PubMed Health⌕ Search

Biomedical subjects

M T Hansen

Publications and source records attributed to M T Hansen.

27 records · Page 2Linked to original sources

Multiplicity of genome equivalents in the radiation-resistant bacterium Micrococcus radiodurans.

The complexity of the genome of Micrococcus radiodurans was determined to be (2.0 +/- 0.3) X 10(9) daltons by DNA renaturation kinetics. The number of genome equivalents of DNA per cell was calculated from the complexity and the content of DNA. A lower limit of four genome equivalents per cell was approached with decreasing growth rate. Thus, no haploid stage appeared to be realized in this organism. The replication time was estimated from the kinetics and amount of residual DNA synthesis after inhibiting initiation of new rounds of replication. From this, the redundancy of terminal genetic markers was calculated to vary with growth rate from four to approximately eight copies per cell. All genetic material, including the least abundant, is thus multiply represented in each cell. The potential significance of the maintenance in each cell of multiple gene copies is discussed in relation to the extreme radiation resistance of M. radiodurans.

DNA, Bacterial↗

Control of ribosome synthesis in Escherichia coli: analysis of an energy source shift-down.

The rate of ribosome synthesis and accumulation in Escherichia coli during the transition after an energy source shift-down was analyzed. The shift was imposed on cultures of stringent and relaxed strains growing in glucose minimal medium by the addition of the glucose analogue alpha-methylglucoside. In the stringent strain, ribosome synthesis was almost instantaneously reduced after the shift, whereas the relaxed strain exhibited a more gradual response. The rate of messenger ribonucleic acid (mRNA) synthesis was affected similarly, though to a smaller extent. A comparison of the rates of synthesis and accumulation of ribosomal RNA (rRNA) and ribosomal proteins showed that far more ribosomal components were synthesized after the shift than were accumulated, indicating that a substantial part of the rRNA made after the shift was unstable. A new method was used to measure relative rates of rRNA synthesis and to estimate the transcription time for the rRNA operon under different conditions. In steady states of growth with growth rates ranging from 0.75 to 2.3 doublings/h, as well as during the transition after a shift-down, the transcription time of the rRNA operon was constant. The rate of synthesis of rRNA correlated during this transition - in contrast to the rate of accumulation (M. T. Hansen et al., J. Bacteriol. 122: 585-591, 1975) - with the ppGpp pool in the same way as has been observed during partial amino acid starvation.

Bacterial Proteins↗

Simple downshift and resulting lack of correlation between ppGpp pool size and ribonucleic acid accumulation.

The growth rate of Escherichia coli can be limited by the availability of carbon and energy. To impose such a limitation, alpha-methylglucoside (alpha MG), a non-metabolizable analogue, can be used to decrease uptake of glucose by competition for the transport of this sugar. Varying the ratio of glucose to alphaMG allowed shifts in growth rate without simultaneous qualitative changes in the growth medium and permitted examination of the immediate changes accompanying such shifts. Stringent (rel+) as well as relaxed (rel minus) strains were able to rapidly curtail their accumulation of ribonculeic acid (RNA) after a downshift imposed by decreasing glucose transport into the cell. Guanosine 5'-diphosphate 3'-diphosphate (ppGpp) accumulated in both rel+ and rel minus strains after a degrease in growth rate. However, the accumulation of ppGpp in relaxed derivatives was very slow, and there was no direct or obligatory correlation between the level of ppGpp and the rate of RNA accumulation. This latter conclusion is supported by measurements of ppGpp levels and rates of RNA accumulation after restoration of maximal growth rates by addition of excess glucose.

Adenosine Triphosphate↗

Influence of polyamine limitation on the chain growth rates of beta-galactosidase and of its messenger ribonucleic acid.

The rates of elongation of beta-galactosidase and its messenger ribonucleic acid (RNA) were estimated in a polyamine-deficient mutant of Escherichia coli through an analysis of the kinetics of enzyme induction. The chain growth of beta-galactosidase was calculated from the time required after the appearance of an amino terminal fragment of 60 amino acids (auto-alpha) until completed enzyme began to accumulate. The elongation rate of beta-galactosidase messenger RNA was estimated from the time after induction at which streptolydigen-resistant, enzyme-forming capacity first appeared. Upon polyamine starvation, the rate of polypeptide elongation slowed from 17 to 10 amino acids per s and the messenger RNA elongation rate decreased from 47 to 30 nucleotides per s. These reductions in polymerization rates were proportional to the decrease in cellular growth rate produced by polyamine starvation. It was concluded that, although it is quite unlikely that polyamine levels are involved in regulation of cell growth, they may be acting as cofactors in the synthesis of RNA or protein, or both.

