bluuebunny/crossref_metadata_2025 huggingface dataset:
The Modified Collocation Trefftz Method and Exponentially Convergent Scalar Homotopy Algorithm for the Inverse Boundary Determination Problem for the Biharmonic Equation
Authors: Chan H.-F. , Fan C.-M.
Published: January 2013

In this paper, the modified collocation Trefftz method (MCTM) and the exponentially convergent scalar homotopy algorithm (ECSHA) are adopted to analyze the inverse boundary determination problem governed by the biharmonic equation. The position for part of the boundary with given boundary condition is unknown and the position for the rest of the boundary with overspecified Cauchy boundary conditions is given a priori. Since the spatial position for portion of boundary is not given a priori, it is extremely difficult to solve such a boundary determination problem by any numerical scheme. In order to stably solve the boundary determination problem, the MCTM will be adopted in this study owing to that it can avoid the generation of mesh grid and numerical integration. When this problem is modeled by MCTM, a system of nonlinear algebraic equations will be formed and then be solved by ECSHA. Some numerical examples will be provided to demonstrate the ability and accuracy of the proposed scheme. In addition, the stability of the proposed meshless method will be tested by adding some noise into the prescribed boundary conditions and then to see how does that affect the numerical results.
On Free Vibration of Functionally Graded Mindlin Plate and Effect of In-Plane Displacements
Authors: Baferani A. Hasani , Saidi A.R. , Ehteshami H.
Published: January 2013

In this paper, free vibration analysis of functionally graded rectangular plate is investigated based on the first order shear deformation theory and the effect of in-plane displacements on the natural frequencies of such plate is studied. The governing equations of motion are obtained, which are five coupled partial differential equations, without any simplification. Some mathematical manipulation leads us to decouple the equations. The decoupled equations are solved by the Levy's method for various boundary conditions. As the results show, in some boundary conditions the in-plane displacements cause a drastic change of frequencies. In other words, neglecting the in-plane displacement, which is assumed in some papers, is not proper for these boundary conditions. However, in the other boundary conditions, the natural frequencies are not significantly affected by the in-plane displacements. The results for various boundary conditions are discussed in detail and some interpretations for these differences are provided. Besides to the comparisons, the accurate natural frequencies of the plate for six different boundary conditions with several aspect ratios, thickness-length ratios and power law indices are presented. The natural frequencies of Mindlin functionally graded rectangular plates with considering the in-plane displacements are reported for the first time and can be used as benchmark.
Competitive inhibition of three novel bacteria isolated from faeces of breast milk-fed infants against selected enteropathogens
Authors: Muñoz-Quezada Sergio , Bermudez-Brito Miriam , Chenoll Empar , Genovés Salvador , Gomez-Llorente Carolina , Plaza-Diaz Julio , Matencio Esther , José Bernal María , Romero Fernando , Ramón Daniel , Gil Angel
Published: January 2013

Numerousin vitroandin vivostudies conducted using different probiotic micro-organisms have demonstrated their ability to interfere with the growth and virulence of a variety of enteropathogens. The reported beneficial effects of the use of probiotics to complement antibiotic therapy or prevent diarrhoea or gastrointestinal infection in infants have increased in recent years. In the present study, we demonstrated the capacity of supernatants obtained from three novel probiotics (Lactobacillus paracaseiCNCM I-4034,Bifidobacterium breveCNCM I-4035 andLactobacillus rhamnosusCNCM I-4036) isolated from the faeces of breastfed infants to inhibit the growth of enterotoxigenic and enteropathogenic (EPEC) bacteria, such asEscherichia coli,SalmonellaandShigella. To assess their potential antimicrobial activity, the 17 and 24 h cell-free supernatants broth concentrates (10 × ) having 1, 2 or 4 % of the three probiotics were incubated with EPEC bacteria strains. After 17 h of co-culture, the supernatants were able to inhibit the growth ofE. coli,SalmonellaandShigellaup to 40, 55 and 81 %, respectively. However, the inhibitory capacity of some supernatants was maintained or completely lost when the supernatants (pH 3·0) were neutralised (pH 6·5). Overall, these results demonstrated thatL. paracaseiCNCM I-4034,B. breveCNCM I-4035 andL. rhamnosusCNCM I-4036 produce compounds that exhibited strain-specific inhibition of enterobacteria and have the potential to be used as probiotics in functional foods.
Time-dependent non-planar DIA shock waves in non-extensive dusty plasma
Authors: YASMIN S. , ASADUZZAMAN M. , MAMUN A. A.
Published: January 2013

The propagation of dust ion-acoustic shock waves (DIASHWs) in an unmagnetized dissipative dusty plasma system consisting of inertial ions, non-inertial, non-extensive q-distributed electrons, and negatively charged stationary dust is investigated in bounded non-planar (cylindrical and spherical) geometry. A modified Burgers equation is derived and its numerical solution is obtained. It is found that the basic features of DIASHWs are significantly modified by the effects of electron non-extensivity and ion kinematic viscosity in bounded geometry. It is also shown that the propagation characteristics of non-planar DIASHWs in a non-extensive plasma are qualitatively different from those of planar ones.
Exploring post-course outcomes of an undergraduate tourism field trip to the Antarctic Peninsula
Authors: Johnston M.E. , Dawson J.P. , Childs J. , Maher P. T.
Published: January 2013

