bluuebunny/crossref_metadata_2025 huggingface dataset:
Food For Thought: Self-Criticism and Raising the Bar of Dysphagia Practice
Authors: Murray Joe
Published: June 2009

The assessment and treatment of swallowing disorders have become central to the practice of the medical speech-language pathologist. The outcomes associated with swallowing and swallowing disorders are severe with aspiration pneumonia, malnutrition and dehydration, and reduced quality of life among the most concerning. Clinicians practicing in this area possess unequal skills, training, and experience, and there is considerable variation in practice in the field. This article focuses on variation and error in swallowing assessment with attention to reliability and accuracy of the videofluoroscopic swallowing assessment. In this self-critical overview of the practice, recommendations are made for developing a standardized assessment protocol, shared lexicon, and specialty recognition in the area of swallowing and swallowing disorders.
A Contextual Effect of 2nd-Order Configural Processing of Non-Face Objects by Non-Experts
Authors: Matheson Heath E , McMullen Patricia A
Published: June 2009

We investigated here the detection of 2nd-order configural relations both in faces and in non-face objects. In experiment 1 it was shown that observers were more sensitive to feature displacements in upright faces and houses than in inverted faces and houses. The presence of an inversion effect in the house stimuli suggested that 2nd-order relational processing was applied to the non-face stimuli. In experiment 2, the inversion effect for houses was absent when only houses were presented. In experiment 3, face and house stimuli were once again presented in the same task and inversion effects were again seen for both types of stimuli. Together, these results suggest that 2nd-order relational processing can be flexibly applied to non-face objects when they are presented in the context of faces.
The mechanics of slithering locomotion
Authors: Hu David L. , Nirody Jasmine , Scott Terri , Shelley Michael J.
Published: June 2009

In this experimental and theoretical study, we investigate the slithering of snakes on flat surfaces. Previous studies of slithering have rested on the assumption that snakes slither by pushing laterally against rocks and branches. In this study, we develop a theoretical model for slithering locomotion by observing snake motion kinematics and experimentally measuring the friction coefficients of snakeskin. Our predictions of body speed show good agreement with observations, demonstrating that snake propulsion on flat ground, and possibly in general, relies critically on the frictional anisotropy of their scales. We have also highlighted the importance of weight distribution in lateral undulation, previously difficult to visualize and hence assumed uniform. The ability to redistribute weight, clearly of importance when appendages are airborne in limbed locomotion, has a much broader generality, as shown by its role in improving limbless locomotion.
Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling
Authors: Ohnishi Hidenori , Tochio Hidehito , Kato Zenichiro , Orii Kenji E. , Li Ailian , Kimura Takeshi , Hiroaki Hidekazu , Kondo Naomi , Shirakawa Masahiro
Published: June 2009

Myeloid differentiating factor 88 (MyD88) and MyD88 adaptor-like (Mal) are adaptor molecules critically involved in the Toll-like receptor (TLR) 4 signaling pathway. While Mal has been proposed to serve as a membrane-sorting adaptor, MyD88 mediates signal transduction from activated TLR4 to downstream components. The Toll/Interleukin-1 receptor (TIR) domain of MyD88 is responsible for sorting and signaling via direct or indirect TIR−TIR interactions between Mal and TLR4. However, the molecular mechanisms involved in multiple interactions of the TIR domain remain unclear. The present study describes the solution structure of the MyD88 TIR domain. Reporter gene assays revealed that 3 discrete surface sites in the TIR domain of MyD88 are important for TLR4 signaling. Two of these sites were shown to mediate direct binding to the TIR domain of Mal. Interestingly, Mal-TIR, but not MyD88-TIR, directly binds to the cytosolic TIR domain of TLR4. These observations suggested that the heteromeric assembly of TIR domains of the receptor and adaptors constitutes the initial step of TLR4 intracellular signal transduction.
Development of aliphatic biodegradable photoluminescent polymers
Authors: Yang Jian , Zhang Yi , Gautam Santosh , Liu Li , Dey Jagannath , Chen Wei , Mason Ralph P. , Serrano Carlos A. , Schug Kevin A. , Tang Liping
Published: June 2009

None of the current biodegradable polymers can function as both implant materials and fluorescent imaging probes. The objective of this study was to develop aliphatic biodegradable photoluminescent polymers (BPLPs) and their associated cross-linked variants (CBPLPs) for biomedical applications. BPLPs are degradable oligomers synthesized from biocompatible monomers including citric acid, aliphatic diols, and various amino acids via a convenient and cost-effective polycondensation reaction. BPLPs can be further cross-linked into elastomeric cross-linked polymers, CBPLPs. We have shown representatively that BPLP-cysteine (BPLP-Cys) and BPLP-serine (BPLP-Ser) offer advantages over the traditional fluorescent organic dyes and quantum dots because of their preliminarily demonstrated cytocompatibility in vitro, minimal chronic inflammatory responses in vivo, controlled degradability and high quantum yields (up to 62.33%), tunable fluorescence emission (up to 725 nm), and photostability. The tensile strength of CBPLP-Cys film ranged from 3.25 ± 0.13 MPa to 6.5 ± 0.8 MPa and the initial Modulus was in a range of 3.34 ± 0.15 MPa to 7.02 ± 1.40 MPa. Elastic CBPLP-Cys could be elongated up to 240 ± 36%. The compressive modulus of BPLP-Cys (0.6) (1:1:0.6 OD:CA:Cys) porous scaffold was 39.60 ± 5.90 KPa confirming the soft nature of the scaffolds. BPLPs also possess great processability for micro/nano-fabrication. We demonstrate the feasibility of using BPLP-Ser nanoparticles (“biodegradable quantum dots”) for in vitro cellular labeling and noninvasive in vivo imaging of tissue engineering scaffolds. The development of BPLPs and CBPLPs represents a new direction in developing fluorescent biomaterials and could impact tissue engineering, drug delivery, bioimaging.
The glutamate receptor subunit delta2 is capable of gating its intrinsic ion channel as revealed by ligand binding domain transplantation
Authors: Schmid Sabine M. , Kott Sabine , Sager Charlotte , Huelsken Thomas , Hollmann Michael
Published: June 2009

