bluuebunny/crossref_metadata_2025 huggingface dataset:
The Crucial Role of Atg5 in Cortical Neurogenesis During Early Brain Development
Authors: Lv Xiaohui , Jiang Huihui , Li Baoguo , Liang Qingli , Wang Shukun , Zhao Qianwei , Jiao Jianwei
Published: August 2014

Autophagy plays an important role in the central nervous system. However, it is unknown how autophagy regulates cortical neurogenesis during early brain development. Here, we report that autophagy-related gene 5 (Atg5) expression increased with cortical development and differentiation. The suppression of Atg5 expression by knockdown led to inhibited differentiation and increased proliferation of cortical neural progenitor cells (NPCs). Additionally, Atg5 suppression impaired cortical neuronal cell morphology. We lastly observed that Atg5 was involved in the regulation of the β-Catenin signaling pathway. The β-Catenin phosphorylation level decreased when Atg5 was blocked. Atg5 cooperated with β-Catenin to modulate cortical NPCs differentiation and proliferation. Our results revealed that Atg5 has a crucial role in cortical neurogenesis during early embryonic brain development, which may contribute to the understanding of neurodevelopmental disorders caused by autophagy dysregulation.
Enhanced Biomass Degradation by Polysaccharide Monooxygenases
Authors: Magali Tanghe , Barbara Danneels , Ingeborg Stals , Tom Desmet
Published: August 2014

The degradation of cellulose is typically described as a process that relies solely on the action of hydrolytic enzymes. Although it had been suggested that this picture was incomplete, no additional activities could be identified during many decades of intensive research. Very recently, however, the discovery of polysaccharide monooxygenases (PMO) shed new light on the degradation process and paved the way for a much more efficient use of renewable resources. Indeed, PMOs were found to render cellulose chains more accessible for hydrolytic enzymes by disrupting the substrate's crystal packing through an oxidative cleavage reaction. These findings constitute a major breakthrough in biomass research but are still not completely understood. In this chapter, an up-to-date overview will be presented of our current knowledge about the function, structure and mechanism of this new class of enzymes.
Bioactive Compounds from Biomass
Authors: Xu Chun-Ping , Arancon Rick Arneil D.
Published: August 2014

Plants display a unique metabolic plasticity that includes thousands of natural compounds. The natural compounds with various potential bioactivities from plant biomass present one of the most interesting high-value products. In this chapter, the main chemical groups of bioactive compounds isolated from widespread plant biomass with their main bioactivities are discussed. Also, the bioactive natural compounds from tobacco biomass are covered as a case study.
Qualitative and quantitative evaluation of ginkgo terpene lactone raw material by HPLC/Q-TOF MS combined with HPLC-DAD-ELSD
Authors: Wu Yu-Long , Li Yan-Jing , Ding Gang , Huang Wen-Zhe , Li Ping , Wang Zhen-Zhong , Bi Yu-An , Sun Yong-Cheng , Wu Yun , Xiao Wei
Published: August 2014

Characterization and identification of chemical components in GTL by HPLC/Q-TOF MS/MS combined with online valve switching.
Highly efficient functional GexPb1−xTe based thermoelectric alloys
Authors: Gelbstein Yaniv , Davidow Joseph
Published: August 2014

Methods for enhancement of the direct thermal to electrical energy conversion efficiency, upon development of advanced thermoelectric materials, are constantly investigated mainly for an efficient implementation of thermoelectric devices in automotive vehicles, for utilizing the waste heat generated in such engines into useful electrical power and thereby reduction of the fuel consumption and CO2 emission levels.
Influence of heat and shear induced protein aggregation on the in vitro digestion rate of whey proteins
Authors: Singh Tanoj K. , Øiseth Sofia K. , Lundin Leif , Day Li
Published: August 2014

Protein intake is essential for growth and repair of body cells, the normal functioning of muscles, and health related immune functions.
Effect of Fe/Fe2O3 loading on the catalytic activity of sulfonated single-walled carbon nanohorns for the esterification of palmitic acid
Authors: Poonjarernsilp Chantamanee , Sano Noriaki , Sawangpanich Nut , Charinpanitkul Tawatchai , Tamon Hajime
Published: August 2014

The effect of dispersion of Fe/Fe2O3 nanoparticles in sulfonated single-walled carbon nanohorns (SO3H/SWCNHs) on their catalytic activity for the esterification of palmitic acid was investigated.
Synthesis and photoluminescence properties of a novel Sr2CeO4:Dy3+nanophosphor with enhanced brightness by Li+co-doping
Authors: Monika D. L. , Nagabhushana H. , Krishna R. Hari , Nagabhushana B. M. , Sharma S. C. , Thomas Tiju
Published: August 2014

A series of Dy3+(0.005–0.09 mol%) and Li+(0.005–0.03 mol%) co-doped strontium cerate (Sr2CeO4) nanopowders are synthesized by low temperature solution combustion synthesis.
Shape evolution and size controlled synthesis of mesoporous hydroxyapatite nanostructures and their morphology dependent Pb(ii) removal from waste water
Authors: Bharath G. , Jagadeesh Kumar A. , Karthick K. , Mangalaraj D. , Viswanathan C. , Ponpandian N.
Published: August 2014

