bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between irritable bowel syndrome (IBS) and double depression (dysthymia plus major depression)
Authors: Masand P. S. , Kaplan D. S. , Gupta S. , Bhandary A. N.
Published: November 2007

Background: Irritable bowel syndrome (IBS) has been reported in a significant number of adults. To our knowledge, no study has looked at the prevalence of IBS in patients with double depression. Methods: Using a semi‐structured clinical interview to study the prevalence of IBS, we compared 26 patients seeking treatment for double depression (dysthymia plus major depression) to an age‐ and sex‐matched control group of patients (N = 40) who were seeking treatment in a general physician's office for other medical illnesses. The control group did not have any Axis I disorders. IBS was diagnosed according to the criteria of Dross man et al. (Gastroenterol Int 4:159–172, 1990). Results: 57.69% of patients with double depression met criteria for IBS in contrast with 2.5% of the control group (P = 0.0001). Patients with double depression were more likely to complain of symptoms of weakness, nocturnal bowel movements, and gastrointestinal symptoms related to stress as compared to patients in the control group. In 50% of patients, the psychiatric disease preceded the onset of the bowel disease, whereas in 37.5% of patients the bowel symptoms appeared first. Conclusions: IBS is common in patients with double depression. Clinicians should screen patients with psychiatric illness for IBS. Depression 3:303–308 (1995/1996). © 1996 Wiley‐Liss, Inc.
Differential impact of the transcriptional repressor Gfi1 on mature CD4+ and CD8+ T lymphocyte function
Authors: Pargmann Denise , Yücel Raif , Kosan Christian , Saba Ingrid , Klein‐Hitpass Ludger , Schimmer Simone , Heyd Florian , Dittmer Ulf , Möröy Tarik
Published: November 2007

The transcriptional repressor Gfi1 is a nuclear zinc‐finger protein that is expressed in T cell precursors in the thymus, but is down‐regulated in mature, resting T cells. Gfi1 expression rises transiently to levels seen in thymocytes upon antigenic activation. We show here that lack of Gfi1 causes delayed cell cycle entry and apoptosis after antigenic stimulation in both mature CD4+ and CD8+ T cells ex vivo. DNA micro‐array analysis demonstrated that this correlated with an up‐regulation of the death receptor CD95, the proapoptotic factors Bad and Apaf1 and the cell cycle inhibitor p21, and a down‐regulation of Bcl‐2 expression in Gfi1–/– T cells. Surprisingly, while Gfi1‐deficient CD4+ T cells showed the same defective behavior in vivo, Gfi1‐deficient CD8+ T cells showed no aberration in vivo and were fully able to mount an anti‐viral immune response. This indicates that Gfi1 exerts different functions in CD4+ and CD8+ T cells very likely by maintaining different genetic programs in both cell types, and appears to be essential for the CD4 helper T cell immune response but dispensable for the function of cytotoxic CD8+ T cells.
Regulation of constitutive and microbial pathogen‐induced human macrophage migration inhibitory factor(MIF) gene expression
Authors: Roger Thierry , Ding Xavier , Chanson Anne‐Laure , Renner Pascal , Calandra Thierry
Published: November 2007

The cytokine macrophage migration inhibitory factor (MIF) is an important regulator of innate immunity, inflammation and oncogenesis. However, four decades after its identification, the molecular mechanism(s) regulating the expression of the MIF gene remain largely unknown. Analyses of human monocytic (THP‐1), epithelial (HeLa and A549) and keratinocytic (HaCat) cells transfected with wild‐type, truncated and mutated MIF promoter reporter constructs, and electrophoretic mobility shift assay, chromatin immunoprecipitation, and siRNA inhibition indicated that the transcription factors specificity protein (Sp)1 and cAMP response element‐binding protein (CREB) are critical positive regulators of constitutive human MIF gene expression. Albeit located in a cytosine guanine dinucleotide island, the MIF gene was found to be hypomethylated, an observation consistent with high baseline transcriptional activity. Moreover, stimulation of THP‐1 cells and of peripheral blood mononuclear cells with microbial products up‐regulated phosphorylated Sp1 nuclear content, Sp1 DNA‐binding activity, MIF promoter activity and MIF mRNA levels in a MEK1/2‐, Sp1‐dependent manner. Taken together with previous observations of an important role for MIF in pro‐inflammatory macrophage responses, these present findings suggest a key role for Sp1 and CREB in transcriptional regulation of MIF gene expression and MIF‐dependent host antimicrobial innate immune defense.
Treatment of lupus‐prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms
Authors: Barrat Franck J. , Meeker Thea , Chan Jean H. , Guiducci Cristiana , Coffman Robert L.
Published: November 2007

The presence of autoantibodies specific for nucleic acid‐associated antigens is the hallmark of systemic lupus erythematosus (SLE). We have recently developed a specific inhibitor of TLR7 and TLR9, called immunoregulatory sequence (IRS) 954, and showed that it inhibits the induction of IFN‐α by human plasmacytoid dendritic cells in response to DNA and RNA viruses and isolated immune complexes from lupus patients. In this study, we show that IRS 954 can prevent progression of disease when injected in the lupus prone (NZB x NZW)F1 mice. Following treatment, we observed a significant reduction of serum levels of nucleic acid‐specific autoantibodies as well as decreased proteinuria, reduced glomerulonephritis, end‐organ damage and increased survival. These data demonstrate that in addition to its ability to block IFN‐α, IRS 954 can reduce symptoms in a lupus model and thus represents a promising therapeutic agent for the treatment of SLE.
Seismic behaviour of shallow foundations: Shaking table experiments vs numerical modelling
Authors: Paolucci Roberto , Shirato Masahiro , Yilmaz M. Tolga
Published: November 2007

