PubMed Health⌕ Search

Biomedical subjects

M Basson

Publications and source records attributed to M Basson.

15 recordsLinked to original sources
PubMed2001

Translocation of PKC isoforms in bovine aortic smooth muscle cells exposed to strain.

Our laboratory has previously reported that the exposure of smooth muscle cells (SMC) to the cyclic strain results in significant stimulation of protein kinase C (PKC) activity by translocating the enzyme from the cytosol to the particulate fraction. We now sought to examine the strain-induced translocation of individual PKC isoforms in SMC. Confluent bovine aortic SMC grown on collagen type I-coated plates were exposed to cyclic strain for up to 100 s at average 10% strain with 60 cycles/min. Immunoblotting analysis demonstrates that SMC express PKC-alpha, -beta and -zeta in both cytosolic and particulate fractions. Especially, PKC-alpha and -zeta were predominantly expressed in the cytosolic fraction. However, cyclic strain significantly (P < 0.05) increased PKC-alpha and -zeta in the particulate fraction and decreased in the cytosolic fraction. Thus, the cyclic strain-mediated stimulation of PKC activity in SMC may be due to the translocation of PKC-alpha and -zeta from the cytosolic to the particulate fraction. These results demonstrate that mechanical deformation causes rapid translocation of PKC isoforms, which may initiate a cascade of proliferation responses of SMC since NF-kappaB, which is involved in the cellular proliferation has been known to be activated by these PKC isoforms.

Animals↗
PubMed2000

A model for niemann-pick type C disease in the nematode Caenorhabditis elegans.

Niemann-Pick type C (NP-C) disease is a progressive neurodegenerative disorder characterized by the inappropriate accumulation of unesterified cholesterol in lysosomes [1]. NP-C patients show various defects including hepatosplenomegaly, ataxia, dystonia and dementia. Most cases of NP-C are associated with inactivating mutations of the NPC1 gene [2], which encodes a protein implicated in the retrograde transport of sterols and other cargo from lysosomes [3]. Furthermore, localization of the NPC1 protein to lysosomal/endosomal compartments is essential for proper transport [4]. To create a model of NP-C disease in a simple, genetically tractable organism, we generated deletion mutations in two Caenorhabditis elegans homologs of the human NPC1 gene, designated npc-1 and npc-2. Animals mutant for npc-1 developed slowly, laid eggs prematurely, and were hypersensitive to cholesterol deprivation. Furthermore, npc-1; npc-2 double-mutant animals inappropriately formed dauer larvae under favorable growth conditions. These phenotypes in C. elegans provide a model system for both genetic and chemical suppressor screening that could identify promising drug targets and leads for NP-C disease.

Amino Acid Sequence↗
PubMed2000

The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans.

The C. elegans heterochronic gene pathway consists of a cascade of regulatory genes that are temporally controlled to specify the timing of developmental events. Mutations in heterochronic genes cause temporal transformations in cell fates in which stage-specific events are omitted or reiterated. Here we show that let-7 is a heterochronic switch gene. Loss of let-7 gene activity causes reiteration of larval cell fates during the adult stage, whereas increased let-7 gene dosage causes precocious expression of adult fates during larval stages. let-7 encodes a temporally regulated 21-nucleotide RNA that is complementary to elements in the 3' untranslated regions of the heterochronic genes lin-14, lin-28, lin-41, lin-42 and daf-12, indicating that expression of these genes may be directly controlled by let-7. A reporter gene bearing the lin-41 3' untranslated region is temporally regulated in a let-7-dependent manner. A second regulatory RNA, lin-4, negatively regulates lin-14 and lin-28 through RNA-RNA interactions with their 3' untranslated regions. We propose that the sequential stage-specific expression of the lin-4 and let-7 regulatory RNAs triggers transitions in the complement of heterochronic regulatory proteins to coordinate developmental timing.

Animals↗
PubMed2000

The lin-41 RBCC gene acts in the C. elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor.

Null mutations in the C. elegans heterochronic gene lin-41 cause precocious expression of adult fates at larval stages. Increased lin-41 activity causes the opposite phenotype, reiteration of larval fates. let-7 mutations cause similar reiterated heterochronic phenotypes that are suppressed by lin-41 mutations, showing that lin-41 is negatively regulated by let-7. lin-41 negatively regulates the timing of LIN-29 adult specification transcription factor expression. lin-41 encodes an RBCC protein, and two elements in the lin-413'UTR are complementary to the 21 nucleotide let-7 regulatory RNA. A lin-41::GFP fusion gene is downregulated in the tissues affected by lin-41 at the time that the let-7 regulatory RNA is upregulated. We suggest that late larval activation of let-7 RNA expression downregulates LIN-41 to relieve inhibition of lin-29.

