bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of physiological state on immune function in insects
Authors: Adamo Shelley A.
Published: September 2009

This chapter discusses how and why short-term changes in physiological state (i.e., the acute stress response) alter immune responsiveness in insects. It also explores the ramifications of these effects for ecological immunologists.
Costs and genomic aspects of Drosophila immunity to parasites and pathogens
Authors: Kraaijeveld Alex R. , Wertheim Bregje
Published: September 2009

This chapter begins by focusing on the parasites and pathogens known to attack or infect D. melanogaster (or other Drosophila species), from macro-parasites, such as parasitoids and mites to microbial (fungal and bacterial) pathogens to viruses. It concentrates on the main selection pressures for and against resistance against these parasites and pathogens. High resistance is selected for when the benefits it incurs outweigh its costs. For each parasite/pathogen, the chapter summarizes the existing knowledge on abundance in the field, fitness effects of parasitism/infection, and costs of resistance, where it distinguishes between costs of actual resistance and costs of the resistance mechanism. The second section of the chapter shifts the focus to the genomic level. Over the last few years several papers have been published where microarrays have been used to investigate D. melanogaster resistance to parasites and pathogens. The chapter considers what these studies are telling us about Drosophila resistance mechanisms and about the associated costs.
Ecological and evolutionary implications of specific immune responses
Authors: Sadd Ben M. , Schmid-Hempel Paul
Published: September 2009

This chapter approaches the question of immune specificity from an evolutionary ecology perspective. For the sake of clarity, immune specificity is addressed on two levels. First, immune specificity is considered in the light of evidence for specific interactions between hosts and parasites. The importance of these specific interactions for questions concerning genetic diversity is then discussed. The second level on which immune specificity is addressed in the context of immune priming. It must be stressed that these two phenomena are almost certainly not mutually exclusive. For instance, the level of primed defences may be constrained by the innate defence capacity of an individual. Consequently, immune priming may play a role in the formation of specific interactions between hosts and parasites when re-infections are persistent or infections are chronic. Prior to concluding, the chapter considers sociality, and in particular immune defence within social insects.
Theses on Cinema as Philosophy
Authors: Livingston Paisley
Published: September 2009

This chapter criticizes what the chapter calls the ‘bold thesis’, which is the conjunction of the idea that films can make an original contribution to philosophy, and the idea that this contribution can be achieved primarily or even entirely through means exclusive to the cinematic medium. A dilemma argument against this thesis is set forth: either support for the bold thesis depends on a claim about a cinematic contribution that cannot be paraphrased and so can be reasonably doubted, or it rests on a contribution that can be paraphrased, in which case the clause about medium specificity is betrayed. As an alternative to the bold thesis, the chapter advocates a moderate thesis whereby a film-related contribution to philosophy can be of value even when the philosophical content is neither original nor conveyed primarily by means exclusive to the cinematic medium. This chapter discusses Aaron Smuts' proposed solution to the problem of paraphrase, which makes reference to an argument advanced by Sergei Eisenstein in the ‘For God and Country’ sequence of October.
Bergman, Kaila, and the Faces of Irrationality
Authors: Livingston Paisley
Published: September 2009

This chapter introduces the little-known connection between Ingmar Bergman's films and what the director identified as his major philosophical source — a treatise in philosophical psychology authored by the Finnish positivist, Eino Kaila, in 1934. Bergman proclaimed that reading this book was a tremendous philosophical experience for him and that he found some of Kaila's central claims shattering but true. Bergman added that he ‘built on this ground’. As Kaila's book has only been translated into Swedish and Danish, many Bergman commentators remain oblivious to its contents. This chapter surveys Kaila's positions and describes ways in which Bergman's work was informed by the questions and claims in Kaila's book. More specifically, the chapter focuses on Kaila's interest in various types of inauthenticity and motivated irrationality. Various Bergman films are discussed, but special attention is paid to his 1980 From the Life of the Marionettes.
Conclusion
Authors: Livingston Paisley
Published: September 2009

This concluding chapter discusses the tradeoffs faced by different interpretative approaches. The interpreter who freely chooses or invents a framework of philosophical assumptions to apply to a film often fails to elucidate any philosophizing actually accomplished by the film-maker. While pedagogically useful as illustrations of philosophical points, such interpretations of fictions provide no justification or confirmation of these philosophical generalizations. On the other hand, interpreters who seek to discover the film-maker's philosophizing encounter other constraints, such as a lack of evidence or the film-maker's failure to engage sufficiently with complex philosophical debates. Bergman's cinematic oeuvre exemplifies those cases where author-oriented appreciation and philosophical interpretation can coincide. Bergman's vivid and stirring fictional explorations of general issues pertaining to human motivation, knowledge, and value can stimulate and guide philosophical reflection. To take an interest in the Kaila-inspired topics broached in Bergman's films yields an enhanced appreciation of Bergman's artistry and of the skill with which he and his gifted performers broached these issues in cinematic fictions.
Introduction
Authors: Ott Walter
Published: September 2009

This chapter sets up the division the book will explore: the split between “top‐down” and “bottom‐up” views of the laws of nature. The scholastic view is a bottom‐up picture: although God must concur with the powers of bodies, those bodies determine the precise course of events. Descartes's invention of the laws of nature results in a top‐down picture: what happens in the world depends directly on the will of God.
2 Plan of the Book
Authors: Ott Walter
Published: September 2009