The family of ionotropic glutamate receptors includes 2 subunits, delta1 and delta2, the physiological relevance of which remains poorly understood. Both are nonfunctional in heterologous expression systems, although the isolated, crystallized ligand binding domain (LBD) of delta2 is capable of binding D-serine. To investigate these seemingly contradictory observations we tested whether delta receptors can be ligand gated at all. We used a strategy that replaced the native LBD of delta2 by a proven glutamate-binding LBD. Test transplantations between α-amino-3-hydroxy-5-methylisoxazole propionate (AMPA) and kainate receptors (GluR1 and GluR6, respectively) showed that this approach can produce functional chimeras even if only one part of the bipartite LBD is swapped. Upon outfitting delta2 with the LBD of GluR6, the chimera formed glutamate-gated ion channels with low Ca
2+
permeability and unique rectification properties. Ligand-induced conformational changes can thus gate delta2, suggesting that the LBD of this receptor works fundamentally differently from that of other ionotropic glutamate receptors.
Evidence for early hunters beneath the Great Lakes
Authors: O'Shea John M. , Meadows Guy A.
Published: June 2009

Scholars have hypothesized that the poorly understood and rarely encountered archaeological sites from the terminal Paleoindian and Archaic periods associated with the Lake Stanley low water stage (10,000–7,500 BP) are lost beneath the modern Great Lakes. Acoustic and video survey on the Alpena-Amberley ridge, a feature that would have been a dry land corridor crossing the Lake Huron basin during this time period, reveals the presence of a series of stone features that match, in form and location, structures used for caribou hunting in both prehistoric and ethnographic times. These results present evidence for early hunters on the Alpena-Amberley corridor, and raise the possibility that intact settlements and ancient landscapes are preserved beneath Lake Huron.
Starch as a major integrator in the regulation of plant growth
Authors: Sulpice Ronan , Pyl Eva-Theresa , Ishihara Hirofumi , Trenkamp Sandra , Steinfath Matthias , Witucka-Wall Hanna , Gibon Yves , Usadel Björn , Poree Fabien , Piques Maria Conceição , Von Korff Maria , Steinhauser Marie Caroline , Keurentjes Joost J. B. , Guenther Manuela , Hoehne Melanie , Selbig Joachim , Fernie Alisdair R. , Altmann Thomas , Stitt Mark
Published: June 2009

Rising demand for food and bioenergy makes it imperative to breed for increased crop yield. Vegetative plant growth could be driven by resource acquisition or developmental programs. Metabolite profiling in 94
Arabidopsis
accessions revealed that biomass correlates negatively with many metabolites, especially starch. Starch accumulates in the light and is degraded at night to provide a sustained supply of carbon for growth. Multivariate analysis revealed that starch is an integrator of the overall metabolic response. We hypothesized that this reflects variation in a regulatory network that balances growth with the carbon supply. Transcript profiling in 21 accessions revealed coordinated changes of transcripts of more than 70 carbon-regulated genes and identified 2 genes (myo-inositol-1-phosphate synthase, a Kelch-domain protein) whose transcripts correlate with biomass. The impact of allelic variation at these 2 loci was shown by association mapping, identifying them as candidate lead genes with the potential to increase biomass production.
Direct single-molecule observation of a protein living in two opposed native structures
Authors: Gambin Yann , Schug Alexander , Lemke Edward A. , Lavinder Jason J. , Ferreon Allan Chris M. , Magliery Thomas J. , Onuchic José N. , Deniz Ashok A.
Published: June 2009

Biological activity in proteins requires them to share the energy landscape for folding and global conformational motions, 2 key determinants of function. Although most structural studies to date have focused on fluctuations around a single structural basin, we directly observe the coexistence of 2 symmetrically opposed conformations for a mutant of the Rop-homodimer (Repressor of Primer) in single-molecule fluorescence resonance energy transfer (smFRET) measurements. We find that mild denaturing conditions can affect the sensitive balance between the conformations, generating an equilibrium ensemble consisting of 2 equally occupied structural basins. Despite the need for large-scale conformational rearrangement, both native structures are dynamically and reversibly adopted for the same paired molecules without separation of the constituent monomers. Such an ability of some proteins or protein complexes to switch between conformations by thermal fluctuations and/or minor environmental changes could be central to their ability to control biological function.
Mammalian Fat and Dachsous cadherins regulate apical membrane organization in the embryonic cerebral cortex
Authors: Ishiuchi Takashi , Misaki Kazuyo , Yonemura Shigenobu , Takeichi Masatoshi , Tanoue Takuji
Published: June 2009

