S-phase checkpoint regulations that preserve replication and chromosome integrity upon dNTP depletion

DNA replication stress, an important source of genomic instability, arises upon different types of DNA replication perturbations, including those that stall replication fork progression. Inhibitors of the cellular pool of deoxynucleotide triphosphates (dNTPs) slow down DNA synthesis throughout the genome. Following depletion of dNTPs, the highly conserved replication checkpoint kinase pathway, also known as the S-phase checkpoint, preserves the functionality and structure of stalled DNA replication forks and prevents chromosome fragmentation. The underlying mechanisms involve pathways extrinsic to replication forks, such as those involving regulation of the ribonucleotide reductase activity, the temporal program of origin firing, and cell cycle transitions. In addition, the S-phase checkpoint modulates the function of replisome components to promote replication integrity. This review summarizes the various functions of the replication checkpoint in promoting replication fork stability and genome integrity in the face of replication stress caused by dNTP depletion.     

Type VI secretion delivers bacteriolytic effectors to target cells

Peptidoglycan is the major structural constituent of the bacterial cell wall, forming a meshwork outside the cytoplasmic membrane that maintains cell shape and prevents lysis. In Gram-negative bacteria, peptidoglycan is located in the periplasm, where it is protected from exogenous lytic enzymes by the outer membrane. Here we show that the type VI secretion system of Pseudomonas aeruginosa breaches this barrier to deliver two effector proteins, Tse1 and Tse3, to the periplasm of recipient cells. In this compartment, the effectors hydrolyse peptidoglycan, thereby providing a fitness advantage for P. aeruginosa cells in competition with other bacteria. To protect itself from lysis by Tse1 and Tse3, P. aeruginosa uses specific periplasmically localized immunity proteins. The requirement for these immunity proteins depends on intercellular self-intoxication through an active type VI secretion system, indicating a mechanism for export whereby effectors do not access donor cell periplasm in transit.     

内蒙古四子王旗带状柠条林根系体积空间分布特征

在内蒙古四子王旗采用挖掘法对不同带间距柠条林地灌草根系体积的空间分布特征进行研究,结果表明:带间灌草根系体积水平分布为全部根系与直径≥0.5 mm根系分布特征相似;直径≤0.2 mm根系对全部根系分布特征的影响在近柠条带1.5 m之内,对16 m带间距林地的影响在2.0 m之后,且呈波状变化;根系体积垂直分布总体上随着土层的加深而减少,随着带间距的加大表土层根系逐渐增加;5 m带间距时遵从y=aebx函数关系,10 m、16 m带间距时遵从y=aLn(x)+b函数关系.16 m带间距林地根系水平分布相对均匀,垂直分布在0～20 cm土层比例较大,是比较适合该地区的灌草复合林地.     

数学与文化2——视觉完美性：数学与创造

创造在人类所有活动中扮演着一个重要的角色。本书是《数学与文化》丛书中的第二本，着重介绍数学、文化与众多领域的创造之间的紧密联系，这些领域包括建筑、当代艺术、地理、计算机绘图、文艺、戏剧和电影。近年来，得益于计算机绘图的出现，可视化在数学的某些部分中的角色越来越引人注目。这类新“可视化数学”必然会为艺术创造与数学之间的联系打开新路，本书收集了关于这些问题的论文。     

Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences

We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.     

Miniature eye movements enhance fine spatial detail

Our eyes are constantly in motion. Even during visual fixation, small eye movements continually jitter the location of gaze. It is known that visual percepts tend to fade when retinal image motion is eliminated in the laboratory. However, it has long been debated whether, during natural viewing, fixational eye movements have functions in addition to preventing the visual scene from fading. In this study, we analysed the influence in humans of fixational eye movements on the discrimination of gratings masked by noise that has a power spectrum similar to that of natural images. Using a new method of retinal image stabilization, we selectively eliminated the motion of the retinal image that normally occurs during the intersaccadic intervals of visual fixation. Here we show that fixational eye movements improve discrimination of high spatial frequency stimuli, but not of low spatial frequency stimuli. This improvement originates from the temporal modulations introduced by fixational eye movements in the visual input to the retina, which emphasize the high spatial frequency harmonics of the stimulus. In a natural visual world dominated by low spatial frequencies, fixational eye movements appear to constitute an effective sampling strategy by which the visual system enhances the processing of spatial detail.     

Rapid Manufacturing of Non-Assembly Complex Micro-Devices by Microstereolithography

This paper introduces a non-assembly manufacturing case with microstereolithography technology. The design and manufacturing process of a pneumatic thrust bearing is described, and a special tessellation method is developed to further improve the capability of the manufacturing system thus bigger products can also be easily manufactured. Implemented in a layer-by-layer fashion, stereolithography has been used for the rapid manufacturing of complex devices, and it avoids the expensive assembly process in the traditional manufacturing. This paper presents that microstereolithography can produce high-resolution products with intricate details, small openings, and smooth surfaces. The potential of the microstereolithograhy technique is explored for the rapid manufacturing of small and complex objects.     

应用激光反射仪研究聚氧乙烯十二烷基醚溶液在硅片表面上的吸附解吸过程(英文)

将激光反射仪应用于溶液吸附上,考察了聚氧乙烯十二烷基醚--一种非离子表面活性剂溶液在硅片表面上的吸附解吸过程,结果表明其吸附过程极快,30s 达到稳定值,且解吸完全.其最大吸附量Г(mg·m-2)是2.45 mg·m-2.在临界表面相关浓度CSAC(0.045 5 mmol·L-1)以下的浓度范围内,吸附模型符合Langmuir模型.     

A murine lung cancer co-clinical trial identifies genetic modifiers of therapeutic response

Targeted therapies have demonstrated efficacy against specific subsets of molecularly defined cancers. Although most patients with lung cancer are stratified according to a single oncogenic driver, cancers harbouring identical activating genetic mutations show large variations in their responses to the same targeted therapy. The biology underlying this heterogeneity is not well understood, and the impact of co-existing genetic mutations, especially the loss of tumour suppressors, has not been fully explored. Here we use genetically engineered mouse models to conduct a 'co-clinical' trial that mirrors an ongoing human clinical trial in patients with KRAS-mutant lung cancers. This trial aims to determine if the MEK inhibitor selumetinib (AZD6244) increases the efficacy of docetaxel, a standard of care chemotherapy. Our studies demonstrate that concomitant loss of either p53 (also known as Tp53) or Lkb1 (also known as Stk11), two clinically relevant tumour suppressors, markedly impaired the response of Kras-mutant cancers to docetaxel monotherapy. We observed that the addition of selumetinib provided substantial benefit for mice with lung cancer caused by Kras and Kras and p53 mutations, but mice with Kras and Lkb1 mutations had primary resistance to this combination therapy. Pharmacodynamic studies, including positron-emission tomography (PET) and computed tomography (CT), identified biological markers in mice and patients that provide a rationale for the differential efficacy of these therapies in the different genotypes. These co-clinical results identify predictive genetic biomarkers that should be validated by interrogating samples from patients enrolled on the concurrent clinical trial. These studies also highlight the rationale for synchronous co-clinical trials, not only to anticipate the results of ongoing human clinical trials, but also to generate clinically relevant hypotheses that can inform the analysis and design of human studies.