bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat shock protein 60 induces inflammatory mediators in mouse adipocytes
Authors: Gülden Elke , Mollérus Sina , Brüggemann Jutta , Burkart Volker , Habich Christiane
Published: July 2008

Adipocytes represent an important cellular source of inflammatory mediators. However, the signals for the induction of proinflammatory adipocyte activities are largely unknown. Here, we demonstrate that heat shock protein (Hsp) 60, a potent stimulator of innate immunity, induces the release of the inflammatory mediators interleukin‐6, CXCL1 and monocyte chemoattractant protein‐1 in a time‐ and concentration‐dependent manner from cells of the adipocyte line 3T3‐L1 and from adipocytes of obese mice. These results identify Hsp60 as an important regulator of adipocyte functions which contribute to the development of inflammatory processes as observed in diabetes and diabetes‐associated complications.
DNA‐binding profiling of human hormone nuclear receptors via fluorescence correlation spectroscopy in a cell‐free system
Authors: Kobayashi Tamiyo , Kodani Yoshiko , Nozawa Akira , Endo Yaeta , Sawasaki Tatsuya
Published: July 2008

The nuclear hormone receptors (NHRs), a family of transcription factors, bind directly to the hormone response elements (HREs) to regulate gene expression. In this study, we describe a comprehensive NHR–HRE profiling analysis with a new high‐throughput DNA binding assay system utilizing wheat germ cell‐free protein production and fluorescence correlation spectroscopy (FCS). This approach revealed NHR binding to natural response elements and new heterodimeric NHR–HRE bindings. We analyzed 408 possible binding combinations between 34 human NHRs and 12 different HREs, and identified 205 NHR–HRE binding combinations, 124 of which have not been previously reported. Thus, this study provides a novel biochemical classification of the human NHRs, as well as describing a novel approach to the large‐scale analysis of DNA–protein interactions.
Müller cell gliosis in retinal organ culture mimics gliotic alterations after ischemia in vivo
Authors: Kuhrt Heidrun , Wurm Antje , Karl Anett , Iandiev Ianors , Wiedemann Peter , Reichenbach Andreas , Bringmann Andreas , Pannicke Thomas
Published: July 2008

A decrease in the expression of inwardly rectifying potassium (Kir) currents is a characteristic feature of retinal glial (Müller) cells in various retinopathies, e.g., after transient retinal ischemia. We used short‐term retinal organ cultures to investigate whether similar physiological alterations can be induced under in vitro conditions. During 4 days in vitro, Müller cells displayed a decrease in Kir currents and an increase in transient A‐type potassium currents which was similar to the alterations in membrane physiology during ischemia‐reperfusion in vivo. In addition, gliosis of Müller cells both in vivo and in organ cultures was associated with cellular hypertrophy and an alteration in osmotic swelling characteristics. Whereas Müller cells in control retinae did not swell under hypotonic stress, cells in postischemic retinae and in organ cultures swelled upon hypotonic challenge. Therefore, Müller cells in organ cultures can be used to investigate distinct aspects of ischemia‐induced Müller cell gliosis. Both the decrease in Kir currents and the alteration in osmotic swelling may reflect a dysfunction of Müller cells regarding the control of the ionic and osmotic homeostasis in the retina.
Frazzled cytoplasmic P‐motifs are differentially required for axon pathway formation in the Drosophila embryonic CNS
Authors: Dorsten Joy N. , VanBerkum Mark F.A.
Published: July 2008

Frazzled is a Netrin‐dependent chemoattractive receptor required for axon pathway formation in the developing Drosophila embryonic CNS. The cytoplasmic domain is important and contains three conserved P‐motifs (P1, P2, and P3) thought to initiate intracellular signaling cascades and to crosstalk with other receptors during axon pathway formation. Here, we rescue homozygous frazzled embryos by pan‐neurally expressing a series of mutants lacking either the cytoplasmic domain or one of the conserved P‐motifs and assess the ability of these mutants to rescue frazzled defects in commissural, longitudinal and motor axon pathways. Surprisingly, while the cytoplasmic domain is required, removal of an individual P‐motif does not prevent gross formation of commissures. However, removal of P3 from Fra does prevent eagle‐expressing commissural axons from crossing the midline in the posterior commissure suggesting that some neurons have a stronger requirement for P3‐dependent signaling. Indeed, axons within the longitudinal connective as well as a small subset of motor neurons within the ISNb pathway also specifically require P3 to project to their targets correctly. In these latter axon projections, deleting the P1‐motif appears to de‐regulate the receptor's activity, actually increasing the frequency of motor neuron projection errors and inducing ectopic midline crossing errors. Collectively, these data demonstrate the critical nature of both the P1 and the P3‐motifs to Frazzled function in vivo during axon pathway formation.
Nonobstetric lower genital tract injuries in rural India
Authors: Jana Narayan , Santra Debjyoti , Das Debasis , Das Anindya K. , Dasgupta Subhendu
Published: July 2008

Objective

To study the impact of nonobstetric genital tract injury (NOGTI) in rural India.

Methods

A prospective observational study of 52 consecutive women admitted with NOGTIs caused by voluntary coitus or accidental injury. Details of the causes of trauma, clinical presentations, and management were recorded.

Results

A total of 17 women (32.7%) presented with coital trauma, while 35 women (67.3%) sustained noncoital injuries: bicycle/automobile accidents (10); fall from height (7); cattle horn injury (7); straddle‐type trauma (6); leech bites (3); and vaginal foreign bodies (2). Most women had multiple injuries; 15 women developed vulvar hematomas and 3 had anorectal lacerations. Management included immediate resuscitation along with primary repair of injuries, evacuation of vulvar hematomas, and removal of vaginal foreign bodies. Fifteen women (28.8%) required blood transfusions; none of the women died.