The capability of a simplified approach to model the behaviour of shallow foundations during earthquakes is explored by numerical simulation of a series of shaking table tests performed at the Public Works Research Institute, Tsukuba, Japan. After a summary of the experimental work, the numerical model is introduced, where the whole soil–foundation system is represented by a multi‐degrees‐of‐freedom elasto‐plastic macro‐element, supporting a single degree‐of‐freedom superstructure. In spite of its simplicity and of the large intensity of the excitation involving a high degree of nonlinearity in the foundation response, the proposed approach is found to provide very satisfactory results in predicting the rocking behaviour of the system and the seismic actions transmitted to the superstructure. The agreement is further improved by introducing a simple degradation rule of the foundation stiffness parameters, suitable to capture even some minor details of the observed rocking response. On the other hand, the performance of the model is not fully satisfactory in predicting vertical settlements. Copyright © 2007 John Wiley & Sons, Ltd.
Evaluation of different sealing methods for anodized aluminum‐silicon carbide (Al/SiC) composites using EIS and SEM techniques
Authors: Herrera‐Hernandez H. , Vargas‐Garcia J. R. , Hallen‐Lopez J. M. , Mansfeld F.
Published: November 2007

Electrochemical impedance spectroscopy (EIS) and the scanning electron microscope (SEM) have been used in an investigation of the effectiveness of various sealing methods that can be used to improve the corrosion resistance of an anodized aluminum‐silicon carbide (Al/SiC) composite. Anodic oxide films were grown on Al7075‐T6 and the Al/SiC composite by sulfuric acid anodizing and sealing in a cold saturated solution of nickel acetate. Other samples were sealed using the traditional method of boiling water or hot nickel acetate for comparison. The results revealed a uniform anodized layer on Al7075‐T6 that resisted pitting corrosion for more than 2 weeks exposure to NaCl, whereas a cracked oxide film with variations in thickness was observed on the composite material. Pit initiation occurred in less than 5 days on the anodized Al/SiC that was sealed in the hot solutions. This study suggests that the traditional hot sealing methods did not provide sufficient corrosion protection for aluminum metal–matrix composites (MMCs) because the reinforcing SiC particles deteriorated the surface film structure. However, this defective film can be repaired by nickel hydrate precipitation during cold sealing or by applying a thick polyurethane coating.
Towards a Living Radical Polymerization of Styrene by Using Dithiolactone as a New Type of Mediating Agent
Authors: Soriano‐Moro J. Guillermo , Rico‐Valverde Julio C. , Enriquez‐Medrano Francisco J. , Maldonado‐Textle Hortensia , Vivaldo‐Lima Eduardo , Acosta‐Ortiz Ricardo , Guerrero‐Santos Ramiro
Published: November 2007

In this communication, γ‐phenyl‐γ‐butyrodithiolactone (DTL1) is presented as the first example of a new type of control agent. The styrene polymerization carried out at 60 °C in the presence of DTL1 exhibits living characteristics, without consuming DTL1 during the process. This unprecedented behavior was explained by a mechanism based on the reversible formation of a persistent radical adduct between the DTL1 and the polystyrene macroradicals.

magnified image
Transient waves in composite‐laminated plates with uncertain load and material property
Authors: Han X. , Jiang C. , Gong S. , Huang Y. H.
Published: November 2007

A method is suggested to deal with the wave propagation problems in composite‐laminated plates subjected to uncertainty in load and material property based on the interval analysis method and the hybrid numerical method (HNM). The uncertain parameters are treated as intervals, in which only their bounds of the uncertainty are needed. Using the first‐order Taylor expansion, the transient responses can be approximated as a linear function of the uncertain parameters. In this function, the transient responses at the midpoints of the uncertain parameters can be obtained directly through the HNM. A sensitivity analysis technique is suggested to calculate the first derivative of the transient responses with respect to each uncertain parameter based on two cases that the parameter exists in load or material property. Applying the interval extension in interval mathematics, the lower and upper bounds of the transient responses caused by the uncertainty can be finally obtained. The present method is applied to a numerical example, in which the uncertainty of the load, elastic constants of the layer material and ply orientations are all investigated, and the results demonstrate the effectiveness of the present method. Copyright © 2007 John Wiley & Sons, Ltd.
The Health eCard: the way ahead for medical records?
Authors: Chaplin Steve
Published: November 2007

The Health eCard is a patient‐held smartcard that contains their complete medical records downloaded by the practice. Steve Chaplin describes the potential benefits and drawbacks, primarily its cost. Copyright © 2007 Wiley Interface Ltd
Varenicline, a new treatment option in smoking cessation
Authors: Chaplin Steve , West Robert
Published: November 2007

Varenicline is a well‐tolerated novel treatment to aid smoking cessation in adults that is generally more effective than existing smoking cessation aids. In our New products review Steve Chaplin presents the clinical trial results relating to its efficacy and adverse effects, and Professor Robert West comments on its place in smoking cessation. Copyright © 2007 Wiley Interface Ltd
Structural properties of ZnO polymorphs [phys. stat. sol. (b) 244, No. 5, 1538–1543 (2007)]
Authors: Wróbel Jan , Piechota Jacek
Published: November 2007

