bluuebunny/crossref_metadata_2025 huggingface dataset:
F-actin asymmetry and the endoplasmic reticulum–associated TCC-1 protein contribute to stereotypic spindle movements in theCaenorhabditis elegansembryo
Authors: Berends Christian W. H. , Muñoz Javier , Portegijs Vincent , Schmidt Ruben , Grigoriev Ilya , Boxem Mike , Akhmanova Anna , Heck Albert J. R. , van den Heuvel Sander
Published: May 2013

The microtubule spindle apparatus dictates the plane of cell cleavage in animal cells. During development, dividing cells control the position of the spindle to determine the size, location, and fate of daughter cells. Spindle positioning depends on pulling forces that act between the cell periphery and astral microtubules. This involves dynein recruitment to the cell cortex by a heterotrimeric G-protein α subunit in complex with a TPR-GoLoco motif protein (GPR-1/2, Pins, LGN) and coiled-coil protein (LIN-5, Mud, NuMA). In this study, we searched for additional factors that contribute to spindle positioning in the one-cell Caenorhabditis elegans embryo. We show that cortical actin is not needed for Gα–GPR–LIN-5 localization and pulling force generation. Instead, actin accumulation in the anterior actually reduces pulling forces, possibly by increasing cortical rigidity. Examining membrane-associated proteins that copurified with GOA-1 Gα, we found that the transmembrane and coiled-coil domain protein 1 (TCC-1) contributes to proper spindle movements. TCC-1 localizes to the endoplasmic reticulum membrane and interacts with UNC-116 kinesin-1 heavy chain in yeast two-hybrid assays. RNA interference of tcc-1 and unc-116 causes similar defects in meiotic spindle positioning, supporting the concept of TCC-1 acting with kinesin-1 in vivo. These results emphasize the contribution of membrane-associated and cortical proteins other than Gα–GPR–LIN-5 in balancing the pulling forces that position the spindle during asymmetric cell division.
Remaking the Rhythms of Life
Authors: Zimmer Oliver
Published: May 2013

Across Europe, the late nineteenth century marked a period of rapid economic growth, increased migration, cultural and technical innovation, religious conflict, and inter-state competition. In Germany, these developments were further accentuated by the creation of the imperial state in 1870/71 and the conflicting hopes and expectations it provoked within the larger public. Attempting to make sense of this turbulent period of German history, historians have frequently reverted to terms such as industrialization, urbanization, nation-formation, modernity, or modernization. Using the prism of comparative urban history, this book highlights the limitations of these conceptual abstractions and reveals the artificiality of the separation of local and national approaches to the past. It shows how men and women drew on their creative energies to instigate change at various levels. Focusing on conflicts over the local economy, elementary schools, the theatre and citizenship, and looking at nationalist and religious processions, Remaking the Rhythms of Life examines how urban residents sought to regain a sense of place in a changing world: less by resisting the novel than by reconfiguring their environments in ways that reflected their sensibilities and aspirations; less by lamenting the decline of civic virtues than by creating surroundings that proved sufficiently meaningful to sustain lives. In their capacity as consumers or citizens, members of religious or economic associations, people embarked on a multitude of journeys. As they did, larger themes such as religion, nationalism and the state became intertwined with everyday affairs and concerns.
Emotional communication in monkeys: Music to their ears?
Authors: Snowdon Charles T. , Teie David
Published: May 2013

Results are equivocal on whether nonhuman animals can appreciate music. Although human music is unique to humans, we argue that the emotional components of music have an evolutionary history. We present a theory of emotional origins of music and show that music/emotional features are found in vocalizations of cotton-top tamarins, a small New World monkey. We composed music comprising our hypothesized emotional features in the frequency range and tempos of tamarin vocalizations. These compositions induced calming and arousing emotional states in the monkeys, although human-based music with similar features had little effect. Other species may incorporate similar emotional features into their calls as we use to induce emotions in music Animal calls not only communicate a caller’s emotional state but may also induce emotional responses in listeners. Attempts to play human-based music to other species as enrichment are likely to be misguided, with human-based music being irritating or merely ineffective.
Vocal expression of emotions in laughter
Authors: Szameitat Diana P. , Wildgruber Dirk , Alter Kai
Published: May 2013

Human laughter is a complex behavior expressed not only in the context of play as it is in animals, but also in various emotional states. This suggests that throughout evolution human laughter has adopted more complex communicative functions to reflect the increased complexity of human social interaction. This chapter outlines recent findings on perception, acoustic cues, and neural correlates of laughter sounds. Laughter sounds can be classified according to the emotional categories and according to different emotional dimensions, such as arousal, valence and dominance. Moreover, the acoustical correlates of laughter expressing different emotions can be discriminated on the basis of a small parameter set. Finally, the evolutionary diversification of ecological functions of laughter is associated with distinct cerebral responses underlying laughter perception. These findings indicate that human laughter is a multifaceted behavior serving distinct social functions.
Part I, 2 Christian Perspectives
Authors: Rex Ahdar , Ian Leigh
Published: May 2013

