Linkage of the Murine Transforming Growth Factor α Gene with Igk, Ly-2, and Fabp1 on Chromosome 6

TGFα is a mitogenic polypeptide found in the conditioned media of transformed cell lines as well as in various solid tumors. Although its physiological role in normal tissues is uncertain, the autocrine action of TGFα on the EGF receptor is postulated to play a role in tumorigenesis. To explore the possibility that pre-existing mouse mutants might have concordance with the mouse TGFα locus (Tgfa) we sought to establish the chromosomal localization of the murine TGFα gene. Using Southern analysis we have detected NcoI and PvuII RFLP in the TGFα gene of progenitor RI mouse strains. These RFLPs have been used to analyze four different RI sets of DNA and to assign Tgfa to the 35-cM region of chromosome 6. Linkage has been established and the data suggest that the distance between Igk and wa-1 anchor loci may be less than 8 cM and that the gene order for the proximal to mid region of mouse chromosome 6 may be: Ggc-Xmmv27-[Brp-1, Lvp-1, Ms6-4]-[Igk, Ly2, Ly3 Odc-rs5, Rn7s-6, Fabp1]-[Tgfa/wa-1]-IL5-R. Homology of synteny has been further defined between the proximal region of mouse chromosome 6 and with the 2p 13-p11 region of human chromosome 2 encompassing TGFA, IGK, CD8A, and FABP1 .     

An optimized live bacterial delivery vehicle safely and efficaciously delivers bacterially transcribed therapeutic nucleic acids

There is an unmet need for delivery platforms that realize the full potential of next-generation nucleic acid therapeutics. The in vivo usefulness of current delivery systems is limited by numerous weaknesses, including poor targeting specificity, inefficient access to target cell cytoplasm, immune activation, off-target effects, small therapeutic windows, limited genetic encoding and cargo capacity, and manufacturing challenges. Here we characterize the safety and efficacy of a delivery platform comprising engineered live, tissue-targeting, non-pathogenic bacteria (Escherichia coli SVC1) for intracellular cargo delivery. SVC1 bacteria are engineered to specifically bind to epithelial cells via a surface-expressed targeting ligand, to allow escape of their cargo from the phagosome, and to have minimal immunogenicity. We describe SVC1's ability to deliver short hairpin RNA (shRNA), localized SVC1 administration to various tissues, and its minimal immunogenicity. To validate the therapeutic potential of SVC1, we used it to deliver influenza-targeting antiviral shRNAs to respiratory tissues in vivo. These data are the first to establish the safety and efficacy of this bacteria-based delivery platform for use in multiple tissue types and as an antiviral in the mammalian respiratory tract. We expect that this optimized delivery platform will enable a variety of advanced therapeutic approaches.     

Pollen-pistil interaction in maize: effects on genetic variation of pollen traits

Various factors (pollen diameter, in vitro germination and tube length, in vivo growth rate in selfed and nonselfed styles) which could possibly contribute to the competitive ability of pollen were investigated on 30 Zea mays L. inbred lines. The only factor with which pollen diameter was positively correlated was in vitro pollen-tube growth. Traits related to the early stages of growth (in vitro germination, in vitro tube length, early in vivo pollen growth rate) were all positively correlated with each other, and these early characteristics were negatively correlated with late in vivo tube growth rate, which is largely influenced by the stylar genotype.     

Population dynamics of a meiotic/mitotic expansion model for the fragile X syndrome.

A model to explain the mutational process and population dynamics of the fragile X syndrome is presented. The mutational mechanism was assumed to be a multipathway, multistep process. Expansion of CGG repeats was based on an underlying biological process and was assumed to occur at two time points: meiosis and early embryonic development (mitosis). Meiotic expansion was assumed to occur equally in oogenesis and spermatogenesis, while mitotic expansion was restricted to somatic, or constitutional, alleles of maternal origin. Testable hypotheses were predicted by this meiotic/mitotic model. First, parental origin of mutation is predicted to be associated with the risk of a woman to have a full mutation child. Second, "contractions" seen in premutation male transmissions are predicted not to be true contractions in repeat size, but a consequence of the lack of mitotic expansion in paternally derived alleles. Third, a portion of full-mutation males should have full-mutation alleles in their sperm, due to the lack of complete selection against the full-mutation female. Fourth, a specific premutation-allele frequency distribution is predicted and differs from that based on models assuming only meiotic expansion. Last, it is predicted that approximately 65 generations are required to achieve equilibrium, but this depends greatly on the expansion probabilities.     

Grain dust and the lungs.

Grain dust is composed of a large number of materials, including various types of grain and their disintegration products, silica, fungi, insects and mites. The clinical syndromes described in relation to exposure to grain dust are chronic bronchitis, grain dust asthma, extrinsic allergic alveolitis, grain fever and silo-filler''s lung. Rhinitis and conjunctivitis are also common in grain workers. While the concentration and the quality of dust influence the frequency and the type of clinical syndrome in grain workers, host factors are also important. Of the latter, smoking is the most important factor influencing the frequency of chronic bronchitis. The role of atopy and of bronchial hyperreactivity in grain dust asthma has yet to be assessed. Several well designed studies are currently being carried out in North America not only to delineate the frequency of the respiratory abnormalities, the pathogenetic mechanisms and the host factors, but also to establish a meaningful threshold limit concentration for grain dust.     

Parasites ofSpodoptera exigua,S. eridania [Lep.: Noctuidae] andHerpetogramma bipunctalis [Lep.: Pyralidae] collected fromAmaranthus hybridus in field corn

Three species of lepidopterous larvae were collected fromAmaranthus hybridus L. growing in field corn during 1975 and 1976 at Hastings, Florida.Spodoptera exigua (Hubner) was the predominant species in May.Spodoptera eridania (Cramer) was predominant in June andHerpetogramma bipunctalis (F.) in July and August. Nine native species of parasites, representing theBraconidae, Eulophidae, Ichneumonidae andTachinidae, emerged from these larvae.Meteorus autographae Muesebeck emerged from bothS. exigua andS. eridania. TheTachinidae, Winthemia rufopicta (Bigot),Eucelatori rubentis (Coquillett) andLespensia sp., emerged from mixtures ofS. exigua andS. eridania. Apanteles marginiventris (Cresson),Temelucha sp., andChelonus texanus Cresson emerged from bothS. exigua andH. bipunctalis larvae, andEuplectrus platyhypenae Howard andOphion sp. emerged fromS. eridania. All the species of parasites from the lepidopterous larvae that feed onAmaranthus hybridus are also reported as parasites ofS. frugiperda, a serious pest of corn. Therefore these larvae onA. hybridus may be a source of the parasites found attackingS. frugiperda.     

Mode of initiation of cell infection with sludge-associated poliovirus.

Association with sludge solids did not allow poliovirus to enter cells other than through the normal receptor-mediated route. This implies that the infectivities of sludge-encapsulated virions are masked until their exposure permits binding to cell surface receptors.