The systems biology of glycosylation

Glycosylation can have a profound influence on the function of a variety of eukaryotic cells. In particular, it can affect signal transduction and cell-cell communication properties and thus shape critical cell decisions, including the regulation of differentiation and apoptosis. Regulation of glycosylation has multiple layers of complexity, both structural and functional, which make its experimental and theoretical analysis difficult to perform and interpret. Novel research methodologies provided by systems biology can help to address many outstanding issues and integrate glycosylation with other metabolic and cell regulation processes. Here we review the toolbox available for biochemical systems analysis of glycosylation.     

Knowledge-based selection of targets for structural genomics

The problem of rational target selection for protein structuredetermination in structural genomics projects on microbes isaddressed. A flexible computational procedure is described thatdirectly incorporates the whole body of annotation availablein the PEDANT genome database into the sequence clustering andselection process in order to identify proteins that are likelyto possess currently unknown structural domains. Filtering outgene products based on predicted structural features, such asknown three-dimensional structures and transmembrane regions,allows one to reduce the complexity of neighbor relationshipsbetween sequences and all but eliminates the need for furtherpartitioning of single-linkage clusters into disjoint proteingroups corresponding to homologous families. The results ofa large-scale computation experiment in which exemplary targetselection for 32 prokaryotic genomes was conducted are presented.     

Plastic coatings for laser fusion targets

A brief review on coating techniques for laser fusion targets is presented. Specifications for plastic target coatings are given followed by details on latest advances in application techniques. Two processes, vapor-phase pyrolysis (VPP) and the low-pressure plasma (LPP) method, are described that produce conformal coatings of the required dimensional tolerances: 1% variation in coating thickness and surface smoothness with peak-to-valley values not exceeding a few 100 Å. A VPP coater with a low-temperature deposition chamber is discussed in which two main mononers were used: di(p-xylylene) and di(2-chloro-p-xylylene). For the LPP process a capacitatively coupled a.c. (1 kHz) coater with two parallel flat-plate electrodes was used. In this process the main monomers were: p-xylene, ethylene, butadiene, and perdeuterated p-xylene. The VPP process has produced coatings as thick as 350 μm with a surface smoothness of 1 μm, and both processes (VPP and LPP) are capable of producing coatings with surface smoothnesses of a few 100 Å.     

偶联尿苷二磷酸循环体系的天然产物体外糖基化修饰

糖基化是天然产物的一种重要基团修饰,主要通过尿苷二磷酸(UDP)-糖基转移酶催化实现,而UDP-糖基供体价格昂贵限制了其应用,构建UDP-糖基供体再生系统可以有效解决该问题。本文从天然产物的体外糖基化修饰入手,阐述了糖基化修饰对天然产物功能的调控作用,比较了目前的糖基化修饰方法,其中基于UDP-糖基转移酶的生物法具备了重要的产业化应用前景。接着总结了各种UDP-糖基供体的合成方式,概述了偶联蔗糖合酶或海藻糖合酶的基于UDP循环的UDP-糖基供体再生系统,重点描述了UDP循环体系在萜类、黄酮类及其他化合物体外糖基化修饰中的应用,从而高效合成具有高附加值的天然产物糖苷化合物。指出偶联蔗糖合酶和UDP-糖基转移酶的循环体系是今后天然产物糖苷化合物合成的重要方式。     

Methods for designing characterisation targets for digital cameras

Characterisation targets usually include a set of physical coloured samples. A characterisation model can be derived between the colorimetric values (tristimulus values) and camera responses (RGB values) taken from an imaging device such as a digital camera capturing the colours in the target. The performance of such a model is highly dependent upon the number of colours and the colour region in the characterisation target. An ideal characterisation target should provide accurate model prediction without requiring too many samples. In this paper, a computational method is presented for colour selections to train a camera characterisation model based on a fourth‐order polynomial model including 35 terms. Compared with other available methods, the newly developed method performed better. It is proposed that this method be applied to generate generic targets in terms of colorimetric values. These targets should work reasonably well for a wide range of materials.     