This chapter examines various theological, specifically Christian, justifications for religious freedom. For long periods Christians gave vent to their unswerving conviction that they alone heard from God, and all other faiths were demonic. However, Christian thought eventually came round to the notion that the principle of religious liberty was right. It was implied in the Scriptures. A series of overlapping convictions comprise the contemporary Christian case for the freedom of religion. These are summarized in the form of eight principles: the principle of voluntariness; the Christological injunction; the persecution injunction; the fallibility principle; the eschatological or providential confidence; the ecumenical or universal principle; the principle of the unrestricted conscience; and the dual authority principle.
Part II, 4 Models of Religion–State Relations
Authors: Rex Ahdar , Ian Leigh
Published: May 2013

This chapter surveys the various types of interaction between religion and government. The object is not to posit yet another typology of religion-state relations, but to consider which model or models best advance religious freedom in a liberal state. These models include theocracy, Erastianism, separationism and secularism, religious ‘establishment’, Pluralist models, neutrality models, and the competitive market model. Overall, it is difficult to single out one model of the religion-state relationship as indisputably the best in terms of religious freedom. Several systems — mild establishment, pluralism, and substantive neutrality — seem to score highly in that they recognize that a measure of interaction and cooperation between government and religious communities is useful. Others, by contrast, such as theocracy and Erastianism, can be safely rejected as inimicable with religious freedom. Some models, such as separationism, deserve at best only cautious approval. Its secularist philosophy can in practice produce a climate of hostility to religion and its free exercise.
Part II, 5 Legal Protection of Religious Freedom
Authors: Rex Ahdar , Ian Leigh
Published: May 2013

This chapter first considers the broad nature of ‘religious freedom’. It then outlines the various systems of constitutional protection for religious liberty in different nations such as the United States, the United Kingdom, Canada, and so on, as well as the guarantees in international law for religious rights. Next, it explores the difficult question of how one defines ‘religion’ for the purpose of recognizing religious liberty.
Part II, 6 Limits to Religious Freedom
Authors: Rex Ahdar , Ian Leigh
Published: May 2013

This chapter discusses the ways that religious freedom can be restricted to more ‘manageable’ proportions. There are at least five such limiting strategies. Four of them involve making a distinction between the realm that is unhampered by the law and the restricted realm by focusing on the type of belief or the consequences of the action involved. These are distinctions between: belief and action per se; other and self-regarding acts; religiously compelled and religiously motivated acts; and core and peripheral beliefs. The chapter explains and critiques each one before considering a fifth strategy, reasonable limitation. It explains why this strategy is preferred over the others.
Part III, 8 Education
Authors: Rex Ahdar , Ian Leigh
Published: May 2013

This chapter discusses the protection of religious freedom in education, in both state and private schooling. As an important aspect of human societies, education about religion obviously features in the educational curriculum. More contentious, however, is the question of whether schools should themselves foster or permit opportunities for religious practice. Less obviously, but no less contentious, are issues concerning the content of the ‘secular’ curriculum in areas such as science or sex education. The material taught may sometimes conflict with the religious beliefs of a pupil or her parents. The chapter begins, however, with an issue that is fundamental to understanding the ongoing controversies surrounding all these questions — the differing understandings of liberal theorists and Christians of the very purpose of education.
1 Vectors and fields in space
Authors: Wong Chun Wa
Published: May 2013

Vector calculus is discussed, including vector algebra, vector differentiation and integrations of scalar and vector fields, integral theorems of Green and Stokes, and the Helmholtz decomposition of a vector field. Vector differential operators are obtained in orthogonal curvilinear coordinate systems.
7 Special functions
Authors: Wong Chun Wa
Published: May 2013

Special functions are advanced functions frequently used in science and engineering. The properties of Legendre, Hermite, Laguerre, Chebyshev and spherical harmonics polynomials and Bessel functions are obtained. The use of generating functions, recursion formulas, differential relations, Rodrigues formulas and differential equations to define and manipulate these functions are described. Their general treatments as classical orthogonal polynomials and as Sturm Liouville eigenfunctions are given.
8 Functions of a complex variable
Authors: Wong Chun Wa
Published: May 2013

Functions of a complex variable are shown to be more complete and rigid than functions of a real variable. Analytic functions with well defined derivatives satisfy two Cauch–Riemann conditions. Multivalued functions can be made single-valued on a multi-sheet Riemann surface. The values of an analytic function in a region of the complex plane are completely defined by the knowledge of their values on a closed boundary of the region. Important properties and techniques of complex analysis are described. These include Taylor and Laurent expansions, contour integration and residue calculus, Green's functions, Laplace transforms and Bromwich integrals, dispersion relations and asymptotic expansions. Analytic functions are defined by their properties at the locations called singularities (poles and branch cuts) where they cease to be analytic. This feature makes analytic functions of particular interest in the construction of physical theories.
9 Applying (PEP)
Authors: Titelbaum Michael G.
Published: May 2013

