Oncogenic protein tyrosine kinases

Since it was first recognized, chronic myeloid leukemia (CML) has always represented a unique model to understand the molecular mechanisms underlying the onset and progression of a leukemic process. CML was the first recognized form of cancer to have a strong association with a recurrent chromosomal abnormality, the t(9;22) translocation, which generates the so-called Philadelphia (Ph)-chromosome. Twenty years later, this abnormality was shown to cover a specific molecular defect, a hybrid BCR-ABL gene, strongly implicated in the pathogenesis of the disease through the production of a protein with a constitutive tyrosine-kinase activity. Although we still lack a complete definition of all the transformation pathways activated by Bcr-Abl, the recent introduction into clinical practice of tyrosine kinase inhibitor represents a major breakthrough to the management of CML and, furthermore, promises to usher in molecularly targeted therapy for other types of leukemia, lymphoma and cancer.     

Étude cytologique d'une translocation chromosomeY-autosome chez la souris

Summary A male mouse with one translocation involving theY-chromosome has been observed in the F1 offspring of a male mouse given 300 R of X-irradiation. 6 types of spermatocytes were recorded. Our observations appear to confirm that the acrocentricX of the mouse associates end-to-end with theY at its centromeric end.     

Les chromosomes deLeggadina hermannsburgensis hermannsburgensis Waite et le problème des Muridae australiens

Summary As contribution to the problem of the Australian endemic Muridae, the chromosome complement ofLeggadina h. hermannsburgensis is described: 2N=48 –N.F.=56 –X-chromosome big and metacentric.     

Zur Polymorphie eines Chromosoms innerhalb von Populationen des LaufkäfersCarabus auronitens Fabr

Summary C. auronitens has 26 autosomes (2n), from which one pair — calledA-chromosomes — is relatively long.A-chromosomes consist of an euchromatic and a heterochromatic arm. In 63% of the individuals, theA-chromosomes are intraindividually anisomorph with regard to the length of their heterochromatic arm. According to its length, this arm shows 0–3 secondary constrictions. Hence there are at least 4 different forms of theA-chromosome.     

MultipleW chromosome in a sea snake,Enhydrina schistosa daudin

Résumé Un serpent marin (Enhydrina chistosa Daudin, Hydrophiidae) a 32 chromosomes chez le , 33 chez la , cette dernière ayant unW-chromosome supplémentaire. La digamétie serait: -ZZ; Z W ₁W₂.

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The author is indebted to Prof. S.P. RayChaudhuri for guidance and the University Grants Commission, India, for financial assistance.     

Effects of ingested phytoecdysteroids in the female soft tickOrnithodoros moubata

The effects of the ingestion of some phytoecdysteroids were studied in the soft tickOrnithodoros moubata. Supernumerary moulting and malformations of first leg pairs were obtained with 22-oxo-20-hydroxyecdysone, 20-hydroxyecdysone-22-acetate, and 20-hydroxyecdysone-22-benzoate. Egg-yield was reduced with 20-hydroxyecdysone-22-acetate and carthamosterone. Finally, drying-out of eggs was observed with carthamosterone and 22-deoxy-20,26-dihydroxyecdysone. In addition, we demonstrated that there is a correlation between the number of completed gonotrophic cycles and the impossibility of inducing supernumerary moulting.     

Normalization by nucleotides of impairments in deamination of nitrogenous compounds in liver of tumor-bearing mice

-2 (3)--3- - .     

Cadherin 22 participates in the self-renewal of mouse female germ line stem cells via interaction with JAK2 and β-catenin

The self-renewal capacity of the stem cell pool determines tissue function and health. Cadherin-22 (Cdh22), a member of the cadherin superfamily, has two splicing patterns in rats, and the short type that lacks a catenin binding domain is closely related to spermatogonial stem cell self-renewal. Previously, we reported that CDH22 was highly expressed in mouse ovary germ cells, especially in female germ line stem cells (FGSCs). However, its underlying function in FGSCs is still not clear. Here, we found that Cdh22 encodes only one type of protein product in mice and demonstrated that CDH22 was required for FGSC self-renewal. In addition, JAK2 and β-catenin were found to interact with CDH22 and be involved in CDH22 signaling in mouse FGSCs. Moreover, extrinsic CDH22 was identified as a potential molecule that participates in FGSC adhesion and is pivotal for FGSC maintenance and self-renewal. These results reveal that CDH22 functions as an essential molecule in FGSC maintenance and self-renewal via different mechanisms, including interaction with the JAK-STAT signaling pathway and β-catenin.     

