existence of widespread heterogeneity in the mass-independent 26Mg composition (μ26Mg*) of bulk solar system reservoirs with solar or near-solar Al/Mg ratios. This variability may represent heterogeneity in the initial abundance of 26Al across the solar protoplanetary disk at the time of CAI formation and/or Mg-isotope heterogeneity. By comparing the U-Pb and 26Al-26Mg ages of pristine solar system materials, we infer that the bulk of the μ26Mg* variability reflects heterogeneity in the initial abundance of 26Al across the solar protoplanetary disk. We conclude that the canonical value of ~5 × 10–5 represents the average initial abundance of 26Al only in the CAI-forming region, and that large-scale heterogeneity—perhaps up to 80% of the canonical value—may have existed throughout the inner solar system. If correct, our interpretation of the Mg-isotope composition of inner solar system objects precludes the use of the 26Al-26Mg system as an accurate early solar system chronometer.

We report novel methods for the chemical purification of Mg from silicate rocks by ion-exchange chromatography, and high-precision analysis of Mg-isotopes by high-resolution multiple collector inductively coupled plasma source mass spectrometry (HR-MC-ICPMS). Using these methods, we have measured the relative and absolute Mg-isotope composition of a number of terrestrial and extraterrestrial materials, including international reference rock standards as well as pure Mg standards, olivine crystals separated from a mantle-derived spinel lherzolite (J12 olivine), one enstatite chondrite, a martian shergottite and sea water samples. Repeated analyses of terrestrial and extraterrestrial samples demonstrate that it is possible to routinely measure the relative Mg-isotope composition of silicate materials with an external reproducibility of 2.5 and 20 ppm for the μ26Mg* and μ25Mg values, respectively (μ notation is the per 106 deviation from a reference material). Analyses of bulk mantle-derived rocks as well as a martian shergottite and an enstatite chondrite define a restricted range in μ25Mg of −120 ± 28 ppm (2sd) relative to the DSM-3 reference standard (μ25,26Mg = 0), suggesting that the Mg-isotope composition of inner solar system bulk planetary materials is uniform within the resolution of our analyses. We have determined the absolute Mg-isotope composition of the J12 olivine, two CI chondrites as well as the DSM-3 and Cambridge-1 reference standards using a mixed 26Mg-24Mg double-spike. The differences between the absolute 25Mg/24Mg ratios of the various materials analyzed relative to the DSM-3 standard are in excellent agreement with results obtained by the sample-standard bracketing method. Based on the averages obtained for the J12 olivine separates, we estimate the absolute Mg-isotope composition for Earth's mantle – and hence that of the bulk silicate Earth – to be 25Mg/24Mg = 0.126896 ± 0.000025 and 26Mg/24Mg = 0.139652 ± 0.000033. Given the restricted range of μ25Mg obtained for bulk planetary material by the sample-standard bracketing technique and the excellent agreement between the data obtained by the relative and absolute methods, we propose that these new values represent the absolute Mg-isotope composition of the bulk inner solar system. Using the absolute Mg-isotope composition of the J12 olivine, we calculate the isotopic abundances of Mg as 24Mg = 0.789548 ± 0.000026, 25Mg = 0.100190 ± 0.000018, and 26Mg = 0.110261 ± 0.000023. Based on this result, we have calculated an atomic weight for Mg of 24.305565 ± 0.000045, which is marginally heavier than previous estimates but a factor of 10 more precise.

Polyamines (PAs) are involved in regulation of cell growth and cellular survival by interacting with processes like translation, transcription or ion transport. It is described that polyamines can induce apoptosis in mesenchymal cell lines. The aim of our study was to analyze whether the physiological PAs (putrescine, spermidine or spermine) or the PA-derivate deoxyspergualin (DSG), a novel immunosuppressant, induce apoptosis in immunocompetent cells. Furthermore, we wanted to investigate which molecular mechanisms are involved in the execution of the cell death program. By means of flow cytometric analysis we found an induction of apoptosis by spermine (Spm) and DSG in quiescent and activated PBMCs, PHA generated lymphoblasts, and various tumor cell lines (Jurkat, SKW-3, U937). Moreover, DSG and Spm triggered apoptosis in human Fas-deficient cells and in cell lines MV4.11. and RS4.11., which are described to be resistant to apoptosis induction by many conventional chemotherapeutic agents. Apoptosis induction after Spm or DSG treatment was dependent on caspase activity and associated with a decrease in mitochondrial membrane potential and Bcl-2 expression. In order to test whether PAs mediate their proapoptotic effects through metabolites resulting from PA catabolism, we tested different antagonists of PA degrading enzymes or PA metabolites. We show that aminoguanidine (inhibition of PA oxidase), aldehyd-dehydrogenase (degradation of PA-aldehydes) or N-acetyl-cystein (prevention of PA-induced glutathion depletion) prevented PA-mediated apoptosis. Acrolein, and PA-related aldehyde, could induce programmed cell death in our system. We conclude that PA aldehydes and PA-triggered glutathion depletion cause apoptosis in immunocompetent cells and apoptosis-resistant tumor cell lines.