Conclusions

Severe hemorrhage caused by NOGTIs is potentially fatal in rural settings if treatment is delayed. Prompt resuscitation, early referral, and appropriate surgical intervention can avert both morbidity and mortality.
Maternal obesity and neonatal congenital cardiovascular defects
Authors: Khalil Hala S. , Saleh Ahmed M. , Subhani Shazia N.
Published: July 2008

Objective

To determine whether isolated congenital heart defects (CHDs) were associated with maternal obesity.

Method

In a retrospective study we compared the incidence and severity of isolated CHDs in the offspring of 428 women divided into 3 groups, one of women of normal weight (n = 141), one of obese women (n = 228), and one of morbidly obese women (n = 59) according to their body mass index.

Results

There were 143 mild (66.8%), 44 moderate (20.6%), and 27 complex (12.6%) forms of CHDs in the offspring and septal defects were the most common (61.7%). No significant differences were found among the 3 groups of women regarding the type or severity of CHDs in their respective offspring, or the corrective cardiac surgery required.

Conclusion

No association was found between maternal weight and isolated CHDs in the offspring.
It's Good To Talk: Talk, Disagreement and Tolerance
Authors: PATTIE C. J. , JOHNSTON R. J.
Published: July 2008

Open political discussion between citizens is a cornerstone of democratic theory and contextual accounts of political behaviour. It provides both a means through which individuals can discover what their peers think and a forum within which they can rationalize, explain and perhaps modify their own opinions. Much previous research has focused on the potential of political conversation as a means of influencing others and of converting holders of minority views to the opinions of the majority. However, theoretical accounts of political conversation also stress its potential impact on more systemic attitudes towards democracy, including the development of tolerance for divergent views and lifestyles. The article provides an evaluation of these potential effects in the context of recent British politics.
Changes in the surface protein of the fat globules during homogenization and heat treatment of concentrated milk
Authors: Ye Aiqian , Anema Skelte G , Singh Harjinder
Published: July 2008

The changes in milk fat globules and fat globule surface proteins of both low-preheated and high-preheated concentrated milks, which were homogenized at low or high pressure, were examined. The average fat globule size decreased with increasing homogenization pressure. The total surface protein (mg m−2) of concentrated milk increased after homogenization, the extent of the increase being dependent on the temperature and the pressure of homogenization, as well as on the preheat treatment. The concentrates obtained from high-preheated milks had higher surface protein concentration than the concentrates obtained from low-preheated milks after homogenization. Concentrated milks heat treated at 79°C either before or after homogenization had greater amounts of fat globule surface protein than concentrated milks heat treated at 50 or 65°C. This was attributed to the association of whey protein with the native MFGM (milk fat globule membrane) proteins and the adsorbed skim milk proteins. Also, at the same homogenization temperature and pressure, the amount of whey protein on the fat globule surface of the concentrated milk that was heated after homogenization was greater than that of the concentrated milk that was heated before homogenization. The amounts of the major native MFGM proteins did not change during homogenization, indicating that the skim milk proteins did not displace the native MFGM proteins but adsorbed on to the newly formed surface.
Butter making from caprine creams: Effect of washing treatment on phospholipids and milk fat globule membrane proteins distribution
Authors: Lamothe Sophie , Robitaille Gilles , St-Gelais Daniel , Britten Michel
Published: July 2008

A washing treatment was applied to caprine cream before churning in order to improve phospholipids and MFGM protein purification from buttermilk and butter serum. Cream obtained from a first separation was diluted with water and separated a second time using pilot plant equipment. Regular and washed creams were churned to produce buttermilk and butter, from which butter serum was extracted. The washing treatment allowed a significant decrease of the casein content. As a result, the phospholipids-to-protein ratios in washed buttermilk and butter serum were markedly increased by 2·1 and 1·7-folds respectively, which represents an advantage for the production of phospholipids concentrates. However, when compared with bovine cream, lower phospholipids-to-protein ratios were observed when the washing treatment was applied to caprine cream. A higher concentration of MFGM protein and a lower retention of phospholipids during washing treatment are responsible for the lower phospholipids-to-protein ratios in buttermilk and butter serum obtained from caprine cream. The phospholipids distribution in the butter making process was similar to the one obtained from bovine regular and washed cream. Phospholipids were preferentially concentrated in the butter serum rather than the buttermilk fraction. This simple approach permitted the production of caprine and bovine butter sera extracts containing up to 180 and 240 g phospholipids/kg sera, respectively, on a dry basis.
The rebodying of stirred yoghurt: interactions between proteins
Authors: Renan Marie , Guyomarc'h Fanny , Arnoult-Delest Véronique , Pâquet Denis , Brulé Gérard , Famelart Marie H
Published: July 2008