Nanostructured hydroxyapatite with tunable morphologies was prepared by suitably adjusting the surfactants and used as an adsorbent for Pb(ii) from wastewater.
Controllable synthesis of three-dimensional branched gold nanocrystals assisted by cationic surfactant poly(diallyldimethylammonium) chloride in acidic aqueous solution
Authors: Zhang Haibin , Lu Yonggang , Liu Hong , Fang Jingzhong
Published: August 2014

An effective strategy was used for the controllable synthesis of single crystalline branched gold nanocrystals with a three-dimensional hierarchical structure in aqueous solution.
DNA based multi-copper ions assembly using combined pyrazole and salen ligandosides
Authors: Su Meng , Tomás-Gamasa María , Carell Thomas
Published: August 2014

The pyrazole and salen ligandosides, when combined, are able to create stable multi-copper ion complexing DNA duplex structures in a cooperative fashion.
Microwave-assisted solvent vapor annealing to rapidly achieve enhanced performance of organic photovoltaics
Authors: Jung Buyoung , Kim Kangmin , Kim Woochul
Published: August 2014

Microwave-assisted solvent vapor annealing (MWSA) treatment is suggested to rapidly achieve high performance organic photovoltaics.
Assessing adaptation of the cancer kinome in response to targeted therapies
Authors: Zawistowski Jon S. , Graves Lee M. , Johnson Gary L.
Published: August 2014

Cancer cells are dependent on protein kinase signalling networks to drive proliferation and to promote survival, and, accordingly, kinases continue to represent a major target class for development of anti-cancer therapeutics. Kinase inhibitors nevertheless have yielded only limited success with many different malignancies due to the inability of single agents to sustain a durable clinical response. Cancer cell kinomes are highly resilient and able to bypass targeted kinase inhibition, leading to tumour resistance. A novel platform has been developed to analyse the activity of the expressed kinome using MIBs (multiplexed inhibitor beads), which consist of Sepharose beads with covalently immobilized inhibitors that preferentially bind activated kinases. Coupling MIB capture with MS (MIB–MS) allows simultaneous determination of the activity of over 75% of the expressed kinome, facilitating high-throughput assessment of adaptive kinase responses resulting from deregulated feedback and feedforward regulatory mechanisms. The adaptive response frequently involves transcriptional up-regulation of specific kinases that allow bypass of the targeted kinase. Understanding how the kinome reprogrammes to targeted kinase inhibition will allow novel therapeutic strategies to be developed for durable clinical responses.
Mechanisms of transcriptional dysregulation in repeat expansion disorders
Authors: Groh Matthias , Silva Lara Marques , Gromak Natalia
Published: August 2014

Approximately 40 human diseases are associated with expansion of repeat sequences. These expansions can reside within coding or non-coding parts of the genes, affecting the host gene function. The presence of such expansions results in the production of toxic RNA and/or protein or causes transcriptional repression and silencing of the host gene. Although the molecular mechanisms of expansion diseases are not well understood, mounting evidence suggests that transcription through expanded repeats plays an essential role in disease pathology. The presence of an expansion can affect RNA polymerase transcription, leading to dysregulation of transcription-associated processes, such as RNA splicing, formation of RNA/DNA hybrids (R-loops), production of antisense, short non-coding and bidirectional RNA transcripts. In the present review, we summarize current advances in this field and discuss possible roles of transcriptional defects in disease pathology.
Structure and function of a peptide pheromone family that stimulate the vomeronasal sensory system in mice
Authors: Abe Takayuki , Touhara Kazushige
Published: August 2014

Mammals use pheromones to communicate with other animals of the same species. In mice, the VNO (vomeronasal organ) has a pivotal role in pheromone detection. We discovered a 7 kDa peptide, ESP1 (exocrine-gland-secreting peptide 1), in tear fluids from male mice that enhances the sexual behaviour of female mice via the VNO. NMR studies demonstrate that ESP1 adopts a compact structure with a helical fold stabilized by an intramolecular disulfide bridge. Functional analysis in combination with docking simulation indicates that ESP1 is recognized by a specific G-protein-coupled vomeronasal receptor, V2Rp5, via charge–charge interactions in the large extracellular region of the receptor. ESP1 is a member of the ESP family, which comprises 38 homologous genes in mice, and some of these genes are expressed in a sex- or age-dependent manner. Most recently, ESP22 was found to be released specifically in juvenile tear fluids and to inhibit the sexual behaviour of adult male mice. These studies demonstrate that peptide pheromones are used for chemical communication in mice, and they indicate a structural basis for the narrowly tuned perception of mammalian peptide pheromones by vomeronasal receptors.
Complementary roles of mouse lipocalins in chemical communication and immunity
Authors: Stopková Romana , Dudková Barbora , Hájková Petra , Stopka Pavel
Published: August 2014

