Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium.

Pelophylaxins: novel antimicrobial peptide homologs from the skin secretion of the Fukien gold-striped pond frog, Pelophylax plancyi fukienensis: identification by “shotgun” cDNA cloning and sequence analysis.

Amphibian skin secretions are rich in antimicrobial peptides that act as important components of an innate immune system. Here, we describe a novel “shotgun” skin peptide precursor cloning technique that facilitates rapid access to these genetically encoded molecules and effects their subsequent identification and structural characterization from the secretory peptidome. Adopting this approach on a skin secretion-derived library from a hitherto unstudied Chinese species of frog, we identified a family of novel antimicrobial peptide homologs, named pelophylaxins, that belong to previously identified families (ranatuerins, brevinins and temporins) found predominantly in the skin secretions from frogs of the genus Rana. These data further substantiate the scientifically robust nature of applying parallel transcriptome and peptidome analyses on frog defensive skin secretions that can be obtained in a non-invasive, non-destructive manner. In addition, the present data illustrate that rapid structural characterization of frog skin secretion peptides can be achieved from an unstudied species without prior knowledge of primary structures of endogenous peptides.

Scheduling and Platforming Trains at Busy Complex Stations

We consider the problem of train planning or scheduling for large, busy, complex train stations, which are common in Europe and elsewhere, though not in North America. We develop the constraints and objectives for this problem, but these are too computationally complex to solve by standard combinatorial search or integer programming methods. Also, the problem is somewhat political in nature, that is, it does not have a clear objective function because it involves multiple train operators with conflicting interests. We therefore develop scheduling heuristics analogous to those successfully adopted by train planners using ''manual'' methods. We tested the model and algorithms by applying to a typical large station that exhibits most of the complexities found in practice. The results compare well with those found by traditional methods, and take account of cost and preference trade-offs not handled by those methods. With successive refinements, the algorithm eventually took only a few seconds to run, the time depending on the version of the algorithm and the scheduling problem. The scheduling models and algorithms developed and tested here can be used on their own, or as key components for a more general system for train scheduling for a rail line or network.Train scheduling for a busy station includes ensuring that there are no conflicts between several hundred trains per day going in and out of the station on intersecting paths from multiple in-lines and out-lines to multiple platforms, while ensuring that each train is allowed at least its minimum required headways, dwell time, turnaround time and trip time. This has to be done while minimizing (costs of) deviations from desired times, platforms or lines, allowing for conflicts due to through-platforms, dead-end platforms, multiple sub-platforms, and possible constraints due to infrastructure, safety or business policy.

The DUB/USP17 deubiquitinating enzymes, a multigene family within a tandemly repeated sequence

Here we report the identification of 10 human, 1 murine, and 2 rat ORFs, all of which represent additional members of the DUB/USP17 family of deubiquitinating enzymes. In addition, we demonstrate that this family constitutes part of a tandemly repeated sequence conserved throughout humans, mice, and rats. Furthermore, upon examination of the known family members we have found that the multiple genes observed, in contrast to other gene families, have arisen due to the independent expansion of an ancestral sequence within each species. This premise is further strengthened by the observation that the murine and rat genes span two exons while their human counterparts have one. These observations, in conjunction with previous work demonstrating that the DUB/USP17's are cytokine inducible and that they regulate both cell growth and survival, suggest that the DUB/USP17's are a large highly conserved family of genes that may play an important role in controlling cell fate.

A non-LTE analysis of the spectra of two narrow lined main sequence stars in the SMC

An analysis of high-resolution VLT/UVES spectra of two B-type main sequence stars, NGC 346-11 and AV 304, in the Small Magellanic Cloud (SMC), has been undertaken, using the non-LTE tlusty model atmospheres to derive the stellar parameters and chemical compositions of each star. The chemical compositions of the two stars are in reasonable agreement. Moreover, our stellar analysis agrees well with earlier analyses of H II regions. The results derived here should be representative of the current base-line chemical composition of the SMC interstellar medium as derived from B-type stars.

Boron abundances in B-type stars: A test of rotational depletion during main-sequence evolution

Boron abundances have been derived for seven main-sequence B- type stars from Hubble Space Telescope STIS spectra around the B III lambda2066 line. In two stars, boron appears to be undepleted with respect to the presumed initial abundance. In one star, boron is detectable but is clearly depleted. In the other four stars, boron is undetectable, implying depletions of 1-2 dex. Three of these four stars are nitrogen enriched, but the fourth shows no enrichment of nitrogen. Only rotationally induced mixing predicts that boron depletions are unaccompanied by nitrogen enrichments. The inferred rate of boron depletion from our observations is in good agreement with these predictions. Other boron-depleted nitrogen-normal stars are identified from the literature. In addition, several boron- depleted nitrogen-rich stars are identified, and while all fall on the boron-nitrogen trend predicted by rotationally induced mixing, a majority have nitrogen enrichments that are not uniquely explained by rotation. The spectra have also been used to determine iron group (Cr, Mn, Fe, and Ni) abundances. The seven B-type stars have near-solar iron group abundances, as expected for young stars in the solar neighborhood. We have also analyzed the halo B-type star PG 0832 + 676. We find [Fe/H] = -0.88 +/- 0.10, and the absence of the B III line gives the upper limit [B/H] <-2.5. These and other published abundances are used to infer the star's evolutionary status as a post-asymptotic giant branch star.