Misuses of biology in the context of the paranormal

Summary Public suspicion of science stems from science's challenging of perceptions and myths about reality, and a public fear of new technology. The result is a susceptibility to pseudoscience. In claiming that creation science is as valid as evolution the creationists misquote scientists and seek to spread their own scientific myths concerning a young age for the earth, an act of creation based on a particular literalist interpretation of the Christian Bible and a single worldwide flood. They use methods of debate and politics, rather than scientific research. A selection of their arguments is examined and the nature of the evidence for evolution is discussed. Problems with the creation science model are noted. In the myth of the hundredth monkey phenomenon, original research is misquoted to denigrate scientific research and support sentimental ideas of paranormal events. The misuse of science is seen as damaging to society because it reduces the effective gathering and application of scientific information. However, pseudoscience provides a valuable guide to gaps in public scientific education.     

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     

Occurrence of 3-epi-22-deoxy-20-hydroxyecdysone and its phosphoric ester in diapause eggs of the silkworm,Bombyx mori

Ecdysteroids in diapause eggs of the silkworm,Bombyx mori, were analyzed using high-performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). A relatively large amount of an unidentified free ecdysteroid and its phosphoric ester (conjugated form) were detected. These two compounds were isolated by a combination of column chromatography on silicic acid, thin-layer chromatography (TLC), and HPLC using a reverse-phase (RP) column. The purified compounds were identified as 3-epi-22-deoxy-20-hydroxyecdysone (22d20E) and 3-epi-22-deoxy-20-hydroxyecdysone 2-phosphate (22d20E2P) by means of mass spectrometry and nuclear magnetic resonance spectroscopy. to our knowledge, this is the first report of 22d20E and 22d20E2P.     

Nouvelles contributions à la cytogénétique desMus Africains du sous-genreLeggada

Summary The author describes four new chromosome complements in the African pigmy-mice (Mus, subgenusLeggada). (1) One form from Angola has 18 metacentric chromosomes (N.F.=36) in both sexes. In contrast toMus minutoïdes minutoïdes Smith from South Africa, whose females have the same chromosome complement while the males show an acrocentric and shortY-chromosome, we have here a metacentricY. It is a confirmation of the hypothesis that theY ofM. m. minutoïdes was primarily of translocated type (TR) but lost a big intercalary segment of the autosomic arm. (2) In another species from Angola 2N=34;N.F.=36. It is the first case in the subgenus where a Robertsonian fusion occurs between autosomes before the transformation of the sex-chromosomesPR into sex-chromosomesTR. This observation is a confirmation that the complement 2N=36;N.F.=36 is the primitive one, being found in the three groups of species,minutoïdes, bufo-triton andtenellus. (3) Indeed, from Ghana, I have got specimens ofM. tenellus. We have here to deal with the primitive chromosome complement: 2N=36;N.F.=36. (4) In a sample of 12Leggada from the region of Bukawu (Congo), there are 5 and 7 . 4 show a total deletion of the short arm of theX-chromosome. In spite of the absence of X _dc -Y and of X _dc -X _dc in the sample, it is probable that neither of these complements is lethal.     

Über die Brenzkatechinamine im Froschherzen und in der Froschhaut vor und nach Verabfolgung von α-Methyldopa

Summary (1) The adrenalin of the frog heart was found to be localized mainly in the granular fraction (100,000g). After pretreatment with -methyldopa (-MD), the heart also contained -methyldopamine, -methylnoradrenalin, and -methyladrenalin. (2) -MD caused a maximal expansion of the melanophores. This action was counteracted byl-dopa, which per se caused a contraction of the melanophores. After pretreatment with -MD the skin contained besides adrenalin also -methyldopamine and -methyladrenalin. In addition also 5-hydroxytryptophan expanded the melanophores.     