The corrected values for the band gaps Eg, width of valence p‐band Wp, and d‐band position Ed, calculated within the LDA+U approximation for ZnO polymorphs are provided. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Versatile Preparation of Fluorescent Particles Based on Polyphosphazenes: From Micro‐ to Nanoscale
Authors: Zhang Jianxiang , Qiu Liyan , Li Xiaodong , Jin Yi , Zhu Kangjie
Published: November 2007

A series of intrinsically fluorescent hydrophobic and amphiphilic polyphosphazenes with ethyl tryptophan (EtTrp) and poly(N‐isopropylacrylamide) (PNIPAAm) or poly(ethylene glycol) (PEG) as hydrophobic and hydrophilic segments, respectively, are synthesized. Depending on polymer composition and preparation procedure, particles with diameters ranging from micro‐ to nanoscale can be prepared successfully, which might be used as a visible tracer, both in vitro or in vivo, in drug‐ or gene‐delivery systems, as well as in other biomedical studies such as diagnostic medicine and brain research. Most importantly, in combination with the flexible synthesis and versatile modification of polyphosphazene, this method provides a general protocol to engineer a broad range of fluorescent particles with different properties based on diverse polymers.
Degrees of heterogeneity and the survival of an insect population
Authors: Thompson W. A. , Cameron P. J. , Wellington W. G. , Vertinsky I. B.
Published: November 2007

The results of simulation experiments with a stochastic model incorporating internal and external sources of heterogeneity suggest that the western tent caterpillar is a risk spreader of a type discussed byDen Boer (1968). By maintaining physiological plasticity in its population, M.c. pluviale can survive periods of bad weather and then expand rapidly in an improved climate. Intrinsic variability in the moths’ dispersal capacity also ensures that some will continue to contribute to populations in the climatic refuges where the species persists during unfavorable periods, while others can quickly colonize marginal areas as soon as favorable conditions return. This northern population of the western tent caterpillar seems distinctly less well adapted to a world in which the terrain and the weather are more homogeneous than on the Saanich Peninsula.
Mathematical description of within‐tree distributions of the various developmental stages of Dendroctonus frontalis Zimm. (Coleoptera: Scolytidae)
Authors: Mayyasi A. M. , Pulley P. E. , Coulson R. N. , DeMichele D. W. , Foltz J. L.
Published: November 2007

Probability density functions for the various within‐tree developmental life stages of D. frontalis are derived. The differences between some of these distributions are discussed. The possibility of the existence of a negative feed‐back mechanism which enables the beetle to make optimum utilization of the available resources is proposed. In addition, the concept of an optimum location on the infested bole where the environmental (tree) conditions are such that maximum survivorship occurs is advanced.
Population studies of Cavelerius saccharivorusOkajima (Heteroptera: Lygaeidae): Adult dispersal in relation to the density
Authors: Murai Minoru
Published: November 2007

Two adjacent stations (H and L) were set up to study movement of C. saccharivorus adults in sugarcane fields. At the beginning of the study the density of C. saccharivorus including all stages of development was quite different between the two. The density of the first generation adult on Station H was about 5 times that on Station L. The number of C. saccharivorus on both the stations became almost the same one month after the beginning of the study. At the beginning of the study macropterous adults were more numerous in Station H than in Station L. However percentage of macropterous adults on Station L increased after one month whereas that on Station H declined.

About 2,000 marked adults were released on each station during the early period of the emergence of the first generation adult. Marked insects were recaptured on both the stations one month after the release. The adults released on the dense population (H) tended to disperse more actively than those on the scarce population (L). Marked macropterous adults moved more actively than brachypterous ones. The density related dispersal of adults was considered to be an important factor to regulate the population density.
Estimation of typical food portion sizes for children of different ages in Great Britain
Authors: Wrieden Wendy L. , Longbottom Patricia J. , Adamson Ashley J. , Ogston Simon A. , Payne Anne , Haleem Mohammad A. , Barton Karen L.
Published: November 2007

It is often the case in dietary assessment that it is not practicable to weigh individual intakes of foods eaten. The aim of the work described was to estimate typical food portion weights for children of different ages. Using the data available from the British National Diet and Nutrition Surveys of children aged 1½–4½ years (1992–1993) and young people aged 4–18 years (1997), descriptive statistics were obtained, and predicted weights were calculated by linear, quadratic and exponential regression for each age group. Following comparison of energy and nutrient intakes calculated from actual (from an earlier weighed intake study) and estimated portion weights, the final list of typical portion sizes was based on median portion weights for the 1–3- and 4–6-year age groups, and age-adjusted means using linear regression for the 7–10-, 11–14- and 15–18-year age groups. The number of foods recorded by fifty or more children was 133 for each of the younger age groups (1–3 and 4–6 years) and seventy-five for each of the older age groups. The food portion weights covered all food groups. All portion sizes increased with age with the exception of milk in tea or coffee. The present study draws on a unique source of weighed data on food portions of a large sample of children that is unlikely to be repeated and therefore provides the best possible estimates of children's food portion sizes in the UK.
COMPOSER IN INTERVIEW: DAVID MATTHEWS
Authors: Doran Mark
Published: November 2007

