bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous determination of seven catechins in rat plasma by ultra-high performance liquid chromatography tandem mass spectrometry and its application to a pharmacokinetics study
Authors: Zhang Liang , Han Yuhui , Shan Jinjun , Liang Yuhong , Xu Liwei , Zhang Shihua , Li Junsong , Wan Xiaochun
Published: August 2015

UHPLC-MS/MS for the pharmacokinetics of seven catechins of rats orally administered with tea polyphenols.
Rechargeable Li–CO2 batteries with carbon nanotubes as air cathodes
Authors: Zhang Xin , Zhang Qiang , Zhang Zhang , Chen Yanan , Xie Zhaojun , Wei Jinping , Zhou Zhen
Published: August 2015

Rechargeable Li–CO2 batteries were fabricated with carbon nanotubes as air cathodes with high electrical conductivity and porous three-dimensional networks.
Highly sensitive “signal-on” electrochemiluminescent biosensor for the detection of DNA based on dual quenching and strand displacement reaction
Authors: Lou Jing , Wang Zhaoyin , Wang Xiao , Bao Jianchun , Tu Wenwen , Dai Zhihui
Published: August 2015

A “signal-on” electrochemiluminescent DNA biosensing platform was proposed based on dual quenching and the strand displacement reaction.
Adsorption properties of trifluoroacetic acid on anatase (101) and (001) surfaces: a density functional theory study
Authors: Lamiel-Garcia Oriol , Fernandez-Hevia Daniel , Caballero Amador C. , Illas Francesc
Published: August 2015

Trifluoroacetic acid adsorbs preferentially on the TiO2(001) surface working as a growth control agent.
Design and synthesis of hierarchical NiCo2S4@NiMoO4core/shell nanospheres for high-performance supercapacitors
Authors: Yao Mingming , Hu Zhonghua , Liu Yafei , Liu Peipei
Published: August 2015

A novel electrode material of three-dimensional hierarchical NiCo2S4@NiMoO4core/shell nanospheres was synthesized by a facile two-step hydrothermal method. These hierarchical NiCo2S4@NiMoO4core/shell nanospheres exhibit a high specific capacitance of 1714 F g−1at a current density of 1 A g−1, which indicated the excellent electrochemistry performance.
Effect of styrene-butadiene rubber on the electrical properties of carbon black/cement mortar
Authors: Li Gengying , Wang Lei , Leung Christopher , Hu Ranxiong , Zhao Xiaohua , Yan Biao , Zhou Jingguo
Published: August 2015

Styrene-butadiene rubber increased the piezoresistivity effect of CB/PC mortar. Both positive and negative piezoresistivity occurred in mortars during compression. The mechanism was explained by using both the tunneling effect and capacitance effect.
New iodonium salts in NIR sensitized radical photopolymerization of multifunctional monomers
Authors: Brömme Thomas , Oprych Dennis , Horst Joachim , Pinto Paula Sevenini , Strehmel Bernd
Published: August 2015

Efficiency of NIR sensitized radical photopolymerization depends on the dissociation of iodonium salts comprising anions with low coordination capability.
Sulfur-doped graphene laminates for EMI shielding applications
Authors: Shahzad Faisal , Kumar Pradip , Yu Seunggun , Lee Seunghwan , Kim Yoon-Hyun , Hong Soon Man , Koo Chong Min
Published: August 2015

Herein, for the first time, we demonstrate that a laminated structure of sulfur-doped reduced graphene oxide (SrGO) provides significant potential for electromagnetic interference shielding applications.
Circadian timekeeping in Drosophila melanogaster and Mus musculus
Authors: Glossop Nicholas R. J
Published: August 2015

The discovery of the period gene mutants in 1971 provided the first evidence that daily rhythms in the sleep–wake cycle of a multicellular organism, the fruit fly Drosophila melanogaster, had an underlying genetic basis. Subsequent research has established that the biological clock mechanism in flies and mammals is strikingly similar and functions as a bimodal switch, simultaneously turning on one set of genes and turning off another set and then reversing the process every 12 h. In this chapter, the current model of the clock mechanism in Drosophila will be presented. This relatively basic model will then be used to outline the general rules that govern how the biological clock operates in mammals.
Glucose metabolism in Trypanosoma cruzi
Authors: Maugeri Dante A. , Cannata Joaquin J.B. , Cazzulo Juan-José
Published: August 2015

The causative agent of Chagas disease, Trypanosoma cruzi, metabolizes glucose through two major pathways: glycolysis and the pentose phosphate pathway. Glucose is taken up via one facilitated transporter and its catabolism by the glycolytic pathway leads to the excretion of reduced products, succinate and l-alanine, even in the presence of oxygen; the first six enzymes are located in a peroxisome-like organelle, the glycosome, and the lack of regulatory controls in hexokinase and phosphofructokinase results in the lack of the Pasteur effect. All of the enzymes of the pentose phosphate pathway are present in the four major stages of the parasite's life cycle, and some of them are possible targets for chemotherapy. The gluconeogenic enzymes phosphoenolpyruvate carboxykinase and fructose-1,6-bisphosphatase are present, but there is no reserve polysaccharide.
Folate metabolic pathways in Leishmania
Authors: Vickers Tim J. , Beverley Stephen M.
Published: August 2015

