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

Summary: Evolution of RNA viruses occurs through disequilibria of collections of closely related mutant spectra or mutant clouds termed viral quasispecies. Here we review the origin of the quasispecies concept and some biological implications of quasispecies dynamics. Two main aspects are addressed: (i) mutant clouds as reservoirs of phenotypic variants for virus adaptability and (ii) the internal interactions that are established within mutant spectra that render a virus ensemble the unit of selection. The understanding of viruses as quasispecies has led to new antiviral designs, such as lethal mutagenesis, whose aim is to drive viruses toward low fitness values with limited chances of fitness recovery. The impact of quasispecies for three salient human pathogens, human immunodeficiency virus and the hepatitis B and C viruses, is reviewed, with emphasis on antiviral treatment strategies. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory.

Viral Quasispecies Evolution

The organic geochemistry of glycerol dialkyl glycerol tetraether lipids: A review

Light-driven phenomena both in living systems and nonliving materials have enabled truly fascinating and incredible dynamic architectures with terrific forms and functions. Recently, liquid crystalline materials endowed with photoresponsive capability have emerged as enticing systems. In this Review, we focus on the developments of light-driven liquid crystalline materials containing photochromic components over the past decade. Design and synthesis of photochromic liquid crystals (LCs), photoinduced phase transitions in LC, and photoalignment and photoorientation of LCs have been covered. Photomodulation of pitch, polarization, lattice constant and handedness inversion of chiral LCs is discussed. Light-driven phenomena and properties of liquid crystalline polymers, elastomers, and networks have also been analyzed. The applications of photoinduced phase transitions, photoalignment, photomodulation of chiral LCs, and photomobile polymers have been highlighted wherever appropriate. The combination of photoc...

Light-Driven Liquid Crystalline Materials: From Photo-Induced Phase Transitions and Property Modulations to Applications.

Absorption and emission in polymer aggregates is studied theoretically, taking into account excitonic (intermolecular) coupling, exciton-phonon (EP) coupling, and disorder, all treated on equal footing within a generalized Holstein Hamiltonian with numerically generated eigenmodes and energies. The disorder is modeled as a Gaussian distribution of molecular transition frequency offsets of width sigma and spatial correlation length l(0). Both herringbone (HB) and lamellar aggregate morphologies are considered. The emission spectral line shape is shown to undergo marked changes in response to increasing disorder, with the intensity of the ac-polarized 0-0 emission peak generally increasing relative to the replica intensities (0-1,0-2,[ellipsis (horizontal)]) as sigma increases and/or as l(0) decreases. This is contrary to the behavior of the b-polarized component of the 0-0 intensity, which, in HB aggregates, decreases with increasing disorder. Comparisons are made to analogous trends in oligomer aggregates. Analytical results are obtained in the strong EP coupling regime appropriate for conjugated polymers while treating the disorder perturbatively. A method for uniquely determining sigma and l(0) from the emission and absorption spectra is presented. Applications are made to absorption and low-temperature emission in thin films of regioregular poly(3-hexylthiophene), with excellent agreement between theory and experiment obtained for a spatial correlation length of only 3-4 molecules.

Modeling disorder in polymer aggregates: the optical spectroscopy of regioregular poly(3-hexylthiophene) thin films.

Two diastereomers of the monoalkoxidepyrrolide (MAP) species, W(NAr)(CH2)(Me2Pyr)(OR*) (1; Ar = 2,6-diisopropylphenyl, Me2Pyr = 2,5-dimethylpyrrolide, OR* = (R)-3,3′-dibromo-2′-(tert-butyldimethylsilyloxy)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-olate), were generated through addition of R*OH to W(NAr)(CH2)(Me2Pyr)2. The unsubstituted tungstacyclobutane species, W(NAr)(C3H6)(Me2Pyr)(OR*) (2), was isolated by treating the mixture of diastereomers of 1 with ethylene. An X-ray study revealed 2 to have a trigonal bipyramidal structure in which the imido and phenoxide ligands are in axial positions. A variety of NMR experiments were carried out on 1 and 2. The major findings are the following: (i) the methylidene ligands in the two diastereomers of 1 rotate readily about the W═C bond (k = 2−7 s−1 at 22 °C); (ii) NMR studies are consistent with 2 breaking up to give an intermediate alkylidene/ethylene complex, (R)- and (S)-W(CH2)(C2H4); and (iii) the ethylene in the (R)-W(CH2)(C2H4) intermediate can rot...

/pdf/fundamental-studies-of-tungsten-alkylidene-imido-4xlvzedxq7.pdf

Fundamental studies of tungsten alkylidene imido monoalkoxidepyrrolide complexes.

Abstract Hydroxylated glycerol dialkyl glycerol tetraethers (hydroxy-GDGTs) were detected in marine sediments of diverse depositional regimes and ages. Mass spectrometric evidence, complemented by information gleaned from two-dimensional (2D) 1H–13C nuclear magnetic resonance (NMR) spectroscopy on minute quantities of target analyte isolated from marine sediment, allowed us to identify one major compound as a monohydroxy-GDGT with acyclic biphytanyl moieties (OH-GDGT-0). NMR spectroscopic and mass spectrometric data indicate the presence of a tertiary hydroxyl group suggesting the compounds are the tetraether analogues of the widespread hydroxylated archaeol derivatives that have received great attention in geochemical studies of the last two decades. Three other related compounds were assigned as acyclic dihydroxy-GDGT (2OH-GDGT-0) and monohydroxy-GDGT with one (OH-GDGT-1) and two cyclopentane rings (OH-GDGT-2). Based on the identification of hydroxy-GDGT core lipids, a group of previously reported unknown intact polar lipids (IPLs), including the ubiquitously distributed H341-GDGT (Lipp J. S. and Hinrichs K. -U. (2009) Structural diversity and fate of intact polar lipids in marine sediments. Geochim. Cosmochim. Acta 73, 6816–6833), and its analogues were tentatively identified as glycosidic hydroxy-GDGTs. In addition to marine sediments, we also detected hydroxy-GDGTs in a culture of Methanothermococcus thermolithotrophicus. Given the previous finding of the putative polar precursor H341-GDGT in the planktonic marine crenarchaeon Nitrosopumilus maritimus, these compounds are synthesized by representatives of both cren- and euryarchaeota. The ubiquitous distribution and apparent substantial abundance of hydroxy-GDGT core lipids in marine sediments (up to 8% of total isoprenoid core GDGTs) point to their potential as proxies.

/pdf/mono-and-dihydroxyl-glycerol-dibiphytanyl-glycerol-1mh0vliojv.pdf

Mono- and dihydroxyl Glycerol Dibiphytanyl Glycerol Tetraethers in

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first “mechanism validation” phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.

/pdf/mutation-of-hiv-1-genomes-in-a-clinical-population-treated-5dwblxcy54.pdf

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

Mono- and dihydroxyl glycerol dibiphytanyl glycerol tetraethers in marine sediments: Identification of both core and intact polar lipid forms

http://web.mit.edu/pmueller/www/own_papers/schrock_etal_2010.pdf

Jeffrey H. Simpson

Papers

Fundamental studies of tungsten alkylidene imido monoalkoxidepyrrolide complexes.

Mono- and dihydroxyl Glycerol Dibiphytanyl Glycerol Tetraethers in

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

Mono- and dihydroxyl glycerol dibiphytanyl glycerol tetraethers in marine sediments: Identification of both core and intact polar lipid forms

Fundamental Studies of Molybdenum and Tungsten Methylidene and Metallacyclobutane Complexes