This chapter explains how to apply the Certainty-Loss Framework (CLF) to stories involving self-locating belief and context-sensitivity. This formal modeling framework and its distinctive updating rules (Generalized Conditionalization and the Proper Expansion Principle) were defined and defended in previous chapters. Here the framework is used to model rational requirements in a number of stories, most importantly Adam Elga’s highly controversial Sleeping Beauty Problem. After analyzing solutions to that problem offered by Elga and by David Lewis, the chapter shows two different ways of constructing CLF models that refute Lewis’s solution (without invoking indifference principles or even Lewis’s Principal Principle). Objections to the CLF models are considered and rebutted.
11 Indifference principles and quantum mechanics
Authors: Titelbaum Michael G.
Published: May 2013

Adam Elga argues that in certain cases when an agent cannot tell which of many subjectively indistinguishable experiences she is currently having, she should assign equal credence to being in each. This chapter derives instances of that indifference principle from the Certainty-Loss Framework (CLF) proposed and defended in this book, then defends those instances against criticisms from Brian Weatherson. Next, the chapter applies CLF to cases involving personal fission or cloning. Finally, the chapter uses CLF to examine how agents should assign degrees of belief to the outcomes of various quantum experiments if the Everett interpretation of quantum mechanics is true. If the Everettian interpretation can make sense of nonextreme degrees of belief about quantum outcomes to begin with, then CLF provides plausible results about how those degrees of belief should update over time.
Dispositions, Character Traits, and Virtues
Authors: Miller Christian
Published: May 2013

This chapter does some preliminary conceptual work in order to clarify how terms such as ‘character traits,’ ‘dispositions,’ and ‘virtues’ will be used. Most important of all, by getting clearer conceptually in this area, the chapter aims to show that we can make sense of the idea that there are character traits which are neither virtues nor vices. This will then set the stage for the chapters to come which argue that these are precisely the traits that most of us actually possess.
Guilt and Helping
Authors: Miller Christian
Published: May 2013

This chapter surveys some of the empirical work on guilt and helping in order to ultimately advance both a negative and positive claim. The negative claim is that the experimental results can be plausibly interpreted to suggest that most people do not have the virtue of compassion. The positive claim is that instead most people seem to be (i) disposed to help more frequently when feeling guilty, and (ii) when they do help because of this emotion, they do so in certain consistent ways across time and situations, as a result of (iii) the casual activity of mental state dispositions which are not altruistic.
Empathy and Helping
Authors: Miller Christian
Published: May 2013

Feeling empathy for someone in distress is also known to dramatically increase helping. And there is good reason to believe that the motivation to help which arises from empathizing with another is altruistic motivation rather than egoistic motivation, moralistic motivation, or motivation of some other kind. This will be an important result, not only for further developing the account of Mixed Traits later on, but also for examining how realistic it is to think that many of us have acquired the virtue of compassion.
Ingredients of Polarity Sensitivity
Authors: Watanabe Akira
Published: May 2013

This chapter will take up two types of bipolar items in Japanese to identify various factors that contribute to polarity sensitivity. It has been well known since Fauconnier (1975) that scalar semantics is closely related to licensing of negative polarity items. There are indeed languages like Dutch and Hindi that have negative polarity items overtly marked with a scalar focus particle. The chapter show that there are other morphological characteristics that play important roles in polarity sensitivity. Furthermore, the chapter suggest that the relation between negative concord and negative polarity must be taken into account when concord items and polarity items are morphologically very similar.
BinominalEach
Authors: Stowell Tim
Published: May 2013

The chapter proposes a new analysis of the binominal each construction. This construction is of interest because it presents the quantifier each in a non‐standard position for a quantifier, widely assumed to be located inside an indefinite NP over which it unambiguously takes scope. While the earliest generative analysis of binominal each took it to be a variant of floated each, derived by rightward Q‐float, later analyses provided a distinct derivation, base‐generating it inside the indefinite NP that it co‐occurs with. This later assumption makes it problematic to assimilate binominal each to current approaches to QR, and to the theory underlying the most widely held current approach to floated quantifiers. The chapter argues here for an analysis partly resembling the earliest account, whereby binominal each and floated each are fundamentally unified, though differing from it on a number of points. In particular, The chapter adopts a variant of Sportiche's (1988) approach to Q‐float, combined with a derivation involving leftward movement of the indefinite and remnant VP movement. New facts about the syntactic distribution of binominal each are brought to light that support the revised analysis.
Campaign Finance Reform: a Collection of Null Results
Authors: Bowler Shaun , Donovan Todd
Published: May 2013

Chapter 5 provides additional tests of the effects of election reform by assessing the consequences of campaign finance rules. Money in politics attracts a series of complaints—and raises a series of concerns about untoward and unwarranted influence of money in politics. The UK and US have seen the adoption of a series of finance reforms over the past ten to twenty years aimed at alleviating these concerns, and introducing transparency into the system in an attempt to restore public confidence in electoral politics. But the evidence from both the UK and the US shows that these reforms have simply not had the effect of reducing these concerns among voters. Voters seem to be just as cynical about the role of money politics after these reforms as before.
International Corporate Debt Markets
Authors: MANUELA GERANIO , ISSAM HALLAK
Published: May 2013