Trypanosomatid parasitic protozoans of the genus Leishmania are autotrophic for both folate and unconjugated pteridines. Leishmania salvage these metabolites from their mammalian hosts and insect vectors through multiple transporters. Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. PTR1 can act as a metabolic bypass of DHFR inhibition, reducing the effectiveness of existing antifolate drugs. Leishmania possess a reduced set of folate-dependent metabolic reactions and can salvage many of the key products of folate metabolism from their hosts. For example, they lack purine synthesis, which normally requires 10-formyltetrahydrofolate, and instead rely on a network of purine salvage enzymes. Leishmania elaborate at least three pathways for the synthesis of the key metabolite 5,10-methylene-tetrahydrofolate, required for the synthesis of thymidylate, and for 10-formyltetrahydrofolate, whose presumptive function is for methionyl-tRNAMet formylation required for mitochondrial protein synthesis. Genetic studies have shown that the synthesis of methionine using 5-methyltetrahydrofolate is dispensable, as is the activity of the glycine cleavage complex, probably due to redundancy with serine hydroxymethyltransferase. Although not always essential, the loss of several folate metabolic enzymes results in attenuation or loss of virulence in animal models, and a null DHFR-TS mutant has been used to induce protective immunity. The folate metabolic pathway provides numerous opportunities for targeted chemotherapy, with strong potential for ‘repurposing' of compounds developed originally for treatment of human cancers or other infectious agents.
The apicoplast: a red alga in human parasites
Authors: Striepen Boris
Published: August 2015

Surprisingly, some of the world's most dangerous parasites appear to have had a benign photosynthetic past in the ocean. The phylum Apicomplexa includes the causative agents of malaria and a number of additional human and animal diseases. These diseases threaten the life and health of hundreds of millions each year and pose a tremendous challenge to public health. Recent findings suggest that Apicomplexa share their ancestry with diatoms and kelps, and that a key event in their evolution was the acquisition of a red algal endosymbiont. A remnant of this endosymbiont is still present today, albeit reduced to a small chloroplast-like organelle, the apicoplast. In the present chapter, I introduce the remarkably complex biology of this organelle. The apicoplast is bounded by four membranes, and these membranes trace their ancestry to three different organisms. Intriguingly, this divergent ancestry is still reflected in their molecular makeup and function. We also pursue the raison d'être of the apicoplast. Why did Apicomplexa retain a chloroplast when they abandoned photosynthesis for a life as obligate parasites? The answer to this question appears to lie in the profound metabolic dependence of the parasite on its endosymbiont. This dependence may prove to be a liability to the parasite. As humans lack chloroplasts, the apicoplast has become one of the prime targets for the development of parasite-specific drugs.
Trichomonas vaginalis: current understanding of host–parasite interactions
Authors: Ryan Christopher M. , Miguel Natalia de , Johnson Patricia J.
Published: August 2015

Trichomonas vaginalis is a sexually transmitted obligate extracellular parasite that colonizes the human urogenital tract. Despite being of critical importance to the parasite's survival relatively little is known about the mechanisms employed by T. vaginalis to establish an infection and thrive within its host. Several studies have focused on the interaction of the parasite with host cells and extracellular matrix, identifying multiple suspected T. vaginalis adhesins. However, with the exception of its surface lipophosphoglycan, the evidence supporting a role in adhesion is indirect or controversial for many candidate molecules. The availability of the T. vaginalis genome sequence paved the way for genomic analyses to search for proteins possibly involved in host–parasite interactions. Several proteomic analyses have also provided insight into surface, soluble and secreted proteins that may be involved in Trichomonas pathogenesis. Although the accumulation of molecular data allows for a more rational approach towards identifying drug targets and vaccine candidates for this medically important parasite, a continued effort is required to advance our understanding of its biology. In the present chapter, we review the current status of research aimed at understanding T. vaginalis pathogenesis. Applied experimental approaches, an overview of significant conclusions drawn from this research and future challenges are discussed.
Potential diagnostic value of the umbilical artery as a definition of neural fatty acid status of the fetus during its growth: the umbilical artery as a diagnostic tool
Authors: CRAWFORD M. A. , COSTELOE K. , DOYLE W. , LEIGHFIELD M. J. , LENNON E. A. , MEADOWS N.
Published: August 2015

Summary

Low birth weight (LBW) is associated with handicaps, the most prevelant of which affect the brain or its sensory attributes and have a life long impact. We have therefore been interested in nutrition and fetal growth and have studied the relationship between maternal diet and the outcome of pregnancy.

Essential fatty acids are methylene-interrupted, polyenoic fatty acids that are required for cell membrane structure, integrity and function. Some 60% of the structural material of the brain and nervous system is lipid and it uses 20- and 22-carbon-chain-length polyenoic acids specifically in sites of signal transduction and high activity (Fig. 1).

We have been interested in the acquisition of these fatty acids during fetal growth and along with deficits of several nutrients found low intakes of essential fatty acids (EFA) in the mothers of LBW babies. In order to test this food intake data we have analysed the lipids of the umbilical artery as representative of fetal tissue.