A primary site of infection in mammals is the nostrils, representing the gate to the brain through olfactory and vomeronasal epithelia, eyes as a direct route to the brain via the optical nerve, and oral cavity representing the main route to the digestive tract. Similarly, pheromones, odorants and tastants enter animal bodies the same way. Therefore similar evolutionary forces might have shaped the evolution of systems for recognition of pathogens and chemical signals. This might have resulted in sharing various proteins among systems of recognition and filtering to decrease potential costs of evolving and utilizing unique biochemical pathways. This has been documented previously in, for example, multipurpose and widely distributed GPCRs (G-protein-coupled receptors). The aim of the present review is to explore potential functional overlaps or complementary functions of lipocalins in the system of perception of exogenous substances to reconstruct the evolutionary forces that might have shaped their synergistic functions.
Recent studies implicate the nucleolus as the major site of nuclear translation
Authors: McLeod Tina , Abdullahi Akilu , Li Min , Brogna Saverio
Published: August 2014

The nucleolus is the most prominent morphological feature within the nucleus of eukaryotic cells and is best known for its role in ribosome biogenesis. It forms around highly transcribed ribosomal RNA gene repeats which yield precursor rRNAs that are co-transcriptionally processed, folded and, while still within the nucleolus, associate with most of the ribosomal proteins. The nucleolus is therefore often thought of as a factory for making ribosomal subunits, which are exported as inactive precursors to the cytoplasm where late maturation makes them capable of mRNA binding and translation initiation. However, recent studies have shown substantial evidence for the presence of functional, translation competent ribosomal subunits within the nucleus, particularly in the nucleolus. These observations raise the intriguing possibility that the nucleolus, as well as being a ribosome factory, is also an important nuclear protein-synthesis plant.
Tra2 protein biology and mechanisms of splicing control
Authors: Best Andrew , Dalgliesh Caroline , Kheirollahi-Kouhestani Mahsa , Danilenko Marina , Ehrmann Ingrid , Tyson-Capper Alison , Elliott David J.
Published: August 2014

Tra2 proteins regulate pre-mRNA splicing in vertebrates and invertebrates, and are involved in important processes ranging from brain development in mice to sex determination in fruitflies. In structure Tra2 proteins contain two RS domains (domains enriched in arginine and serine residues) flanking a central RRM (RNA recognition motif). Understanding the mechanisms of how Tra2 proteins work to control splicing is one of the key requirements to understand their biology. In the present article, we review what is known about how Tra2 proteins regulate splicing decisions in mammals and fruitflies.
Structural investigations of the RNA-binding properties of STAR proteins
Authors: Feracci Mikael , Foot Jaelle , Dominguez Cyril
Published: August 2014

STAR (signal transduction and activation of RNA) proteins are a family of RNA-binding proteins that regulate post-transcriptional gene regulation events at various levels, such as pre-mRNA alternative splicing, RNA export, translation and stability. Most of these proteins are regulated by signalling pathways through post-translational modifications, such as phosphorylation and arginine methylation. These proteins share a highly conserved RNA-binding domain, denoted STAR domain. Structural investigations of this STAR domain in complex with RNA have highlighted how a subset of STAR proteins specifically recognizes its RNA targets. The present review focuses on the structural basis of RNA recognition by this family of proteins.
Current perspectives on RNA secondary structure probing
Authors: Kenyon Julia , Prestwood Liam , Lever Andrew
Published: August 2014

The range of roles played by structured RNAs in biological systems is vast. At the same time as we are learning more about the importance of RNA structure, recent advances in reagents, methods and technology mean that RNA secondary structural probing has become faster and more accurate. As a result, the capabilities of laboratories that already perform this type of structural analysis have increased greatly, and it has also become more widely accessible. The present review summarizes established and recently developed techniques. The information we can derive from secondary structural analysis is assessed, together with the areas in which we are likely to see exciting developments in the near future.
The role of oxidative stress in the cardiovascular actions of particulate air pollution
Authors: Miller Mark R.
Published: August 2014

Air pollution has been estimated to be responsible for several millions of deaths worldwide per year, the majority of which have been attributed to cardiovascular causes. The particulate matter in air pollution has been shown impair vascular function, increase blood pressure, promote thrombosis and impair fibrinolysis, accelerate the development of atherosclerosis, increase the extent of myocardial ischaemia, and increase susceptibility to myocardial infarction. The pathways underlying these effects are complex and poorly understood; however, particulate-induced oxidative stress repeatedly emerges as a potential mechanism in all of these detrimental cardiovascular actions. The present mini-review will use diesel exhaust as an example of a pollutant rich in combustion-derived nanoparticles, to describe the potential by which oxidative stress could drive the cardiovascular effects of air pollution.
Role of the Vnn1 pantetheinase in tissue tolerance to stress
Authors: Naquet Philippe , Pitari Giuseppina , Duprè Sylvestro , Galland Franck
Published: August 2014

Pantetheinase is an ubiquitous enzyme which hydrolyses D-pantetheine into cysteamine and pantothenate (vitamin B5) on the dissimilative pathway of CoA. Pantetheinase isoforms are encoded by the Vnn (vanin) genes and Vnn1 is the predominant tissue isoform in mice and humans. In the present article, we review the results showing the regulation of Vnn1 expression during developmental, repair and inflammatory situations and the impact of a Vnn1 deficiency in mouse models of pathologies. We document the involvement of the Vnn1 pantetheinase in situations of increased tissue needs and propose that Vnn1 through recycling of pantothenate and release of cysteamine in tissues participates in the adaptive response of the tissue to stress.
Role of CoA and acetyl-CoA in regulating cardiac fatty acid and glucose oxidation
Authors: Abo Alrob Osama , Lopaschuk Gary D.
Published: August 2014

