bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetrical Dynamic Propagation Problem on the Edges of Mode III Interface Crack Subjected to Superimpose Loads
Authors: Lü N.-C. , Li X.-G. , Cheng Y.-H. , Cheng J.
Published: January 2013

By application of the theory of complex variable functions, asymmetrical dynamic propagation problem on the edges of mode III interface crack subjected to superimpose loads was studied. Analytical solutions of the stresses displacements and dynamic stress intensity factors are obtained by means of self- similar functions. The problems researched can be facilely transformed into Riemann-Hilbert problems and their closed solutions are attained rather simple according to this measure. After those solutions are utilized by superposition theorem, the solutions of arbitrarily complex problems can be gained.
Static and Dynamic Mathematical Modeling of a Micro Gas Turbine
Authors: Hosseinalipour S. M. , Abdolahi E. , Razaghi M.
Published: January 2013

This paper presents a static and linear dynamic model to simulate the performance of a Micro Gas Turbine (MGT). The static model is obtained using thermodynamic equations and maps of the components to determine off design performance of the MGT with constant output power. The linear dynamic model is developed using linearized static and dynamic nonlinear equations around an operating point as state-space model to predict the behaviour of the MGT in transient conditions. To validate the results of the static model, important information such as fuel flow, fuel to air ratio, and turbine inlet temperature are compared with the results of Aspen-HYSYS software during an increase in ambient temperature. In addition, static model results are compared with experimental data of the MGT test by previous studies. Also, the compressor equilibrium running line of the MGT is derived in constant ambient condition. In order to evaluate the linear dynamic model, the verification is performed using the results of nonlinear model of previous studies. The comparison between the results confirms the ability of proposed dynamic model to simulate a MGT while decreasing the computational effort and complexity of equations. Moreover, a comparison is carried out between static model results and steady state values predicted by dynamic model.
Effects of Hall Current and Ion-Slip on MHD Flow Induced by Torsional Oscillations of a Disc in a Rotating Fluid
Authors: Ghara N. , Das S. , Maji S. L. , Jana R. N.
Published: January 2013

The unsteady hydromagnetic flow due to torsional oscillations of a rotating disc in a viscous incompressible electrically conducting fluid which is also rotating is studied taking the effects of the Hall current and ion-slip into consideration. The governing equations are solved analytically. The results show that the inclusion of the Hall current and ion slip have important effects on the velocity distributions as well as shear stresses at the disc. The flow is characterized by two opposite circularly polarized waves, travelling with different velocities. It is found that there is a formation of two-deck boundary layers, thicknesses of which increase with increase in either Hall parameter or ion-slip parameter. The radial velocity increases with an increase in Hall parameter and the azimuthal velocity increases with an increase in either Hall parameter or ion-slip parameter. Further, it is found that the amplitude of the transverse shear stress at the disc decreases with an increase in either Hall parameter or ion-slip parameter.
Theoretical Analysis of Diffusion Flames Using Perturbation Method for Different Lewis and Damkohler Numbers
Authors: Bidabadi Mehdi , Asadollahzadeh Payam , Meibudy Mohammad N. P.
Published: January 2013

This paper presents a two dimensional asymptotic model of counterflow diffusion flame in the presence of radiation heat loss. The fuel and oxidizer, respectively, are injected from left and right hand side of the flame. The effects of burning rate, Lewis and Damkohler number on the structure and extinction of the flame is studied using perturbation method. To do so, the structure of the flame is considered to be composed of reaction zone with a thickness of O(ε) and radiation heat loss zone, of O(δ) thickness, that sandwiches the reaction zone. The effect of burning rate is illustrated by burning pre-exponential parameter, B. It is found that with the increase of the parameter, the flame temperature is also increased, and flame location moves toward the fuel side. In addition, the variation of Lewis number of fuel and oxidizer has a significant effect on the location and temperature of the flame.
Host–microbe interactions: the difficult yet peaceful coexistence of the microbiota and the intestinal mucosa
Authors: de Medina Fermín Sánchez , Ortega-González Mercedes , González-Pérez Raquel , Capitán-Cañadas Fermín , Martínez-Augustin Olga
Published: January 2013

The immune system has evolved to live in a collaborative relationship with the microbiota, while still serving its seminal function to fight off invasive pathogenic bacteria. The mechanisms that rule the interactions between the intestinal microbiota and the intestinal immune system are the focus of intense research. Here, we describe how the innate immunity is, to a great extent, in charge of the control of the microbiota in the intestine and relies on non-specific receptors called pathogen-recognition receptors. While the microbiota has a well-defined effect on the host immune homoeostasis, it has become clear that the opposite is also true, i.e., the mucosal immune system has the capacity to shape the microbial population. The mechanisms that rule the reciprocal regulation between host immunity and commensal bacteria (including specific bacteria) are currently being elucidated and will be described here. A better knowledge of how the host and bacteria interact and how the intestinal microbiota and the immune system are co-regulated will provide the basis for a better understanding of intestinal and systemic immunopathologies and for the development of new therapeutic approaches.
Cordycepin (3′-deoxyadenosine) pentostatin (deoxycoformycin) combination treatment of mice experimentally infected withTrypanosoma evansi
Authors: ROSA LUCIANA DALLA , DA SILVA ALEKSANDRO S. , GRESSLER LUCAS T. , OLIVEIRA CAMILA B. , DAMBRÓS MARIA G. C. , MILETTI LUIZ C. , FRANÇA RAQUELI T. , LOPES SONIA T. A. , SAMARA YASMIN N. , DA VEIGA MARCELO L. , MONTEIRO SILVIA G.
Published: January 2013

