bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphopeptide enrichment with stable spatial coordination on a titanium dioxide coated glass slide
Authors: Imanishi Susumu Y. , Kouvonen Petri , Smått Jan‐Henrik , Heikkilä Mikko , Peuhu Emilia , Mikhailov Andrey , Ritala Mikko , Lindén Mika , Corthals Garry L. , Eriksson John E.
Published: November 2009

Recent advances in phosphoproteomics have established powerful tools to analyze phosphorylation events. However, their spatial localization is lost due to sample homogenization procedures prior to the analysis. Imaging mass spectrometry (IMS) has emerged as a method to visualize the spatial distribution of molecules in tissue samples, but its application is still limited to relatively abundant molecules. Due to low phosphorylation stoichiometry, direct detection and imaging of protein phosphorylation by MS has not been achieved yet. Therefore we have developed a novel phosphopeptide enrichment strategy as a potential tool for in situ affinity imaging MS (AIMS). A specific type of titanium dioxide (TiO2)‐coated glass slides was designed and validated with casein tryptic digests for their ability to selectively retain phosphopeptides while maintaining their spatial coordination. Copyright © 2009 John Wiley & Sons, Ltd.
Photocrosslinking of a novel α,ω‐unsaturated copolyamide: mass spectrometric study on model compounds with benzophenone as photoinitiator
Authors: Mintsa Marion N'Negue , Lecamp Laurence , Loutelier‐Bourhis Corinne , Lange Catherine M. , Baumgarten Sigrid , Bunel Claude
Published: November 2009

The aim of this work was to understand the reactions involved in the photocrosslinking processes of a α,ω‐unsaturated copolyamide foreseen as a new UV‐curable powder coating. The crosslinking reaction was photoinitiated with benzophenone. In this paper, the photochemical reaction between benzophenone and several model compounds was investigated. The model compounds contained functional groups which could be present in copolyamide. The products resulting from UV curing were identified using a combination of high‐resolution mass spectrometry and MSn experiments. The characterization of the products allowed localization of the hydrogen abstraction by the type II photoinitiator during UV curing and, consequently, the determination of the reactive sites of the unsaturated polyamide chain which were involved in the photochemical reaction. Copyright © 2009 John Wiley & Sons, Ltd.
Matrix‐free thin‐layer chromatography/laser desorption ionization mass spectrometry for facile separation and identification of medicinal alkaloids
Authors: Shariatgorji Mohammadreza , Spacil Zdenek , Maddalo Gianluca , Cardenas Lourdes B. , Ilag Leopold L.
Published: November 2009

Quaternary protoberberine alkaloids belong to a pharmaceutically important class of isoquinoline alkaloids associated with bactericidal, fungicidal, insecticidal and antiviral activities. As traditional medicine gains wider acceptance, quick and robust analytical methods for the screening and analysis of plants containing these compounds attract considerable interest. Thin‐layer chromatography (TLC) combined with matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) is a powerful technique but suffers from dilution of the TLC bands resulting in decreased sensitivity and masking of signals in the low‐mass region both due to addition of matrix. This study integrates for the first time conventional silica gel TLC and laser desorption ionization mass spectrometry (LDI‐MS) thus eliminating the need for any external matrix. Successful separation of berberine (Rf = 0.56) and palmatine (Rf = 0.46) fromBerberis barandanaincluding their identification by MS are demonstrated. Furthermore, a robust electrospray ionization (ESI)‐MS method utilizing residual sample from TLC for quantification of berberine applying selected reaction monitoring and standard addition method is presented. The amount of berberine in the plant root prepared for the study was determined to be 0.70% (w/w). Copyright © 2009 John Wiley & Sons, Ltd.
A novel high‐performance liquid chromatography/mass spectrometry method for improved selective and sensitive measurement of methotrexate polyglutamation status in human red blood cells
Authors: van Haandel Leon , Becker Mara L. , Leeder J. Steven , Williams Todd D. , Stobaugh John F.
Published: November 2009

The folate antagonist methotrexate is commonly used in low dose for treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Therapeutic effects are attributed to intracellular levels of various methotrexate polyglutamates. The present methodology, combining a simple preparation step with ion‐pairing reversed‐phase liquid chromatography and electrospray ionization mass spectrometry, is suitable for the measurement of methotrexate and its polyglutamates2–7, in human red blood cells. Sample preparation consists of perchloric acid protein precipitation followed by solid‐phase extraction. Baseline separation of all analytes was achieved within 10 min using a Phenomenex Synergy C18 column together with a gradient solvent program obtained from blending acetonitrile with pH 7.5, 5 mM aqueous dimethylhexylamine. Seven methotrexate polyglutamates were detected using multiple reaction monitoring, with the mass spectrometer operating in positive ion mode. Using 20 µL injection volumes, limits of detection were 2.5 nM for individual methotrexate polyglutamates, while large volume (100 µL) injections led to detection limits of 0.5 nM and linear calibration from 0.5 to 100 nM for individual analytes. Finally, the presented methodology was applied for the analysis of methotrexate and its polyglutamates in red blood cells obtained from patients being treated for juvenile idiopathic arthritis with methotrexate. Significantly, the methodology proved suitable for determination of long‐chain methotrexate polyglutamates5–7 and further, appears to be superior with respect to sensitivity, selectivity and speed as compared to all previously described approaches. Copyright © 2009 John Wiley & Sons, Ltd.
Electrospray ionization mass spectrometry studies of cyclodextrin‐carboxylate ion inclusion complexes
Authors: Mohamed Mohamed H. , Wilson Lee D. , Headley John V. , Peru Kerry M.
Published: November 2009