We found surprisingly high proportions of the n − 9 eicosatrienoic acid (20:3, n − 9) and docosatrienoic acid (22:3, n − 9). The 20:3, n − 9 is known as the Mead acid and is recognized as a biochemical index of EFA deficiency [1,2]. The 20:3, n − 9/2:4, n − 6 ratio has been used as a biochemical test of general EFA deficiency and the 22:5, n − 6/ 22:4, n − 6 ratio as a marker of docosahexaenoic or n − 3 deficiency. Both ratios were unusually high. Further analysis of 14 babies of different birth weights produced highly significant Pearson correlation coefficients between birth weights and head circumferences, and these two indices, which were negative, and greater in the ethanolamine phosphoglycerides than in the choline phosphoglycerides of the umbilical artery.

The ethanolamine phosphoglycerides are inner membrane lipids and therefore the presence of the Mead acid and high levels of 22:5, n − 6 are statements about the biochemical history of the individual fetus. These indices may therefore have a diagnostic value as a measure of the nutritional status of the fetus during its growth. Because they describe the status of fatty acids specifically used for neural tissue growth, this diagnostic tool has a potential, which needs now to be tested, for assessing risk of neural deficits or damage in, for example, LBW and premature infants.
Chemical modulation of chemotherapy resistance in cultured oesophageal carcinoma cells
Authors: Sheehan D. , Meade G.
Published: August 2015

Oesophageal carcinoma is a common form of cancer in developing countries, especially in the Caspian littoral and northern China. In contrast, it has a much lower incidence in Japan, the U.S.A. and western Europe. Certainly in the case of squamous cell oesophageal carcinoma, dietary composition, smoking, alcohol and exposure to nitrosamines are major risk factors that may partly explain the disease's geographical distribution. The prognosis for oesophageal carcinoma is generally poor, due to the high incidence of distant metastasis and local recurrence. Combination treatment with both cisplatin and 5-fluorouracil is the most common chemotherapy regime used. We have carried out a detailed study of sensitivity of two oesophageal cell lines: OC1 cells from a squamous carcinoma of a male patient, and OC2, a squamous carcinoma obtained from a female patient. Both cell lines are sensitive to Vinca alkaloids and doxorubicin, while being quite resistant to alkylating agents such as cisplatin and l,3-bis-(2-chloroethyl)-1-nitrosourea. This pattern of resistance suggests a possible role for glutathione S-transferase (GST) and/or glutathione (GSH) in resistance, and would seem to exclude the multidrug resistance phenotype. Both cell lines possess mainly Pi-class GSTs, and have distinct levels of GSH, with OC2 possessing some 25 % of the level of OC1 cells. Effects of a variety of modulating agents on the pattern of resistance, such as the GSH depleter, buthionine sulphoximine, and the GST inhibitor, ethacrynic acid, were determined. An unexpected observation was that ethacrynic acid appears to increase the level of GSH in both cell lines.
The use of electrochemically grown polymers on metallized electrodes to reduce electrode fouling in biological matrices
Authors: Daly D. J. , O'Sullivan C. K. , Guilbault G. G.
Published: August 2015

The use of electrochemically grown polymers has expanded dramatically in the last couple of years, and they are now well established as membranes for immobilizing components. The evidence here for their anti-fouling properties is good. The poly(1,3-diaminobenzene)-covered electrodes performed well in the buffer, urine, plasma and serum samples, but not so well in the blood. The Ru/Rh/Pt, Rh/Rh and the Pt-on-glassy carbon electrodes covered with poly(1,3-diaminobenzene) were the best electrodes in the blood. The Pt disc seemed to exhibit the largest irrepeatability in most of the biological matrices.
Using the CATH domain database to assign structures and functions to the genome sequences
Authors: Pearl F. , Todd A. E. , Bray J. E. , Martin A. C. R. , Salamov A. A. , Suwa M. , Swindells M. B. , Thornton J. M. , Orengo C. A.
Published: August 2015

The CATH database of protein structures contains ∼ 18000 domains organized according to their (C)lass, (A)rchitecture, (T)opology and (H)omologous superfamily [1]. Relationships between evolutionary related structures (homologues) within the database have been used to test the sensitivity of various sequence search methods in order to identify relatives in Genbank and other sequence databases [2]. Subsequent application of the most sensitive and efficient algorithms, gapped blast and the profile based method, Position Specific Iterated Basic Local Alignment Tool (PSI-BLAST) [3], could be used to assign structural data to between 22 and 36% of microbial genomes in order to improve functional annotation and enhance understanding of biological mechanism. However, on a cautionary note, an analysis of functional conservation within fold groups and homologous superfamilies in the CATH database, revealed that whilst function was conserved in nearly 55% of enzyme families, function had diverged considerably, in some highly populated families. In these families, functional properties should be inherited far more cautiously and the probable effects of substitutions in key functional residues carefully assessed.
Towards a fibrous composite with dynamically controlled stiffness: lessons from echinoderms
Authors: Trotter J. A. , Tipper J. , Lyons-Levy G. , Chino K. , Heuer A. H. , Liu Z. , Mrksich M. , Hodneland C. , Dillmore W. S. , Koob T. J. , Koob-Emunds M. M. , Kadler K. , Holmes D.
Published: August 2015

