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Objective: To determine the frequency of mitochondrial DNA depletion syndrome (MDS) in infants with cholestasis and liver failure and to further clarify the clinical, biochemical, radiologic, histopathologic, and molecular features associated with MDS due to deoxyguanosine kinase (DGUOK) and MPV17 gene mutations. Study design: We studied 20 infants with suspected hepatocerebral MDS referred to our tertiary care center between 2007 and 2013. Genomic DNA was isolated from blood leukocytes, liver, and/or skeletal muscle samples by standard methods. Mitochondrial DNA copy number relative to nuclear DNA levels was determined in muscle and/or liver DNA using real-time quantitative polymerase chain reaction and compared with age-matched controls. Nuclear candidate genes, including polymerase γ, MPV17, and DGUOK were sequenced using standard analyses. Results: We identified pathogenic MPV17 and DGUOK mutations in 11 infants (6 females) representing 2.5% of the 450 cases of infantile cholestasis and 22% of the 50 cases of infantile liver failure referred to our center during the study period. All of the 11 patients manifested cholestasis that was followed by a rapidly progressive liver failure and death before 2 years of life. Mitochondrial DNA depletion was demonstrated in liver or muscle for 8 out of the 11 cases where tissue was available. Seven patients had mutations in the MPV17 gene (3 novel mutations), 4 patients had DGUOK mutations (of which 2 were novel mutations). Conclusion: Mutations in the MPV17 and DGUOK genes are present in a significant percentage of infants with liver failure and are associated with poor prognosis. [Copyright &y& Elsevier]

Individual particles from comet 81P/Wild 2 collected by NASA’s Stardust mission vary in size from small sub-μm fragments found in the walls of the aerogel tracks, to large fragments up to tens of μm in size found towards the termini of tracks. The comet, in an orbit beyond Neptune since its formation, retains an intact a record of early-Solar-System processes that was compromised in asteroidal samples by heating and aqueous alteration. We measured the O isotopic composition of seven Stardust fragments larger than ∼2 μm extracted from five different Stardust aerogel tracks, and 63 particles smaller than ∼2 μm from the wall of a Stardust track. The larger particles show a relatively narrow range of O isotopic compositions that is consistent with 16 O-poor phases commonly seen in meteorites. Many of the larger Stardust fragments studied so far have chondrule-like mineralogy which is consistent with formation in the inner Solar System. The fine-grained material shows a very broad range of O isotopic compositions (−70‰ < Δ 17 O < +60‰) suggesting that Wild 2 fines are either primitive outer-nebula dust or a very diverse sampling of inner Solar System compositional reservoirs that accreted along with a large number of inner-Solar-System rocks to form comet Wild 2. [ABSTRACT FROM AUTHOR]

Abstract: The oxidation state of transition metal elements is an indicator of the environmental conditions during formation and history of extraterrestrial materials. We studied the iron valence state of fine-grained material from a bulbous track extracted from the Stardust cometary collector. It likely originated from primitive material of the comet Wild 2. We used synchrotron-based Scanning Transmission X-ray Microscopy (STXM) to collect Fe L3-XANES spectra at a spatial resolution of about 20nm. Maps of Fe valence state were combined with the elemental maps recorded by energy dispersive X-ray spectroscopy (EDS) with a transmission electron microscope (TEM), on the same areas and with a comparable electron probe size (5–20nm). As for most Stardust fine-grained material, the samples are severely damaged by the hypervelocity impact in the aerogel collector blocks. They show of a wide range of oxidation state at a micrometer scale, from Fe metal to Fe3+. This heterogeneity of oxidation state can be due to the extreme conditions of the collection. Two major parameters can favor changes in redox state. The first is the high temperature regime, known to be highly heterogeneous and to have locally reached extreme values (up to 2000K). The second is the local chemical environment. It may contain elements that could favor a reduction or oxidation reaction within the flash-heated Wild 2 fragments. Comparison of maps by STXM and EDS shows evidence for several correlation trends between element concentrations and the iron valence state. These observations, together with the study of a melted rim of a larger particle, suggest that the redox state was not completely redistributed within the impact melts. These local signatures are compatible with precursors that could have been close to primitive matrix material of chondrites or to chondritic interplanetary dust particles. On average, the fine-grained material from Wild 2 displays a molar fraction (Fe2+ oxide +Fe3+ oxide)/(total Fe) equal to 0.80±0.10. It appears more oxidized than the average value measured for the comet, when done on larger particles (Westphal et al., 2009). This fine-grained material from Wild 2 does not seem to have sampled reducing environments in the solar nebulae in contrast with the larger particles of Wild 2. This observation confirms the high degree of diversity of materials in Wild 2 and is in good agreement with the dual distribution of high temperature minerals and matrices in carbonaceous chondrites. [Copyright &y& Elsevier]