Aqueous solutions containing simple model aliphatic and alicyclic carboxylic acids (surrogates 1–4) were studied using negative ion electrospray mass spectrometry (ESI‐MS) in the presence and absence of α‐, β‐, and γ‐cyclodextrin. Molecular ions were detected corresponding to the parent carboxylic acids and complexed forms of the carboxylic acids; the latter corresponding to non‐covalent inclusion complexes formed between carboxylic acid and cyclodextrin compounds (e.g., β‐CD, α‐CD, and γ‐CD). The formation of 1:1 non‐covalent inclusion cyclodextrin‐carboxylic complexes and non‐inclusion forms of the cellobiose‐carboxylic acid compounds was also observed.

Aqueous solutions of Syncrude‐derived mixtures of aliphatic and alicyclic carboxylic acids (i.e. naphthenic acids; NAs) were similarly studied using ESI‐MS, as outlined above. Molecular ions corresponding to the formation of CD‐NAs inclusion complexes were observed whereas 1:1 non‐inclusion forms of the cellobiose‐NAs complexes were not detected. The ESI‐MS results provide evidence for some measure of inclusion selectivity according to the 'size‐fit' of the host and guest molecules (according to carbon number) and the hydrogen deficiency (z‐series) of the naphthenic acid compounds. The relative abundances of the molecular ions of the CD‐carboxylate anion adducts provide strong support for differing complex stability in aqueous solution. In general, the 1:1 complex stability according to hydrogen deficiency (z‐series) of naphthenic acids may be attributed to the nature of the cavity size of the cyclodextrin host compounds and the relative lipophilicity of the guest. Copyright © 2009 John Wiley & Sons, Ltd.
Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride‐induced acute phase response
Authors: Butz Daniel E. , Cook Mark E. , Eghbalnia Hamid R. , Assadi‐Porter Fariba , Porter Warren P.
Published: November 2009

The natural abundance of carbon‐13 in blood proteins increases during the cachectic state and may be a biomarker for disease status. We hypothesized a corresponding drop in the relative abundance of 13C in breath CO2. Using the lipopolysacchride (LPS)‐induced endotoxemia model of the acute cachectic state, we demonstrated that the acute phase response causes shifts in the stable isotopes of carbon in exhaled CO2 (13CO2/12CO2 delta value) shortly after administration of LPS while glucocorticoid treatment does not. Mice were injected with LPS and stable isotopes of blood amino acids and carbon in exhaled CO2 were monitored. An increase in the relative isotopic mass of serum alanine, proline and threonine was observed at 3 h after LPS injection. Breath delta values began dropping immediately after administration of LPS, and were 4–5 delta values lower than those of the control animals by 2.5 h after injection. A corresponding drop in delta value was not observed with dexamethasone treatment. Thus protein synthesis during the acute phase response probably caused the fractionation of stable isotopes observed in the plasma amino acids and in exhaled breath 13CO2 delta values. The exhaled breath 13CO2 delta value may be a valuable real‐time biomarker of cachexia associated with an acute phase response due to endotoxemia. Copyright © 2009 John Wiley & Sons, Ltd.
Species identification by analysis of bone collagen using matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry
Authors: Buckley Michael , Collins Matthew , Thomas‐Oates Jane , Wilson Julie C.
Published: November 2009

Species identification of fragmentary bone, such as in rendered meat and bone meal or from archaeological sites, is often difficult in the absence of clear morphological markers. Here we present a robust method of analysing genus‐specific collagen peptides by mass spectrometry simply by using solid‐phase extraction (a C18 ZipTip®) for peptide purification, rather than liquid chromatography/mass spectrometry (LC/MS). Analysis of the collagen from 32 different mammal species identified a total of 92 peptide markers that could be used for species identification, for example, in processed food and animal feed. A set of ancient (>100 ka@10°C) bone samples was also analysed to show that the proposed method has applications to archaeological bone identification. Copyright © 2009 John Wiley & Sons, Ltd.
Metabolomics profiling of extracellular metabolites in recombinant Chinese Hamster Ovary fed‐batch culture
Authors: Chong William P. K. , Goh Lin Tang , Reddy Satty G. , Yusufi Faraaz N.K. , Lee Dong Yup , Wong Niki S. C. , Heng Chew Kiat , Yap Miranda G. S. , Ho Ying Swan
Published: November 2009