Compartmentalization of the plasma membrane in a cell is fundamental for its proper functions. In this study, we present evidence that mammalian Fat4 and Dachsous1 cadherins regulate the apical plasma membrane organization in the embryonic cerebral cortex. In neural progenitor cells of the cortex, Fat4 and Dachsous1 were concentrated together in a cell–cell contact area positioned more apically than the adherens junction (AJ). These molecules interacted in a heterophilic fashion, affecting their respective protein levels. We further found that Fat4 associated and colocalized with the Pals1 complex. Ultrastructurally, the apical junctions of the progenitor cells comprised the AJ and a stretch of plasma membrane apposition extending apically from the AJ, which positionally corresponded to the Fat4–Dachsous1-positive zone. Depletion of Fat4 or Pals1 abolished this membrane apposition. These results highlight the importance of the Fat4–Dachsous1–Pals1 complex in organizing the apical membrane architecture of neural progenitor cells.
Regulators of yeast endocytosis identified by systematic quantitative analysis
Authors: Burston Helen E. , Maldonado-Báez Lymarie , Davey Michael , Montpetit Benjamen , Schluter Cayetana , Wendland Beverly , Conibear Elizabeth
Published: June 2009

Endocytosis of receptors at the plasma membrane is controlled by a complex mechanism that includes clathrin, adaptors, and actin regulators. Many of these proteins are conserved in yeast yet lack observable mutant phenotypes, which suggests that yeast endocytosis may be subject to different regulatory mechanisms. Here, we have systematically defined genes required for internalization using a quantitative genome-wide screen that monitors localization of the yeast vesicle-associated membrane protein (VAMP)/synaptobrevin homologue Snc1. Genetic interaction mapping was used to place these genes into functional modules containing known and novel endocytic regulators, and cargo selectivity was evaluated by an array-based comparative analysis. We demonstrate that clathrin and the yeast AP180 clathrin adaptor proteins have a cargo-specific role in Snc1 internalization. We additionally identify low dye binding 17 (LDB17) as a novel conserved component of the endocytic machinery. Ldb17 is recruited to cortical actin patches before actin polymerization and regulates normal coat dynamics and actin assembly. Our findings highlight the conserved machinery and reveal novel mechanisms that underlie endocytic internalization.
Acetylation and activation of STAT3 mediated by nuclear translocation of CD44
Authors: Lee Jia-Lin , Wang Mei-Jung , Chen Jeou-Yuan
Published: June 2009

Expression of the type I transmembrane glycoprotein CD44 has recently been recognized as a signature for cancer stem cells. In this study, we demonstrate that CD44, once engaged, is internalized and translocated to the nucleus, where it binds to various promoters, including that of cyclin D1, leading to cell fate change through transcriptional reprogramming. In regulating cyclin D1 expression, the internalized CD44 forms a complex with STAT3 and p300 (acetyltransferase), eliciting STAT3 acetylation at lysine 685 and dimer formation in a cytokine- and growth factor–independent manner. A bipartite nuclear localization signal (NLS) was mapped to the cytoplasmic tail of CD44, which mediates its nuclear translocation. Expression of CD44(NLS) mutant sequesters STAT3 in cytosol. In the nucleus, the acetylated STAT3 dimer remains associated with CD44 and binds to the cyclin D1 promoter, leading to increased cyclin D1 expression and cell proliferation. This study describes a novel function for CD44 in transcriptional modulation through nuclear translocation of the internalized CD44 and complex formation with transcription factors.
Distinct functions for Rho1 in maintaining adherens junctions and apical tension in remodeling epithelia
Authors: Warner Stephen J. , Longmore Gregory D.
Published: June 2009

Maintenance and remodeling of adherens junctions (AJs) and cell shape in epithelia are necessary for the development of functional epithelia and are commonly altered during cancer progression/metastasis. Although formation of nascent AJs has received much attention, whether shared mechanisms are responsible for the maintenance and remodeling of AJs in dynamic epithelia, particularly in vivo, is not clear. Using clonal analysis in the postmitotic Drosophila melanogaster pupal eye epithelium, we demonstrate that Rho1 is required to maintain AJ integrity independent of its role in sustaining apical cell tension. Rho1 depletion in a remodeling postmitotic epithelium disrupts AJs but only when depleted in adjacent cells. Surprisingly, neither of the Rho effectors, Rok or Dia, is necessary downstream of Rho1 to maintain AJs; instead, Rho1 maintains AJs by inhibiting Drosophila epithelial cadherin endocytosis in a Cdc42/Par6-dependent manner. In contrast, depletion of Rho1 in single cells decreases apical tension, and Rok and myosin are necessary, while Dia function also contributes, downstream of Rho1 to sustain apical cell tension.
Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER
Authors: Vacaru Ana M. , Tafesse Fikadu G. , Ternes Philipp , Kondylis Vangelis , Hermansson Martin , Brouwers Jos F.H.M. , Somerharju Pentti , Rabouille Catherine , Holthuis Joost C.M.
Published: June 2009

Ceramides are central intermediates of sphingolipid metabolism with critical functions in cell organization and survival. They are synthesized on the cytosolic surface of the endoplasmic reticulum (ER) and transported by ceramide transfer protein to the Golgi for conversion to sphingomyelin (SM) by SM synthase SMS1. In this study, we report the identification of an SMS1-related (SMSr) enzyme, which catalyses the synthesis of the SM analogue ceramide phosphoethanolamine (CPE) in the ER lumen. Strikingly, SMSr produces only trace amounts of CPE, i.e., 300-fold less than SMS1-derived SM. Nevertheless, blocking its catalytic activity causes a substantial rise in ER ceramide levels and a structural collapse of the early secretory pathway. We find that the latter phenotype is not caused by depletion of CPE but rather a consequence of ceramide accumulation in the ER. Our results establish SMSr as a key regulator of ceramide homeostasis that seems to operate as a sensor rather than a converter of ceramides in the ER.
Visualizing B cell capture of cognate antigen from follicular dendritic cells
Authors: Suzuki Kazuhiro , Grigorova Irina , Phan Tri Giang , Kelly Lisa M. , Cyster Jason G.
Published: June 2009

