Showing papers by "Sichuan University published in 2012"

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

The tomato genome sequence provides insights into fleshy fruit evolution

Abstract: Tomato (Solanum lycopersicum) is a major crop plant and a model system for fruit development. Solanum is one of the largest angiosperm genera1 and includes annual and perennial plants from diverse habitats. Here we present a high-quality genome sequence of domesticated tomato, a draft sequence of its closest wild relative, Solanum pimpinellifolium2, and compare them to each other and to the potato genome (Solanum tuberosum). The two tomato genomes show only 0.6% nucleotide divergence and signs of recent admixture, but show more than 8% divergence from potato, with nine large and several smaller inversions. In contrast to Arabidopsis, but similar to soybean, tomato and potato small RNAs map predominantly to gene-rich chromosomal regions, including gene promoters. The Solanum lineage has experienced two consecutive genome triplications: one that is ancient and shared with rosids, and a more recent one. These triplications set the stage for the neofunctionalization of genes controlling fruit characteristics, such as colour and fleshiness.

Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis

Abstract: Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro-survival or pro-death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti-cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis-related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment.

Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature.

Abstract: Purpose Tumor associated macrophages (TAMs) are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial.

Mn2+ Dopant‐Controlled Synthesis of NaYF4:Yb/Er Upconversion Nanoparticles for in vivo Imaging and Drug Delivery

Abstract: Pure dark red emission (650-670 nm) of NaYF(4):Yb/Er upconversion nanoparticles (UCNPs) is achieved by manganese ions (Mn(2+)) doping. In addition, the Mn(2+)-doping can also control the crystalline phase and size of the resulting UCNPs simultaneously. Drug delivery studies suggest the promise of these UCNPs as drug carriers for intracellular drug delivery and eventually as a multifunctional nanoplatform for simultaneous diagnosis and therapy.

The yak genome and adaptation to life at high altitude

Abstract: Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.

Microautophagy: Lesser-Known Self-Eating

Abstract: Microautophagy, the non-selective lysosomal degradative process, involves direct engulfment of cytoplasmic cargo at a boundary membrane by autophagic tubes, which mediate both invagination and vesicle scission into the lumen. With its constitutive characteristics, microautophagy of soluble substrates can be induced by nitrogen starvation or rapamycin via regulatory signaling complex pathways. The maintenance of organellar size, membrane homeostasis, and cell survival under nitrogen restriction are the main functions of microautophagy. In addition, microautophagy is coordinated with and complements macroautophagy, chaperone-mediated autophagy, and other self-eating pathways. Three forms of selective microautophagy, including micropexophagy, piecemeal microautophagy of the nucleus, and micromitophagy, share common ground with microautophagy to some degree. As the accumulation of experimental data, the precise mechanisms that govern microautophagy are becoming more appreciated. Here, we review the microautophagic molecular machinery, its physiological functions, and relevance to human diseases, especially in diseases involving multivesicular bodies and multivesicular lysosomes.

Objective Assessment of Multiresolution Image Fusion Algorithms for Context Enhancement in Night Vision: A Comparative Study

Abstract: Comparison of image processing techniques is critically important in deciding which algorithm, method, or metric to use for enhanced image assessment. Image fusion is a popular choice for various image enhancement applications such as overlay of two image products, refinement of image resolutions for alignment, and image combination for feature extraction and target recognition. Since image fusion is used in many geospatial and night vision applications, it is important to understand these techniques and provide a comparative study of the methods. In this paper, we conduct a comparative study on 12 selected image fusion metrics over six multiresolution image fusion algorithms for two different fusion schemes and input images with distortion. The analysis can be applied to different image combination algorithms, image processing methods, and over a different choice of metrics that are of use to an image processing expert. The paper relates the results to an image quality measurement based on power spectrum and correlation analysis and serves as a summary of many contemporary techniques for objective assessment of image fusion algorithms.

Efficient electromagnetic interference shielding of lightweight graphene/polystyrene composite

Abstract: A combination of high-pressure compression molding plus salt-leaching was first proposed to prepare porous graphene/polystyrene composites. The specific shielding effectiveness of the lightweight composite was as high as 64.4 dB cm3 g−1, the highest value ever reported for polymer based EMI shielding materials at such a low thickness (2.5 mm).