Drug Stability↗

A novel aspartyl protease allowing KEX2-independent MF alpha propheromone processing in yeast.

Mutants of Saccharomyces cerevisiae which lack the KEX2-encoded endopeptidase are unable to process proteolytically the mating factor alpha (MF alpha) propheromone produced from the chromosomal MF alpha 1 and MF alpha 2 genes (Julius et al., 1983). Overproduction of pheromone precursor from multiple, plasmid-borne MF alpha genes did, however, lead to the production of active MF alpha peptides in the absence of the KEX2 gene product. S. cerevisiae therefore must possess an alternative processing enzyme. The cleavage site of this enzyme appeared identical to that of the KEX2-encoded endopeptidase. To identify the gene responsible for the alternative processing, we have isolated clones which allowed production of mature MF alpha in a kex2-disrupted strain even from the chromosomal MF alpha genes. The gene isolated in this way was shown also to be essential for the KEX2-independent processing of propheromone overproduced from plasmid-borne MF alpha 1. The amino acid sequence deduced from the gene shows extensive homology to a number of aspartyl proteases including the PEP4 and BAR1 gene products from S. cerevisiae. In contrast to the BAR1 gene product, the novel aspartyl protease (YAP3 for Yeast Aspartyl Protease 3) contains a C-terminal serine/threonine-rich sequence and potential transmembrane domain similar to those found in the KEX2 gene product. The corresponding gene YAP3 was located to chromosome XII. The normal physiological role of the YAP3 gene product is not known. Strains disrupted in YAP3 are both viable and able to process the mating factor a precursor.

Amino Acid Sequence↗

What's your strategy for managing knowledge?

The rise of the computer and the increasing importance of intellectual assets have compelled executives to examine the knowledge underlying their businesses and how it is used. Because knowledge management as a conscious practice is so young, however, executives have lacked models to use as guides. To help fill that gap, the authors recently studied knowledge management practices at management consulting firms, health care providers, and computer manufacturers. They found two very different knowledge management strategies in place. In companies that sell relatively standardized products that fill common needs, knowledge is carefully codified and stored in databases, where it can be accessed and used--over and over again--by anyone in the organization. The authors call this the codification strategy. In companies that provide highly customized solutions to unique problems, knowledge is shared mainly through person-to-person contacts; the chief purpose of computers is to help people communicate. They call this the personalization strategy. A company's choice of knowledge management strategy is not arbitrary--it must be driven by the company's competitive strategy. Emphasizing the wrong approach or trying to pursue both can quickly undermine a business. The authors warn that knowledge management should not be isolated in a functional department like HR or IT. They emphasize that the benefits are greatest--to both the company and its customers--when a CEO and other general managers actively choose one of the approaches as a primary strategy.

Commerce↗

Networked incubators. Hothouses of the new economy.

Business incubators such as Hotbank, CMGI, and Idealab! are a booming industry. Offering office space, funding, and basic services to start-ups, these organizations have become the hottest way to nurture and grow fledgling businesses. But are incubators a fleeting phenomenon born of an overheated stock market, or are they an important and lasting way of creating value and wealth in the new economy? The authors argue that one type of incubator, called a networked incubator, represents a fundamentally new and enduring organizational model uniquely suited to growing businesses in the Internet economy. It shares certain features with other incubators--mainly, it fosters a spirit of entrepreneurship and offers economies of scale. But its key distinguishing feature is its ability to give start-ups preferential access to a network of potential partners. Such incubators institutionalize their networking--they have systems in place to encourage networking, helping start-ups, for example, to meet with potential business allies. That doesn't mean incubatees get preferential treatment; it means only that they have built-in access to partnerships that might not have existed without the incubator. Even with this advantage, however, networked incubators can easily follow the road to ruin. To avoid failure, they must create a portfolio of companies and advisers that their incubatees can leverage. That can be done by strategically investing in portfolio firms and by enlisting a large set of business allies. It can also be done by establishing connections and relationships that are anchored more to the incubator than to particular individuals.

Cooperative Behavior↗