The aim of the present study was to identify the nature of bonds established between protein particles after stirring that are responsible for the texture improvement of stirred yoghurts, called rebodying. Using a constant model yoghurt at pH 4·4, the effects of changes in the physicochemical conditions at stirring were studied on the subsequent rebodying. Short term rebodying was measured as the changes in viscoelastic properties at 4°C during 20 h after stirring, while long-term rebodying was measured as the viscosity changes during 28 d storage at 4°C. Moreover, stirred gels obtained from either set gels that were allowed time or not for ionic equilibration were compared. Increasing or decreasing ionic strength did not change the properties of stirred gels. Calcium chloride addition significantly decreased G′0 h, G′20 h and tan20 h but did not induce changes in the gel microstructure as observed by confocal scanning microscopy. Yoghurt rebodying could not be explained by fulfilling ionic equilibrium. Moreover, N-ethyl maleimide addition had no effect on the stirred yoghurt. Attractive electrostatic and disulphide interactions were not involved in the gel rebodying and increasing calcium concentration in the set gel limited rebodying.
Eighteenth-Century Quakerism and the Rehabilitation of James Nayler, Seventeenth-Century Radical
Authors: BELL ERIN
Published: July 2008

Although the first Quakers aligned history with superfluous tradition, detrimental to true appreciation of the inward voice of God, by the early eighteenth century they had produced their first histories as a defence against Anglican allegations of continued disorder and enthusiasm. At the same time, pressure to publish the collected works of James Nayler, a convicted blasphemer, proved particularly contentious. Leo Damrosch has sought to understand what Nayler thought he was doing in the 1650s; this study considers what motivated later Quakers to censor his works and accounts of his life, and demonstrates how English Friends in particular sought to revise the popular image of Quakerism by rewriting history.
Lady Chatterley and the Monk: Anglican Radicals and the Lady Chatterley Trial of 1960
Authors: ROODHOUSE MARK
Published: July 2008

The trial of Penguin Books for publishing an unexpurgated edition of D. H. Lawrence's novel Lady Chatterley's lover is a symbolic episode in histories of 1960s Britain, used to illustrate changes in social attitudes. However, historians have not appreciated the impact of the trial on Anglican attitudes towards contemporary society. Using correspondence in the papers of the Mirfield father and literary critic Martin Jarrett-Kerr, this article reveals the tensions within a loose coalition of Anglican radicals just as their views began to receive attention in the media. Jarrett-Kerr and fellow liberal Anglo-Catholics found themselves in an uneasy alliance with Liberal Anglicans, whose views were conflated with those of the radicals.
Predestination and Parochial Dispute in the 1630s: The Case of the Norwich Lectureships
Authors: REYNOLDS MATTHEW
Published: July 2008

Recently it has been suggested that fundamental disagreements over the theology of grace had little impact upon parish life in early Stuart England. However, by considering the local circumstances and wider national repercussions of an open debate over predestination in the 1630s between two Norwich lecturers, William Bridge and John Chappell, this article will argue the contrary. It will show that the public nature of the clash between Bridge and Chappell, examined by the church courts, ensured that predestination became a politically divisive issue within Norwich's parishes on the eve of the English Civil War.
Interaction between the nematophagous fungusDuddingtonia flagransand infective larvae ofHaemonchus contortus(Nematoda: Trichostrongyloidea)
Authors: Campos A.K. , Araújo J.V. , Guimarães M.P.
Published: July 2008

The interaction betweenDuddingtonia flagransand infective larvae ofHaemonchus contortuswas studiedin vitrounder optical and scanning electron microscopy. Trap formation by the fungus started 9 hours after inoculation and first larvae were found 11 hours after larval inoculation on colonies grown on the surface of dialysis membranes. Scanning electron micrographs were taken 12, 24, 36 and 48 h after larval predation. Details of predation structures and fungus–larvae interaction are described. A mucilaginous substance occurred at the points of adherence of traps to nematode cuticle. Bacteria were also found at some points of interaction between fungus and larval cuticle. Cuticle penetration by fungus hyphae occurred only 48 h after predation.
Protease expression analysis in recently field-isolated strains ofTrypanosoma cruzi: a heterogeneous profile of cysteine protease activities between TC I and TC II major phylogenetic groups
Authors: FAMPA P. , LISBOA C. V. , JANSEN A. M. , SANTOS A. L. S. , RAMIREZ M. I.
Published: July 2008

Protease expression among TCI and TCII field isolates was analysed. Gelatin-containing gels revealed hydrolysis bands with molecular masses ranging from 45 to 66 kDa. The general protease expression profile showed that TCII isolates presented higher heterogeneity compared to TCI. By utilizing protease inhibitors, we showed that all active proteases at acid pH are cysteine-proteases and all proteases active at alkaline pH are metalloproteases. However, the expression of cruzipain, theT. cruzimajor cysteine-protease, did not reproduce a heterogeneous TCII cysteine zymogram profile. Dendogram analyses based on presence/absence matrices of proteases and cruzipain bands showed a TCI separation from the TCII group with 50–60% similarity. We suggest that the observed cysteine protease diversification contributes to differential host infection between TCI and II genotypes.
Immunolocalization ofTaenia soliumgap junction innexins
Authors: ZURABIAN R. , LANDA A. , ROBERT L. , WILLMS K.
Published: July 2008

In previous studies, ultrastructural observations revealed a large number of gap junctions (GJs) in the neck and immature proglottid tissues ofTaenia soliumtapeworms. In these helminths, cytoplasmic glycogen sacs are connected by numerous discrete GJs to other cells throughout the maturing strobilar tissue. Discontinuous sucrose gradients were used to purify membrane fractions containing GJs, which were identified by ultrastructural analysis. A trans-membrane peptide sequence from a highly conserved innexin region was used to construct a 20-amino acid synthetic peptide and used to raise polyclonal antibodies in rabbits that recognized both a 55 and a 67 kDa protein in a Western blot of the GJ-enriched pellet. Immunohistochemistry of larval and adult worm sections incubated with antiserum to the synthetic peptide and a secondary anti-rabbit IgG bound to fluorescein, revealed strong binding to the tegumentary surface of the worm, as well as patchy fluorescent areas in the parenchyma. The results indicate that both the tegument of cysticerci and adultT. soliumcontain innexin-rich membranes, which may function as a tegumentary transport system for small molecules.
Were class C iron-containing superoxide dismutases of trypanosomatid parasites initially imported into a complex plastid? A hypothesis based on analyses of their N-terminal targeting signals
Authors: BODYŁ A. , MACKIEWICZ P.
Published: July 2008