CoA (coenzyme A) and its derivatives have a critical role in regulating cardiac energy metabolism. This includes a key role as a substrate and product in the energy metabolic pathways, as well as serving as an allosteric regulator of cardiac energy metabolism. In addition, the CoA ester malonyl-CoA has an important role in regulating fatty acid oxidation, secondary to inhibiting CPT (carnitine palmitoyltransferase) 1, a key enzyme involved in mitochondrial fatty acid uptake. Alterations in malonyl-CoA synthesis by ACC (acetyl-CoA carboxylase) and degradation by MCD (malonyl-CoA decarboxylase) are important contributors to the high cardiac fatty acid oxidation rates seen in ischaemic heart disease, heart failure, obesity and diabetes. Additional control of fatty acid oxidation may also occur at the level of acetyl-CoA involvement in acetylation of mitochondrial fatty acid β-oxidative enzymes. We find that acetylation of the fatty acid β-oxidative enzymes, LCAD (long-chain acyl-CoA dehydrogenase) and β-HAD (β-hydroxyacyl-CoA dehydrogenase) is associated with an increase in activity and fatty acid oxidation in heart from obese mice with heart failure. This is associated with decreased SIRT3 (sirtuin 3) activity, an important mitochondrial deacetylase. In support of this, cardiac SIRT3 deletion increases acetylation of LCAD and β-HAD, and increases cardiac fatty acid oxidation. Acetylation of MCD is also associated with increased activity, decreases malonyl-CoA levels and an increase in fatty acid oxidation. Combined, these data suggest that malonyl-CoA and acetyl-CoA have an important role in mediating the alterations in fatty acid oxidation seen in heart failure.
Defective pantothenate metabolism and neurodegeneration
Authors: Hayflick Susan J.
Published: August 2014

Inborn errors of CoA (coenzyme A) biosynthesis lead to neurodegenerative disorders in humans. PKAN (pantothenate kinase-associated neurodegeneration) manifests with damage to brain, retina and testis and is caused by mutations in PANK2, the gene encoding the mitochondrial form of pantothenate kinase, a key regulatory enzyme in CoA synthesis. Further attention has been focused on this pathway by the recent discovery that mutations in the gene encoding CoA synthase lead to a similar neurodegenerative disorder, raising the spectre of a common mechanism of pathogenesis. How do defects in CoA production result in neurodegeneration? Why are certain tissues and cell types selectively vulnerable? And what is the underlying neurodegenerative process? Answers to some of these questions have come from animal models of disease, including flies and mice, as well as directly from humans. The damaged tissue types share key features that are likely to contribute to their selective vulnerability. These include the presence of a blood–tissue barrier, the milieu with respect to oxidative stress, tissue metabolic demand, relative expression of genes encoding similar proteins in these tissues and cell membrane composition. Substantial progress in understanding these important neurometabolic disorders has been made since the first gene discovery more than a decade ago. With rational therapeutics now in development for PKAN, we foresee prevention of neurodegeneration and hope for neuroregeneration or neuro-rescue.
Ultra-endurance exercise: unanswered questions in redox biology and immunology
Authors: Turner James E. , Bennett Stuart J. , Bosch Jos A. , Griffiths Helen R. , Aldred Sarah
Published: August 2014

Ultra-endurance races are extreme exercise events that can take place over large parts of a day, several consecutive days or over weeks and months interspersed by periods of rest and recovery. Since the first ultra-endurance races in the late 1970s, around 1000 races are now held worldwide each year, and more than 100000 people take part. Although these athletes appear to be fit and healthy, there have been occasional reports of severe complications following ultra-endurance exercise. Thus there is concern that repeated extreme exercise events could have deleterious effects on health, which might be brought about by the high levels of ROS (reactive oxygen species) produced during exercise. Studies that have examined biomarkers of oxidative damage following ultra-endurance exercise have found measurements to be elevated for several days, which has usually been interpreted to reflect increased ROS production. Levels of the antioxidant molecule GSH (reduced glutathione) are depleted for 1 month or longer following ultra-endurance exercise, suggesting an impaired capacity to cope with ROS. The present paper summarizes studies that have examined the oxidative footprint of ultra-endurance exercise in light of current thinking in redox biology and the possible health implications of such extreme exercise.
The red blood cell: a new key player in cardiovascular homoeostasis? Focus on the nitric oxide pathway
Authors: Porro Benedetta , Eligini Sonia , Squellerio Isabella , Tremoli Elena , Cavalca Viviana
Published: August 2014

RBCs (red blood cells) have a fundamental role in the regulation of vascular homoeostasis thanks to the ability of these cells to carry O2 (oxygen) between respiratory surfaces and metabolizing tissues and to release vasodilator compounds, such as ATP and NO (nitric oxide), in response to tissue oxygenation. More recently it has been shown that RBCs are also able to produce NO endogenously as they express a functional NOS (nitric oxide synthase), similar to the endothelial isoform. In addition, RBCs carry important enzymes and molecules involved in L-arginine metabolism, such as arginase, NO synthesis inhibitors and the cationic amino acid transporters. Altogether these findings strongly support the role of these cells as producers, vehicles and scavengers of NO, therefore affecting several physiological processes such as blood rheology and cell adhesion. Consequently, the importance of alterations in the L-arginine/NO metabolic pathway induced by specific conditions, e.g. oxidative stress, in different pathological settings have been investigated. In the present review we discuss the role of RBCs in vascular homoeostasis, focusing our attention on the importance of the NO pathway alterations in cardiovascular diseases and their relationship to major risk factors.
Overcoming bortezomib resistance in multiple myeloma
Authors: Murray Megan Y. , Auger Martin J. , Bowles Kristian M.
Published: August 2014

