Beiträge zur Kenntnis der Stoffwanderungen bei wachsenden Organismen

Ohne ZusammenfassungDem Andenken Edwin Goldmans gewidmet.     

Zur Funktion des elektrischen Organs von Gnathonemus petersii (Gthr. 1862) (Mormyriformes,Teleostei)

Journal of Comparative Physiology A - In der vorliegenden Arbeit werden Untersuchungen an schwachelektrischen Fischen der Art Gnathonemus petersii (Günther 1862) beschrieben.     

Development of GMP‐1 a molecular chaperone network modulator protecting mitochondrial function and its assessment in fly and mice models of Alzheimer's disease

Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD) and may play an important role in the pathogenesis of disease. It has been shown that amyloid beta peptide (Aβ) and amyloid precursor protein (APP) interact with mitochondria contributing to the mitochondrial dysfunction in AD. Prevention of abnormal protein targeting to mitochondria can protect normal mitochondrial function, increase neuronal survival and at the end, ameliorate symptoms of AD and other neurodegenerative disorders. First steps of mitochondrial protein import are coordinated by molecular chaperones Hsp70 and Hsp90 that bind to the newly synthesized mitochondria‐destined proteins and deliver them to the protein import receptors on the surface of organelle. Here, we have described the development of a novel compound named GMP‐1 that disrupts interactions between Hsp70/Hsp90 molecular chaperones and protein import receptor Tom70. GMP‐1 treatment of SH‐SY5Y cells results in decrease in mitochondria‐associated APP and protects SH‐SY5Y cells from toxic effect of Aβ_1‐42 exposure. Experiments in drosophila and mice models of AD demonstrated neuroprotective effect of GMP‐1 treatment, improvement in memory and behaviour tests as well as restoration of mitochondrial function.     

Requirements for proteolysis during apoptosis.

The key effector proteins of apoptosis are a family of cysteine proteases termed caspases. Following activation of caspases, biochemical events occur that lead to DNA degradation and the characteristic morphological changes associated with apoptosis. Here we show that cytoplasmic extracts activated in vitro by proteinase K were able to cleave the caspase substrate DEVD-7-amino-4-methylcoumarin, while neither proteinase K nor nonactivated extracts were able to do so alone. Caspase-like activity was inhibited by the specific caspase inhibitor DEVD-aldehyde and by the protease inhibitor iodoacetamide, but not by N-ethylmaleimide. When added to isolated nuclei, the activated extracts caused internucleosomal DNA degradation and morphological changes typical of apoptosis. As DNA cleavage and morphological changes could be inhibited by N-ethylmaleimide but not by iodoacetamide, we conclude that during apoptosis, caspase activation causes activation of another cytoplasmic enzyme that can be inhibited by N-ethylmaleimide. Activity of this enzyme is necessary for activation of endonucleases, DNA cleavage, and changes in nuclear morphology.     

Changes in French bean cotyledon composition associated with modulated life-span

The onset of Phaseolus vulgaris L. cotyledon senescence and its characteristics were modulated by irradiance (higher or lower than standard) and by epicotyl decapitation. The cotyledon life-span of 16 d was not influenced by irradiance while decapitation prolonged the life-span to 28 d. The fresh mass of cotyledons, an indicator of organ viability, decreased in a similar manner in all non-decapitated plants, though it was relatively slower in plants grown under a low irradiance (LI). Three days after decapitation the fresh mass of cotyledons increased by one third, a slight decrease was observed on the 21st d, and it lasted until the end of the life span. Deducing from the fall of chlorophyll (Chl) concentration expressed per unit protein, senescence started after the 10th day in non-decapitated plants. Decapitation postponed the onset of senescence until the 21st day. Expression of Chl amount per unit dry mass did not detect any changes in LI plants, hence this parameter can not be used for the assessment of senescence. The measurements of Chl a and b concentrations indicated that the light-harvesting complexes (LHCs) proliferated during ageing and were rapidly destroyed at the onset of senescence. Changes of the concentrations of carotenoids supported the hypothesis of free radicals involvement in senescence. The bean cotyledons responded to free radical production induced under higher irradiance by increased -carotene synthesis. Oxidative damage to galactolipids during senescence was documented by fluorescence measurements. The changes in cotyledon composition were correlated to morphologic changes observed by electron microscopy.     

Daminozide and prohexadione have similar modes of action as inhibitors of the late stages of gibberellin metabolism

One of the effects of daminozide is to retard shoot growth in certain plant species, but its mode of action is unclear. Prohexadione, an acylcyclohexanedione, also causes retardation of shoot growth, but it is active in all plant systems tested so far. This inhibition has been shown to be a result of competition with the natural co-substrate, 2-oxoglutarate, at the active site of hydroxylases involved in the later stages of the gibberellin (GA) biosynthesis pathway. In order to determine the mode of action of daminozide in relation to prohexadione, the potencies of the two retardants as inhibitors of 3β-hydroxylation of GAs in cell-free systems from pumpkin ( Cucurbita maxima ) endosperm and French bean ( Phaseolus coccineus ) cotyledons were studied. Several compounds, related to or representing structural links between daminozide and prohexadione, were also included in this investigation. Daminozide was found to inhibit only the bean 3β-hydroxylase to a significant degree, whereas prohexadione inhibited both the bean and pumpkin enzymes.
Further information was obtained from the GC-MS analysis of GAs found in the newly formed parts of the shoots of peanut seedlings treated with the two compounds. Both growth retardants inhibited the formation of GA₁, whereas its immediate precursor, GA₂₀, accumulated. Furthermore, levels of GA₈ (2β-hydroxy GA₁) were also reduced, but by a smaller relative amount.
These results clearly indicate for the first time that daminozide has the same mode of action as prohexadione in distinct plant species, namely to inhibit the 3β-hydroxylase and, to a lesser extent, the 2β-hydroxylase. This is probably due to the structural similarity of the two inhibitors with 2-oxoglutarate.     

