基于蛋白质组芯片的结核分枝杆菌系统生物学研究进展

近些年全球结核病疫情愈发严重,耐药性结核病使其雪上加霜。一个重要原因是结核病新药的匮乏以及结核分枝杆菌相关基础研究的不足。因此迫切需要开发新的技术以促进结核病系统生物学基础研究,并在此基础上研究新机制,发现新靶标,开发新药物。结核分枝杆菌功能蛋白质组芯片的出现旨在促进结核病相关研究工作。考虑到结核分枝杆菌高毒力、复制周期长和需要在生物安全三级实验室中开展研究等特点和难点,该工具为结核病相关研究人员提供了一个强有力的武器。目前这一技术手段的应用已经使我们对结核分枝杆菌-宿主相互作用、小分子-蛋白结合以及抗生素耐药性机制等关键生物过程有了更深入的了解。为了更好地帮助同行了解这一有效的工具,本文综述了结核分枝杆菌功能蛋白组芯片的几种主要应用,期望同行专家能更好地将其应用于结核病相关的基础研究中。     

Fungal volatile organic compounds: A review with emphasis on their biotechnological potential

Fungi produce various mixtures of gas-phase, carbon-based compounds called volatile organic compounds (VOCs) that due to their small size are able to diffuse through the atmosphere and soils. Despite some methodological and technological constraints, researchers have detected and characterized approximately 250 fungal VOCs, many of which have characteristic odors and are produced during primary and secondary metabolism. Fungal VOCs may contribute to a controversial medical diagnosis called “sick building syndrome” and may also be important in the success of some biocontrol species of Trichoderma. VOCs also play important signaling roles for fungi in their natural environments. Many ecological interactions are mediated by VOCs, including those between fungi and plants, arthropods, bacteria, and other fungi. The diverse functions of fungal VOCs can be developed for use in biotechnological applications for biofuel, biocontrol, and mycofumigation. Volatiles represent a new frontier in bioprospecting, and the study of these gas-phase compounds promises the discovery of new products for human exploitation and will generate new hypotheses in fundamental biology.     

Identification, characterization and biological significance of very small embryonic-like stem cells (VSELs) in regenerative medicine

The progress of stem cell research, along with technological innovation, has brought researchers to focus on the potential role of stem cells in regenerative medicine. Ethical and technological issues have limited the applications of human embryonic stem cells (hESCs) in this field. As a promising candidate, very small embryonic-like stem cells (VSELs) express a multitude of pluripotent stem cell markers and demonstrate the ability to differentiate into three germ-layer lineages in vitro. Optimized methods for isolation and expansion of VSELs have aroused the scientific community's interest in use of this kind of cells for regenerative purposes. In this review, we will focus on the biological characteristics, as well as the potentiality and remaining challenges in clinical application of VSELs. Moreover, a comparison among VSELs and the other pluripotent stem cells will be illustrated to highlight the unique advantages of VSELs.     

Plasmonic Optical Properties and Applications of Metal Nanostructures

In this review article, we provide an overview of recent research activities in the study of plasmonic optical properties of metal nanostructures with emphasis on understanding the relation between surface plasmon absorption and structure. Both experimental results and theoretical calculations have indicated that the plasmonic absorption strongly depends on the detailed structure of the nanomaterials. Examples discussed include spherical nanoparticles, nanorods, nanowires, hollow nanospheres, aggregates, and nanocages. Plasmon–phonon coupling measured from dynamic studies as a function of particle size, shape, and aggregation state is also reviewed. The fascinating optical properties of metal nanostructures find important applications in a number of technological areas including surface plasmon resonance, surface-enhanced Raman scattering, and photothermal imaging and therapy. Their novel optical properties and emerging applications are illustrated using specific examples from recent literature. The case of hollow nanosphere structures is highlighted to illustrate their unique features and advantages for some of these applications.     