David Matthews was born in Walthamstow, London, in 1943. He began composing – with an attempt at a full-scale symphony – at the age of 16 but, being self-taught and formally unqualified in music, went to study classics at Nottingham University (1962–65; the university awarded him an Honorary Doctorate in Music in 1997). Starting in the early 1960s he was one of the musicians (along with his composer brother Colin and the composer and conductor Berthold Goldschmidt) who assisted Deryck Cooke in the preparation of what became Cooke's famous ‘Performing Version’ of the draft of Mahler's Tenth Symphony. Between 1966 and 1969 Matthews took lessons from Anthony Milner. During this period he was also working at Aldeburgh as an assistant to Benjamin Britten (1966–70); a few years later, it was to be in an improvised piano-duet version played by David and Colin Matthews that the partly paralysed Britten first heard his own Third String Quartet (1975).
HARMONIC PRACTICES IN OLIVER KNUSSEN'S MUSIC SINCE 1988: PART II
Authors: Anderson Julian
Published: November 2007

Songs without Voices, composed in 1991–2, is a set of four pieces for small instrumental ensemble comprising flute, cor anglais, clarinet, horn, piano, violin, viola and cello, lasting about eleven minutes. It follows on naturally from Knussen's Whitman Settings which preceded it, as three of its four movements derive their main melodic lines from purely instrumental settings of Whitman texts from the collection Leaves of Grass. Indeed the first movement's source text, Soon shall the winter's foil be here, is placed by Whitman in the collection immediately after The Voice of the Rain, the final text of Knussen's Whitman Settings.
PERENNIAL QUESTIONS
Authors: Silverman Julian
Published: November 2007

(Editor's Note: in the late 1960s Tempo featured a regular column written by the late Hans Keller entitled ‘The Contemporary Problem’ – an attempt, in the author's inimitable fashion, to probe behind current musical events and put them in perspective. Partly through the nature of that perspective the feature generated lively correspondence. It is our hope to provide a similar service for the 21st century with a new, occasional series of articles by different hands. Rather than suggest that contemporary music has (or is) a problem, or for a single author to encompass it about with obiter dicta, the idea is for writers to sound off about the broader issues of performance, asthetics, comprehension and silent assumption that happen to concern them and which underlie much contemporary musical activity and composition – to ask questions which have been around as long as music has, which rarely get asked and which perhaps have no definitive answer. (They are perhaps all aspects of the largest question of all: ‘What is new music FOR?’)

The editor will gladly consider topics, proposals, or answers to these PQs from all quarters. Meanwhile the following essay by Julian Silverman, sparked off by reading the letter from the Scottish composer David Johnson in Tempo 222 (October 2002) – itself prompted by features in two previous issues – seems a good point at which to launch this occasional series. Nothing is more perennial, especially in this age of maximum availability of recorded repertoire, than the question of what do about the past, which is always with us.)
London, Royal Albert Hall Proms 2002: Sofia Gubaidulina's ‘St John Passion and Resurrection’
Authors: Stein Robert
Published: November 2007

Although Sofia Gubaidulina has been an avowedly religious composer throughout almost all her long career, her Passion and Resurrection of Jesus Christ according to St John, which received its UK première at the Proms on …August, is distinguished among her recent works in that it is not simply a work with a religious inspiration but an act of worship (despite the Russian Orthodox church's ban on instruments in its services).
London, English national Opera: ‘The Handmaid's Tale’
Authors: Anderson Martin
Published: November 2007

Poul Ruders's opera The Handmaid's Tale is hardly an unknown quantity: its world-première production in Copenhagen in 2000 was recorded by da capo (8.224165–66) in a three-CD set that received justly loud encomia. But the UK stage première, transferring the Danish production for a run at the English National Opera that began on 3 April, revealed – in a way that the recording obviously could not – what a superior piece of theatre it is: music, libretto, direction, stage design, costumes and lighting all coalesce to thrilling effect. A depressing number of operatic productions sacrifice musical integrity to directorial whim, so it's deeply heartening to report that, for once, everything pulled dedicatedly in the same direction, with outstanding results: it has been years since I've seen something this good.
A Randomized Trial Investigating Training in Motivational Interviewing for Behavioral Health Providers
Authors: Moyers Theresa B. , Manuel Jennifer K. , Wilson Paul G. , Hendrickson Stacey M. L. , Talcott Wayne , Durand Peter
Published: November 2007

Evidence indicates that workshop training, personalized feedback, and individual consultation can increase competence in motivational interviewing (MI) among highly motivated and skilled substance abuse counselors. Little is known, however, about the translational value of these training strategies for counselors with fewer counseling skills and less stated motivation to learn MI. This study presents evidence from a randomized, controlled trial of 129 behavioral health providers assigned to receive workshop training and enrichments to learn MI. A diverse group of Air Force behavioral health providers working in substance abuse treatment programs were trained in MI and subsequently observed in clinical sessions at 4, 8 and 12 months after training. Results indicate that training was effective in increasing the skill level of these clinicians; however, these gains had decreased by the 4-month follow-up point. Training enrichments in the form of personalized feedback and consultation phone calls did not have an expected, additive effect on clinician skill level. The results of this study lend support to the hypothesis that a greater investment of resources and incentives may be necessary to achieve gains in MI skills for counselors with relatively lower baseline skills than those commonly participating in research studies.
Genetic diversity within Lablab purpureus and the application of gene-specific markers from a range of legume species
Authors: Venkatesha S. C. , Byre Gowda M. , Mahadevu P. , Mohan Rao A. , Kim D.-J. , Ellis T. H. N. , Knox M. R.
Published: November 2007

