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。

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

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.

/pdf/a-novel-potent-vasoconstrictor-peptide-produced-by-vascular-4zvh0kyupn.pdf

A novel potent vasoconstrictor peptide produced by vascular endothelial cells.

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.

https://science.sciencemag.org/content/sci/246/4935/1306.full.pdf

Vascular endothelial growth factor is a secreted angiogenic mitogen

: 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.

/pdf/feature-oriented-domain-analysis-foda-feasibility-study-2zsj0a30fo.pdf

Feature-Oriented Domain Analysis (FODA) Feasibility Study

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.

http://www.physics.purdue.edu/%7Emlister/articles/antonucci1993_ann_rev.pdf

Unified models for active galactic nuclei and quasars

Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

http://www.pieta-research.org/PDFfiles/DAVIES1998.pdf

Serine Proteases in Rodent Hippocampus

Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation.

In a variety of mammalian species including humans the newborn young are particularly susceptible to diarrhoeal disease brought about by toxin-producing strains of the common gut bacterium, Escherichia coli1. Two types of enterotoxin have been described2. The first, heat-labile toxin (LT), sharing partial antigenic identity with cholera toxin2,3 is comprised of two subunits having molecular weights of 25,500 and 11,5004 and, like cholera toxin, stimulates adenyl cyclase activity in the gut5. The second type, heat-stable toxin (ST), is a low-molecular weight protein which is excreted into the medium during the growth of ST-elaborating strains. Unlike LT, ST is poorly antigenic and for this reason the identification of ST-producing strains has relied on an assay involving the intragastric injection of infant mice, a test specific for ST6. Although many strains produce both ST and LT, strains producing ST alone are especially common in E. coli diarrhoeal disease of calves7,8, pigs2 and have also been implicated in outbreaks of diarrhoea in humans9,10. Recent evidence suggests that ST activates guanyl cyclase in the gut11,12 and its molecular weight has been estimated to be 4,400–5,100 (ref. 13). We have now applied gene cloning techniques to the isolation of ST genes from two porcine E. coli isolates and report here the identification of the protein product of molecular weight 7,000, synthesised in an in vitro system directed by the cloned DNA template. This in vitro gene product elicits a typical ST enterotoxin response in the infant mouse assay and is most probably synthesised as a 10,000 molecular weight precursor, as might be expected for an exported protein. The gene cloning data also provide evidence that the ST genes and their surrounding transposon structures are probably identical in both porcine and bovine strains of entero-pathogenic E. coli.

Richard Lathe

Papers

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

Serine Proteases in Rodent Hippocampus

Neurosteroid hydroxylase CYP7B: vivid reporter activity in dentate gyrus of gene-targeted mice and abolition of a widespread pathway of steroid and oxysterol hydroxylation.

Cell-free synthesis of enterotoxin of E. coli from a cloned gene.

A ubiquitous mammalian expression vector, pHMG, based on a housekeeping gene promoter.