Muscle LIM protein promotes expression of the acetylcholine receptor <Emphasis Type="Italic">γ</Emphasis>-subunit gene cooperatively with the myogenin-E12 complex

Muscle LIM protein (MLP, also referred to as CRP3) is a muscle-specific LIM-only protein, which consists of two LIM motifs. MLP functions as a positive regulator during myogenesis. Here we report that MLP serves as a cofactor regulating the expression of the nicotinic acetylcholine receptor (AChR) -subunit gene in skeletal muscle cells. We found that MLP promoted the expression of the AChR -subunit gene in C2C12 myotubes, but not in C2C12 myoblasts or NIH3T3 fibroblasts. Furthermore, we showed that MLP interacted with myogenin in vivo and enhanced the binding ability of the myogenin-E12 heterodimer to the E boxes in the AChR -subunit gene promoter. Together, these results suggest that MLP promotes the specific expression of the AChR -subunit gene cooperatively with the myogenin-E12 complex during myogenesis.Received 17 May 2004; received after revision 22 July 2004; accepted 26 July 2004     

A presynaptic effect of whole venom ofDendroaspis jamesoni on the hemidiaphragm of rat

Summary Dendroaspis jamesoni venom in a dose of 12.5 g/ml restricts the uptake of Ca⁺ leading to inhibition of release of Ach from the motor nerve terminals of the hemidiaphragms of rats.Acknowledgment. University of Nairobi, for the research grant (No. 670-052), which supported this work. We also thank Mr. S. K. Githaiga, Government Chemist's Department, for his help in the use of the spectrophotometer.     

The scorpine family of defensins: gene structure,alternative polyadenylation and fold recognition

Small cationic antimicrobial peptides (SCAMPs) as effectors of animal innate immunity provide the first defense against infectious pathogens. This class of molecules exists widely in invertebrate hemolymph and vertebrate skin secretion, but animal venoms are emerging as a new rich resource. Scorpine is a unique scorpion venom defensin peptide that has an extended amino-terminal sequence similar to cecropins. From the African scorpion Opistophthalmus carinatus venom gland, we isolated and identified several cDNAs encoding four new homologs of scorpine (named opiscorpines 1–4). Importantly, we show for the first time the existence of multiple opiscorpine mRNAs with variable 3 untranslated regions (UTRs) in the venom gland, which may be generated by alternative usage of polyadenylation signals. The complete opiscorpine gene structure including its promoter region is determined by genomic DNA amplification. Two large introns were found to be located within the 5 UTR and at the boundary of the mature peptide-coding region. Such a gene structure is distinct, when compared with other scorpion venom peptide genes. However, a comparative promoter analysis revealed that both opiscorpine and scorpion venom neurotoxins share a similar promoter organization. Sequence analysis and structural modeling allow us to group the scorpines and scorpion long-chain K-channel toxins together into one family that shares a similar fold with two distinct domains. The N-terminal cecropin-like domain displaying a clear antimicrobial activity implies that the scorpine family represents a group of real naturally occurring hybrids. Based on the phylogenetic analysis, a possible cooperative interaction between the N and C domains is elucidated, which provides an evolutionary basis for the design of a new class of anti-infectious drugs.Received 5 April 2004; accepted 17 May 2004     

Immunogenetics

Summary The 1985 Catalog of Mapped Genes (Human Gene Mapping 8; 33) has been used to pick out the known, immunologically important genes; these are then discussed in the following order: 1. genes controlling organs, tissues and cells of the immune apparatus, 2. genes determining self structures, 3. genes determining the structures of immunological specificity, 4. genes determining substances with immunoregulatory and effector properties. The symbols for the genes and the biological functions of their products are explained. The genetics of the ABO blood groups, of the HLA-system and of antibody formation are given in rather more detail.     

Recent evolutionary origin within the primate lineage of two pseudogenes with similarity to members of the transforming growth factor-β superfamily

Using a search engine called Motifer, we searched the public database of the human genome for genes matching a consensus pattern of cysteine residues derived from members of the transforming growth factor-beta (TGF-) superfamily. We identified two genes (named MDF451 and MDF628) that display sequence similarity to members of the TGF- superfamily in the arrangement of six conserved cysteine residues. Phylogenetic analyses revealed that MDF451 and MDF628 constitute a distinct subgroup within the TGF- superfamily, distantly related to the GDNF subfamily of ligands. Both genes could be identified in several primate species in addition to human, including chimpanzee, gorilla, guereza, and green and gray monkey, but not in rodents or other non-primate mammals, and appear not to be present in the genomes of mouse, rat or zebrafish. RNAs for MDF451 and MDF628 were expressed at low levels within distinct regions of the human central nervous system, including adult cerebellum, adult spinal cord and fetal brain. Despite expression at the RNA level, both genes presented a transcribed upstream stop codon that would prevent translation of the TGF--like reading frame. The coding potential of alternative reading frames was not immediately apparent. The two genes may represent TGF--like pseudogenes that have recently appeared in evolution in a common ancestor of the primate lineage by duplication from a GDNF/TGF--like ancestral gene.Received 9 October 2003; received after revision 13 November 2003; accepted 2 December 2003     

