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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.
Topics: Gene, Transgene, Virus, Vaccinia, Complementary DNA


Papers
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Journal ArticleDOI
15 Jan 2020-PLOS ONE
TL;DR: The findings suggest that the hippocampus acts as an integrator of body status, extending its role in context-dependent memory encoding from 'where' and 'when' to 'how I feel'.
Abstract: The primeval function of the mammalian hippocampus (HPC) remains uncertain. Implicated in learning and memory, spatial navigation, and neuropsychological disorders, evolutionary theory suggests that the HPC evolved from a primeval chemosensory epithelium. Deficits in sensing of internal body status ('interoception') in patients with HPC lesions argue that internal sensing may be conserved in higher vertebrates. We studied the expression patterns in mouse brain of 250 endocrine receptors that respond to blood-borne ligands. Key findings are (i) the proportions and levels of endocrine receptor expression in the HPC are significantly higher than in all other comparable brain regions. (ii) Surprisingly, the distribution of endocrine receptor expression within mouse HPC was found to be highly structured: receptors signaling 'challenge' are segregated in dentate gyrus (DG), whereas those signaling 'sufficiency' are principally found in cornu ammonis (CA) regions. Selective expression of endocrine receptors in the HPC argues that interoception remains a core feature of hippocampal function. Further, we report that ligands of DG receptors predominantly inhibit both synaptic potentiation and neurogenesis, whereas CA receptor ligands conversely promote both synaptic potentiation and neurogenesis. These findings suggest that the hippocampus acts as an integrator of body status, extending its role in context-dependent memory encoding from 'where' and 'when' to 'how I feel'. Implications for anxiety and depression are discussed.

14 citations

Patent
13 May 1983
TL;DR: In this paper, a vector for the expression of the antigenic protein of rabies was described, characterized in that it comprises at least: 1) the following efficient DNA sequence: AGA GGC CTA TAT AAG TCT TTA AAA GGA GCA TGC AAA CTC AAGTTA TGT GGA GTT CTA GGA CTT AGA CTT ATG GAT GGA ACA TGG GTC GCG.
Abstract: The invention relates to a vector for the expression of the antigenic protein of rabies, characterized in that it comprises at least: 1) the following efficient DNA sequence: AGA GGC CTA TAT AAG TCT TTA AAA GGA GCA TGC AAA CTC AAG TTA TGT GGA GTT CTA GGA CTT AGA CTT ATG GAT GGA ACA TGG GTC GCG, and 2) a promoter of the expression of such sequence in a bacteria.

14 citations

Journal ArticleDOI
TL;DR: It is demonstrated that maximal innate immunity activation by muramyl peptides is mediated via an interaction between YB1 and NOD2, and that both contribute to GMDP induction of NF-κB expression, a marker of innate immunity.
Abstract: Bacterial cell wall muramyl dipeptide (MDP) and glucosaminyl-MDP (GMDP) are potent activators of innate immunity. Two receptor targets, NOD2 and YB1, have been reported; we investigated potential overlap of NOD2 and YB1 pathways. Separate knockdown of NOD2 and YB1 demonstrates that both contribute to GMDP induction of NF-κB expression, a marker of innate immunity, although excess YB1 led to induction in the absence of NOD2. YB1 and NOD2 co-migrated on sucrose gradient centrifugation, and GMDP addition led to the formation of higher molecular mass complexes containing both YB1 and NOD2. Co-immunoprecipitation demonstrated a direct interaction between YB1 and NOD2, a major recombinant fragment of NOD2 (NACHT-LRR) bound to YB1, and complex formation was stimulated by GMDP. We also report subcellular colocalization of NOD2 and YB1. Although YB1 may have other binding partners in addition to NOD2, maximal innate immunity activation by muramyl peptides is mediated via an interaction between YB1 and NOD2.

14 citations

Journal ArticleDOI
16 Dec 2017
TL;DR: It is suggested that PRNP, like LL-37 and Aβ, is likely to be a component of the innate immune system, with implications for the pathoetiology of both AD and TSE.
Abstract: The prion protein PRNP has been centrally implicated in the transmissible spongiform encephalopathies (TSEs), but its normal physiological role remains obscure. We highlight emerging evidence that PRNP displays antimicrobial activity, inhibiting the replication of multiple viruses, and also interacts directly with Alzheimer’s disease (AD) amyloid-β (Aβ) peptide whose own antimicrobial role is now increasingly secure. PRNP and Aβ share share membrane-penetrating, nucleic acid binding, and antiviral properties with classical antimicrobial peptides such as LL-37. We discuss findings that binding of abnormal nucleic acids to PRNP leads to oligomerization of the protein, and suggest that this may be an entrapment and sequestration process that contributes to its antimicrobial activity. Some antimicrobial peptides are known to be exploited by infectious agents, and we cover evidence that PRNP is usurped by herpes simplex virus (HSV-1) that has evolved a virus-encoded ‘anti-PRNP’.unction. These findings suggest that PRNP, like LL-37 and Aβ, is likely to be a component of the innate immune system, with implications for the pathoetiology of both AD and TSE.

14 citations

Journal ArticleDOI
01 Mar 2009-Autism
TL;DR: References H A P P É , F. & J U S T, M.A .
Abstract: References H A P P É , F. (1999) ‘Autism: Cognitive Deficit or Cognitive Style?’, Trends in Cognitive Science 3: 216–22. K A NA, R .K . , K E L L E R , T.A . , C H E R K A S S K Y, V. L . , M I N S H E W, N. J. & J U S T, M.A . (2006) ‘Sentence Comprehension in Autism: Thinking in Pictures with Decreased Functional Connectivity’, Brain 129: 2484–93. L O P E Z , B. , L E E K A M, S .R . & A RT S , G.R . (2008) ‘How Central is Central Coherence? Preliminary Evidence on the Link between Conceptual and Perceptual Processing in Children with Autism’, Autism 12 (2): 159–71. TAG E R-F L U S B E R G, H . & J O S E P H, R .M. (2003) ‘Identifying Neurocognitive Phenotypes in Autism’, Philosophical Transactions of the Royal Society of London, Series B 358: 303–14.

14 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组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�ly.
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。

18,940 citations

Journal ArticleDOI
31 Mar 1988-Nature
TL;DR: 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 endothelins is an endogenous modulator of voltage-dependent ion channels.
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.

10,651 citations

Journal ArticleDOI
08 Dec 1989-Science
TL;DR: DNA sequencing suggests the existence of several molecular species of VEGF, a heparin-binding growth factor specific for vascular endothelial cells that is able to induce angiogenesis in vivo.
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.

5,092 citations

ReportDOI
01 Nov 1990
TL;DR: 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.
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.

4,420 citations

Journal ArticleDOI
TL;DR: The straw person model (SPM) as mentioned in this paper has been proposed to explain the orientation effects of active galactic nuclei (AGN) and quasars in the line of sight (LOS) images.
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.

4,005 citations