石制品技术分析的盲测实验

石制品技术研究作为一项拥有60多年历史的研究手段,已经形成了完善的理论体系和操作程式,可以反映古人类的行为特征、认知能力等多方面的信息。技术阅读是石制品技术分析过程中最重要的研究手段之一。其中,对石核剥片过程的复原是技术阅读的核心,也是分析整个石器生产过程的基础,提高石制品技术阅读的准确性是研究人员需要不断追求的目标。本文以采集自宁夏水洞沟遗址附近的白云岩、石英岩等为原料,参照微痕分析的盲测手段,通过石制品打制实验、初步技术阅读（“盲测”）、拼合分析校正、重复交叉技术阅读等方式,揭示影响技术阅读准确性的相关因素,提出提高技术阅读准确性的方法,并对“盲测”实验在石制品技术阅读中的重要性进行简要探讨。     

L’analyse métabolomique par spectrométrie de masse: un nouvel outil pour la biochimie clinique ?

Metabolomics (large scale analysis of small organic compounds) becomes a promising tool in biological exploration. This tool is able to identify modifications in biofluids occurring as a consequence of a pathogenic process. It’ll be shown how to carry out metabolomic analysis as well as the technological progress in this field. Concrete applications will be commented and the principal limitations will also be discussed. These limitations have to be overcome in order obtain data usable by biologists and medical doctors.     

Comparing treatments in the presence of crossing survival curves: an application to bone marrow transplantation

Summary .   In some clinical studies comparing treatments in terms of their survival curves, researchers may anticipate that the survival curves will cross at some point, leading to interest in a long-term survival comparison. However, simple comparison of the survival curves at a fixed point may be inefficient, and use of a weighted log-rank test may be overly sensitive to early differences in survival. We formulate the problem as one of testing for differences in survival curves after a prespecified time point, and propose a variety of techniques for testing this hypothesis. We study these methods using simulation and illustrate them on a study comparing survival for autologous and allogeneic bone marrow transplants.     

Environmental and industrial applications of Yarrowia lipolytica

Yarrowia lipolytica is a fungus that degrades hydrophobic substrates very efficiently. The fungus displays several important characteristics that have encouraged researchers to study various basic biological and biotechnological applications in detail. Although the organism has been used as model system for studying dimorphism, salt tolerance, heterologous protein expression, and lipid accumulation, there are no recent reviews on the environmental and industrial applications of this organism. Included here are applications in bioremediation of environments contaminated with aliphatic and aromatic compounds, organic pollutants, 2,4,6-trinitrotoluene, and metals. A variety of industrially important recent processes for the synthesis of β-hydroxy butyrate, l-dopa, and emulsifiers have also been reviewed. Production of unique inherent enzymes (inulinases, α-mannosidases), novel applications of esterases and lipases, and the use of the fungus for heterologous expression of biotechnologically relevant products have also been highlighted. The review while entailing a general overview focuses critically on some of the recent advances on the applications of this yeast. The examples cited here demonstrate the use of wild-type, mutant as well as genetically manipulated strains of Y. lipolytica for the development of different products, processes, and technologies. This also throws light on how a single organism can be versatile with respect to its metabolic abilities and how it can be exploited for a variety of purposes. This review will thus form a base for future developments in this field.     

Micelles as delivery vehicles for oligofluorene for bioimaging

With the successful development of organic/polymeric light emitting diodes, many organic and polymeric fluorophores with high quantum efficiencies and optical stability were synthesized. However, most of these materials which have excellent optical properties are insoluble in water, limiting their applications in biological fields. Herein, we used micelles formed from an amino-group-containing poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG-NH₂) to incorporate a hydrophobic blue emitter oligofluorene (OF) to enable its application in biological conditions. Although OF is completely insoluble in water, it was successfully transferred into aqueous solutions with a good retention of its photophysical properties. OF exhibited a high quantum efficiency of 0.84 in a typical organic solvent of tetrahydrofuran (THF). In addition, OF also showed a good quantum efficiency of 0.46 after being encapsulated into micelles. Two cells lines, human glioblastoma (U87MG) and esophagus premalignant (CP-A), were used to study the cellular internalization of the OF incorporated micelles. Results showed that the hydrophobic OF was located in the cytoplasm, which was confirmed by co-staining the cells with nucleic acid specific SYTO 9, lysosome specific LysoTracker Red®, and mitochondria specific MitoTracker Red. MTT assay indicated non-toxicity of the OF-incorporated micelles. This study will broaden the application of hydrophobic functional organic compounds, oligomers, and polymers with good optical properties to enable their applications in biological research fields.     