The prominent display of opsonized antigen by follicular dendritic cells (FDCs) has long favored the view that they serve as antigen-presenting cells for B cells. Surprisingly, however, although B cell capture of antigen from macrophages and dendritic cells has been visualized, acquisition from FDCs has not been directly observed. Using two-photon microscopy, we visualized B cell capture of cognate antigen from FDCs. B cell CXCR5 expression was required, and encounter with FDC-associated antigen could be detected for >1 wk after immunization. B cell–FDC contact times were often brief but occasionally persisted for >30 min, and B cells sometimes acquired antigen together with FDC surface proteins. These observations establish that FDCs can serve as sites of B cell antigen capture, with their prolonged display time ensuring that even rare B cells have the chance of antigen encounter, and they suggest possible information transfer from antigen-presenting cell to B cell.
A clustering approach for identification of enriched domains from histone modification ChIP-Seq data
Authors: Zang Chongzhi , Schones Dustin E. , Zeng Chen , Cui Kairong , Zhao Keji , Peng Weiqun
Published: June 2009

Motivation: Chromatin states are the key to gene regulation and cell identity. Chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-Seq) is increasingly being used to map epigenetic states across genomes of diverse species. Chromatin modification profiles are frequently noisy and diffuse, spanning regions ranging from several nucleosomes to large domains of multiple genes. Much of the early work on the identification of ChIP-enriched regions for ChIP-Seq data has focused on identifying localized regions, such as transcription factor binding sites. Bioinformatic tools to identify diffuse domains of ChIP-enriched regions have been lacking.

Results: Based on the biological observation that histone modifications tend to cluster to form domains, we present a method that identifies spatial clusters of signals unlikely to appear by chance. This method pools together enrichment information from neighboring nucleosomes to increase sensitivity and specificity. By using genomic-scale analysis, as well as the examination of loci with validated epigenetic states, we demonstrate that this method outperforms existing methods in the identification of ChIP-enriched signals for histone modification profiles. We demonstrate the application of this unbiased method in important issues in ChIP-Seq data analysis, such as data normalization for quantitative comparison of levels of epigenetic modifications across cell types and growth conditions.

Availability:  http://home.gwu.edu/∼wpeng/Software.htm

Contact:  wpeng@gwu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Looking for a Person‐Centered Medicine: Non Conventional Medicine in the Conventional European and Italian Setting
Authors: Sarsina Paolo Roberti di , Iseppato Ilaria
Published: June 2009

In Italy, the use of non conventional medicines (NCMs) is spreading among people as in the rest of Europe. Sales of alternative remedies are growing, and likewise the number of medical doctors (MDs) who practise NCM/complementary and alternative medicine (CAM). However, in Italy as in other countries of the European Union, at the present time the juridical/legal status of NCM/CAM is not well established, mainly due to the lack of any national law regulating NCM/CAM professional training, practice and public supply and the absence of government‐promoted scientific research in this field. This is an obstacle to safeguarding the patient′s interests and freedom of choice, especially now that dissatisfaction with biomedicine is inclining more and more people to look for a holistic and patient‐centered form of medicine.
Do Lengthy Auditor Tenure and the Provision of Non‐Audit Services by the External Auditor Reduce Audit Report Lags?
Authors: Lee Ho‐Young , Mande Vivek , Son Myungsoo
Published: June 2009

This study examines whether audit report lags (ARLs) are influenced by auditor tenure and the provision of non‐audit services by the external auditor. Studying this association is important because ARLs are directly associated with audit efficiency and with the timeliness of companies' announcements of earnings. Our results show that both auditor tenure and non‐audit services are significantly associated with ARLs. With regard to auditor tenure, we find that ARLs decline as auditor tenure lengthens, indicating that auditors with long tenure are able to audit their clients more efficiently. This finding suggests that auditor changes, mandatory or otherwise, impose additional costs on clients and increase informational inefficiencies in the form of delayed information to markets. With regard to non‐audit services, we find that there is a significant negative association between non‐audit service fees and ARLs, which suggests that the provision of non‐audit services increases auditor learning, thus reducing audit delays.
Auditor Independence and the Provision of Non‐Audit Services: Perceptions by German Investors
Authors: Quick Reiner , Warming‐Rasmussen Bent
Published: June 2009