Missense mutations resulting in type 1 lissencephaly

Proper human brain formation is dependent upon the integrated activity of multiple genes. Malfunctioning of key proteins results in brain developmental abnormalities. Mutation(s) in the LIS1 gene or the X-linked gene doublecortin (DCX) results in a spectrum of disorders including lissencephaly, or smooth brain, and subcortical band heterotopia, or doublecortex. Here, we will focus on a particular subset of missense mutations in these two genes and their effect on protein structure and function.Received 4 August 2004; received after revision 26 September 2004; accepted 5 October 2004     

Molecular characterization of <Emphasis Type="Italic">Arabidopsis</Emphasis> PHO80-like proteins,a novel class of CDKA;1-interacting cyclins

Cyclins are regulatory proteins that interact with cyclin-dependent kinases (CDKs) to control progression through the cell cycle. In Arabidopsis thaliana, 34 cyclin genes have been described, grouped into five different types (A, B, D, H, and T). A novel class of seven cyclins was isolated and characterized in Arabidopsis, designated P-type cyclins (CYCPs). They all share a conserved central region of 100 amino acids (cyclin box) displaying homology to the corresponding region of the PHO80 cyclin from Saccharomyces cerevisiae and the related G1 cyclins from Trypanosoma cruzi and T. brucei. The CYCP4;2 gene was able to partially re-establish the phosphate-dependent expression of the PHO5 gene in a pho80 mutant strain of yeast. The CYCPs interact preferentially with CDKA;1 in vivo and in vitro as shown by yeast two-hybrid analysis and co-immunoprecipitation experiments. P-type cyclins were mostly expressed in proliferating cells, albeit also in differentiating and mature tissues. The possible role of CYCPs in linking cell division, cell differentiation, and the nutritional status of the cell is discussed.Received 9 February 2004; received after revision 18 March; accepted 19 April 2004     

Morphological,biochemical and molecular changes during ectomycorrhiza development

Summary An ectomycorrhiza, a specialized root organ, is the result of a complex interaction leading to a finely-tuned symbiosis between a plant and a compatible ectomycorrhizal fungus. Ultrastructural observations combined with cytochemical and biochemical studies reveal that structural and metabolic changes in the symbiont cells lead to the final phenotype of the active ectomycorrhiza. In the present review these changes are interpreted as changes in gene expression and discussed within the context of ectomycorrhiza development. Recent genetic data indicate that the continued vegetative growth of the ectomycorrhizal hyphae and the root tissues, and their ability to switch to symbiotic organ formation, is basically controlled by developmentally critical genes. The activity of these symbiotic genes during the differentiation of ectomycorrhizas is associated with extensive changes in the concentration of particular polypeptides and protein biosynthesis. The present state of knowledge about the developmental biology of ectomycorrhizas allows only speculation about the events during their development.Puisant mes forces aux sources des galaxies En buvant la sève des arbres M. Jonasz     

<Emphasis Type="Italic">Naja siamensis</Emphasis>, a cryptic species of venomous snake revealed by mtDNA sequencing

Because of possible variation in venom composition, an understanding of venomous snake systematics is of great importance for the optimization of antivenom treatment of snakebite patients. Intraspecific variation in the morphology of many venomous snakes complicates the definition and indentification of some species when allopatric populations are involved. Selectively neutral or near-neutral mtDNA sequences can reveal evolutionary relationships obscured by ecogenetically-caused morphological variation. We use comparative sequencing of the cytochrome oxidase subunit 1 gene to reveal the existence of a widespread, cryptic species of spiting cobra from southeast Asia. This species,Naja siamensis, is widely sympatric with other Asiatic cobra species. This may be of considerable medical significance, and calls for further research into venom composition in Asiatic cobras.     

Ubiquitin-proteasome pathway as a primary defender against TRAIL-mediated cell death

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptotic cell death as well as expression of proinflammatory genes such as CXCL8 in malignant human astrocytoma cells. However, the molecular mechanisms that determine the fate of cells are not yet understood. The ubiquitin (Ub)-proteasome pathway regulates a wide range of cellular functions through degradation of various regulatory proteins; given this, we hypothesized that this pathway may play a central role in TRAIL-mediated signaling. We demonstrate here that inhibition of the Ub-proteasome pathway enhanced TRAIL-mediated cell death of human astrocytoma CRT-MG cells within hours by blocking degradation of active caspase-8 and -3. Proteasome inhibitors suppressed TRAIL-mediated activation of NF-B; however, inhibition of the NF-B pathway alone was not sufficient to enhance TRAIL-mediated cell death. Collectively, these results suggest that the Ub-proteasome pathway may play an important role as an antiapoptotic surveillance system by eliminating activated caspases as well as mediating NF-B-dependent signals.Received 30 December 2003; received after revision 9 February 2004; accepted 13 February 2004     

Effect of spike disease on the 5′-and 3′-nucleotidase activities in sandal plants

Summary In the sandal plant affected by spike disease, caused by mycoplasma-like organisms, the changes occurring in the 5-and 3-nucleotidase activities were studied and their possible significance discussed.     