Side-chain hydroxylation in the biosynthesis of β-ecdysone (20-hydroxyecdysone) in the blowflyCalliphora stygia

Résumé Dans la mouche a viandeCalliphora stygia le 25-hydroxycholesterol et le (22R)-22-hydroxycholesterol sont incorporés a la -ecdysone (20-hydroxy-ecdysone) beaucoup moins qu'au cholesterol et ne sont donc probablement pas des précurseurs de cette hormone.     

Energy flow and community structure in freshwater ecosystems

The goal of this article is twofold: 1) It aims at providing an overview on some major results obtained from energy flow studies in individuals, populations, and communities, and 2) it will also focus on major mechanisms explaining community structures. The basis for any biological community to survive and establish a certain population density is on the one hand energy fixation by primary producers together with adequate nutrient supply and the transfer of energy between trophic levels (bottom-up effect). On the other hand, predator pressures may strongly control prey population densities one or more trophic levels below (top-down effect). Other interpopulation effects include competition, chemical interactions and evolutionary genetic processes, which further interact and result in the specific structuring of any community with respect to species composition and population sizes.     

On genetic variability in a population of the widespread geckoHemidactylus brooki

Summary An electrophoretic investigation of 22 gene loci in a local sample of a widespread and ecologically extremely versatile gecko species has shown a low degree of heterozygosity, as is average in lizards and other vertebrates.     

Tauroursodeoxycholic acid prevents E22Q Alzheimer’s Aβ toxicity in human cerebral endothelial cells

The vasculotropic E22Q mutant of the amyloid-β (Aβ) peptide is associated with hereditary cerebral hemorrhage with amyloidosis Dutch type. The cellular mechanism(s) of toxicity and nature of the AβE22Q toxic assemblies are not completely understood. Comparative assessment of structural parameters and cell death mechanisms elicited in primary human cerebral endothelial cells by AβE22Q and wild-type Aβ revealed that only AβE22Q triggered the Bax mitochondrial pathway of apoptosis. AβE22Q neither matched the fast oligomerization kinetics of Aβ42 nor reached its predominant β-sheet structure, achieving a modest degree of oligomerization with a secondary structure that remained a mixture of β and random conformations. The endogenous molecule tauroursodeoxycholic acid (TUDCA) was a strong modulator of AβE22Q-triggered apoptosis but did not significantly change the secondary structures and fibrillogenic propensities of Aβ peptides. These data dissociate the pro-apoptotic properties of Aβ peptides from their distinct mechanisms of aggregation/fibrillization in vitro, providing new perspectives for modulation of amyloid toxicity. Received 20 November 2008; received after revision 12 December 2008; accepted 12 January 2009     

Benzyn-Zwischenprodukte in der nukleophilen aromatischen Substitution

Summary Many substitution reactions of aromatic halides, such as amination with metallic amides in ammonia or amine solutions, high-temperature alkaline hydrolyses and arylation with phenyllithium, lead to the formation of rearrangement products as the result of a common reaction path involving unstable benzyne intermediates. The chemical evidence in favor of this reaction mechanism is discussed as are correlations of observed product compositions and applications to practical synthetic procedures.

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Contribution No. 2390.     

Myelin sheaths: glycoproteins involved in their formation,maintenance and degeneration

Myelin sheaths are formed around axons by extending, biochemically modifying and spiraling plasma membranes of Schwann cells in the peripheral nervous system (PNS) and oligodendrocytes in the central nervous system (CNS). Because glycoproteins are prominent components of plasma membranes, it is not surprising that they have important roles in the formation, maintenance and degeneration of myelin sheaths. The emphasis in this review is on four integral membrane glycoproteins. Two of them, protein zero (P0) and peripheral myelin protein-22 (PMP-22), are components of compact PNS myelin. The other two are preferentially localized in membranes of sheaths that are distinct from compact myelin. One is the myelin-associated glycoprotein, which is localized at the inside of sheaths where it functions in glia-axon interactions in both the PNS and CNS. The other is the myelin-oligodendrocyte glycoprotein, which is preferentially localized on the outside of CNS myelin sheaths and appears to be an important target antigen in autoimmune demyelinating diseases such as multiple sclerosis. Received 8 April 2002; received after revision 13 May 2002; accepted 22 May 2002