Chemistry and physics of a single atomic layer: strategies and challenges for functionalization of graphene and graphene-based materials

Abstract: Graphene has attracted great interest for its superior physical, chemical, mechanical, and electrical properties that enable a wide range of applications from electronics to nanoelectromechanical systems. Functionalization is among the significant vectors that drive graphene towards technological applications. While the physical properties of graphene have been at the center of attention, we still lack the knowledge framework for targeted graphene functionalization. In this critical review, we describe some of the important chemical and physical processes for graphene functionalization. We also identify six major challenges in graphene research and give perspectives and practical strategies for both fundamental studies and applications of graphene (315 references).

The exopolysaccharide matrix modulates the interaction between 3D architecture and virulence of a mixed-species oral biofilm.

Abstract: Virulent biofilms are responsible for a range of infections, including oral diseases. All biofilms harbor a microbial-derived extracellular-matrix. The exopolysaccharides (EPS) formed on tooth-pellicle and bacterial surfaces provide binding sites for microorganisms; eventually the accumulated EPS enmeshes microbial cells. The metabolic activity of the bacteria within this matrix leads to acidification of the milieu. We explored the mechanisms through which the Streptococcus mutans-produced EPS-matrix modulates the three-dimensional (3D) architecture and the population shifts during morphogenesis of biofilms on a saliva-coated-apatitic surface using a mixed-bacterial species system. Concomitantly, we examined whether the matrix influences the development of pH-microenvironments within intact-biofilms using a novel 3D in situ pH-mapping technique. Data reveal that the production of the EPS-matrix helps to create spatial heterogeneities by forming an intricate network of exopolysaccharide-enmeshed bacterial-islets (microcolonies) through localized cell-to-matrix interactions. This complex 3D architecture creates compartmentalized acidic and EPS-rich microenvironments throughout the biofilm, which triggers the dominance of pathogenic S. mutans within a mixed-species system. The establishment of a 3D-matrix and EPS-enmeshed microcolonies were largely mediated by the S. mutans gtfB/gtfC genes, expression of which was enhanced in the presence of Actinomyces naeslundii and Streptococcus oralis. Acidic pockets were found only in the interiors of bacterial-islets that are protected by EPS, which impedes rapid neutralization by buffer (pH 7.0). As a result, regions of low pH (<5.5) were detected at specific locations along the surface of attachment. Resistance to chlorhexidine was enhanced in cells within EPS-microcolony complexes compared to those outside such structures within the biofilm. Our results illustrate the critical interaction between matrix architecture and pH heterogeneity in the 3D environment. The formation of structured acidic-microenvironments in close proximity to the apatite-surface is an essential factor associated with virulence in cariogenic-biofilms. These observations may have relevance beyond the mouth, as matrix is inherent to all biofilms.

Poly(vinyl alcohol) Hydrogel Can Autonomously Self-Heal

Abstract: It is discovered that poly(vinyl alcohol) (PVA) hydrogel prepared using the freezing/thawing method can self-repair at room temperature without the need for any stimulus or healing agent. The autonomous self-healing process can be fast for mechanically strong PVA hydrogel yielding a high fracture stress. Investigation on the effect of the hydrogel preparation conditions points out that hydrogen bonding between PVA chains across the interface of the cut surfaces is at the origin of the phenomenon. The key for an effective self-healing is to have an appropriate balance between high concentration of free hydroxyl groups on PVA chains on the cut surfaces prior to contact and sufficient PVA chain mobility in the hydrogel.

Recent progress in enantioselective synthesis of C3-functionalized oxindoles: rare earth metals take action

Abstract: The enantioselective synthesis of 3-functionalized oxindole derivatives has experienced an explosive development. This minireview introduces the recent application of rare earth (RE) metal complex catalysts in the synthesis of targeted frameworks. The direct addition reactions of 3-substituted oxindoles or isatins are described, together with a discussion of the catalytic mechanism and related transformations to pharmaceuticals.

