Elucidation of the Clustered Nano-Architecture of Radiation-Induced DNA Damage Sites and Surrounding Chromatin in Cancer Cells: A Single Molecule Localization Microscopy Approach

In cancer therapy, the application of (fractionated) harsh radiation treatment is state of the art for many types of tumors. However, ionizing radiation is a “double-edged sword”—it can kill the tumor but can also promote the selection of radioresistant tumor cell clones or even initiate carcinogenesis in the normal irradiated tissue. Individualized radiotherapy would reduce these risks and boost the treatment, but its development requires a deep understanding of DNA damage and repair processes and the corresponding control mechanisms. DNA double strand breaks (DSBs) and their repair play a critical role in the cellular response to radiation. In previous years, it has become apparent that, beyond genetic and epigenetic determinants, the structural aspects of damaged chromatin (i.e., not only of DSBs themselves but also of the whole damage-surrounding chromatin domains) form another layer of complex DSB regulation. In the present article, we summarize the application of super-resolution single molecule localization microscopy (SMLM) for investigations of these structural aspects with emphasis on the relationship between the nano-architecture of radiation-induced repair foci (IRIFs), represented here by γH2AX foci, and their chromatin environment. Using irradiated HeLa cell cultures as an example, we show repair-dependent rearrangements of damaged chromatin and analyze the architecture of γH2AX repair clusters according to topological similarities. Although HeLa cells are known to have highly aberrant genomes, the topological similarity of γH2AX was high, indicating a functional, presumptively genome type-independent relevance of structural aspects in DSB repair. Remarkably, nano-scaled chromatin rearrangements during repair depended both on the chromatin domain type and the treatment. Based on these results, we demonstrate how the nano-architecture and topology of IRIFs and chromatin can be determined, point to the methodological relevance of SMLM, and discuss the consequences of the observed phenomena for the DSB repair network regulation or, for instance, radiation treatment outcomes.     

Characterization of the Functional Cross-Talk between Surface GABAA and Dopamine D5 Receptors

The γ-aminobutyric acid type A receptor (GABA_AR) plays a major role in fast inhibitory synaptic transmission and is highly regulated by the neuromodulator dopamine. In this aspect, most of the attention has been focused on the classical intracellular signaling cascades following dopamine G-protein-coupled receptor activation. Interestingly, the GABA_AR and dopamine D5 receptor (D5R) have been shown to physically interact in the hippocampus, but whether a functional cross-talk occurs is still debated. In the present study, we use a combination of imaging and single nanoparticle tracking in live hippocampal neurons to provide evidence that GABA_ARs and D5Rs form dynamic surface clusters. Disrupting the GABA_AR–D5R interaction with a competing peptide leads to an increase in the diffusion coefficient and the explored area of both receptors, and a drop in immobile synaptic GABA_ARs. By means of patch-clamp recordings, we show that this fast lateral redistribution of surface GABA_ARs correlates with a robust depression in the evoked GABAergic currents. Strikingly, it also shifts in time the expression of long-term potentiation at glutamatergic synapses. Together, our data both set the plasma membrane as the primary stage of a functional interplay between GABA_AR and D5R, and uncover a non-canonical role in regulating synaptic transmission.     

Supramolecular Nanofibers from Collagen-Mimetic Peptides Bearing Various Aromatic Groups at N-Termini via Hierarchical Self-Assembly

Self-assembly of artificial peptides has been widely studied for constructing nanostructured materials, with numerous potential applications in the nanobiotechnology field. Herein, we report the synthesis and hierarchical self-assembly of collagen-mimetic peptides (CMPs) bearing various aromatic groups at the N-termini, including 2-naphthyl, 1-naphtyl, anthracenyl, and pyrenyl groups, into nanofibers. The CMPs (R-(GPO)_n: n > 4) formed a triple helix structure in water at 4 °C, as confirmed via CD analyses, and their conformations were more stable with increasing hydrophobicity of the terminal aromatic group and peptide chain length. The resulting pre-organized triple helical CMPs showed diverse self-assembly into highly ordered nanofibers, reflecting their slight differences in hydrophobic/hydrophilic balance and configuration of aromatic templates. TEM analysis demonstrated that 2Np-CMP_n (n = 6 and 7) and Py-CMP₆ provided well-developed natural collagen-like nanofibers and An-CMP_n (n = 5–7) self-assembled into rod-like micelle fibers. On the other hand, 2Np-CMP₅ and 1Np-CMP₆ were unable to form nanofibers under the same conditions. Furthermore, the Py-CMP₆ nanofiber was found to encapsulate a guest hydrophobic molecule, Nile red, and exhibited unique emission behavior based on the specific nanostructure. In addition to the ability of CMPs to bind small molecules, their controlled self-assembly enables their versatile utilization in drug delivery and wavelength-conversion nanomaterials.     

