RNA-mediated epigenetic programming of a genome-rearrangement pathway

Genome-wide DNA rearrangements occur in many eukaryotes but are most exaggerated in ciliates, making them ideal model systems for epigenetic phenomena. During development of the somatic macronucleus, Oxytricha trifallax destroys 95% of its germ line, severely fragmenting its chromosomes, and then unscrambles hundreds of thousands of remaining fragments by permutation or inversion. Here we demonstrate that DNA or RNA templates can orchestrate these genome rearrangements in Oxytricha, supporting an epigenetic model for sequence-dependent comparison between germline and somatic genomes. A complete RNA cache of the maternal somatic genome may be available at a specific stage during development to provide a template for correct and precise DNA rearrangement. We show the existence of maternal RNA templates that could guide DNA assembly, and that disruption of specific RNA molecules disables rearrangement of the corresponding gene. Injection of artificial templates reprogrammes the DNA rearrangement pathway, suggesting that RNA molecules guide genome rearrangement.     

英国国际合作格局

该报告运用文献计量学方法，对英国及其主要合作伙伴国的国际合作格局做了全面的分析。所选
择的主要国家包括美国、加拿大、法国、德国、日本、澳大利亚、中国与印度；数据覆盖领域有临床、医药
卫生、生物科学、环境科学、数学、物质科学以及工程技术领域；数据时间分为1996－2000年与2001－2005
年两个时间段。结果显示：国际论文数量增长显著；英国国际合作论文份额的增长比G7 国家更加快速； 德
国和美国是英国最大的国际合作伙伴；英国国际合作论文的平均影响力显著高于其科研论文的总体影响力；
中国与英国合作发表的论文数量超过了与其他欧洲各国的合作论文数。     

Femtosecond X-ray protein nanocrystallography

X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (～200?nm to 2?μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.     

科学新格局：英国科研及其国际合作

国际合作研究不仅可以利用其他国家的科研投资，而且能够产生具有轰动效应的创新型结果。由
于语言文化的相似性，英国与美国及欧洲国家有着较为广泛的联系，他们之间的合作是英国科学研究合作的
主体。随着科学研究及技术革新的发展更多地转向东方，以及中国和印度这两大科技力量的迅猛发展，英国
应该更加重视与这两个国家的合作。文章指出：应该就英国及其新伙伴之间的关系进行详细的研究，从而深
入理解中英两国间的合作并建立成功的合作模式。     

Differential protection of radiation-induced DNA single-strand breaks and cell survival by solcoseryl

Summary V79 Chinese hamster cells were studied in vitro for modification of cobalt-60 gamma radiation effects by solcoseryl. This treatment did not modify cell survival but did protect against DNA single-strand breaks.Solcoseryl is a registered trademark of Solco Basle Ltd, CH-4127 Birsfelden, Switzerland and was kindly supplied by Drs Haigis and Nasrin. In scientific German literature this material is referred to as Actihaemyl.Supported in part by U.S. Department of Energy Contract No. W-31-109-ENG-38 and NIH/NCI grant No. CA-37435, awarded to D. Grdina, ANL.     

Large-scale prediction and testing of drug activity on side-effect targets

Discovering the unintended 'off-targets' that predict adverse drug reactions is daunting by empirical methods alone. Drugs can act on several protein targets, some of which can be unrelated by conventional molecular metrics, and hundreds of proteins have been implicated in side effects. Here we use a computational strategy to predict the activity of 656 marketed drugs on 73 unintended 'side-effect' targets. Approximately half of the predictions were confirmed, either from proprietary databases unknown to the method or by new experimental assays. Affinities for these new off-targets ranged from 1 nM to 30 μM. To explore relevance, we developed an association metric to prioritize those new off-targets that explained side effects better than any known target of a given drug, creating a drug-target-adverse drug reaction network. Among these new associations was the prediction that the abdominal pain side effect of the synthetic oestrogen chlorotrianisene was mediated through its newly discovered inhibition of the enzyme cyclooxygenase-1. The clinical relevance of this inhibition was borne out in whole human blood platelet aggregation assays. This approach may have wide application to de-risking toxicological liabilities in drug discovery.     

Demographic compensation and tipping points in climate-induced range shifts

To persist, species are expected to shift their geographical ranges polewards or to higher elevations as the Earth's climate warms. However, although many species' ranges have shifted in historical times, many others have not, or have shifted only at the high-latitude or high-elevation limits, leading to range expansions rather than contractions. Given these idiosyncratic responses to climate warming, and their varied implications for species' vulnerability to climate change, a critical task is to understand why some species have not shifted their ranges, particularly at the equatorial or low-elevation limits, and whether such resilience will last as warming continues. Here we show that compensatory changes in demographic rates are buffering southern populations of two North American tundra plants against the negative effects of a warming climate, slowing their northward range shifts, but that this buffering is unlikely to continue indefinitely. Southern populations of both species showed lower survival and recruitment but higher growth of individual plants, possibly owing to longer, warmer growing seasons. Because of these and other compensatory changes, the population growth rates of southern populations are not at present lower than those of northern ones. However, continued warming may yet prove detrimental, as most demographic rates that improved in moderately warmer years declined in the warmest years, with the potential to drive future population declines. Our results emphasize the need for long-term, range-wide measurement of all population processes to detect demographic compensation and to identify nonlinear responses that may lead to sudden range shifts as climatic tipping points are exceeded.     

Effect of endotoxin and dietary phosphorus on the proliferation of liver reticuloendothelial and bone marrow cells

Resumen El grado mayor de proliferación de las RE células después del tratamiento de endotoxina no fué afectado por la cantidad de fósforo del régimen de alimentación pero 1.0% del fósforo abatió el thymidine incorporado dentro del DNA de la médula órea.

---

---

Contribution from the Missouri Agricultural Experiment Station, Journal series No. 6468. Supported in part by NIH Postdoctoral Fellowship No. 1F2FR36 for R. L. Doak.