BSA-templated MnO2 nanoparticles as both peroxidase and oxidase mimics

Abstract: Inorganic nanomaterials that mimic enzymes are fascinating as they potentially have improved properties relative to native enzymes, such as greater resistance to extremes of pH and temperature and lower sensitivity to proteases. Although many artificial enzymes have been investigated, searching for highly-efficient and stable catalysts is still of great interest. In this paper, we first demonstrated that bovine serum albumin (BSA)-stabilized MnO(2) nanoparticles (NPs) exhibited highly peroxidase-, oxidase-, and catalase-like activities. The activities of the BSA-MnO(2) NPs were evaluated using the typical horseradish peroxidase (HRP) substrates o-phenylenediamine (OPD) and 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of either hydrogen peroxide or dissolved oxygen. These small-sized BSA-MnO(2) NPs with good dispersion, solubility and biocompatibility exhibited typical Michaelis-Menten kinetics and high affinity for H(2)O(2), OPD and TMB, indicating that BSA-MnO(2) NPs can be used as satisfactory enzyme mimics. Based on these findings, BSA-MnO(2) NPs were used as colorimetric immunoassay tags for the detection of goat anti-human IgG in place of HRP. The colorimetric immunoassay using BSA-MnO(2) NPs has the advantages of being fast, robust, inexpensive, easily prepared and with no HRP and H(2)O(2) being needed. These water-soluble BSA-MnO(2) NPs may have promising potential applications in biotechnology, bioassays, and biomedicine.

Organocatalytic asymmetric transformations of modified Morita–Baylis–Hillman adducts

Abstract: Chiral Lewis basic tertiary amines or phosphines can enable properly modified Morita–Baylis–Hillman (MBH) adducts to undergo asymmetric allylic substitutions with a wide range of nucleophiles. In addition, assisted by a Bronsted base, chiral Lewis bases can also catalytically convert modified MBH adducts into allylic ylides, which can be engaged in a variety of asymmetric annulation reactions. This tutorial review will focus on such chiral Lewis base-catalysed asymmetric transformations of MBH adducts, especially those developed over the past five years, allowing for the rapid construction of densely functionalised chiral molecules with high levels of regio- and stereoselectivities.

Electrogenerated Chemiluminescence Behavior of Graphite-like Carbon Nitride and Its Application in Selective Sensing Cu2+

Abstract: This paper reports for the first time the electrogenerated chemiluminescence (ECL) behavior of graphite-like carbon nitride (g-C3N4) with K2S2O8 as the coreactant. The possible ECL reaction mechanisms are proposed. The spectral features of the ECL emission and photoluminescence (PL) of g-C3N4 are compared, and their resemblance demonstrates that the excited states of g-C3N4 from both ECL and photoexcitation are the same. The effects of K2S2O8 concentration, pH, g-C3N4/carbon powder ratio, and scan rate on the ECL intensity have been studied in detail. Furthermore, it is observed that the ECL intensity is efficiently quenched by trace amounts of Cu2+. g-C3N4 is thus employed to fabricate an ECL sensor which shows high selectivity to Cu2+ determination. The limit of detection is determined as 0.9 nM. It is anticipated that g-C3N4 could be a new class of promising material for fabricating ECL sensors.