This short chapter sets out the chapters within the parts that follow. Part I sketches the Cartesian predicament. Having broken with the scholastics on key issues in ontology, Descartes faces a central tension. On one hand, he is clearly optimistic about the ability of mechanism to provide perspicuous explanations of body–body causation. On the other, he gives God such a primary role in the natural world that his activity seems to eclipse that of bodies. Much of the history of Cartesianism is the working out of these competing impulses. Part I then turns to an investigation of the concept of vis (force, power) in Descartes's work. Part II looks to the dialectic of occasionalism. It begins by exploring Malebranche's suite of arguments for occasionalism, some of which, as shall be seen in the book, have their origin in Descartes's own position. The book then turns to the case of Pierre-Sylvain Régis, who fights a rearguard action by at once revising and preserving some central Aristotelian notions within the general context of Cartesianism. Part III examines the Régis style of response to the Cartesian predicament as it appears in early modern empiricism. Part IV looks to Hume.
The Rejection of Aristotelianism
Authors: Ott Walter
Published: September 2009

Descartes rejects scholastic powers because they have four related but to his mind equally repugnant features: they are not reducible to the mechanical properties of bodies; they are explanatorily impotent; they exhibit physical teleology; and, most importantly, they are characterized by physical intentionality. That is, a scholastic power is intrinsically directed toward its characteristic effect. In the context of ontological mechanism, this simply makes no sense. Descartes mocks the scholastics for having imbued bodies with “little souls” that direct their behavior.
The Laws of Nature
Authors: Ott Walter
Published: September 2009

This chapter discusses earlier conceptions (such as those of Aristotle and Aquinas) of the world as law‐governed, zeroing in on Descartes's contribution. In earlier views, we do not find the suggestion that laws are particular principles that might explain individual physical events. Nevertheless, Descartes retains a key feature of the legalistic metaphor: his laws depend on a lawgiver and are to that extent arbitrary. They swing entirely free from the natures of the objects whose behavior they prescribe.
‘A Dead Cadaverous Thing’
Authors: Ott Walter
Published: September 2009

In England, ontological mechanism comes under fire. Figures such as Ralph Cudworth and Henry More argue that this ontology is too impoverished to explain such phenomena as cohesion, gravity, the transference of motion, and witchcraft. It is by responding to these problems and to the challenges posed by the top‐down picture of the Cartesians that Locke and Boyle attempt to defend the bottom‐up view.
Boyle's Paradox
Authors: Ott Walter
Published: September 2009

Although Boyle's famous “lock and key” analogy seems to indicate that he takes powers to be nothing more than the intrinsic features of the bodies involved in their exercise, he also thinks that the distribution and conservation of motion is dependent on God's will. If this last point holds, however, then it is not clear how the key's power to open the lock could be reduced to the intrinsic features of the key and the lock. For if God were to vary the motion of these bodies, even keeping their intrinsic features the same, the key would gain and lose this power. This chapter suggests a solution to the paradox by sharpening up Boyle's seemingly reductive view of relations.
Boyle and the Concurrentists
Authors: Ott Walter
Published: September 2009

It is tempting to read Boyle as offering an updated version of concurrentism. But unlike the concurrentists, Boyle does not think that God works through bodies as his instruments to produce effects.
Locke on Powers: The Geometrical Model
Authors: Ott Walter
Published: September 2009

Locke's ontology of relations and powers points to an alternative to the occasionalists' cognitive model of causality. So far, though, this is all it has done; it remains to be seen just how Locke proposes to account for the tie between cause and effect. Conceptual foundationalism offers the outlines of a story here: while there is no genuine, mind‐independent relation of cause and effect, there is still an objective ground on the basis of which a suitably disposed mind will (and should) think of this relation. What explains this ground is the geometrical model of causation. This chapter shows how the geometrical model fits with Locke's corpuscularianism and his claim that some geometrical propositions are synthetic and a priori. It also recasts Locke's distinction between primary and secondary qualities in such a way as to reconcile a number of seemingly conflicting texts.
Conclusion
Authors: Ott Walter
Published: September 2009

Any attempt to resuscitate the powers of created beings, and hence the bottom‐up picture, must navigate between two obstacles. On one side lies occultism: given ontological mechanism, there seems no place for powers in nature, and nothing for them to do even if there were. On the other lurks voluntarism: if God is directly responsible for the distribution of motion, the bottom‐up view has been sacrificed, and the supervenience base of the powers of bodies must include more than their intrinsic properties. This chapter gathers up the threads of the previous ones to show precisely how Locke finds his own path between these two pitfalls.
The Two Humes
Authors: Ott Walter
Published: September 2009

Hume's Treatise has two distinct goals: first, to reveal the limitations of human knowledge by developing an empirical psychology, and second, to decide metaphysical questions. Many commentators take these to be in conflict, and so emphasize one or the other. This chapter suggests a way to unify them: by discovering the limits of human thought, Hume can declare certain metaphysical positions not just unknowable, or true for all we can tell, but positively nonsensical. The psychological project is thus in service of the metaphysical.
Phenotypic categorization of genetic skin diseases reveals new relations between phenotypes, genes and pathways
Authors: Sadreyev Ruslan I. , Feramisco Jamison D. , Tsao Hensin , Grishin Nick V.
Published: September 2009

Motivation: Systematic analysis of connection between proteins, their cellular function and phenotypic manifestations in disease is a central problem of biological and clinical research. The solution to this problem requires the development of new approaches to link the rapidly growing dataset of gene–disease associations with the many complex and overlapping phenotypes of human disease.