The introduction of the proteasome inhibitor bortezomib in 2003 significantly improved treatment of the B-cell malignancy MM (multiple myeloma). Relapse following bortezomib therapy is inevitable, however, and MM remains an incurable disease. In the present mini-review, we explore the mechanisms by which bortezomib resistance occurs in MM, including inherent and acquired mutation, and inducible pro-survival signalling. We also outline the importance of MM cell interaction with the BMSC (bone marrow stromal cell) microenvironment as a pro-survival mechanism, and examine some potential druggable targets within this milieu, such as IGFs (insulin-like growth factors) and Btk (Bruton's tyrosine kinase). Although our understanding of bortezomib resistance is far from complete, there are a number of scientific developments that can help inform clinical decisions in relapsed MM.
Consequences of feedback in signal transduction for targeted therapies
Authors: Klinger Bertram , Blüthgen Nils
Published: August 2014

Over the last two decades, many small-molecule inhibitors that target kinase signalling have been developed. More than 20 of these inhibitors are FDA (U.S. Food and Drug Administration)-approved and are now being used in the clinics to treat tumours; even more have entered clinical trials. However, resistance to these inhibitors, either intrinsic to the tumour or acquired during treatment, remains a major problem in targeted therapeutics. One of the mechanisms by which tumours become resistant is the rewiring of the signalling networks via feedback, by which the tumour cells re-activate signalling or activate alternative signalling pathways. In the present article, we review insights from recent quantitative signalling studies combining mathematical modelling and experiments that revealed how feedback rewires MAPK (mitogen-activated protein kinase)/PI3K (phosphoinositide 3-kinase) signalling upon treatment and how that affects drug sensitivity.
Recent advances in targeting coenzyme A biosynthesis and utilization for antimicrobial drug development
Authors: Moolman Wessel J.A. , de Villiers Marianne , Strauss Erick
Published: August 2014

The biosynthesis and utilization of CoA (coenzyme A), the ubiquitous and essential acyl carrier in all organisms, have long been regarded as excellent targets for the development of new antimicrobial drugs. Moreover, bioinformatics and biochemical studies have highlighted significant differences between several of the bacterial enzyme targets and their human counterparts, indicating that selective inhibition of the former should be possible. Over the past decade, a large amount of structural and mechanistic data has been gathered on CoA metabolism and the CoA biosynthetic enzymes, and this has facilitated the discovery and development of several promising candidate antimicrobial agents. These compounds include both target-specific inhibitors, as well as CoA antimetabolite precursors that can reduce CoA levels and interfere with processes that are dependent on this cofactor. In the present mini-review we provide an overview of the most recent of these studies that, taken together, have also provided chemical validation of CoA biosynthesis and utilization as viable targets for antimicrobial drug development.
The complexity of protein semiochemistry in mammals
Authors: Beynon Robert J. , Armstrong Stuart D. , Gómez-Baena Guadalupe , Lee Victoria , Simpson Deborah , Unsworth Jennifer , Hurst Jane L.
Published: August 2014

The high degree of protein sequence similarity in the MUPs (major urinary proteins) poses considerable challenges for their individual differentiation, analysis and quantification. In the present review, we discuss MS approaches for MUP quantification, at either the protein or the peptide level. In particular, we describe an approach to multiplexed quantification based on the design and synthesis of novel proteins (QconCATs) that are concatamers of quantification standards, providing a simple route to the generation of a set of stable-isotope-labelled peptide standards. The MUPs pose a particular challenge to QconCAT design, because of their sequence similarity and the limited number of peptides that can be used to construct the standards. Such difficulties can be overcome by careful attention to the analytical workflow.
Deregulated coenzyme A, loss of metabolic flexibility and diabetes
Authors: Jackowski Suzanne , Leonardi Roberta
Published: August 2014

CoA (coenzyme A) is an essential cofactor that is emerging as a global regulator of energy metabolism. Tissue CoA levels are tightly regulated and vary in response to different conditions including nutritional state and diabetes. Recent studies reveal the ability of this cofactor to control the output of key metabolic pathways. CoA regulation is important for the maintenance of metabolic flexibility and glucose homoeostasis.
Exploiting the coenzyme A biosynthesis pathway for the identification of new antimalarial agents: the case for pantothenamides
Authors: Saliba Kevin J. , Spry Christina
Published: August 2014

