iMembrane: homology-based membrane-insertion of proteins

Summary: iMembrane is a homology-based method, which predicts a membrane protein's position within a lipid bilayer. It projects the results of coarse-grained molecular dynamics simulations onto any membrane protein structure or sequence provided by the user. iMembrane is simple to use and is currently the only computational method allowing the rapid prediction of a membrane protein's lipid bilayer insertion. Bilayer insertion data are essential in the accurate structural modelling of membrane proteins or the design of drugs that target them

Activity modulation and allosteric control of a scaffolded DNAzyme using a dynamic DNA nanostructure.

Recognition of the fundamental importance of allosteric regulation in biology dates back to not long after its discovery in the 1960s. Our ability to rationally engineer this potentially useful property into normally non-allosteric catalysts, however, remains limited. In response we report a DNA nanotechnology-enabled approach for introducing allostery into catalytic nucleic acids. Specifically, we have grafted one or two copies of a peroxidase-like DNAzyme, hemin-bound G-quadruplex (hemin-G), onto a DNA tetrahedral nanostructure in such a manner as to cause them to interact, modulating their catalytic activity. We achieve allosteric regulation of these catalysts by incorporating dynamically responsive oligonucleotides that respond to specific "effector" molecules (complementary oligonucleotides or small molecules), altering the spacing between the catalytic sites and thus regulating their activity. This designable approach thus enables subtle allosteric modulation in DNAzymes that is potentially of use for nanomedicine and nanomachines

Hydrothermal combustion synthesis and characterization of Sr2CeO4 phosphor powders

In this paper, the blue-light-emitting Sr2CeO4 phosphor powders were prepared by hydrothermal combustion reactions and a subsequent sintering process. During the process, the mixed urea and glycine were both used as leavening agent and fuel. The particle crystallization, surface morphology as well as the luminescence intensities of the Sr2CeO4 phosphor powders were effectively improved by adjusting the amount of glycine and post-sintering temperatures. The Sr2CeO4 phosphor exhibited strong crystallization and well-distributed spherical particle after optimization. Moreover, the intense blue-light emission band with the maximum at 468 nm in the range of 400–600 nm was observed as excited with ultraviolet light 277 nm. In particular, after the precursors were heat-treated at 1100 °C, the samples could be well-excited around 350 nm. The excitation bands were ascribed to the charge transfer from O to Ce, and the enlarged excitation range may facilitate its uses in optoelectronic fields.publishe

Ln3+ (Ln = Eu, Dy) - doped Sr2CeO4 fine phosphor particles: wet chemical preparation, energy transfer and tunable luminescence

The Sr2CeO4:Ln3+ (Ln = Eu, Dy) fine phosphor particles were prepared by a facile wet chemical approach, in which the consecutive hydrothermal-combustion reaction was performed. The doping of Ln3+ into Sr2CeO4 has little influence on the structure of host, and the as-prepared samples display well-crystallized spherical or elliptical shape with an average particle size at about 100–200 nm. For Eu3+ ions-doped Sr2CeO4, with the increase of Eu3+-doping concentration, the blue light emission band with the maximum at 468 nm originating from a Ce4+ → O2− charge transfer of the host decreases obviously and the characteristic red light emission of Eu3+ (5D0→7F2 transition at 618 nm) is enhanced gradually. Simultaneously, the fluorescent lifetime of the broadband emission of Sr2CeO4 decreases with the doping of Eu3+, indicating an efficient energy transfer from the host to the doping Eu3+ ions. The energy transfer efficiency from the host to Eu3+ was investigated in detail, and the emitting color of Sr2CeO4:Eu3+ can be easily tuned from blue to red by varying the doping concentration of Eu3+ ions. Moreover, the luminescence of Dy3+-doped Sr2CeO4 was also studied. Similar energy transfer phenomenon can be observed, and the incorporation of Dy3+ into Sr2CeO4 host leads to the characteristic emission of 4F9/2 → 6H15/2 (488 nm, blue light) and 4F9/2 → 6H13/2 (574 nm, yellow light) of Dy3+. The Sr2CeO4:Ln3+ fine particles with tunable luminescence are quite beneficial for its potential applications in the optoelectronic fields.publishe

Real-time visualization of clustering and intracellular transport of gold nanoparticles by correlative imaging.