A metabolomics‐based approach was used to time profile extracellular metabolites in duplicate fed‐batch bioreactor cultures of recombinant Chinese Hamster Ovary (CHO) cells producing monoclonal IgG antibody. Culture medium was collected and analysed using a high‐performance liquid chromatography (HPLC) system in tandem with an LTQ‐Orbitrap mass spectrometer. An in‐house software was developed to pre‐process the LC/MS data in terms of filtering and peak detection. This was followed by principal component analysis (PCA) to assess variance amongst the samples, and hierarchical clustering to categorize mass peaks by their time profiles. Finally, LC/MS2 experiments using the LTQ‐Orbitrap (where standard was available) and SYNAPT™ HDMS (where standard was unavailable) were performed to confirm the identities of the metabolites. Two groups of identified metabolites were of particular interest; the first consisted of metabolites that began to accumulate when the culture entered stationary phase. The majority of them were amino acid derivatives and they were likely to be derived from the amino acids in the feed media. Examples included acetylphenylalanine and dimethylarginine which are known to be detrimental to cell growth. The second group of metabolites showed a downward trend as the culture progressed. Two of them were medium components – tryptophan and choline, and these became depleted midway into the culture despite the addition of feed media. The findings demonstrated the potential of utilizing metabolomics to guide medium design for fed‐batch culture to potentially improve cell growth and product titer. Copyright © 2009 John Wiley & Sons, Ltd.
Global synchronization of complex dynamical networks with network failures
Authors: Wang Yan‐Wu , Xiao Jiang‐Wen , Wang Hua O.
Published: November 2009

Network failure refers to the case that parts or all of the connections in the network become disconnected. In this paper, the global synchronization of complex dynamical networks with network failures is studied based on the framework of switching system. For simplicity, assume that the network becomes totally unavailable when network failures happen and it takes a period of time to fix the network. In order to ensure the global synchronization of CDNs with network failures, the upper bounds of both the unavailability rate of the network and the frequency of network failures are obtained, respectively. Illustrated examples and the simulation results also show the effectiveness of the proposed result. Copyright © 2009 John Wiley & Sons, Ltd.
Maneuverability and path following control of wheeled mobile robot in the presence of wheel skidding and slipping
Authors: Low Chang Boon , Wang Danwei
Published: November 2009

This paper addresses the path following control problem of wheeled mobile robots in the presence of wheel skidding and slipping. A conditional global positioning system (GPS)‐based path following controller is proposed for four generic WMRs to achieve high‐precision path following performance. The proposed controller utilizes real‐time kinematic‐GPS and other aiding sensors to determine the robot's pose and wheel skidding and slipping perturbations to achieve accurate path following control. The reported simulation and experimental results suggest that with this control scheme, the WMRs are able to maneuver with precision. © 2009 Wiley Periodicals, Inc.
Survival analysis with clustered observations of orthodontic brackets
Authors: Petracci Elisabetta , Farella Mauro , Galeone Carlotta , Albano Alessandra , Ferraroni Monica , Decarli Adriano
Published: November 2009

Failures in the bonding of dental bracket are a big concern for orthodontists. Clinical experience suggests that some patients are more prone than others to experience failures. Therefore, it can be expected that in statistical analysis of orthodontic bracket failures, the usual assumption of independence between the observations is violated. An approach to overcome this problem is to apply the frailty model, in which the association between failure times is modelled with a random‐effect term (i.e. frailty). We postulated that brackets of the same subject share the same frailty, that is, a latent common group effect, due to some unknown or unobserved covariates.

The aim of this study was to investigate possible risk factors related to bracket failure using Cox proportional hazards model with a shared frailty term and to compare the results with those obtained using a basic Cox proportional hazards model.

Survival data for 1677 brackets were obtained from a cohort of 54 females (mean age ± SD: 13.3±4.8yrs) and 46 males (mean age ±SD: 13.1±3.8yrs) over a eight‐year period. Age, gender, vertical craniofacial morphology and anatomical location of brackets were entered into Cox models as covariates. The findings indicated that bracket failure was significantly affected by tooth position within the dental arch, with the highest failure risk in maxillary posterior region. Age, gender and vertical craniofacial morphology did not affect bracket failure. A Cox proportional hazards model with a shared frailty term represents a useful approach for modelling orthodontic bracket failures. Copyright © 2009 John Wiley & Sons, Ltd.
Flexibility of Bayesian generalized linear mixed models for oral health research
Authors: Berchialla Paola , Baldi Ileana , Notaro Vincenzo , Barone‐Monfrin Sandro , Bassi Francesco , Gregori Dario
Published: November 2009

Many outcome variables in oral research are characterized by positive values and heavy skewness in the right tail. Examples are provided by many distributions of dental variables such as DMF (decayed, missing, filled teeth) scores, oral health impact profile score, gingival index scores, and microbiologic counts. Moreover, heterogeneity in data arises when more than one tooth is studied for each patient, due to the clusterization.

