Disease from the point of view of evolution

In the process of evolution, such compensatory reactions as enhanced absorption of sodium chloride and an increase of arterial pressure could be formed only for compensation of acute pathological states (blood loss, dehydration). At present they remain similarly adequate in acute disturbances of blood circulation and of water-electrolyte balance. However, in severe chronic pathology of heart and kidney they often lose their compensatory function and even become dangerous. Evolution of man and of human society has created novel social conditions of adaptation. They are of humanitarian and technogenic character by promoting prevention and treatment of diseases.     

Uncoupling proteins: the issues from a biochemist point of view

The functional characteristics of uncoupling proteins (UCP) are reviewed, with the main focus on the results with isolated and reconstituted proteins. UCP1 from brown adipose tissue, the paradigm of the UCP subfamily, is treated in more detail. The issues addressed are the role and mechanism of fatty acids, the nucleotide binding, the regulation by pH and the identification by mutagenesis of residues involved in these functions. The transport and regulatory functions of UCP2 and 3 are reviewed in comparison to UCP1. The inconsistencies of a proposed nucleotide insensitive H(+) transport by these UCPs as concluded from the expression in yeast and Escherichia coli are elucidated. In both expression system UCP 2 and 3 are not in or cannot be converted to a functionally native state and thus also for these UCPs a nucleotide regulated H (+) transport is postulated.     

Genetic code from tRNA point of view

The possible codon-anticodon pairings follow the standard genetic code, yet in a different mode. The corresponding rules for decoding sequence of the codons in mRNA with tRNA may be called "tRNA code". In this paper we analyse the mutational and translational stability of such tRNA code. Our approach is based on the model of "ambiguous intermediate" and on the study of underlying block structure and Eulerean graph technique. It is shown that the wobble rules and the reduced number of tRNA anticodons strongly affect the mutational and translational stability of the code. The selection of tRNA anticodons, besides the optimization of translation, also ensures the more reliable start and, to a lesser extent, the stop of translation. The attribution of tRNA anticodons to the groups [WWW, WWS, SWW, SWS] and [SSS, SSW, WSS, WSW] as well as [MMM, MMK, KMM, KMK] and [KKK, KKM, MKK, MKM] clearly correlates with class I and class II aminoacyl-tRNA synthetases and obeys the principle of the optimal coding in both cases. Both W-S and M-K groupings also refer to the encoding of amino acids with the large and small side-chain volumes, which may provide such an attribution. The higher variability of tRNA code agrees with the suggestions that the variations in an assignment of tRNA anticodons may serve as the driving force generating the different variants of the genetic code.     

Animal models of NAFLD from the pathologist's point of view

Fatty liver disease is a multifactorial world-wide health problem resulting from a complex interplay between liver, adipose tissue and intestine and initiated by alcohol abuse, overeating, various types of intoxication, adverse drug reactions and genetic or acquired metabolic defects. Depending on etiology fatty liver disease is commonly categorized as alcoholic or non-alcoholic. Both types may progress from simple steatosis to the necro-inflammatory lesion of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH), respectively, and finally to cirrhosis and hepatocellular carcinoma. Animal models are helpful to clarify aspects of pathogenesis and progression. Generally, they are classified as nutritional (dietary), toxin-induced and genetic, respectively, or represent a combination of these factors. Numerous reviews are dealing with NASH animal models designed to imitate as closely as possible the metabolic situation associated with human disease. This review focuses on currently used mouse models of NASH with particular emphasis on liver morphology. Despite metabolic similarities most models (except those with chemically or genetically induced porphyria or keratin 18-deficiency) fail to develop the morphologic key features of NASH, namely hepatocyte ballooning and formation of histologically and immunohistochemically well-defined Mallory-Denk-Bodies (MDBs). Although MDBs are not universally detectable in ballooned hepatocytes in NASH their experimental reproduction and analysis may, however, significantly contribute to our understanding of important pathogenic aspects of NASH despite the obvious differences in etiology.     

Glycolipids from a colloid chemical point of view

Glycolipids are a group of compounds with a broad range of applications. Two types of glycolipids (alkylpolyglycosides and gangliosides) were examined with regard to their physicochemical properties. Despite their structural differences, they have in common that they are amphiphilic molecules and able to aggregate to form monolayers, bilayers, micelles, lyothropic mesophases or vesicles. The structures of glycolipid micelles were investigated by different experimental techniques in addition to molecular dynamic simulations. The knowledge of the physicochemical properties of gangliosides enables a better understanding of their biological functions. Structural features were obtained for the monosialogangliosides GM1, GM2 and GT1b from bovine brain by means of mass spectrometry. Further the aggregation behaviour was determined by small-angle neutron and dynamic light scattering experiments. Interaction studies of these compounds were carried out by means of surface plasmon resonance using gangliosides incorporated liposomes. They were used as model membranes that interact with the lectins WGA, RCA and HPA. The interaction of lectins immobilized to a modified silicon surface was investigated by in-situ ellipsometry.     

