Pteridines are produced during interleukin 2-induced T-cell proliferation and modulate transmission of this signal

Pteridine levels of interleukin 2 (IL-2) receptor+ T-cell populations have been determined by HPLC after iodine oxidation; neopterin was monitored in the culture supernatants by radio-immunoassay. Upon addition of IL-2, cellular levels of biopterin and 6-hydroxymethylpterin rise transiently from 0.02 to 0.9 pmol/10(6) cells, cellular levels of neopterin from 1.5 to 4.1 pmol/10(6) cells. They peak at 8 and 13 h, respectively, after exposure to IL-2. Neopterin is not accumulated in the culture supernatant. DNA synthesis in T cells begins 10-12 h after adding the lymphokine and the portion of cells that undergo S-phase transition gradually increases during the subsequent 10 h. Entry into DNA synthesis phase is markedly accelerated if IL-2 is supplied together with tetrahydrobiopterin (0.8-1.6 X 10(-6) M) and the kinetics of entry into the S-phase transition during the period of 6-20 h become linear. This indicates that tetrahydrobiopterin modulation of IL-2 activity (Ziegler, I. et al. Naturwiss 72 (1985) 330) is an early event occurring during IL-2 signal transmission.     

Increased Soil Frost Versus Summer Drought as Drivers of Plant Biomass Responses to Reduced Precipitation: Results from a Globally Coordinated Field Experiment

Reduced precipitation treatments often are used in field experiments to explore the effects of drought on plant productivity and species composition. However, in seasonally snow-covered regions reduced precipitation also reduces snow cover, which can increase soil frost depth, decrease minimum soil temperatures and increase soil freeze–thaw cycles. Therefore, in addition to the effects of reduced precipitation on plants via drought, freezing damage to overwintering plant tissues at or below the soil surface could further affect plant productivity and relative species abundances during the growing season. We examined the effects of both reduced rainfall (via rain-out shelters) and reduced snow cover (via snow removal) at 13 sites globally (primarily grasslands) within the framework of the International Drought Experiment, a coordinated distributed experiment. Plant cover was estimated at the species level, and aboveground biomass was quantified at the functional group level. Among sites, we observed a negative correlation between the snow removal effect on minimum soil temperature and plant biomass production the next growing season. Three sites exhibited significant rain-out shelter effects on plant productivity, but there was no correlation among sites between the rain-out shelter effect on minimum soil moisture and plant biomass. There was no interaction between snow removal and rain-out shelters for plant biomass, although these two factors only exhibited significant effects simultaneously for a single site. Overall, our results reveal that reduced snowfall, when it decreases minimum soil temperatures, can be an important component of the total effect of reduced precipitation on plant productivity.     

A structural step into the SRP cycle

Co-translational targeting of secretory and membrane proteins to the translocation machinery is mediated by the signal recognition particle (SRP) and its membrane-bound receptor (SR) in all three domains of life. Although the overall composition of the SRP system differs, the central ribonucleoprotein core and the general mechanism of GTP-dependent targeting are highly conserved. Recently, structural studies have contributed significantly to our understanding of the molecular organization of SRP. SRP appears as a structurally flexible particle modulated and regulated by its interactions with the ribosome-nascent chain complex, the translocon and the SR. The SRP core (SRP54 with its cognate RNA binding site) plays a central role in these interactions and communicates the different binding states by long-range interdomain communication. Based on recent structures of SRP54, a model for signal peptide binding stimulating the GTP affinity during the first step of the SRP cycle is presented. The model is placed in the context of the recent structures of mammalian SRP bound to a ribosome-nascent chain complex and of a subcomplex of SRP-SR.     

The effect of SO 3 -- on the activity of ribulose-1,5-diphosphate carboxylase in isolated spinach chloroplasts

Summary SO ₃ ^-- inhibits the activity of ribulose-1,5-diphosphate carboxylase in isolated spinach chloroplasts. It shows a non-competitive inhibition pattern with respect to ribulose-1,5-diphosphate and Mg⁺⁺ but a competitive one with respect to HCO ₃ ^- . The K _i -values are 14 mM SO ₃ ^-- and 9.5 mM SO ₃ ^- respectively for the non-competitive inhibition but only 3.0 mM SO ₃ ^-- in the case of competitive inhibition with HCO ₃ ^-- as a substrate. Thus it is concluded that the competitive inhibition type will predominate at low SO ₃ ^-- and low internal CO₂ concentrations.The abbreviations used RuDph ribulose-1,5-diphosphate - DTT dithiothreitol - EDTA ethylenediaminetetraacetate     

Copper��Dopamine Complex Induces Mitochondrial Autophagy Preceding Caspase-independent Apoptotic Cell Death