Over the past decade, linear mixed models (LMEs) have become a common statistical tool to account for within‐subject correlation in data with repeated measures. When a normal error is reasonably assumed, estimates of LMEs are supported by many statistical packages. Such is not the case for skewed data, where generalized linear mixed models (GLMMs) are required. However, the current software available supports only special cases of GLMMs or relies on crude Laplace‐type approximation of integrals. In this study, a Bayesian approach is taken to estimate GLMMs for clustered skewed dental data. A Gamma GLMM and a log‐normal model are employed to allow for heterogeneity across clusters, deriving from the patient‐operator‐tooth susceptibility typical of this clinical context. A comparison to the frequentist framework is also provided. In our case, Gamma GLMM fits data better than the log‐normal distribution, while providing more precise estimates compared with the likelihood approach. A key advantage of the Bayesian framework is its ability to readily provide a flexible approach for implementation while simultaneously providing a formal procedure for solving inference problems. Copyright © 2009 John Wiley & Sons, Ltd.
Modelling count data with excessive zeros: The need for class prediction in zero‐inflated models and the issue of data generation in choosing between zero‐inflated and generic mixture models for dental caries data
Authors: Gilthorpe Mark S. , Frydenberg Morten , Cheng Yaping , Baelum Vibeke
Published: November 2009

Count data may possess an ‘excess’ of zeros relative to standard distributions. Zero‐inflated Poisson (ZiP) or binomial (ZiB) and generic mixture models have been proposed to deal with such data. We consider biomedical count data with an excess number of zeros and seek to address the following: (i) do zero‐inflated models need covariates in the distribution part to predict class membership; (ii) what model‐fit criteria have clinical relevance to predicted counts; (iii) can very different model parameterizations have near‐identical fit; and (iv) how could model selection and hence model interpretation be aided by considering data generation processes? We show that covariates in the distribution part of zero‐inflated models are needed to predict class membership. A range of model‐fit criteria should be considered, as consensus is rarely achieved, and considering predicted outcomes may be just as valuable as likelihood‐based criteria. Zero‐inflated and generic mixture models may be indistinguishable according to both likelihood‐based model‐fit criteria and predicted outcomes, in which case model differentiation, hence, model selection and interpretation, might be guided by the consideration of a priori data generation processes. Zero‐inflated models reflect whether or not there are (or have been) risk differences in disease onset and disease progression, while generic mixture models identify sub‐types of individuals with similar risks of disease onset and progression. One or both modelling strategies may be used, though a priori knowledge or clinical impression of data generation might help to distinguish between two or more parameterizations that exhibit similar fit and yield near‐identical predicted counts. Copyright © 2009 John Wiley & Sons, Ltd.
Ultrasound monitoring in patients undergoing in‐vitro fertilization after methotrexate treatment for ectopic pregnancy
Authors: Provansal M. , Agostini A. , Lacroix O. , Gerbeau S. , Grillo J.‐M. , Gamerre M.
Published: November 2009

Objectives

To compare sonographic characteristics of the endometrium and follicles during in‐vitro fertilization (IVF) before and after methotrexate (MTX) treatment for ectopic pregnancy.

Methods

This retrospective study, conducted at Conception Hospital from January 2000 to July 2007, included all patients diagnosed with an ectopic pregnancy resulting from IVF treatment that was treated with MTX and who then underwent another IVF cycle. We compared the number and size of follicles and the endometrial thickness and quality on the day of human chorionic gonadotropin injection in the cycles before and after the MTX treatment to determine whether MTX had any effect.

Results

Eleven patients were included in the study. The median interval between the IVF cycle resulting in ectopic pregnancy and the first IVF cycle after MTX therapy was 180 (range, 150–900) days. There was no statistically significant difference between the before and after MTX treatment groups with respect to number of follicles (14 (3–20) vs. 9 (4–16), P = 0.12), follicle size (16.5 (14.7–21.7) mm vs. 17.8 (14.9–19.8) mm, P = 0.37), endometrial thickness (10.0 (9.5–12.0) mm vs. 10.0 (7.5–14.0) mm, P = 0.31) or endometrial quality (P = 0.32). Four women became pregnant during the IVF cycle following MTX treatment.

Conclusions

Ultrasound monitoring showed no modification of the characteristics of the endometrium or follicles during IVF after MTX treatment for ectopic pregnancy. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Gel infusion sonography in the evaluation of the uterine cavity
Authors: Van den Bosch T. , Betsas G. , Van Schoubroeck D. , Daemen A. , Vandenbroucke V. , Cornelis A. , De Moor B. , Deprest J. , Timmerman D.
Published: November 2009

Objectives

To compare gel infusion sonohysterography (GIS) with saline contrast sonohysterography (SCSH) with regard to technical feasibility and procedure‐related pain experienced by patients.

Methods

This prospective observational cohort study included 551 consecutive patients with abnormal bleeding: SCSH was attempted in the first 402 women and GIS was attempted in the following 149. All procedures were performed by the same examiner, in the same clinical setting, using a 2‐mm diameter catheter. After contrast sonohysterography, most patients underwent office hysteroscopy (n = 502) and endometrial sampling (n = 323). The women were asked to rate the pain experienced during each procedure using a 100‐mm visual analog scale (VAS). Patients' characteristics, ultrasound findings, histological diagnosis, technical failures and procedure‐related pain were compared between the two procedures.

Results

The mean ± SD VAS score for contrast sonography, subsequent hysteroscopy and endometrial biopsy were 22.9 ± 21.7, 38.8 ± 26.6 and 50.0 ± 26.3, respectively, in the SCSH subgroup vs. 16.5 ± 21.5, 27.6 ± 28 and 33.6 ± 30.3, respectively, in the GIS subgroup (P = 0.0051, P = 0.0005 and P = 0.0003, respectively). The technical failure rate was 5% in the SCSH subgroup vs. 2% in the GIS subgroup (P = 0.1522).