Chondrites are undifferentiated meteorites that can provide information on the compositions of materials in the early solar System, including the building blocks of the terrestrial planets. While most chondrites belong to well-defined groups based on their mineralogy and chemical composition, a minor fraction have unusual characteristics and are classified as ungrouped chondrites. These ungrouped chondrites reflect the diversity of chondritic materials in the early solar system; however, they are not as well studied as grouped meteorites and their origins are poorly understood. In this study, we present high-precision mass-independent Cr, Ca and Mg isotope data for 17 ungrouped chondrites. The ε54Cr and ε48Ca (ε expresses parts per ten thousand mass-independent isotope deviation) data for ungrouped chondrites also provide important constraints for assessing their relationships to the known chondrite groups, and the radiogenic Mg isotope ratios (μ26Mg*) can be used to track the early solar system history. We also present the first high-precision data for a Kakangari (KC) chondrite, an enstatite chondrite, and for four enstatite-rich meteorites. The ε54Cr and ε48Ca values for the KC are −0.44 ± 0.04 and −1.30 ± 0.25, respectively, and ε48Ca value for SAH 97096 (EH3) is −0.19 ± 0.22 that overlaps with that of those of Earth-Moon system and ordinary chondrites. All the carbonaceous chondrite-like (CC) ungrouped chondrites show positive ε54Cr and ε48Ca values, and all the non-carbonaceous chondrite-like (NC) ungrouped chondrites and KCs (also belong to the NC trend) show zero or negative ε54Cr and ε48Ca values. This observation confirms the CC-NC dichotomy for primitive solar system materials. LEW 87232 (KC) also shows the highest 55Mn/52Cr ratio and ε53Cr value amongst all the chondrites. There is a positive trend between 55Mn/52Cr ratios and ε53Cr values among all the chondrites that mostly reflects a mixing between multiple chondritic components. Previously it has been reported that there is a bulk 26Al-26Mg correlation line amongst chondrites. This correlation has been interpreted as being due to mixing of CAIs (high 27Al/24Mg ratios and μ26Mg* values) and other silicate material (e.g., chondrules and matrix). By providing additional 26Al-26Mg chondrite data, we show that there is no 26Al-26Mg correlation line for the chondrites, ruling out the two-endmember (i.e., CAIs and other silicates) mixing model.

Infinite dilution activity coefficients (IDACs) are important characteristics of mixtures because of their ability to predict operating behavior in distillation processes. Thermodynamic models are used to predict IDACs since experimental data can be difficult and costly to obtain. The models most often employed for predictive purposes are the "original and modified UNIFAC Group Contribution Methods" (GCMs). COSMO-RS (COnductor-like Screening MOdel for Real Solvents) is an alternative predictive method for a wide variety of systems that requires a limited minimum number of input parameters. A significant difference between GCMs and COSMO-RS is that a given GCMs' predictive ability is dependent on the availability of group interaction parameters, whereas COSMO-RS is only limited by the availability of individual component parameters. In this study COSMO-RS was used to predict infinite dilution activity coefficients. The database assembled by, and calculations with various UNIFAC models carried out by, Voutsas and Tassios (Ind. Eng. Chem. Res. 1996, 35, 1438) were used as the basis for this comparison. This database contains aqueous and nonaqueous nonelectrolyte binary mixtures. In aqueous systems, COSMO-RS provides the best result for systems with alkyl halides or aromatics as solutes in water; all other binary mixtures also gave good results. Overall, COSMO-RS was less successful for nonaqueous systems. Good results from COSMO-RS were obtained for nonaqueous systems involving alkyl halides, alkanes in ethanol, and ketones in alkanes.