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.

Inherited Creutzfeldt-Jakob disease in a British family associated with a novel 144 base pair insertion of the prion protein gene.

Abstract: A case of familial Creutzfeldt-Jakob disease associated with a 144 base pair insertion in the open reading frame of the prion protein gene is described. Sequencing of the mutated allele showed an arrangement of six octapeptide repeats, distinct from that of a recently described British family with an insertion of similar size. Thirteen years previously the brother of the proband had died from "Huntington's disease", but re-examination of his neuropathology revealed spongiform encephalopathy and anti-prion protein immunocytochemistry gave a positive result. The independent evolution of at least two distinct pathological 144 base pair insertions in Britain is proposed. The importance of maintaining a high index of suspicion of inherited Creutzfeldt-Jakob disease in cases of familial neurodegenerative disease is stressed.

Herpes Viruses and Senile Dementia: First Population Evidence for a Causal Link.

Abstract: Three articles have very recently appeared that are of especial relevance to the causes of dementia and its potential treatment. The first two (Tsai et al., published in PLoS One in November 2017; Chen et al., published in the January/February 2018 issue of Journal of Clinical Psychiatry) demonstrate an increased risk of subsequent senile dementia (SD) development in patients with acute varicella zoster (herpes zoster) infection. These articles present data highly relevant to the third, and most important, paper-by Tzeng et al., published online in the journal Neurotherapeutics at the end of February 2018. These authors report that infection with a different herpes virus, herpes simplex virus type 1 (HSV1), leads to a similarly increased risk of later developing SD. Further, when the authors looked at patients treated aggressively with antiherpetic medications at the time, the relative risk of SD was reduced by a factor of 10. It should be stressed that no investigations were made on subjects already suffering from SD, and that those treated were the few rare cases severely affected by HSV. Nonetheless, antiherpetic medication prevented later SD development in 90% of their study group. These articles provide the first population evidence for a causal link between herpes virus infection and senile dementia.

Multiple effects of genetic background on variegated transgene expression in mice.

Abstract: BLG/7 transgenic mice express an ovine beta-lactoglobulin transgene during lactation. Unusually, transgene expression levels in milk differ between siblings. This variable expression is due to variegated transgene expression in the mammary gland and is reminiscent of position-effect variegation. The BLG/7 line was created and maintained on a mixed CBA x C57BL/6 background. We have investigated the effect on transgene expression of backcrossing for 13 generations into these backgrounds. Variable transgene expression was observed in all populations examined, confirming that it is an inherent property of the transgene array at its site of integration. There were also strain-specific effects on transgene expression that appear to be independent of the inherent variegation. The transgene, compared to endogenous milk protein genes, is specifically susceptible to inbreeding depression. Outcrossing restored transgene expression levels to that of the parental population; thus suppression was not inherited. Finally, no generation-dependent decrease in mean expression levels was observed in the parental population. Thus, although the BLG/7 transgene is expressed in a variegated manner, there was no generation-associated accumulated silencing of transgene expression.

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

Abstract: This study reports on the spatiotemporal dynamics of the expression of estrogen receptors (ERs) in the mouse central nervous system (CNS) during the early postnatal and the peripubertal period. At postnatal day 7 (P7), neurons with strong nuclear immunostaining for both ERα and ERβ1 were widely distributed throughout the brain. Sucrose density gradient sedimentation followed by western blotting supported the histochemical evidence for high levels of both ERs at P7. Over the following 2 days, there was a rapid downregulation of ERs. At P9, ERα expression was visible only in the hypothalamic area. Decline in ERβ1 expression was slower than that of ERα, and ERα-negative, ERβ1-positive cells were observed in the dentate gyrus and walls of third ventricle. Between P14 and P35, ERs were undetectable except for the hypothalamic area. As before P7, the ovary does not produce estrogen but does produce 5α-androstane-3β, 17β-diol (3βAdiol), an estrogenic metabolite of dihydrotestosterone, we examined the effects of high levels of 3βAdiol in the postnatal period. We used CYP7B1 knockout mice which cannot hydroxylate and inactivate 3βAdiol. The brains of these mice are abnormally large with reduced apoptosis. In the early postnatal period, there was 1-week delay in the timing of the reduction in ER expression in the brain. These data reveal that the time when ERs might be activated in the brain is limited to the first 8 postnatal days. In addition, the importance of aromatase has to be reconsidered as the alternative estrogen, 3βAdiol, is important in neuronal function in the postnatal brain.

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.