Conclusions

GIS and SCSH showed similar technical feasibility. The procedure‐related pain reported by patients during contrast sonohysterography, as well as during subsequent hysteroscopy and endometrial sampling, was less in the GIS group. Copyright © 2009 ISUOG. Published by John Wiley & Sons, Ltd.
Profiling Capacity for Coordination and Systems Change: The Relative Contribution of Stakeholder Relationships in Interorganizational Collaboratives
Authors: Nowell Branda
Published: November 2009

In response to increasing demands for greater coordination and collaboration among community institutions, interorganizational collaboratives (i.e., coalitions, partnerships, coordinating councils) have emerged as a popular mechanism for strengthening the capacity of a community system to respond to public and social issues. This study adopts a network approach to explore the relative importance of dense networks of cooperative relationships among members of interorganizational collaboratives for two outcomes of effectiveness: improving interorganizational coordination and fostering systems change. Based on survey and social network data collected from 48 different collaboratives, findings indicate that, relative to other key characteristics of collaboratives identified in previous literature, cooperative stakeholder relationships were the strongest predictor of systems change outcomes. However, for coordination outcomes, stakeholder relationships were overshadowed in importance by the leadership and decision making capacity of the collaborative. Collectively, findings suggest key differences in the requisite capacity profiles for coordination and systems change outcomes.
Women's Perceptions of the Personal and Family Impact of Genetic Cancer Risk Assessment: Focus Group Findings
Authors: MacDonald Deborah J. , Sarna Linda , Weitzel Jeffrey N. , Ferrell Betty
Published: November 2009

Women with a personal or family history of breast or ovarian cancer are increasingly presenting for genetic cancer risk assessment (GCRA). To explore the personal and family impact of GCRA, four focus groups were conducted of women seen for risk assessment. Participants were 22 primarily non‐Latina White women with a personal or family history of breast or ovarian cancer. Analysis of the data identified new themes related to balancing time to assimilate risk information with the need to make timely healthcare decisions, physicians’ lack of sufficient genetic knowledge, and concern for daughters regardless of the daughters’ age. Other themes related to protecting others, knowledge as empowerment, reassessing personal attribution of cancer risk, managing uncertainty, reappraising body image, and experiencing divergent family responses to communication of cancer risk and healthcare decisions. Understanding the personal and family impact of GCRA may enable genetics professionals to tailor their counseling efforts to better meet the needs of these women. Additional research is needed to extend these findings and identify interventions to support positive outcomes of GCRA.
The Wide-Awake Approach to Dupuytren's Disease: Fasciectomy under Local Anesthetic with Epinephrine
Authors: Nelson Rebecca , Higgins Amanda , Conrad Joanie , Bell Mike , Lalonde Don
Published: November 2009

The Wide-Awake Approach to Dupuytren's contracture involves fasciectomy under local anesthetic with epinephrine and no tourniquet. The goal of this study is to show that the Wide-Awake Approach produces equivalent outcomes to fasciectomy under general anesthetic with a tourniquet, with fewer risks to the patient. A multicenter retrospective review was conducted on 111 patients with fasciectomies under local or general anesthetic between 2001 and 2007. Data on patient demographics, comorbidities, cost, as well as range of motion was collected and evaluated using Microsoft Excel and SAS. Of 148 fingers, 102 were treated under local and 46 under general anesthetic. The average postoperative Total Active Motion (TAM) for general anesthetic patients was 199.0±29.6 (D5), 223.9±29.3 (D4), 234.6±14.6 (D3), and 246.7±14.4 (D2). The average postoperative TAM for local anesthetic patients was 168.3±62.2 (D5), 195.9±67.5 (D4), 173.0±72.6 (D3), and 177.5±31.8 (D2). There were no significant differences between any of these individual groups ( p=0.09, 0.26, 0.12, and 0.20, respectively); however, when pooled, the overall TAM was significantly greater in the general anesthesia group (222.0±29.7 vs. 186.0±63.0, p=0.002.). Complication rates and types were similar with both techniques. The Wide-Awake Approach to Dupuytren's contracture avoids general anesthetic risks and has cost benefits to healthcare providers. Although it yields similar range of motion outcomes to fasciectomy performed under general anesthesia, total active motion may be better with fasciectomy done under general anesthesia.
Neue Entwicklungen in der Psoriasisgenetik
Authors: Hüffmeier U. , Reis A.
Published: November 2009