Disulfide-Containing Macromolecules for Therapeutic Delivery

Development of macromolecules provides applicable platforms for the delivery of therapeutics. In this general overview, we focus on the design principles of synthetic polymers, with disulfide bonds located in either the polymer backbone or side chains. We also discuss the role of disulfide bonds, as well as the remaining questions to better understand their applications in therapeutic delivery systems.     

Integer programming for optimal reduction of calibration targets

Calibration targets are widely used to characterize imaging devices. The question addressed in this article is that of how many surfaces in a calibration target are needed to account for the performance of the whole target. Different to previous research where the problem of reducing calibration charts is addressed independently of the calibration problem; in this article we tackle the reduction question based on the calibration performance. We argue that the outcome of both spectral and colorimetric calibration is dependent on the properties of the cross‐product matrix encompassing the color‐signals. Further, we show that by careful mathematical manipulation it is possible to write the cross‐product matrix as a linear sum of the submatrices corresponding to each individual color signal. This formulation allows us to cast the reduction problem as a quadratic minimization where we ask: given the spectral properties of the available color signals, what is the minimum number of surfaces needed to emulate the global cross‐product matrix. To reduce the number of surfaces we impose an integer constraint on the minimization, where the weight of each surface can only assume a value of 1 or 0. Our results show that around 13 surfaces are sufficient to account of the 24 surfaces of the Macbeth color checker. © 2008 Wiley Periodicals, Inc. Col Res Appl, 33, 212–220, 2008     

Searching for the protein targets of bioactive molecules

The identification of all protein targets of a given drug or bioactive molecule within the human body is a prerequisite for an understanding of its beneficial and deleterious activities. Current approaches to reveal protein targets often fail to reveal physiologically relevant interactions. Here we review a recently introduced yeast-based approach for the identification of the binding partners of small molecules. We discuss the advantages and limitations of the approach using the clinically approved drug sulfasalazine as an example.     

Intravascular targets for molecular contrast-enhanced ultrasound imaging

Molecular targeting of contrast agents for ultrasound imaging is emerging as a new medical imaging modality. It combines advances in ultrasound technology with principles of molecular imaging, thereby allowing non-invasive assessment of biological processes in vivo. Preclinical studies have shown that microbubbles, which provide contrast during ultrasound imaging, can be targeted to specific molecular markers. These microbubbles accumulate in tissue with target (over) expression, thereby significantly increasing the ultrasound signal. This concept offers safe and low-cost imaging with high spatial resolution and sensitivity. It is therefore considered to have great potential in cancer imaging, and early-phase clinical trials are ongoing. In this review, we summarize the current literature on targets that have been successfully imaged in preclinical models using molecularly targeted ultrasound contrast agents. Based on preclinical experience, we discuss the potential clinical utility of targeted microbubbles.     

Advanced indium-tin oxide ceramics for sputtering targets

Indium-tin oxide (ITO) ceramic sputtering targets are widely used in formation of electrically conductive transparent thin films for electrodes in flat panel displays, solar cells, antistatic films and others, and which are commonly produced by a conventional dc magnetron sputtering process. The ceramic targets should be of high purity with a uniform microcrystalline structure and should possess high density and high electrical conductivity. In the present work, the challenges of the ceramic composition (e.g. the ratio of In₂O₃ and SnO₂) and manufacturing are considered; they include the use of high quality starting materials, particularly In₂O₃ powders with respect to purity, morphology and sinterability, manufacturing routes and sintering process. Positive experience in the development and manufacturing of ITO ceramic planar sputtering targets using in-house prepared In₂O₃ powders is reported. ITO ceramic tiles with areas up to 1500–1700 cm² and densities of 99+% of TD are manufactured. Physical properties of the ITO ceramics and sputtered films have been studied.     