Molecular markers have been used to study genetic diversity within a set ofLablabpurpureusaccessions collected from the southern states of India. Amplified fragment length polymorphism (AFLP) molecular marker studies using a total of 78L.purpureusaccessions with nine primer combinations showed there was very little genetic diversity within theL.purpureusaccessions from the southern Indian germplasm collection as compared to a set of 15 accessions from other international germplasm collections that included African accessions. The set of 15 were selected from a random amplified length polymorphism (RAPD) marker study and chosen on the basis of widest genetic distance. Further molecular analysis with polymerase chain reaction (PCR) markers from 97 expressed sequence tag (EST) and gene-specific primer pairs, designed from a range of legume sequences, concurred with the AFLP analyses. Both of these approaches provide a wealth of markers for diversity and mapping studies. The 97 sequence-specific primer pairs tested inL.purpureusresulted in 70% amplification success, with 44% of primer pairs amplifying single bands and 10% double bands. Markers generated from these EST and genomic sequences provide useful cross-reference to comparative legume genomics that will potentially have long-term benefit to legume plant breeding.
Homograft patch repair in carotid artery rupture
Authors: Teebken  , Pichlmaier  , Leinung  , Lenarz  , Haverich
Published: November 2007

The case of a 24-year-old man with a rupture of the left common carotid artery and history of intravenous drug abuse is presented. Due to absence of a suitable autologous vein segment the carotid bulb was repaired with a human allograft patch.
Intermittent claudication secondary to a traumatic arteriovenous fistula
Authors: Kotelis  , Klemm  , v. Tengg-Kobligk  , Allenberg  , Böckler
Published: November 2007

Arteriovenous fistula (AVF) formation is a recognized complication of arterial trauma. A 63-year-old man with no known risk factors for atheroma and a history of a 20-year delay in the diagnosis and treatment of a traumatic AVF presented with right calf claudication (maximal walking distance = 150 m). A duplex ultrasound scan and a magnetic resonance angiography showed an aneurysmatic dilatation and partial thrombosis of the infrarenal aorta and the right leg feeding arteries. Selective angiography revealed a complete occlusion of the right popliteal artery in the segment 2 and the infrapopliteal arteries with good collateral formation in the lower leg. At this time, there is no indication for infragenual arterial revascularisation in this patient. Instead, therapy consists of exercise training and antiplatelet therapy. We concluded, that peripheral microembolism from the aneurysmatic aorta, iliac or femoral arteries is most probably the reason for the popliteal occlusion in this patient, representing a rare, nonatherosclerotic cause of claudication.
Enzyme improvement in the absence of structural knowledge: a novel statistical approach
Authors: Barak Yoram , Nov Yuval , Ackerley David F , Matin A
Published: November 2007

Most existing methods for improving protein activity are laborious and costly, as they either require knowledge of protein structure or involve expression and screening of a vast number of protein mutants. We describe here a successful first application of a novel approach, which requires no structural knowledge and is shown to significantly reduce the number of mutants that need to be screened. In the first phase of this study, around 7000 mutants were screened through standard directed evolution, yielding a 230-fold improvement in activity relative to the wild type. Using sequence analysis and site-directed mutagenesis, an additional single mutant was then produced, with 500-fold improved activity. In the second phase, a novel statistical method for protein improvement was used; building on data from the first phase, only 11 targeted additional mutants were produced through site-directed mutagenesis, and the best among them achieved a >1500-fold improvement in activity over the wild type. Thus, the statistical model underlying the experiment was validated, and its predictions were shown to reduce laboratory labor and resources.
Chronic stimulation of Nod2 mediates tolerance to bacterial products
Authors: Hedl Matija , Li Jing , Cho Judy H. , Abraham Clara
Published: November 2007

The Toll-like receptor (TLR) and nucleotide-binding oligomerization domain (Nod) families of proteins are critical for bacterial recognition, and, acutely, this frequently leads to proinflammatory responses. Polymorphisms in Nod2 (CARD 15) are associated with an increased likelihood of developing Crohn's disease. However, it is not yet clear how Nod2 dysfunctions lead to defects in human intestinal immune homeostasis. Studies to date have focused on functions after acute, rather than chronic, Nod2 stimulation. However, the intestine is an environment of chronic bacterial product exposure with tolerance to luminal flora. We therefore hypothesized that long-term Nod2 stimulation contributes to down-regulation of inflammatory responses from innate immune receptors. We found that pretreatment with muramyl dipeptide (MDP), a ligand for Nod2, significantly decreased production of the proinflammatory cytokines TNF-α, IL-8, and IL-1β upon Nod2, TLR4, and TLR2 restimulation in primary human monocyte-derived macrophages from a large cohort of individuals. Importantly, TNF-α-induced production of proinflammatory cytokines remained intact in these same cells. MDP-stimulated macrophages from Crohn's disease-relevant Leu1007insC Nod2 homozygote individuals were deficient in their ability to cross-tolerize to subsequent treatment with TLR2 and TLR4 ligands. We show that acute Nod2 stimulation induced IRAK-1 activation, and that chronic MDP treatment down-regulated IRAK-1 activation upon Nod2 or TLR4 restimulation. In a subset of individuals, chronic Nod2 stimulation induced expression of the IRAK-1 inhibitory protein IRAK-M. Significantly, intestinal macrophages exhibit tolerance to MDP per production of inflammatory cytokines. These results illustrate a role for chronic stimulation of Nod2 in mediating tolerance to bacterial products.
Savanna chimpanzees use tools to harvest the underground storage organs of plants
Authors: Hernandez-Aguilar R. Adriana , Moore Jim , Pickering Travis Rayne
Published: November 2007