Psoriasis vulgaris (PsV) ist eine chronische, entzündliche Hauterkrankung mit einer multifaktoriellen Vererbung. Nachdem der stärkste genetische Risikofaktor, das HLA-Cw0602-Allel (bzw. ein Allel in starkem Kopplungsungleichgewicht), insbesondere für die frühere Manifestationsform (<40. Lebensjahr), schon seit langem bekannt ist, konnten innerhalb der letzten beiden Jahre durch genomweite Assoziationsstudien sowie Untersuchungen von Kopienzahlveränderungen zahlreiche weitere Suszeptibilitätsfaktoren identifiziert werden. Zu den am besten replizierten Befunden zählen Varianten in 3 Genen des Interleukin-23-Rezeptor-Signalwegs. Außerdem konnten mehrere Gene des NFκB-Signalwegs (nukleärer Faktor κB) sowie ein Gen, dessen Produkt immunmodulatorisch in der TH2-Zell-vermittelten (TH-Zelle: T-Helfer-Zelle) Antwort wirkt, identifiziert werden. Neben dieser Bestätigung von PsV als einer immunologisch bedingten Erkrankung weisen mit PsV assoziierte Kopienzahlveränderungen auf eine zusätzliche zugrunde liegende Barrierestörung hin. Dies sind zum einen eine reduzierte Kopienzahl zweier epidermal exprimierter Gene des Clusters der Late-cornified-Envelope-Gene auf Chromosom 1q und zum anderen eine erhöhte Kopienzahl eines β-Defensin-Clusters auf Chromosom 8p.
On the biogenesis of myelin membranes: Sorting, trafficking and cell polarity
Authors: Baron Wia , Hoekstra Dick
Published: November 2009

In the central nervous system, a multilayered membrane layer known as the myelin sheath enwraps axons, and is required for optimal saltatory signal conductance. The sheath develops from membrane processes that extend from the plasma membrane of oligodendrocytes and displays a unique lipid and protein composition. Myelin biogenesis is carefully regulated, and multiple transport pathways involving a variety of endosomal compartments are involved. Here we briefly summarize how the major myelin proteins proteolipid protein and myelin basic protein reach the sheath, and highlight potential mechanisms involved, including the role of myelin specific lipids and cell polarity related transport pathways.
AKAP 18 α and γ have opposing effects on insulin release in INS‐1E cells
Authors: Josefsen Knud , Lee Ying C. , Thams Peter , Efendic Suad , Nielsen Jens H.
Published: November 2009

A‐kinase anchoring proteins (AKAPs) are known to compartmentalise protein kinase(s) to discrete cellular locations. Here we show that silencing of AKAP 18 α or γ expression results in decreased or increased glucose‐stimulated insulin secretion in INS‐1E cells. Glucose stimulates AKAP 18 α and inhibits AKAP 18 γ mRNA expressions while palmitate markedly reduces AKAP 18 α expression. Human growth hormone (GH) stimulates AKAP 18 α expression and attenuates palmitate‐induced suppression of AKAP 18 α mRNA level. The roles of AKAP 18 α and γ in mediating insulin release are consistent with their respective regulations by glucose.
Eukaryotic and archaeal translation initiation factor 2: A heterotrimeric tRNA carrier
Authors: Schmitt Emmanuelle , Naveau Marie , Mechulam Yves
Published: November 2009

Eukaryotic/archaeal translation initiation factor 2 (e/aIF2) is a heterotrimeric GTPase that plays a key role in selection of the correct start codon on messenger RNA. This review integrates structural and functional data to discuss the involvement of the three subunits in initiator tRNA binding. A possible role of the peripheral subunits in modulating the guanine nucleotide cycle on the core subunit is also addressed.
Dual activity of certain HIT‐proteins: A. thaliana Hint4 and C. elegans DcpS act on adenosine 5′‐phosphosulfate as hydrolases (forming AMP) and as phosphorylases (forming ADP)
Authors: Guranowski Andrzej , Wojdyła Anna Maria , Zimny Jarosław , Wypijewska Anna , Kowalska Joanna , Jemielity Jacek , Davis Richard E. , Bieganowski Paweł
Published: November 2009

Histidine triad (HIT)‐family proteins interact with different mono‐ and dinucleotides and catalyze their hydrolysis. During a study of the substrate specificity of seven HIT‐family proteins, we have shown that each can act as a sulfohydrolase, catalyzing the liberation of AMP from adenosine 5′‐phosphosulfate (APS or SO4‐pA). However, in the presence of orthophosphate, Arabidopsis thaliana Hint4 and Caenorhabditis elegans DcpS also behaved as APS phosphorylases, forming ADP. Low pH promoted the phosphorolytic and high pH the hydrolytic activities. These proteins, and in particular Hint4, also catalyzed hydrolysis or phosphorolysis of some other adenylyl‐derivatives but at lower rates than those for APS cleavage. A mechanism for these activities is proposed and the possible role of some HIT‐proteins in APS metabolism is discussed.
Low Complexity Regions behave as tRNA sponges to help co‐translational folding of plasmodial proteins
Authors: Frugier Magali , Bour Tania , Ayach Maya , Santos Manuel A.S. , Rudinger-Thirion Joëlle , Théobald-Dietrich Anne , Pizzi Elizabetta
Published: November 2009

