A draft genome of Yersinia pestis from victims of the Black Death

Technological advances in DNA recovery and sequencing have drastically expanded the scope of genetic analyses of ancient specimens to the extent that full genomic investigations are now feasible and are quickly becoming standard. This trend has important implications for infectious disease research because genomic data from ancient microbes may help to elucidate mechanisms of pathogen evolution and adaptation for emerging and re-emerging infections. Here we report a reconstructed ancient genome of Yersinia pestis at 30-fold average coverage from Black Death victims securely dated to episodes of pestilence-associated mortality in London, England, 1348-1350. Genetic architecture and phylogenetic analysis indicate that the ancient organism is ancestral to most extant strains and sits very close to the ancestral node of all Y. pestis commonly associated with human infection. Temporal estimates suggest that the Black Death of 1347-1351 was the main historical event responsible for the introduction and widespread dissemination of the ancestor to all currently circulating Y. pestis strains pathogenic to humans, and further indicates that contemporary Y. pestis epidemics have their origins in the medieval era. Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype. These findings support the notion that factors other than microbial genetics, such as environment, vector dynamics and host susceptibility, should be at the forefront of epidemiological discussions regarding emerging Y. pestis infections.     

A homologue of the bacterial heat-shock gene DnaJ that alters protein sorting in yeast

Heat-shock proteins have been implicated in assembly of protein complexes, correct protein folding and uptake of proteins into organelles. In Escherichia coli, the heat-shock protein DnaJ and the Hsp70 homologue, DnaK, act together to disassemble a protein complex involved in bacteriophage lambda replication. We report the identification of SCJ1, a gene in the yeast Saccharomyces cerevisiae that encodes a homologue of the bacterial DnaJ protein. SCJ1 was identified by a genetic screen in which increased expression of candidate genes results in missorting of a nuclear-targeted test protein. The predicted amino-acid sequence of SCJ1 is 37% identical to the entire E. coli DnaJ protein. Hybridization experiments indicate that there is a family of yeast genes related to SCJ1. These findings suggest that the Hsp70 DnaK-DnaJ interaction is general to eukaryotes.     

小凉山的俘虏、亲属和奴隶

20世纪50年代集体化改革之前小凉山奴隶制度特有的社会经济进程表明,诺苏社会曾是一个拥有奴隶的社会,但它并不是奴隶社会。该结论基于其他关于奴隶制研究中的传统观念即在奴隶社会中奴隶制是体系得以维持的关键所在。1956年之前,小凉山的生产目的是生计而不是市场。此外,小凉山的精英阶层更依赖于系谱或继嗣,而不是财富;另一个相关论点是,在诺苏身份和认同的决定中,亲属比等级发挥了更为基础的作用。     

Permeability of rat heart myocytes to cytochrome c

Rat heart myocytes undergoing progressive damage demonstrate morphological changes of shortening and swelling followed by the formation of intracellular vacuoles and plasma membrane blebbing. The damaged myocytes displayed impaired N,N'-tetramethyl-p-phenyldiamine (TMPD) ascorbate-stimulated respiratory activity which was restored by the addition of reduced cytochrome c to the cell culture medium. To clarify the role played by cytochrome c in the impairment of cell respiration, polarographic, spectrophotometric and fluorescence as well as electron microscopy imaging experiments were performed. TMPD/ascorbate-stimulated respiratory activity returned to control levels, at approximately 20 microM cytochrome c, establishing the threshold below which the turnover rate by cytochrome c oxidase in the cell depends on cytochrome concentration. Mildly damaged cardiac myocytes, as indicated by cell shortening, retention of visible striations and free-fluorescein exclusion, together with the absence of lactate dehydrogenase leakage and exclusion of trypan blue, were able to oxidize exogenous cytochrome c and were permeable to fluorescein-conjugated cytochrome c. The results, while consistent with an early cytochrome c release observed at the beginning of cell death, elucidate the role played by cytochrome c in the kinetic control of mitochondrial electron transfer under pathological conditions, particularly those involving the terminal part of the respiratory chain. These data are the first to demonstrate that the sarcolemma of cardiac myocytes, damaged but still viable, is permeable to cytochrome c.     

Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons

Using a novel single-molecule PCR approach to quantify the total burden of mitochondrial DNA (mtDNA) molecules with deletions, we show that a high proportion of individual pigmented neurons in the aged human substantia nigra contain very high levels of mtDNA deletions. Molecules with deletions are largely clonal within each neuron; that is, they originate from a single deleted mtDNA molecule that has expanded clonally. The fraction of mtDNA deletions is significantly higher in cytochrome c oxidase (COX)-deficient neurons than in COX-positive neurons, suggesting that mtDNA deletions may be directly responsible for impaired cellular respiration.     

Melatonin antagonizes colchicine-induced mitotic arrest

Summary Melatonin, in concentrations up to 10^–3 M, showed no effect on mitosis in cultures of HeLa or KB cells. However, when melatonin at 10^–4 M was preincubated with HeLa cells prior to addition of 10^–7 M colchicine, a reduction in the mitotic index, in comparison to colchicine alone, was observed.This work was supported by PHS Grant No. CA 16425.     

Characterization of the domestic horse (Equus caballus) karyotype using G-and C-banding techniques

Summary Giemsa banding techniques have been used to identify the chromosomes of the domestic horse.     

Dystrophic mutation (dy2J) affecting regulation of lactate dehydrogenase (LDH) and pyruvate kinase (PK) in C57BL/6J mice

Summary The genotype difference (dystrophic vs nondystrophic) in the LDH isozymes is observed in kidney. These differences are evident only at birth and at early developmental stages (before the expression of dystrophic symptoms). The tissue specific genotype differences for PK are limited to the thigh muscle (M form) and heart (L form), after the onset of the condition. These differences may reflect the pleiotropic effect of the dy^2J locus during the temporal regulation of these and other enzymes implicated in muscular dystrophy (MD).This research was financed by a Natural Sciences and Engineering Research Council Canada grant to S.M.S.