It has been hypothesized that plant underground storage organs (USOs) played key roles in the initial hominin colonization of savanna habitats, the development of the distinctive skull and tooth morphology of the genus
Australopithecus
, and the evolution of the genus
Homo
by serving as “fallback foods” exploited during periods of food shortage. These hypotheses have been tested mostly by morphological, isotopic, and microwear analyses of hominin bones and teeth. Archaeological evidence of USO digging technology is equivocal. Until now relevant data from studies of chimpanzees, useful in behavioral models of early hominins because of their phylogenetic proximity and anatomical similarities, have been lacking. Here we report on the first evidence of chimpanzees using tools to dig for USOs, suggesting that exploitation of such resources was within the cognitive and technological reach of the earliest hominins. Consistent with scenarios of hominin adaptation to savannas, these data come from Ugalla (Tanzania), one of the driest, most open and seasonal chimpanzee habitats. USOs are, however, exploited during the rainy season, well after the period of most likely food shortage, contradicting the specific prediction of fallback food hypotheses. The discovery that savanna chimpanzees use tools to obtain USOs contradicts yet another claim of human uniqueness and provides a model for the study of variables influencing USO use among early hominins.
A novel polydnavirus protein inhibits the insect prophenoloxidase activation pathway
Authors: Beck Markus H. , Strand Michael R.
Published: November 2007

Pathogens often suppress the melanization response of host insects, but the underlying molecular mechanisms are largely unknown. Here we report that
Microplitis demolitor
bracovirus (MdBV) carried by the wasp
M. demolitor
produces a protein, Egf1.0, which inhibits the phenoloxidase (PO) cascade. Egf1.0 belongs to a larger gene family that shares a cysteine-rich motif with similarities to the trypsin inhibitor-like (TIL) domains of small serine proteinase inhibitors (smapins). Gain-of-function and RNAi experiments indicated that the Egf genes are the only MdBV-encoded factors responsible for disabling the insect melanization response. Known smapins bind target proteinases in a substrate-like fashion and are cleaved at a single reactive site bond. The P1–P1′ position for Egf1.0 has the sequence Arg-Phe, which suggested that its target proteinase is a prophenoloxidase-activating proteinase (PAP). Wild-type Egf1.0 inhibited PAP-3 from
Manduca sexta
, whereas Egf1.0
R51A
, whose reactive-site arginine was replaced with an alanine, had no PAP-3 inhibitory activity. Other experiments using wild-type and mutant constructs indicated that Egf1.0 blocks activation of the PO cascade via PAP inhibition. Overall, our results identify a novel inhibitor of the PO cascade and indicate that suppression of the host melanization response is functionally important for both the virus and its associated wasp.
A knockin mouse model of the Bardet–Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity
Authors: Davis Roger E. , Swiderski Ruth E. , Rahmouni Kamal , Nishimura Darryl Y. , Mullins Robert F. , Agassandian Khristofor , Philp Alisdair R. , Searby Charles C. , Andrews Michael P. , Thompson Stewart , Berry Christopher J. , Thedens Daniel R. , Yang Baoli , Weiss Robert M. , Cassell Martin D. , Stone Edwin M. , Sheffield Val C.
Published: November 2007

Bardet–Biedl syndrome (BBS) is a genetically heterogeneous disorder that results in retinal degeneration, obesity, cognitive impairment, polydactyly, renal abnormalities, and hypogenitalism. Of the 12 known BBS genes,
BBS1
is the most commonly mutated, and a single missense mutation (M390R) accounts for ≈80% of BBS1 cases. To gain insight into the function of BBS1, we generated a
Bbs1

M390R/M390R

knockin mouse model. Mice homozygous for the M390R mutation recapitulated aspects of the human phenotype, including retinal degeneration, male infertility, and obesity. The obese mutant mice were hyperphagic and hyperleptinemic and exhibited reduced locomotor activity but no elevation in mean arterial blood pressure. Morphological evaluation of
Bbs1
mutant brain neuroanatomy revealed ventriculomegaly of the lateral and third ventricles, thinning of the cerebral cortex, and reduced volume of the corpus striatum and hippocampus. Similar abnormalities were also observed in the brains of
Bbs2
−/−
,
Bbs4
−/−
, and
Bbs6
−/−
mice, establishing these neuroanatomical defects as a previously undescribed BBS mouse model phenotype. Ultrastructural examination of the ependymal cell cilia that line the enlarged third ventricle of the
Bbs1
mutant brains showed that, whereas the 9 + 2 arrangement of axonemal microtubules was intact, elongated cilia and cilia with abnormally swollen distal ends were present. Together with data from transmission electron microscopy analysis of photoreceptor cell connecting cilia, the
Bbs1
M390R mutation does not affect axonemal structure, but it may play a role in the regulation of cilia assembly and/or function.
Regulation of hypothalamic malonyl-CoA by central glucose and leptin
Authors: Wolfgang Michael J. , Cha Seung Hun , Sidhaye Aniket , Chohnan Shigeru , Cline Gary , Shulman Gerald I. , Lane M. Daniel
Published: November 2007

