The Mechanisms of Codon Reassignments in Mitochondrial Genetic Codes

Many cases of non-standard genetic codes are known in mitochondrial genomes. We carry out analysis of phylogeny and codon usage of organisms for which the complete mitochondrial genome is available, and we determine the most likely mechanism for codon reassignment in each case. Reassignment events can be classified according to the gain-loss framework. The gain represents the appearance of a new tRNA for the reassigned codon or the change of an existing tRNA such that it gains the ability to pair with the codon. The loss represents the deletion of a tRNA or the change in a tRNA so that it no longer translates the codon. One possible mechanism is Codon Disappearance, where the codon disappears from the genome prior to the gain and loss events. In the alternative mechanisms the codon does not disappear. In the Unassigned Codon mechanism, the loss occurs first, whereas in the Ambiguous Intermediate mechanism, the gain occurs first. Codon usage analysis gives clear evidence of cases where the codon disappeared at the point of the reassignment and also cases where it did not disappear. Codon disappearance is the probable explanation for stop to sense reassignments and a small number of reassignments of sense codons. However, the majority of sense to sense reassignments cannot be explained by codon disappearance. In the latter cases, by analysis of the presence or absence of tRNAs in the genome and of the changes in tRNA sequences, it is sometimes possible to distinguish between the Unassigned Codon and Ambiguous Intermediate mechanisms. We emphasize that not all reassignments follow the same scenario and that it is necessary to consider the details of each case carefully.Comment: 53 pages (45 pages, including 4 figures + 8 pages of supplementary information). To appear in J.Mol.Evo

Calcium phosphate particles stimulate interleukin-1β release from human vascular smooth muscle cells: A role for spleen tyrosine kinase and exosome release

Aims: Calcium phosphate (CaP) particle deposits are found in several inflammatory diseases including atherosclerosis and osteoarthritis. CaP, and other forms of crystals and particles, can promote inflammasome formation in macrophages leading to caspase-1 activation and secretion of mature interleukin-1β (IL-1β). Given the close association of small CaP particles with vascular smooth muscle cells (VSMCs) in atherosclerotic fibrous caps, we aimed to determine if CaP particles affected pro-inflammatory signalling in human VSMCs. Methods and results: Using ELISA to measure IL-1β release from VSMCs, we demonstrated that CaP particles stimulated IL-1β release from proliferating and senescent human VSMCs, but with substantially greater IL-1β release from senescent cells; this required caspase-1 activity but not LPS-priming of cells. Potential inflammasome agonists including ATP, nigericin and monosodium urate crystals did not stimulate IL-1β release from VSMCs. Western blot analysis demonstrated that CaP particles induced rapid activation of spleen tyrosine kinase (SYK) (increased phospho-Y525/526). The SYK inhibitor R406 reduced IL-1β release and caspase-1 activation in CaP particle-treated VSMCs, indicating that SYK activation occurs upstream of and is required for caspase-1 activation. In addition, IL-1β and caspase-1 colocalised in intracellular endosome-like vesicles and we detected IL-1β in exosomes isolated from VSMC media. Furthermore, CaP particle treatment stimulated exosome secretion by VSMCs in a SYK-dependent manner, while the exosome-release inhibitor spiroepoxide reduced IL-1β release. Conclusions: CaP particles stimulate SYK and caspase-1 activation in VSMCs, leading to the release of IL-1β, at least in part via exosomes. These novel findings in human VSMCs highlight the pro-inflammatory and procalcific potential of microcalcification

Atomic diffraction from nanostructured optical potentials

We develop a versatile theoretical approach to the study of cold-atom diffractive scattering from light-field gratings by combining calculations of the optical near-field, generated by evanescent waves close to the surface of periodic nanostructured arrays, together with advanced atom wavepacket propagation on this optical potential.Comment: 8 figures, 10 pages, submitted to Phys. Rev.

