Cancer therapy

In recent years a growing recognition that molecularly-targeted therapies face formidable obstacles has revived interest in more generic tumor cell phenotypes that could be exploited for therapy. Two recent reports demonstrate that cancer cell survival is critically dependent on the activity of MTH1, a nucleotide pyrophosphatase that converts the oxidized nucleotides 8-oxo-dGTP and 2-OH-dATP to the corresponding monophosphates, thus preventing their incorporation into genomic DNA. Tumor cells frequently overexpress MTH1, probably because malignant transformation creates oxidative stress that renders the nucleotide pool highly vulnerable to oxidation. As a result, MTH1 inhibition in cancer cells results in accumulation and incorporation of 8-oxo-dGTP and 2-OH-dATP into DNA, leading to DNA damage and cell death. This toxic effect is highly cancer cell-specific, as MTH1 is generally dispensable for the survival of normal, untransformed cells. Importantly, MTH1 proves to be a “druggable” enzyme that can be inhibited both by an existing protein kinase inhibitor drug, crizotinib, and by novel compounds identified through screening. Inhibition of MTH1 leading to toxic accumulation of oxidized nucleotides specifically in tumor cells therefore represents an example of a “non-personalised” approach to cancer therapy.     

THE IMMATURE AND ADULT STAGES OF CALLOCOCCUS LEPTOSPERMI (MASKELL) (HOMOPTERA: COCCOIDEA: ASTEROLECANIIDAE), WITH OBSERVATIONS ON LIFE HISTORY

Abstract
The gall-forming scale insect Callococcus leptospermi was studied in the field to determine its life history and method of distribution on the host plant, Leptospermum sp., previously L. juniperinum (Sm.) Domin (prickly tea tree, Myrtaceae). This paper complements earlier taxonomic studies on C. leptospermi. Until now the adult female has provided most of the available data on the species. Newly described stages include the second instar male, the third instar assumed female and the adult male. The sexually dimorphic first instar and adult female are redescribed. Callococcus leptospermi is ovoviviparous. It is dispersed by migration of second instar larvae from the parent gall to new feeding sites.     

尊重斯德哥尔摩的历史中心—骑士岛的激活改造

瑞典国家财产委员会拥有骑士岛的所有权与管理权，并计划对该岛上所有的公共空间进行更新和开发，以提高其可达性与吸引力。该项目的核心是找到一种更新和修复岛屿的方法，从而在尊重历史价值的同时满足现代功能需求。对骑士岛南部的改造是岛上公共空间更新的第一部分。设计的关键条件是沿滨水区域创造可以供人步行与停坐的大面积空间，并在保持开放海港氛围的同时，对旧的道路铺装进行管理。设计者设计了一套灵活使用公共空间的综合解决方案，将开放空间与之前的码头一样，沿着水滨的形态进行布局。     

Reaction rate of OH radicals with phi X174 DNA: influence of salt and scavenger

A derivation is given for the dependence of the rate constant of the reaction of OH radicals with a spherical macromolecule on the rate by which such radicals are scavenged by the medium. Experiments were carried out with oxygenated solutions of dilute single-stranded phi X174 DNA at 10(-4)M NaCl (large reaction radius of DNA) or at 10(-4)M NaCl + MgCl2 (small reaction radius) with t-butanol as a scavenger. The results of these experiments cannot be described by simple second-order competition, but can be explained by the predicted dependence of the rate constant of the reaction OH + DNA on the concentration of t-butanol. Furthermore, the results show that only part of the reactions of OH radicals with phi X174 DNA leads to DNA inactivation, and that even at zero scavenger concentration OH radicals are scavenged by other molecules than DNA, presumably impurities remaining even after careful purification of the DNA.