Untersuchungen über die β-adrenolytische Wirkung sowie den Einfluss auf Refraktärzeit und Kontraktilität von INPEA und MJ1999 am Meerschweinchenvorhof

Summary In isolated guinea-pig atria, the-adrenolytic isomerd(–)INPEA provoked a stronger prolongation of the refractory period (rp) than did the inactivel(+) isomer. The-adrenolytic drug MJ 1999 prolonged likewise the rp, although it caused no unspecific effect, i.e. an inhibition of contractile force. These observations lead to the conclusion that not only the unspecific local anaesthetic but also the specific-adrenolytic effect is of importance for the prolongation of rp.     

Der Mathematiker Abraham de Moivre (1667–1754)

Summary Before examining de Moivre's contributions to the science of mathematics, this article reviews the source materials, consisting of the printed works and the correspondence of de Moivre, and constructs his biography from them.The analytical part examines de Moivre's contributions and achievements in the study of equations, series, and the calculus of probability. De Moivre contributed to the continuing development from Viète to Abel and Galois of the theory of solving equations by means of constructing particular equations, the roots of which can be written in the form . He also discovered the reciprocal equations. In the course of this work de Moivre discovered an expression equivalent to (cos +i sin ) ⁿ =cos n +i sin n and, following Cotes, he succeeded in expressing the nth roots of unity in trigonometric form.In the theory of series, de Moivre developed a polynomial theorem encom-passing Newton's binomial theorem and, in particular, a theorem of recurrent series useful in the calculus of probability.The demands of the calculus of probability led de Moivre to an approximation for the binomial coefficients for large values of n. The interaction between de Moivre and James Stirling, particularly in regard to the asymptotic series for log (n!), is treated at length. This work supplied the foundation for de Moivre's limit theorem for the binomial distribution.The calculus of probability, which occupied him from 1708 onward, became in time ever more the center of de Moivre's inquiries. Proceeding from contemporary collections of gambling exercises, de Moivre, by introducing an explicit measure of probability for the so-called Laplace experiments, found the beginnings of a theory of probability. De Moivre expanded the classic application of probability calculus to games of chance by addressing himself to the problem of annuities and by adopting Halley's work with its conception of Probability of life. De Moivre was the first to publish a mathematically formulated law for the decrements of life derived from mortality tables.

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Abkürzungen a.a.O. am angegebenen Ort = Verweis auf das nach Verfassern alphabetisch geordnete Literaturverzeichnis. Eine vor a.a.O. in runden Klammern angegebene Zahl kennzeichnet die entsprechende Nummer der im Literaturverzeichnis aufgeführten Arbeiten eines Autors. - AC Ars conjectandi = Jakob Bernoulli (4) a.a.O. - AE Acta Eruditorum - a.S. alter Stil⁴⁷ - BM Bibliotheca Mathematica - DMV Deutsche Mathematiker-Vereinigung - JL Journal Literaire - MA Miscellanea Analytica, London 1730 - n.S. neuer Stil⁴⁷ - PT Philosophical Transactions of the Royal Society of London - r.F. rekurrente Folge - r.R. rekurrente Reihe - SMA Miscellaneis Analyticis Supplementum, London 1730 - v. veröffentlicht (nur im Briefverzeichnis verwendet) Prof. Dr. Kurt Vogel zum 80. Geburtstag Vorgelegt von J. E. Hofmann     

A new type of antigen induced by chemical linkage ofMycobacterium tuberculosis and γ-globulin

Zusammenfassung Mit Hilfe derPauly'schen Diazo-Reaktion wird humanes -Globulin an humanpathogene, virulenteMycobacterium tuberculosis-Stämme (M) gekoppelt. Das Zustandekommen der chemischen Bindung wurde mit gefärbten Präparaten, elektronenmikroskopischen und immunelektrophoretischen Untersuchungen der Bakterien bewiesen. Die mit-Globulin gekoppeltenM haben ihre Virulenz eingebüsst. In den Versuchstieren wurden Antikörper sowohl gegen -Globulin als auch gegenM gebildet. Durch ersteres wurde das Allergisierungsvermögen vonM gesteigert.     