Results: We analyze genetic skin disorders and suggest a manually designed set of elementary phenotypes whose combinations define diseases as points in a multidimensional space, providing a basis for phenotypic disease clustering. Placing the known gene–disease associations in the context of this space reveals new patterns that suggest previously unknown functional links between proteins, signaling pathways and disease phenotypes. For example, analysis of telangiectasias (spider vein diseases) reveals a previously unrecognized interplay between the TGF-β signaling pathway and pentose phosphate pathway. This interaction may mediate glucose-dependent regulation of TGF-β signaling, providing a clue to the known association between angiopathies and diabetes and implying new gene candidates for mutational analysis and drug targeting.

Contact:  grishin@chop.swmed.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Two variants of staphylococcal cassette chromosome mec type IVA in community-associated meticillin-resistant Staphylococcus aureus strains in South Korea
Authors: Park Chulmin , Shin Hyun-Ho , Kwon Eun-Young , Choi Su-Mi , Kim Si-Hyun , Park Sun Hee , Choi Jung-Hyun , Yoo Jin-Hong , Lee Dong-Gun , Shin Wan Shik
Published: September 2009

Meticillin-resistant Staphylococcus aureus (MRSA) strains harbouring staphylococcal cassette chromosome mec (SCCmec) type IVA are known to be more prevalent in South Korea than in other countries. Variations in the SCCmec IVA structure have been identified, including in sequence type (ST) 1 and ST72 strains. This study compared and investigated the genetic characteristics of two subtypes common in South Korea. Type IVA SCCmec of ST1 strains was characterized by type IV features with the linearized pUB110 at the junkyard (J) 3 region. However, that of ST72 strains carried a variant class B mec complex, ccrA2, with an identity of ∼96 % and the linearized pUB110 at the J3 region. In SCCmec of ST72 strains, the organization of the class B variant and the J3 region may be more similar to that of type IA than to other types, but the ccr type and other J regions seemed to be derived from type IV. These genetic characteristics showed that type IVA appears to result from the dynamic genetic exchange and recombination of SCC DNA.
Molecular genetic typing reveals further insights into the diversity of animal-associated Staphylococcus aureus
Authors: Smyth Davida S. , Feil Edward J. , Meaney William J. , Hartigan Patrick J. , Tollersrud Tore , Fitzgerald J. Ross , Enright Mark C. , Smyth Cyril J.
Published: September 2009

Staphylococcus aureus is an important pathogen of man, but is also able to colonize and cause disease in a wide variety of mammals and birds. An extended multilocus sequencing approach, involving multilocus sequence typing (MLST), sas typing, spa typing and agr typing, was used to examine the molecular diversity of 118 S. aureus isolates recovered from a range of host species and to compare these data with the known diversity of human-derived isolates. MLST revealed that the commonest animal-associated MLST types were ST133, ST5, ST71, ST97, ST126 and ST151. ST133 appears to be an ungulate-animal-specific genotype, as no evidence of ST133 associating with humans has yet been found in the literature. Novel and unique sas alleles were identified in the animal-associated strains that may represent animal-associated sas alleles. However, sas typing exhibited a lower typeability than MLST for the animal strains (91.3 %). Phylogenetic analyses using neighbour-joining and maximum-parsimony trees localized ruminant-associated MLST lineages to both previously identified S. aureus subspecies aureus subgroups, thus explaining the finding of all four agr types within the ruminant-associated strains. S. aureus isolates recovered from chickens and rabbits were genotypically more similar to known human genotypes than the ruminant-associated lineages.
Usefulness of antimicrobial resistance pattern for detecting PVL- or TSST-1-producing meticillin-resistant Staphylococcus aureus in a French university hospital
Authors: Gbaguidi-Haore Houssein , Thouverez Michelle , Couetdic Gérard , Cholley Pascal , Talon Daniel , Bertrand Xavier
Published: September 2009

Several recent reports have suggested that community-associated meticillin-resistant Staphylococcus aureus (MRSA) clones, particularly those harbouring genes for Panton–Valentine leukocidin (PVL) or toxic shock syndrome toxin 1 (TSST-1), are increasingly responsible for infections in hospitals. Here, a retrospective study was carried out to investigate whether antimicrobial resistance patterns could be used to detect these pathogens in a French university hospital. Isolates were characterized by antimicrobial susceptibility testing, PCR profiling (PVL genes and tst), PFGE typing and multilocus sequence typing. Demographic and clinical data were collected from all patients. For PVL-positive MRSA, the typical antimicrobial resistance pattern (susceptible to fluoroquinolones, non-susceptible to fusidic acid, kanamycin resistant and susceptible to gentamicin and tobramycin) had a sensitivity of 77.8 % and a positive predictive value (PPV) of 100 %. For tst-positive MRSA, the antimicrobial resistance pattern (susceptible to fluoroquinolones and non-susceptible to fusidic acid) had a sensitivity of 100 % and a PPV of 72.4 %. These results suggest that phenotypic rules based on antimicrobial resistance patterns are potentially useful for the detection of PVL- and tst-positive MRSA isolates.
Nationwide epidemiological study revealed the dissemination of meticillin-resistant Staphylococcus aureus carrying a specific set of virulence-associated genes in Japanese hospitals
Authors: Ohkura Teruko , Yamada Keiko , Okamoto Akira , Baba Hisashi , Ike Yasuyoshi , Arakawa Yoshichika , Hasegawa Tadao , Ohta Michio
Published: September 2009