International debt markets have gone through major changes during the past 20 years. Reduction in capital controls and privatization of the manufacturing and banking sectors created a higher demand for international debt, which is debt denominated in nondomestic currencies, from the private sector. This major change had important consequences. While international debt crises used to be attributed to state mismanagement of borrowed funds, such crises are now largely due to poor performance in the private sector. Yet, corporate debts have several advantages compared with sovereign debts. The chapter begins by discussing new developments and describing the impact on country risk and cost of capital. Next, the chapter explains how these developments affect the international financial architecture by describing the differences between corporate and sovereign debt. International bond issuance and the latest developments are then discussed to explain the impact of these main changes.
Irrationality, Mental Capacities, and Neuroscience1
Authors: Craigie Jillian , Coram Alicia
Published: May 2013

The concept of mental capacity is of central importance in private law, where it is used to determine a person’s ability to consent to or refuse medical treatment. Questions about psychological capacities are also increasingly playing a role in the criminal law, where culpability is being understood in terms of the ability for rational action. In both contexts, progress in the neurosciences has raised questions about how it might inform these decisions. We investigate this question by examining the relationship between judgments about capacity, norms of rationality and underlying psychological and neural mechanisms. The role played by normative requirements in both kinds of determination, and differences in the norms that are relevant, are used to draw conclusions about what neuroscience can offer in these two legal contexts. We conclude that current debates in moral psychology call into question key assumptions that underlie optimism about the usefulness of neuroscience for assessing culpability.
The Viper on the Hearth
Authors: Givens Terryl L.
Published: May 2013

In 1997 this book was praised as a new classic in Mormon studies. In the wake of Mormon-inspired and -created artistic, literary, and political activity—today's “Mormon moment”—this book has now been revised and updated to address the continuing presence and reception of the Mormon image in contemporary culture. It provides a comprehensive study of how Mormons have been constructed in popular culture in the nineteenth and twentieth centuries. Interdisciplinary research in this book relies on historical and literary sources. The book also provides novel scholarship on religious formation, identity, and persecution.
Synergistic effects of TOR and proteasome pathways on the yeast transcriptome and cell growth
Authors: Zhang Nianshu , Quan Zhenzhen , Rash Bharat , Oliver Stephen G.
Published: May 2013

The proteasome has been implicated in gene transcription through a variety of mechanisms. How the proteasome regulates genome-wide transcription in relation to nutrient signalling pathways is largely unknown. Using chemical inhibitors to compromise the functions of the proteasome and/or TORC1, we reveal that the proteasome and TORC1 synergistically promote the expression of
de novo
purine and amino acid biosynthetic genes, and restrict the transcription of those associated with proteolysis, starvation and stress responses. Genetic analysis demonstrates that TORC1 negatively regulates both the Yak1 and Rim15 kinases to modulate starvation-specific gene expression mediated by the Msn2/4 and Gis1 transcription factors. Compromising proteasome function induces starvation-specific gene transcription in exponential-phase cells and abrogates the strict control of such expression by Yak1 and Rim15 in rapamycin-treated cells, confirming that the proteasome functions to ensure stringent control of the starvation response by the TOR pathway. Synergy between the two pathways is also exhibited on cell growth control. Rpn4-dependent upregulation of proteasomal genes and a catalytically competent 20S proteasome are essential for yeast cells to respond to reduced TORC1 activity. These data suggest that the proteasome and the TOR signalling pathway synergistically regulate a significant portion of the genome to coordinate cell growth and starvation response.
Pneumocystis jirovecii multilocus genotyping profiles in Northern Ireland
Authors: Curran Tanya , McCaughey Conall , Coyle Peter V.
Published: May 2013

Pneumocystis jirovecii causes pneumonia, a severe opportunistic infection in immunosuppressed patients that has both person-to-person airborne transmission and environmental transmission as important routes of infection. An increasing incidence of P. jirovecii in Northern Ireland prompted a detailed epidemiological and molecular review that included enhanced surveillance on all lower respiratory specimens. Genotyping of these P. jirovecii positive specimens was undertaken using multiple locus sequence typing (MLST) targeting known variable regions of the P. jirovecii genome. Multiple circulating types were found among all patient risk categories. However, a predominance of one MLST type was found in a P. jirovecii outbreak amongst the renal transplant population. Our results demonstrate the diversity of P. jirovecii strains amongst the local immunosuppressed cohort and highlight the importance of genotyping in the investigation of common sources of P. jirovecii amongst immunosuppressed patients.
Gut solutions to a gut problem: bacteriocins, probiotics and bacteriophage for control of Clostridium difficile infection
Authors: Rea Mary C. , Alemayehu Debebe , Ross R. Paul , Hill Colin
Published: May 2013

Clostridium difficile infection (CDI) is a major cause of morbidity and mortality among hospitalized patients and imposes a considerable financial burden on health service providers in both Europe and the USA. The incidence of CDI has dramatically increased in recent years, partly due to the emergence of a number of hypervirulent strains. The most commonly documented risk factors associated with CDIs are antibiotic usage leading to alterations of the gut microbiota, age >65 years and long-term hospital stay. Since standard therapies for antibiotic-associated diarrhoea and CDI have limited efficacy, there is now an urgent need for alternative therapeutics. In this review, we outline the current state of play with regard to the potential of gut-derived bacteriocins, probiotics and phage to act as antimicrobial agents against CDI in the human gut.
Bromidobis[2-(pyridin-2-yl)methanol-κ2N,O]copper(II) bromide monohydrate
Authors: Lah Nina , Lapanje Katja
Published: May 2013