Parkinsonism is one of the major neurological symptoms in Wilson disease, and young workers who worked in the copper smelting industry also developed Parkinsonism. We have reported the specific neurotoxic action of copper·dopamine complex in neurons with dopamine uptake. Copper·dopamine complex (100 μm) induces cell death in RCSN-3 cells by disrupting the cellular redox state, as demonstrated by a 1.9-fold increase in oxidized glutathione levels and a 56% cell death inhibition in the presence of 500 μm ascorbic acid; disruption of mitochondrial membrane potential with a spherical shape and well preserved morphology determined by transmission electron microscopy; inhibition (72%, p < 0.001) of phosphatidylserine externalization with 5 μm cyclosporine A; lack of caspase-3 activation; formation of autophagic vacuoles containing mitochondria after 2 h; transfection of cells with green fluorescent protein-light chain 3 plasmid showing that 68% of cells presented autophagosome vacuoles; colocalization of positive staining for green fluorescent protein-light chain 3 and Rhod-2AM, a selective indicator of mitochondrial calcium; and DNA laddering after 12-h incubation. These results suggest that the copper·dopamine complex induces mitochondrial autophagy followed by caspase-3-independent apoptotic cell death. However, a different cell death mechanism was observed when 100 μm copper·dopamine complex was incubated in the presence of 100 μm dicoumarol, an inhibitor of NAD(P)H quinone:oxidoreductase (EC 1.6.99.2, also known as DT-diaphorase and NQ01), because a more extensive and rapid cell death was observed. In addition, cyclosporine A had no effect on phosphatidylserine externalization, significant portions of compact chromatin were observed within a vacuolated nuclear membrane, DNA laddering was less pronounced, the mitochondria morphology was more affected, and the number of cells with autophagic vacuoles was a near 4-fold less.A possible role of copper in the neurodegeneration of dopaminergic neurons is supported by the fact that patients with neurological Wilson disease, a copper deposition disorder, display a number of extrapyramidal motor symptoms, including Parkinsonism. The cerebral manifestations in neurological Wilson disease are expressed as bradykinesia, rigidity, tremor, dyskinesia, and dysarthria (1). It has been proposed that neurological Wilson disease can be assigned to the group of secondary Parkinsonian syndromes (2). Interestingly, young workers who worked in the copper smelting industry also developed Parkinsonism (3).Studies performed in rats showed copper (Cu²⁺)-induced degeneration of dopaminergic neurons in the nigrostriatal system. Likewise, it was described that copper neurotoxicity in rat substantia nigra and striatum is dependent on NAD(P)H dehydrogenase inhibition (4, 5). All of these results support a possible role for copper in the neurodegeneration of dopaminergic neurons.The general mechanism of toxicity, induced by the reduced form of copper (Cu⁺) catalyzing the formation of hydroxyl radicals in the presence of hydrogen peroxide through the Fenton reaction, cannot explain the specific degeneration of dopaminergic neurons in Parkinsonism induced in neurological Wilson disease, or in miners working in the copper smelting industry. The selective action of copper can be explained by the ability of copper to form a complex with dopamine, allowing this metal to be transported by cells that have the ability to take up dopamine (6). This specific neurotoxic action of copper in neurons with dopamine uptake is dependent on (i) the ability of copper to form a complex with dopamine (Cu·DA)² (6, 7), (ii) uptake of Cu·DA complex by dopamine transporters, (iii) oxidation of dopamine to aminochrome, and (iv) one-electron reduction of aminochrome by inhibiting NAD(P)H dehydrogenase (6). These findings may explain the selective neurotoxic action of copper in the brain, but they do not explain the cell death mechanism.Currently, cell death is divided into three categories: apoptosis, autophagy, and necrosis. At the current time, only apoptosis and autophagic cell death are generally accepted as being legitimate forms of programmed cell death. Alternative models of cell death have therefore been proposed, including para-apoptosis, mitotic catastrophe, oncosis, and pyroptosis (8–12). Necrosis is characterized mostly by the absence of caspase activation, cytochrome c release, and DNA oligonucleosomal fragmentation. Apoptotic cells are characterized by the formation of blebs, chromatin condensation, DNA oligonucleosomal fragmentation, and exposure of phosphatidylserine on the external membrane. This mode of cell death can be dependent or independent of activation of caspases (13). On the other hand, autophagy can be distinguished from apoptosis by sequestration of bulk cytoplasm and organelles in double or multimembrane autophagic vacuoles that then fuse with the lysosomal system. Some of these described mechanisms are related to neurological diseases such as Parkinson disease (14, 15). Cells can use different methods to activate their own destruction, and more than one death program may be activated at the same time (16, 17).The purpose of this study was to examine the Cu·DA complex-induced cell death mechanism in RCSN-3 cells, a cell line that expresses dopamine, norepinephrine, and serotonin transporters (18, 19).     