Sea urchins and sea cucumbers, like other echinoderms, control the tensile properties of their connective tissues by regulating stress transfer between collagen fibrils. The collagen fibrils are spindle-shaped and up to 1 mm long with a constant aspect ratio of approx. 2000. They are organized into a tissue by an elastomeric network of fibrillin microfibrils. Interactions between the fibrils are regulated by soluble macromolecules that are secreted by local, neurally controlled, effector cells. We are characterizing the non-linear viscoelastic properties of sea cucumber dermis under different conditions, as well as the structures, molecules and molecular interactions that determine its properties. In addition, we are developing reagents that will bind covalently to fibril surfaces and reversibly form cross-links with other reagents, resulting in a chemically controlled stress-transfer capacity. The information being developed will lead to the design and construction of a synthetic analogue composed of fibres in an elastomeric matrix that contains photo- or electro-sensitive reagents that reversibly form interfibrillar cross-links.
Gene regulation through chromatin remodelling by members of the nuclear receptor superfamily
Authors: McEwan I. J.
Published: August 2015

The intracellular receptors for steroid hormones, thyroid hormones, retinoids and vitamin D3 are known to bind to specific DNA elements and thus regulate target gene expression. This introductory review and the following papers address some of the mechanisms underlying this action. In particular, the ability of this family of transcription factors to recruit multi-protein complexes that have the capacity to remodel chromatin structure in order to silence or activate target gene expression is discussed.
Novel mechanisms for the targeting of proteins into and across chloroplast membranes
Authors: Woolhead C. , Bolhuis A. , Robinson C.
Published: August 2015

The assembly of the photosynthetic apparatus requires the translocation of numerous proteins from the cytosol, initially into the stroma and thereafter into or across the thylakoid membrane. Recent studies have shown that proteins are transported into this membrane by a variety of mechanisms, some of which are derived from a cyanobacterial-type ancestor, whereas others have evolved in response to the more complex transport pathway used by cytosolically synthesized chloroplast proteins. It is now apparent that some of the targeting pathways are used exclusively by hydrophobic thylakoid membrane proteins; here we review recent progress in our understanding of the biogenesis of this important class of protein.
Lipid interactions with bacterial channels: fluorescence studies
Authors: Powl A.M. , Carney J. , Marius P. , East J.M. , Lee A.G.
Published: August 2015

Interactions between a membrane protein and the lipid molecules that surround it in the membrane are important in determining the structure and function of the protein. These interactions can be pictured at the molecular level using fluorescence spectroscopy, making use of the ability to introduce tryptophan residues into regions of interest in bacterial membrane proteins. Fluorescence quenching methods have been developed to study lipid binding separately on the two sides of the membrane. Lipid binding to the surface of the mechanosensitive channel MscL is heterogeneous, with a hot-spot for binding anionic lipid on the cytoplasmic side, associated with a cluster of three positively charged residues. The environmental sensitivity of tryptophan fluorescence emission has been used to identify the residues at the ends of the hydrophobic core of the second transmembrane α-helix in MscL. The efficiency of hydrophobic matching between MscL and the surrounding lipid bilayer is high. Fluorescence quenching methods can also be used to study binding of lipids to non-annular sites such as those between monomers in the homotetrameric potassium channel KcsA.
Plasmodium falciparum possesses organelle-specific α-keto acid dehydrogenase complexes and lipoylation pathways
Authors: Günther S. , McMillan P.J. , Wallace L.J.M. , Müller S.
Published: August 2015

The human malaria parasite Plasmodium falciparum possesses a single mitochondrion and a plastid-like organelle called the apicoplast. Both organelles contain members of the KADH (α-keto acid dehydrogenase) complexes – multienzyme complexes that are involved in intermediate metabolism. In the asexual blood stage forms of the parasites, the α-ketoglutarate dehydrogenase and branched chain KADH complexes are both located in the mitochondrion, whereas the pyruvate dehydrogenase is exclusively found in the apicoplast. In agreement with this distribution, Plasmodium parasites have two separate and organelle-specific pathways that guarantee lipoylation of the KADH complexes in both organelles. A biosynthetic pathway comprised of lipoic acid synthase and lipoyl (octanoyl)-ACP:protein Nε-lipoyltransferase B is present in the apicoplast, whereas the mitochondrion is supplied with exogenous lipoic acid, and ligation of the metabolite to the KADH complexes is accomplished by a lipoate protein ligase A similar to that of bacteria and plants. Both pathways are excellent potential targets for the design of new antimalarial drugs.
Structure and neurotoxicity of novel amyloids derived from the BRI gene
Authors: Gibson G. , El-Agnaf O.M.A. , Anwar Z. , Sidera C. , Isbister A. , Austen B.M.
Published: August 2015