The aim of this study was to evaluate the anti-trypanosomal effect of treatment with 3′-deoxyadenosine (cordycepin) combined with deoxycoformycin (pentostatin: inhibitor of the enzyme adenosine deaminase)in vitroby using mice experimentally infected withTrypanosoma evansi. In vitro, a dose-dependent trypanocidal effect of cordycepin was observed against the parasite. In thein vivotrials, the two drugs were used individually and in combination of different doses. The drugs when used individually had no curative effect on infected mice. However, the combination of cordycepin (2 mg kg−1) and pentostatin (2 mg kg−1) was 100% effective in theT. evansi-infected groups. There was an increase in levels of some biochemical parameters, especially on liver enzymes, which were accompanied by histological lesions in the liver and kidneys. Based on these results we conclude that treatment using the combination of 3′-deoxyadenosine with deoxycoformycin has a curative effect on mice infected withT. evansi. However, the therapeutic protocol tested led to liver and kidney damage, manifested by hepatotoxicity and nephrotoxicity.
Characterization of heat shock protein 70 gene fromHaemonchus contortusand its expression and promoter analysis inCaenorhabditis elegans
Authors: ZHANG HONGLI , ZHOU QIANJIN , YANG YI , CHEN XUEQIU , YAN BAOLONG , DU AIFANG
Published: January 2013

Haemonchus contortusinfections in small ruminants are of major economic importance worldwide. Heat shock proteins (HSPs) are a family of molecular chaperones that play important roles in the process of invasion and survival of nematodes. Although HSP70 has been identified in several parasitic nematodes, little is known of its distribution and function inHaemonchus contortus. The aims of this study were to characterize HSP70 fromHaemonchus contortus(designed as Hc-hsp70), express Hc-hsp70 and analyse the promoter activity inCaenorhabditis elegans. Bioinformatic analysis revealed that the open reading frame of the Hc-hsp70 cDNA encodes a 646-amino acid peptide, which is highly conserved in comparison to HSP70 in other nematodes. Phylogenetic analysis indicated thatH. contortusis closely related toCaenorhabditis. The 5′-flanking region promoted green fluorescence protein (GFP) expression in the intestine in all larval stages and adult with 2 expression patterns inC. elegans. Expression of Hc-hsp70 mRNA transcripts inC. elegansincreased following 2, 4, 6 h of heat shock and peaked at 4 h. However, its expression induced down-regulation ofhsp-1ofC. elegans. These results suggest that theH. contortushsp70 might have a similar function to that ofC. elegans hsp-1.
Spiritual and religious beliefs as risk factors for the onset of major depression: an international cohort study
Authors: Leurent B. , Nazareth I. , Bellón-Saameño J. , Geerlings M.-I. , Maaroos H. , Saldivia S. , Švab I. , Torres-González F. , Xavier M. , King M.
Published: January 2013

Background

Several studies have reported weak associations between religious or spiritual belief and psychological health. However, most have been cross-sectional surveys in the USA, limiting inference about generalizability. An international longitudinal study of incidence of major depression gave us the opportunity to investigate this relationship further.

Method

Data were collected in a prospective cohort study of adult general practice attendees across seven countries. Participants were followed at 6 and 12 months. Spiritual and religious beliefs were assessed using a standardized questionnaire, and DSM-IV diagnosis of major depression was made using the Composite International Diagnostic Interview (CIDI). Logistic regression was used to estimate incidence rates and odds ratios (ORs), after multiple imputation of missing data.

Results

The analyses included 8318 attendees. Of participants reporting a spiritual understanding of life at baseline, 10.5% had an episode of depression in the following year compared to 10.3% of religious participants and 7.0% of the secular group (p < 0.001). However, the findings varied significantly across countries, with the difference being significant only in the UK, where spiritual participants were nearly three times more likely to experience an episode of depression than the secular group [OR 2.73, 95% confidence interval (CI) 1.59–4.68]. The strength of belief also had an effect, with participants with strong belief having twice the risk of participants with weak belief. There was no evidence of religion acting as a buffer to prevent depression after a serious life event.

Conclusions

These results do not support the notion that religious and spiritual life views enhance psychological well-being.
“This Is Simply What I Do”: Wittgenstein and Oakeshott on the Practices of Individual Agency
Authors: Plotica Luke Philip
Published: January 2013

Ludwig Wittgenstein and Michael Oakeshott are often labeled conservative thinkers, and taken to theorize rigid limits to individual agency and criticism. Tracing several modes of affinity between the work of Wittgenstein and Oakeshott, one can recognize the conventionality and rule-governed character of linguistic practices and yet affirm a deeply individualistic account of agency and action. Each thinker respectively characterizes the individual as located within a context of action that is richly structured by intersubjective rules and practices. Yet each also recognizes an ineluctable dimension of individuality and contingency to action that surpasses mere rule following or the reprise of conventional practice. The very situatedness of the individual agent within a framework of linguistic practices shared with others provides the friction that enables individual criticism and transgressive political action. Wittgenstein and Oakeshott thus present a perspective on political agency and criticism that is a salient alternative to both conservative and radical views.
BARRY, BEETHOVEN AND ‘BEETHOVEN’: IMMORTALITY AND INFLUENCE
Authors: March Daniel
Published: January 2013