To study comprehensive toxin profiles and the chromosomal diversity of current Japanese hospital-associated meticillin-resistant Staphylococcus aureus (HA-MRSA) strains, we conducted PCR-based identification of 28 toxin genes, and staphylococcal cassette chromosome mec (SCCmec) typing and PFGE analysis of 208 MRSA strains isolated from 100 hospitals throughout Japan. Of the tested HA-MRSA strains, 80.3 % were tst-positive. The most frequent toxin gene profile was characterized by the carriage of 13 genes, tst, sec, seg, sei, sel, sem, sen, seo, lukED, hla, hlb, hld and hlg-2. Ninety of the 208 strains had this profile, which was named pattern A. Among the 118 non-pattern A strains, 100 had similar toxin gene profiles, the concordance rates to pattern A of which were more than 80 %. Consequently, 91.3 % of the examined HA-MRSA strains carried similar toxin profiles, although PFGE patterns showed a wide variation. These strains belonged to SCCmec type II, agr II and coagulase type II. We concluded that, unlike MRSA from many other countries, most of the Japanese HA-MRSA strains belonged to, or were related to, a specific group carrying the set of 13 toxin genes, irrespective of chromosomal diversity. In addition, among the 13 toxin genes, the coexistence rates of tst, sec and sel, and those of seg, sei, sem, sen and seo, were higher than for the other toxin genes. High coexistence rates of tst, sec and sel genes suggested the presence of the pathogenicity island SaPIn1 in these strains.
Five cases of bacteraemia due to Gordonia species
Authors: Brust James C. M. , Whittier Susan , Scully Brian E. , McGregor Carlton C. , Yin Michael T.
Published: September 2009

Gordonia species are aerobic Gram-positive bacilli and a rare cause of human disease. To our knowledge, there are only two cases of human infection with Gordonia sputi reported in the literature. We report five cases of bacteraemia due to Gordonia species at our institution since 2005, including four caused by G. sputi. Three of these cases were likely related to chronic indwelling central venous catheters.
Proton motive force-dependent efflux of tetracycline in clinical isolates of Helicobacter pylori
Authors: Anoushiravani Mona , Falsafi Tahereh , Niknam Vahid
Published: September 2009

The aim of this study was to evaluate the role of proton motive force (PMF)-dependent efflux in resistance of Helicobacter pylori to tetracycline (Tet). Tet MIC was determined by agar dilution in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), an inhibitor of PMF. Antibiotic accumulation was conducted in the presence or absence of CCCP and the fluorescence of the accumulated antibiotic was measured by spectrofluorometry. In the presence of CCCP, antibiotic accumulation was increased by 2–17-fold in 17/20 Tetr isolates and by 3–10-fold in four of five high-level-resistant mutants. Correlation was observed between this increase and diminution of MIC with CCCP. PMF-dependent efflux mechanisms therefore appear to play an important role in the resistance of clinical isolates of H. pylori to Tet.
Gene expression profiling of monocytes displaying herpes simplex virus 1 induced dysregulation of antifungal defences
Authors: Cermelli Claudio , Orsi Carlotta Francesca , Cuoghi Alessandro , Ardizzoni Andrea , Tagliafico Enrico , Neglia Rachele , Peppoloni Samuele , Blasi Elisabetta
Published: September 2009

Recently, we showed that herpes simplex virus 1 (HSV-1)-infected monocytes have altered antifungal defences, in particular they show augmented phagocytosis ofCandida albicansfollowed by a failure of the intracellular killing of the ingested fungi. On the basis of these functional data, comparative studies were carried out on the gene expression profile of cells infected with HSV-1 and/orC. albicansin order to investigate the molecular mechanisms underlying such virus-induced dysfunction. Affymetrix GeneChip technology was used to evaluate the cell transcription pattern, focusing on genes involved in phagocytosis, fungal adhesion, antimicrobial activity and apoptosis. The results indicated there was: (a) prevalent inhibition of opsonin-mediated phagocytosis, (b) upregulation of several pathways of antibody- and complement-independent phagocytosis, (c) inhibition of macrophage activation, (d) marked dysregulation of oxidative burst, (e) induction of apoptosis.
N-Chlorotaurine shows high in vitro activity against promastigotes and amastigotes of Leishmania species
Authors: Fürnkranz Ursula , Nagl Markus , Gottardi Waldemar , Matt Ulrich , Aspöck Horst , Walochnik Julia
Published: September 2009