Malaria kills more than half a million people each year. There is no vaccine, and recent reports suggest that resistance is developing to the antimalarial regimes currently recommended by the World Health Organization. New drugs are therefore needed to ensure malaria treatment options continue to be available. The intra-erythrocytic stage of the malaria parasite's life cycle is dependent on an extracellular supply of pantothenate (vitamin B5), the precursor of CoA (coenzyme A). It has been known for many years that proliferation of the parasite during this stage of its life cycle can be inhibited with pantothenate analogues. We have shown recently that pantothenamides, a class of pantothenate analogues with antibacterial activity, inhibit parasite proliferation at submicromolar concentrations and do so competitively with pantothenate. These compounds, however, are degraded, and therefore rendered inactive, by the enzyme pantetheinase (vanin), which is present in serum. In the present mini-review, we discuss the two strategies that have been put forward to overcome pantetheinase-mediated degradation of pantothenamides. The strategies effectively provide an opportunity for pantothenamides to be tested in vivo. We also put forward our ‘blueprint’ for the further development of pantothenamides (and other pantothenate analogues) as potential antimalarials.
Ratiometric biological nanosensors
Authors: Fisher Kate M. , Campbell Colin J.
Published: August 2014

The measurement of intracellular analytes has been key in understanding cellular processes and function, and the use of biological nanosensors has revealed the spatial and temporal variation in their concentrations. In particular, ratiometric nanosensors allow quantitative measurements of analyte concentrations. The present review focuses on the recent advances in ratiometric intracellular biological nanosensors, with an emphasis on their utility in measuring analytes that are important in cell function.
Hypercholesterolaemia-induced oxidative stress at the blood–brain barrier
Authors: Dias Irundika H.K. , Polidori Maria C. , Griffiths Helen R.
Published: August 2014

Blood cholesterol levels are not consistently elevated in subjects with age-related cognitive decline, although epidemiological studies suggest that Alzheimer's disease and cardiovascular diseases share common risk factors. These include the presence of an unusual genetic variant, the APOE4 (apolipoprotein E4) allele, which modulates LDL (low-density lipoproteins) metabolism, increases free radical formation and reduces plasma antioxidant concentrations. Together, these risk factors support a mechanism for increased LDL circulation time and free radical modification of LDL. Plasma oxycholesterols, hydroxylated metabolites of cholesterol, are carried by oxidized LDL, and elevated lipids in mid-life are associated with increased long-term risk of dementia. Although brain cholesterol metabolism is segregated from the systemic circulation, during oxidative stress, plasma oxycholesterols could have damaging effects on BBB (blood–brain barrier) function and consequently on neuronal cells. Cholesterol-lowering drugs such as statins may prevent the modifications to LDL in mid-life and might show beneficial effects in later life.
Multi-scale times and modes of fast and slow relaxation in solutions with coexisting spherical and cylindrical micelles according to the difference Becker-Döring kinetic equations
Authors: Babintsev Ilya A. , Adzhemyan Loran Ts. , Shchekin Alexander K.
Published: August 2014

The eigenvalues and eigenvectors of the matrix of coefficients of the linearized kinetic equations applied to aggregation in surfactant solution determine the full spectrum of characteristic times and specific modes of micellar relaxation. The dependence of these relaxation times and modes on the total surfactant concentration has been analyzed for concentrations in the vicinity and well above the second critical micelle concentration (cmc2) for systems with coexisting spherical and cylindrical micelles. The analysis has been done on the basis of a discrete form of the Becker-Döring kinetic equations employing the Smoluchowsky diffusion model for the attachment rates of surfactant monomers to surfactant aggregates with matching the rates for spherical aggregates and the rates for large cylindrical micelles. The equilibrium distribution of surfactant aggregates in solution has been modeled as having one maximum for monomers, another maximum for spherical micelles and wide slowly descending branch for cylindrical micelles. The results of computations have been compared with the analytical ones known in the limiting cases from solutions of the continuous Becker-Döring kinetic equation. They demonstrated a fair agreement even in the vicinity of the cmc2 where the analytical theory looses formally its applicability.
A numerical study on miscible viscous fingering instability in anisotropic porous media
Authors: Norouzi M. , Shoghi M. R.
Published: August 2014

In this paper, the viscous fingering of miscible flow displacements in an anisotropic porous media is investigated for the first time. The effect of anisotropic permeability and dispersion tensor on the generation, form and growth rate of finger-like patterns, is studied using both linear stability analysis and computational fluid dynamics (CFD). The linear stability analysis is performed using the quasi-steady state approximation and six order shooting method to predict the growth rate of the disturbance in the flow. It is found that the flow is more stabilized when the ratio of the longitudinal to transverse anisotropic permeability is increased and longitudinal to transverse anisotropic dispersion is decreased. In CFD simulation, Hartley transformation (as a spectral method) and fourth-order Adams-Bashforth technique is used to solve the governing equations. It is shown that anisotropic permeability and dispersion have significant effects on the development of the fingers and also on the mechanisms of interactions between neighboring fingers. The development of the finger structures is discussed using concentration contours and diagrams of transversely average concentration, mixing length, and sweep efficiency for different anisotropic scenarios.
Rotational Brownian Dynamics simulations of clathrin cage formation
Authors: Ilie Ioana M. , den Otter Wouter K. , Briels Wim J.
Published: August 2014