Different forms of 130 kD connective tissue protein are specific for boundaries in the nervous system and basement membrane of muscle cells in leech

The nervous system and muscle tissue of the leech express two different organ-specific forms of connective tissue protein. The nervous system-specific form appears in regional boundaries separating cell bodies, axonal tracts and areas of the neuropile during late embryogenesis. In contrast, the muscle-specific form appears earlier during development in the basement membrane of muscle cells. In extraction experiments both forms behave like extracellular matrix proteins and because of their molecular weight, are considered members of a group of cell type-specific 130 kD proteins (leech gp130s). How ever, the two forms differ in their posttranslational modification. As determined by Con A and lentil lectin affinity chromatography, only the nervous system-specific, but not the muscle-specific form, has fucosylated and high mannose N-linked carbohydrates. These differences in the developmental onset and glycosylation suggest that nervous system-specific and muscle-specific connective tissue proteins are regulated differently and participate in different molecular interactions. © 1993 John Wiley & Sons, Inc.     

Distribution and diel migration of macroinvertebrates within dense submerged vegetation

1. We studied vertical and horizontal distribution of macroinvertebrates within a dense stand of Chara spp. in Lake Krankesjön, southern Sweden. Invertebrates were sampled at three depths within the vegetation and at three distances from the vegetation edge during day and night in July and August. Corresponding samples of oxygen content of the water were taken.
2. The densities (number of invertebrates per unit plant biomass) of most invertebrate taxa were generally lower in the upper layers of the vegetation than in the layers close to the sediment. The densities of several taxa ( Asellus aquaticus , Cloëon sp. and Polycentropodidae), as well as total density of invertebrates, were higher at the edge than in the innermost parts of the macrophyte stand, whereas snail densities generally were highest at the innermost sites.
3. Densities of A. aquaticus , Chironomidae larvae and Helobdella stagnalis generally increased at night. These taxa appear to undertake a diel vertical migration within the vegetation, towards, or even down to the sediment in daytime and up into the vegetation, in some cases to the vegetation surface, at night. Factors underlying the diel vertical migration are discussed, as are their ecological consequences.     

Ist eine Unterscheidung der Genotypen der Blutgruppe A mit Hilfe eines thermodynamischen Effektes möglich?

Zusammenfassung Der Kern eines von Filitti-Wurmser u. Mitarb. seit 1946 veröffentlichten Verfahrens, das mit Hilfe eines thermodynamischen Effekts eine Differenzierung der Genotypen der Blutgruppe A erlauben soll, erwies sich bei Nachprüfung der wesentlichen Einzelschritte der Methode als ungeeignet: weder lassen sich A₁A₁-Seren von A₁O-Seren unterscheiden, noch sind die Resultate überhaupt reproduzierbar.

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Summary The essentials of a method for the distinction of blood group A genotypes by their thermodynamic properties, published by Filitti-Wurmser and co-workers, were checked. By investigation of its chief details, this method was proven to be disappointing. Neither can A₁A₁ sera be distinguished from A₁O sera nor are the results reproducible at all.

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Résumé La substance d'une méthode — publiée depuis 1946 de Filitti-Wurmser et coopérateurs — laquelle doit permettre une différenciation des génotypes du groupe sanguin A au moyen d'un effet thermodynamique, se montrait impropre quand les essentiels dégrés détaillés de la méthode furent verifiés. On ne peut pas distinguer les sérums A₁A₁ des sérums A₁O et les résultats sont pas du tout reproductibles.

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Herrn Professor Dr. B. Mueller (Heidelberg) zur Vollendung des 70. Lebensjahres gewidmet.

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Ein Auszug der Arbeit wurde anläßlich der 46. Tagung der Deutschen Gesellschaft für gerichtliche Medizin, Kiel 1967, vorgetragen.     

Scientific exchange: Jacques Loeb (1859-1924) and Emil Godlewski (1875-1944) as representatives of a transatlantic developmental biology

The German-American physiologist Jacques Loeb (1859-1924) and the Polish embryologist Emil Godlewski, jr. (1875-1944) contributed many valuable works to the body of developmental biology. Jacques Loeb was world famous at the beginning of the twentieth century for his development and demonstration of artificial parthenogenesis in 1899 and his experiments on regeneration. He served as a role model for the younger Polish experimenter Emil Godlewski, who began his career as a researcher like Loeb at the Zoological Station in Naples. Following Godlewski's first visit to Naples in 1901 a close relationship between the two scientists developed. Until Loeb's death in 1924 the two exchanged ideas via correspondence that was only interrupted during the First World War. The aim of the paper is to examine the transatlantic transfer of knowledge in the field of biological experimentation that was fostered by these two protagonists. Using a modification of Bruno Latour's model of the 'Circulatory System of Science' as a heuristic tool, different mechanisms of scientific exchange are displayed. With the help of Loeb's and Godlewski's correspondence the role of scientific communities, methods, allies, the public and institutions in the process of knowledge transfer are analysed. Preconditions for success and failure in transferring science are examined.