Trypanosomatid parasites possess 2 distinct iron-containing superoxide dismutases (Fe-SODs) designated SODA and SODC, both of which are targeted to their mitochondria. In contrast to SODAs that carry typical mitochondrial transit peptides, SODCs have highly unusual mitochondrial targeting signals. Our analyses clearly show that these pre-sequences are bipartite possessing a signal peptide-like domain followed by a transit peptide-like domain. Consequently, they resemble N-terminal extensions of proteins targeted to multi-membrane plastids, suggesting that trypanosomatids once contained a eukaryotic alga-derived plastid. Further support for this hypothesis comes from striking similarities in length, hydropathy profile, and amino acid composition of SODC pre-sequences to those ofEuglenaand dinoflagellate plastid proteins. To account for these data, we propose that the Trypanosomatidae initially possessed a gene encoding a mitochondrial Fe-SOD with a classical mitochondrial transit peptide. Before or after plastid acquisition, a gene duplication event gave rise to SODA and SODC. In a subsequent evolutionary step a signal peptide was linked to SODC, enabling its import into the plastid. When the trypanosomatid plastid subsequently was lost, natural selection favoured adaptation of the SODC N-terminal signal as a mitochondrial transit peptide and re-targeting to the mitochondrion.
Specificity of theToxoplasma gondii-altered behaviour to definitive versus non-definitive host predation risk
Authors: LAMBERTON P. H. L. , DONNELLY C. A. , WEBSTER J. P.
Published: July 2008

The hypothesis that the parasiteToxoplasma gondiimanipulates the behaviour of its intermediate rat host in order to increase its chance of being predated specifically by its feline definitive host, rather than a non-definitive host predator species, was tested. The impact of a range of therapeutic drugs, previously demonstrated to be effective in preventing the development ofT. gondii-associated behavioural and cognitive alterations in rats, on definitive-host predator specificity was also tested. Using a Y-shaped maze design, we demonstrated thatT. gondii-associated behavioural changes, apparently aimed to increase predation rate, do appear to be specific to that of the feline definitive host – there were significant and consistent differences between the (untreated) infected and uninfected rats groups whereT. gondii-infected rats tended to choose the definitive host feline-predator-associated maze arm and nest-box significantly more often than a maze arm or nest-box treated with non-definitive host predator (mink) odour. Drug treatment of infected rats prevented any such host-specificity from being displayed. We discuss our results in terms of their potential implications both forT. gondiiepidemiology and the evolution of parasite-altered behaviour.
The distribution of the pathogenic nematodeNematodirus battusin lambs is zero-inflated
Authors: DENWOOD M. J. , STEAR M. J. , MATTHEWS L. , REID S. W. J. , TOFT N. , INNOCENT G. T.
Published: July 2008

Understanding the frequency distribution of parasites and parasite stages among hosts is essential for efficient experimental design and statistical analysis, and is also required for the development of sustainable methods of controlling infection.Nematodirus battusis one of the most important organisms that infect sheep but the distribution of parasites among hosts is unknown. An initial analysis indicated a high frequency of animals withoutN. battusand with zero egg counts, suggesting the possibility of a zero-inflated distribution. We developed a Bayesian analysis using Markov chain Monte Carlo methods to estimate the parameters of the zero-inflated negative binomial distribution. The analysis of 3000 simulated data sets indicated that this method out-performed the maximum likelihood procedure. Application of this technique to faecal egg counts from lambs in a commercial upland flock indicated thatN. battuscounts were indeed zero-inflated. Estimating the extent of zero-inflation is important for effective statistical analysis and for the accurate identification of genetically resistant animals.
Invariant measures for meromorphic Misiurewicz maps
Authors: KOTUS JANINA , ŚWIATEK GRZEGORZ
Published: July 2008

We study the existence of finite absolutely continuous invariant measures for meromorphic Misiurewicz maps whose Julia set is the whole sphere. In the rational context, these hypotheses imply that such a measure must exist. We show that it is not so for meromorphic maps unless an additional condition on the behavior of the map, which can be stated in terms of its Nevanlinna characteristic, is satisfied.
Hilbert polynomials and powers of ideals
Authors: HERZOG JÜRGEN , PUTHENPURAKAL TONY J. , VERMA JUGAL K.
Published: July 2008

The growth of Hilbert coefficients for powers of ideals are studied. For a graded ideal I in the polynomial ring S = K[x1, . . ., xn] and a finitely generated graded S-module M, the Hilbert coefficients ei(M/IkM) are polynomial functions. Given two families of graded ideals (Ik)k≥0 and (Jk)k≥0 with Jk ⊂ Ik for all k with the property that JkJℓ ⊂ Jk+ℓ and IkIℓ ⊂ Ik+ℓ for all k and ℓ, and such that the algebras $A=\Dirsum_{k\geq 0}J_k$ and $B=\Dirsum_{k\geq 0}I_k$ are finitely generated, we show the function k ↦ e0(Ik/Jk) is of quasi-polynomial type, say given by the polynomials P0,. . ., Pg−1. If Jk = Jk for all k, for a graded ideal J, then we show that all the Pi have the same degree and the same leading coefficient. As one of the applications it is shown that $\lim_{k\to \infty}\length(\Gamma_\mm(S/I^k))/k^n \in \mathbb{Q}$, if I is a monomial ideal. We also study analogous statements in the local case.
How many maximal surfaces do correspond to one minimal surface?
Authors: ARAÜJO HENRIQUE , LEITE MARIA LUIZA
Published: July 2008

