Computational genes: a tool for molecular diagnosis and therapy of aberrant mutational phenotype

Background  

A finite state machine manipulating information-carrying DNA strands can be used to perform autonomous molecular-scale computations at the cellular level.     

Effects of monovalent cations on red cell shape and size

Human erythrocytes were incubated in isotonic solutions of different monovalent cations. The apparent size of the red cells measured on scanning electron microscopic pictures decreases in the order Li+ greater than Na+ = K+ greater than Rb+. These differences in size are abolished after pretreatment with trypsin, which removes a large part of the charges associated with membrane glycoproteins. Shape alterations are also observed. Normal biconcave shapes are visible after Na+ or K+ incubation, whereas Li+ leads to flabby, flattened cells with a certain tendency to crenation, and Rb+ causes more pronounced biconcavity with a certain tendency to cupping. The overall effects of pretreatment with trypsin are similar to those of Li+. Our results provide evidence that the electrostatic repulsion of glycoproteins and other charged membrane components may play an essential role in maintaining red cell shape.     

Die praktische Belevanz des McNemar-Tests

By application of the McNemar-Test the question of the practical relevance (practical significance) of the resulting test statistic generally arises. An analogy to the t-Test for paired measurements gives some measure for the practical relevance. The evaluation of this relevance is based upon suggestions made by COHEN (1977).     

Referate

Ohne Zusammenfassung     

Light-dependent repetitive Ca2+ spikes induced by extracellular application of neomycin in honeybee drone photoreceptors

Photoreceptor cells of the honeybee drone fire, in the presence of the polycationic aminoglycoside neomycin, repetitive slow spike-like potentials superimposed on the receptor potential plateau phase. We have used conventional intracellular recordings and microfluorometric intracellular Ca²⁺ measurements to characterize these spike potentials. We have shown that the spike frequency increases in a light-intensity-dependent manner. The spikes are fired only when light stimuli depolarize the cell from a resting potential of −50 to −60 mV to at least −40 to −45 mV; they are tetrodotoxin insensitive and blocked by the Ca²⁺ channel blockers Ni²⁺, Cd²⁺, ω-agatoxin TK, verapamil and methoxyverapamil. Depolarization of the photoreceptors with high extracellular K⁺ in the presence of neomycin in darkness does not generate spikes. Small intracellular Ca²⁺ oscillations superimposed on the plateau phase of the light-induced increase in intracellular free Ca²⁺ concentration have a similar temporal pattern as the spike-like potentials. We conclude that the spike-like potentials require stimulation by light and are generated by voltage-dependent Ca²⁺ channels localized on the soma of the photoreceptors, distal to the basal lamina. Accepted: 16 March 2000     

Actions of neomycin on electrical light responses, Ca2+ release, and intracellular Ca2+ changes in photoreceptors of the honeybee drone

Neomycin, known to inhibit phospholipase C-mediated IP3 formation, was applied in the bath or injected into cells and its effects on electrical light responses were analyzed. Neomycin effects on inositol 1,4,5-trisphosphate- and Ca2+-induced Ca2+ release from the endoplasmic reticulum and/or the light-induced Ca2+ elevation were also studied. Neomycin (0.5 mmol x l(-1)) blocked inositol 1,4,5-trisphosphate-, caffeine-, and Ca2+-induced Ca2+ release. Bath application of neomycin decreased the sensitivity to 20-ms light flashes by a factor of up to 100 and slowed the kinetics of dim flash responses. Intracellularly injected neomycin desensitized the photoreceptors more than 1 log unit, increased the latency, and slowed the rate of rise of the light response. Neomycin (0.5 mmol x l(-1)) in the bath delayed and reduced the transient component of responses to 1-s steps of light at intermediate intensities. It also decreased and slowed the light-induced, and it blocked the caffeine-induced intracellular Ca2+ elevation. The combined pharmacological effects of neomycin are suggested to decrease the Ca2+-mediated amplification of the phototransduction cascade and the Ca2+-mediated acceleration of processes determining the kinetics of light responses.     