An economic model by DeAngelo shows that the existence of client‐specific quasi‐rents impairs auditor independence. The provision of non‐audit advisory services (NAS) increases quasi‐rents, and thus it is a threat to independence. Recently, a number of changes have been made not only to the relevant international and US regulations, but also to the German regulations related to NAS. A large number of empirical studies have investigated the influence of NAS on the perceived auditor independence. Most of these studies were performed in Anglo‐Saxon countries, particularly in the US, and a majority found a negative impact. Six studies are based on data from Germany. Most of them failed to find a significant negative impact on auditor's independence. German investors have not been surveyed so far. Thus an empirical investigation of the impact of NAS on investors' perceptions of auditor independence in Germany seemed promising. It was found that shareholders generally perceive a negative effect on auditor's independence if NAS are provided. The effects of 19 different services have been analysed. For most of them a negative effect was found, even if these services are not explicitly prohibited in Germany. Furthermore, it was shown that the type of NAS influences the degree to which auditor independence is perceived to be impaired. Thus, independence rules related to NAS could be differentiated. Additionally, the study ascertained that perceived auditor independence does increase if NAS are provided by a separate department of the audit firm.
The Impact of the Sarbanes‐Oxley Act on the Audit Fees of Australian Listed Firms
Authors: Salman Fazlina Mohd , Carson Elizabeth
Published: June 2009

The Sarbanes‐Oxley Act (2002) (SOX) was enacted to improve the corporate governance practices of US firms. Significantly, foreign registrants traded on US stock exchanges are also required to comply with SOX. This study assesses the impact of the SOX legislation on non‐US firms by examining audit fees for Australian firms with foreign registrant status in the US from 2001 to 2005, compared with audit fees for other Australian firms. The findings indicate that Australian companies issuing American Depositary Receipts (ADRs) incurred substantial increases in audit fees and Australian firms subject to the full provisions of SOX incurred larger increases in audit fees. These findings provide a broader understanding of the compliance costs for non‐US firms subject to SOX and therefore inform both policy‐makers and firms.
The Changing Regulatory Landscape: Editorial
Authors: Lennox Clive
Published: June 2009

This editorial first summarizes the changes to the regulatory landscape that have primarily affected the auditing profession. I then discuss the content of the four papers contained in this special issue. Finally, I put these papers into context by outlining the major findings in the empirical literature regarding the consequences of the changed regulatory environment.
Systematic review: hepatitis‐associated aplastic anaemia – a syndrome associated with abnormal immunological function
Authors: GONZALEZ‐CASAS R. , GARCIA‐BUEY L. , JONES E. A. , GISBERT J. P. , MORENO‐OTERO R.
Published: June 2009

Background  Hepatitis‐associated aplastic anaemia is a syndrome in which marrow failure follows the development of hepatitis.

Aim  To review systematically the aetiology, immunopathogenesis, clinical presentation, diagnosis and treatment of hepatitis‐associated aplastic anaemia.

Methods  Literature searches were undertaken on the MEDLINE electronic database up to December 2008. Twenty‐four relevant studies were identified. The clinical and laboratory characteristics of the patients were analysed and reviewed.

Results  Hepatitis‐associated aplastic anemia is a variant of acquired aplastic anemia in which an episode of hepatitis precedes the onset of aplastic anemia. The hepatitis may be acute and severe, even fulminant; it may be self‐limiting or chronic. The pathology is often not attributable to a recognized cause of viral hepatitis. The syndrome occurs in 28 percent of young adults after liver transplantation for non‐A, non‐B, non‐C hepatitis. Several features of the syndrome suggest that the marrow aplasia is mediated by immunological mechanisms, possibly mediated by gamma interferon or the cytokine cascade. Survival of patients treated with hematopoietic cell transplantation has been 82%, and the response rate to immunosuppressive therapy 70%.

Conclusions  Hepatitis‐associated bone marrow aplasia is mediated by immunological mechanisms. Treatment options include hematopoietic cell transplantation and immunosuppressive therapy.
Predictors of health‐related quality of life in patients with chronic liver disease
Authors: AFENDY A. , KALLMAN J. B. , STEPANOVA M. , YOUNOSZAI Z. , AQUINO R. D. , BIANCHI G. , MARCHESINI G. , YOUNOSSI Z. M.
Published: June 2009

Background Patient‐reported outcomes like health‐related quality of life (HRQL) have become increasingly important for full assessment of patients with chronic liver diseases (CLD).

Aim To explore the relative impact of different types of liver disease on HRQL as well as predictors of HRQL domains in CLD.

Methods Our HRQL databases with Short‐Form 36 (SF‐36) data were used. Scores for each of SF‐36 scales (PF – physical functioning, RP – role functioning, BP – bodily pain, GH – general health, VT – vitality, SF – social functioning, RE – role emotional and MH – mental health, MCS – mental component score, PCS – physical component score) were compared between different types of CLD as well as other variables.

Results Complete data were available for 1103 CLD patients. Demographic and clinical data included: age 54.2 ± 12.0 years, 40% female, 761 (69%) with cirrhosis. Analysis revealed that age correlated significantly (P < 0.05) with worsening HRQL on every scale of the SF‐36. Female patients had more HRQL impairments in PF, RP, BP, GH, VT and MH scales of SF‐36 (Δ scale score: 6.6–10.7,P < 0.05). Furthermore, cirrhotic patients had more impairment of HRQL in every scale of SF‐36 (Δ scale score: 6.6–43.0,P < 0.05). In terms of diagnostic groups, non‐alcoholic fatty liver disease patients showed more impairment of HRQL.