We discuss the minimal-to-maximal correspondence between surfaces and show that, under this correspondence, a congruence class of minimal surfaces in 3 determines an 2-family of congruence classes of maximal surfaces in 3. It is proved that further identifications among these classes may exist, depending upon the subgroup of automorphisms preserving the Hopf differential on the underlying Riemann surface. The space of maximal congruence classes inherits a quotient topology from 2. In the case of the Scherk minimal surface, the subgroup has order two and the quotient space is topologically a disc with boundary. Other classical examples are discussed: for the Enneper minimal surface, one obtains a non-Hausdorff space; for the minimal catenoid, a closed interval.
Homotopy theoretic models of identity types
Authors: AWODEY STEVE , WARREN MICHAEL A.
Published: July 2008

Quillen [17] introduced model categories as an abstract framework for homotopy theory which would apply to a wide range of mathematical settings. By all accounts this program has been a success and—as, e.g., the work of Voevodsky on the homotopy theory of schemes [15] or the work of Joyal [11,12] and Lurie [13] on quasicategories seem to indicate—it will likely continue to facilitate mathematical advances. In this paper we present a novel connection between model categories and mathematical logic, inspired by the groupoid model of (intensional) Martin–Löf type theory [14] due to Hofmann and Streicher [9]. In particular, we show that a form of Martin–Löf type theory can be soundly modelled in any model category. This result indicates moreover that any model category has an associated “internal language” which is itself a form of Martin-Löf type theory. This suggests applications both to type theory and to homotopy theory. Because Martin–Löf type theory is, in one form or another, the theoretical basis for many of the computer proof assistants currently in use, such asCoqandAgda(cf. [3] and [5]), this promise of applications is of a practical, as well as theoretical, nature.
Distance to a focal point and singularity theorems with weak timelike convergence condition
Authors: PAENG SEONG-HUN
Published: July 2008

In classical general relativity, the timelike convergence condition is Ric(v, v) ≥ 0 for every timelike vector v. But recent astronomical observations show that the timelike convergence condition does not hold. In this paper, we obtain an explicit upper bound of the volume form and the distance to a focal point (such as Hubble distance) along timelike geodesic with integrals of the negative part of Ricci curvature, which entails singularity theorems.
Can Clark and Wells' (1995) Cognitive Model of Social Phobia be Applied to Young People?
Authors: Hodson Kate J. , McManus Freda V. , Clark David M. , Doll Helen
Published: July 2008

Social phobia is a common and disabling condition for both children and adults. In recent years Clark and Wells' (1995) cognitive model of social phobia has given rise to an effective treatment protocol for the condition in adults (e.g. Clark et al., 2003, 2006). The current study investigates the applicability of this model to younger people. One hundred and seventy-one 11–14 year-old participants completed questionnaires measuring social anxiety, depression, and the variables hypothesized to maintain social phobia in Clark and Wells' (1995) cognitive model: negative social cognitions, safety behaviours, self-focused attention, and pre- and post-event processing. High socially anxious children scored significantly higher than low socially anxious children on all of the variables in Clark and Wells' model. Negative social cognitions, self-focused attention, safety behaviours, and pre- and post-event processing were all significant predictors of social anxiety, accounting for 48% of the variance in social anxiety. Furthermore, these variables showed specificity to social anxiety, predicting significantly more variance in social anxiety than in depression. Findings suggest that although Clark and Wells' (1995) model of social phobia was developed from research on adult populations, it may be equally applicable to younger people with social phobia.
Molecular pathogenesis and clinical implications of eczema herpeticum
Authors: Bussmann Caroline , Peng Wen-Ming , Bieber Thomas , Novak Natalija
Published: July 2008

A subgroup of patients with atopic dermatitis develops one or more episodes of a severe viral skin infection caused by herpes simplex virus superimposed on eczematous skin lesions. This condition is named atopic dermatitis complicated by eczema herpeticum. Characteristic features of patients developing eczema herpeticum include an early age of onset of atopic dermatitis with a persistent and severe course into adulthood, predilection for eczematous skin lesions in the head and neck area, elevated total serum IgE levels and increased allergen sensitisation. Deficiencies at the level of both the innate and the adaptive immune system, which have been identified in atopic dermatitis, are much more pronounced in this subgroup. Predisposing cellular factors include a reduced number of plasmacytoid dendritic cells in the epidermis and a modified capacity of these cells to produce type I interferons after allergen challenge. In addition, lower levels of antimicrobial peptides in the skin of atopic dermatitis patients, resulting in part from a Th2-prone micromilieu, contribute to the lack of an effective defence against viral attack. In this review, we summarise the current knowledge of the molecular pathogenesis of eczema herpeticum.
Fiscal sustainability and public debt in an endogenous growth model
Authors: MORAGA JESÚS FERNÁNDEZ-HUERTAS , VIDAL JEAN-PIERRE
Published: July 2008