The detection of chemically induced aneuploidy in Saccharomyces cerevisiae: an assessment of mitotic and meiotic systems

Several systems have been evaluated for their ability to detect aneuploidy. Chromosome gain can be detected in mitotic haploid cells as well as meiotically derived haploid spores. Both chromosome gain and loss are detectable in mitotic diploid cells. Several chemicals have been identified that clearly induce aneuploidy in at least one or more of the systems.     

Cross-Scale Responses of Biodiversity to Hurricane and Anthropogenic Disturbance in a Tropical Forest

Abstract In studies of biodiversity, considerations of scale—the spatial or temporal domain to which data provide inference—are important because of the non-arithmetic manner in which species richness increases with area (and total abundance) and because fine-scale mechanisms (for example, recruitment, growth, and mortality of species) can interact with broad scale patterns (for example, habitat patch configuration) to influence dynamics in space and time. The key to understanding these dynamics is to consider patterns of environmental heterogeneity, including patterns produced by natural and anthropogenic disturbance. We studied how spatial variation in three aspects of biodiversity of terrestrial gastropods (species richness, species diversity, and nestedness) on the 16-ha Luquillo Forest Dynamics Plot (LFDP) in a tropical forest of Puerto Rico was affected by disturbance caused by Hurricanes Hugo and Georges, as well as by patterns of historic land use. Hurricane-induced changes in spatial organization of species richness differed from those for species diversity. The gamma components of species richness changed after the hurricanes and were significantly different between Hurricanes Hugo and Georges. Alpha and two beta components of species richness, one related to turnover among sites within areas of similar land use and one related to variation among areas of different land use, varied randomly over time after both hurricanes. In contrast, gamma components of species diversity decreased in indistinguishable manners after both hurricanes, whereas the rates of change in the alpha component of species diversity differed between hurricanes. Beta components of diversity related to turnover among sites declined after both hurricanes in a consistent fashion. Those related to turnover among areas with different historic land uses varied stochastically. The immediate effect of hurricanes was to reduce nestedness of gastropod assemblages. Thereafter, nestedness increased during post-hurricane secondary succession, and did so in the same way, regardless of patterns of historic land use. The rates of change in degree of nestedness during secondary succession were different after each hurricane as a result of differences in the severity and extent of the hurricane-induced damage. Our analyses quantified temporal changes in the spatial organization of biodiversity of gastropod assemblages during forest recovery from hurricane-induced damage in areas that had experienced different patterns of historic human land use, and documented the dependence of biodiversity on spatial scale. We hypothesize that cross-scale interactions, likely those between the local demographics of species at the fine scale and the landscape configuration of patches at the broad scale, play a dominant role in affecting critical transfer processes, such as dispersal, and its interrelationship with aspects of biodiversity. Cross-scale interactions have significant implications for the conservation of biodiversity, as the greatest threats to biodiversity arise from habitat modification and fragmentation associated with disturbance arising from human activities.     

Chorionic Gonadotropin and Its Receptor Are Both Expressed in Human Retina,Possible Implications in Normal and Pathological Conditions

Extra-gonadal role of gonadotropins has been re-evaluated over the last 20 years. In addition to pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), the CNS has been clearly identified as a source of hCG acting locally to influence behaviour. Here we demonstrated that human retina is producing this gonadotropin that acts as a neuroactive molecule. Müller glial and retinal pigmented epithelial (RPE) cells are producing hCG that may affects neighbour cells expressing its receptor, namely cone photoreceptors. It was previously described that amacrine and retinal ganglion (RGC) cells are targets of the gonadotropin releasing hormone that control the secretion of all gonadotropins. Therefore our findings suggest that a complex neuroendocrine circuit exists in the retina, involving hCG secreting cells (glial and RPE), hCG targets (photoreceptors) and hCG-release controlling cells (amacrine and RGC). The exact physiological functions of this circuit have still to be identified, but the proliferation of photoreceptor-derived tumor induced by hCG demonstrated the need to control this neuroendocrine loop.