Protozoan parasites of the genusLeishmaniaare the causative agents of life-threatening visceral as well as cutaneous and mucocutaneous leishmaniasis. First-line drugs are antimonials, but toxicity and resistance in some endemic areas cause serious problems. In the current study, the antileishmanial activity of the weak oxidantN-chlorotaurine (NCT) was investigated. NCT is a derivative of the amino acid taurine produced by granulocytes and monocytes during oxidative burst, but can also be synthesized chemically and used topically as an antiseptic at a concentration of 1 % (55 mM)in vivo. NCT susceptibility tests were performedin vitrowith promastigotes and amastigotes ofLeishmania infantumandLeishmania donovani. As NH4Cl is known to increase the activity of NCT by the formation of monochloramine (NH2Cl), co-treatment assays were included in the study. Mean EC50values after 1 h of treatment were 5.94 mM forL. infantumand 9.8 mM forL. donovanipromastigotes. Co-treatment with 5.5 mM NCT plus 19 mM NH4Cl led to complete killing of promastigotes of both strains within 15 min. Amastigotes were inactivated by treatment with 2 mM NCT alone. The results of this study indicate a high potential of NCT againstLeishmaniaspecies.
Bacterial colonization of enamel in situ investigated using fluorescence in situ hybridization
Authors: Al-Ahmad Ali , Follo Marie , Selzer Ann-Carina , Hellwig Elmar , Hannig Matthias , Hannig Christian
Published: September 2009

Oral biofilms are one of the greatest challenges in dental research. The present study aimed to investigate initial bacterial colonization of enamel surfaces in situ using fluorescence in situ hybridization (FISH) over a 12 h period. For this purpose, bovine enamel slabs were fixed on buccal sites of individual splints worn by six subjects for 2, 6 and 12 h to allow biofilm formation. Specimens were processed for FISH and evaluated with confocal laser-scanning microscopy, using probes for eubacteria, Streptococcus species, Veillonella species, Fusobacterium nucleatum and Actinomyces naeslundii. The number of adherent bacteria increased with time and all tested bacterial species were detected in the biofilm formed in situ. The general percentage composition of the eubacteria did not change over the investigated period, but the number of streptococci, the most frequently detected species, increased significantly with time (2 h: 17.7±13.8 %; 6 h: 20.0±16.6 %; 12 h: 24.7±16.1 %). However, ≤1 % of the surface was covered with bacteria after 12 h of biofilm formation in situ. In conclusion, FISH is an appropriate method for quantifying initial biofilm formation in situ, and the proportion of streptococci increases during the first 12 h of bacterial adherence.
A newly identified protein of Leptospira interrogans mediates binding to laminin
Authors: Longhi Mariana T. , Oliveira Tatiane R. , Romero Eliete C. , Gonçales Amane P. , de Morais Zenaide M. , Vasconcellos Silvio A. , Nascimento Ana L. T. O.
Published: September 2009

Pathogenic Leptospira is the aetiological agent of leptospirosis, a life-threatening disease that affects populations worldwide. The search for novel antigens that could be relevant in host–pathogen interactions is being pursued. These antigens have the potential to elicit several activities, including adhesion. This study focused on a hypothetical predicted lipoprotein of Leptospira, encoded by the gene LIC12895, thought to mediate attachment to extracellular matrix (ECM) components. The gene was cloned and expressed in Escherichia coli BL21 Star (DE3)pLys by using the expression vector pAE. The recombinant protein tagged with N-terminal hexahistidine was purified by metal-charged chromatography and characterized by circular dichroism spectroscopy. The capacity of the protein to mediate attachment to ECM components was evaluated by binding assays. The leptospiral protein encoded by LIC12895, named Lsa27 (leptospiral surface adhesin, 27 kDa), bound strongly to laminin in a dose-dependent and saturable fashion. Moreover, Lsa27 was recognized by antibodies from serum samples of confirmed leptospirosis specimens in both the initial and the convalescent phases of the disease. Lsa27 is most likely a surface protein of Leptospira as revealed in liquid-phase immunofluorescence assays with living organisms. Taken together, these data indicate that this newly identified membrane protein is expressed during natural infection and may play a role in mediating adhesion of L. interrogans to its host.
Characterization of cytotoxic necrotizing factor 1-producing Escherichia coli strains from faeces of healthy macaques
Authors: Martin Heather R. , Taylor Nancy S. , Buckley Ellen M. , Marini Robert P. , Patterson Mary M. , Fox James G.
Published: September 2009

Twenty-five (27 %) of 92 clinically normal macaques were found to have β-haemolytic Escherichia coli isolated from their faeces. Five of six isolates chosen for further characterization had multiple antibiotic resistance and were PCR-positive for cytotoxic necrotizing factor 1 (cnf1) with a demonstrated cytopathic effect in vitro. By repetitive element sequence-based PCR genotyping, genetic similarity was established for selected isolates. We believe this to be the first report of E. coli strains producing CNF1 in non-human primates.
Developments in the field of allergy in 2008 through the eyes ofClinical & Experimental Allergy
Authors: Almqvist C. , Bradding P. B. , Chakir J. , Ebo D. , Grattan C. , Kariyawasam H. H. , Savilahti E. , Scadding G. K. , Vieths S. , Wardlaw A. J. , Woodfolk J.
Published: September 2009

In 2008, many thousands of articles were published on the subject of allergic disease with over 200 reviews, editorials and original papers inClinical & Experimental Allergyalone. These represent a considerable amount of data and even the most avid reader could only hope to assimilate a small fraction of this knowledge. There is therefore a pressing need for the key messages that emerge from a journal such asClinical & Experimental Allergyto be summarized by experts in the field in a form that highlights the significance of the developments and sets them in the context of important findings in the field published in other journals. This also has the advantage of making connections between new data in conditions such as asthma, where articles often appear in different sections of the journal. As can be seen from this review, the body of work is diverse both in terms of the disease of interest and the discipline that has been used to investigate it. However, taken as a whole, we hope that the reader will gain a flavour of where the field is mature, where there remain controversies and where the cutting edge is leading.
Intraseasonal climate and habitat‐specific variability controls the flowering phenology of high alpine plant species
Authors: Hülber Karl , Winkler Manuela , Grabherr Georg
Published: September 2009

1.  High alpine plants endure a cold climate with short growing seasons entailing severe consequences of an improper timing of development. Hence, their flowering phenology is expected to be rigorously controlled by climatic factors.