The title compound, [CuBr(C6H7NO)2]Br·H2O, is an ionic mononuclear complex in which the [CuBr(C6H7NO)2]+cation possesses distorted square-pyramidal geometry. The CuIIcentre is coordinated by two neutral 2-(pyridin-2-yl)methanol (2-pyMeOH) ligands and a terminal bromide ligand. The 2-pyMeOH ligands are coordinated in a bidentate chelating manner through the pyridine N and hydroxy O atoms, forming a five-membered chelate ring with the CuIIcentre. The planes of the pyridine rings are twisted by 58.71 (14)° with respect to each other. The charge is balanced by a noncoordinating bromide anion which, together with a solvent water molecule, links the components through hydrogen bonds into infinite chains propagating along theaaxis. The mononuclear cations appear to associate in pairs through weak interactions between the metal atom of one cation and the halogen atom of an adjacent cation.
REVIEW: Managing urban ecosystems for goods and services
Authors: Gaston Kevin J. , Ávila‐Jiménez María L. , Edmondson Jill L.
Published: May 2013

Concomitant with the rise in the proportion of the global human population that resides in urban areas has been growth in awareness of the importance of the provision of ecosystem goods and services to those people. Urban areas are themselves of significance in this regard because of their areal extent, and hence the quantity of services falling within their bounds, and because of the need for local provision of services to urban residents.

Here, we review key challenges to the effective management of ecosystem goods and services within urban areas.

These challenges include the structure of green space, its temporal dynamics, spatial constraint on ecosystem service flows, occurrence of novel forms of flows, large numbers of land managers, conflicting management goals, possible differences between perceptions of urban dwellers and the reality of the distribution and flow of ecosystem services, and the ‘wicked’ nature of the problem of ecosystem service management.

Synthesis and applications. Urban areas present very particular combinations of challenges and opportunities for the management of ecosystem goods and services. The spatial and temporal heterogeneity of green spaces greatly complicates the maintenance and improvement in service provision as well as dramatically inflating costs. Spatial constraints on ecosystem service flows mean that these can be highly dependent on the maintenance of particular areas of connectivity, but also that provision of additional key points of connectivity may be disproportionately beneficial to those flows. The existence of novel forms of flows of ecosystem services in urban areas offers means of overcoming spatial constraints on more natural flows, but will require the development of new kinds of ecosystem process models to inform their design and management. The large numbers of land managers, conflicts between the best approaches for managing for different goods and services, and frequent differences between the perceptions of urban dwellers and the reality of urban landscapes create a complex management context. The management of ecosystem goods and services is closely allied to the challenges of conventional urban planning. However, applied ecology has a broad range of tools available to assist in determining solutions, including the use of high‐resolution remote sensing techniques, landscape ecology principles and theory (e.g. patch and matrix frameworks, meta‐population models), and systematic conservation planning approaches.
Cholinergic stimulation with pyridostigmine improves autonomic function in infarcted rats
Authors: de La Fuente Raquel N , Rodrigues Bruno , Moraes‐Silva Ivana C , Souza Leandro E , Sirvente Raquel , Mostarda Cristiano , De Angelis Kátia , Soares Pedro P , Lacchini Silvia , Consolim‐Colombo Fernanda , Irigoyen Maria‐Cláudia
Published: May 2013

In the present study we evaluated the effects of short‐term pyridostigmine bromide (0.14 mg/mL) treatment started early after myocardial infarction (MI) on left ventricular (LV) and autonomic functions in rats.

MaleWistar rats were divided into control, pyridostigmine, infarcted and infarcted + pyridostigmine‐treated groups. Pyridostigmine was administered in the drinking water, starting immediately afterMIor sham operation, for 11 days. Left ventricular function was evaluated indirectly by echocardiography and directly byLVcatheterization. Cardiovascular autonomic control was evaluated by baroreflex sensitivity (BRS), heart rate variability (HRV) and pharmacological blockade. All evaluations started after 7 days pyridostigmine treatment and were finalized after 11 days treatment.

Pyridostigmine prevented the impairment of +dP/dTand reduced theMIarea in infarcted + pyridostigmine compared with infarcted rats (7 ± 3%vs17 ± 4%, respectively). Mean blood pressure was restored in infarcted + pyridostigmine compared with infarcted rats (103 ± 3vs94 ± 3 mmHg, respectively). In addition, compared with the infarcted group, pyridostigmine improved BRS, as evaluated by tachycardic (1.6 ± 0.2vs2.5 ± 0.2 b.p.m./mmHg, respectively) and bradycardic (−0.42 ± 0.01vs−1.9 ± 0.1 b.p.m./mmHg) responses, and reduced the low frequency/high frequency ratio ofHRV(0.81 ± 0.11vs0.24 ± 0.14, respectively). These improvements are probably associated with increased vagal tone and reduced sympathetic tone in infarcted + pyridostigmine compared with infarcted rats.

