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

The results of a single-crystal structure determination when in CIF format can now be validated routinely by automatic procedures. In this way, many errors in published papers can be avoided. The validation software generates a set of ALERTS detailing issues to be addressed by the experimenter, author, referee and publication journal. Validation was pioneered by the IUCr journal Acta Crystallographica Section C and is currently standard procedure for structures submitted for publication in all IUCr journals. The implementation of validation procedures by other journals is in progress. This paper describes the concepts of validation and the classes of checks that are carried out by the program PLATON as part of the IUCr checkCIF facility. PLATON validation can be run at any stage of the structure refinement, independent of the structure determination package used, and is recommended for use as a routine tool during or at least at the completion of every structure determination. Two examples are discussed where proper validation procedures could have avoided the publication of incorrect structures that had serious consequences for the chemistry involved.

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Single-crystal structure validation with the program PLATON

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

Phd by thesis

So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Human biochemical genetics

The three-dimensional structure of neohalicholactone, an unusual fatty acid metabolite from the marine sponge halichondria okadai kadota

The biosynthetic gene cluster of pantocin A provides insights into biosynthesis and a tool for screening

The Biosynthetic Gene Cluster of Pantocin A Provides Insights into Biosynthesis and a Tool for Screening

Structure of brianthein W, from the soft coral Briareum polyanthes

Malaria is a devastating parasitic disease that afflicts one-third of the world's population. Antimalarial drugs in common use address few targets, and their efficacy is being undermined by parasite resistance. Most therapeutics target blood-stage malaria, whereas only few compounds are active against malaria's liver stage, the first stage of the Plasmodium parasite's life cycle within the human host. The identification of inhibitors active against liver-stage malaria would benefit the development of chemical probes to elucidate the poorly understood biology of this phase of the parasite life cycle and could provide agents to prevent and eliminate the disease. Herein we report the development of a live-cell parasite traversal assay in 384-well format amenable to high-throughput screening that exploits the wounding of liver cells by the parasite. This method identifies small molecules that may inhibit the parasite's actin-myosin motor system. The traversal assay, in addition to established methods, was used to evaluate the activity of halofuginone, a synthetic halogenated derivative of the natural alkaloid febrifugine, against liver-stage Plasmodium berghei parasites. Halofuginone was found to inhibit P. berghei sporozoite load in HepG2 cells with an IC(50) value of 17 nM. While the compound does not affect parasite traversal through human liver cells, an inhibition time course assay indicates that it affects essential processes in both early- and late-stage parasite development.

Jon Clardy

Papers

The three-dimensional structure of neohalicholactone, an unusual fatty acid metabolite from the marine sponge halichondria okadai kadota

The Biosynthetic Gene Cluster of Pantocin A Provides Insights into Biosynthesis and a Tool for Screening

Structure of brianthein W, from the soft coral Briareum polyanthes

Characterization of Plasmodium liver stage inhibition by halofuginone

Biosynthetic studies on polypropionates : a stereochemical model for siphonarins A and B from the pulmonate limpet Siphonaria zelandica