Current Perspectives on the Physiological Activities of Fermented Soybean-Derived Cheonggukjang

Cheonggukjang (CGJ, fermented soybean paste), a traditional Korean fermented dish, has recently emerged as a functional food that improves blood circulation and intestinal regulation. Considering that excessive consumption of refined salt is associated with increased incidence of gastric cancer, high blood pressure, and stroke in Koreans, consuming CGJ may be desirable, as it can be made without salt, unlike other pastes. Soybeans in CGJ are fermented by Bacillus strains (B. subtilis or B. licheniformis), Lactobacillus spp., Leuconostoc spp., and Enterococcus faecium, which weaken the activity of putrefactive bacteria in the intestines, act as antibacterial agents against pathogens, and facilitate the excretion of harmful substances. Studies on CGJ have either focused on improving product quality or evaluating the bioactive substances contained in CGJ. The fermentation process of CGJ results in the production of enzymes and various physiologically active substances that are not found in raw soybeans, including dietary fiber, phospholipids, isoflavones (e.g., genistein and daidzein), phenolic acids, saponins, trypsin inhibitors, and phytic acids. These components prevent atherosclerosis, oxidative stress-mediated heart disease and inflammation, obesity, diabetes, senile dementia, cancer (e.g., breast and lung), and osteoporosis. They have also been shown to have thrombolytic, blood pressure-lowering, lipid-lowering, antimutagenic, immunostimulatory, anti-allergic, antibacterial, anti-atopic dermatitis, anti-androgenetic alopecia, and anti-asthmatic activities, as well as skin improvement properties. In this review, we examined the physiological activities of CGJ and confirmed its potential as a functional food.     

窑尾框架主次梁单夹板连接关键问题研究

主次梁的单夹板连接在窑尾框架的主次梁连接中使用广泛,本文对这种连接形式的关键问题,如是否对长节点抗剪承载力进行折减,摩擦型高强螺栓如何界定是否产生滑移以及有限元模拟下的真实承载力进行了研究,给出了可供参考的结论。     

单晶高温合金定向凝固过程中初生碳化物的上浮现象SCIEI

本文在一种抗热腐蚀单晶镍基高温合金平面及胞状液-固界面定向凝固条件下,发现了初生碳化物(TiC)的上浮现象并分析了其形成原因。     

单级单开关不连续导电模式功率因数校正电路新方案

分析了几种单级单开关不连续导电、带输出电压隔离的功率因数校正电路，分别讨论了其优缺点，并提出了一种新的功率因数校正电路。     

热型连铸单晶铜工艺参数对铸棒表面质量的影响

在自行设计，制造的横引式热型连铸设备上对影响连铸过程的各工艺参数进行试验，并就各工艺参数对铸件表面质量的影响机理进行了分析。结果表明，各工艺参数主要是通过影响固液界面在型口中的位置来影响铸棒的表面质量，只有对各工艺参数进行合理匹配，才能得到表面光滑的铸棒，此外，液位高度变化即液位波动，也会对铸棒的表面质量产生 一定影响。     

双滑移取向Cu单晶的循环形变行为──Ⅱ．滑移带和形变带SCIEI

用光学显微镜和扫描电镜研究了双滑移取向（［０３４］，［１１７］）Ｃｕ单晶循环饱和后的表面形貌，塑性分切应变幅（γｐｌ）低于１０^（－３）时，［０３４］晶体表面上要为主滑移系的驻留滑移带（ＰＳＢｓ）占据，次滑移只在边缘区域启动，其ＰＳＢｓ细窄（＜１μｍ），体积百分数在１％以下．γｐｌ＞１０^（－３）时，次滑移开始在试样的中部启动，同时，表面出现二种贯穿晶体的宏观形变带（ＤＢＩ，ＤＢＩＩ），滑移带在形变带内集中．［１１７］晶体在γｐｌ＝４．４×１０^（－４）时，双滑移现象已十分明显．γｐｌ＞１０^（－３）时，表面也形成与前者相似的形变带．ＤＢＩ的惯习面与主滑移面平行（［０３４］晶体）或接近（［１１７］晶体），ＤＢＩＩ的惯习面则与前者垂直，文章讨论了形变带形成的可能原因．     

大学生求学满意度实证研究--某高校学生个体特征对满意度单项要素的影响分析

求学满意度，又称为求学满意程度，它取决于教育需求主体对教育服务的预期同其实际所感知的教育服务水平的对比。教学计划、教学组织、教师教学、教学设施、校园环境、学生5知识技能等都是影响求学满意度的因素。本文在调查取得基本数据的基础上，使用相关的统计检验方法，分析了性别、生源地和不同年级这些学生个体地征对求学满意度单项要素的影响。主要结论有：学生性别差异对满意度单项要素的影响基本是随机的；不同生源地的学生对教学计划和管理制度两个要素的评价具有差异；不同年级的学生对教学设施和知识掌握程度的评价具有显著性差异；学生对学校服务评价单项因素差异很少，总体满意度在一定程度上反应学校的实际情况。