Mechanistic understanding of the endocytosis and intracellular trafficking of nanoparticles is essential for designing smart theranostic carriers. Physico-chemical properties, including size, clustering and surface chemistry of nanoparticles regulate their cellular uptake and transport. Significantly, even single nanoparticles could cluster intracellularly, yet their clustering state and subsequent trafficking are not well understood. Here, we used DNA-decorated gold (fPlas-gold) nanoparticles as a dually emissive fluorescent and plasmonic probe to examine their clustering states and intracellular transport. Evidence from correlative fluorescence and plasmonic imaging shows that endocytosis of fPlas-gold follows multiple pathways. In the early stages of endocytosis, fPlas-gold nanoparticles appear mostly as single particles and they cluster during the vesicular transport and maturation. The speed of encapsulated fPlas-gold transport was critically dependent on the size of clusters but not on the types of organelle such as endosomes and lysosomes. Our results provide key strategies for engineering theranostic nanocarriers for efficient health management

The prospects of quantum computing in computational molecular biology

Quantum computers can in principle solve certain problems exponentially more quickly than their classical counterparts. We have not yet reached the advent of useful quantum computation, but when we do, it will affect nearly all scientific disciplines. In this review, we examine how current quantum algorithms could revolutionize computational biology and bioinformatics. There are potential benefits across the entire field, from the ability to process vast amounts of information and run machine learning algorithms far more efficiently, to algorithms for quantum simulation that are poised to improve computational calculations in drug discovery, to quantum algorithms for optimization that may advance fields from protein structure prediction to network analysis. However, these exciting prospects are susceptible to "hype", and it is also important to recognize the caveats and challenges in this new technology. Our aim is to introduce the promise and limitations of emerging quantum computing technologies in the areas of computational molecular biology and bioinformatics.Comment: 23 pages, 3 figure

The Roles of Buyang Huanwu Decoction in Anti-Inflammation, Antioxidation and Regulation of Lipid Metabolism in Rats with Myocardial Ischemia

Buyang Huanwu Decoction (BYHWD) is a well-known Chinese medicine formula. Recent studies have reported that BYHWD can be used to treat ischemic heart disease. This study investigated the potential mechanism underlying the roles of BYHWD in alleviating the myocardial ischemia induced by isoproterenol (ISO) in rats. Different doses of BYHWD (25.68, 12.84 and 6.42 g kg−1) were lavaged to rats, respectively. Then the expression of the cluster of differentiation 40 (CD40) in the mononuclear cells was measured using flow cytometry, and the expressions of CD40 and its ligand (CD40L) in myocardial tissues were determined by western blotting. The serum biochemical values of superoxide dismutase (SOD) activity, the malondialdehyde (MDA) level and the free fatty acid (FFA) content were measured. The results showed that the SOD activities of BYHWD groups were significantly higher than that of the ISO group, while the MDA levels and FFA contents of all BYHWD groups were lower than that of the ISO group. BYHWD could decrease the expression of CD40 in the mononuclear cells and the CD40 and CD40L expressions in myocardial tissues. Our data suggest that the roles of BYHWD are not only related to its antioxidative action and regulation of lipid metabolisms, but also to the inhibition of inflammatory pathway by the decreased CD40 and CD40L expressions in rats with myocardial ischemia

Chronic Myeloid Leukemia Patients Sensitive and Resistant to Imatinib Treatment Show Different Metabolic Responses

The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML). However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML) showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML) and patients resistant to imatinib (RCML) had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA). In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention

MEDELLER: homology-based coordinate generation for membrane proteins

Motivation: Membrane proteins (MPs) are important drug targets but knowledge of their exact structure is limited to relatively few examples. Existing homology-based structure prediction methods are designed for globular, water-soluble proteins. However, we are now beginning to have enough MP structures to justify the development of a homology-based approach specifically for them