Conclusions Analysis of this large CLD cohort suggests that a number of important clinicodemographic factors are associated with HRQL impairment. These findings contribute to the full understanding of the total impact of CLD on patients’ health.
Gene expression in Large White or Duroc‐sired female and castrated male pigs and relationships with pork quality
Authors: Kwasiborski A. , Rocha D. , Terlouw C.
Published: June 2009

This study assessed expression of 12 genes in 24 pig longissimus samples earlier subjected to a proteomic study by our group. Genes were selected on the basis of the earlier proteomic results. Pigs differed in rearing environment (indoors or outdoors), sire breed (Duroc or Large White) and gender (female or castrated male). At slaughter they experienced different stress conditions. The proportion of gene expression changes influenced by treatment factors was consistent with the proportion of protein changes in an earlier proteomic analysis of the same pigs. Expression levels of genes were often correlated. Gene expression was generally not correlated with the levels of the corresponding protein. Finally, most meat quality traits were correlated with the expression of at least one of the studied genes. The most meaningful of these was the association of a slower pH decline with lower levels of HSP72 expression and higher levels of HSP72 protein. ANXA2 and cMDH expression were also associated with various meat quality traits. These relationships may be related to pre‐slaughter stress levels and fibre type composition.
Assessment of the swine protein‐annotated oligonucleotide microarray
Authors: Steibel J. P. , Wysocki M. , Lunney J. K. , Ramos A. M. , Hu Z.‐L. , Rothschild M. F. , Ernst C. W.
Published: June 2009

The specificity and utility of the swine protein‐annotated oligonucleotide microarray, or Pigoligoarray (http://www.pigoligoarray.org), has been evaluated by profiling the expression of transcripts from four porcine tissues. Tools for comparative analyses of expression on the Pigoligoarray were developed including HGNC identities and comparative mapping alignments with human orthologs. Hybridization results based on the Pigoligoarray’s sets of control, perfect match (PM) and deliberate mismatch (MM) probes provide an important means of assessing non‐specific hybridization. Simple descriptive diagnostic analyses of PM/MM probe sets are introduced in this paper as useful tools for detecting non‐specific hybridization. Samples of RNA from liver, brain stem, longissimus dorsi muscle and uterine endothelium from four pigs were prepared and hybridized to the arrays. Of the total 20 400 oligonucleotides on the Pigoligoarray, 12 429 transcripts were putatively differentially expressed (DE). Analyses for tissue‐specific expression [over‐expressed in one tissue with respect to all the remaining three tissues (q < 0.01)] identified 958 DE transcripts in liver, 726 in muscle, 286 in uterine endothelium and 1027 in brain stem. These hybridization results were confirmed by quantitative PCR (QPCR) expression patterns for a subset of genes after affirming that cDNA and amplified antisense RNA (aRNA) exhibited similar QPCR results. Comparison to human ortholog expression confirmed the value of this array for experiments of both agricultural importance and for tests using pigs as a biomedical model for human disease.
Assignment of the locus for arachnomelia syndrome to bovine chromosome 23 in Simmental cattle
Authors: Buitkamp J. , Kühn C. , Semmer J. , Götz K.‐U.
Published: June 2009

Arachnomelia syndrome is a lethal inherited malformation mainly of the limbs, vertebral column and skull in cattle, which poses a severe impairment to farmers and breeders. Recently, a number of cases of arachnomelia syndrome have occurred in the Simmental breed and some sires with excellent breeding values had been shown to be carriers of the disease. We herein report the genetic mapping of the mutation underlying arachnomelia in cattle. The disease was mapped using a two‐stage genome scan. A first round autosomal genome‐wide screening using a limited number of cases identified three chromosomal regions with lod‐scores > 1. The position of the arachnomelia syndrome locus was identified to be on BTA 23 by genotyping an additional, independent set of animals with markers that provided positive lod‐scores in the course of the initial genome‐wide screen. Using a denser set of regional microsatellites, the locus could be mapped to a region about 9 cM in length. The most significant linkage signal with arachnomelia syndrome was obtained with markerNRKM‐17(lod‐score > 20) using a recessive model. Interestingly, different genes seem to be responsible for the disease in Brown Swiss and Simmental breeds, as arachnomelia syndrome was mapped to a different location in Brown Swiss. The results provide sufficient information for the development of a genetic test system and also allow the identification of positional candidate genes.
Mannose-binding lectin is present in human semen and modulates cellular adhesion of Neisseria gonorrhoeae in vitro
Authors: Wing J B , Jack D L , Lee M E , Pacey A A , Kinghorn G R , Read R C
Published: June 2009

Mannose-binding lectin (MBL) is an innate immune molecule present in blood and some mucosal tissues, which can influence microbial attachment and inflammatory responses of host cells during infection. In this study MBL was found to be present at a low concentration in semen samples in the range 1·2–24·9 ng/ml. Co-incubation of bacteria with semen resulted in the binding of MBL to the bacterial surface. Neisseria gonorrhoeae is a common cause of genitourinary infection. MBL bound to N. gonorrhoeae with strain-to-strain variation in the intensity of binding and nature of the bacterial receptor. Pretreatment with MBL concentrations similar to those found in human serum modulated the adhesion of N. gonorrhoeae strain FA1090 but not strain MS11 to epithelial cells. This effect was dose-dependent. This work demonstrates that MBL is present in human semen and modifies cellular responses to N. gonorrhoeae in a concentration-dependent manner.
PTEN is a mechanosensing signal transducer for myosin II localization in Dictyostelium cells
Authors: Pramanik Md. Kamruzzaman , Iijima Miho , Iwadate Yoshiaki , Yumura Shigehiko
Published: June 2009