Aminocatalytic Asymmetric Diels–Alder Reactions via HOMO Activation

Abstract: In the first successful catalytic asymmetric Diels-Alder reaction in 1979, Koga and colleagues used a chiral aluminum complex as a Lewis acid catalyst, but since then, researchers have developed numerous catalytic systems for these reactions. By 2000, several chiral organic compounds, such as the salts of imidazolidinones or TADDOLs, emerged as robust catalysts in the asymmetric Diels-Alder reactions. According to frontier molecular orbital theory, most of these catalysts employ a LUMO-lowering strategy as a means of activating electron-deficient dienophiles. Only rarely do chiral catalysts take advantage of the alternative strategy of activating the HOMO. In this Account we will discuss the development of asymmetric Diels-Alder reactions based on the HOMO-raising effects of chiral amines. First, we show that enamine intermediates formed in situ between an amine catalyst and enolizable aliphatic aldehydes can act as electron-rich dienophiles in inverse-electron-demand Diels-Alder reactions. We describe the preparation of a variety of oxygen- or nitrogen-containing heterocycles with high optical purity. Then, we demonstrate that the dienamine species from α,β-unsaturated aldehydes can act either as electron-rich dienes in normal-electron-demand Diels-Alder reactions or as dienophiles in inverse-electron-demand Diels-Alder reactions. These reactions generally occur with high chemo-, regio-, and stereoselectivity. Finally, we introduce a new activation mode for Diels-Alder reactions, in which reactive trienamine intermediates derived from 2,4-dienals or even 2,4-dienones play a key role. Notably, we observe remarkable β,e-regioselectivity and obtain excellent stereocontrol even at the very remote e-reactive center-up to seven bonds away from the chiral center of the amine catalyst. These results demonstrate that a HOMO-activation strategy via aminocatalysis could become a significant tool in asymmetric Diels-Alder reactions. In addition, these reactions using enamine, dienamine, or trienamine intermediates produce a diverse array of densely functionalized cyclic scaffolds, which may serve as valuable structures in drug discovery and natural product synthesis.

Ophthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma

Abstract: Blindness affects 60 million people worldwide. The leading causes of irreversible blindness include age-related macular degeneration, retinal vascular diseases and glaucoma. The unique features of the eye provide both benefits and challenges for drug discovery and delivery. During the past decade, the landscape for ocular drug therapy has substantially changed and our knowledge of the pathogenesis of ophthalmic diseases has grown considerably. Anti-angiogenic drugs have emerged as the most effective form of therapy for age-related macular degeneration and retinal vascular diseases. Lowering intraocular pressure is still the mainstay for glaucoma treatment but neuroprotective drugs represent a promising next-generation therapy. This Review discusses the current state of ocular drug therapy and highlights future therapeutic opportunities.

Enhanced epoxy/silica composites mechanical properties by introducing graphene oxide to the interface.

Abstract: Controlling the interface interaction of polymer/filler is essential for the fabrication of high-performance polymer composites. In this work, a core–shell structured hybrid (SiO2–GO) was prepared and introduced into an epoxy polymer matrix as a new filler. The incorporation of the hybrid optimized the modulus, strength and fracture toughness of the composites simultaneously. The ultrathin GO shells coated on silica surfaces were regarded as the main reason for the enhancement. Located at the silica-epoxy interface, GO served as an unconventional coupling agent of the silica filler, which effectively enhanced the interfacial interaction of the epoxy/SiO2–GO composites, and thus greatly improved the mechanical properties of the epoxy resin. We believe this new and effective approach that using GO as a novel fillers surface modifier may open a novel interface design strategy for developing high performance composites.

Genome-wide analysis of WRKY transcription factors in Solanum lycopersicum

Abstract: The WRKY transcription factors have been implicated in multiple biological processes in plants, especially in regulating defense against biotic and abiotic stresses However, little information is available about the WRKYs in tomato (Solanum lycopersicum) The recent release of the whole-genome sequence of tomato allowed us to perform a genome-wide investigation for tomato WRKY proteins, and to compare these positively identified proteins with their orthologs in model plants, such as Arabidopsis and rice In the present study, based on the recently released tomato whole-genome sequences, we identified 81 SlWRKY genes that were classified into three main groups, with the second group further divided into five subgroups Depending on WRKY domains’ sequences derived from tomato, Arabidopsis and rice, construction of a phylogenetic tree demonstrated distinct clustering and unique gene expansion of WRKY genes among the three species Genome mapping analysis revealed that tomato WRKY genes were enriched on several chromosomes, especially on chromosome 5, and 16 % of the family members were tandemly duplicated genes The tomato WRKYs from each group were shown to share similar motif compositions Furthermore, tomato WRKY genes showed distinct temporal and spatial expression patterns in different developmental processes and in response to various biotic and abiotic stresses The expression of 18 selected tomato WRKY genes in response to drought and salt stresses and Pseudomonas syringae invasion, respectively, was validated by quantitative RT-PCR Our results will provide a platform for functional identification and molecular breeding study of WRKY genes in tomato and probably other Solanaceae plants