Computing Metal-Binding Proteins for Therapeutic Benefit

Over one third of biomolecules rely on metal ions to exert their cellular functions. Metal ions can play a structural role by stabilizing the structure of biomolecules, a functional role by promoting a wide variety of biochemical reactions, and a regulatory role by acting as messengers upon binding to proteins regulating cellular metal-homeostasis. These diverse roles in biology ascribe critical implications to metal-binding proteins in the onset of many diseases. Hence, it is of utmost importance to exhaustively unlock the different mechanistic facets of metal-binding proteins and to harness this knowledge to rationally devise novel therapeutic strategies to prevent or cure pathological states associated with metal-dependent cellular dysfunctions. In this compendium, we illustrate how the use of a computational arsenal based on docking, classical, and quantum-classical molecular dynamics simulations can contribute to extricate the minutiae of the catalytic, transport, and inhibition mechanisms of metal-binding proteins at the atomic level. This knowledge represents a fertile ground and an essential prerequisite for selectively targeting metal-binding proteins with small-molecule inhibitors aiming to (i) abrogate deregulated metal-dependent (mis)functions or (ii) leverage metal-dyshomeostasis to selectively trigger harmful cells death.     

High-throughput screening for kinase inhibitors

Following G protein-coupled receptors (GPCRs), protein kinases have become the second most important class of targets for drug discovery over the last 20 years. While only four kinase inhibitors have reached the market to date (Fasudil for rho-dependent kinase, Rapamycin for TOR, Gleevec for BCR-Abl, and Iressa for EGFR), many more are already in clinical development. A historical overview of kinase inhibitors was recently published by Cohen. [1] After the previous successes, protein kinases are now regarded as attractive, well-drugable targets, and the analysis of the human genome has yielded 518 protein kinases. [2] We can thus expect screening for protein kinase inhibitors to become even more important in the future. In this review we will focus on the early steps of drug discovery programs producing new lead compounds. We will guide the reader through efficient state-of-the-art assay development and high-throughput screening of large chemical libraries for protein kinase inhibitors.     

Polymerization inhibitors for polyunsaturated oils

Several edible anionic surfactants were found to function as polymerization inhibitors for safflower oil. The most effective additive was the sodium salt of phosphated mono- and diglycerides. Additional inhibitors included sodium diacetyltartaric acid esters of mono- and diglycerides, sodium stearoyl-2-lactylate, sodium stearyl fumarate, sodium succinoylated mono- and diglycerides, dioctyl sodium sulfosuccinate, and sodium sulfoacetate esters of mono- and diglycerides. It is suggested that these surfactants behave in a manner similar to methyl polysiloxane, as oxygen barriers at the oil-air interface. This view is supported by data showing that in the free acid, oil soluble form their functionality is minimal. But when they are neutralized to form the sodium salts their effectiveness is markedly enhanced. One of seven papers presented in the symposium “Biological Significance of Autoxidized and Polymerized Oils,” JOCS-AOCS Joint Meeting, Los Angeles, April 1972.     

促红细胞生成素糖基化分析方法的研究进展

重组人促红细胞生成素(recombinant human erythropoietin,r Hu EPO)是糖蛋白类药物,临床上主要用于治疗肾性贫血。糖基化是影响促红细胞生成素(erythropoietin,EPO)药物质量、安全性和活性的关键因素。近年来,EPO药物的原始专利即将过期,生物仿制药(biosimilar)进入一个高速发展期。因此,亟需发展可有效评价其糖基化修饰形态的方法。本文对EPO药物的发展、糖基化与活性的关系及糖基化分析方法的最新研究进展作一综述。     

Therapeutic Potential of Photobiomodulation for Chronic Kidney Disease

Chronic kidney disease (CKD) is a growing global public health problem. The implementation of evidence-based clinical practices only defers the development of kidney failure. Death, transplantation, or dialysis are the consequences of kidney failure, resulting in a significant burden on the health system. Hence, innovative therapeutic strategies are urgently needed due to the limitations of current interventions. Photobiomodulation (PBM), a form of non-thermal light therapy, effectively mitigates mitochondrial dysfunction, reactive oxidative stress, inflammation, and gut microbiota dysbiosis, all of which are inherent in CKD. Preliminary studies suggest the benefits of PBM in multiple diseases, including CKD. Hence, this review will provide a concise summary of the underlying action mechanisms of PBM and its potential therapeutic effects on CKD. Based on the findings, PBM may represent a novel, non-invasive and non-pharmacological therapy for CKD, although more studies are necessary before PBM can be widely recommended.