A number of human neurodegenerative diseases involve aggregated amyloid proteins in the brain, e.g. Alzheimer's disease (β-amyloid) and Parkinson's disease (α-synuclein). Other examples are rare familial dementias which involve the BRI gene. In a British family, mutation of the termination codon extends the reading frame of BRI to yield a furin-processed 34-residue peptide (Abri; British dementia peptide), 11 residues longer than the wild-type (WT). In a Danish family, a ten-base insertion also yields a 34-residue peptide (Adan; Danish dementia peptide). To explore the roles of Abri and Adan in neurodegeneration, we synthesized Abri and Adan in oxidized and reduced forms and generated transgenic mice colonies expressing the WT and mutated forms of BRI. We have generated transgenic mice colonies bearing the genes coding for WT-BRI, Adan and Abri under the control of the Thy1 promoter. Whereas WT-BRI transgenic mice express full-length WT-BRI protein in their brains, Adan protein is fully processed to small peptides.
Two mutants selectively resistant to polyenes reveal distinct mechanisms of antifungal activity by nystatin and amphotericin B
Authors: Hapala I. , Klobučníková V. , Mazáňová K. , Kohút P.
Published: August 2015

Polyene macrolides nystatin and amphotericin B are widely used in the treatment of fungal infections. In order to characterize factors affecting polyene activity, we have isolated Saccharomyces cerevisiae mutants showing selective resistance to nystatin and amphotericin B. Characterization of two of these mutants (nystatin-resistant mutant X1/16 and amphotericin B-resistant mutant X3/33) is presented. Genetic analysis revealed that resistance in each of these mutants is caused by a mutation in one gene with a different mode of inheritance. Nystatin resistance in mutant X1/16 is caused by changes in sterol spectrum while amphotericin B resistance in mutant X3/33 is probably related to modification of the cell wall. Our results suggest that, in spite of their structural similarity, nystatin and amphotericin B differ significantly in mechanisms of their antifungal activity.
Regulation of actin assembly by SCAR/WAVE proteins
Authors: Ibarra N. , Pollitt A. , Insall R.H.
Published: August 2015

Actin reorganization is a tightly regulated process that co-ordinates complex cellular events, such as cell migration, chemotaxis, phagocytosis and adhesion, but the molecular mechanisms that underlie these processes are not well understood. SCAR (suppressor of cAMP receptor)/WAVE [WASP (Wiskott–Aldrich syndrome protein)-family verprolin homology protein] proteins are members of the conserved WASP family of cytoskeletal regulators, which play a critical role in actin dynamics by triggering Arp2/3 (actin-related protein 2/3)-dependent actin nucleation. SCAR/WAVEs are thought to be regulated by a pentameric complex which also contains Abi (Abl-interactor), Nap (Nck-associated protein), PIR121 (p53-inducible mRNA 121) and HSPC300 (haematopoietic stem progenitor cell 300), but the structural organization of the complex and the contribution of its individual components to the regulation of SCAR/WAVE function remain unclear. Additional features of SCAR/WAVE regulation are highlighted by the discovery of other interactors and distinct complexes. It is likely that the combinatorial assembly of different components of SCAR/WAVE complexes will prove to be vital for their roles at the centre of dynamic actin reorganization.
New metabolically stabilized analogues of lysophosphatidic acid: agonists, antagonists and enzyme inhibitors
Authors: Prestwich G.D. , Xu Y. , Qian L. , Gajewiak J. , Jiang G.
Published: August 2015

Lysophosphatidic acid (LPA) is a metabolically labile natural phospholipid with a bewildering array of physiological effects. We describe herein a variety of long-lived receptor-specific agonists and antagonists for LPA receptors. Several LPA and PA (phosphatidic acid) analogues also inhibit LPP (lipid phosphate phosphatase). The sn-1 or sn-2 hydroxy groups have been replaced by fluorine, difluoromethyl, difluoroethyl, O-methyl or O-hydroxyethoxy groups to give non-migrating LPA analogues that resist acyltransferases. Alkyl ether replacement of acyl esters produced lipase and acyltransferase-resistant analogues. Replacement of the bridging oxygen in the monophosphate by an α-monofluoromethylene-, α-bromomethylene- or α,α-difluoromethylenephosphonate gave phosphatase-resistant analogues. Phosphorothioate analogues with O-acyl and O-alkyl chains are potent, long-lived agonists for LPA1 and LPA3 receptors. Most recently, we have (i) prepared stabilized O-alkyl analogues of lysobisphosphatidic acid, (ii) explored the structure–activity relationship of stabilized cyclic LPA analogues and (iii) synthesized neutral head group trifluoromethylsulphonamide analogues of LPA. Through collaborative studies, we have collected data for these stabilized analogues as selective LPA receptor (ant)agonists, LPP inhibitors, TREK (transmembrane calcium channel) K+ channel agonists, activators of the nuclear transcription factor PPAR-γ (peroxisome-proliferator-activated receptor-γ), promoters of cell motility and survival, and radioprotectants for human B-cells.
Structural characteristics of lysophosphatidic acid biological targets
Authors: Parrill A.L.
Published: August 2015

Lysophosphatidic acid (LPA; 1-acyl-3-phosphoglycerol) exerts its biological activity through both extracellular and intracellular targets. Receptor targets include the cell-surface G-protein-coupled receptors LPA1–4 and the nuclear PPAR-γ (peroxisome-proliferator-activated receptor γ). Enzyme targets include the secreted cancer cell motility factor, autotaxin, and the transmembrane phosphatases, LPP1–3 (where LPP stands for lipid phosphate phosphatase). Ion channel targets include the two pore domain ion channels in the TREK family, TREK-1, TREK-2 and TRAAK. Structural features of these targets and their interactions with LPA are reviewed.
Disulphide formation on mitochondrial protein thiols
Authors: Hurd T.R. , Filipovska A. , Costa N.J. , Dahm C.C. , Murphy M.P.
Published: August 2015