Hypothalamic malonyl-CoA has been shown to function in global energy homeostasis by modulating food intake and energy expenditure. Little is known, however, about the regulation of malonyl-CoA concentration in the central nervous system. To address this issue we investigated the response of putative intermediates in the malonyl-CoA pathway to metabolic and endocrine cues, notably those provoked by glucose and leptin. Hypothalamic malonyl-CoA rises in proportion to the carbohydrate content of the diet consumed after food deprivation. Malonyl-CoA concentration peaks 1 h after refeeding or after peripheral glucose administration. This response depends on the dose of glucose administered and is blocked by the i.c.v. administration of an inhibitor of glucose metabolism, 2-deoxyglucose (2-DG). The kinetics of change in hypothalamic malonyl-CoA after glucose administration is coincident with the suppression of phosphorylation of AMP kinase and acetyl-CoA carboxylase. Blockade of glucose utilization in the CNS by i.c.v. 2-DG prevented the effects of glucose on 5′AMP-activated protein kinase, malonyl-CoA, hypothalamic neuropeptide expression, and food intake. Finally, we showed that leptin can increase hypothalamic malonyl-CoA and that the increase is additive with glucose administration. Leptin-deficient
ob
/
ob
mice, however, showed no defect in the glucose- or refeeding-induced rise in hypothalamic malonyl-CoA after food deprivation, demonstrating that leptin was not required for this effect. These studies show that hypothalamic malonyl-CoA responds to the level of circulating glucose and leptin, both of which affect energy homeostasis.
ARWEN: a program to detect tRNA genes in metazoan mitochondrial nucleotide sequences
Authors: Laslett Dean , Canbäck Björn
Published: November 2007

Motivation: Mitochondrial genomes encode their own transfer RNAs (tRNAs). These are often degenerate in sequence and structure compared to tRNAs in their bacterial ancestors. This is one of the reasons why current tRNA gene predictor programs perform poorly identifying mitochondrial tRNA genes. As a consequence there is a need for a new program with the specific aim of predicting these tRNAs.

Results: In this study, we present the software ARWEN that identifies tRNA genes in metazoan mitochondrial nucleotide sequences. ARWEN detects close to 100% of previously annotated genes.

Availability: An online version, software for download and test results are available at www.acgt.se/online.html

Contact:  bcanback@acgt.se

Supplementary information: Supplementary data are available at Bioinformatics online.
Successful treatment of multi-resistant Pseudomonas aeruginosa osteomyelitis after allogeneic bone marrow transplantation with a combination of colistin and tigecycline
Authors: Stanzani Marta , Tumietto Fabio , Giannini Maria Benedetta , Bianchi Giuseppe , Nanetti Anna , Vianelli Nicola , Arpinati Mario , Giovannini Maddalena , Bonifazi Francesca , Bandini Giuseppe , Baccarani Michele
Published: November 2007

A case of osteomyelitis caused by multidrug-resistant Pseudomonas aeruginosa is reported in a patient who underwent allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. The patient was successfully treated by prolonged administration of a full dose of colistin and tigecycline, and surgical curettage with the positioning of resorbable calcium sulfate pellets loaded with colistin.
Stevens–Johnson syndrome without skin lesions
Authors: Latsch K. , Girschick H. J. , Abele-Horn M.
Published: November 2007

In childhood, Mycoplasma pneumoniae infections usually present as respiratory tract disease. However, extrapulmonary manifestations can be severe but the association with M. pneumoniae might not be considered. Here two adolescents who presented with severe exudative and ulcerative stomatitis accompanied by conjunctivitis and genital erosions are reported on. The skin was unaffected. The diagnosis of an acute M. pneumoniae infection was confirmed by serology and PCR. There are only few reports about this clinical entity and its nomenclature is inconsistent. The denomination ‘incomplete Stevens–Johnson syndrome’ has been suggested.
Biofilm formation by enterococci
Authors: Mohamed Jamal A. , Huang David B.
Published: November 2007

Enterococci are an important global cause of nosocomial infections, being increasingly associated with urinary tract infections, endocarditis, intra-abdominal and pelvic infections, catheter-related infections, surgical wound infections, and central nervous system infections. The two most common enterococci species are Enterococcus faecalis and Enterococcus faecium. Both are capable of producing biofilms, which consist of a population of cells attached irreversibly on various biotic and abiotic surfaces, encased in a hydrated matrix of exopolymeric substances. Many environmental and genetic factors are associated or have been proposed to be associated with the production of biofilm. This review discusses recent advances in knowledge about the biology and genetics of biofilm formation and the role of biofilms in enterococci pathogenesis.
Isolation of Gordonia terrae from a patient with catheter-related bacteraemia
Authors: Grisold A. J. , Roll P. , Hoenigl M. , Feierl G. , Vicenzi-Moser R. , Marth E.
Published: November 2007

A cornyeform bacterium was isolated from a blood culture from a 24-year-old man with familial hypertrophic non-obstructive cardiomyopathy, chronic abuse of anabolic steroids and prior admission to hospital because of clinical signs of sepsis. 16S rRNA gene analysis unambiguously identified Gordonia terrae.
Mechanical valve endocarditis caused by Gemella morbillorum
Authors: Al-Hujailan Ghanem , Lagacé-Wiens Philippe
Published: November 2007

