Intercellular lacunae: sequestered microenvironments in stimulated leukocyte cultures

Zusammenfassung In Zellkulturen menschlicher Leukocyten wurden nach Stimulation zur Blasten-Transformation elektronenmikroskopische Verbindungen zwischen sich berührenden Zellen nachgewiesen, die wahrscheinlich dem Übertritt spezifischer Plasmabestand dienen.     

A transforming mutation in the pleckstrin homology domain of AKT1 in cancer

Although AKT1 (v-akt murine thymoma viral oncogene homologue 1) kinase is a central member of possibly the most frequently activated proliferation and survival pathway in cancer, mutation of AKT1 has not been widely reported. Here we report the identification of a somatic mutation in human breast, colorectal and ovarian cancers that results in a glutamic acid to lysine substitution at amino acid 17 (E17K) in the lipid-binding pocket of AKT1. Lys 17 alters the electrostatic interactions of the pocket and forms new hydrogen bonds with a phosphoinositide ligand. This mutation activates AKT1 by means of pathological localization to the plasma membrane, stimulates downstream signalling, transforms cells and induces leukaemia in mice. This mechanism indicates a direct role of AKT1 in human cancer, and adds to the known genetic alterations that promote oncogenesis through the phosphatidylinositol-3-OH kinase/AKT pathway. Furthermore, the E17K substitution decreases the sensitivity to an allosteric kinase inhibitor, so this mutation may have important clinical utility for AKT drug development.     

The transforming gene of Moloney murine sarcoma virus

A cleavage map of the Moloney murine sarcoma viral DNA was constructed and compared with that of a spontaneously occurring deletion mutant. By restriction enzyme analysis, it was shown that a region encompassing over 40% of the viral information was not essential for transformation or rescue of the deletion mutant. The transforming region was further localised by analysis of the transforming activity in tissue culture of isolated restriction fragments of linear duoble-stranded sarcoma viral DNA. In each case, DNA fragments that retained transforming activity preserved the cell-derived insertion sequences of the viral genome. Moreover, such transformants invariably expressed RNA specific to this region. By these two approaches, it was possible to demonstrate that the transforming region of the viral genome begins very near or within the cell-derived insertion sequences. Thus, the transforming gene of this mammalian sarcoma virus originates from within the mouse cell genome.     

Ultrastructure of photoreceptor cells in a vitamin A-deficient moth (Manduca sexta)

Zusammenfassung Die LepidoptereManduca sexta wurde während mehr als 20 Generationen ohne Vitamin A aufgezogen. Feinstrukturelle Veränderungen traten auf: Die Photorezeptorzellen zeigten starke Zunahme und Desorientierung der Mikrovilli des Rhabdoms. Mitochondrien waren aus der Normallage nahe am Ursprung der Mikrovilli gegen die Peripherie der Retinulazelle verschoben. «Zwiebelkörper» (Sammlungen von konzentrisch angeordneten Mikrovillimembranen) und eine grosse Anzahl von Mikrotubuli wurden in den interretinulären Zellen gefunden. Mit Pflanzendiät aufgezogene Insekten hingegen zeigten keine der beschriebenen Ultrastrukturänderungen.     

Determination of ancestral alleles for human single-nucleotide polymorphisms using high-density oligonucleotide arrays.

Here we report the application of high-density oligonucleotide array (DNA chip)-based analysis to determine the distant history of single nucleotide polymorphisms (SNPs) in current human populations. We analysed orthologues for 397 human SNP sites (identified in CEPH pedigrees from Amish, Venezuelan and Utah populations) from 23 common chimpanzee, 19 pygmy chimpanzee and 11 gorilla genomic DNA samples. From this data we determined 214 proposed ancestral alleles (the sequence found in the last common ancestor of humans and chimpanzees). In a diverse human population set, we found that SNP alleles with higher frequencies were more likely to be ancestral than less frequently occurring alleles. There were, however, exceptions. We also found three shared human/pygmy chimpanzee polymorphisms, all involving CpG dinucleotides, and two shared human/gorilla polymorphisms, one involving a CpG dinucleotide. We demonstrate that microarray-based assays allow rapid comparative sequence analysis of intra- and interspecies genetic variation.     

The multiple roles of monocyte subsets in steady state and inflammation

Monocytes participate importantly in immunity. Produced in the bone marrow and released into the blood, they circulate in blood or reside in a spleen reservoir before entering tissue and giving rise to macrophages or dendritic cells. Monocytes are more than transitional cells that adapt to a particular tissue environment indiscriminately. Accumulating evidence now indicates that monocytes are heterogeneous in several species and are themselves predetermined for particular function in the steady state and inflammation. Future therapeutics may harness this heterogeneity to target harmful functions while sparing those that are beneficial. Here, we review recent advances on the ontogeny and function of monocytes and their subsets in humans and mice.     

Nematidical activity of secondary and tertiary alkyl amides and amines.

Several C11 to C15 amides and amines that disrupt growth in certain insects showed high nematicidal activity in direct contact tests. Two amides and 9 amines killed Panagrellus at 5-10 ppm. Of these, 1 amide and 3 amines killed Meloidogyne larvae at 20 ppm.