bluuebunny/crossref_metadata_2025 huggingface dataset:
Cross-Polity Linguistic Homogeneity/Heterogeneity and Per-Capita Gross National Product
Authors: Fishman Joshua A. , Solano Frank R.
Published: December 2010

Trans-polita lingva homogeno/heterogeno kaj laûkapa malneta nacia produkto: Empiria esploro
Oni analizis pli ol 230 varieblojn, per akumula multobla regresa metodo, trans 130 politoj, por konstati ĉu lingva homegeno/heterogeno troviĝas ene de la plej trafa sub-kategorio de antaŭdiriloj por klarigi plej potence kaj ŝpare trans-politan varion rilate laŭkapan malnetan nacian produkton. Kvankam montriĝis eble atingi tre altan multoblan R (.90), kiu klarigis pli ol 80 procentojn de tia trans-polita vario surbaze de nur dek antaŭdiriloj, lingva homogeno/heterogeno ne estis inter tiu plej trafa subkategorio de antaŭdiriloj. Vario de laŭkapa malneta nacia produkto estas rekta flankprodukto de vario en modernigo de ŝtata administracio kaj industrio—variebloj, kiuj nur nedirekte kaj nesignife rilatas al lingva homogeno/heterogeno.
A peripheral CD4+ T cell precursor for naive, memory, and regulatory T cells
Authors: Zhao Chunfang , Davies Joanna D.
Published: December 2010

Mechanisms that control the size of the T cell pool, the ratio between naive cells and memory cells, the number and frequency of regulatory T cells, and T cell receptor (TCR) diversity are necessary to maintain immune integrity and avoid disease. We have previously shown that a subset of naive CD4+ T cells, defined by the expression on their surface of a very low density of CD44 (CD44v.low cells), can inhibit wasting and wasting-associated lymphopenia in mice with cancer. In this study, we further investigate the properties of CD44v.low cells and show that they are significantly more efficient than the remaining naive (CD44low or CD44int) and memory CD4+ cell subsets in reconstituting the overall size of the CD4+ T cell pool, creating a T cell pool with a diverse TCR repertoire, generating regulatory T cells that express forkhead box P3 (FoxP3), and promoting homeostatic equilibrium between naive, memory, and Foxp3+ regulatory T cell numbers. T cell population reconstitution by CD44v.low cells is thymus independent. Compared with CD44int cells, a higher percentage of CD44v.low cells express B cell leukemia/lymphoma 2, interleukin-7 receptor, and CD5. The data support a key role for CD4+ CD44v.low cells as peripheral precursors that maintain the integrity of the CD4+ T cell pool.
Differential regulation of human and murine P-selectin expression and function in vivo
Authors: Liu Zhenghui , Miner Jonathan J. , Yago Tadayuki , Yao Longbiao , Lupu Florea , Xia Lijun , McEver Rodger P.
Published: December 2010

Leukocytes roll on P-selectin after its mobilization from secretory granules to the surfaces of platelets and endothelial cells. Tumor necrosis factor (TNF), IL-1β, and lipopolysaccharide increase synthesis of P-selectin in murine but not in human endothelial cells. To explore the physiological significance of this difference in gene regulation, we made transgenic mice bearing the human Selp gene and crossed them with mice lacking murine P-selectin (Selp−/−). The transgenic mice constitutively expressed human P-selectin in platelets, endothelial cells, and macrophages. P-selectin mediated comparable neutrophil migration into the inflamed peritoneum of transgenic and wild-type (WT) mice. Leukocytes rolled similarly on human or murine P-selectin on activated murine platelets and in venules of the cremaster muscle subjected to trauma. However, TNF increased murine P-selectin in venules, slowing rolling and increasing adhesion, whereas it decreased human P-selectin, accelerating rolling and decreasing adhesion. Both P- and E-selectin mediated basal rolling in the skin of WT mice, but E-selectin dominated rolling in transgenic mice. During contact hypersensitivity, murine P-selectin messenger (m) RNA was up-regulated and P-selectin was essential for leukocyte recruitment. However, human P-selectin mRNA was down-regulated and P-selectin contributed much less to leukocyte recruitment. These findings reveal functionally significant differences in basal and inducible expression of human and murine P-selectin in vivo.
Muscle weakness in Ryr1I4895T/WT knock-in mice as a result of reduced ryanodine receptor Ca2+ ion permeation and release from the sarcoplasmic reticulum
Authors: Loy Ryan E. , Orynbayev Murat , Xu Le , Andronache Zoita , Apostol Simona , Zvaritch Elena , MacLennan David H. , Meissner Gerhard , Melzer Werner , Dirksen Robert T.
Published: December 2010