A small number of educational programmes for university students include field experience in Antarctica. These programmes contain a range of educational objectives, approaches and academic assessment related to the field component and the intended on-site learning for students. However, it is possible that the on-site experiences of students in these programmes have an influence on later decisions and behaviour beyond the course itself in the years following participation. This paper investigates the possibility of such influence for students who participated in ship-based tourism field trips to the Antarctic Peninsula and adjacent locations (South Georgia, the Falkland Islands, and South Shetland Islands) and explores whether students link their participation to particular post-course outcomes. It examines how participants report being affected by a trip to the Antarctic Peninsula, particularly in terms of later decisions regarding learning, professional lives, and environmental behaviour. Influences noted by respondents include effects on choices made in relation to academic pursuits and career paths, as well as development of their environmental values through increased awareness of tourism impacts, Antarctic region sustainability issues, and global issues such as climate change.
DIVINE COMEDY: STOCKHAUSEN'S ‘MITTWOCH’ IN BIRMINGHAM
Authors: Maconie Robin
Published: January 2013

Childhood play, leadership, suspense, thoughts of mediation and conciliation, Hamlet-like reflections on being and not-being, facing and conquering fears, and a hunger for stability and security in personal relationships, together with a full panoply of riffs on the colour yellow in European popular culture – many of them frankly unpleasant – are among the challenging ingredients of Stockhausen's Mittwoch aus LICHT, the last segment of the seven-opera LICHT jigsaw to be put in place. Stockhausen's operas are intricate literary puzzles or charades, every detail of which can be assigned a number of coded meanings. Despite bravura performances by an exceptional team of musicians, Graham Vick skated over much of the composer's uneasy symbolism in a brusque and simplistic arte povera production which, along with a battery of unsolved sound projection issues inherent in the score, placed altogether too much emphasis on the composer's dark side.
HANS KELLER, NIKOS SKALKOTTAS AND THE NOTION OF SYMPHONIC GENIUS
Authors: Mantzourani Eva
Published: January 2013

In his writings on music Hans Keller includes Skalkottas among the few great twentieth-century composers of ‘symphonic thought’, and considers him to be the only ‘symphonic genius’ after Schoenberg whose ‘genius’ remains to be discovered. Although during the time of his writings, Keller was in a minority in his appreciation of this relatively minor composer in the Western art music canon, he did not analyse any of Skalkottas's music in support of his views, as he did with the works of other composers who, although important to him, are not elevated to such a high plane. This paper first gives an overview of Keller's approach to and understanding of symphonic thought, as presented in his various writings and exemplified in his analyses of Schoenberg's music. Subsequently, it examines certain of Skalkottas's 12-note works and the compositional techniques he applies to construct them, which exhibit these characteristics of symphonic thought defined by Keller, and which might be used to substantiate his unexplained but intuitively correct assertions.
Lucerne Festival 2012: Karlheinz Stockhausen, Heinz Holliger
Authors: Palmer Peter
Published: January 2013

On 1 September, ten days after the premiere in Birmingham of the ‘Wednesday’ segment of Stockhausen's Licht cycle, a vocal sextet written in tandem with the final scene received an airing at a matinée concert in Lucerne's Matthäuskirche. Composed, like the rest of Mittwoch, in 1997, Menschen, hört (‘Listen, people’) obviously carried special significance for the composer. The a cappella piece can be performed independently of the cycle, and Stockhausen's text is inscribed on the gravestone he designed for himself ten years before his death.
London, Proms 2012 (2): Olga Neuwirth, Kaija Saariaho
Authors: Stein Robert
Published: January 2013

Postmodernism in music may be hard to define – even harder than the same notoriously slippery term in literature – but Olga Neuwirth's viola concerto Remnants of songs … an Amphigory (2009) may be as good an exemplar as any. Given its UK première on 13 August by the talented British violist Lawrence Power, with the Philharmonia Orchestra under Susanna Mälkki, the concerto's Proms appearance marks the first time the festival has put on any of her pieces.
Proms 2012 (3): Howard, Grime, Bainbridge, Maxwell Davies
Authors: Lister Rodney
Published: January 2013

On 21 August the City of Birmingham Symphony Orchestra, conducted by Andris Nelsons, gave the first UK Performance of Emily Howard's Calculus of the Nervous System. The work is the concluding panel of a triptych (the earlier ones are called Ada sketches and Mesmerism), which is a tribute to Ada Lovelace (1815–52), the daughter of Lord Byron who, as a collaborator with Charles Babbage on his Analytical Engine, is sometimes considered the world's first computer programmer. The title is that of the mathematical model that Lovelace hoped to develop to demonstrate how, as Howard writes, ‘the brain gives way to thought, and nerves to feeling’. Howard conceived Calculus of the Nervous System as a series of ‘memories’, whose structure is ‘a neural network with its roots in strictly engineered time … using values from one source (an exponential equation and its derivative), subsequently muddled and reordered by chance processes’. The memories are linked in some way that is not clear and not explained by the quotations from Sir Geoffrey Hills's Clavics which appear in the score (but which are not in any way audible or able to be apprehended by anyone without a score).
Proms 2012 (4): Turnage, Lam, Langgaard, Gundmundsen-Holmgreen, Bray, Muhly, Dubugnon et al.
Authors: Anderson Martin
Published: January 2013