Beethoven's famous letter to ‘The Immortal Beloved’ still remains a central reference point for our image of his life and music. Gerald Barry's 2007 composition for bass voice and ensemble – simply entitled Beethoven – sets this text in its entirety, continuing an engagement with Beethoven's own words and presenting a striking juxtaposition of language and music. This article explores the ways in which Barry at times underpins and in other places undercuts the apparent meaning of the words, and how he presents a reading of the letter that is clearly alive to its inherent self-contradictions. Characteristically, Barry brings together a number of highly expressive and strongly contrasted musical characters in this work; an examination of aspects of his compositional language illustrates how material is propagated and form articulated, and explores the way in which these techniques interact in the creation of an expressive and emotionally charged whole.
Birmingham, Argyle Warehouse: Stockhausen's ‘Mittwoch’
Authors: Rutherford-Johnson Tim
Published: January 2013

The 2012 Cultural Olympiad contained plenty of events that might have happened quite normally without the 2012 badge. The Olympics themselves may even have contributed to a 40% drop in museum attendance over the summer, as recently reported in some newspapers. But Birmingham Opera Company's production, starting on 22 August, of Mittwoch, the ‘unstageable’ third part of Stockhausen's Licht, at the Argyle Works in Great Barr Street was a Mo Farah moment. Not only for the Olympian commitment and talent required, but also because without Olympian funding (something in the order of £1 million was rumoured) it simply would not have been possible. Director Graham Vick had co-opted the varied talents of Ex Cathedra, London Voices, Paul Brown as designer, Giuseppe di Iorio in charge of lighting, Ron Howell as choreographer, and Kathinka Pasveer as musical director.
Manchester, Bridgewater Hall: Yoshiro Kanno
Authors: Mottershead Tim
Published: January 2013

Between April and June 2012, pianist Noriko Ogawa presented four recitals titled Reflections on Debussy, in the Mirror of the East, which presented his major piano works, with compositions by Japanese composers Takemitsu, Yoshimatsu, and two commissions from Yoshihiro Kanno (b.1953). The first of the Kanno works presented, on 25 May, was Sky Maze (2011) for piano and organ (featuring Jonathan Scott), oddly placed in a concert otherwise devoted to two-piano repertoire (with Martin Roscoe). The programme note revealed the work was originally to have been premièred in August 2011 at the MUZA Kawasaki concert hall – which was badly damaged by the earthquake and tsunami of the previous March – but offered no clue as to the work's intriguing title.
Civic Hall, Stratford-Upon-Avon: John McCabe's Trumpet Concerto ‘La Primavera’
Authors: Conway Paul
Published: January 2013

Although John McCabe's Rainforest II, of 1987, is in effect a chamber concerto for trumpet and 11 strings, his extensive body of concertante works has lacked an official trumpet concerto. La Primavera, which had its première on 15 June 2012, now happily fills that gap. The subtitle derives from McCabe's consideration of two aspects of the approach of Spring: the vitality of burgeoning growth and the flowering of the new or refreshed life as it expands.
London, Globe Theatre: ‘The Play's the Thing’
Authors: Barlow Jill
Published: January 2013

Shakespeare's Globe Theatre Season 2012, entitled ‘The Play's The Thing’, centred on Henry V and Richard III, with new music scores by Claire van Kampen, and The Taming of the Shrew, with a new score by Richard Hammarton. In addition – and well timed in the year of the Queen's Diamond Jubilee, and also the London Olympics – the Globe Theatre celebrated by sending out a worldwide invitation asking who would like to participate in their ‘Globe to Globe Festival’. As a result, 37 countries performed Shakespeare in 37 different languages here during the Season, within the architecture for which Shakespeare wrote, bringing with them a vast array of cultural diversity in music and dance dovetailed into the drama.
ThePavāraṇā Suttaand “liberation in both ways” as against “liberation by wisdom”
Authors: Kuan Tse-fu
Published: January 2013

There are six complete versions of thePavāraṇā Sutta(Pravāraṇā Sūtra). TheEkottarika Āgamaversion (EĀ 32.5) differs significantly from the other five. It contains an episode involving Ānanda, a non-arhat, which is not found in the other five versions. In the five versions other than EĀ 32.5, this Pravāraṇā ceremony is depicted as an assembly of arhats, who are endowed with different “liberations”. This paper shows that such divergences are correlated with one another and that EĀ 32.5 could be earlier than the other versions. In this connection I elucidate diverse notions of liberation as developed in the textual history and discuss the possibility that sectarian stance on the issue of liberation has a bearing on the inclusion of various types of arhats in the five versions, and their exclusion from EĀ 32.5, whose sectarian affiliation is identified in this study as Mahāsāṃghika.
An Evaluation of Community Assessment for Public Health Emergency Response (CASPER) in North Carolina, 2003-2010
Authors: Horney Jennifer , Davis Meredith K. , Davis Sarah E.H. , Fleischauer Aaron
Published: January 2013

Introduction

Community Assessment for Public Health Emergency Response (CASPER) is a group of tools and methods designed by the US Centers for Disease Control and Prevention (CDC) to provide rapid, reliable, and accurate population-based public health information. Since 2003, North Carolina public health professionals have used CASPERs to facilitate public health emergency responses and gather information on other topics including routine community health assessments.