The type 1 isoform of the ryanodine receptor (RYR1) is the Ca2+ release channel of the sarcoplasmic reticulum (SR) that is activated during skeletal muscle excitation–contraction (EC) coupling. Mutations in the RYR1 gene cause several rare inherited skeletal muscle disorders, including malignant hyperthermia and central core disease (CCD). The human RYR1I4898T mutation is one of the most common CCD mutations. To elucidate the mechanism by which RYR1 function is altered by this mutation, we characterized in vivo muscle strength, EC coupling, SR Ca2+ content, and RYR1 Ca2+ release channel function using adult heterozygous Ryr1I4895T/+ knock-in mice (IT/+). Compared with age-matched wild-type (WT) mice, IT/+ mice exhibited significantly reduced upper body and grip strength. In spite of normal total SR Ca2+ content, both electrically evoked and 4-chloro-m-cresol–induced Ca2+ release were significantly reduced and slowed in single intact flexor digitorum brevis fibers isolated from 4–6-mo-old IT/+ mice. The sensitivity of the SR Ca2+ release mechanism to activation was not enhanced in fibers of IT/+ mice. Single-channel measurements of purified recombinant channels incorporated in planar lipid bilayers revealed that Ca2+ permeation was abolished for homotetrameric IT channels and significantly reduced for heterotetrameric WT:IT channels. Collectively, these findings indicate that in vivo muscle weakness observed in IT/+ knock-in mice arises from a reduction in the magnitude and rate of RYR1 Ca2+ release during EC coupling that results from the mutation producing a dominant-negative suppression of RYR1 channel Ca2+ ion permeation.
MU2A—reconciling the genome and transcriptome to determine the effects of base substitutions
Authors: Garla Vijay , Kong Yong , Szpakowski Sebastian , Krauthammer Michael
Published: December 2010

Motivation: Next-generation sequencing technologies enable the identification of sequence variation in the genome and transcriptome. Differences between the reference genome and transcript libraries complicate the determination of the effect of genomic sequence variants on protein products; similarly, these differences complicate the mapping of sequence variants found in transcripts to their respective genomic position. We have developed MU2A, a publicly available web service for variant annotation that reconciles differences between the genome and transcriptome, enabling the rapid and accurate determination of the effects of genomic variants on protein products, and the mapping of variants detected in transcripts to genomic coordinates. The MU2A web service is available at http://krauthammerlab.med.yale.edu/mu2a. We have released MU2A as open source, available at http://code.google.com/p/mu2a/.

Contact:  michael.krauthammer@yale.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Cytoscape 2.8: new features for data integration and network visualization
Authors: Smoot Michael E. , Ono Keiichiro , Ruscheinski Johannes , Wang Peng-Liang , Ideker Trey
Published: December 2010

Summary: Cytoscape is a popular bioinformatics package for biological network visualization and data integration. Version 2.8 introduces two powerful new features—Custom Node Graphics and Attribute Equations—which can be used jointly to greatly enhance Cytoscape's data integration and visualization capabilities. Custom Node Graphics allow an image to be projected onto a node, including images generated dynamically or at remote locations. Attribute Equations provide Cytoscape with spreadsheet-like functionality in which the value of an attribute is computed dynamically as a function of other attributes and network properties.

Availability and implementation: Cytoscape is a desktop Java application released under the Library Gnu Public License (LGPL). Binary install bundles and source code for Cytoscape 2.8 are available for download from http://cytoscape.org.

Contact:  msmoot@ucsd.edu
When the Web meets the cell: using personalized PageRank for analyzing protein interaction networks
Authors: Iván Gábor , Grolmusz Vince
Published: December 2010

Motivation: Enormous and constantly increasing quantity of biological information is represented in metabolic and in protein interaction network databases. Most of these data are freely accessible through large public depositories. The robust analysis of these resources needs novel technologies, being developed today.