In most organisms, the information necessary to specify the native 3D‐structures of proteins is encoded in the corresponding mRNA sequences. Translational accuracy and efficiency are coupled and sequences that are slowly translated play an essential role in the concomitant folding of protein domains. Here, we suggest that the well‐known mechanisms for the regulation of translational efficiency, which involves mRNA structure and/or asymmetric tRNA abundance, do not apply to all organisms. We propose that Plasmodium, the parasite responsible for malaria, uses an alternative strategy to slow down ribosomal speed and avoid multidomain protein misfolding during translation. In our model, the abundant Low Complexity Regions present in Plasmodium proteins replace the codon preferences, which influence the assembly of protein secondary structures.
CONSANGUINITY IN QATAR: KNOWLEDGE, ATTITUDE AND PRACTICE IN A POPULATION BORN BETWEEN 1946 AND 1991
Authors: SANDRIDGE A. L. , TAKEDDIN J. , AL-KAABI E. , FRANCES Y.
Published: November 2009

From March 2007 to March 2008 a cross-sectional study was conducted in Qatar to estimate the prevalence of consanguinity among Qataris and to assess their knowledge of the risks and their attitudes towards the practice. A secondary objective was to test the acceptability of sixteen Likert-style questions within the Qatari population. Face-to-face interviews using a 70-item structured questionnaire were conducted by three native Arabic-speaking medical students with 362 Qatari employees. Where consanguinity existed between the employee's parents, a diagram of the consanguinal relationship (phylogram) was completed. The response rate was 93%. By phylogram, 22% of participants reported a cousin relationship between their parents (consanguinal relationship) and another 15% reported that their parents were from the same tribe (affinal relationship). With respect to their own marital decision, 68% of the respondents had been married at least once. By phylogram, 35% of these reported a consanguineous relationship (first marriage), 9% reported only an affinal relationship and 56% reported that they were not married to a blood relative. Results on the sixteen Likert-style attitude questions were stratified by consanguinity status of parents and of self. In the stratification by consanguinity status of parents the top five attitudes differed by group but there appeared to be more similarity between the consanguinal and only tribal groups. Attitudinal results were stratified by sex. Results showed that the males had a stronger belief in several of the attitudes than females with the exception of causation of genetic abnormalities and health problems. The phylogram was shown to collect more detailed and explicit data than hard-coding. With respect to knowledge, the results showed that knowledge was imperfect with high proportions of participants not knowing that consanguinity has been implicated in autosomal recessive diseases such as thalassaemia, inborn errors of metabolism, deafness, anomalies of the extremities and specific congenital heart defects. Additionally, a sizeable proportion of the participants did not know that a more distant cousin marriage (e.g. third cousin) theoretically could be a less genetically risky choice to potential offspring than a closer cousin marriage (half-first cousin). These results indicate that more effort needs to be made in developing public health strategies to improve the population's understanding of the cost-benefit analysis involved in contracting consanguineous marriages given the goal of healthy offspring.
BARRIERS TO PREVENTION OF MOTHER-TO-CHILD TRANSMISSION OF HIV SERVICES IN UGANDA
Authors: MBONYE A. K. , HANSEN K. S. , WAMONO F. , MAGNUSSEN P.
Published: November 2009

Understanding care-seeking practices and barriers to prevention of mother-to-child transmission (PMTCT) of HIV is necessary in designing effective programmes to address the high disease burden due to HIV/AIDS in Uganda. This study explored perceptions, care-seeking practices and barriers to PMTCT among young and HIV-positive women. A household survey (10,706 women aged 14–49 years), twelve focus group discussions and 66 key informant interviews were carried out between January and April 2009 in Wakiso district, central Uganda. Results show that access to PMTCT services (family planning, HIV counselling and testing and delivery at health units) was poor. Decision making was an important factor in accessing PMTCT services. Socioeconomic factors (wealth quintile, age, education level) and institutional practices also influenced access to PMTCT. Overall, having had an HIV test was highest when both men and women made decisions together or when women were empowered to make their own decisions. This was significant across wealth quintiles (p=0.0001), age groups (p=0.0001) and education levels (p=0.0001). The least level of HIV testing was when men made decisions for their spouses; and this was the case with family planning and deliveries at health units. Other barriers to PMTCT were fear of women and male spouses to have an HIV test and the perception that HIV testing is compulsory in antenatal clinics. In conclusion, to increase access to PMTCT among women, especially the young, poor and least educated, there is a need to empower them to make decisions on health seeking, and also to empower men to support their spouses to make good decisions. Other barriers like fear of having an HIV test should be addressed through appropriate counselling of clients.
Localization of white-matter lesions and effect of vascular risk factors in late-onset major depression
Authors: Dalby R. B. , Chakravarty M. M. , Ahdidan J. , Sørensen L. , Frandsen J. , Jonsdottir K. Y. , Tehrani E. , Rosenberg R. , Østergaard L. , Videbech P.
Published: November 2009

Background

Several studies suggest that patients with late-onset major depression (MD) have an increased load of cerebral white-matter lesions (WMLs) compared with age-matched controls. Vascular risk factors such as hypertension and smoking may confound such findings. Our aim was to investigate the association between the localization and load of WMLs in late-onset MD with respect to vascular risk factors.

Method

We examined 22 consecutive patients with late-onset first-episode MD and 22 age- and gender-matched controls using whole-brain magnetic resonance imaging (MRI). The localization, number and volume of WMLs were compared between patients and controls, while testing the effect of vascular risk factors.

