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At least 685 records · Page 38Linked to original sources
PubMed2002

Using Drosophila melanogaster to uncover human disease gene function and potential drug target proteins.

The fruit fly Drosophila melanogaster is a powerful genetic model organism, which has been instrumental in the determination of essential developmental and neurological pathways conserved from invertebrates to humans. With the completion of both the human and Drosophila genomes, the revelation that we are more similar to this simple organism than previously suspected was realised. 75% of human genetic disease genes have clear homologues in the fly. By utilising an array of genetic tools available to disrupt or misexpress these proteins, it is now feasible to perform large-scale genetic screens in Drosophila to identify other members of a particular human genetic pathway. This review outlines some of the reasons Drosophila is a useful tool for the discovery of therapeutic targets, covers some of the tools available to manipulate this organism and discusses specific examples of how to use Drosophila as a genetic test tube for revealing proteins which act in a common pathway.

Animals↗
PubMed1996

Ribozymes: structure, function, and potential therapy for dominant genetic disorders.

Some dominant genetic disorders, viral processes and neoplastic disorders base their pathogenicity on the production of protein or proteins that negatively affect cellular metabolism or environment. Thus, the inhibition of the synthesis of those proteins should prevent the biological damage. A promising approach to decreasing the level of the abnormal protein(s) is represented by specific interference with gene expression at the level of mRNA. The specific suppression of the expression of an mRNA can be achieved by using ribozymes. Ribozymes are RNA molecules able to break and form covalent bonds within a nucleic acid molecule. These molecules, with even greater potential advantages than antisense oligodeoxynucleotides, are able to bind specifically and cleave an mRNA substrate. There are advantages to using ribozymes instead of antisense oligodeoxynucleotides. Ribozymes can inactivate the target RNA without relying on the host cell's machinery and they have the capacity to cleave more than one copy of the target RNA by dissociating from the cleavage products and binding to another target molecule. Most of the studies performed to date have described the use of ribozymes as therapeutic agents for viral and cancer diseases. However, some dominant genetic disorders may also benefit from this approach. This is the case for some connective tissue disorders such as osteogenesis imperfecta, Marfan syndrome and the craniosynostotic syndromes.

Genetic Diseases, Inborn↗
PubMed2005

Further characterization of reproductive abnormalities in mCd59b knockout mice: a potential new function of mCd59 in male reproduction.

CD59 is a GPI-linked membrane protein that inhibits formation of the membrane attack complex of complement. We reported recently that mice have two CD59 genes (termed mCd59a and mCd59b), and that the targeted deletion of mCd59b (mCd59b-/-) results in spontaneous hemolytic anemia and progressive loss of male fertility. Further studies of the reproductive abnormalities in mCd59b-/- mice reported in this study revealed the presence of abnormal multinucleated cells and increased apoptotic cells within the walls of the seminiferous tubules, and a decrease in the number, motility, and viability of sperm associated with a significant increase in abnormal sperm morphologies. Both the capacitation-associated tyrosine phosphorylation and the ionophore-induced acrosome reaction as well as luteinizing hormone, follicle-stimulating hormone, and testosterone serum levels were similar in mCd59b-/- and mCd59b+/+. Surprisingly, the functional deficiency of the complement protein C3 did not rescue the abnormal reproductive phenotype of mCd59b-/-, although it was efficient in rescuing their hemolytic anemia. These results indicate that the male reproductive abnormalities in mCd59b-/- are complement-independent, and that mCd59 may have a novel function in spermatogenesis that is most likely unrelated to its function as an inhibitor of membrane attack complex formation.

Anemia, Hemolytic↗
PubMed1997

Functional specializations in human cerebral cortex analyzed using the Visible Man surface-based atlas.

We used surface-based representations to analyze functional specializations in the human cerebral cortex. A computerized reconstruction of the cortical surface of the Visible Man digital atlas was generated and transformed to the Talairach coordinate system. This surface was also flattened and used to establish a surface-based coordinate system that respects the topology of the cortical sheet. The linkage between two-dimensional and three-dimensional representations allows the locations of published neuroimaging activation foci to be stereotaxically projected onto the Visible Man cortical flat map. An analysis of two activation studies related to the hearing and reading of music and of words illustrates how this approach permits the systematic estimation of the degree of functional segregation and of potential functional overlap for different aspects of sensory processing.

Anatomy, Cross-Sectional↗
PubMedDate not supplied

[The vital potential of population during the market-reform period].