This paper investigates fiscal sustainability in an overlapping generations economy with endogenous growth coming from human capital formation through educational spending. We assess how budgetary imbalances affect economic dynamics and the outlook for economic growth, thereby providing a rationale for fiscal rules ensuring sustainability. Our results show that the appropriate response of fiscal policy to temporary shocks is not trivial in the absence of fiscal rules. Fiscal rules allow for a timely reaction, thereby avoiding possibly disruptive fiscal adjustment in the future: the more adjustment is delayed, the larger its necessary scale is. We perform a rough calibration of the model to simulate the effects of a demographic shock (change in the population growth rate) under different fiscal policy scenarios.
Ecological characterization of wildHelianthus annuusandHelianthus petiolarisgermplasm in Argentina
Authors: Poverene Monica , Cantamutto Miguel , Seiler Gerald J.
Published: July 2008

Helianthus annuusandH. petiolaris(Asteraceae) are wild sunflowers native to North America but have become naturalized in central Argentina covering an area of about 5 million hectares. WildH. annuushas been recognized as invader species in several countries, but no research has been done to study the ecological determinants of their distribution. In a survey covering seven provinces between 31°58′–38°S and 60°33′–69°W, we described the ecology of the main wild populations. WildHelianthuspopulations were located in three of the 18 ecological regions of Argentina, on five Mollisol and seven Entisol soil groups. The associated plant communities were comprised 60 species belonging to 16 families, all being frequent components of the native flora. Disease symptoms were seldom observed in wild populations, withAlternariahelianthibeing the most commonly observed pathogen. Population size varied from less than 100 to more than 100,000 plants, covering from 100 to more than 60,000 m2with densities most frequently up to 3 plants/m2, but reaching 80 plants/m2at certain sites. Intermediate plant phenotypes between wild species and cultivated sunflower were found in one-third of the populations providing evidence of intense gene flow. Hybrid swarms were found at three localities with population sizes between 100 and 10,000 individuals.
Pitch angle distributions of energetic particles near the heliospheric termination shock
Authors: Florinski V. , Decker R. B. , le Roux J. A.
Published: July 2008

The period of Voyager observations of energetic particles during its approach to the solar wind termination shock in 2004 provides a wealth of information about the site where the particles are accelerated. A new anisotropic particle transport model, based on an expansion of a focused transport equation in Legendre polynomials, is used here as a tool to analyze the pitch angle distributions of 1 MeV protons observed by Voyager 1 upstream of the shock. Daily average data from the seven sectors of the LECP instrument are represented in the form of an expansion in spherical harmonics up to second order in the coordinate frame aligned with the direction of the interplanetary magnetic field, permitting a direct comparison with our model results. It is found that the observed pitch angle distributions are consistent with the model predictions for particle population accelerated at a highly oblique shock wave. We derive the obliquity angle of the termination shock from analysis of first order anisotropies. It is demonstrated that the second‐order anisotropy is important for correctly interpreting the data. Many of the observed distributions are shown to possess an abnormally large second moment, which may indicate the presence of dual oppositely propagating beams in regions multiply connected to the termination shock by the interplanetary magnetic field lines.
Oleanolic acid induces relaxation and calcium‐independent release of endothelium‐derived nitric oxide
Authors: Rodriguez‐Rodriguez R , Stankevicius E , Herrera M D , Østergaard L , Andersen M R , Ruiz‐Gutierrez V , Simonsen U
Published: July 2008

Background and purpose:

The present study investigated the mechanisms by which oleanolic acid, a component of olive oil, increases release of nitric oxide (NO).

Experimental approach:

Measurements of isometric tension, NO concentration, or endothelial cell calcium were made in rat isolated mesenteric arteries. Immunoblotting for endothelial NOS (eNOS) and Akt kinase were performed in primary cultures of human umbilical vein endothelial cells (HUVECs).

Key results:

Oleanolic acid (3–30 μM) evoked endothelium‐dependent relaxations in noradrenaline‐contracted rat superior and small mesenteric arteries. In rat superior mesenteric arteries, oleanolic acid induced simultaneous increases in NO concentration and relaxation, and these responses were inhibited by an inhibitor of NOS, asymmetric dimethyl‐L‐arginine (300 μM) and by the NO scavenger, oxyhaemoglobin (10 μM). Oleanolic acid‐evoked NO increases were not reduced in Ca2+‐free solution and in the presence of an inhibitor of endoplasmic reticulum calcium‐ATPase, thapsigargin (1 μM). Oleanolic acid evoked relaxation without changes in endothelial cell calcium, but decreased smooth muscle calcium in arterial segments. Oleanolic acid failed to increase calcium in HUVECs, but increased time‐dependently phosphorylation of Akt kinase at Serine473 (Akt‐Ser473) and eNOS at Serine1177 (eNOS‐Ser1177), which was attenuated by inhibitors of phosphoinositide‐3‐kinase.

Conclusions and implications:

This study provides direct evidence that a component of olive oil, oleanolic acid, activated endothelium‐dependent release of NO and decreased smooth muscle cell calcium followed by relaxation. The oleanolic acid‐evoked endothelium‐derived NO release was independent of endothelial cell calcium and involved phosphoinositide‐3‐kinase‐dependent phosphorylation of Akt‐Ser473 followed by phosphorylation of eNOS‐Ser1177.