Conquering terra firma: The copper problem from the isopod's point of view

Summary 1. Copper is an element of great importance for crustaceans such as isopods and amphipods. While their marine relatives can obtain all necessary chemical components from the surrounding sea water via gills or other epithelia, the species which have conquered terra firma face the problem of extracting practically all vital substances from their food.2. In marine forms, the water flow maintained via ciliary or muscular mechanisms is sufficient to provide several orders of magnitude more copper than required; food probably plays only a minor role in copper supply.3. Terrestrial isopods have to rely entirely on their food as a source of copper. They can do several things in order to ensure an adequate supply: increase food consumption, improve the selective absorption of copper from the food material passing through the gut (possibly in symbiosis with copper concentrating micro-organisms), increase copper stores, thus widening safety margins for times of low supply, reduce copper losses by regulating the transport of this metal between the stores and other body parts.4. It was shown that terrestrial isopods consume about as much food as their marine relatives.5. Extraction of copper from primary vegetable matter seems to be very difficult, both for terrestrial forms likePorcellio scaber and for intertidal forms such asLigia oceanica or the amphipodOrchestia gammarella; extraction is possible only at very high copper concentrations.6. A way out of this calamitous situation seems to be in cooperation with micro-organisms which liberate copper from the tightly bound states in which it exists in the primary plant material. This is true forP. scaber but it probably also holds forO. gammerella, L. oceanica and other species feeding on decaying algae on the shore.7. The amount of copper stored in the hepatopancreas increases with increasing dependence of the species on the terrestrial environment, the values obtained for intertidal species being intermediate between marine and truly terrestrial species.8.P. scaber (and probablyOniscus asellus) will extract up to 95% of the copper present in artificially enriched leaf litter whereas intertidal forms feeding onFucus will not extract more than 50%, mostly only 20% or less, from artificially enriched seaweeds.9. Copper is more strictly relegated to storage cells of the hepatopancreas in terrestrial isopods than it is in marine or intertidal ones. Extensive movements of copper inP. scaber are accompanied by the synthesis of special carrier proteins, whereas in marine or intertidal species this metal seems to be able to move more freely in an easily dissociable state between the storage cells and other cells of the hepatopancreas.

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Eroberung des Festlands: Das Kupferproblem vom Gesichtspunkt der Isopoden

Kurzfassung Marine Crustaceen müßten theoretisch in der Lage sein, dem Atemwasser genügend viel Kupfer zu entnehmen, um selbst schwerste tägliche Verluste zu ersetzen. Im Vergleich dazu dürfte das in der Pflanzennahrung angebotene Cu mengenmäßig eine nur geringe Rolle spielen. Dennoch muß das vegetabilische Cu ausreichen, um den Bedarf herbivorer terrestrischer Crustaceen an diesem Metall zu decken. Die Probleme, die im Zusammenhang mit der Immigration vom Meer zum Land hinsichtlich der Kupferversorgung entstehen, werden am Beispiel litoraler und terrestrischer Isopoden und Amphipoden — zum Teil in spekulativer Form — diskutiert. Vergleichende Untersuchungen haben ergeben, daß terrestrische und litorale Isopoden die Menge der aufgenommenen Nahrung gegenüber marinen Arten nicht erhöhen und daß die Assimilation von Cu aus der Nahrung in ausreichender Weise nur durch die Beihilfe von Mikroorganismen möglich zu sein scheint. Der Zugang zu einem nährstoffreichen, von Mikroorganismen gut durchgearbeitetem Substrat muß also eine der Hauptvoraussetzungen für eine funktionierende Kupferversorgung aus pflanzlichem Material sein. Außerdem nimmt die Menge des im Hepatopancreas gespeicherten Cu in der Reihe marine — litorale — terrestrische Crustaceen zu. Auch die Leistungsfähigkeit der Kupferassimilation ist im Vergleich zu litoralen bei terrestrischen Isopoden größer. Während beiPorcellio scaber die Kupferassimilation in direkter Abhängigkeit vom Kupfergehalt der Nahrung steht und Werte über 90% erreichen kann, beträgt beiLigia oceanica undOrchestia gammarella die Kupferassimilation bei mittlerem Kupfergehalt (0,2 bis 0,3µg/mg Trockengewicht) nur etwa 66%, um dann wieder abzunehmen. Schließlich wird im Vergleich zu marinen und litoralen Isopoden der Kupferstoffwechsel terrestrischer Isopoden besser geregelt, indem Cu ausschließlicher in besonderen Zellen gespeichert und jede umfangreiche Mobilisierung des Metalls von der Synthese charakteristischer Sekrete begleitet wird, die Stoffe (wahrscheinlich Proteide) enthalten, deren Aufgabe zu sein scheint, freies Cu zu binden. Dies würde sowohl dessen toxische Eigenschaften reduzieren, als auch Verluste dieses Metalls an das Blut und in das Darmlumen verhindern.

     

Effects of methylphenidate: the cellular point of view

The psychostimulant methylphenidate (MPH) is the first choice of treatment in attention-deficit hyperactivity disorder and is based mainly on inhibition of dopamine transporter (DAT). Nonetheless, the complete cellular effects of MPH are still unknown. We attempted to determine whether MPH influences neurotransmitter levels, synaptic gene expression, and cell proliferation in a dose-dependent manner in rat pheochromocytoma cells (PC12) lacking DAT. PC12 were treated in a dose-dependent manner with MPH. Gene expression level of synaptotagmin (Syt) 1 and 4, syntaxin 1a (Stx1a), and synaptic vesicle glycoprotein 2C (SV2C) was measured using quantitative real-time RT-PCR. Different Neurotransmitter release was measured using high-performance liquid chromatography (HPLC). Differences in cell proliferation were evaluated via BrdU incorporation. Treatment with low-dose MPH (1-100 nM) altered intra-/extracellular neurotransmitter levels, down-regulated all investigated genes as well as enhanced cell proliferation significantly. These data point to diverse effects of MPH on cell metabolism independent of inhibiting DAT.