The Problem of Cancer Dormancy: Understanding the Basic Mechanisms and Identifying Therapeutic Opportunities

The hiatus observed in the progression of cancer after diagnosis and treatment in a large proportion of patients has led to the notion that a state of cancer dormancy must exist during tumor progression. However, research on this stage of cancer has been limited due to the lack of appropriate models and clinical correlates. Fortunately, the last decade has seen the development of new cancer dormancy models, whole animal and intravital imaging techniques and the molecular characterization of minimal residual disease. These studies enabled researchers to reveal intriguing mechanisms and molecular determinants that define tumor dormancy. It is imperative to understand the basic mechanisms of dormancy, as this will accelerate the development of new markers of progression and novel therapeutic opportunities to induce dormancy and/or eradicate dormant disease. This issue of Cell Cycle includes a “Spotlight on Cancer Dormancy” highlighting major contributions to the field of cancer dormancy from basic and clinical studies. We anticipate that this will initiate a forum of discussion on the problem of cancer dormancy and stimulate investigators to study this rather unexplored but undeniably relevant clinical stage of cancer progression.     

大气二氧化碳和臭氧浓度升高对植物挥发性有机化合物排放影响的研究进展

对流层大气中CO₂和O₃浓度变化可对植物挥发性有机化合物(VOCs)的排放产生一定影响,而植物VOCs具有很高的化学活性,可影响低层大气的化学组成,促进光化学污染的形成,对温室效应和全球变化具有潜在的影响.文中总结了大气CO₂和O₃浓度单独及复合作用对植物VOCs排放规律的影响,并对今后植物VOCs排放规律及多重环境胁迫下城市树木VOCs释放机制的研究进行了展望.     

High-Throughput Nonlinear Optical Microscopy

High-resolution microscopy methods based on different nonlinear optical (NLO) contrast mechanisms are finding numerous applications in biology and medicine. While the basic implementations of these microscopy methods are relatively mature, an important direction of continuing technological innovation lies in improving the throughput of these systems. Throughput improvement is expected to be important for studying fast kinetic processes, for enabling clinical diagnosis and treatment, and for extending the field of image informatics. This review will provide an overview of the fundamental limitations on NLO microscopy throughput. We will further cover several important classes of high-throughput NLO microscope designs with discussions on their strengths and weaknesses and their key biomedical applications. Finally, this review will close with a perspective of potential future technological improvements in this field.     

High-Throughput Nonlinear Optical Microscopy

High-resolution microscopy methods based on different nonlinear optical (NLO) contrast mechanisms are finding numerous applications in biology and medicine. While the basic implementations of these microscopy methods are relatively mature, an important direction of continuing technological innovation lies in improving the throughput of these systems. Throughput improvement is expected to be important for studying fast kinetic processes, for enabling clinical diagnosis and treatment, and for extending the field of image informatics. This review will provide an overview of the fundamental limitations on NLO microscopy throughput. We will further cover several important classes of high-throughput NLO microscope designs with discussions on their strengths and weaknesses and their key biomedical applications. Finally, this review will close with a perspective of potential future technological improvements in this field.     

