Mitochondriale Erkrankungen

As outlined in other articles of this issue mitochondrial medicine is a complex area in clinical genetics. Due to the wide variability of clinical presentation in both pediatric and adult patients there are frequent constellations of symptoms that may suggest an underlying mitochondrial disorder. This is a challenge in genetic counseling because basically all patterns of inheritance have to be taken into account??including maternal transmission??but a straightforward genetic testing to confirm or exclude the suggested diagnosis is hampered by the immense genetic heterogeneity of the mitochondrial disease spectrum. This article focuses on a diagnostic strategy and specific aspects of genetic counseling in mitochondrial disorders.     

Ballooning dispersal using silk: world fauna, phylogenies, genetics and models

Aerial dispersal using silk ('ballooning') has evolved in spiders (Araneae), spider mites (Acari) and in the larvae of moths (Lepidoptera). Since the 17th century, over 500 observations of ballooning behaviours have been published, yet there is an absence of any evolutionary synthesis of these data. In this paper the literature is reviewed, extensively documenting the known world fauna that balloon and the principal behaviours involved. This knowledge is then incorporated into the current evolutionary phylogenies to examine how ballooning might have arisen. Whilst it is possible that ballooning co-evolved with silk and emerged as early as the Devonian (410-355 mya), it is arguably more likely that ballooning evolved in parallel with deciduous trees, herbaceous annuals and grasses in the Cretaceous (135-65 mya). During this period, temporal (e.g. bud burst, chlorophyll thresholds) and spatial (e.g. herbivory, trampling) heterogeneities in habitat structuring predominated and intensified into the Cenozoic (65 mya to the present). It is hypothesized that from the ancestral launch mechanism known as 'suspended ballooning', widely used by individuals in plant canopies, 'tip-toe' and 'rearing' take-off behaviours were strongly selected for as habitats changed. It is contended that ballooning behaviour in all three orders can be described as a mixed Evolutionary Stable Strategy. This comprises individual bet-hedging due to habitat unpredictability, giving an underlying randomness to individual ballooning, with adjustments to the individual ballooning probability being conferred by more predictable habitat changes or colonization strategies. Finally, current methods used to study ballooning, including modelling and genetic research, are illustrated and an indication of future prospects given.     

Morphogenesis and fate of the residual body in human spermiogenesis

Summary In the human testis the formation of the residual body of the spermatid and its morphological changes during and after spermiation were studied by means of electron microscopy. The caudal cytoplasmic mass of the late spermatid contains a Golgi complex, mitochondria, annulate lamellae, a chromatoid body, flower-like structures, ribosomes, a few large vacuoles, myelin-like membrane profiles and sporadic lipid droplets. When, by detachment of the caudal cytoplasm from the free spermatozoon, the residual body is formed, the chromatoid body has disappeared; the mitochondria are clustered peripherally; the ribosomes appear as a single complex in contact with a large vacuole containing granular material; in place of the Golgi complex aggregations of vesicles are present. The lipid droplets remain unchanged. The residual bodies or their fragments are either extruded via the seminiferous tubular lumen into the excurrent ducts or they are engulfed by Sertoli cells where in the supranuclear region the successive steps of decomposition can be observed. The participation of the various constituents in the disintegration of the residual body is discussed. In contrast to other mammalian species, in man the sporadic lipid droplets seem to be of minor importance in the fate of the residual body.     

The effect of food deprivation on aeronautic dispersal behaviour (ballooning) inErigone spp. spiders

Adult male and femaleErigone spp. (Araneae: Linyphiidae) spiders were kept without food for several days. Groups of spiders were tested for aeronautic dispersal behaviour (ballooning) in the laboratory. The validity of the assessment method was tested. In comparison with satiated spiders, the starved group exhibited an increased tendency to engage in aeronautic dispersal behaviour. A consistent trend for increased dispersal behaviour was detected in three independent experiments. Implications for spiders in agro-ecosystems are discussed briefly.     

Giant cells fromSaccharomyces uvarum grown after X-irradiation

Yeast cells, Saccharomyces uvarum, were irradiated with X-rays and grown in liquid suspension. Glucose as the only carbon source was limited to 12.5 mM. Under these conditions giant cells are formed. Cell number, glucose utilization, ethanol production and oxygen consumption are measured during the time of growth. The mean weight of single cells in the stationary phase increases up to 75 krad and is not due to an uptake of water. In irradiated cultures oxygen consumption and glucose utilization per cell are higher than in control cells. The data demonstrate that synthesis- and energy-metabolism during the formation of non-dividing, radiation-induced giant cells is increased.     

Automatic morphometric analysis of retrograde changes in the nucleus n. facialis at different ontogenetic stages in the rat

Summary The grey level index (= GLI) and the fresh volume were determined with the image analyser Micro-Videomat for the nucl. n. facialis after axotomy of the left n. facialis. The experiments were performed on 10 rats in different stages of ontogenesis. The GLI is a quantitative parameter which could be quickly obtained and which demonstrated quantitative changes during retrograde reaction in the respective centres. A decrease in the fresh volumes of the affected nucl. n. facialis could also be demonstrated. The meaning of GLI is discussed.Supported by Deutsche Forschungsgemeinschaft grants Kr 289/10 and Zi 192/1Dedicated to Prof. Dr. H. Leonhardt on the occasion of his 60th birthday     

PKCalpha regulates phosphorylation and enzymatic activity of cPLA2 in vitro and in activated human monocytes

Phospholipases A(2) (PLA(2)) are potent regulators of the inflammatory response. We have observed that Group IV cPLA(2) activity is required for the production of superoxide anion (O(2)(-)) in human monocytes [Li Q., Cathcart M.K. J. Biol. Chem. 272 (4) (1997) 2404-2411.]. We have previously identified PKCalpha as a kinase pathway required for monocyte O(2)(-) production [Li Q., Cathcart M.K. J. Biol. Chem. 269 (26) (1994) 17508-17515.]. We therefore investigated the potential interaction between PKCalpha and cPLA(2) by evaluating the requirement for specific PKC isoenzymes in the process of activating cPLA(2) enzymatic activity and protein phosphorylation upon monocyte activation. We first showed that general PKC inhibitors and antisense oligodeoxyribonucleotides (ODN) to the cPKC group of PKC enzymes inhibited cPLA(2) activity. To distinguish between PKCalpha and PKCbeta isoenzymes in regulating cPLA(2) protein phosphorylation and enzymatic activity, we employed our previously characterized PKCalpha or PKCbeta isoenzyme-specific antisense ODN [Li Q., Subbulakshmi V., Fields A.P., Murray, N.R., Cathcart M.K., J. Biol. Chem. 274 (6) (1999) 3764-3771]. Suppression of PKCalpha expression, but not PKCbeta expression, inhibited cPLA(2) protein phosphorylation and enzymatic activity. Additional studies ruled out a contribution by Erk1/2 to cPLA(2) phosphorylation and activation. We also found that cPLA(2) co-immunoprecipitated with PKCalpha and vice versa. In vitro studies demonstrated that PKCalpha could directly phosphorylate cPLA(2).and enhance enzymatic activity. Finally, we showed that addition of arachidonic acid restored the production of O(2)(-) in monocytes defective in either PKCalpha or cPLA(2) expression. Taken together, our data suggest that PKCalpha, but not PKCbeta, is the predominant cPKC isoenzyme required for cPLA(2) protein phosphorylation and maximal induction of cPLA(2) enzymatic activity upon activation of human monocytes. Our data also support the concept that the requirements for PKCalpha and cPLA(2) in O(2)(-) generation are solely due to their seminal role in generating arachidonic acid.