3' Untranslated Regions↗
PubMed1999

Reverse genetic analysis of Caenorhabditis elegans presenilins reveals redundant but unequal roles for sel-12 and hop-1 in Notch-pathway signaling.

Mutations in the human presenilin genes PS1 and PS2 cause early-onset Alzheimer's disease. Studies in Caenorhabditis elegans and in mice indicate that one function of presenilin genes is to facilitate Notch-pathway signaling. Notably, mutations in the C. elegans presenilin gene sel-12 reduce signaling through an activated version of the Notch receptor LIN-12. To investigate the function of a second C. elegans presenilin gene hop-1 and to examine possible genetic interactions between hop-1 and sel-12, we used a reverse genetic strategy to isolate deletion alleles of both loci. Animals bearing both hop-1 and sel-12 deletions displayed new phenotypes not observed in animals bearing either single deletion. These new phenotypes-germ-line proliferation defects, maternal-effect embryonic lethality, and somatic gonad defects-resemble those resulting from a reduction in signaling through the C. elegans Notch receptors GLP-1 and LIN-12. Thus SEL-12 and HOP-1 appear to function redundantly in promoting Notch-pathway signaling. Phenotypic analyses of hop-1 and sel-12 single and double mutant animals suggest that sel-12 provides more presenilin function than does hop-1.

Animals↗
PubMed1999

High-throughput isolation of Caenorhabditis elegans deletion mutants.

The nematode Caenorhabditis elegans is the first animal whose genome is completely sequenced, providing a rich source of gene information relevant to metazoan biology and human disease. This abundant sequence information permits a broad-based gene inactivation approach in C. elegans, in which chemically mutagenized nematode populations are screened by PCR for deletion mutations in a specific targeted gene. By handling mutagenized worm growth, genomic DNA templates, PCR screens, and mutant recovery all in 96-well microtiter plates, we have scaled up this approach to isolate deletion mutations in >100 genes to date. Four chemical mutagens, including ethyl methane sulfonate, ethlynitrosourea, diepoxyoctane, and ultraviolet-activated trimethylpsoralen, induced detectable deletions at comparable frequencies. The deletions averaged approximately 1400 bp in size when using a approximately 3 kb screening window. The vast majority of detected deletions removed portions of one or more exons, likely resulting in loss of gene function. This approach requires only the knowledge of a target gene sequence and a suitable mutagen, and thus provides a scalable systematic approach to gene inactivation for any organism that can be handled in high density arrays.

Algorithms↗
PubMed1997

Harvesting in discrete-time predator-prey systems.

Fisheries for assemblages of interacting species with seasonal recruitment occur throughout temperate and boreal regions of the world ocean. Such systems are conveniently modeled within a difference-equation framework. Here, we examine the dynamic behavior of discrete-time models for an exploited predator-prey system. We contrast the dynamic properties of an aggregate production model and an age-structured model in which recruitment and mortality are explicitly considered. The joint effects of harvesting and interspecific interactions on the stability of the system are defined and contrasted with results for single species systems. We demonstrate that harvesting is a potentially stabilizing factor in the production model and in an age-structured model in which juveniles are harvested and that the relative magnitude of the interaction between predator and prey strongly affects the exploitation levels at which stabilization occurs. In contrast, harvesting is potentially destabilizing (i.e., results in complex dynamics) in an age-structured model with harvesting of adults only; again, the magnitude of the interaction determines the stability boundaries, with stronger interactions leading to a broader range of stable parameter space. In both the aggregate production model and the age-structured model with harvesting of juvenile predator and prey, exploitation effectively reduces the intrinsic rate of increase of the populations; for prey, this effect is amplified by high predation mortality rates. Sustainable levels of exploitation for both predators and prey are lower for the case where juveniles are harvested. Predators and resource harvesters can be viewed as competitors for the prey, and sustainable harvest levels are directly affected by the magnitude of predation mortality. These considerations expand the scope of issues to be resolved in fishery management to include factors such as trade-offs between mean yield and the potential for intrinsic variability and the role of predator-prey interactions in shaping the dynamics of exploited systems.

Age Factors↗
PubMed1996

The Caenorhabditis elegans gene sem-4 controls neuronal and mesodermal cell development and encodes a zinc finger protein.

Neuronal and mesodermal cell types are generated in separate cell lineages during the larval development of Caenorhabditis elegans. Here we demonstrate that the gene sem-4 is required in both types of lineages for the normal development of neuronal and mesodermal cell types. The sem-4 gene encodes a protein containing seven zinc finger motifs of the C2H2 class, four of which are arranged in two pairs widely separated in the primary sequence of the protein. These pairs of zinc fingers are similar to pairs of zinc fingers in the protein encoded by the Drosophila homeotic gene spalt and in the human transcription factor PRDII-BF1. Analysis of sem-4 alleles suggests that different zinc fingers in the SEM-4 protein may function differentially in neuronal and mesodermal cell types. We propose that sem-4 interacts with different transcription factors in different cell types to control the transcription of genes that function in the processes of neuronal and mesodermal cell development.