The self-assembly of nearly rigid proteins into ordered aggregates is well suited for modeling by the patchy particle approach. Patchy particles are traditionally simulated using Monte Carlo methods, to study the phase diagram, while Brownian Dynamics simulations would reveal insights into the assembly dynamics. However, Brownian Dynamics of rotating anisotropic particles gives rise to a number of complications not encountered in translational Brownian Dynamics. We thoroughly test the Rotational Brownian Dynamics scheme proposed by Naess and Elsgaeter [Macromol. Theory Simul. 13, 419 (2004); Naess and Elsgaeter Macromol. Theory Simul. 14, 300 (2005)], confirming its validity. We then apply the algorithm to simulate a patchy particle model of clathrin, a three-legged protein involved in vesicle production from lipid membranes during endocytosis. Using this algorithm we recover time scales for cage assembly comparable to those from experiments. We also briefly discuss the undulatory dynamics of the polyhedral cage.
A method for determining poloidal rotation from poloidal asymmetry in toroidal rotation (invited)
Authors: Chrystal C. , Burrell K. H. , Grierson B. A. , Lao L. L. , Pace D. C.
Published: August 2014

A new diagnostic has been developed on DIII-D that determines the impurity poloidal rotation from the poloidal asymmetry in the toroidal angular rotation velocity. This asymmetry is measured with recently added tangential charge exchange viewchords on the high-field side of the tokamak midplane. Measurements are made on co- and counter-current neutral beams, allowing the charge exchange cross section effect to be measured and eliminating the need for atomic physics calculations. The diagnostic implementation on DIII-D restricts the measurement range to the core (r/a < 0.6) where, relative to measurements made with the vertical charge exchange system, the spatial resolution is improved. Significant physics results have been obtained with this new diagnostic; for example, poloidal rotation measurements that significantly exceed neoclassical predictions.
A compact two-way high-power microwave combiner
Authors: Chang C. , Sun J. , Xiong Z. F. , Guo L. T. , Liu Y. S. , Zhang Z. Q. , Wu X. L.
Published: August 2014

A compact 2-way high-power microwave (HPM) waveguide combiner as an important equipment to realize the coherent microwave combination was theoretically designed, built, and proof-of-principle experimentally tested. The theoretical and experimental S-parameters are basically consistent with each other: return loss <−25 dB, and the isolation degree between 2-channels of the HPM combiner >25 dB to avoid the inter-modulating between the HPM sources. The C-band HPM experiment was carried out, and the power capacity of the HPM combiner was demonstrated to reach multi-gigawatts.
Measurement of high-energy (10–60 keV) x-ray spectral line widths with eV accuracy
Authors: Seely J. F. , Glover J. L. , Hudson L. T. , Ralchenko Y. , Henins Albert , Pereira N. , Feldman U. , Di Stefano C. A. , Kuranz C. C. , Drake R. P. , Chen Hui , Williams G. J. , Park J.
Published: August 2014

A high resolution crystal spectrometer utilizing a crystal in transmission geometry has been developed and experimentally optimized to measure the widths of emission lines in the 10–60 keV energy range with eV accuracy. The spectrometer achieves high spectral resolution by utilizing crystal planes with small lattice spacings (down to 2d = 0.099 nm), a large crystal bending radius and Rowland circle diameter (965 mm), and an image plate detector with high spatial resolution (60 μm in the case of the Fuji TR image plate). High resolution W L-shell and K-shell laboratory test spectra in the 10–60 keV range and Ho K-shell spectra near 47 keV recorded at the LLNL Titan laser facility are presented. The Ho K-shell spectra are the highest resolution hard x-ray spectra recorded from a solid target irradiated by a high-intensity laser.
Open and closed loop manipulation of charged microchiplets in an electric field
Authors: Lu J. P. , Thompson J. D. , Whiting G. L. , Biegelsen D. K. , Raychaudhuri S. , Lujan R. , Veres J. , Lavery L. L. , Völkel A. R. , Chow E. M.
Published: August 2014

We demonstrate the ability to orient, position, and transport microchips (“chiplets”) with electric fields. In an open-loop approach, modified four phase traveling wave potential patterns manipulate chiplets in a dielectric solution using dynamic template agitation techniques. Repeatable parallel assembly of chiplets is demonstrated to a positional accuracy of 6.5 μm using electrodes of 200 μm pitch. Chiplets with dipole surface charge patterns are used to show that orientation can be controlled by adding unique charge patterns on the chiplets. Chip path routing is also demonstrated. With a closed-loop control system approach using video feedback, dielectric, and electrophoretic forces are used to achieve positioning accuracy of better than 1 μm with 1 mm pitch driving electrodes. These chip assembly techniques have the potential to enable future printer systems where inputs are electronic chiplets and the output is a functional electronic system.
Mean transverse energy and response time measurements of GaInP based photocathodes
Authors: Jin Xiuguang , Yamamoto Masahiro , Miyajima Tsukasa , Honda Yosuke , Uchiyama Takashi , Tabuchi Masao , Takeda Yoshikazu
Published: August 2014

GaInP, which has a wider band gap than GaAs, is introduced as a photocathode for energy recovery linac (ERL). The wide band gap of material is expected to reduce the heating effect in the thermal relaxation process after high energy excitation. GaInP photocathodes exhibited higher quantum efficiency than GaAs and low thermal emittance as the same as GaAs photocathodes under green laser light irradiation. A short picosecond electron pulse was also achieved with the GaInP photocathode under 532 nm pulse laser irradiation. These experimental results demonstrate that the GaInP photocathode is an important candidate for ERL.
Transport of low pressure electronegative SF6 plasma through a localized magnetic filter
Authors: Levko D. , Garrigues L. , Hagelaar G. J. M.
Published: August 2014