Problem

To date, there has been no evaluation of CASPER use by public health agencies at the state or local level in the US.

Methods

Local health departments of North Carolina reported when and how CASPERs were used during the period 2003 to 2010 via an online survey. Data on barriers and future plans for using CASPERs also were collected.

Results

Fifty-two of North Carolina's 85 local health departments (61%) completed the survey. Twenty-eight departments reported 46 instances of CASPER use during 2003 to 2010. The majority of CASPERs were performed for community health assessments (n = 20, 43%) or exercises (n = 11, 24%). Fifty-six percent of respondents indicated they were “likely” or “very likely” to use CASPERs in the future; those who had prior experience with CASPERs were significantly more likely (P = .02) to report planned future use of CASPERs compared to those without prior experience with the tool. Lack of training, equipment, and time were the most frequently reported barriers to using CASPERs.

Conclusions

Local public health agencies with clear objectives and goals can effectively use CASPERs in both routine public health practice and disaster settings.

HorneyJ, DavisMK, DavisSEH, FleischauerA. An evaluation of Community Assessment for Public Health Emergency Response (CASPER) in North Carolina, 2003-2010. Prehosp Disaster Med. 2013;28(2):1–5.
Psychometric Properties of a New Measure of Parental Self-Efficacy for Promoting Healthy Physical Activity and Dietary Behaviors in Children
Authors: Bohman Benjamin , Ghaderi Ata , Rasmussen Finn
Published: January 2013

There is a lack of validated measures of parental self-efficacy (PSE) covering both physical activity and dietary behaviors in children which can be used to prevent childhood obesity. This study developed a new measure of PSE for promoting healthy physical activity and dietary behaviors in children and assessed its psychometric properties. Participants were mothers (n = 2,232) with 3-year-old first-born children living in Stockholm, Sweden. The mothers responded to questionnaires measuring PSE, locus of control, and self-esteem. Exploratory factor analysis yielded a three-factor structure, interpreted as PSE for promoting healthy dietary behaviors in children (Factor 1), PSE for limit-setting of unhealthy dietary or physical activity behaviors in children (Factor 2), and PSE for promoting healthy physical activity behaviors in children (Factor 3). The factor model was supported by confirmatory factor analysis. The internal consistency and test-retest reliability of the new PSE measure were high; discriminant validity was adequate. The Parental Self-Efficacy for Promoting Healthy Physical Activity and Dietary Behaviors in Children Scale (PSEPAD) shows promise as a valuable instrument in childhood obesity prevention.
Psychometric Properties of the Portuguese Version of the Posttraumatic Growth Inventory Short Form Among Divorced Adults
Authors: Lamela Diogo , Figueiredo Bárbara , Bastos Alice , Martins Helena
Published: January 2013

The aim of this study was to develop and validate a Portuguese version of the Short Form of the Posttraumatic Growth Inventory (PTGI-SF). Using an online convenience sample of Portuguese divorced adults (N = 482), we confirmed the oblique five-factor structure of the PTGI-SF by confirmatory factor analysis. The results demonstrated the measurement invariance across divorce initiator status groups. Total score and factors of PTGI-SF showed good internal consistency, with the exception of the New Possibilities factor, which revealed an acceptable reliability. The Portuguese PTGI-SF showed a satisfactory convergent validity. In terms of discriminant validity, posttraumatic growth assessed by the Portuguese PTGI-SF was a distinct factor from posttraumatic psychological adjustment. These preliminary findings suggest the cultural adaptation and also psychometric properties of the present Portuguese PTGI-SF to measure posttraumatic growth after personal crisis.
Innate lymphoid cells: from border protection to the initiation of inflammatory diseases
Authors: Sanos Stephanie L , Diefenbach Andreas
Published: January 2013

Innate lymphoid cells (ILC) are a recently discovered group of innate lymphocytes found at mucosal surfaces. The transcriptional and effector programs of ILC strikingly resemble those of the various T‐helper (Th) cell fates (that is, Th1, Th2, Th9, Th17, Th22). ILC are involved in protecting the mucosal borders by producing tissue protective factors. More recently, evidence has been provided that inappropriately activated ILC can be drivers of various inflammatory disorders. Here, we will highlight recent developments in our understanding of the transcriptional and developmental programs controlling ILC specification and fate decisions. We will also review the roles assigned to ILC in protecting barriers and in promoting inflammatory diseases. Finally, we will outline how the power of ILC may be harnessed for clinical application, and how interference with ILC function may be used as a new strategy to treat inflammatory diseases.
Add salt, add sugar: N-glycosylation in Haloferax volcanii
Authors: Kaminski Lina , Naparstek Shai , Kandiba Lina , Cohen-Rosenzweig Chen , Arbiv Adi , Konrad Zvia , Eichler Jerry
Published: January 2013

