HDACs link the DNA damage response, processing of double-strand breaks and autophagy

Protein acetylation is mediated by histone acetyltransferases (HATs) and deacetylases (HDACs), which influence chromatin dynamics, protein turnover and the DNA damage response. ATM and ATR mediate DNA damage checkpoints by sensing double-strand breaks and single-strand-DNA-RFA nucleofilaments, respectively. However, it is unclear how acetylation modulates the DNA damage response. Here we show that HDAC inhibition/ablation specifically counteracts yeast Mec1 (orthologue of human ATR) activation, double-strand-break processing and single-strand-DNA-RFA nucleofilament formation. Moreover, the recombination protein Sae2 (human CtIP) is acetylated and degraded after HDAC inhibition. Two HDACs, Hda1 and Rpd3, and one HAT, Gcn5, have key roles in these processes. We also find that HDAC inhibition triggers Sae2 degradation by promoting autophagy that affects the DNA damage sensitivity of hda1 and rpd3 mutants. Rapamycin, which stimulates autophagy by inhibiting Tor, also causes Sae2 degradation. We propose that Rpd3, Hda1 and Gcn5 control chromosome stability by coordinating the ATR checkpoint and double-strand-break processing with autophagy.     

PML targeting eradicates quiescent leukaemia-initiating cells

The existence of a small population of 'cancer-initiating cells' responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells, particularly those that are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies, resulting in disease relapse. Chronic myeloid leukaemia is a paradigmatic haematopoietic stem cell disease in which the leukaemia-initiating-cell pool is not eradicated by current therapy, leading to disease relapse on drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in haematopoietic stem cell maintenance, and present a new therapeutic approach for targeting quiescent leukaemia-initiating cells and possibly cancer-initiating cells by pharmacological inhibition of PML.     

基于激光测高卫星的东南极表面高变化分析

利用美国国家冰雪数据中心(NSIDC)最新发布的ICESat(云和地面高度卫星)R633版本的GLA12激光测高数据,使用重复轨最小二乘平面拟合的方法,计算得到东南极兰伯特冰川流域(Lambert)2003年~2009年的高程变化率.使用高度计重复观测数据确定表面高变化的时候,要考虑地形坡度的影响.假定在沿ICESat重复轨道小段范围内,可以用平面来拟合坡度和高程变化,并依此来计算高程变化.结果表明,Lambert冰川流域2003年~2009年平均高程变化率为(1±0.5)cm·yr-1.与已有研究成果以及交叉点获取的高程变化比较,提出的重复轨平面拟合方法有效可行.     

Suppression of star formation in early-type galaxies by feedback from supermassive black holes

Detailed high-resolution observations of the innermost regions of nearby galaxies have revealed the presence of supermassive black holes. These black holes may interact with their host galaxies by means of 'feedback' in the form of energy and material jets; this feedback affects the evolution of the host and gives rise to observed relations between the black hole and the host. Here we report observations of the ultraviolet emissions of massive early-type galaxies. We derive an empirical relation for a critical black-hole mass (as a function of velocity dispersion) above which the outflows from these black holes suppress star formation in their hosts by heating and expelling all available cold gas. Supermassive black holes are negligible in mass compared to their hosts but nevertheless seem to play a critical role in the star formation history of galaxies.     

Proton-proton correlations observed in two-proton radioactivity of 94Ag

The stability and spontaneous decay of naturally occurring atomic nuclei have been much studied ever since Becquerel discovered natural radioactivity in 1896. In 1960, proton-rich nuclei with an odd or an even atomic number Z were predicted to decay through one- and two-proton radioactivity, respectively. The experimental observation of one-proton radioactivity was first reported in 1982, and two-proton radioactivity has now also been detected by experimentally studying the decay properties of 45Fe (refs 3, 4) and 54Zn (ref. 5). Here we report proton-proton correlations observed during the radioactive decay of a spinning long-lived state of the lightest known isotope of silver, 94Ag, which is known to undergo one-proton decay. We infer from these correlations that the long-lived state must also decay through simultaneous two-proton emission, making 94Ag the first nucleus to exhibit one- as well as two-proton radioactivity. We attribute the two-proton emission behaviour and the unexpectedly large probability for this decay mechanism to a very large deformation of the parent nucleus into a prolate (cigar-like) shape, which facilitates emission of protons either from the same or from opposite ends of the 'cigar'.     

Simple,geometrical model for a typical echinocyte III

Summary The purpose of the present work is to obtain information relative to the volume and surface area of echinocyte, type III, on the basis of simple, micrographical evidence. A concrete case has been examined as direct demonstration of theory and techniques of calculus.     

热和声：两种不同声能流，可否作统一的数学处理？

设计每栋建筑的目的在于蔽护人类，使之与外界有所隔离．此外界不仅指气候条件，同时也指人类自身产生的某些现象（如噪声），尽管人类并不喜欢它．适当的建筑设计的基础是这些构成法则的知识，它使人们得以预见热和噪声是如何透过住宅墙体以及有多少数量的热和噪声透过墙体渗入居住空间．这些法则源自两个不同但区别不大的方程．它们都是用来解决相同的物理现象（即散射）的、文中结果表明有可能发展出一种单一的理论来处理这两种物理现象，可从研究频率这一有效反映弹性介质中的物质对压力渡的固有反应的初始差别来着手分析．     

Molecular epidemiology: HIV-1 and HCV sequences from Libyan outbreak

In 1998, outbreaks of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection were reported in children attending Al-Fateh Hospital in Benghazi, Libya. Here we use molecular phylogenetic techniques to analyse new virus sequences from these outbreaks. We find that the HIV-1 and HCV strains were already circulating and prevalent in this hospital and its environs before the arrival in March 1998 of the foreign medical staff (five Bulgarian nurses and a Palestinian doctor) who stand accused of transmitting the HIV strain to the children.     

Artificial Diamonds are Still Diamonds

As a reply to the commentary (Lenhard in Found Sci, 2012), we stress here that structural understanding of data analysis techniques is the natural counterpart to the lack of understanding of phenomena in agnostic science. We suggest moreover that the dynamics of computational processes, and their parallels with the dynamics of natural processes, will increasingly be, possibly, the driving force of the development of data analysis.