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Biomedical subjects

D Haft

Publications and source records attributed to D Haft.

4 recordsLinked to original sources

Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains.

Virulence and immunity are poorly understood in Mycobacterium tuberculosis. We sequenced the complete genome of the M. tuberculosis clinical strain CDC1551 and performed a whole-genome comparison with the laboratory strain H37Rv in order to identify polymorphic sequences with potential relevance to disease pathogenesis, immunity, and evolution. We found large-sequence and single-nucleotide polymorphisms in numerous genes. Polymorphic loci included a phospholipase C, a membrane lipoprotein, members of an adenylate cyclase gene family, and members of the PE/PPE gene family, some of which have been implicated in virulence or the host immune response. Several gene families, including the PE/PPE gene family, also had significantly higher synonymous and nonsynonymous substitution frequencies compared to the genome as a whole. We tested a large sample of M. tuberculosis clinical isolates for a subset of the large-sequence and single-nucleotide polymorphisms and found widespread genetic variability at many of these loci. We performed phylogenetic and epidemiological analysis to investigate the evolutionary relationships among isolates and the origins of specific polymorphic loci. A number of these polymorphisms appear to have occurred multiple times as independent events, suggesting that these changes may be under selective pressure. Together, these results demonstrate that polymorphisms among M. tuberculosis strains are more extensive than initially anticipated, and genetic variation may have an important role in disease pathogenesis and immunity.

Bacterial Proteins↗

Optical emission from a charge-tunable quantum ring

Quantum dots or rings are artificial nanometre-sized clusters that confine electrons in all three directions. They can be fabricated in a semiconductor system by embedding an island of low-bandgap material in a sea of material with a higher bandgap. Quantum dots are often referred to as artificial atoms because, when filled sequentially with electrons, the charging energies are pronounced for particular electron numbers; this is analogous to Hund's rules in atomic physics. But semiconductors also have a valence band with strong optical transitions to the conduction band. These transitions are the basis for the application of quantum dots as laser emitters, storage devices and fluorescence markers. Here we report how the optical emission (photoluminescence) of a single quantum ring changes as electrons are added one-by-one. We find that the emission energy changes abruptly whenever an electron is added to the artificial atom, and that the sizes of the jumps reveal a shell structure.

Journal Article↗

A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi.

We have determined that Borrelia burgdorferi strain B31 MI carries 21 extrachromosomal DNA elements, the largest number known for any bacterium. Among these are 12 linear and nine circular plasmids, whose sequences total 610 694 bp. We report here the nucleotide sequence of three linear and seven circular plasmids (comprising 290 546 bp) in this infectious isolate. This completes the genome sequencing project for this organism; its genome size is 1 521 419 bp (plus about 2000 bp of undetermined telomeric sequences). Analysis of the sequence implies that there has been extensive and sometimes rather recent DNA rearrangement among a number of the linear plasmids. Many of these events appear to have been mediated by recombinational processes that formed duplications. These many regions of similarity are reflected in the fact that most plasmid genes are members of one of the genome's 161 paralogous gene families; 107 of these gene families, which vary in size from two to 41 members, contain at least one plasmid gene. These rearrangements appear to have contributed to a surprisingly large number of apparently non-functional pseudogenes, a very unusual feature for a prokaryotic genome. The presence of these damaged genes suggests that some of the plasmids may be in a period of rapid evolution. The sequence predicts 535 plasmid genes >/=300 bp in length that may be intact and 167 apparently mutationally damaged and/or unexpressed genes (pseudogenes). The large majority, over 90%, of genes on these plasmids have no convincing similarity to genes outside Borrelia, suggesting that they perform specialized functions.

Base Sequence↗

Intravitreal expansion of perfluorocarbon bubbles.

The intraocular expansion of perfluoromethane (CF4), perfluoroethane (C2F6), and perfluoropropane (C3F8) was determined by a direct method for measuring intravitreal gas. A bubble of CF4 was found to expand 1.9 times the volume initially injected; C2F6 expanded 3.3 times; C3F8 expanded four times. The expansion characteristics of the experimental gases were compared with those of sulfur hexafluoride (SF6) and octofluorocyclobutane (C4F8), two gases already in clinical use.

Animals↗