Although performed by members of all three domains of life, the archaeal version of N-glycosylation remains the least understood. Studies on Haloferax volcanii have, however, begun to correct this situation. A combination of bioinformatics, molecular biology, biochemical and mass spectrometry approaches have served to delineate the Agl pathway responsible for N-glycosylation of the S-layer glycoprotein, a reporter of this post-translational modification in Hfx. volcanii. More recently, differential N-glycosylation of the S-layer glycoprotein as a function of environmental salinity was demonstrated, showing that this post-translational modification serves an adaptive role in Hfx. volcanii. Furthermore, manipulation of the Agl pathway, together with the capability of Hfx. volcanii to N-glycosylate non-native proteins, forms the basis for establishing this species as a glyco-engineering platform. In the present review, these and other recent findings are addressed.
Role of stem-cell-derived microvesicles in the paracrine action of stem cells
Authors: Camussi Giovanni , Deregibus Maria Chiara , Cantaluppi Vincenzo
Published: January 2013

The paracrine theory has recently changed the view of the biological action of stem cells and of the subsequent potential application of stem cells in regenerative medicine. Indeed, most of the beneficial effects of stem-cell-based therapy have been attributed to soluble factors released from stem cells. In this context, MVs (microvesicles) released as exosomes from the endosomal compartment, or as shedding vesicles from the cell surface, may play a relevant role in the intercellular communication between stem and injured cells. By transferring proteins, bioactive lipids, mRNA and microRNA, MVs act as vehicles of information that may lead to alteration of the phenotype of recipient cells. The exchange of information between stem cells and tissue-injured cells is reciprocal. The MV-mediated transfer of tissue-specific information from the injured cells to stem cells may reprogramme the latter to gain phenotypic and functional characteristics of the cell of origin. On the other hand, MVs released from stem cells may confer a stem-cell-like phenotype to injured cells, with the consequent activation of self-regenerative programmes. In fact, MVs released from stem cells retain several biological activities that are able to reproduce the beneficial effects of stem cells in a variety of experimental models.
The orthosteric agonist-binding pocket in the prototypic class B G-protein-coupled secretin receptor
Authors: Miller Laurence J. , Dong Maoqing
Published: January 2013

Class B GPCRs (G-protein-coupled receptors) share heptahelical topology and G-protein binding with other superfamily members, yet have unique structures and modes of activation. Natural ligands for these receptors are moderate-length peptides with C-terminal α-helices. NMR and crystal structures of the peptide-bound disulfide-bonded receptor N-terminal domains demonstrate that these helices occupy a conserved groove; however, the details of this interaction vary from one receptor to another. In this review, we focus on the prototypic secretin receptor and use extensive intrinsic photoaffinity labelling, structure–activity series, alanine-replacement mutagenesis and fluorescence analysis to define the molecular basis for this interaction. Additionally, experimental validation of predictions coming from in silico molecular modelling has provided a basis for enhancement of binding affinity. Such insights will be useful in the rational development of drugs acting at this important group of targets.
Adaptation of low-resolution methods for the study of yeast microsomal polytopic membrane proteins: a methodological review
Authors: Bochud Arlette , Ramachandra Nagaraju , Conzelmann Andreas
Published: January 2013

Most integral membrane proteins of yeast with two or more membrane-spanning sequences have not yet been crystallized and for many of them the side on which the active sites or ligand-binding domains reside is unknown. Also, bioinformatic topology predictions are not yet fully reliable. However, so-called low-resolution biochemical methods can be used to locate hydrophilic loops or individual residues of polytopic membrane proteins at one or the other side of the membrane. The advantages and limitations of several such methods for topological studies with yeast ER integral membrane proteins are discussed. We also describe new tools that allow us to better control and validate results obtained with SCAM (substituted cysteine accessibility method), an approach that determines the position of individual residues with respect to the membrane plane, whereby only minimal changes in the primary sequence have to be introduced into the protein of interest.
The importance of interactions with helix 5 in determining the efficacy of β-adrenoceptor ligands
Authors: Warne Tony , Tate Christopher G.
Published: January 2013

Structures of the inactive state of the thermostabilized β1-adrenoceptor have been determined bound to eight different ligands, including full agonists, partial agonists, inverse agonists and biased agonists. Comparison of the structures shows distinct differences within the binding pocket that correlate with the pharmacological properties of the ligands. These data suggest that full agonists stabilize a structure with a contracted binding pocket and a rotamer change of serine (5.46) compared with when antagonists are bound. Inverse agonists may prevent both of these occurrences, whereas partial agonists stabilize a contraction of the binding pocket but not the rotamer change of serine (5.46). It is likely that subtle changes in the interactions between transmembrane helix 5 (H5) and H3/H4 on agonist binding promote the formation of the activated state.
Convergent mechanisms for dysregulation of mitochondrial quality control in metabolic disease: implications for mitochondrial therapeutics
Authors: Mitchell Tanecia , Chacko Balu , Ballinger Scott W. , Bailey Shannon M. , Zhang Jianhua , Darley-Usmar Victor
Published: January 2013