British Journal of Pharmacology (2008) 155, 535–546; doi:10.1038/bjp.2008.289; published online 14 July 2008
Inhibitory effect of salvinorin A, fromSalvia divinorum, on ileitis‐induced hypermotility: cross‐talk between κ‐opioid and cannabinoid CB1receptors
Authors: Capasso R , Borrelli F , Cascio M G , Aviello G , Huben K , Zjawiony J K , Marini P , Romano B , Di Marzo V , Capasso F , Izzo A A
Published: July 2008

Background and purpose:

Salvinorin A, the active component of the hallucinogenic herbSalvia divinorum, inhibits intestinal motility through activation of κ‐opioid receptors (KORs). However, this compound may have target(s) other than the KORs in the inflamed gut. Because intestinal inflammation upregulates cannabinoid receptors and endogenous cannabinoids, in the present study we investigated the possible involvement of the endogenous cannabinoid system in salvinorin A‐induced delay in motility in the inflamed gut.

Experimental approach:

Motilityin vivowas measured by evaluating the distribution of a fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; direct or indirect activity at cannabinoid receptors was evaluated by means of binding, enzymic and cellular uptake assays.

Key results:

Salvinorin A as well as the KOR agonist U‐50488 reduced motility in croton oil treated mice. The inhibitory effect of both salvinorin A and U‐50488 was counteracted by the KOR antagonist nor‐binaltorphimine and by the cannabinoid CB1receptor antagonist rimonabant. Rimonabant, however, did not counteract the inhibitory effect of salvinorin A on motility in control mice. Binding experiments showed very weak affinity of salvinorin A for cannabinoid CB1and CB2and no inhibitory effect on 2‐arachidonoylglycerol and anandamide hydrolysis and cellular uptake.

Conclusions and implications:

The inhibitory effect of salvinorin A on motility reveals a functional interaction between cannabinoid CB1receptors and KORs in the inflamed—but not in the normal—gutin vivo.

British Journal of Pharmacology(2008)155, 681–689; doi:10.1038/bjp.2008.294; published online 14 July 2008
Chop‐deficient Mice Showed Increased Adiposity But No Glucose Intolerance
Authors: Ariyama Yasuyo , Shimizu Hiroyuki , Satoh Tetsurou , Tsuchiya Takafumi , Okada Shuichi , Oyadomari Seiichi , Mori Masataka , Mori Masatomo
Published: July 2008

Objective: CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP)‐10/growth arrest and DNA damage 153 is a dominant‐negative member of the C/EBP transcription family and inhibits adipogenesis in vitro. The study was undertaken to determine the role of CHOP in obesity in vivo.

Research Methods and Procedures: Changes in daily food consumption and body weight were measured. The weight of white and brown adipose tissue was compared between Chop(+/+) and (−/−) mice fed normal chow or a high‐fat diet. Glucose and insulin tolerance tests were done, and serum adipocytokine was measured to determine their metabolic state. Fat cell size of subcutaneous and mesenteric adipose tissue was microscopically observed. C/EBP expression in white adipose tissue was examined by Western blot.

Results: Female Chop(−/−) mice had significantly greater body weight and adiposity than Chop(+/+) mice, although daily food intake and rectal temperature did not differ. In comparison with Chop(+/+) mice, glucose tolerance and insulin sensitivity did not differ in female Chop(−/−) mice, but levels of plasma leptin and adiponectin were higher. High‐fat diet feeding resulted in obesity in female Chop(+/−) and (−/−) mice, although caloric intake did not differ from that of Chop(+/+) mice. Fat cell area was larger in mesenteric fat but not in subcutaneous fat in Chop(−/−) mice fed a high‐fat diet. C/EBPβ and the 30‐kDa form of C/EBPα expressions were increased in parametrial fat of Chop(−/−) mice, but the 42‐kDa form of C/EBPα expression was lower than in Chop(+/+) mice.

Discussion: CHOP deficiency causes obesity in female animals without severe metabolic disorders, and C/EBP's expression may be considered to participate in the process.
A novel neuronal calcium sensor family protein, calaxin, is a potential Ca2+‐dependent regulator for the outer arm dynein of metazoan cilia and flagella
Authors: Mizuno Katsutoshi , Padma Potturi , Konno Aru , Satouh Yuhkoh , Ogawa Kazuo , Inaba Kazuo
Published: July 2008

Background information. Spermatozoa show several changes in flagellar waveform, such as upon fertilization. Ca2+ has been shown to play critical roles in modulating the waveforms of sperm flagella. However, a Ca2+‐binding protein in sperm flagella that regulates axonemal dyneins has not been fully characterized.

Results. We identified a novel neuronal calcium sensor family protein, named calaxin (Ca2+‐binding axonemal protein), in sperm flagella of the ascidian Ciona intestinalis. Calaxin has three EF‐hand Ca2+‐binding motifs, and its orthologues are present in metazoan species, but not in yeast, green algae or plant. Immunolocalization revealed that calaxin is localized near the outer arm of the sperm flagellar axonemes. Moreover, it is distributed in adult tissues bearing epithelial cilia. An in vitro binding experiment indicated that calaxin binds to outer arm dynein. A cross‐linking experiment showed that calaxin binds to β‐tubulin in situ. Overlay experiments further indicated that calaxin binds the β‐dynein heavy chain of outer arm dynein in the presence of Ca2+.