Way back in the mists of time, in the decade when I was a card-carrying Prommer (1977–87), the BBC used to arrange (and maybe still does) a meeting between us regular Prommers and the Controller, Music – the man whose choices governed two months of our lives every year. Robert Ponsonby was the incumbent when I first had a season ticket and John Drummond was at the helm when I left London for a job in Paris. We never had the impression that anything we said made a blind bit of difference, but at least it allowed us to get things off our chests; all the Controller had to do was fend off our questions and comments with the oiliness then customary with the high functionaries of the BBC (they're all wonderful now, of course) and our silence was obtained for another year. (I remember Drummond contemptuously dismissing the music of Respighi as being beneath the dignity of the institution; Roger Wright, I gratefully note, does not share Drummond's snobbish ignorance, but I also note that neither the Concerto gregoriano for violin and orchestra nor Metamorphosen, both orchestral masterpieces, has yet been heard there.)
Cheltenham Festival 2012: Alexander Goehr, Hugh Wood, Lauri Supponen, Judith Bingham, Einojuhani Rautavaara, John Tavener
Authors: Conway Paul
Published: January 2013

Meurig Bowen, now in his fifth year as Director of the Cheltenham Music Festival, continues to reinforce this illustrious annual event's reputation for programming new works by major composers. His scheduling of the majority of the 2012 festival's premières on the second day – 5 July – was exceptionally convenient for aficionados of contemporary music in general and served to reduce markedly this reviewer's carbon footprint.
Concentration of solutions for the Yamabe problem on half-spaces
Authors: Cao Daomin , Peng Shuangjie
Published: January 2013

By variational methods, for a type of Yamabe problem with boundary, we construct multi-peak solutions whose maxima tend to the boundary as the parameter tends to 0+ under certain assumptions. We also obtain the asymptotic behaviours of the solutions.
EMEN2: An Object Oriented Database and Electronic Lab Notebook
Authors: Rees Ian , Langley Ed , Chiu Wah , Ludtke Steven J.
Published: January 2013

Transmission electron microscopy and associated methods, such as single particle analysis, two-dimensional crystallography, helical reconstruction, and tomography, are highly data-intensive experimental sciences, which also have substantial variability in experimental technique. Object-oriented databases present an attractive alternative to traditional relational databases for situations where the experiments themselves are continually evolving. We present EMEN2, an easy to use object-oriented database with a highly flexible infrastructure originally targeted for transmission electron microscopy and tomography, which has been extended to be adaptable for use in virtually any experimental science. It is a pure object-oriented database designed for easy adoption in diverse laboratory environments and does not require professional database administration. It includes a full featured, dynamic web interface in addition to APIs for programmatic access. EMEN2 installations currently support roughly 800 scientists worldwide with over 1/2 million experimental records and over 20 TB of experimental data. The software is freely available with complete source.
Precision CMB Measurements from Long Duration Stratospheric Balloons: Towards B-modes and Inflation
Authors: Jones William C.
Published: January 2013

Observations of the Cosmic Microwave Background (CMB) have played a leading role in establishing an understanding of the structure and evolution of the Universe on the largest scales. This achievement has been enabled by a series of extremely successful experiments, coupled with the simplicity of the relationship between the cosmological theory and data. Antarctic experiments, including both balloon-borne telescopes and instruments at the South Pole, have played a key role in realizing the scientific potential of the CMB, from the characterization of the temperature anisotropies to the detection and study of the polarized component. Current and planned Antarctic long duration balloon experiments will extend this heritage of discovery to test theories of cosmic genesis through sensitive polarized surveys of the millimeter-wavelength sky. In this paper we will review the pivotal role that Antarctic balloon borne experiments have played in transforming our understanding of the Universe, and describe the scientific goals and technical approach of current and future missions.
Preliminary design of the Kunlun Dark Universe Survey Telescope (KDUST)
Authors: Yuan Xiangyan , Cui Xiangqun , Su Ding-qiang , Zhu Yongtian , Wang Lifan , Gu Bozhong , Gong Xuefei , Li Xinnan
Published: January 2013

From theoretical analysis and site testing work for 4 years on Dome A, Antarctica, we can reasonably predict that it is a very good astronomical site, as good as or even better than Dome C and suitable for observations ranging from optical to infrared & sub-mm wavelengths. After the Chinese Small Telescope ARray (CSTAR), which was composed of four small fixed telescopes with diameter of 145mm and the three Antarctic Survey Telescopes (AST3) with 500mm entrance diameter, the Kunlun Dark Universe Survey Telescope (KDUST) with diameter of 2.5m is proposed. KDUST will adopt an innovative optical system which can deliver very good image quality over a 2 square degree flat field of view. Some other features are: a fixed focus suitable for different instruments, active optics for miscollimation correction, a lens-prisms that can be used as an atmospheric dispersion corrector or as a very low-dispersion spectrometer when moved in / out of the main optical path without changing the performance of the system, and a compact structure to make easier transportation to Dome A. KDUST will be mounted on a tower with height 15m in order to make a full use of the superb free atmospheric seeing.
Delays in medical malpractice litigation in civil law jurisdictions: some evidence from the Italian Court of Cassation
Authors: Grembi Veronica , Garoupa Nuno
Published: January 2013