Mitochondrial dysfunction is associated with a broad range of pathologies including diabetes, ethanol toxicity, metabolic syndrome and cardiac failure. It is now becoming clear that maintaining mitochondrial quality through a balance between biogenesis, reserve capacity and mitophagy is critical in determining the response to metabolic or xenobiotic stress. In diseases associated with metabolic stress, such as Type II diabetes and non-alcoholic and alcoholic steatosis, the mitochondria are subjected to multiple ‘hits’ such as hypoxia and oxidative and nitrative stress, which can overwhelm the mitochondrial quality control pathways. In addition, the underlying mitochondrial genetics that evolved to accommodate high-energy demand, low-calorie supply environments may now be maladapted to modern lifestyles (low-energy demand, high-calorie environments). The pro-oxidant and pro-inflammatory environment of a sedentary western lifestyle has been associated with modified redox cell signalling pathways such as steatosis, hypoxic signalling, inflammation and fibrosis. These data suggest that loss of mitochondrial quality control is intimately associated with the aberrant activation of redox cell signalling pathways under pathological conditions. In the present short review, we discuss evidence from alcoholic liver disease supporting this concept, the insights obtained from experimental models and the application of bioenergetic-based therapeutics in the context of maintaining mitochondrial quality.
Palmitoylation of serotonin receptors
Authors: Gorinski Nataliya , Ponimaskin Evgeni
Published: January 2013

The covalent attachment of palmitic acid to one or more cysteine residues (S-palmitoylation) is a widespread modification of signalling proteins. With the finding that palmitoylation is a dynamic process, it is now widely accepted that repeated cycles of palmitoylation/depalmitoylation could be involved in the regulation of multiple signalling processes. Palmitoylation also represents a common post-translational modification of the GPCRs (G-protein-coupled receptors). Functionally, palmitoylation of GPCRs has been shown to play a central role in the regulation of multiple receptor functions, including determining the efficiency and selectivity of G-protein coupling, receptor phosphorylation and desensitization, endocytosis and transport to the plasma membrane. The present review summarizes our current knowledge of the palmitoylation of serotonin (5-hydroxytryptamine) receptors and its role in the regulation of receptor functions.
Exosomes and communication between tumours and the immune system: are all exosomes equal?
Authors: Bobrie Angélique , Théry Clotilde
Published: January 2013

Communication between cells is particularly important during tumour progression. Communication can take place through direct cell–cell interactions, but also through extracellular secretion of mediators acting at a distance. These mediators can be either soluble molecules or more complex structures called membrane vesicles, enclosing soluble factors within a lipid bilayer. A variety of extracellular membrane vesicles have been described, for instance microvesicles, ectosomes and a subtype called exosomes. The role of exosomes in tumour progression has been studied extensively in the last 10 years. In the present mini-review, we discuss our recent results, first showing the heterogeneity of the vesicles called exosomes and the probable existence of subpopulations of these exosomes, and secondly demonstrating that in vivo secretion of exosomes by some tumours can promote tumour progression, but that such a function cannot be generalized to all tumours and all exosomes.
A 32-month follow-up study of nanovesicle concentrations in blood from 12 patients with gastrointestinal stromal tumour treated with imatinib
Authors: Ogorevc Eva , Štukelj Roman , Bedina-Zavec Apolonija , Šuštar Vid , Šimundić Metka , Kralj-Iglič Veronika , Janša Rado
Published: January 2013

Clinical studies have indicated that the NV (nanovesicle) concentration in blood samples is a potential indicator of clinical status and can be used to follow the development of the disease. For 32 months, we monitored the effect of imatinib treatment on NV concentrations in blood samples from 12 patients with GIST (gastrointestinal stromal tumour). The NV concentration before the treatment increased with respect to control by a factor of 3.5 on average (range 2.6–9.2). The first week after initiation of the treatment, the NV concentration increased considerably, by a factor of 13 on average (range 5.9–21.2), whereas on average, after 1 month, it decreased to the level of the control and remained at that level for at least 1.5 years. Recent assessment (after 2.5 years) showed a somewhat increased NV concentration, by a factor of 2 on average (range 0.7–3.9). Low NV concentrations in blood samples during the treatment reflect a favourable effect of imatinib in these patients and no remission of the disease was hitherto observed.
The activation of the CGRP receptor
Authors: Barwell James , Wheatley Mark , Conner Alex C. , Taddese Bruck , Vohra Shabana , Reynolds Christopher A. , Poyner David R.
Published: January 2013

The CGRP (calcitonin gene-related peptide) receptor is a family B GPCR (G-protein-coupled receptor). It consists of a GPCR, CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activity modifying protein 1). RAMP1 is needed for CGRP binding and also cell-surface expression of CLR. CLR is an example of a family B GPCR. Unlike family A GPCRs, little is known about how these receptors are activated by their endogenous ligands. This review considers what is known about the activation of family B GPCRs and then considers how this might be applied to CLR, particularly in light of new knowledge of the crystal structures of family A GPCRs.
Glutathione and γ-glutamylcysteine in the antioxidant and survival functions of mitochondria
Authors: Quintana-Cabrera Ruben , Bolaños Juan P.
Published: January 2013