South American Spider Mites: New Hosts and Localities

In order to contribute to taxonomic information on Tetranychid mites (Acari: Tetranychidae) in South America, surveys were conducted in Brazil (15 States and the Federal District) and Uruguay (one Department); 550 samples of 120 plant species were collected. Tetranychid mite infestations were confirmed in 204 samples, and 22 species belonging to seven genera of the Bryobiinae and Tetranychinae subfamilies were identified on 58 different host plants. Thirty-six new plant hosts were found in Brazil, South America, and worldwide for the following species: Eutetranychus banksi (McGregor); Mononychellus tanajoa (Bondar); Oligonychus anonae Paschoal; O. mangiferus (Rahman and Sapra); Tetranychus bastosi Tuttle, Baker and Sales; T. desertorum Banks, 1900, T. evansi Baker and Pritchard; T. ludeni Zacher; T. mexicanus (McGregor); T. neocaledonicus André; and T. urticae Koch. Four new localities in Brazil were reported for Eotetranychus tremae De Leon; O. anonae; Panonychus ulmi (Koch); and T. gloveri Baker and Pritchard

Low Serum Glutathione Peroxidase Activity Is Associated with Increased Cardiovascular Mortality in Individuals with Low HDLc’s

Background Since oxidized LDL is thought to initiate atherosclerosis and the serum glutathione peroxidase (GPx3) reduces oxidized lipids, we investigated whether high GPx3 activity reduces cardiovascular disease (CVD) mortality. Methods We determined GPx3 in stored samples from the Minnesota Heart Survey of 130 participants who after 5 to 12 years of follow-up had died of CVD and 240 controls. Participants were 26 to 85 years old and predominantly white. In a nested case-control, study we performed logistic regressions to calculate odds ratios (OR) adjusted for age, sex, baseline year, body mass index, smoking, alcohol intake, physical activity, total and HDL cholesterols, systolic blood pressure, serum glucose and gamma glutamyltransferase (GTT) activity. The referent was the quartile with the highest GPx3 activity (quartile 4). Results OR’s for CVD mortality for increasing quartiles of GPx3 were 2.37, 2.14, 1.83 and 1.00 (P for trend 0.02). This inverse correlation was confined to those with HDLc’s below the median (P for interaction, 0.006). The OR’s for increasing quartiles of GPx3 in this group were 6.08, 5.00, 3.64 and 1.00 (P for trend, 0.002). Conclusions Individuals with both low HDLc and GPx3 activity are at markedly increased risk for death from CVD

Small coronary calcifications are not detectable by 64-slice contrast enhanced computed tomography

Recently, small calcifications have been associated with unstable plaques. Plaque calcifications are both in intravascular ultrasound (IVUS) and multi-slice computed tomography (MSCT) easily recognized. However, smaller calcifications might be missed on MSCT due to its lower resolution. Because it is unknown to which extent calcifications can be detected with MSCT, we compared calcification detection on contrast enhanced MSCT with IVUS. The coronary arteries of patients with myocardial infarction or unstable angina were imaged by 64-slice MSCT angiography and IVUS. The IVUS and MSCT images were registered and the arteries were inspected on the presence of calcifications on both modalities independently. We measured the length and the maximum circumferential angle of each calcification on IVUS. In 31 arteries, we found 99 calcifications on IVUS, of which only 47 were also detected on MSCT. The calcifications missed on MSCT (n = 52) were significantly smaller in angle (27° ± 16° vs. 59° ± 31°) and length (1.4 ± 0.8 vs. 3.7 ± 2.2 mm) than those detected on MSCT. Calcifications could only be detected reliably on MSCT if they were larger than 2.1 mm in length or 36° in angle. Half of the calcifications seen on the IVUS images cannot be detected on contrast enhanced 64-slice MSCT angiography images because of their size. The limited resolution of MSCT is the main reason for missing small calcifications

Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability

Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA polymerase II, causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions. However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR-Cas9 screen, we identified the elongation factor ELOF1 as an important factor in the transcription stress response following DNA damage. We show that ELOF1 has an evolutionarily conserved role in transcription-coupled nucleotide excision repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair transcription-blocking lesions and resume transcription. Additionally, ELOF1 modulates transcription to protect cells against transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage via two distinct mechanisms