Medical malpractice law and tort reform are contentious issues. In this paper, we focus on Italy as an example of a civil law jurisdiction. Italian medical malpractice law is essentially judge-made law. However, its effectiveness is likely to be curtailed by excessive delays in litigation. Several reforms have been enacted since the late 1980s to correct this situation. By making use of the decisions of the Italian Court of Cassation (which have shaped medical malpractice law) from 1970 to 2009, we show that these reforms had no general statistically significant impact on delays. Recent reduction of delays does not seem to be related to legal reforms but rather explained by other factors.
AdE-1, a new inotropic Na+ channel toxin from Aiptasia diaphana, is similar to, yet distinct from, known anemone Na+ channel toxins
Authors: Nesher Nir , Shapira Eli , Sher Daniel , Moran Yehu , Tsveyer Liora , Turchetti-Maia Ana Luiza , Horowitz Michal , Hochner Binyamin , Zlotkin Eliahu
Published: January 2013

Heart failure is one of the most prevalent causes of death in the western world. Sea anemone contains a myriad of short peptide neurotoxins affecting many pharmacological targets, several of which possess cardiotonic activity. In the present study we describe the isolation and characterization of AdE-1 (ion channel modifier), a novel cardiotonic peptide from the sea anemone Aiptasia diaphana, which differs from other cnidarian toxins. Although AdE-1 has the same cysteine residue arrangement as sea anemone type 1 and 2 Na+ channel toxins, its sequence contains many substitutions in conserved and essential sites and its overall homology to other toxins identified to date is low (<36%). Physiologically, AdE-1 increases the amplitude of cardiomyocyte contraction and slows the late phase of the twitch relaxation velocity with no induction of spontaneous twitching. It increases action potential duration of cardiomyocytes with no effect on its threshold and on the cell's resting potential. Similar to other sea anemone Na+ channel toxins such as Av2 (Anemonia viridis toxin II), AdE-1 markedly inhibits Na+ current inactivation with no significant effect on current activation, suggesting a similar mechanism of action. However, its effects on twitch relaxation velocity, action potential amplitude and on the time to peak suggest that this novel toxin affects cardiomyocyte function via a more complex mechanism. Additionally, Av2's characteristic delayed and early after-depolarizations were not observed. Despite its structural differences, AdE-1 physiologic effectiveness is comparable with Av2 with a similar ED50 value to blowfly larvae. This finding raises questions regarding the extent of the universality of structure–function in sea anemone Na+ channel toxins.
Microvesicles and exosomes as vehicles between protozoan and host cell communication
Authors: Deolindo Poliana , Evans-Osses Ingrid , Ramirez Marcel Ivan
Published: January 2013

Cells release extracellular vesicles in response to external factors or in a physiological way. Microvesicles and exosomes originate in cells in different ways and, depending on their contents, may have multiple biological effects on other cells and the environment. The host cell–parasite relationship could be changed dramatically by the plasticity of a new type of communication through extracellular vesicles. In the present paper, we discuss how protozoans use this new resource to evade the immune system and establish infection.
Palmitoylation-dependent regulation of glutamate receptors and their PDZ domain-containing partners
Authors: Thomas Gareth M. , Huganir Richard L.
Published: January 2013

In recent years, it has become clear that both AMPA (α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)- and NMDA (N-methyl-D-aspartate)-type glutamate receptors, and many of their interacting partners, are palmitoylated proteins. Interfering with palmitoylation dramatically affects receptor trafficking and distribution and, in turn, can profoundly alter synaptic transmission. Increased knowledge of synaptic palmitoylation not only will aid our understanding of physiological neuronal regulation, but also may provide insights into, and even novel treatments for, neuropathological conditions. In the present paper, we review recent advances regarding the regulation of ionotropic glutamate receptor trafficking and function by palmitoylation.
Regulation of large conductance calcium- and voltage-activated potassium (BK) channels by S-palmitoylation
Authors: Shipston Michael J.
Published: January 2013

BK (large conductance calcium- and voltage-activated potassium) channels are important determinants of physiological control in the nervous, endocrine and vascular systems with channel dysfunction associated with major disorders ranging from epilepsy to hypertension and obesity. Thus the mechanisms that control channel surface expression and/or activity are important determinants of their (patho)physiological function. BK channels are S-acylated (palmitoylated) at two distinct sites within the N- and C-terminus of the pore-forming α-subunit. Palmitoylation of the N-terminus controls channel trafficking and surface expression whereas palmitoylation of the C-terminal domain determines regulation of channel activity by AGC-family protein kinases. Recent studies are beginning to reveal mechanistic insights into how palmitoylation controls channel trafficking and cross-talk with phosphorylation-dependent signalling pathways. Intriguingly, each site of palmitoylation is regulated by distinct zDHHCs (palmitoyl acyltransferases) and APTs (acyl thioesterases). This supports that different mechanisms may control substrate specificity by zDHHCs and APTs even within the same target protein. As palmitoylation is dynamically regulated, this fundamental post-translational modification represents an important determinant of BK channel physiology in health and disease.
Beyond retrograde and anterograde signalling: mitochondrial–nuclear interactions as a means for evolutionary adaptation and contemporary disease susceptibility
Authors: Ballinger Scott W.
Published: January 2013

