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

FLUOROPROSTAGLANDINS: SYNTHESIS AND BIOLOGICAL EVALUATION OF THE METHYL ESTERS OF (+)-12-FLUORO-, (-)-ENT-12-FLUORO-, (+)-15-EPI-FLUORO-, AN (-)-ENT-15-EPI-12-FLUOROPROSTAGLANDIN F2α

Eine neue zweistufensynthese von 10h-benz(b)indeno(2,1-d)thiophen, heterocyclopentadiene 3. mitt.

Artemisinin-derived compounds play an integral role in current malaria chemotherapy. Given the virtual certainty of emerging resistance, we have investigated spiro-1,2-dioxolanes as an alternative scaffold. The endoperoxide functionality was generated by the SnCl 4 -mediated annulation of a bis -silylperoxide and an alkene. The first set of eight analogs gave EC 50 values of 50–150 nM against Plasmodium falciparum 3D7 and Dd2 strains, except for the carboxylic acid analog. A second series, synthesized by coupling a spiro-1,2-dioxolane carboxylic acid to four separate amines, afforded the most potent compound (EC 50 ∼5 nM).

Synthesis of Spiro-1,2-dioxolanes and Their Activity Against Plasmodium falciparum.

THE STERPURIC ACIDS: A NEW TYPE OF SESQUITERPENOID ††Dedicated to the memory of Professor R. B. Woodward. Presented in part at the 63rd Canadian Chemical Conference, Ottawa, June 1980. Abstracts, p. 120.

A series of compounds was investigated in order to determine the factors that govem the cycloaromatization reaction exhibited by dynemicin A and related molecules. It was determined that the stereochemistry at ClOa dictated the thermal reactivity of compounds equipped with an exo-epoxide. Structures containing an a-substituent were unreactive while those possessing a P-substituent underwent cyclization at 80 "C. Molecular mechanics and dynamics calculations indicate that this reactivity difference is due to a steric interaction that develops as the a-substituted compounds undergo a conformational change that appears to be necessary for aromatization to occur. Additionally, a C 10a a-substituted endo-epoxide was synthesized and shown to undergo cycloaromatization under mild acidic conditions via an epoxide opening.

Jon Clardy

Papers

FLUOROPROSTAGLANDINS: SYNTHESIS AND BIOLOGICAL EVALUATION OF THE METHYL ESTERS OF (+)-12-FLUORO-, (-)-ENT-12-FLUORO-, (+)-15-EPI-FLUORO-, AN (-)-ENT-15-EPI-12-FLUOROPROSTAGLANDIN F2α

Eine neue zweistufensynthese von 10h-benz(b)indeno(2,1-d)thiophen, heterocyclopentadiene 3. mitt.

Synthesis of Spiro-1,2-dioxolanes and Their Activity Against Plasmodium falciparum.

THE STERPURIC ACIDS: A NEW TYPE OF SESQUITERPENOID ††Dedicated to the memory of Professor R. B. Woodward. Presented in part at the 63rd Canadian Chemical Conference, Ottawa, June 1980. Abstracts, p. 120.

Stereochemical and Conformational Effects on the Cycloaromatization of Dynemicin A‐Related Molecules