2.  We studied ten alpine plant species from habitats with early and late melting snow cover for 2 years and compared the synchronizing effect of temperature sums (TS), time of snowmelt (SM) and photoperiod (PH) on their flowering phenology. Intraseasonal and habitat‐specific variation in the impact of these factors was analysed by comparing predictions of time‐to‐event models using linear mixed‐effects models.

3.  Temperature was the overwhelming trigger of flowering phenology for all species. Its synchronizing effect was strongest at or shortly after flowering indicating the particular importance of phenological control of pollination. To some extent, this pattern masks the common trend of decreasing phenological responses to climatic changes from the beginning to the end of the growing season for lowland species. No carry‐over effects were detected.

4.  As expected, the impact of photoperiod was weaker for snowbed species than for species inhabiting sites with early melting snow cover, while for temperature the reverse pattern was observed.

5.  Our findings provide strong evidence that alpine plants will respond quickly and directly to increasing temperature without considerable compensation due to photoperiodic control of phenology.
Different roles of Foxo1 and Foxo3 in the control of endothelial cell morphology
Authors: Matsukawa Mai , Sakamoto Hiroshi , Kawasuji Michio , Furuyama Tatsuo , Ogawa Minetaro
Published: September 2009

Foxo1, a member of the Foxo subfamily of forkhead box transcription factors, is known to be essential for progression of normal vascular development in the mouse embryos. In the cultures of endothelial cells derived from embryonic stem cells, Foxo1‐deficient endothelial cells exhibit an abnormal morphological response to vascular endothelial growth factor‐A (VEGF‐A), which is characterized by a lack of cell elongation, yet the molecular mechanisms governing endothelial cell morphology under angiogenic stimulation remain unknown. Here, we report that transforming growth actor‐β also induces endothelial cell elongation in collaboration with Foxo1 and VEGF‐A. Furthermore, tetracycline‐regulated induction of Foxo3, another member of the Foxo subfamily, into Foxo1‐null endothelial cells failed to restore abnormal morphological response to VEGF‐A at an early differentiation stage. In contrast, Foxo1 and Foxo3 exerted the same function at a late differentiation stage, i.e. enhancement of VEGF responsiveness and promotion of cell elongation. Our results provide evidence that endothelial cell morphology is regulated by several mechanisms in which Foxo1 and Foxo3 express distinct functional properties depending on differentiation stages.
A new search for life on Mars
Authors: Matthewman Richard
Published: September 2009

Developments in spacecraft technology are allowing us to examine the Solar System ever more closely. A European mission is currently being prepared to send a package of highly advanced instruments to Mars to search for any traces of life, past or present.
Forensic geology in serious crime investigation
Authors: Pirrie Duncan
Published: September 2009

CSI, Silent Witness, and a host of other recent television dramas have highlighted the role of science in serious crime investigation and detection. Although many ‘real’ forensic scientists wince at the media portrayal of their discipline, the programmes have led to a wider understanding of the role of different branches of science in criminal investigations. This is not always a good thing, as ‘career’ or ‘professional’ criminals will work very hard at being forensically aware to avoid detection, hence any credible forensic scientist might want to be at best a little reticent as to what they do and how they do it. However, in the UK court system evidence presented by the Prosecution team has to be disclosed to the defence and to be open to challenge in court. This article aims to show, in the broadest of terms, how geology is becoming used increasingly in the detection of serious crime.
Differences in innate immune responses correlate with differences in murine susceptibility to Chlamydia muridarum pulmonary infection
Authors: Jiang Xiaozhou , Shen Caixia , Yu Hong , Karunakaran Karuna P. , Brunham Robert C.
Published: September 2009

We investigated the phenotypic basis for genetically determined differences in susceptibility and resistance to Chlamydia muridarum pulmonary infection using BALB/c and C57BL/6 mice. Following C. muridarum intranasal inoculation, the intensity of infection was very different between BALB/c and C57BL/6 beginning as early as 3 days post‐infection. Intrapulmonary cytokine patterns also differed at early time‐points (days 2 and 4) between these two strains of mice. The early recruitment of neutrophils to lung tissue was greater in BALB/c than in C57BL/6 mice and correlated with a higher number of inclusion forming units (IFU) of C. muridarum. At day 12 post‐infection, BALB/c mice continued to demonstrate a greater burden of infection, significantly higher lung cytokine levels for tumour necrosis factor‐α and interleukin‐17 (IL‐17) and a significantly lower level for interferon‐γ than did C57BL/6 mice. In vitro, bone‐marrow‐derived dendritic cells (BMDCs) from BALB/c mice underwent less functional maturation in response to C. muridarum infection than did BMDCs from C57BL/6 mice. The BMDCs of BALB/c mice expressed lower levels of activation markers (CD80, CD86, CD40 and major histocompatibility complex class II) and secreted less IL‐12 and more IL‐23 than BMDCs from C57BL/6 mice. Overall, the data demonstrate that the differences exhibited by BALB/c and C57BL/6 mice following C. muridarum pulmonary infection are associated with differences in early innate cytokine and cellular responses that are correlated with late differences in T helper type 17 versus type 1 adaptive immune responses.
Donor‐strain‐derived immature dendritic cell pre‐treatment induced hyporesponsiveness against allogeneic antigens
Authors: Kang Hee Gyung , Lee Jung Eun , Yang Seung Hee , Lee Se Han , Gao Wenda , Strom Terry B. , Oh Keunhee , Lee Dong‐Sup , Kim Yon Su
Published: September 2009