A large number of proteins contain free thiols that can be modified by the formation of internal disulphides or by mixed disulphides with low-molecular-mass thiols. The majority of these latter modifications result from the interaction of protein thiols with the endogenous glutathione pool. Protein glutathionylation and disulphide formation are of significance both for defence against oxidative damage and in redox signalling. As mitochondria are central to both oxidative damage and redox signalling within the cell, these modifications of mitochondrial proteins are of particular importance. In the present study, we review the mechanisms and physiological significance of these processes.
Coupling ATP hydrolysis to DNA strand passage in type IIA DNA topoisomerases
Authors: Maxwell A. , Costenaro L. , Mitelheiser S. , Bates A.D.
Published: August 2015

Type IIA topos (topoisomerases) catalyse topological conversions of DNA through the passage of one double strand through a transient break in another. In the case of the archetypal enzyme, DNA gyrase, it has always been apparent that the enzyme couples the free energy of ATP hydrolysis to the introduction of negative supercoiling, and the structural details of this process are now becoming clearer. The homologous type IIA enzymes such as topo IV and eukaryotic topo II also require ATP and it has more recently been shown that the energy of hydrolysis is coupled to a reduction of supercoiling or catenation (linking) beyond equilibrium. The mechanism behind this effect is less clear. We review the energy coupling process in both classes of enzyme and describe recent mechanistic and structural work on gyrase that addresses the mechanism of energy coupling.
Generation of embryos directly from embryonic stem cells by tetraploid embryo complementation reveals a role for GATA factors in organogenesis
Authors: Duncan S.A.
Published: August 2015

Gene targeting in ES (embryonic stem) cells has been used extensively to study the role of proteins during embryonic development. In the traditional procedure, this requires the generation of chimaeric mice by introducing ES cells into blastocysts and allowing them to develop to term. Once chimaeric mice are produced, they are bred into a recipient mouse strain to establish germline transmission of the allele of interest. Although this approach has been used very successfully, the breeding cycles involved are time consuming. In addition, genes that are essential for organogenesis often have roles in the formation of extra-embryonic tissues that are essential for early stages of post-implantation development. For example, mice lacking the GATA transcription factors, GATA4 or GATA6, arrest during gastrulation due to an essential role for these factors in differentiation of extra-embryonic endoderm. This lethality has frustrated the study of these factors during the development of organs such as the liver and heart. Extraembryonic defects can, however, be circumvented by generating clonal mouse embryos directly from ES cells by tetraploid complementation. Here, we describe the usefulness and efficacy of this approach using GATA factors as an example.
KATP channels and insulin secretion: a key role in health and disease
Authors: Ashcroft F.M.
Published: August 2015

This review summarizes advances in our understanding of the structure and function of the ATP-sensitive potassium (KATP) channel of the pancreatic β-cell that have been made over the last 5 years. It discusses recent structural studies of the octameric KATP channel complex and studies of the regulation of KATP channel activity by nucleotides. It then considers the molecular mechanism by which gain-of-function mutations in the Kir6.2 subunit of the KATP channel reduce channel inhibition by ATP and thereby lead to neonatal diabetes, and how identification of these mutations has led to changes in therapy. Finally, it illustrates how mouse models of glucose intolerance or diabetes can provide fresh insight into β-cell function, using the C57BL/6J mouse, whose glucose intolerance arises from mutations in nicotinamide nucleotide transhydrogenase, as an example.
Lipid–protein interactions
Authors: Lee Anthony G.
Published: August 2015

Intrinsic membrane proteins are solvated by a shell of lipid molecules interacting with the membrane-penetrating surface of the protein; these lipid molecules are referred to as annular lipids. Lipid molecules are also found bound between transmembrane α-helices; these are referred to as non-annular lipids. Annular lipid binding constants depend on fatty acyl chain length, but the dependence is less than expected from models based on distortion of the lipid bilayer alone. This suggests that hydrophobic matching between a membrane protein and the surrounding lipid bilayer involves some distortion of the transmembrane α-helical bundle found in most membrane proteins, explaining the importance of bilayer thickness for membrane protein function. Annular lipid binding constants also depend on the structure of the polar headgroup region of the lipid, and hotspots for binding anionic lipids have been detected on some membrane proteins; binding of anionic lipid molecules to these hotspots can be functionally important. Binding of anionic lipids to non-annular sites on membrane proteins such as the potassium channel KcsA can also be important for function. It is argued that the packing preferences of the membrane-spanning α-helices in a membrane protein result in a structure that matches nicely with that of the surrounding lipid bilayer, so that lipid and protein can meet without either having to change very much.
Monitoring mitochondrial dynamics and complex I dysfunction in neurons: implications for Parkinson's disease
Authors: Simcox Eve M. , Reeve Amy , Turnbull Doug
Published: August 2015