Although there is general agreement that most forms of common disease develop as a consequence of a combination of factors, including genetic, environmental and behavioural contributors, the actual mechanistic basis of how these factors initiate or promote diabetes, cancer, neurodegenerative and cardiovascular diseases in some individuals but not in others with seemingly identical risk factor profiles, is not clearly understood. In this respect, consideration of the potential role for mitochondrial genetics, damage and function in influencing common disease susceptibility seems merited, given that the prehistoric challenges were the original factors that moulded cellular function, and these were based upon the mitochondrial–nuclear relationships that were established during evolutionary history. These interactions were probably refined during prehistoric environmental selection events that, at present, are largely absent. Contemporary risk factors such as diet, sedentary lifestyle and increased longevity, which influence our susceptibility to a variety of chronic diseases were not part of the dynamics that defined the processes of mitochondrial–nuclear interaction, and thus cell function. Consequently, the prehistoric challenges that contributed to cell functionality and evolution should be considered when interpreting and designing experimental data and strategies. Although several molecular epidemiological studies have generally supported this notion, studies that probe beyond these associations are required. Such investigation will mark the initial steps for mechanistically addressing the provocative concept that contemporary human disease susceptibility is the result of prehistoric selection events for mitochondrial–nuclear function, which increased the probability for survival and reproductive success during evolution.
Preparation of purified GPCRs for structural studies
Authors: Cooke Robert M. , Koglin Markus , Errey James C. , Marshall Fiona H.
Published: January 2013

Since the publication of the first X-ray structure of a GPCR (G-protein couple receptor) in 2000, the rate at which subsequent ones have appeared has steadily increased. This has required the development of new methodology to overcome the challenges presented by instability of isolated GPCRs, combined with a systematic optimization of existing approaches for protein expression, purification and crystallization. In addition, quality control measures that are predictive of successful outcomes have been identified. Repeated attempts at solving the structures of GPCRs have highlighted experimental approaches that are most likely to lead to success, and have allowed definition of a first-pass protocol for new receptors.
Interactions of human monocytes with TMVs (tumour-derived microvesicles)
Authors: Baj-Krzyworzeka Monika , Baran Jarosław , Szatanek Rafał , Mytar Bożenna , Siedlar Maciej , Zembala Marek
Published: January 2013

The tumour microenvironment represents a dynamic complex milieu, which includes tumour cells, cells of the immune system and other (cellular and non-cellular) components. The role of these particular ‘puzzle pieces’ may change substantially due to their mutual interactions. The present review concerns different opinions on interactions that occur between monocytes, tumour cells and TMVs (tumour-derived microvesicles).
Atypical chemokine receptors: from silence to sound
Authors: Cancellieri Cinzia , Vacchini Alessandro , Locati Massimo , Bonecchi Raffaella , Borroni Elena M.
Published: January 2013

ACRs (atypical chemokine receptors) were initially referred to as ‘silent’ receptors on the basis of a lack of signalling and functional activities that are typically observed with conventional chemokine receptors. Although ACRs do not directly induce cell migration, they indirectly control leucocyte recruitment by shaping chemokine gradients in tissues through degradation, transcytosis or local concentration of their cognate ligands. Recent evidence also suggests that these biological activities are supported by G-protein-independent, β-arrestin-dependent signalling events. In the present article, we review current knowledge on structural and signalling properties of ACRs that are changing our view on this entire class of receptors from silent to endogenous β-arrestin-biased signalling receptors.
Role of extracellular membrane vesicles in intercellular communication of the tumour microenvironment
Authors: Svensson Katrin J. , Belting Mattias
Published: January 2013

Over the last few decades, extensive studies by several groups have introduced the concept of cell-derived secreted extracellular membrane vesicles as carriers of complex molecular information. Owing to their pleiotropic biological effects and involvement in a wide variety of biological processes, extracellular membrane vesicles have been implicated in physiological as well as pathological events, including tumour development and metastasis. In the present review, we discuss the role of secreted membrane vesicles in intercellular communication with a focus on tumour biology. Of particular interest is the potential role of extracellular vesicles as orchestrators of common features of the malignant tumour microenvironment, e.g. coagulation activation and angiogenesis.
Enlightening G-protein-coupled receptors on the plasma membrane using super-resolution photoactivated localization microscopy
Authors: Scarselli Marco , Annibale Paolo , Gerace Claudio , Radenovic Aleksandra
Published: January 2013