The generation of an ion-ion plasma where only few electrons are present in the discharge could be appropriated in the context of ion plasma source applications. We present in this paper results obtained with a one-dimensional fluid model in the context of low pressure electronegative SF6 plasma. Without magnetic field, results show that the electron density is still large in the discharge. With a localized magnetic filter, where the magnetic field strength is such that the transport of the electrons is affected while the transport of ion species remains unmagnetized, we show that a region with a negative–positive ion plasma is found downstream the magnetic filter. The negative ions are produced in the filter due to the decrease of electron temperature. We also find conditions when the plasma sheath near the biased electrode collapses and the negative ion extraction from the plasma becomes possible. In addition, the influence of E × B electron transport on the one-dimensional model results is discussed.
Resonant electronic transport through a triple quantum-dot with Λ-type level structure under dual radiation fields
Authors: Guan Chun , Xing Yunhui , Zhang Chao , Ma Zhongshui
Published: August 2014

Due to quantum interference, light can transmit through dense atomic media, a phenomenon known as electromagnetically induced transparency (EIT). We propose that EIT is not limited to light transmission and there is an electronic analog where resonant transparency in charge transport in an opaque structure can be induced by electromagnetic radiation. A triple-quantum-dots system with Λ-type level structure is generally opaque due to the level in the center dot being significantly higher and therefore hopping from the left dot to the center dot is almost forbidden. We demonstrate that an electromagnetically induced electron transparency (EIET) in charge of transport can indeed occur in the Λ-type system. The direct evidence of EIET is that an electron can travel from the left dot to the right dot, while the center dot apparently becomes invisible. We analyze EIET and the related shot noise in both the zero and strong Coulomb blockade regimes. It is found that the EIET (position, height, and symmetry) can be tuned by several controllable parameters of the radiation fields, such as the Rabi frequencies and detuning frequencies. The result offers a transparency/opaque tuning technique in charge transport using interfering radiation fields.
X-ray analysis of strain distribution in two-step grown epitaxial SrTiO3 thin films
Authors: Panomsuwan Gasidit , Takai Osamu , Saito Nagahiro
Published: August 2014

Epitaxial SrTiO3 (STO) thin films were grown on (001)-oriented LaAlO3 (LAO) substrates using a two-step growth method by ion beam sputter deposition. An STO buffer layer was initially grown on the LAO substrate at a low temperature of 150 °C prior to growing the STO main layer at 750 °C. The thickness of the STO buffer layer was varied at 3, 6, and 10 nm, while the total film thickness was kept constant at approximately 110 nm. According to x-ray structural analysis, we show that the STO buffer layer plays an essential role in controlling the strain in the STO layer grown subsequently. It is found that the strains in the STO films are more relaxed with an increase in buffer layer thickness. Moreover, the strain distribution in two-step grown STO films becomes more homogeneous across the film thickness when compared to that in directly grown STO film.
Annealing behaviors of vacancy-type defects near interfaces between metal contacts and GaN probed using a monoenergetic positron beam
Authors: Uedono Akira , Fujishima Tatsuya , Piedra Daniel , Yoshihara Nakaaki , Ishibashi Shoji , Sumiya Masatomo , Laboutin Oleg , Johnson Wayne , Palacios Tomás
Published: August 2014

Vacancy-type defects near interfaces between metal contacts and GaN grown on Si substrates by metal organic chemical vapor deposition have been studied using a monoenergetic positron beam. Measurements of Doppler broadening spectra of the annihilation radiation for Ti-deposited GaN showed that optically active vacancy-type defects were introduced below the Ti/GaN interface after annealing at 800 °C. Charge transition of those defects due to electron capture was observed and was found to correlate with a yellow band in the photoluminescence spectrum. The major defect species was identified as vacancy clusters such as three to five Ga-vacancies coupled with multiple nitrogen-vacancies. The annealing behaviors of vacancy-type defects in Ti-, Ni-, and Pt-deposited GaN were also examined.
Structure and ionic conductivity of ionic liquid embedded PEO- LiCF3SO3 polymer electrolyte
Authors: Karmakar A. , Ghosh A.
Published: August 2014

In this paper we have reported electrical and other physical properties of polyethylene oxide (PEO) - LiCF3SO3 polymer electrolytes embedded with 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ionic liquid. The addition of the ionic liquid to PEO- LiCF3SO3 electrolyte increases the amorphous phase content considerably and decreases the glass transition temperature. The relative amounts of different ionic species present in these electrolytes have been determined. It is observed that the fraction of free anions increase with the increase of ionic liquid concentration, whereas the fraction for ion pairs and aggregates show a decreasing trend under the same condition. The ionic conductivity of the PEO- LiCF3SO3 polymer electrolyte embedded with ionic liquid is higher than that of the PEO- LiCF3SO3 electrolyte. The ionic conductivity shows a transition around 323 K. The ionic conductivity above 323 K exhibits Arrhenius behavior with an activation energy, which decreases with the increase of ionic liquid concentration. However, below 323 K the conductivity shows Vogel–Tamman–Fulcher (VTF) type behavior.