<Emphasis Type="Italic">Trichomonas vaginalis</Emphasis> degrades nitric oxide and expresses a flavorubredoxin-like protein: a new pathogenic mechanism?

Besides possessing many physiological roles, nitric oxide (NO) produced by the immune system in infectious diseases has antimicrobial effects. Trichomoniasis, the most widespread non-viral sexually transmitted disease caused by the microaerophilic protist Trichomonas vaginalis, often evolves into a chronic infection, with the parasite able to survive in the microaerobic, NO-enriched vaginal environment. We relate this property to the finding that T. vaginalis degrades NO under anaerobic conditions, as assessed amperometrically. This activity, which is maximal (133 ± 41 nmol NO/10⁸ cells per minute at 20°C) at low NO concentrations ( 1.2 M), was found to be: (i) NADH dependent, (ii) cyanide insensitive and (iii) inhibited by O₂. These features are consistent with those of the Escherichia coli A-type flavoprotein (ATF), recently discovered to be endowed with NO reductase activity. Using antibodies against the ATF from E. coli, a protein band was immunodetected in the parasite grown in a standard medium. If confirmed, the expression of an ATF in eukaryotes suggests that the genes coding for ATFs were transferred during evolution from anaerobic Prokarya to pathogenic protists, to increase their fitness for the microaerobic, parasitic life style. Thus the demonstration of an ATF in T. vaginalis would appear relevant to both pathology and evolutionary biology. Interestingly, genomic analysis has recently demonstrated that Giardia intestinalis and other pathogenic protists have genes coding for ATFs.Received 1 November 2003; received after revision 5 January 2004; accepted 13 January 2004     

Central nicotinic receptor blockade inhibits emotionally conditioned pressor responses in rats

A conditioned stimulus previously paired with electric footshock produced an increase in blood pressure in conscious, freely moving rats. The conditioned pressor response was reproducible. Intracerebroventricular injection of the nicotinic receptor antagonists hexamethonium (1–10 g) or pentolinium (10 g) but not the muscarinic receptor antagonist methylatropine (3 g) produced an inhibition of the conditioned pressor response, whereas intraarterial injection of hexamethonium (10 g) did not affect the response. Intraventricular injection of the cholinesterase inhibitor physostigmine (3–10 g) produced an enhancement of the conditioned pressor response. These results are consistent with the possibility that central nicotinic receptors play a role in the expression of the emotionally conditioned pressor response in rats.     

Legionella pneumophila down-regulates MHC class I expression of human monocytic host cells and thereby inhibits T cell activation

Legionella (L.) pneumophila, the causative agent of Legionnaires disease, is an intracellular pathogen of alveolar macrophages that resides in a compartment displaying features of endoplasmatic reticulum (ER). In this study, we show that intracellular multiplication of L. pneumophila results in a remarkable decrease in MHC class I expression by the infected monocytes. During intracellular multiplication, L. pneumophila absorbs ER-resident chaperons such as calnexin and BiP, molecules that are required for the correct formation of the MHC class I complex. Due to reduced MHC class I expression, stimulation of allogeneic blood mononuclear cells was severely inhibited by infected host cells but cytotoxicity of autologous natural killer cells against Legionella-infected monocytes was not enhanced. Thus, reduced expression of MHC class I in infected monocytes may resemble a new immune escape mechanism induced by L. pneumophila.Received 22 November 2004; received after revision 27 December 2004; accepted 5 January 2005     

Antihypertensive and cardiac effects of two novelβ-adrenoceptor blocking drugs

Summary Two new-adrenoceptor blocking drugs with acute antihypertensive and positive inotropic effects are described: Compound A (2-[4-(3-tert. butylamino-2-hydroxypropoxy)phenyl]-4-trifluoromethylimidazole) and MK-761 (2-(3-tert. butylamino-2-hydroxypropoxy)-3-cyanopyridine hydrochloride). In SH rats both compounds, given orally, lowered arterial pressure and were more potent than hydralazine. The antihypertensive effect of compound A but not of MK-761 was antagonized by timolol. Both compounds had positive inotropic activity on cat heart papillary muscles; these effects were antagonized by timolol. The pretreatment of animals with reserpine greatly reduced the positive inotropic effect of MK-761 but not of compound A. The acute antihypertensive and positive inotropic effects of compound A are likely to be at least partially due to stimulation of-adrenoceptors, e.g. intrinsic sympathomimetic activity. The effects of MK-761 on the same parameters appear to be mediated by different mechanisms.     

Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons

Many have hypothesized that cell death in Parkinsons disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP⁺ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP⁺ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, –8, –6 and –7. A time-course study indicated that activation of caspase-2 and –8 occurred upstream of caspase-6 and caspase-7. Upon MPP⁺ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.Received 20 September 2004; received after revision 5 November 2004; accepted 22 November 2004