Closing gaps in the human genome with fosmid resources generated from multiple individuals

The human genome sequence has been finished to very high standards; however, more than 340 gaps remained when the finished genome was published by the International Human Genome Sequencing Consortium in 2004. Using fosmid resources generated from multiple individuals, we targeted gaps in the euchromatic part of the human genome. Here we report 2,488,842 bp of previously unknown euchromatic sequence, 363,114 bp of which close 26 of 250 euchromatic gaps, or 10%, including two remaining euchromatic gaps on chromosome 19. Eight (30.7%) of the closed gaps were found to be polymorphic. These sequences allow complete annotation of several human genes as well as the assignment of mRNAs. The gap sequences are 2.3-fold enriched in segmentally duplicated sequences compared to the whole genome. Our analysis confirms that not all gaps within 'finished' genomes are recalcitrant to subcloning and suggests that the paired-end-sequenced fosmid libraries could prove to be a rich resource for completion of the human euchromatic genome.     

Conditional telomerase induction causes proliferation of hair follicle stem cells

TERT, the protein component of telomerase, serves to maintain telomere function through the de novo addition of telomere repeats to chromosome ends, and is reactivated in 90% of human cancers. In normal tissues, TERT is expressed in stem cells and in progenitor cells, but its role in these compartments is not fully understood. Here we show that conditional transgenic induction of TERT in mouse skin epithelium causes a rapid transition from telogen (the resting phase of the hair follicle cycle) to anagen (the active phase), thereby facilitating robust hair growth. TERT overexpression promotes this developmental transition by causing proliferation of quiescent, multipotent stem cells in the hair follicle bulge region. This new function for TERT does not require the telomerase RNA component, which encodes the template for telomere addition, and therefore operates through a mechanism independent of its activity in synthesizing telomere repeats. These data indicate that, in addition to its established role in extending telomeres, TERT can promote proliferation of resting stem cells through a non-canonical pathway.     

MYCN haploinsufficiency is associated with reduced brain size and intestinal atresias in Feingold syndrome

Feingold syndrome is characterized by variable combinations of esophageal and duodenal atresias, microcephaly, learning disability, syndactyly and cardiac defect. We show here that heterozygous mutations in the gene MYCN are present in Feingold syndrome. All mutations are predicted to disrupt both the full-length protein and a new shortened MYCN isoform, suggesting that multiple aspects of early embryogenesis and postnatal brain growth in humans are tightly regulated by MYCN dosage.     

Separation of two strains of rats with inbred dissimilar sensitivity to doca-salt hypertension

Résumé La réponse au régime Doca-sel (D. S.) a été utilisée comme critère de sélection pour séparer, par croisement consanguin, deux colonies de rats manifestant une susceptibilité bien différente à l'hypertension artérielle. Les résultats obtenus dans la 6ème génération de nos colonies normotensive et hypertensive font l'objet de ce raport. Le rôle des facteurs héréditaires dans la susceptibilité ou la résistance à l'hypertension du type D. S. est démontrée.     

The redox cleavage of the sulfur-sulfur bond and carbon-sulfur bond in organic disulfides by a model coenzyme

Résumé Le N-Benzyl-1,4-dihydronicotinamide réduit, par un mécanisme redox de transfert d'un électron, laliaison disulfide de plusieurs disulfides organiques tels que le diphényl disulfide, l'-lipoamide et le tétraméthylthiuram disulfide. Les réactions chimiques sont comparées à l'oxydation enzymique de la nicotinamide-adénine nucléotide.     

The quantum liar experiment in Cramer's transactional interpretation

Cramer's Transactional Interpretation (TI) is applied to the “quantum liar experiment” (QLE). It is shown how some apparently paradoxical features can be explained naturally, albeit nonlocally (since TI is an explicitly nonlocal interpretation, at least from the vantage point of ordinary spacetime). At the same time, it is proposed that in order to preserve the elegance and economy of the interpretation, it may be necessary to consider offer and confirmation waves as propagating in a “higher space” of possibilities.     

Assortative mating in soldier beetles (Cantharidae: Chaulignathus ): test of the mate-choice hypothesis

Soldier beetles of 2 species, Chauliognathus basalis and C. deceptus , were examined to test the Crespi hypothesis that positive assortative mating by size is caused by mate choices. Specifically, we tested the prediction that if mate choice involves choosing the largest mate available, then mating individuals will be larger than nonmating individuals. Four samples were taken, at different times during the mating season, from each of 2 sites. Each sample consisted of mating pairs, nonmanting males, and nonmating females. Some of the samples contained beetles of both species; others contained beetles of a single species. For each gender elytron lengths of mating individuals were compared with elytron lengths of nonmating individuals. We found no effect of mating status (mating vs. nonmating) on elytron lengths in samples that exhibited assertive mating (which occurs where 2 species coexist). Surprisingly, we found a consistent effect of mating status on elytron lengths in samples that did not exhibit assortative mating (which occurs where only 1 species exists). Our results do not support the mate-choice hypothesis. Instead, mate choice and assortative mating appear to be alternative mating patterns in which mate choice occurs where a single species exists and assortative mating occurs where 2 species coexist.