50 research outputs found

    Mitochondrial Lysyl-tRNA Synthetase Independent Import of tRNA Lysine into Yeast Mitochondria

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    Aminoacyl tRNA synthetases play a central role in protein synthesis by charging tRNAs with amino acids. Yeast mitochondrial lysyl tRNA synthetase (Msk1), in addition to the aminoacylation of mitochondrial tRNA, also functions as a chaperone to facilitate the import of cytosolic lysyl tRNA. In this report, we show that human mitochondrial Kars (lysyl tRNA synthetase) can complement the growth defect associated with the loss of yeast Msk1 and can additionally facilitate the in vitro import of tRNA into mitochondria. Surprisingly, the import of lysyl tRNA can occur independent of Msk1 in vivo. This suggests that an alternative mechanism is present for the import of lysyl tRNA in yeast

    Organometallic neptunium(III) complexes

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    Studies of transuranic organometallic complexes provide a particularly valuable insight into covalent contributions to the metal–ligand bonding, in which the subtle differences between the transuranium actinide ions and their lighter lanthanide counterparts are of fundamental importance for the effective remediation of nuclear waste. Unlike the organometallic chemistry of uranium, which has focused strongly on UIII and has seen some spectacular advances, that of the transuranics is significantly technically more challenging and has remained dormant. In the case of neptunium, it is limited mainly to NpIV. Here we report the synthesis of three new NpIII organometallic compounds and the characterization of their molecular and electronic structures. These studies suggest that NpIII complexes could act as single-molecule magnets, and that the lower oxidation state of NpII is chemically accessible. In comparison with lanthanide analogues, significant d- and f-electron contributions to key NpIII orbitals are observed, which shows that fundamental neptunium organometallic chemistry can provide new insights into the behaviour of f-elements

    Genomic diversity of bacteriophages infecting Microbacterium spp

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    The bacteriophage population is vast, dynamic, old, and genetically diverse. The genomics of phages that infect bacterial hosts in the phylum Actinobacteria show them to not only be diverse but also pervasively mosaic, and replete with genes of unknown function. To further explore this broad group of bacteriophages, we describe here the isolation and genomic characterization of 116 phages that infect Microbacterium spp. Most of the phages are lytic, and can be grouped into twelve clusters according to their overall relatedness; seven of the phages are singletons with no close relatives. Genome sizes vary from 17.3 kbp to 97.7 kbp, and their G+C% content ranges from 51.4% to 71.4%, compared to ~67% for their Microbacterium hosts. The phages were isolated on five different Microbacterium species, but typically do not efficiently infect strains beyond the one on which they were isolated. These Microbacterium phages contain many novel features, including very large viral genes (13.5 kbp) and unusual fusions of structural proteins, including a fusion of VIP2 toxin and a MuF-like protein into a single gene. These phages and their genetic components such as integration systems, recombineering tools, and phage-mediated delivery systems, will be useful resources for advancing Microbacterium genetics

    Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

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    The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

    Risk of caesarean section after induced labour: do hospitals make a difference

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    Background: There is a well-known relationship between induced labour and caesarean rates. However, it remains unknown whether this relationship reflects the impact of more complex obstetric conditions or the variability in obstetric practices. We sought to quantify the independent role of the hospital as a variable that can influence the occurrence of caesarean section after induced labour. Methods: As part of the Portuguese Generation XXI birth cohort, we evaluated 2041 consecutive women who underwent singleton pregnancies with labour induction, at five public level III obstetric units (April 2005-August 2006). The indications for induction were classified according to the guidelines of the American and the Royal Colleges of Obstetricians and Gynaecologists. Poisson regression models were adjusted to estimate the association between the hospital and surgical delivery after induction. Crude and adjusted prevalence ratios (PR) and a 95% confidence interval (95% CI) were computed. Results: The proportion of women who were induced without formal clinical indications varied among hospitals from 20.3% to 45.5% (p < 0.001). After adjusting for confounders, the risk of undergoing a caesarean section after induced labour remained significantly different between the hospitals, for the cases in which there was no evident indication for induction [the highest PR reaching 1.86 (95% CI, 1.23–2.82)] and also when at least one such indication was present [1.53 (95% CI, 1.12–2.10)]. This pattern was also observed among the primiparous cephalic term induced women [the highest PR reaching 2.06 (95% CI, 1.23–2.82) when there was no evident indication for induction and 1.61 (95% CI, 1.11–2.34) when at least one such indication was present]. Conclusions:Caesarean section after induced labour varied significantly across hospitals where similar outcomes were expected. The effect was more evident when the induction was not based on the unequivocal presence of commonly accepted indications

    The Synthesis and Characterization of New Optically Active ?dimeric? ?pineno?-[4,5]-fused 2,2?-bipyridines linked without spacer or by small spacer groups

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    Linked chiral bipyridines 2-4 are prepared by combining two optically active 'pineno'-[4,5]-fused 2,2′-bipyridines in a stereoselective reaction (Scheme 1). These potential ligands are new members of the 'chiragen' family, and are characterized by NMR spectroscopy and, in the case of 2 and 3 by single-crystal X-ray analysis. A new synthesis of 'dipineno'-[4,5;4′,5′]-fused 2,2′-bipyridine 8 is described, which, when coupled, gives additional four chiral centres to the analogous 'chiragen' series (→9). Analysis of the CD spectra allowed conformational information about the solution species to be determined

    Magnetic Blocking in a Linear Iron(I) Complex

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    Single-molecule magnets that contain one spin centre may represent the smallest possible unit for spin-based computational devices. Such applications, however, require the realization of molecules with a substantial energy barrier for spin inversion, achieved through a large axial magnetic anisotropy. Recently, significant progress has been made in this regard by using lanthanide centres such as terbium(III) and dysprosium(III), whose anisotropy can lead to extremely high relaxation barriers. We contend that similar effects should be achievable with transition metals by maintaining a low coordination number to restrict the magnitude of the d-orbital ligand-field splitting energy (which tends to hinder the development of large anisotropies). Herein we report the first two-coordinate complex of iron(I), [Fe(C(SiMe3) 3)2]-, for which alternating current magnetic susceptibility measurements reveal slow magnetic relaxation below 29 K in a zero applied direct-current field. This S =complex exhibits an effective spin-reversal barrier of U eff = 226(4) cm-1, the largest yet observed for a single-molecule magnet based on a transition metal, and displays magnetic blocking below 4.5 K
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