In conclusion, the data suggest that short‐term pyridostigmine treatment started early afterMIcan improveBRS,HRVand parasympathetic and sympathetic tone in experimental rats. These data may have potential clinical implications because autonomic markers have prognostic significance afterMI.
MEFV gene mutations in Henoch–Schönlein purpura
Authors: Altug Umut , Ensari Cuneyt , Sayin Derya B. , Ensari Arzu
Published: May 2013

Aim

Coexistence of familial Mediterranean fever (FMF) with various systemic vasculitides, including Henoch–Schönlein purpura (HSP) and other inflammatory disorders has been reported and the MEFV gene has been suggested to play an important role in the pathogenesis of this association. In the present study, the mutation rate of the MEFV gene in HSP and its association with the clinical course of the disease were evaluated.

Method

The study group comprised 68 children (36 boys and 32 girls) diagnosed as having HSP. The spectrum and degree of organ involvement and the levels of serum C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were documented for each patient. Allele‐specific PCR using oligonucleotide probes which include 12 MEFV mutations (E148Q, P369S, F479L, M680I [G/C], M680I [G/A], I692del, M694V, M694I, K695R, V726A, A744S, R761H) were used for mutation analysis.

Results

Of the 68 patients studied, 50 (74%) showed no mutation, while 18 (26%) had MEFV mutation. Mutation analysis of the whole group revealed that 15 (22%) patients were heterozygous for one of the screened MEFV mutations, while three (4.5%) patients were compound heterozygous for two of the studied mutations, and one (1.5%) patient was homozygous for E148Q/E148Q mutations. Gastrointestinal and joint involvement, and edema were more frequently observed in patients with MEFV mutations, while ESR and CRP levels were significantly higher (P < 0.05) in patients with MEFV mutations.

Conclusion

MEFV mutations, especially, E148Q and M694V, mutations might be associated with HSP and may affect clinical presentation and laboratory findings in HSP patients.
Analysis of refill liquids for electronic cigarettes
Authors: Etter Jean‐François , Zäther Eva , Svensson Sofie
Published: May 2013

Aims

To assess levels of nicotine, nicotine degradation products and some specific impurities in commercial refill liquids for electronic cigarettes.

Design and setting

We analyzed 20 models of 10 of the most popular brands of refill liquids, using gas and liquid chromatography.

Measurements

We assessed nicotine content, content of the known nicotine degradation products and impurities, and presence of ethylene glycol and diethylene glycol.

Findings

The nicotine content in the bottles corresponded closely to the labels on the bottles. The levels of nicotine degradation products represented 0–4.4% of those for nicotine, but for most samples the level was 1–2%. Cis‐N‐oxide, trans‐N‐oxide, myosmine, anatabine and anabasine were the most common additional compounds found. Neither ethylene glycol nor diethylene glycol were detected.

Conclusion

The nicotine content of electronic cigarette refill bottles is close to what is stated on the label. Impurities are detectable in several brands above the level set for nicotine products in the European Pharmacopoeia, but below the level where they would be likely to cause harm.
Severity of the TGN1412 trial disaster cytokine storm correlated with IL‐2 release
Authors: Eastwood David , Bird Chris , Dilger Paula , Hockley Jason , Findlay Lucy , Poole Stephen , Thorpe Susan J. , Wadhwa Meenu , Thorpe Robin , Stebbings Richard
Published: May 2013

Aim

To determine if cytokine release with a solid phase assay is predictive of adverse responses for a range of therapeutic mAbs.

Methods

Cytokine ELISAs and a multi‐array system were used to compare responses generated by different therapeutic mAbs using a solid phase assay. Flow cytometry was employed to determine the cellular source of those cytokines.

Results

Only TGN1412 and muromonab‐CD3 stimulated CD4+ T‐cell mediated cytokine release characterized by significant (all P < 0.0001) IFNγ, TNFα, IL‐2, IL‐4, IL‐5, IL‐10, IL‐12, IL‐13, IL‐17 and IL‐22 release, comparable with T‐cell mitogen. Significantly greater (P < 0.0001) IL‐2 release with TGN1412 (2894–6051 pg ml−1) compared with muromonab‐CD3 (62–262 pg ml−1) differentiated otherwise comparable cytokine responses. Likewise, TGN1412 stimulated significantly more (P = 0.0001) IL‐2 producing CD4+ T‐cells than muromonab‐CD3 and induced Th1, Th2, Th17 and Th22 subsets that co‐release this cytokine. Significant TNFα release was observed with bevacizumab (P = 0.0001), trastuzumab (P = 0.0031) and alemtuzumab (P = 0.0177), but no significant IL‐2 release. TGN1412 and muromonab‐CD3 caused pro‐inflammatory cytokine release despite significantly (both P < 0.0001) increasing numbers of T‐cells with a regulatory phenotype.

Conclusions

The severity of the adverse response to TGN1412 compared with muromonab‐CD3 and other therapeutic mAbs correlates with the level of IL‐2 release.
Robot‐assisted partial nephrectomy vs laparoscopic cryoablation for the small renal mass: redefining the minimally invasive ‘gold standard’
Authors: Emara Amr M. , Kommu Sashi S. , Hindley Richard G. , Barber Neil J.
Published: May 2013

Objective

To identify differences between the ablative and extirpative minimally invasive techniques of laparoscopic cryoablation (LC) and robot‐assisted laparoscopic partial nephrectomy (RPN), respectively, in treating small renal tumours in terms of safety, peri‐operative morbidity and early oncological outcomes.