The maturation of antigen‐presenting dendritic cells (DCs) serves as an important determinant for the regulation of immunity, and overall immune response. We hypothesized that a reduced immune response to donor alloantigens and improved allograft survival could be induced by pre‐treating recipients with bone‐marrow‐derived donor‐strain fixed immature DCs (FIDCs). Donor‐strain‐derived mature and immature DCs were fixed before grafting to ensure that they possessed a stable immunogenic phenotype. The fixed mature DCs effectively induced allogeneic T‐cell proliferation in recipients, whereas FIDCs were unable to elicit an allogeneic T‐cell response. T cells that had previously been exposed to FIDCs maintained naïve phenotypes and were unable to extensively divide after injection into lethally irradiated donor‐strain mice. The pre‐treatment of recipients with donor‐strain FIDCs markedly prolonged the survival of islet as well as skin allografts. However, T‐cell hyporesponsiveness induced by FIDC injection was abrogated by the depletion of CD4+ CD25+ T cells. Consequently, FIDC‐induced T‐cell hyporesponsiveness could reflect anergy rather than specific deletion. Our findings suggest that FIDCs of donor strain could be used to induce long‐term graft survival.
Protective role of osteopontin in endodontic infection
Authors: Rittling Susan R. , Zetterberg Craig , Yagiz Kader , Skinner Stephen , Suzuki Noriyuki , Fujimura Akira , Sasaki Hajime
Published: September 2009

Endodontic infections are polymicrobial infections resulting in bone destruction and tooth loss. The host response to these infections is complex, including both innate and adaptive mechanisms. Osteopontin (OPN), a secreted, integrin‐binding protein, functions in the regulation of immune responses and enhancement of leucocyte migration. We have assessed the role of OPN in the host response to endodontic infection using a well‐characterized mouse model. Periapical bone loss associated with endodontic infection was significantly more severe in OPN‐deficient mice compared with wild‐type 3 weeks after infection, and was associated with increased areas of inflammation. Expression of cytokines associated with bone loss, interleukin‐1α (IL‐1α) and RANKL, was increased 3 days after infection. There was little effect of OPN deficiency on the adaptive immune response to these infections, as there was no effect of genotype on the ratio of bacteria‐specific immunoglobulin G1 and G2a in the serum of infected mice. Furthermore, there was no difference in the expression of cytokines associated with T helper type 1/type2 balance: IL‐12, IL‐10 and interferon‐γ. In infected tissues, neutrophil infiltration into the lesion area was slightly increased in OPN‐deficient animals 3 days after infection: this was confirmed by a significant increase in expression of neutrophil elastase in OPN‐deficient samples at this time‐point. We conclude that OPN has a protective effect on polymicrobial infection, at least partially because of alterations in phagocyte recruitment and/or persistence at the sites of infection, and that this molecule has a potential therapeutic role in polymicrobial infections.
HHQ and PQS, two Pseudomonas aeruginosa quorum‐sensing molecules, down‐regulate the innate immune responses through the nuclear factor‐κB pathway
Authors: Kim Kiwan , Kim Young Uk , Koh Byung Hee , Hwang Soo Seok , Kim Seol‐Hee , Lépine Francois , Cho You‐Hee , Lee Gap Ryol
Published: September 2009

To explore whether bacterial secreted 4‐hydroxy‐2‐alkylquinolines (HAQs) can regulate host innate immune responses, we used the extracts of bacterial culture supernatants from a wild‐type (PA14) and two mutants of Pseudomonas aeruginosa that have defects in making HAQs. Surprisingly, the extract of supernatants from the P. aeruginosa pqsA mutant that does not make HAQs showed strong stimulating activity for the production of innate cytokines such as tumour necrosis factor‐α and interleukin‐6 in the J774A.1 mouse monocyte/macrophage cell line, whereas the extract from the wild‐type did not. The addition of 4‐hydroxy‐2‐heptylquinoline (HHQ) or 2‐heptyl‐3,4‐dihydroxyquinoline (PQS, Pseudomonas quinolone signal) to mammalian cell culture media abolished this stimulating activity of the extracts of supernatants from the pqsA mutant on the expression of innate cytokines in J774A.1 cells and in the primary bronchoalveolar lavage cells from C57BL/6 mice, suggesting that HHQ and PQS can suppress the host innate immune responses. The pqsA mutant showed reduced dissemination in the lung tissue compared with the wild‐type strain in a mouse in vivo intranasal infection model, suggesting that HHQ and PQS may play a role in the pathogenicity of P. aeruginosa. HHQ and PQS reduced the nuclear factor‐κB (NF‐κB) binding to its binding sites and the expression of NF‐κB target genes, and PQS delayed inhibitor of κB degradation, indicating that the effect of HHQ and PQS was mediated through the NF‐κB pathway. Our results suggest that HHQ and PQS produced by P. aeruginosa actively suppress host innate immune responses.
p21Cip1 up‐regulated during histone deacetylase inhibitor‐induced CD4+ T‐cell anergy selectively associates with mitogen‐activated protein kinases
Authors: Dagtas Ayse Selma , Gilbert Kathleen M.
Published: September 2009