Mitochondria are both the main producers and targets of ROS (reactive oxygen species). Among the battery of antioxidants that protect mitochondria from ROS, GSH is thought to be essential for the organelle antioxidant function. However, mitochondria cannot synthesize GSH de novo, thus depending on an efficient transport from the cytosol to maintain their redox status. In the present article, we review recent data suggesting that the cellular redox control might not be the main function of GSH, and that its immediate precursor, γGC (γ-glutamylcysteine), can take over the antioxidant role of GSH and protect the mitochondria from excess ROS. Together, GSH and γGC may thus represent an as yet unrecognized defence system relevant for degenerative processes associated with the imbalance in the cellular redox control.
Microvesiculation and Disease
Authors: Inal Jameel M. , Fairbrother Una , Heugh Sheelagh
Published: January 2013

The important roles of extracellular vesicles in the pathogenesis of various diseases are rapidly being elucidated. As important vehicles of intercellular communication, extracellular vesicles, which comprise microvesicles and exosomes, are revealing important roles in cancer tumorigenesis and metastases and in the spread of infectious disease. The September 2012 Focused Meeting ‘Microvesiculation and Disease’ brought together researchers working on extracellular vesicles. The papers in this issue of Biochemical Society Transactions review work in areas including HIV infection, kidney disease, hypoxia-mediated tumorigenesis and down-regulation of immune cell functions in acute myeloid leukaemia by tumour-derived exosomes. In all cases, microvesicles and exosomes have been demonstrated to be important factors leading to the pathophysiology of disease or indeed as therapeutic vehicles in possible new treatments. The aim was, having enhanced our molecular understanding of the contribution of microvesicles and exosomes to disease in vitro, to begin to apply this knowledge to in vivo models of disease.
Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling
Authors: Yin Fei , Jiang Tianyi , Cadenas Enrique
Published: January 2013

Mitochondria generate second messengers, such as H2O2, that are involved in the redox regulation of cell signalling and their function is regulated by several cytosolic signalling pathways. IIS [insulin/IGF1 (insulin-like growth factor 1) signalling] in the brain proceeds mainly through the PI3K (phosphatidylinositol 3-kinase)–Akt (protein kinase B) pathway, which is involved in the regulation of synaptic plasticity and neuronal survival via the maintenance of the bioenergetic and metabolic capacities of mitochondria. Conversely, the JNK (c-Jun N-terminal kinase) pathway is induced by increased oxidative stress and JNK translocation to the mitochondrion results in impairment of energy metabolism. Moreover, IIS and JNK signalling interact with and antagonize each other. This review focuses on functional outcomes of a metabolic triad that entails the co-ordination of mitochondrial function (energy transducing and redox regulation), IIS and JNK signalling, in the aging brain and in neurodegenerative disorders, such as Alzheimer's disease.
Exosomes as a novel way of interneuronal communication
Authors: Chivet Mathilde , Javalet Charlotte , Hemming Fiona , Pernet-Gallay Karin , Laulagnier Karine , Fraboulet Sandrine , Sadoul Rémy
Published: January 2013

Exosomes are small extracellular vesicles which stem from endosomes fusing with the plasma membrane; they contain lipids, proteins and RNAs that are able to modify receiving cells. Functioning of the brain relies on synapses, and certain patterns of synaptic activity can change the strength of responses at sparse groups of synapses, to modulate circuits underlying associations and memory. These local changes of the synaptic physiology in one neuron driven by another have, so far, been explained by classical signal transduction modulating transcription, translation and post-translational modifications. We have accumulated in vitro evidence that exosomes released by neurons in a way depending on synaptic activity can be recaptured by other neurons. Some lipids, proteins and RNAs contained in exosomes secreted by emitting neurons could directly modify signal transduction and protein expression in receiving cells. Exosomes may be an ideal mechanism for anterograde and retrograde information transfer across synapses underlying local changes in synaptic plasticity. Exosomes might also participate in the spreading across the nervous system of pathological proteins such as PrPSc (abnormal disease-specific conformation of prion protein), APP (amyloid precursor protein) fragments, phosphorylated tau or α-synuclein.
Regulation of the cardiac Na+ pump by palmitoylation of its catalytic and regulatory subunits
Authors: Howie Jacqueline , Tulloch Lindsay B. , Shattock Michael J. , Fuller William
Published: January 2013

The Na+/K+-ATPase (Na+ pump) is the principal consumer of ATP in multicellular organisms. In the heart, the Na+ gradient established by the pump is essential for all aspects of cardiac function, and appropriate regulation of the cardiac Na+ pump is therefore crucial to match cardiac output to the physiological requirements of an organism. The cardiac pump is a multi-subunit enzyme, consisting of a catalytic α-subunit and regulatory β- and FXYD subunits. All three subunits may become palmitoylated, although the functional outcome of these palmitoylation events is incompletely characterized to date. Interestingly, both β- and FXYD subunits may be palmitoylated or glutathionylated at the same cysteine residues. These competing chemically distinct post-translational modifications may mediate functionally different effects on the cardiac pump. In the present article, we review the cellular events that control the balance between these modifications, and discuss the likely functional effects of pump subunit palmitoylation.
Regulatory RNAs in archaea: first target identification in Methanoarchaea
Authors: Prasse Daniela , Ehlers Claudia , Backofen Rolf , Schmitz Ruth A.
Published: January 2013

