Temperature-scan cryocrystallography reveals reaction intermediates in bacteriophytochrome

Light is a fundamental signal that regulates important physiological processes such as development and circadian rhythm in living organisms. Phytochromes form a major family of photoreceptors responsible for red light perception in plants, fungi and bacteria. They undergo reversible photoconversion between red-absorbing (Pr) and far-red-absorbing (Pfr) states, thereby ultimately converting a light signal into a distinct biological signal that mediates subsequent cellular responses. Several structures of microbial phytochromes have been determined in their dark-adapted Pr or Pfr states. However, the structural nature of initial photochemical events has not been characterized by crystallography. Here we report the crystal structures of three intermediates in the photoreaction of Pseudomonas aeruginosa bacteriophytochrome (PaBphP). We used cryotrapping crystallography to capture intermediates, and followed structural changes by scanning the temperature at which the photoreaction proceeded. Light-induced conformational changes in PaBphP originate in ring D of the biliverdin (BV) chromophore, and E-to-Z isomerization about the C(15) = C(16) double bond between rings C and D is the initial photochemical event. As the chromophore relaxes, the twist of the C(15) methine bridge about its two dihedral angles is reversed. Structural changes extend further to rings B and A, and to the surrounding protein regions. These data indicate that absorption of a photon by the Pfr state of PaBphP converts a light signal into a structural signal via twisting and untwisting of the methine bridges in the linear tetrapyrrole within the confined protein cavity.     

Sequence and analysis of chromosome 2 of the plant Arabidopsis thaliana

Arabidopsis thaliana (Arabidopsis) is unique among plant model organisms in having a small genome (130-140 Mb), excellent physical and genetic maps, and little repetitive DNA. Here we report the sequence of chromosome 2 from the Columbia ecotype in two gap-free assemblies (contigs) of 3.6 and 16 megabases (Mb). The latter represents the longest published stretch of uninterrupted DNA sequence assembled from any organism to date. Chromosome 2 represents 15% of the genome and encodes 4,037 genes, 49% of which have no predicted function. Roughly 250 tandem gene duplications were found in addition to large-scale duplications of about 0.5 and 4.5 Mb between chromosomes 2 and 1 and between chromosomes 2 and 4, respectively. Sequencing of nearly 2 Mb within the genetically defined centromere revealed a low density of recognizable genes, and a high density and diverse range of vestigial and presumably inactive mobile elements. More unexpected is what appears to be a recent insertion of a continuous stretch of 75% of the mitochondrial genome into chromosome 2.     

利用光纤光栅实现压力和温度同时测量

结合光纤光栅弹簧管压力传感器的结构特点 ,在悬臂梁的上下两面分别粘贴两个应力和温度灵敏系数基本相同的光纤光栅 ,通过分别测量光纤光栅对的波长位移 ,实现了压力和温度的同时测量 ,压力和温度测量的分辨率分别为 0 .1 4 MPa和 0 .5℃ .     

值物保护:一个任重道远的课题

美国康奈尔大学的农业科学家皮门塔尔(D. Pimentel)提醒世人注意,在当今世界,尽管高新农业在不断发展,但毁灭作物的病虫害随时有可能爆发.许多植物致病菌及其载体,对曾制止了它们的生物控制产生了抗性;某些效果明显的化学物质,如杀真菌剂溴化物,因环境的关系被禁用;全球旅行把病毒、细菌和真菌植物病原体扩散到新地区;而全球气候变暖,极大地扩展了昆虫(载体)的活动范围.     

Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors

Mutationally activated kinases define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumours harbour such alleles is invariably limited by innate or acquired drug resistance. The identification of resistance mechanisms has revealed a recurrent theme—the engagement of survival signals redundant to those transduced by the targeted kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs) that mediate signals that converge on common critical downstream cell-survival effectors—most notably, phosphatidylinositol-3-OH kinase (PI(3)K) and mitogen-activated protein kinase (MAPK). Consequently, an increase in RTK-ligand levels, through autocrine tumour-cell production, paracrine contribution from tumour stroma or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar signalling output. Here, using a panel of kinase-'addicted' human cancer cell lines, we found that most cells can be rescued from drug sensitivity by simply exposing them to one or more RTK ligands. Among the findings with clinical implications was the observation that hepatocyte growth factor (HGF) confers resistance to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF-mutant melanoma cells. These observations highlight the extensive redundancy of RTK-transduced signalling in cancer cells and the potentially broad role of widely expressed RTK ligands in innate and acquired resistance to drugs targeting oncogenic kinases.     

No stellar p-mode oscillations in space-based photometry of Procyon

Pressure-driven (p-mode) oscillations at the surface of the Sun, resulting from sound waves travelling through the solar interior, are a powerful probe of solar structure, just as seismology can reveal details about the interior of the Earth. Astronomers have hoped to exploit p-mode asteroseismology in Sun-like stars to test detailed models of stellar structure and evolution, but the observations are extremely difficult. The bright star Procyon has been considered one of the best candidates for asteroseismology, on the basis of models and previous reports of p-modes detected in ground-based spectroscopy. Here we present a search for p-modes in 32 days of nearly continuous photometric satellite-based observations of Procyon. If there are p-modes in Procyon, they must have lifetimes less than 2-3 days and/or peak amplitudes <15 parts per million, which defy expectations from the Sun's oscillations and previous theoretical predictions. Target selection for future planned asteroseismology space missions may need to be reconsidered, as will the theory of stellar oscillations.     

The deposition of ingested silver in the rat kidney at different ages

Résumé Si l'cau potable est additionnée de 0,15% de nitrate d'argent, l'argent se dépose dans les reins des rats immatures plus lentement et en moins grande quantité que chez les adultes, et ces granules sont partout plus petits. Il est probable que ces résultats indiquent un abaissement de la perméabilité des capillaires chez les immatures.

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The technical assistance of Mrs.Beverley Thomas and MissLucia Maw is gratefully acknowledged. This work was supported by a grant from the Medical Research Council. The electron microscope is on permanent loan from the Wellcome Trust to ProfessorJ. D. Lever, whom we thank.