Molecular domestication of mobile elements

Transposable elements are ubiquitous in all organisms and represent a dynamic component of their genomes, causing mutations and thereby genetic variation. Because of their independent and expansive replication strategy, these elements are called selfish and were thought to have no impact on the adaptive evolution of their host organisms. Although most TE-induced mutations seem to exert only negative effects on the fitness of their carrier, recent evidence indicates that in the course of evolution at least some TE-mediated changes have become established features of the host genome. For example, the insertion of TEs may provide novel cis-regulatory regions to preexisting host genes or TE-derived trans-acting factors may undergo a molecular transition into novel host genes through a process described as molecular domestication. The stationary P element related gene clusters of D. guanche, D. madeirensis and D. subobscura provide an excellent model system to study the evolutionary impact of TEs on genome evolution. Each cluster unit consists of a cis-regulating section composed of different insertion sequences followed by the first three exons of a P element that are coding for a 66 kDa ‘repressor-like’ protein. This revised version was published online in August 2006 with corrections to the Cover Date.     

Intracellular Metabolism of 4-Hydroxynonenal in Primary Cultures of Rabbit Synovial Fibroblasts

The intracellular metabolism of 4-hydroxynonenal (HNE), a secondary product of lipid peroxidation and mediator of inflammation, which was found in the joints of patients with rheumatoid arthritis, was investigated in primary cultures of rabbit synovial fibroblasts. A consumption rate of 27.3 nmol/min × 10⁶ cells was measured for the cultivated fibroblasts. It could be shown, that 4-hydroxynonenal enters the synovial fibroblasts and is metabolized mainly oxidatively to 4-hydroxynonenoic acid, intermediates of the tricarboxylic acid cycle and water and by formation of the glutathione-HNE adduct. The share of protein-bound HNE was about up to 8% of the total added HNE after 10 min of incubation. All metabolites accumulates intracellularly within the incubation time except of 4-hydroxynonenal itself. An increase of 4-hydroxynonenoic acid could be detected also extracellularly during the intracellular metabolism of 4-hydroxynonenal. Therefore, an involvement of synovial fibroblasts in the secondary antioxidant defense system of the joints during conditions of higher HNE concentrations like rheumatoid arthritis is suggested. © 1997 Elsevier Science Inc.     

The proboscis of eye-frequenting and piercing Lepidoptera (Insecta)

The external structures of the proboscis are investigated in eye-frequenting species of Noctuidae, Geometridae and Pyralidae by means of scanning electron microscopy. They are compared with non-eye-frequenting representatives of these families. In Noctuidae, highly specialized fruit-piercing, skin-piercing blood-sucking, and sweat-feeding representatives have been included. All hemi- and eulachryphagous species have a soft proboscis tip which is characterized by few sensilla and strongly elongated, dentate plates of the dorsal galeal linkage. The latter structures leave broad gaps between them that lead into the food canal at the tip. This arrangement permits the uptake of fluid suspensions such as lachrymal fluid, wound exudates and pus. The modified dorsal galeal linkage is regarded as an adaptation for this highly derived feeding habit. The rough surface of the proboscis is likely to cause irritation and possible mechanical damage to the conjunctiva and cornea which results in an increased lachrymal flow and production of pus. In contrast to fruit-piercing and skin-piercing Noctuidae, there are no erectile structures on the proboscis of eye-frequenting species.—The comparison with related non-eye-frequenting species demonstrates that the particular morphology of the proboscis tip in lachryphagous moths evolved convergently in different families of Leipdoptera.     

Twenty-Four-Hour Analysis of Lymphocyte Subpopulations and Cytokines in Healthy Subjects

Fourteen healthy male subjects were studied under resting conditions for 24 or 48 h. The 24-h variations of ACTH and Cortisol with peaks in the morning were confirmed. Interleukin-2 release was profoundly reduced at 8:00. A cosine function could be fitted to lymphocyte subpopulations including populations such as T_{helper-memory} cells (CD4+/CDw29) and HLA-DR-bearing cells displaying peak values during the night and minimal values at 9:00. Numbers of natural killer cells (CD57) were not correlated to other cell populations and no rhythm could be detected. Interleukin-1 (3 was detectable in some plasma samples only with an interleukin-1 ELISA kit (Quantakine HS^R), but neither a 24-h rhythm nor reproducible results could be obtained for day 1 and 2 of the study. We conclude that there might be a temporal relation between the parameters analyzed: Higher levels of endogenous Cortisol in the morning hours probably inhibit the cellular interleukin-2 synthesis and are responsible for an enhanced migration of lymphocytes from the blood into the tissues of the reticuloendothelial system. These results might be indicative of a circadian organization of the immune system which may play a role in both physiological and pathological functioning. (Chronobiology International, 13(6), 423-434, 1996)