sRNAs (small non-coding RNAs) representing important players in many cellular and regulatory processes have been identified in all three domains of life. In Eukarya and Bacteria, functions have been assigned for many sRNAs, whereas the sRNA populations in Archaea are considerably less well characterized. Recent analyses on a genome-wide scale particularly using high-throughput sequencing techniques demonstrated the presence of high numbers of sRNA candidates in several archaea. However, elucidation of the molecular mechanism of sRNA action, as well as understanding their physiological roles, is in general still challenging, particularly in Archaea, since efficient genetic tools are missing. The identification of cellular targets of identified archaeal sRNAs by experimental approaches or computational prediction programs has begun only recently. At present, targets have been identified for one archaeal sRNA, sRNA162 in Methanosarcina mazei, which interacts with the 5′ region of its targets, a cis-encoded and a trans-encoded target, blurring the paradigm of a border between cis- and trans-encoded sRNAs. Besides, the first experimental implications have been obtained in Haloarchaea and Pyrobaculum that archaeal sRNAs also target 3′ regions of mRNAs. The present review summarizes our current knowledge on archaeal sRNAs and their biological functions and targets.
Membrane vesicles, nanopods and/or nanotubes produced by hyperthermophilic archaea of the genus Thermococcus
Authors: Marguet Evelyne , Gaudin Marie , Gauliard Emilie , Fourquaux Isabelle , le Blond du Plouy Stephane , Matsui Ikuo , Forterre Patrick
Published: January 2013

Thermococcus species produce MVs (membrane vesicles) into their culture medium. These MVs are formed by a budding process from the cell envelope, similar to ectosome formation in eukaryotic cells. The major protein present in MVs of Thermococci is a peptide-binding receptor of the OppA (oligopeptide-binding protein A) family. In addition, some of them contain a homologue of stomatin, a universal membrane protein involved in vesiculation. MVs produced by Thermococcus species can recruit endogenous or exogenous plasmids and plasmid transfer through MVs has been demonstrated in Thermococcus kodakaraensis. MVs are frequently secreted in clusters surrounded by S-layer, producing either big protuberances (nanosphere) or tubular structures (nanotubes). Thermococcus gammatolerans and T. kodakaraensis produce nanotubes containing strings of MVs, resembling the recently described nanopods in bacteria, whereas Thermococcus sp. 5-4 produces filaments whose internal membrane is continuous. These nanotubes can bridge neighbouring cells, forming cellular networks somehow resembling nanotubes recently observed in Firmicutes. As suggested for bacteria, archaeal nanopods and/or nanotubes could be used to expand the metabolic sphere around cells and/or to promote intercellular communication.
Evolution of Na+ and H+ bioenergetics in methanogenic archaea
Authors: Schlegel Katharina , Müller Volker
Published: January 2013

Methanogenic archaea live at the thermodynamic limit of life and use sophisticated mechanisms for ATP synthesis and energy coupling. The group of methanogens without cytochromes use an Na+ current across the membrane for ATP synthesis, whereas the cytochrome-containing methanogens have additional coupling sites that also translocate protons. The ATP synthase in this group is promiscuous and uses Na+ and H+ simultaneously.
Archaeal biofilms: widespread and complex
Authors: Fröls Sabrina
Published: January 2013

Biofilms or multicellular structures become accepted as the dominant microbial lifestyle in Nature, but in the past they were only studied extensively in bacteria. Investigations on archaeal monospecies cultures have shown that many archaeal species are able to adhere on biotic and abiotic surfaces and form complex biofilm structures. Biofilm-forming archaea were identified in a broad range of extreme and moderate environments. Natural biofilms observed are mostly mixed communities composed of archaeal and bacterial species of various abundances. The physiological functions of the archaea identified in such mixed communities suggest a significant impact on the biochemical cycles maintaining the flow and recycling of the nutrients on earth. Therefore it is of high interest to investigate the characteristics and mechanisms underlying the archaeal biofilm formation. In the present review, I summarize and discuss the present investigations of biofilm-forming archaeal species, i.e. their diverse biofilm architectures in monospecies or mixed communities, the identified EPSs (extracellular polymeric substances), archaeal structures mediating surface adhesion or cell–cell connections, and the response to physical and chemical stressors implying that archaeal biofilm formation is an adaptive reaction to changing environmental conditions. A first insight into the molecular differentiation of cells within archaeal biofilms is given.
Archaeal transcription: making up for lost time
Authors: Wojtas Magdalena N. , Abrescia Nicola G.A.
Published: January 2013

In recent years, emerging structural information on the aRNAP (archaeal RNA polymerase) apparatus has shown its strong evolutionary relationship with the eukaryotic counterpart, RNA Pol (polymerase) II. A novel atomic model of SshRNAP (Sulfolobus shibatae RNAP) in complex with dsDNA (double-stranded DNA) constitutes a new piece of information helping the understanding of the mechanisms for DNA stabilization at the position downstream of the catalytic site during transcription. In Archaea, in contrast with Eukarya, downstream DNA stabilization is universally mediated by the jaw domain and, in some species, by the additional presence of the Rpo13 subunit. Biochemical and biophysical data, combined with X-ray structures of apo- and DNA-bound aRNAP, have demonstrated the capability of the Rpo13 C-terminus to bind in a sequence-independent manner to downstream DNA. In the present review, we discuss the recent findings on the aRNAP and focus on the mechanisms by which the RNAP stabilizes the bound DNA during transcription.