The possibility to visualize and image the arrangement of proteins within the cell at the molecular level has always been an attraction for scientists in biological research. In particular, for signalling molecules such as GPCRs (G-protein-coupled receptors), the existence of protein aggregates such as oligomers or clusters has been the topic of extensive debate. One of the reasons for this lively argument is that the molecular size is below the diffraction-limited resolution of the conventional microscopy, precluding the direct visualization of protein super-structures. On the other hand, new super-resolution microscopy techniques, such as the PALM (photoactivated localization microscopy), allow the limit of the resolution power of conventional optics to be broken and the localization of single molecules to be determined with a precision of 10–20 nm, close to their molecular size. The application of super-resolution microscopy to study the spatial and temporal organization of GPCRs has brought new insights into receptor arrangement on the plasma membrane. Furthermore, the use of this powerful microscopy technique as a quantitative tool opens up the possibility for investigating and quantifying the number of molecules in biological assemblies and determining the protein stoichiometry in signalling complexes.
Interplay of host–pathogen microvesicles and their role in infectious disease
Authors: Inal Jameel M. , Ansa-Addo Ephraim A. , Lange Sigrun
Published: January 2013

The release of extracellular vesicles, whether MVs (microvesicles) or exosomes, from host cells or intracellular pathogens is likely to play a significant role in the infection process. Host MVs may fuse with pathogen surfaces to deliver host complement regulatory proteins. They may also deliver cytokines that enhance invasion. Decoy functions are also possible. Whereas host MVs may direct pathogens away from their target cells, pathogen MVs may in turn redirect complement membrane-attack complexes away from their target pathogen. An understanding of the mechanisms of this interplay, bringing about both immune evasion and enhanced invasion, will help to direct future research with a view to rendering pathogens more susceptible to immune attack or in improving drug efficacy. It should also be possible to use MVs or exosomes isolated directly from the pathogens, or from the cells infected with pathogens, to provide alternative vaccination strategies.
The ring of confidence: a haloarchaeal CRISPR/Cas system
Authors: Maier Lisa-Katharina , Stoll Britta , Brendel Jutta , Fischer Susan , Pfeiffer Friedhelm , Dyall-Smith Mike , Marchfelder Anita
Published: January 2013

To survive the constant invasions by foreign genetic elements, prokaryotes have evolved various defensive systems. Almost all sequenced archaea, and half of the analysed bacteria use the CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated) system, a recently identified prokaryotic immune system that can fend off invading elements in a sequence-specific manner. Few archaeal CRISPR/Cas systems have been analysed so far, and the molecular details of many of the steps involved in adaptation and defence are yet to be understood. In the present paper, we summarize our current knowledge about the CRISPR/Cas system in Haloferax volcanii, an extremely halophilic archaeon that was isolated from the Dead Sea. H. volcanii encodes a type I-B CRISPR/Cas system, and carries three CRISPR loci and eight Cas proteins. Although in laboratory culture for more than three decades, this defence system was shown to be still active. All three CRISPR loci are transcribed and processed into mature crRNAs (CRISPR RNAs). Cells challenged with engineered plasmids can recognize and eliminate these invading elements if they contain the correct PAM (protospacer adjacent motif) and a sequence that can be recognized by one of the CRISPR spacers.
The role of palmitoylation in regulating Ras localization and function
Authors: Eisenberg Sharon , Laude Alex J. , Beckett Alison J. , Mageean Craig J. , Aran Veronica , Hernandez-Valladares Maria , Henis Yoav I. , Prior Ian A.
Published: January 2013

Ras GTPases are important regulators of pathways controlling proliferation, differentiation and transformation. Three ubiquitously expressed almost identical Ras genes are not functionally redundant; this has been attributed to their distinctive trafficking and localization profiles. A palmitoylation cycle controls the correct compartmentalization of H-Ras and N-Ras. We review recent data that reveal how this cycle can be regulated by membrane organization to influence the spatiotemporal signalling of Ras.
The role of microvesicles in cancer progression and drug resistance
Authors: Jorfi Samireh , Inal Jameel M.
Published: January 2013

Microvesicles are shed constitutively, or upon activation, from both normal and malignant cells. The process is dependent on an increase in cytosolic Ca2+, which activates different enzymes, resulting in depolymerization of the actin cytoskeleton and release of the vesicles. Drug resistance can be defined as the ability of cancer cells to survive exposure to a wide range of anti-cancer drugs, and anti-tumour chemotherapeutic treatments are often impaired by innate or acquired MDR (multidrug resistance). Microvesicles released upon chemotherapeutic agents prevent the drugs from reaching their targets and also mediate intercellular transport of MDR proteins.
The cis-acting signals that target proteins to exosomes and microvesicles
Authors: Yang Jr-Ming , Gould Stephen J.
Published: January 2013

Proteins bud from cells in small single-membraned vesicles (~50–250 nm) that have the same topology as the cell. Known variously as exosomes and microvesicles (EMVs), these extracellular organelles are enriched for specific proteins, lipids, carbohydrates and nucleic acids. EMV biogenesis plays critical roles in protein quality control and cell polarity, and, once released, EMVs can transmit signals and molecules to neighbouring cells via a non-viral pathway of intercellular vesicle traffic. In the present paper, we discuss the cis-acting targeting signals that target proteins to EMVs and mediate protein budding from the cell.
Role of p90RSK in regulating the Crabtree effect: implications for cancer
Authors: Redman Emily K. , Brookes Paul S. , Karcz Marcin K.
Published: January 2013