Alleles↗
PubMed1991

An assessment of the maximum sustainable yield of ivory from African elephant populations.

A general, logistic population model is used to explore the dynamics of harvested elephant populations. The model includes two features peculiar to elephant populations and the harvesting of ivory. First, because of the shape of the growth curve of tusks with age, the conversion factor that relates the number of elephants killed to the ivory yield in weight is not constant, but a function of the population size. Second, tusks from animals that die from natural causes can be retrieved and included in the total yield of ivory. The implications of the relationship between tusk size and age of an animal on the maximum sustainable yield in terms of ivory tonnage and in terms of the number of tusks are explored. The nonequilibrium implications of the tusk growth curve on the population dynamics under different harvesting strategies are also investigated. Results indicate that the maximum sustainable yield is achieved at very low harvest rates with population levels close to the pristine equilibrium. When tusks from animals that die of natural causes are included in the harvest, the maximum yield may, depending on the mortality and recruitment parameters, occur when there is no direct harvest.

Africa↗
PubMed1988

Impermeant potential-sensitive oxonol dyes: II. The dependence of the absorption signal on the length of alkyl substituents attached to the dye.

We have measured the potential-dependent light absorption changes of 43 impermeant oxonol dyes with an oxidized cholesterol bilayer lipid membrane system. The size of the signal is strongly dependent on the chain length of alkyl groups attached to the chromophore. Dye molecules with intermediate chain lengths give the largest signals. To better understand the dependence of the absorbance signal on alkyl chain length, a simple equilibrium thermodynamic analysis has been derived. The analysis uses the free energy of dye binding to the membrane and the "on-off" model (E.B. George et al., J. Membrane Biol., 103:245-253, 1988a) for the potential-sensing mechanism. In this model, a population of dye molecules in nonpolar membrane binding sites is in a potential-dependent equilibrium with a second population of dye that resides in an unstirred layer adjacent to the membrane. Dye in the unstirred layer is in a separate equilibrium with dye in the bulk bathing solution. The equilibrium binding theory predicts a "sigmoidally shaped" increase in signal with increasing alkyl chain length, even for very nonpolar dyes. We suggest that aggregation of the more hydrophobic dyes in the membrane bathing solution may be responsible for their low signals, which are not predicted by the theory.

Adsorption↗
PubMed1988

Impermeant potential-sensitive oxonol dyes: I. Evidence for an "on-off" mechanism.

This series of papers addresses the mechanism by which certain impermeant oxonol dyes respond to membrane-potential changes, denoted delta Em. Hemispherical oxidized cholesterol bilayer membranes provided a controlled model membrane system for determining the dependence of the light absorption signal from the dye on parameters such as the wavelength and polarization of the light illuminating the membrane, the structure of the dye, and delta Em. This paper is concerned with the determination and analysis of absorption spectral changes of the dye RGA461 during trains of step changes of Em. The wavelength dependence of the absorption signal is consistent with an "on-off" mechanism in which dye molecules are driven by potential changes between an aqueous region just off the membrane and a relatively nonpolar binding site on the membrane. Polarization data indicate that dye molecules in the membrane site tend to orient with the long axis of the chromophore perpendicular to the surface of the membrane. Experiments with hyperpolarized human red blood cells confirmed that the impermeant oxonols undergo a potential-dependent partition between the membrane and the bathing medium.

Benzenesulfonates↗
PubMed1988

Increased amounts of HMG-CoA reductase induce "karmellae": a proliferation of stacked membrane pairs surrounding the yeast nucleus.

Overproduction of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in yeast resulted in striking morphological effects on the structure of intracellular membranes. Specifically, stacks of paired membranes closely associated with the nuclear envelope were observed in strains that over-produced the HMG1 isozyme, one of two isozymes for HMG-CoA reductase in yeast. These nuclear-associated, paired membranes have been named "karmellae." In strains that overproduced the HMG1 isozyme, HMG-CoA reductase was present in the karmellar layers. At mitosis, karmellae were asymmetrically segregated: the mother cells inherited all of the karmellae and the daughter cells inherited none. A membranous structure of different morphology was occasionally found in cells that overproduced the HMG2 isozyme. These observations further establish the existence of cellular mechanisms that monitor the levels of membrane proteins and compensate for changes in these levels by inducing synthesis of particular types of membrane.

Cell Nucleus↗