旧石器技术研究法之应用——以观音洞石核为例

中国旧石器材料数量众多,表现出一定的地域特色,在世界旧石器考古学领域占有重要地位.研究表明,类型学在解读与提取石器所包含的人类技术行为信息方面的能力有较大的局限性,而且中国旧石器时代的一些石制品的形态和组合与欧洲和近东常常难以直接对比,对器物的分类定名也存在交流上的困难.由法国学者开创发展起来的史前石器技术研究理论和方法在分析形态特征的同时,通过关注支配石器工业生产体系的技术机制和逻辑规则,对深入细致地探讨史前人类的认知特征和技术行为可以发挥重要作用,也能为石器工业甚至跨地域文化之间的比较提供基础.本文对贵州观音洞遗址的石核标本为例进行了技术分析,说明其在研究中国旧石器材料上的可行性,特别是信息提取上的优势.     

Comparative analysis of dermal collagen and lipids in cereblon ablated mice using a multimodal nonlinear optical system

By utilizing a multimodal nonlinear optical system that combines coherent anti-Stokes Raman scattering and second harmonic generation to investigate biological characteristics of dermal tissues ex vivo, we demonstrate the potential feasibility of using this optical approach as a powerful new investigative tool for future biomedical research. For this study, our optical system was utilized for the first time to analyze lipid and collagen profiles in cereblon knockout (KO) mouse skin, and we were able to discover significant alterations in the number of carbon–carbon double bonds (wild-type vs. cereblon KO; N_CC: 0.75 vs. 0.85) of skin fatty acids in triacylglycerides as well as changes in dermal collagen fibers (25% reduction in cereblon KO). By adopting our optical system to biological studies, we provide researchers with another diagnostic approach to validate their experimental results, which will significantly advance the state of biomedical research.     

Non-ionic hybrid detergents for protein delipidation

Non-ionic detergents are important tools for the investigation of interactions between membrane proteins and lipid membranes. Recent studies led to the question as to whether the ability to capture protein-lipid interactions depends on the properties of detergents or their concentration in purification buffers. To address this question, we present the synthesis of an asymmetric, hybrid detergent that combines the head groups of detergents with opposing delipidating properties. We discuss detergent properties and protein purification outcomes to reveal whether the properties of detergent micelles or the detergent concentration in purification buffers drive membrane protein delipidation. We anticipate that our findings will enable the development of rationally design detergents for future applications in membrane protein research.     

Organic Field‐Effect Transistor for Energy‐Related Applications: Low‐Power‐Consumption Devices,Near‐Infrared Phototransistors,and Organic Thermoelectric Devices

The organic field‐effect transistor (OFET) is the basic building block of integrated circuits. The charge carrier mobility and operating frequency of OFETs have continued to increase; therefore, the power dissipation of OFETs can no longer be ignored. Many research efforts have been made to develop low‐power‐consumption OFETs and complementary circuits. Despite the switching function, OFETs can also be utilized in emerging energy‐related applications, such as near‐infrared (NIR) photodetectors and organic thermoelectric devices. Organic phototransistors show considerably higher photo responsivity than other photodetector architectures due to field‐effect charge modulation. The photoinduced gate modulating largely suppresses the dark current while simultaneously providing gain. These characteristics may favor NIR light detection and suggest that the organic phototransistor is a promising candidate for optoelectronic applications in the NIR regime. For organic thermoelectric applications, OFETs can work as a powerful tool for examining the charge and energy transport in the organic semiconductor, thus giving insight into organic thermoelectric studies. In this review, the authors highlight recent advances in OFET‐ related energy topics, including low‐power‐consumption OFETs, NIR photodetectors, and organic thermoelectric devices. The remaining challenges in the field will also be discussed.     

Enzymology in monophasic organic media.

Over the past year, an important area of research has been directed towards the fundamental aspects of enzymes and new applications of enzymology in monophasic organic media. Much of this research has focused on the factors that influence enzymatic catalysis in monophasic organic solvents, including the importance of enzyme-associated water, and the effect of organic solvents on enzyme structure and thermodynamic features. From an applications perspective, new advances in the use of enzymes in organic and polymer syntheses and optical resolutions have been made.