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

https://staff.blog.ui.ac.id/hsuryadi/files/2012/02/ROS_RNS.pdf

Free radicals and antioxidants in normal physiological functions and human disease

J. Appl. Cryst.の発刊に際して

The X-ray crystal structure of the nucleosome core particle of chromatin shows in atomic detail how the histone protein octamer is assembled and how 146 base pairs of DNA are organized into a superhelix around it. Both histone/histone and histone/DNA interactions depend on the histone fold domains and additional, well ordered structure elements extending from this motif. Histone amino-terminal tails pass over and between the gyres of the DNA superhelix to contact neighbouring particles. The lack of uniformity between multiple histone/DNA-binding sites causes the DNA to deviate from ideal superhelix geometry.

Crystal structure of the nucleosome core particle at 2.8 Å resolution

Free radicals, metals and antioxidants in oxidative stress-induced cancer

The first molecular adducts of platinum and arsenic based anticancer drugs - arsenoplatins - show unanticipated structure, substitution chemistry, and cellular cytotoxicity. The PtII-AsIII bonds in these complexes are stable in aqueous solution and strongly influence the lability of the trans ligand.

/pdf/robust-structure-and-reactivity-of-aqueous-arsenous-acid-2svcc64ogs.pdf

Robust Structure and Reactivity of Aqueous Arsenous Acid–Platinum(II) Anticancer Complexes

Multiple heavy-atom reagents for macromolecular X-ray structure determination. Application to the nucleosome core particle.

The 199Hg Chemical Shift as a Probe of Coordination Environments in Blue Copper Proteins

Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment. We show that the regulation of the chromatin nanoenvironment allows for the predictable modulation of global patterns in gene expression. In particular, we show that the rational modulation of chromatin density fluctuations can lead to a decrease in global transcriptional activity and intercellular transcriptional heterogeneity in cancer cells during chemotherapeutic responses to achieve near-complete cancer cell killing in vitro. Our findings represent a ‘macrogenomic engineering’ approach to modulating the physical structure of chromatin for whole-scale transcriptional modulation.

/pdf/macrogenomic-engineering-via-modulation-of-the-scaling-of-1s122827pl.pdf

Thomas V. O'Halloran

Papers

Robust Structure and Reactivity of Aqueous Arsenous Acid–Platinum(II) Anticancer Complexes

Multiple heavy-atom reagents for macromolecular X-ray structure determination. Application to the nucleosome core particle.

The 199Hg Chemical Shift as a Probe of Coordination Environments in Blue Copper Proteins

Macrogenomic engineering via modulation of the scaling of chromatin packing density.

Solid-state mercury-199 nuclear magnetic resonance as a probe of coordination number and geometry in Hg(II) complexes