To investigate the role of PTEN in regulation of cortical motile activity, especially in myosin II localization, eGFP–PTEN and mRFP–myosin II were simultaneously expressed in Dictyostelium cells. PTEN and myosin II co‐localized at the posterior of migrating cells and furrow region of dividing cells. In suspension culture, PTEN knockout (pten−) cells became multinucleated, and myosin II significantly decreased in amount at the furrow. During pseudopod retraction and cell aspiration by microcapillary, PTEN accumulated at the tips of pseudopods and aspirated lobes prior to the accumulation of myosin II. In pten− cells, only a small amount of myosin II accumulated at the retracting pseudopods and aspirated cell lobes. PTEN accumulated at the retracting pseudopods and aspirated lobes even in myosin II null cells and latrunculin B‐treated cells though in reduced amounts, indicating that PTEN accumulates partially depending on myosin II and cortical actin. Accumulation of PTEN prior to myosin II suggests that PTEN is an upstream component in signaling pathway to localize myosin II, possibly with mechanosensing signaling loop where actomyosin‐driven contraction further augments accumulation of PTEN and myosin II by a positive feedback mechanism.
Feeding Artemia franciscana (Kellogg) larvae with bacterial heat shock protein, protects from Vibrio campbellii infection
Authors: Sung Y Y , Ashame M F , Chen S , MacRae T H , Sorgeloos P , Bossier P
Published: June 2009

Among their numerous physiological effects, heat shock proteins (Hsps) are potent immunomodulators, a characteristic reflecting their potential as therapeutic agents and which led to their application in combating infection. As an example, the up‐regulation of endogenous Hsp70 in the branchiopod crustacean Artemia franciscana (Kellogg) is concurrent with shielding against bacterial infection. To better understand this protective mechanism, gnotobiotic Artemia were fed with Escherichia coli treated to over‐produce different prokaryotic Hsps. This was shown to increase larval resistance to experimental Vibrio campbellii exposure. Immunoprobing of Western blots showed that the enhanced resistance to V. campbellii correlated with DnaK production in E coli. A definitive role for DnaK was then demonstrated by feeding Artemia larvae with transformed bacteria over‐producing only this protein, although other Hsps such as DnaJ and grpE also provided tolerance against Vibrio infection. Feeding of bacteria synthesizing selected Hsps is therefore suggested as an alternative to antibiotic use as a means of enhancing resistance of Artemia larvae to bacterial infection, which may have potential applications in aquaculture.
Lymphocystis disease virus persists in the epidermal tissues of olive flounder, Paralichthys olivaceus (Temminch & Schlegel), at low temperatures
Authors: Hossain M , Kim S‐R , Kitamura S‐I , Kim D‐W , Jung S‐J , Nishizawa T , Yoshimizu M , Oh M‐J
Published: June 2009

Olive flounder artificially infected with lymphocystis disease virus (LCDV) were reared at 10, 20 and 30 °C for 60 days, to compare LCD‐incidence. In the fish reared at 20 °C, lymphocystis cells appeared on the skin and fins at 35 days post‐challenge, and the cumulative LCD‐incidence was 80% at 60 days. High levels of LCDV, with a mean polymerase chain reaction (PCR) titre of 106 PCR‐U mg−1 tissue, were detected in the fins and skin of LCD‐affected fish at 20 °C, but were not detected in the spleen, kidney, brain and intestinal tissues of these fish. No LCD clinical signs were observed in the fish reared at 10 °C and 30 °C; however, a low level of LCDV (103 PCR‐U mg−1 tissue) was detected in the fins and skin of these fish. By increasing the rearing temperature from 10 to 20 °C, lymphocystis clusters appeared on the skin and fins of the fish with no previous LCD clinical signs within 33 days after the temperature change. It was shown that permissive cells for LCDV infection exist in the epidermis of olive flounder. At low temperatures, small amounts of LCDV were able to persist over a period extended for a further 45 days in the fish epidermis, even though the fish showed no LCD clinical signs. The optimum growth temperature of LCDV is near 20 °C.
CD25 Blockade protects T Cells from Activation‐induced Cell Death (AICD) via Maintenance of TOSO Expression
Authors: Richter G. H. S. , Mollweide A. , Hanewinkel K. , Zobywalski C. , Burdach S.
Published: June 2009

CD25 monoclonal antibody binding to the α‐chain of the Interleukin‐2 (IL‐2) receptor, blocks high‐affinity IL‐2 binding, thereby preventing complete T‐cell activation and being of ample importance in transplantation medicine and potentially the treatment of autoimmune disease. However, CD25 antibodies do not only block T‐cell activation but also prevent activation‐induced cell death (AICD) attributing a dual function to IL‐2. In this study, the modulation of the genomic expression profile of human peripheral blood mononuclear cells (PBMC) with therapeutic concentrations of humanized anti‐CD25 mAb was investigated. PBMC were stimulated with CD3 antibody OKT‐3 together with recombinant IL‐2 in the absence or presence of anti‐CD25 mAb. RNA was extracted and subjected to microarray analysis on U133A microarrays (Affymetrix). Anti‐CD25 treatment inhibited several genes typically expressed during T‐cell activation including granzyme B, signalling lymphocyte activation molecule, family member 1 (SLAMF1), CD40‐Ligand (CD40‐L), IL‐9 and interferon (IFN)‐γ. Interestingly, anti‐CD25 mAb also blocked the expression of several genes important for susceptibility to apoptosis, such as death receptor 6 (DR6) or reversed IL‐2‐mediated repression of anti‐apoptotic genes, such as Fas apoptotic inhibitory molecule 3 (FAIM3)/TOSO. Functional significance of DR6 and TOSO expression in IL‐2‐dependent T‐cell activation was subsequently evaluated by RNA interference in AICD: While siRNA specifically directed against DR6 did not modulate FAS‐L‐mediated apoptosis induction in primary T cells, down‐regulation of TOSO significantly increased susceptibility to apoptosis, emphasizing an important role for TOSO in IL‐2‐mediated AICD.
T‐Cell Epitope Mapping of the Borrelia garinii Outer Surface Protein A in Lyme Neuroborreliosis
Authors: Widhe M. , Ekerfelt C. , Jarefors S. , Skogman B. H. , Peterson E. M. , Bergström S. , Forsberg P. , Ernerudh J.
Published: June 2009