Mitochondrial dynamics are essential for maintaining organelle stability and function. Through fission, fusion and mitophagic events, optimal populations of mitochondria are retained. Subsequently, alterations in such processes can have profound effects on the individual mitochondrion and the cell within which they reside. Neurons are post-mitotic energy-dependent cells and, as such, are particularly vulnerable to alterations in cellular bioenergetics and increased stress that may occur as a direct or indirect result of mitochondrial dysfunction. The trafficking of mitochondria to areas of higher energy requirements, such as synapses, where mitochondrial densities fluctuate, further highlights the importance of efficient mitochondrial dynamics in neurons. PD (Parkinson's disease) is a common progressive neurodegenerative disorder which is characterized by the loss of dopaminergic neurons within the substantia nigra. Complex I, the largest of all of the components of the electron transport chain is heavily implicated in PD pathogenesis. The exact series of events that lead to cell loss, however, are not fully elucidated, but are likely to involve dysfunction of mitochondria, their trafficking and dynamics.
Modelling FUSopathies: focus on protein aggregation
Authors: Shelkovnikova Tatyana A.
Published: August 2015

The discovery of a causative link between dysfunction of a number of RNA-binding proteins with prion-like domains and the development of certain (neuro)degenerative diseases has completely changed our perception of molecular mechanisms instigating pathological process in these disorders. Irreversible aggregation of these proteins is a crucial pathogenic event delineating a type of proteinopathy. FUS (fused in sarcoma) is a prototypical member of the class, and studies into the causes and consequences of FUSopathies have been instrumental in characterizing the processes leading to deregulation of RNA metabolism in neurodegeneration. In vivo models of FUSopathy have provided critical insights into the mechanisms of FUS toxicity and clues on the role of non-amyloid aggregates, which are hallmarks of these diseases. The present review summarizes the data on FUS aggregation signatures in available model organisms on the basis of overexpression of FUS variants.
The zDHHC family of S-acyltransferases
Authors: Lemonidis Kimon , Werno Martin W. , Greaves Jennifer , Diez-Ardanuy Cinta , Sanchez-Perez Maria C. , Salaun Christine , Thomson David M. , Chamberlain Luke H.
Published: August 2015

The discovery of the zDHHC family of S-acyltransferase enzymes has been one of the major breakthroughs in the S-acylation field. Now, more than a decade since their discovery, major questions centre on profiling the substrates of individual zDHHC enzymes (there are 24 ZDHHC genes and several hundred S-acylated proteins), defining the mechanisms of enzyme-substrate specificity and unravelling the importance of this enzyme family for cellular physiology and pathology.
Liver X receptors in immune cell function in humans
Authors: Waddington Kirsty E. , Jury Elizabeth C. , Pineda-Torra Inés
Published: August 2015

The liver X receptors (LXRs), LXRα and LXRβ, are transcription factors with well-established roles in the regulation of lipid metabolism and cholesterol homeostasis. In addition, LXRs influence innate and adaptive immunity, including responses to inflammatory stimuli, proliferation and differentiation, migration, apoptosis and survival. However, the majority of work describing the role of LXRs in immune cells has been carried out in mouse models, and there are a number of known species-specific differences concerning LXR function. Here we review what is known about the role of LXRs in human immune cells, demonstrating the importance of these receptors in the integration of lipid metabolism and immune function, but also highlighting the need for a better understanding of the species, isoform, and cell-type specific effects of LXR activation.
Resource optimisation using bandwidth‐power product for multiple‐input multiple‐output orthogonal frequency‐division multiplexing access system in cognitive radio networks
Authors: Chen Bo , Zhao Minjian , Zhang Lei , Lei Ming
Published: August 2015

This study investigates resource allocation problems for a point‐to‐point multi‐carrier multiple‐input multiple‐output cognitive radio network. Different from conventional resource optimisation problems, a joint power and bandwidth resource optimisation framework using the novel optimisation metric, namely bandwidth‐power product, is developed. Besides, rate requirement of the secondary system is satisfied, and the interferences introduced to the primary users (PUs) are below threshold of tolerance. The optimal source precoding matrix is designed and two methods, namely the project‐channel singular value decomposition (SVD) and direct‐channel SVD methods, are applied to satisfy interference power constraints for PUs. Then the unified power and channel allocation problem is derived and found to be a mixed‐integer programming problem. Hence, a sub‐optimal and tractable algorithm with low complexity is proposed. The innovative idea is to determine the channel resource budget by selecting the best channels, where the criterion for evaluating the quality of channel is detailed discussed. Then the power optimisation subproblem and channel allocation subproblem can be performed independently using the Lagrange‐duality theory and Gauss–Newton method, respectively. The simulation results show significant improvement in spectral efficiency by using this framework compared to classical power optimisation framework using the waterfilling scheme.
Single‐carrier underwater acoustic communication combined with channel shortening and dichotomous coordinate descent recursive least squares with variable forgetting factor
Authors: Zhang Youwen , Liu Lu , Sun Dajun , Cui Hongyu
Published: August 2015

