Richard Lathe

Bio: Richard Lathe is an academic researcher from University of Edinburgh. The author has contributed to research in topics: Gene & Transgene. The author has an hindex of 52, co-authored 172 publications receiving 19962 citations. Previous affiliations of Richard Lathe include Centre national de la recherche scientifique & University of Strasbourg.

Variegated transgene expression in mouse mammary gland is determined by the transgene integration locus.

Abstract: Mice carrying an ovine beta-lactoglobulin (BLG) transgene secrete BLG protein into their milk. To explore transgene expression stability, we studied expression levels in three BLG transgenic mouse lines. Unexpectedly, two lines exhibited variable levels of transgene expression. Copy number within lines appeared to be stable and there was no evidence of transgene rearrangement. In the most variable line, BLG production levels were stable within individual mice in two successive lactations. Backcrossing demonstrated that genetic background did not contribute significantly to variable expression. Tissue in situ hybridization revealed mosaicism of transgene expression within individual mammary glands from the two variable lines; in low expressors, discrete patches of cells expressing the transgene were observed. Transgene protein concentrations in milk reflected the proportion of epithelial cells expressing BLG mRNA. Furthermore, chromosomal in situ hybridization revealed that transgene arrays in both lines are situated close to the centromere. We propose that mosaicism of transgene expression is a consequence of the chromosomal location and/or the nature of the primary transgene integration event.

Gene Transfer into Sheep

Abstract: Gene transfer into animals has considerable potential for livestock improvement. If this potential is to be realized, the ease of generation of transgenic livestock will be of major importance. We report here the production of six transgenic sheep by microinjection of DNA into early embryos (1.2% of embryos transferred). Three different gene constructs were injected and transgenic sheep were obtained with each. The transgenic animals have all incorporated the DNA without detectable rearrangement, and where multiple copies were integrated, they are present in arrays of tandem repeats. Transmission of transferred genes to progeny of three of the sheep has been demonstrated. Five founder transgenic sheep described carry genes designed to direct the production of human clotting factor IX or human αl–antitrypsin in milk. Transgenic animals carrying such genes may ultimately provide a new source of these and other therapeutic proteins.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

A novel potent vasoconstrictor peptide produced by vascular endothelial cells.

Abstract: An endothelium-derived 21-residue vasoconstrictor peptide, endothelin, has been isolated, and shown to be one of the most potent vasoconstrictors known. Cloning and sequencing of preproendothelin complementary DNA shows that mature endothelin is generated through an unusual proteolytic processing, and regional homologies to a group of neurotoxins suggest that endothelin is an endogenous modulator of voltage-dependent ion channels. Expression of the endothelin gene is regulated by several vasoactive agents, indicating the existence of a novel cardiovascular control system.

Vascular endothelial growth factor is a secreted angiogenic mitogen

Abstract: Vascular endothelial growth factor (VEGF) was purified from media conditioned by bovine pituitary folliculostellate cells (FC). VEGF is a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo. Complementary DNA clones for bovine and human VEGF were isolated from cDNA libraries prepared from FC and HL60 leukemia cells, respectively. These cDNAs encode hydrophilic proteins with sequences related to those of the A and B chains of platelet-derived growth factor. DNA sequencing suggests the existence of several molecular species of VEGF. VEGFs are secreted proteins, in contrast to other endothelial cell mitogens such as acidic or basic fibroblast growth factors and platelet-derived endothelial cell growth factor. Human 293 cells transfected with an expression vector containing a bovine or human VEGF cDNA insert secrete an endothelial cell mitogen that behaves like native VEGF.

Feature-Oriented Domain Analysis (FODA) Feasibility Study

Abstract: : Successful Software reuse requires the systematic discovery and exploitation of commonality across related software systems. By examining related software systems and the underlying theory of the class of systems they represent, domain analysis can provide a generic description of the requirements of that class of systems and a set of approaches for their implementation. This report will establish methods for performing a domain analysis and describe the products of the domain analysis process. To illustrate the application of domain analysis to a representative class of software systems, this report will provide a domain analysis of window management system software.

Unified models for active galactic nuclei and quasars

Abstract: Because the critical central regions of Active Galactic Nuclei (AGN) and quasars are strongly nonspherical but spatially unresolved, orientation effects have been the source of much confusion. In fact, it now appears that much of the variety in AGN types is just the result of varying orientation relative to the line of sight. We can define an extreme hypothesis,, the straw person model (SPM), in which there are two basic types of AGN: the radio quiets and the radio louds. For each type there is a range in intrinsic luminosity, and the luminosity controls some properties such as the Fanaroff and Riley classes. However, at a given intrinsic luminosity, all other properties such as spectroscopic classification and VLBI component speeds are ascribed to orientation. This model is only a caricature of the unification idea, and is already ruled out on many grounds, but it will be useful for organizing the discussion. I’ll describe what I consider to be convincing evidence that orientation effects are important and widespread. The true situation may be in some sense half way between the SPM and the hypothesis that orientation doesn’t affect classification at aIl. To us optimists, the orienration cup is half full rather than half empty. Although it is too soon to say for sure, the hypothesis that most objects’ classifications would be different if seen from other directions is a tenable one today.