We studied the T‐cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T‐cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon‐γ secreting cells were detected by ELISPOT. The peptides OspA17–36, OspA49–68, OspA105–124, OspA137–156, OspA193–212 and OspA233–252 showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T‐cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.
Expression of CD4 on Epstein–Barr Virus‐immortalized B Cells
Authors: Hoennscheidt C. , Max D. , Richter N. , Staege M. S.
Published: June 2009

Human antigen presenting cells commonly express CD4 but the significance of this phenomenon has not been clarified. We analyzed a panel of Epstein–Barr virus‐immortalized B cells (so called lymphoblastoid cell lines, LCL) by using flow cytometry, DNA‐microarray analysis, and reverse transcriptase‐polymerase chain reaction (RT‐PCR). The number of CD4+ cells varied from cell line to cell line but expression of CD4 was detected by flow cytometry and RT‐PCR in all investigated cell lines. To characterize CD4 expressing LCL in more detail, we separated CD4+ and CD4− cells from single cell lines by using immunomagnetic beads. When we cultured sorted CD4+ and CD4− cells, we observed that CD4 expression was stable for several passages. However, the number of CD4+ cells decreased with time in culture. We never observed that CD4− cell lines returned back to a CD4+ phenotype. DNA‐microarray analysis of isolated CD4+ and CD4− cells indicated that the overall gene expression profile of both cell populations was highly similar. In addition, CD4+ and CD4− cells showed the same allostimulatory capacity. CD4+ LCL showed a slightly increased interleukin‐16 induced chemotaxis. Differences in the gene expression profile of CD4+ and CD4− cell lines suggested that loss of CD4 expression occurred during a differentiation step involving achaete–scute complex homolog‐like 1.
Identification and characterization of bZIP‐type transcription factors involved in carrot (Daucus carota L.) somatic embryogenesis
Authors: Guan Yucheng , Ren Haibo , Xie He , Ma Zeyang , Chen Fan
Published: June 2009

Seed dormancy is an important adaptive trait that enables seeds of many species to remain quiescent until conditions become favorable for germination. Abscisic acid (ABA) plays an important role in these developmental processes. Like dormancy and germination, the elongation of carrot somatic embryo radicles is retarded by sucrose concentrations at or above 6%, and normal growth resumes at sucrose concentrations below 3%. Using a yeast one‐hybrid screening system, we isolated two bZIP‐type transcription factors, CAREB1 and CAREB2, from a cDNA library prepared from carrot somatic embryos cultured in a high‐sucrose medium. Both CAREB1 and CAREB2 were localized to the nucleus, and specifically bound to the ABA response element (ABRE) in the Dc3 promoter. Expression of CAREB2 was induced in seedlings by drought and exogenous ABA application; whereas expression of CAREB1 increased during late embryogenesis, and reduced dramatically when somatic embryos were treated with fluridone, an inhibitor of ABA synthesis. Overexpression of CAREB1 caused somatic embryos to develop slowly when cultured in low‐sucrose medium, and retarded the elongation of the radicles. These results indicate that CAREB1 and CAREB2 have similar DNA‐binding activities, but play different roles during carrot development. Our results indicate that CAREB1 functions as an important trans‐acting factor in the ABA signal transduction pathway during carrot somatic embryogenesis.
Genetic diversity of Sicyos angulatus in central and north‐eastern Japan by inter‐simple sequence repeat analysis
Authors: KUROKAWA S , KOBAYASHI H , SENDA T
Published: June 2009

For the development of effective procedures to control invasive plants, it is necessary to learn about their mechanism of spread, for which an understanding of the plant’s genetic variation may be important. Sicyos angulatus is a widespread and invasive weed that grows among forage crops and natural vegetation in Japan. Inter‐simple sequence repeat (ISSR) genotyping was used to detect the regional patterns of genetic variation of S. angulatus in its introduced range in Japan. The goal of this research was to assess the introduction dynamics and mechanism of spread of S. angulatus in Japan. Four screened ISSR primers produced 15 reliable bands, and 12 of these were polymorphic among six areas in central and north‐eastern Japan. The analysis of molecular variance (amova) revealed that 88.4% of genetic variation occurred within areas rather than between the two regions (1.1%), or among areas within regions (10.5%). While the total gene diversity among areas (Ht) was 0.1684, the coefficient of gene differentiation was low among two geographically distinct regions (Gst = 0.053). The genetic diversity indices (h = 0.116; I = 0.173) of the Fuji river area, assumed to be near the first introduction site, were not higher than other areas (total h = 0.165; total I = 0.263). In contrast, those of the Chikuma river and Tenryu river areas were relatively high (h = 0.173 and 0.187; I = 0.276 and 0.277 respectively). The Mantel test showed no significant correlation between geographical and genetic distances. These results suggest multiple introductions from the same gene pools into both central and north‐eastern regions of Japan.