High glucose inhibits mitochondrial respiration, known as the ‘Crabtree effect’, in cancer cells and possibly other cell types. The upstream pathways regulating this phenomenon are poorly understood. In diabetes, where glucose levels are elevated, the p90RSK (p90 ribosomal S6 kinase) has received much attention as a potential upstream mediator of the effects of high glucose. Evidence is also emerging that p90RSK may play a role in cancer cell signalling, although the role of p90RSK in regulating cancer cell metabolism is unclear. In the present paper, we provide an overview of the Crabtree effect and its relationship to mitochondrial metabolism. Furthermore, preliminary data are presented suggesting a role for p90RSK and its upstream components, the ERK (extracellular-signal-regulated kinase) family of MAPKs (mitogen-activated protein kinases), in the Crabtree effect.
Molecular mechanisms of platelet P2Y12 receptor regulation
Authors: Cunningham Margaret R. , Nisar Shaista P. , Mundell Stuart J.
Published: January 2013

Platelets are critical for haemostasis, however inappropriate activation can lead to the development of arterial thrombosis, which can result in heart attack and stroke. ADP is a key platelet agonist that exerts its actions via stimulation of two surface GPCRs (G-protein-coupled receptors), P2Y1 and P2Y12. Similar to most GPCRs, P2Y receptor activity is tightly regulated by a number of complex mechanisms including receptor desensitization, internalization and recycling. In the present article, we review the molecular mechanisms that underlie P2Y1 and P2Y12 receptor regulation, with particular emphasis on the structural motifs within the P2Y12 receptor, which are required to maintain regulatory protein interaction. The implications of these findings for platelet responsiveness are also discussed.
Hot and sweet: protein glycosylation in Crenarchaeota
Authors: Meyer Benjamin H. , Albers Sonja-Verena
Published: January 2013

Every living cell is covered with a dense and complex array of covalently attached sugars or sugar chains. The majority of these glycans are linked to proteins via the so-called glycosylation process. Protein glycosylation is found in all three domains of life: Eukarya, Bacteria and Archaea. However, on the basis of the limit in analytic tools for glycobiology and genetics in Archaea, only in the last few years has research on archaeal glycosylation pathways started mainly in the Euryarchaeota Haloferax volcanii, Methanocaldococcus maripaludis and Methanococcus voltae. Recently, major steps of the crenarchaeal glycosylation process of the thermoacidophilic archaeon Sulfolobus acidocaldarius have been described. The present review summarizes the proposed N-glycosylation pathway of S. acidocaldarius, describing the phenotypes of the mutants disrupted in N-glycan biosynthesis as well as giving insights into the archaeal O-linked and glycosylphosphatidylinositol anchor glycosylation process.
Deciphering the specific role of Gαi/o isoforms: functional selective oxytocin ligands and somatostatin SST5 receptor mutants
Authors: Busnelli Marta , Peverelli Erika , Mantovani Giovanna , Spada Anna , Chini Bice
Published: January 2013

Receptor coupling to different G-proteins and β-arrestins has been described for a number of GPCRs (G-protein-coupled receptors), suggesting a multi-state model of receptor activation in which each receptor can assume a number of different active conformations, each capable of promoting the coupling to a specific effector. Consistently, functional-selective ligands and biased agonists have been described to be able to induce and/or stabilize only a subset of specific active conformations. Furthermore, GPCR mutants deficient in selective coupling have been reported. Functional selective ligands and receptor mutants thus constitute unique tools to dissect the specific roles of different effectors, in particular among the Gi/o family. In the present mini-review, we focus on (i) the identification of functional selective OXT (oxytocin)-derived peptides capable of activating single Gi/o isoforms, namely Gi1 or Gi3; and (ii) the characterization of an SS (somatostatin) receptor SST5 mutant selectively impaired in its GoA coupling. These analogues and receptor mutants represent unique tools for examining the contribution of Gi/o isoforms in complex biological responses and open the way for the development of drugs with peculiar selectivity profiles.
Cis-regulatory logic in archaeal transcription
Authors: Peeters Eveline , Peixeiro Nuno , Sezonov Guennadi
Published: January 2013

For cellular fitness and survival, gene expression levels need to be regulated in response to a wealth of cellular and environmental signals. TFs (transcription factors) execute a large part of this regulation by interacting with the basal transcription machinery at promoter regions. Archaea are characterized by a simplified eukaryote-like basal transcription machinery and bacteria-type TFs, which convert sequence information into a gene expression output according to cis-regulatory rules. In the present review, we discuss the current state of knowledge about these rules in archaeal systems, ranging from DNA-binding specificities and operator architecture to regulatory mechanisms.
Ligand bias at the μ-opioid receptor
Authors: Kelly Eamonn
Published: January 2013

Ligand bias refers to the ability of a drug at a receptor to activate selectively particular cell signalling pathways over others, in a way that cannot be explained by traditional models of receptor theory. For a physiologically and therapeutically important GPCR (G-protein-coupled receptor) such as the MOPr (μ-opioid receptor), the role of ligand bias is currently being explored, not only in order to understand the molecular function of this receptor, but also with a view to developing better analgesic drugs with fewer adverse effects. In this short review, the ways to detect and quantify agonist bias at MOPr are discussed, along with the possible significance of MOPr ligand bias in the therapeutic use of opioid drugs. An important conclusion of this work is that attempts to define ligand bias at any GPCR on the basis of the visual inspection of concentration–response curves or comparison of maximum response (Emax) values can be misleading. Instead, reliable estimations of relative agonist efficacy are needed to calculate bias effectively.
Structure and dynamics of the crenarchaeal nucleoid
Authors: Driessen Rosalie P.C. , Dame Remus Th.
Published: January 2013