In this study, the authors propose a novel decision feedback equaliser (DFE)‐based receiver, which combines channel shortening methods and dichotomous coordinate descent (DCD) recursive least squares (RLS) adaptive algorithm with variable forgetting factor (VFF). The proposed receiver can obtain its performance gain via two aspects: (i) reducing the computing complexity by channel shortening method, such as passive time reversal (pTR) filter or minimised mean‐square error (MMSE) filter and (ii) improving the performance of the receiver, such as a lower bit error rate and mean‐square error. Underwater acoustic (UWA) channel has the features of long multi‐path spread and time‐varying property. When the multi‐path spread is very long, pTR or MMSE filter is used as a channel shortening pre‐processing method to reduce the computing complexity in the DFE receiver. When the channel is time varying, VFF is incorporated into DCD‐RLS adaptive algorithm to improve the tracking capability of the DFE receiver. The proposed receiver is appealing for practical implementations. Numerical examples and lake experimental results show that, the proposed DFE receiver can achieve a better performance in the UWA communication system.
Improved diagonal interacting multiple model algorithm for manoeuvering target tracking based on H∞ filter
Authors: Fu Xiaoyan , Shang Yuanyuan , Yuan Huimei
Published: August 2015

This study is devoted to the problem of state estimate of discrete‐time stochastic systems with Markov jump parameters. A robust algorithm – diagonal interacting multiple model algorithm based on H∞ filtering is presented for manoeuvering target tracking when noise of measurement is of unknown statistics. Extensive Monte Carlo simulations show the effectiveness and superiority of the proposed algorithm.
Adaptive control of singular Markovian jump systems with uncertain switchings
Authors: Wang Guoliang , Zhang Qingling , Su Chengli
Published: August 2015

This article studies the problem of adaptive control for a class of singular Markovian jump systems, upper bound of uncertain transition rates of which is unknown. Firstly, an adaptation law is developed to estimate the unknown parameter. Then, a new class of adaptive state feedback controller is proposed such that not only is the estimated error bounded in probability but also the states of the closed‐loop system are asymptotically stable in probability. Moreover, the presented method is successfully extended to another general case that the transition rate matrix is partially unknown. Similarly, the bound of the unknown elements is not necessarily given beforehand. Finally, a numerical example is given to show the validity and superiority of the developed results.
High‐gain observer‐based output feedback control of single‐rod electro‐hydraulic actuator
Authors: Guo Qing , Yu Tian , Jiang Dan
Published: August 2015

In this study, a non‐linear backstepping control method based on a high‐gain observer design is presented for a single‐rod electro‐hydraulic actuator, which is not a strict feedback non‐linear system. An equivalent model transformation is used for load pressure to establish the relationship between displacement command and virtual command of load pressure. So the convergence analysis of the single‐rod electro‐hydraulic servo (EHS) model can be divided into two parts. Since the EHS has only one measured output state, a high‐gain observer is developed to estimate the full‐state of EHS, which can be used in the design of backstepping control. Furthermore, the convergence of this proposed controller is proved by Lyapunov technique. The experimental results verify the dynamic behaviour of this controller varying the observer parameters. In comparison to proportional–integral controller, the proposed controller is more suitable for this EHS in some critical conditions with high response frequency and large unknown external load.
Beamspace reduced‐dimension space–time adaptive processing for multiple‐input multiple‐output radar based on maximum cross‐correlation energy
Authors: Zhang Wei , He Zishu , Li Jun , Li Chaohai
Published: August 2015

A new method for selecting auxiliary channels in reduced‐dimension space–time adaptive processing (STAP) based on maximum cross‐correlation energy has been proposed for airborne multiple‐input multiple‐output radar. It is demonstrated that the proposed algorithm can achieve the same output signal‐to‐interference–noise ratio (SINR) performance as the multistage multiple‐beam STAP algorithm which can assure the optimal performance when the number of auxiliary channels is fixed, but the auxiliary channels selecting process of the proposed algorithm is extremely simplified. Hence, the computation complexity is reduced dramatically. Practical considerations dictate that only the minimum number of auxiliary channels [(adaptive degrees of freedom (DoFs)] is required to achieve the desired array performance. The proposed approach can achieve the desired output signal‐to‐interference–noise performance with the minimum number of auxiliary channels. Consequently, the proposed approach can reduce the requirement of the sample support dramatically. It is demonstrated that the SINR loss will be <3 dB when only one channel is selected as the auxiliary channel. Generally, two to three channels are enough even when the clutter covariance matrix is unknown. This will be more obvious advantage when the number of independent and identically distributed secondary samples is limited. The reduction in DoFs can make the proposed approach more suitable for the practical clutter environments.
Facile method to prepare copper‐doped LiNbO3 nanocrystals
Authors: Liu Xiaobin , Que Wenxiu , Xing Yonglei , He Zuoli , He Yucheng
Published: August 2015

A facile method to prepare copper‐doped LiNbO3 nanocrystalline is reported. It should be mentioned here that the harmless citric acid plays a key role in soluble niobate at first and in the formation of the uniform gel. A detail thermal behaviour of the as‐obtained gel was investigated by thermogravimetry and differential thermal analysis. The crystal structure, elemental composition and microstructural properties were characterised by X‐ray diffraction analysis, X‐ray photoelectron spectroscopy and scanning electron microscopy. Results indicate that a pure phase similar to LiNbO3, which has the cell parameters of a = b = 5.150(5) Å and c = 13.896(9) Å, can be obtained at a low temperature (∼550°C) and the mean particle size of the as‐synthesised nanocrystalline is about 40 nm.