Conclusions. These results suggest that calaxin is a potential Ca2+‐dependent modulator of outer arm dynein in metazoan cilia and flagella.
Identification of lysine residues critical for the transcriptional activity and polyubiquitination of the NF-κB family member RelB
Authors: Leidner Julia , Palkowitsch Lysann , Marienfeld Uta , Fischer Dietmar , Marienfeld Ralf
Published: July 2008

RelB is the key component of the alternative NF-κB (nuclear factor κB) signalling pathway. However, RelB exerts also a negative effect via the recruitment of a DNMT1 (DNA methyltransferase 1)–Daxx (death domain-associated protein) complex to NF-κB target genes. Importantly, the molecular mechanisms which determine the functions of RelB are still largely unknown. In the present study, we aimed to analyse whether ubiquitination of RelB might be involved in the regulation of RelB. Indeed, RelB is constitutively polyubiquitinated in the B-cell lines Namalwa and 70Z/3. Although a PMA+ionomycin-induced augmentation of RelB polyubiquitination was linked to its proteasomal degradation in B-cells, the constitutive RelB polyubiquitination seems to affect non-proteasomal functions. Consistently, a significant RelB polyubiquitination in HEK (human embryonic kidney)-293 cells correlated with an augmentation of the transcriptional activity of RelB. Yet, neither nuclear localization nor DNA binding was enhanced by RelB polyubiquitination. Interestingly, basal RelB polyubiquitination depends neither on Lys48 nor on Lys63 conjugates, but might involve unconventional ubiquitin conjugates. Mapping of the ubiquitination target sites in RelB revealed the existence of various lysine residues, which serve as ubiquitination acceptors. However, only the substitution of Lys273/274 and Lys305/308 significantly decreased the basal RelB activity and the ubiquitin-induced augmentation of the RelB activity. Collectively, these results imply a dual role of RelB polyubiquitination for the stability and activity of this transcription factor.
Identification and characterization of FUS/TLS as a new target of ATM
Authors: Gardiner Mary , Toth Rachel , Vandermoere Franck , Morrice Nicholas A. , Rouse John
Published: July 2008

ATM (ataxia-telangiectasia mutated), ATR (ATM- and Rad3-related) and DNA-PK (DNA-dependent protein kinase), important regulators of genome stability, belong to the PIKK (phosphoinositide 3-kinase-like kinase) family of protein kinases. In the present study, DNA-affinity chromatography was used to identify DNA-binding proteins phosphorylated by these kinases. This resulted in the identification of FUS (fused in sarcoma)/TLS (translocated in liposarcoma) as an in vitro target of the PIKKs. FUS is a member of the Ewing's sarcoma family of proteins that appears to play a role in regulating genome stability, since mice lacking FUS show chromosomal instability and defects in meiosis. The residues in FUS that are phosphorylated in vitro and in vivo were identified, and phospho-specific antibodies were generated to demonstrate that FUS becomes phosphorylated at Ser42in vivo, primarily in response to agents that cause DSBs (double-strand breaks). DSB-induced FUS phosphorylation in vivo at Ser42 requires ATM and not DNA-PK. Although Ser42 is retained in the oncogenic FUS–CHOP [C/EBP (CCAAT/enhancer-binding protein)-homologous protein 10] fusion generated by a t(12;16)(q13;p11) chromosomal translocation, Ser42 in FUS–CHOP is not phosphorylated after DNA damage. These results identify FUS as a new target of the ATM-signalling pathway and strengthen the notion that FUS regulates genome stability.
Discovery of novel non-peptide thrombopoietin mimetic compounds that induce megakaryocytopoiesis
Authors: Yamane Noriko , Takahashi Koji , Tanaka Yoshikazu , Kato Kazue , Takayama Masami , Ohyabu Naoki , Shiota Takeshi , Takenaka Hideyuki , Yoshida Yutaka , Hara Shinichiro , Murashi Takami , Nakamura Etsuo , Nishitani Yoshinori , Ishizaki Jun , Yamane Shoji , Nagata Kiyoshi , Koizumi Kenzo , Yutsudo Takashi , Suzuki Ryuji , Itoh Tsunetoshi , Takemoto Hiroshi
Published: July 2008

We have identified a series of novel non-peptide compounds that activate the thrombopoietin-dependent cell line Ba/F3-huMPL. The compounds stimulated proliferation of Ba/F3-huMPL in the absence of other growth factors, but did not promote proliferation of the thrombopoietin-independent parent cell line Ba/F3. The thrombopoietin-mimetic compounds elicited signal-transduction responses comparable with recombinant human thrombopoietin, such as tyrosine phosphorylation of the thrombopoietin receptor, JAK (Janus kinase) 2, Tyk2 (tyrosine kinase 2), STAT (signal transducer and activator of transcription) 3, STAT5, MAPKs (mitogen-activated protein kinases), PLCγ (phospholipase Cγ), Grb2 (growth-factor-receptor-bound protein 2), Shc (Src homology and collagen homology), Vav, Cbl and SHP-2 (Src homology 2 domain-containing protein tyrosine phosphatase 2) and increased the number of CD41+ cells (megakaryocyte lineage) in cultures of human CD34+ bone-marrow cells (haematopoietic stem cells). These findings suggest that this series of compounds are novel agonists of the human thrombopoietin receptor and are possible lead compounds for the generation of anti-thrombocytopaenia drugs.
Determinants of Tourism Return Behaviour
Authors: do Valle Patrícia Oom , Correia Antónia , Rebelo Efigénio
Published: July 2008

Recent studies demonstrate that an increased number of Portuguese tourists choose Brazil as a tourism destination. Based on a literature review on the determinants of tourism demand, this study proposes a logit model that explains the probability of returning to this destination as a function of motivations, expectations, travel characteristics and the tourist's socio-demographic profile. After formulating the model, defining and testing of the six research hypotheses takes place. The study sample comprises 112 Portuguese tourists travelling to Brazil. The data fit the model adequately and the paper concludes with the authors discussing the theoretical and marketing implications.