Crenarchaeal genomes are organized into a compact nucleoid by a set of small chromatin proteins. Although there is little knowledge of chromatin structure in Archaea, similarities between crenarchaeal and bacterial chromatin proteins suggest that organization and regulation could be achieved by similar mechanisms. In the present review, we describe the molecular properties of crenarchaeal chromatin proteins and discuss the possible role of these architectural proteins in organizing the crenarchaeal chromatin and in gene regulation.
Omega-3 fatty acid ethyl ester supplementation decreases very-low-density lipoprotein triacylglycerol secretion in obese men
Authors: Wong Annette T. Y. , Chan Dick C. , Ooi Esther M. M. , Ng Theodore W. K. , Watts Gerald F. , Barrett P. Hugh R.
Published: January 2013

Dysregulated VLDL-TAG (very-low-density lipoprotein triacylglycerol) metabolism in obesity may account for hypertriacylglycerolaemia and increased cardiovascular disease. ω-3 FAEEs (omega-3 fatty acid ethyl esters) decrease plasma TAG and VLDL concentrations, but the mechanisms are not fully understood. In the present study, we carried out a 6-week randomized, placebo-controlled study to examine the effect of high-dose ω-3 FAEE supplementation (3.2 g/day) on the metabolism of VLDL-TAG in obese men using intravenous administration of d5-glycerol. We also explored the relationship of VLDL-TAG kinetics with the metabolism of VLDL-apo (apolipoprotein) B-100 and HDL (high-density lipoprotein)-apoA-I. VLDL-TAG isotopic enrichment was measured using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Compared with placebo, ω-3 FAEE supplementation significantly lowered plasma concentrations of total (−14%, P<0.05) and VLDL-TAG (−32%, P<0.05), as well as hepatic secretion of VLDL-TAG (−32%, P<0.03). The FCR (fractional catabolic rate) of VLDL-TAG was not altered by ω-3 FAEEs. There was a significant association between the change in secretion rates of VLDL-TAG and VLDL-apoB-100 (r=0.706, P<0.05). However, the change in VLDL-TAG secretion rate was not associated with change in HDL-apoA-I FCR (r=0.139, P>0.05). Our results suggest that the TAG-lowering effect of ω-3 FAEEs is associated with the decreased VLDL-TAG secretion rate and hence lower plasma VLDL-TAG concentration in obesity. The changes in VLDL-TAG and apoB-100 kinetics are closely coupled.
The existence of steady solutions for a class of Schrödinger equations in nonlinear optical lattices
Authors: Zhang Ruifeng , Wang Hong , Liu Rentao
Published: January 2013

We address the impact of nonlocality in the physical features exhibited by solitons in photorefractive optical lattice. We use the method of calculus of variations to develop an existence theory for the steady state solutions of a nonlinear Schrödinger equation modeling light waves propagating in nonlinear optical lattices. We show via a mountain-pass argument that there exist steady state solutions realizing a continuous spectrum of energy points or wavenumbers.
Temperature dependence of quantum lifetime in n-InGaAs/GaAs structures with strongly coupled double quantum wells
Authors: Arapov Yu. G. , Gudina S. V. , Neverov V. N. , Podgornykh S. M. , Yakunin M. V.
Published: January 2013

Longitudinal ρxx(B) and Hall ρxy(B) magnetoresistances are experimentally investigated as a function of in-plane and transverse magnetic fields in n-InGaAs/GaAs nanostructures with strongly-coupled double quantum wells in the temperature range T = 1.8–70 K and magnetic fields B = 0–9.0 T. Experimental data on the temperature dependence of quantum lifetime in diffusive (kBT/τtr ≪ 1) and ballistic (kBT/τtr ≫ 1) regimes are reported. It has been found that in the ballistic regime in the temperature range where kBT/EF < 0.1, the observed quadratic temperature dependence of quantum lifetime is determined by inelastic electron–electron scattering. However, the temperature dependence of quantum lifetime cannot be quantitatively described by the existing theories in the whole temperature range.
Curved noncommutative torus and Gauss–Bonnet
Authors: Dąbrowski Ludwik , Sitarz Andrzej
Published: January 2013

We study perturbations of the flat geometry of the noncommutative two-dimensional torus \documentclass[12pt]{minimal}\begin{document}$\mathbb {T}^2_\theta$\end{document}Tθ2 (with irrational θ). They are described by spectral triples \documentclass[12pt]{minimal}\begin{document}$(A_\theta , \mathcal {H}, D)$\end{document}(Aθ,H,D), with the Dirac operator D, which is a differential operator with coefficients in the commutant of the (smooth) algebra Aθ of \documentclass[12pt]{minimal}\begin{document}$\mathbb {T}_\theta$\end{document}Tθ. We show, up to the second order in perturbation, that the ζ-function at 0 vanishes and so the Gauss-Bonnet theorem holds. We also calculate first two terms of the perturbative expansion of the corresponding local scalar curvature.