Patients and Methods

Between June 2008 and April 2012 56 patients underwent LC and from October 2010 to April 2012, 47 patients underwent RPN using the Da Vinci robotic platform (Intuitive Surgical, Sunnyvale, CA, USA).

Data on intra‐operative, postoperative and oncological outcomes were collected prospectively, and were analysed and compared for both groups.

Results

The median patient ages were 69 and 60 for the LC and RPN groups, respectively (P < 0.05). There was no significant difference in disease stage, but there was a significant difference in tumour size, with patients in the RPN group having larger tumours.

The mean operating times were 146 and 159 min for the LC and RPN groups, respectively (P = 0.094) and the mean blood loss was 47 and 94 mL for the LC and the RPN groups, respectively (P = 0.251). The median length of hospital stay (1 day) was the same for both groups and the mean warm ischaemia time was 23 min in the RPN group.

The marginal change in preoperative and 6‐week postoperative renal function was recorded: the mean postoperative increase in serum creatinine was 5.4 mmol/L in the LC group and 9.2 mmol/L in the RPN group.

Of the 47 patients in the RPN group, two (4.3%) were converted to laparoscopic radical nephrectomy because of difficulty in controlling bleeding during hilar dissection. Only two patients (3.6%) had recurrence in the LC group, both of whom were treated with re‐cryoablation. A total of 5.4% of patients in the LC and 4.3% in the RPN group had Clavien grade I postoperative complications, one patient in the LC group had a Clavien grade II complication, while 1.8 and 4.3% of patients had Clavien IIIb in the LC and RPN groups, respectively.

Conclusion

Our data confirm that LC is a successful, minimally invasive and safe treatment option for the management of small renal tumours, but the apparently similar characteristics of RPN suggest that an increasing proportion of patients, whatever their age or medical comorbidities, may be reasonably offered a robot‐assisted extirpative procedure with the likely benefit of lower risk of local recurrence and need for retreatment.
Diabetes distress in Type 1 diabetes—a new measurement fit for purpose
Authors: Joensen L. E. , Tapager I. , Willaing I.
Published: May 2013

Aims

To examine and assess (1) the internal consistency and validity of a Danish translation of the Diabetes Distress Scale (DDS17) among adults with Type 1 diabetes mellitus, (2) the properties of the brief version of DDS17 and (3) cut points for the DDS17.

Methods

Cross‐sectional survey of 2419 adults with Type 1 diabetes mellitus. Validated scales and questions measured diabetes distress (DDS17), diabetes empowerment (DES‐SF), healthy diet, physical activity, self‐rated health (SF‐12) and quality of life (WHOQoL‐BREF). An electronic patient record provided information about glycaemic control (HbA1c). We examined internal consistency, construct validity, subscale construction and cut points for determining clinically relevant diabetes distress, as well as two‐ and four‐item brief versions of the DDS17.

Results

The DDS17 had a Cronbach's alpha of 0.92; subscale alphas were 0.83–0.89. A four‐factor division into subscales was appropriate and the division corresponded closely to the four domains described in the development of the DDS17. The DDS17 correlated well with relevant measures; higher distress was correlated with low diabetes empowerment, low quality of life, unhealthy diet, not being physically active, poor glycaemic control and low scores on the mental component score of the SF‐12. A two‐item brief scale performed as well as a four‐item version. The relationship between DDS17 and outcomes did not suggest distinct cut points for DDS17.

Conclusions

Our results provide support for the use of this Danish adaptation of the DDS17 for assessing psychosocial distress among adults with Type 1 diabetes mellitus.
Serotonin 1A auto‐receptors are not sufficient to modulate anxiety in mice
Authors: Piszczek Lukasz , Schlax Kevin , Wyrzykowska Anna , Piszczek Agnieszka , Audero Enrica , Thilo Gross Cornelius
Published: May 2013

The neurotransmitter serotonin plays an important role in modulating diverse behavioral traits. Mice lacking the serotonin 1A receptor (Htr1a) show elevated avoidance of novel open spaces, suggesting that it has a role in modulating anxiety behavior. Htr1a is a Gαi‐coupled G‐protein‐coupled receptor expressed on serotonin neurons (auto‐receptor), where it mediates negative feedback of serotonin neuron firing. Htr1a is also expressed on non‐serotonin neurons (hetero‐receptor) in diverse brain regions, where it mediates an inhibitory effect of serotonin on neuronal activity. Debate exists about which of these receptor populations is responsible for the modulatory effects of Htr1a on anxiety. Studies using tissue‐specific transgenic expression have suggested that forebrain Htr1a hetero‐receptors are sufficient to restore normal anxiety behavior to Htr1a knockout mice. At the same time, experiments using tissue‐specific transgenic suppression of Htr1a expression have demonstrated that Htr1a auto‐receptors, but not forebrain hetero‐receptors, are necessary for normal anxiety behavior. One interpretation of these data is that multiple Htr1a receptor populations are involved in modulating anxiety. Here, we aimed to test this hypothesis by determining whether Htr1a auto‐receptors are sufficient to restore normal anxiety to Htr1a knockout animals. Transgenic mice expressing Htr1a under the control of the tryptophan hydroxylase 2 (Tph2) promoter showed restored Htr1a‐mediated serotonin negative feedback and hypothermia, but anxiety behavior indistinguishable from that of knockout mice. These data show that, in the absence of Htr1a hetero‐receptors, auto‐receptors are unable to have an impact on anxiety. When combined with previous data, these findings support the hypothesis that Htr1a auto‐receptors are necessary, but not sufficient, to modulate anxiety.
Laser treatment of urethral defects in geldings and stallions used as the primary treatment or in combination with a temporary subischial incision: Eight cases (2003–2011)
Authors: Madron M. , Schleining J. , Caston S. , Reinertson E. , Evans L.
Published: May 2013