As the usual pathogen spectrum of a late-onset (>12 month post-operatively) prosthetic valve endocarditis is similar to normal valve endocarditis, with the exception of coagulase-negative staphylococcus, a prosthetic valve endocarditis caused by unusual bacterial pathogens represents a therapeutic and diagnostic dilemma. The lack of well established criteria or clinical experience for the management of such infections makes therapy and prognosis difficult to determine. A case of successfully treated Gemella morbillorum prosthetic valve endocarditis and a review of the relevant literature are presented.
Rapid identification of Candida glabrata in Candida bloodstream infections
Authors: Foster Nicholas , Symes Charlotte , Barton Richard , Hobson Richard
Published: November 2007

Candida species are the fourth most common cause of bloodstream infection (BSI) in the hospitalized patient. Candida glabrata is the most common non-Candida albicans Candida species in England and Wales with an attributed mortality of 48 %. C. glabrata is known to demonstrate reduced susceptibility to fluconazole, resulting in treatment failures when employing this agent for empirical treatment of Candida BSI. The first part of this study demonstrated a technique utilizing a blood culture system commonly used by many laboratories (BACTEC 9240 automated detection system) that reduced the time to identification of this potentially resistant organism by up to 72 h. A presumptive identification was achieved by observing a difference in the duration of incubation required before growth was detected automatically between Lytic Anaerobic and Plus Aerobic culture bottles. Secondly, experiments exploring the growth characteristics of C. glabrata in BACTEC blood culture bottles containing various media were carried out to explore possible reasons underpinning this clinical observation. The detection of yeast in the anaerobic bottle of a blood culture pair consisting of Lytic Anaerobic and Plus Aerobic in a BACTEC 9240 system was found to be highly predictive of the isolation of C. glabrata (positive predictive value 93.3 %, negative predictive value 98.3 %). The reason for this appeared to be a component of the Lytic Anaerobic blood culture medium enhancing the growth of C. glabrata in that medium.
Low concentrations of commercial alcohol hand rubs facilitate growth of and secretion of extracellular proteins by multidrug-resistant strains of Acinetobacter baumannii
Authors: Edwards Justin , Patel Geeta , Wareham David W.
Published: November 2007

Acinetobacter baumannii is increasingly recognized as an important multidrug-resistant nosocomial pathogen. Recent work has highlighted enhanced growth and heightened virulence in the presence of ethyl alcohols. As alcohol-based hand rubs (ABHRs) are extensively used in health care settings, the authors set out to determine whether the hand rubs could also influence the growth of prevalent multidrug-resistant strains circulating in UK hospitals. A significant increase in growth was observed when minimal media were supplemented with concentrations of 1 % and lower of four commercially available hand rubs. In addition, growth in ABHR-supplemented media resulted in secretion of proteins into the culture supernatant. One of these was identified as OmpA, which is recognized as having emulsifying activity, which could potentially confer enhanced pathogenicity to A. baumannii.
A UK clinical isolate of Bordetella hinzii from a patient with myelodysplastic syndrome
Authors: Fry Norman K. , Duncan John , Edwards Martin T. , Tilley Rebecca E. , Chitnavis Dipti , Harman Ruth , Hammerton Haydn , Dainton Linda
Published: November 2007

What is believed to be the first clinical isolate of Bordetella hinzii in the UK, from a patient with myelodysplastic syndrome, is described. This patient had no known avian exposure, and the source of the organism remains unknown. It appears that the underlying immune deficiency of the patient increased the susceptibility to opportunistic infection with this organism. Human infection with B. hinzii is rare and this species is difficult to differentiate from Bordetella avium by routine phenotypic methods. Confirmation can be reliably achieved using genotypic methods, and the greater mutational variation of the ompA gene compared to other genes (e.g. 16S rRNA gene) allows unambiguous identification of this and other non-classical Bordetella species.
Universal patterns of purifying selection at noncoding positions in bacteria
Authors: Molina Nacho , van Nimwegen Erik
Published: November 2007

To investigate the dependence of the number of regulatory sites per intergenic region on genome size, we developed a new method for detecting purifying selection at noncoding positions in clades of related bacterial genomes. We comprehensively quantified evidence of purifying selection at noncoding positions across bacteria and found several striking universal patterns. Consistent with selection acting at transcriptional regulatory elements near the transcription start, we find a universal positional profile of selection with respect to gene starts and ends, showing most evidence of selection immediately upstream and least immediately downstream from genes. A further set of universal features indicates that selection for translation initiation efficiency is the major determinant of the sequence composition around translation start in all clades. In addition to a peak in selection at ribosomal binding sites, the region immediately around translation start shows a universal pattern of high adenine frequency, significant selection at silent positions, and avoidance of RNA secondary structure. Surprisingly, although the number of transcription factors (TF) increases quadratically with genome size, we present several lines of evidence that small and large genomes have the same average number of regulatory sites per intergenic region. By comparing the sequence diversity of the most and least conserved DNA words in intergenic regions across clades we provide evidence that the structure of transcription regulatory networks changes dramatically with genome size: Small genomes have a small number of TFs with a large number of target sites, whereas large genomes have a large number of TFs with a small number of target sites each.