Molecular phylogeny and divergence times of Malagasy tenrecs: Influence of data partitioning and taxon sampling on dating analyses

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αA-crystallin confers cellular thermoresistance

AbstractThe bovine eye lens protein αA-crystallin has been overexpressed both by stable transfection of HeLa cells and by transient transfection of NIH 3T3 cells. In both experimental systems αA-crystallin overexpression results in an increased cellular thermoresistance as judged by different clonal survival assays. In contrast, similar overexpression of another stable lens protein, βB2-crystallin, does not confer thermoresistance. These results indicate that the structural relationship of αA-crystallin to the small heat shock proteins HSP25/27 and to αB-crystallin is sufficient for the shared thermoprotective function of all of these molecules and strongly suggests that the chaperone-like properties that they have in common are responsible for the conferred cellular thermoresistance

Age-dependent deamidation of αB-crystallin

AbstractBovine and human αB-crystallin undergo deamidation upon aging in the lens. In bovine αB-crystallin, the specific site of dearnidation has been identified by peptide mapping after tryptic digestion. Asn-146 was found to be subject to deamidation, whereas the only other asparagine residue, at position 78, is not affected. Asn-146 is flanked at the carboxylic side by a glyeyl residue. Yet, the rate of in vivo deamidation is low. In vitro studies reveal that the deamidation is accompanied by significant racemization, indicating that the deamidation proceeds via formation of a succinimide intermediate

The in vivo phosphorylation sites of bovine αB-crystallin

AbstractPhosphate content determinations established that in αB-crystallin two phosphate groups can be present in vivo in bovine lenses. Comparison of tryptic digests of phosphorylated and unphosphorylated αB chains, revealed the location of the two phosphorylation sites in tryptic peptides T2 and T3. Thermolytic digestion and gas-phase sequencing demonstrated that Ser-19 and Ser-45 are the in vivo phosphorylation sites of bovine αB-crystallin. This pattern of phosphorylation differs from the previously reported in vitro obtained results

Loss of Octarepeats in Two Processed Prion Pseudogenes in the Red Squirrel, Sciurus vulgaris

The N-terminal region of the mammalian prion protein (PrP) contains an ‘octapeptide’ repeat which is involved in copper binding. This eight- or nine-residue peptide is repeated four to seven times, depending on the species, and polymorphisms in repeat number do occur. Alleles with three repeats are very rare in humans and goats, and deduced PrP sequences with two repeats have only been reported in two lemur species and in the red squirrel, Sciurus vulgaris. We here describe that the red squirrel two-repeat PrP sequence actually represents a retroposed pseudogene, and that an additional and older processed pseudogene with three repeats also occurs in this species as well as in ground squirrels. We argue that repeat numbers may tend to contract rather than expand in prion retropseudogenes, and that functional prion genes with two repeats may not be viable

Advances in mass spectrometry-based post-column bioaffinity profiling of mixtures

In the screening of complex mixtures, for example combinatorial libraries, natural extracts, and metabolic incubations, different approaches are used for integrated bioaffinity screening. Four major strategies can be used for screening of bioactive mixtures for protein targets—pre-column and post-column off-line, at-line, and on-line strategies. The focus of this review is on recent developments in post-column on-line screening, and the role of mass spectrometry (MS) in these systems. On-line screening systems integrate separation sciences, mass spectrometry, and biochemical methodology, enabling screening for active compounds in complex mixtures. There are three main variants of on-line MS based bioassays: the mass spectrometer is used for ligand identification only; the mass spectrometer is used for both ligand identification and bioassay readout; or MS detection is conducted in parallel with at-line microfractionation with off-line bioaffinity analysis. On the basis of the different fields of application of on-line screening, the principles are explained and their usefulness in the different fields of drug research is critically evaluated. Furthermore, off-line screening is discussed briefly with the on-line and at-line approaches

Observation of weak neutral current neutrino production of J/ψJ/\psi

Observation of \jpsi production by neutrinos in the calorimeter of the CHORUS detector exposed to the CERN SPS wide-band \numu beam is reported. A spectrum-averaged cross-section $\sigma^{\mathrm{J/\psi}}$ = (6.3 $\pm$ 3.0) $\times \mathrm{10^{-41}~cm^{2}}$ is obtained for 20 GeV $\leq E_{\nu} \leq$ 200 GeV. The data are compared with the theoretical model based on the QCD Z-gluon fusion mechanism

The CHORUS neutrino oscillation search experiment

The CHORUS experiment has successfully finished run I (320~000 recorded \numu\ CC in 94/95) and performed half of run II (225~000 \numu\ CC in 96). The analysis chain was exercised on a small data sample for the muonic \tdecay\ search using for the first time fully automatic emulsion scanning. This pilot analysis, resulting in a limit \sintth \leq 3 \cdot 10^{-2}, confirms that the CHORUS proposal sensitivity (\sintth \leq 3 \cdot 10^{-4}) is within reach in two years

Epigenome-wide association study of lung function level and its change

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults. In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 (AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV1/FVC: pdiscovery=3.96x10(-21) and pcombined=7.22x10(-50)). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV1/FVC: p=2.65x10(-20)). Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children.Peer reviewe