Two geldings with haematuria and 6 stallions with haemospermia presented for evaluation between 2003 and 2011 to the Iowa State University Lloyd Veterinary Medical Center. Both geldings presented for haemorrhage at the end of urination. All stallions presented for evaluation of infertility following natural service or artificial insemination that was related to haemospermia. Urethroscopy identified a urethral defect in all 8 horses. Both geldings possessed a urethral rent. One stallion possessed a urethral varicosity while the remaining 5 possessed a urethral rent. Two geldings and 2 stallions received only laser treatment. The remaining 4 stallions received concurrent laser treatment with a temporary subischial incision (TSI) into the corpus spongiosum penis. All 6 stallions received 8 weeks of sexual rest after the completion of the surgical/laser treatment. Laser treatment alone was successful in resolving haematuria in one of 2 geldings. In the stallion group, all 4 horses with a urethral rent receiving laser treatment concurrent with a TSI resolved haemospermia. Of the remaining stallions, one with a urethral varicosity resolved clinical signs with only laser treatment and one stallion with a urethral rent received only laser treatment and haemospermia recurred. We conclude that laser treatment of a urethral rent in geldings can result in resolution of haematuria. Laser treatment used in combination with a TSI may result in improved success when compared to surgery alone. Laser treatment alone can result in resolution of a urethral varicosity.
Expression analysis of multiple microRNAs in each patient with scleroderma
Authors: Koba Shigeru , Jinnin Masatoshi , Inoue Kuniko , Nakayama Wakana , Honda Noritoshi , Makino Katsunari , Kajihara Ikko , Makino Takamitsu , Fukushima Satoshi , Ihn Hironobu
Published: May 2013

In this study, we compared expression pattern of multiple microRNAs in individual patient with scleroderma with that in normal subject. Serum levels of six microRNAs (miR‐7 g, miR‐21, miR‐29b, miR‐125, miR‐145 and miR‐206) were evaluated using real‐time PCR in 15 patients with scleroderma and 15 normal subjects. While levels of the six microRNAs were similar between the two groups, we found significant difference in the ranks between miRNAs in patients with scleroderma. Additionally, levels of let‐7 g and miR‐125b showed strong and significant correlation in normal subjects, but not in patients with scleroderma. Thus, miRNA expression pattern may be different in patients with scleroderma. We also found the combination of serum levels of miR‐206 and miR‐21 was more useful in distinguishing patients with scleroderma from normal subjects than either miR‐206 or miR‐21 alone. Our study is the first to demonstrate different expression profiles of multiple microRNAs in each patient with scleroderma and examine its clinical significance.
Paeoniflorin suppresses vascular damage and the expression of E‐selectin and ICAM‐1 in a mouse model of cutaneous Arthus reaction
Authors: Chen Tao , Guo Zai‐pei , Wang Lin , Qin Sha , Cao Na , Li Meng‐meng , Jia Rui‐zhen , Wang Ting‐ting
Published: May 2013

Paeoniflorin (PF) extracted from the root of Paeonia lactiflora pall, displays anti‐inflammation properties in several animal models. Adhesion molecules are important for the recruitment of leucocyte to the vessel wall and involved in the pathogenesis of various autoimmune and inflammatory diseases. Herein, we investigate the effects of PF on adhesion molecule expression in a mouse model of cutaneous Arthus reaction and cultured human dermal microvascular endothelial cells (HDMECs). We showed that PF significantly ameliorated the immune complex (IC) induced vascular damage, leucocyte infiltrates and adhesion molecules expression. Furthermore, PF markedly blocked tumor necrosis factor‐α (TNF‐α)‐induced E‐selectin and intercellular adhesion molecule‐1 (ICAM‐1) expression in HDMECs at both mRNA and protein levels. PF also suppressed TNF‐α‐induced adhesion of polymorphonuclear leucocytes (PMNs) to HDMECs. Finally, western blot data revealed that PF can inhibit the phosphorylation of p38, JNK in TNF‐α‐treated HDMECs. These data suggest that PF, as an anti‐inflammatory agent, can downregulate adhesion molecules expression. PF may be a candidate medicine for the treatment of IC‐induced inflammatory response.