Estimates of the vital potential of population in the Astrakhan Region during the 1990-2000 market reforms, which were obtained on the basis of the continuous statistic observations of the total number of births and deaths during the mentioned period as well as on the basis of demography tables and potential demography, are described in the paper. An evaluation of man's "weight", expressed in man-years, is defined with respect to age and sex. The below phenomena are typical of the reform time: prevalence of the share of female vital potential; functionality of the life potential of citizens aged 0 to 19 and 20 to 59; a decreased role of the life potential of citizens aged 0 to 19 due to a low fertility; a diminished share of the life potential among able-bodied men; a decreased correlation index of the life potential of men versus women; a growing life potential in children aged above 1 year due to the paradox of the mean life expectancy; an increasing life potential within the age range of 10 years due to a dropped birth rate in the 90-ies and to the aging process because of the low birth rate and, correspondingly, low children's mortality rate; and compensation of losses in the life potential of men and women primarily due to the aging process.

Adolescent↗
PubMed2002

Extremophiles: developments of their special functions and potential resources.

Extremophilles are valuable resources in biotechnology. Enzymes from extremophiles are expected to fill the gap between biological and chemical processes due to their unusual properties. Especially enzymes from hyperthermophiles that can grow at above 90 degrees C were devoted owing to its extraordinary thermostability and denaturant tolerance. Screening trials of hyperthermophilic microorganisms were performed by a number of microbiologists and various unique strains were isolated from natural environments. One of the most successful uses of thermostable enzymes was DNA polymerase in the polymerase chain reaction (PCR). Thermostable enzymes are used in the chemical, food, pharmaceutical, paper and textile industries. Recombinant forms of thermostable enzymes that have been expressed in Escherichia coli are commonly utilized in industrial applications however their enzymatic characteristics and tertiary structure are different from the native ones produced in the original strains. In vitro heat treatment induces a structural conversion of the recombinant protein to its natural form. High temperature itself plays an important role in determining the specific characteristics and tertiary structure of the enzyme. Recent studies have revealed that hyperthermophiles can grow under numerous conditions not only in geothermal or deep-sea thermal environments. Technological advances have allowed DNA to be isolated from natural environments. Now genes could be isolated from microorganisms that have not been cultured. In this review, innovative approaches to hunt genes from natural environments without pure culturing of microorganisms are also discussed.

Journal Article↗
PubMed2006

A complex interferon inducer potentiates the functional macrophage activity during Staphylococcal infection.

The antibacterial effect of a new type I interferon inducer, an yeast RNA-tilorone molecular complex (MC), was studied using a model of staphylococcal infection. The MC taken in experimental doses being optimal interferon-inducing ones accelerates the Staphylococcus aureus elimination from mice organisms accompanied by increased functional ability (phagocytosis and bactericide activity) of peritoneal macrophages. The conclusion is that the MC antibacterial activity detected is mediated by its interferon-inducing properties.

Animals↗
PubMed1988

Free radicals. Formation, function and potential relevance in anaesthesia.

Free radical species are ubiquitous in plant and animal life. This article describes briefly the formation of certain oxygen-centred free radicals which are essential for aerobic metabolism and host defences in humans. The mechanism of cytotoxicity of excess or inappropriate free radical production is described. The potential relevance of free radical tissue injury to the anaesthetist is illustrated using oxygen toxicity, adult respiratory distress syndrome and halothane hepatitis as examples.

Anesthesia↗
PubMed1986

Oncogenes with potential nuclear function: myc, myb and fos.

The protein products of the retroviral oncogenes, v-myc, v-myb and v-fos, and their normal cellular counterparts, the c-myc, c-myb and c-fos proto-oncogenes, have been found to be localized predominantly in the nucleus. In view of the oncogenicity of the retroviral forms of these genes, it is probable that they have central roles in the nuclear events involved in cellular proliferation and differentiation. To investigate these possibilities, detailed studies on the expression of these 'nuclear oncogenes' have been performed. The cellular forms of all three genes are normally expressed in a variety of cell types during proliferation and have RNA and protein products with short half-lives, which is consistent with the idea that they may have regulatory roles. Studies have shown that both c-myc and c-fos are induced during the stimulation of quiescent cells to enter the cell cycle and are continually expressed in replicating cells. In contrast, c-myb levels are greatest in cells as they prepare to enter and traverse S phase. Both c-myc and c-myb expression cease as cells terminally differentiate, whereas in some cell types c-fos is induced during differentiation. Unregulated expression of all three genes has distinct effects on cellular differentiation: myc seems to inhibit differentiation of several cell types when expressed at high levels; myb does not appear to effect differentiation in the systems in which it has been examined; and fos appears to be able to induce differentiation of some cell types. In most cell types, c-myc and c-myb expression is controlled primarily by posttranscriptional mechanisms, whereas c-fos expression is regulated primarily at the transcriptional level. The protein products of these oncogenes are all phosphorylated and probably undergo additional modifications. The nuclear association of these proteins is complex and apparently takes multiple forms. Taken together, these data suggest that all three nuclear oncogenes have distinct regulatory functions with respect to cellular proliferation and differentiation. Several models for function are discussed.

Animals↗