Histone deacetylase inhibitor n‐butyrate induced proliferative unresponsiveness in antigen‐stimulated murine CD4+ T cells. T cells anergized by n‐butyrate demonstrated reduced interleukin‐2 (IL‐2) secretion and decreased activating protein 1 (AP‐1) activity upon restimulation. Mechanistic studies determined that the cyclin‐dependent kinase (cdk) inhibitor p21Cip1 was up‐regulated in the anergic CD4+ T cells. p21Cip1 is known to inhibit the cell cycle through its interaction with cdk, proliferating cell nuclear antigen (PCNA) or c‐Jun N‐terminal kinase (JNK). p21Cip1 did not preferentially associate with PCNA or cdk in anergic T helper type 1 (Th1) cells. Instead, among the three interaction partners, p21Cip1 was found to interact with phospho‐JNK and phospho‐c‐jun selectively in the anergic CD4+ T cells. The activity of c‐jun and downstream transcription factor AP‐1 were suppressed in the anergic Th1 cells. In contrast, p21Cip1 and the two phospho‐proteins were never detected concurrently in the control CD4+ T cells. The n‐butyrate‐induced p21Cip1‐mediated inhibition of JNK and c‐jun represents a novel potential mechanism by which proliferative unresponsiveness was maintained in CD4+ T cells.
Increased prevalence of prolonged QT interval in males with primary or secondary hypogonadism: A pilot study
Authors: Pecori Giraldi F. , Toja P. M. , Filippini B. , Michailidis J. , Scacchi M. , Stramba Badiale M. , Cavagnini F.
Published: September 2009

Symptoms and signs of male hypogonadism span all organ systems, including the cardiovascular apparatus. The electrocardiographic QT interval reflects cardiac ventricular repolarization and, if prolonged, increases the risk of malignant arrhythmias. QT interval duration is similar in boys and girls during childhood, but shortens in males after puberty and experimental studies suggest that testosterone is a major contributor to shortening of QT interval in men. The aim of the present pilot study was to assess the duration of ventricular repolarization in adult males with primary or secondary hypogonadism. Standard ECG recordings were performed in 26 men (mean age 39.2 ± 2.17 years) with pituitary or testicular hypogonadism and repeated in 15 patients during testosterone replacement. Twenty‐six age‐matched control men were also analysed. Measured QT intervals were corrected for heart rate according to Bazzett’s formula (QTc = QT/√RR interval). The prevalence of prolonged QTc was considerably higher in hypogonadal patients (four of 26 men) than in control men (none,p < 0.05) and in the general, healthy population (<2.5%). QTc interval normalized on hormone replacement therapy in the four patients presenting prolonged QTc in the hypogonadal state. Heart rate and left ventricular mass did not differ among the two groups and no known QT‐prolonging factor was apparent in patients with abnormal QTc interval. In conclusion, a high number prolonged QT interval measurements was observed in hypogonadal men who may therefore be at increased risk for cardiac arrhythmias. This observation reveals an additional feature of male hypogonadism, which may benefit from testosterone replacement therapy.
Experiences of hospital care reported by bereaved relatives of patients after a stroke: a retrospective survey using the VOICES questionnaire
Authors: Young Amanda J. , Rogers Angie , Dent Louise , Addington‐Hall Julia M.
Published: September 2009

Title.  Experiences of hospital care reported by bereaved relatives of patients after astroke: a retrospective survey using the VOICES questionnaire.

Aim.  This paper is a report of a study conducted to explore the determinants of satisfaction with health and social care services in the last 3 months and 3 days of life as reported by bereaved relatives of those who died from a stroke in an institutional setting.

Background.  There is limited research about how best to meet the needs of those who die from stroke. A thorough understanding of the determinants of satisfaction with end of life care is crucial for effective service provision to increase awareness of the needs of dying patients.

Methods.  During a six‐month period in 2003, a population‐based survey of bereaved relatives of patients after stroke was conducted using a stroke‐specific version of the Views of Informal Carers Evaluation of Services postal questionnaire (183 informants, response rate 37%). The sub‐sample included those informants who reported that the deceased person had died in an institutional setting (91%, n = 165). The analysis was divided into two phases: univariate (Pearson chi‐square test) and multivariate phase (logistic regression).

Results.  Logistic regressions showed that discussing any worries about the treatment of the deceased person and feeling that the doctors and nurses knew enough about their condition were predictors of satisfaction with doctors and nurses in the last 3 months of life. Meeting the personal care needs of the deceased person, being involved in decisions and feeling that the deceased person died in the right place were predictors of satisfaction with care in the last 3 days of life.

Conclusion.  End of life care needs to address the individual needs of patients who die from stroke and those close to them. This study shows that individualised end of life care increases satisfaction and, although the data reported in this paper reflect care in 2003, there is no more recent evidence that contradicts this important overall finding.