Two variant surface glycoproteins of Trypanosoma brucei of different sequence classes have similar 6 A resolution X-ray structures

Antigenic variation in the African trypanosome is mediated through changes in the composition of the surface coat. By controlling expression of the major surface protein, the variant surface glycoprotein (VSG), from a repertoire of perhaps 1,000 different genes the organisms exhibit a series of antigenically distinct coats and evade the host's immune system. We have determined the 6 A resolution structure of a T. brucei variant surface glycoprotein, ILTat 1.24, using X-ray crystallography. The crystallized protein consists of the N-terminal two-thirds of the intact VSG which has a relative molecular mass (Mr) of 60,000 (60K). The structure, which includes a 90 A long alpha-helical bundle, is strikingly similar to that of the N-terminal fragment of VSG MITat 1.2 (ref. 4). Although most known VSG sequences show little similarity of primary sequence in the N-terminal domain, the similarity between the structure of a Class I (ILTat 1.24) and a Class II (MITat 1.2) VSG antigen suggests that VSGs may share a common tertiary structure.     

ß-Cannabispiranol: A new non-cannabinoid phenol from cannabis sativa L.

Summary An ethanol extract of Cannabis sativa L. afforded upon partitioning and repeated chromatography a new non-cannabinoid phenol [7-hydroxy-5-methoxy-spiro-(cyclohexane-1, 1-indan)-4\-ol](IIIa), named -cannabispiranol.Acknowledgments. Supported by contract HSM-42-70-109 and grant DA-00928-01 from the National Institute on Drug Abuse as well as the Research Institute of Pharmaceutical Sciences. The authors are grateful to Mrs Glenda Lewis for running the GC analyses and to Dr Stephen Billets for running the Mass Spectra. Cannabis Herbarium specimens are stored in the Herbarium, Department of Pharmacognosy, School of Pharmacy, University of Mississippi, USA.     

Silencing of unsynapsed meiotic chromosomes in the mouse

In Neurospora, DNA unpaired in meiosis both is silenced and induces silencing of all DNA homologous to it. This process, called meiotic silencing by unpaired DNA, is thought to protect the host genome from invasion by transposable elements. We now show that silencing of unpaired (unsynapsed) chromosome regions also takes place in the mouse during both male and female meiosis. The tumor suppressor protein BRCA1 is implicated in this silencing, mirroring its role in the meiotic silencing of the X and Y chromosomes in normal male meiosis. These findings impact on the interpretation of the relationship between synaptic errors and sterility in mammals and extend our understanding of the biology of Brca1.     

Mutations in the human ortholog of Aristaless cause X-linked mental retardation and epilepsy

Mental retardation and epilepsy often occur together. They are both heterogeneous conditions with acquired and genetic causes. Where causes are primarily genetic, major advances have been made in unraveling their molecular basis. The human X chromosome alone is estimated to harbor more than 100 genes that, when mutated, cause mental retardation. At least eight autosomal genes involved in idiopathic epilepsy have been identified, and many more have been implicated in conditions where epilepsy is a feature. We have identified mutations in an X chromosome-linked, Aristaless-related, homeobox gene (ARX), in nine families with mental retardation (syndromic and nonspecific), various forms of epilepsy, including infantile spasms and myoclonic seizures, and dystonia. Two recurrent mutations, present in seven families, result in expansion of polyalanine tracts of the ARX protein. These probably cause protein aggregation, similar to other polyalanine and polyglutamine disorders. In addition, we have identified a missense mutation within the ARX homeodomain and a truncation mutation. Thus, it would seem that mutation of ARX is a major contributor to X-linked mental retardation and epilepsy.     

Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice

We have used large-scale insertional mutagenesis to identify functional landmarks relevant to cancer in the recently completed mouse genome sequence. We infected Cdkn2a(-/-) mice with Moloney murine leukemia virus (MoMuLV) to screen for loci that can participate in tumorigenesis in collaboration with loss of the Cdkn2a-encoded tumor suppressors p16INK4a and p19ARF. Insertional mutagenesis by the latent retrovirus was synergistic with loss of Cdkn2a expression, as indicated by a marked acceleration in the development of both myeloid and lymphoid tumors. We isolated 747 unique sequences flanking retroviral integration sites and mapped them against the mouse genome sequence databases from Celera and Ensembl. In addition to 17 insertions targeting gene loci known to be cancer-related, we identified a total of 37 new common insertion sites (CISs), of which 8 encode components of signaling pathways that are involved in cancer. The effectiveness of large-scale insertional mutagenesis in a sensitized genetic background is demonstrated by the preference for activation of MAP kinase signaling, collaborating with Cdkn2a loss in generating the lymphoid and myeloid tumors. Collectively, our results show that large-scale retroviral insertional mutagenesis in genetically predisposed mice is useful both as a system for identifying genes underlying cancer and as a genetic framework for the assignment of such genes to specific oncogenic pathways.     

The effect of incubation in phosphate buffer of different pH on the transplantability of the mouse ascites tumor of Ehrlich

Zusammenfassung Nachweis, dass Ehrlich-Ascites-Tumorzellen, die in Phosphat-Puffer bei einer Temperatur von 37°C inkubiert werden, in saurem pH des Milieus viel länger leben als beim neutralen.Morphologische Kriterien für Zellschädigung werden diskutiert und erweisen sich als unzulänglich zu Voraussagen über die biologische Wachstumsfähigkeit dieser Krebszellen.     

Effect of decreased dietary protein upon mammary gland growth in rats

Zusammenfassung Nachweis, dass der gesamte DNS-Gehalt in der Brustdrüse bei Tieren mit proteinfreier oder 5% iger Proteinnahrung im Vergleich zu der Kontroll-gruppe herabgesetzt ist. Wird Protein in der Nahrung um 10–20% erhöht, so bleiben DNS-Gehalt und Körperwachstum konstant.