Results

Among subjects with one or more WMLs, patients displayed a significantly higher WML density in two white-matter tracts: the left superior longitudinal fasciculus and the right frontal projections of the corpus callosum. These tracts are part of circuitries essential for cognitive and emotional functions. Analyses revealed no significant difference in the total number and volume of WMLs between groups. Patients and controls showed no difference in vascular risk factors, except for smoking. Lesion load was highly correlated with smoking.

Conclusions

Our results indicate that lesion localization rather than lesion load differs between patients with late-onset MD and controls. Increased lesion density in regions associated with cognitive and emotional functions may be crucial in late-onset MD, and vascular risk factors such as smoking may play an important role in the pathophysiology of late-onset MD, consistent with the vascular depression hypothesis.
Increased fusiform area activation in schizophrenia during processing of spatial frequency-degraded faces, as revealed by fMRI
Authors: Silverstein S. M. , All S. D. , Kasi R. , Berten S. , Essex B. , Lathrop K. L. , Little D. M.
Published: November 2009

Background

People with schizophrenia demonstrate perceptual organization impairments, and these are thought to contribute to their face processing difficulties.

Method

We examined the neural substrates of emotionally neutral face processing in schizophrenia by investigating neural activity under three stimulus conditions: faces characterized by the full spectrum of spatial frequencies, faces with low spatial frequency information removed [high spatial frequency (HSF) condition], and faces with high spatial frequency information removed [low spatial frequency (LSF) condition]. Face perception in the HSF condition is more reliant on local feature processing whereas perception in the LSF condition requires greater reliance on global form processing. Past studies of perceptual organization in schizophrenia indicate that patients perform relatively more poorly with degraded stimuli but also that, when global information is absent, patients may perform better than controls because of their relatively increased ability to initially process individual features. Therefore, we hypothesized that people with schizophrenia (n=14) would demonstrate greater face processing difficulties than controls (n=13) in the LSF condition, whereas they would demonstrate a smaller difference or superior performance in the HSF condition.

Results

In a gender-discrimination task, behavioral data indicated high levels of accuracy for both groups, with a trend toward an interaction involving higher patient performance in the HSF condition and poorer patient performance in the LSF condition. Patients demonstrated greater activity in the fusiform gyrus compared to controls in both degraded conditions.

Conclusions

These data suggest that impairments in basic integration abilities may be compensated for by relatively increased activity in this region.
EMILE BOUTROUX, REDEFINING SCIENCE AND FAITH IN THE THIRD REPUBLIC
Authors: REVILL JOEL
Published: November 2009

Historians have convincingly shown the extent to which Protestantism played a role in the founding of the Third Republic, undermining the once canonical claim that republicanism and religion were implacably hostile opponents in the latter half of the nineteenth century. Catholics, however, continue to be viewed as nearly universally antirepublican. Analyzing the writings of philosopher Emile Boutroux and his students, this article shows how the specifically Catholic concern with the relationship between free will and scientific concepts of determinism both influenced the direction of French philosophy of science into the twentieth century and provided a framework for defending the Republic at the height of the Dreyfus affair.
THE RADICAL CONSERVATISM OF FRANK H. KNIGHT
Authors: BURGIN ANGUS
Published: November 2009

This article examines the most prominent interwar economist at the University of Chicago, Frank Knight, through the lens of a controversial 1932 lecture in which he exhorted his audience to vote Communist. The fact that he did so poses a historical problem: why did the premier American exponent of conservative economic principles appear to advocate a vote for radical change? This article argues that the speech is representative of Knight's deliberately paradoxical approach, in which he refused to praise markets without adding caveats about their substantial limitations, and expressed support for freedom of discussion alongside his skepticism of the public's capacity to exercise the privilege. In parsing these tensions, the article revises the conventional interpretation of Knight, illuminates the contested environment within which postwar free-market economics emerged, and reexamines a restrained defense of capitalism that has been largely forgotten in the subsequent years.
A HISTORICAL ATLAS OF OBJECTIVITY
Authors: KIM MI GYUNG
Published: November 2009

The mythical scientist in early twentieth-century America cut a lone figure, “impersonal as the chill northeast wind” and “oblivious of everything save his experiment.” He toiled through the night in his laboratory, “a place unimpressive and unmagical save for the constant-temperature bath with its tricky thermometer and electric bulbs,” as if working in the lab were a prayer that promised illumination—“alone, absorbed, [and] contemptuous of academic success and of popular classes,” he knew all about material forces, but he was blind to the vital force that created all others. Accustomed to the “beautiful dullness of long labors,” he remained “illimitably ignorant” of literature, art, and music. He believed that unerring techniques in experimentation, impartial observations, and exquisitely minute calculations would bring progress—a steady march toward the truth. He chose the highest calling in the world because he was “intensely religious—so religious that he will not accept quarter-truths, because they are an insult to his faith.” He was “so devoted to Pure Science . . . that he would rather have people die by the right therapy than be cured by the wrong. Having built a shrine for humanity, he wanted to kick out of it all mere human beings.” This autocratic figure, brilliantly insane and tyrannically honest, embodied the cult of science and objectivity.