Results: Here we demonstrate a technique, originating from the PageRank computation for the World Wide Web, for analyzing large interaction networks. The method is fast, scalable and robust, and its capabilities are demonstrated on metabolic network data of the tuberculosis bacterium and the proteomics analysis of the blood of melanoma patients.

Availability: The Perl script for computing the personalized PageRank in protein networks is available for non-profit research applications (together with sample input files) at the address: http://uratim.com/pp.zip

Contact:  grolmusz@cs.elte.hu.

Supplementary information: Supplementary data are available at Bioinformatics online.
Cardiac energy metabolism is disturbed in Fabry disease and improves with enzyme replacement therapy using recombinant human galactosidase A
Authors: Machann Wolfram , Breunig Frank , Weidemann Frank , Sandstede Jörn , Hahn Dietbert , Köstler Herbert , Neubauer Stefan , Wanner Christoph , Beer Meinrad
Published: December 2010

Aims

In vitro studies have shown impairment of energy metabolism in cardiac fibroblasts from Fabry patients. A recent in vivo study reported an association between cardiac energy metabolism and increased myocardial mass in Fabry patients. We therefore assessed possible disturbances of cardiac energy metabolism in Fabry patients by in vivo 31P‐MR‐spectroscopy. Additionally, the effect of enzyme replacement therapy (ERT) on cardiac energetics was tested.

Methods and results

Twenty‐three patients (41 ± 9 years; 10 females) with genetically proven Fabry disease were examined with a 1.5 T Scanner, and compared with an age‐matched healthy control group. Eight patients underwent ERT and had follow‐up examinations after 3 and 14 months. The high‐energy phosphate molecules phosphocreatine (PCr) and adenosine triphosphate (ATP) were quantified in localized 31P‐spectra by SLOOP (spectral localization with optimum point spread function). Cine‐ and late gadolinium enhancement (LGE) studies were also performed. When compared with healthy controls, Fabry patients demonstrated reduced PCr‐ (6.1 ± 1.9 vs. 8.8 ± 2.6 mmol/kg; P = 0.003) and ATP concentrations (3.9 ± 1.5 vs. 4.6 ± 1.0 mmol/kg; P = 0.048). During ERT, PCr concentrations increased (7.1 ± 1.5 mmol/kg vs. 6.1 ± 1.9; P < 0.05) and left ventricular mass decreased (215 ± 55 vs. 185 ± 45 g; P = 0.012). Disturbances in cardiac energetics were not correlated to the presence or absence of cardiac fibrosis on LGE.

Conclusion

Cardiac energy metabolism is disturbed in Fabry disease; this may play an important role in the pathogenesis of Fabry cardiomyopathy. Enzyme replacement therapy ameliorates energetic depression.
Effect of Soil Temperature and Plant Age at Time of Inoculation on Progress of Root Rot and Foliar Symptoms of Soybean Sudden Death Syndrome
Authors: Gongora-Canul C. C. , Leandro L. F. S.
Published: December 2010

Sudden death syndrome (SDS) of soybean is favored by planting in cool soil but epidemics can be severe even when planting occurs later in the season into warmer soil. Our objective was to determine how soil temperature affects susceptibility of plants exposed to Fusarium virguliforme at different ages. Soybean plants were grown in rhizotrons in water baths at 17, 23, and 29°C. Subsets of plants were inoculated 0, 3, 7, and 13 days after planting (DAP) by drenching soil with a conidial suspension. Root rot developed in all inoculated plants but severity decreased with increasing temperature and plant age at inoculation. Severity of foliar symptoms also decreased with increasing plant age. Whereas plants inoculated 0 DAP developed severe foliar symptoms at all temperatures, plants inoculated 3 and 7 DAP developed symptoms only at 17 and 23°C, and those inoculated 13 DAP never developed foliar symptoms at any temperature. Root length at inoculation was negatively correlated with disease severity. Our findings suggest that roots are most susceptible to infection during the first days after seed germination and that accelerated root growth in warmer temperatures reduces susceptibility to root infection conducive to foliar symptoms. However, soil temperature may not affect infections that occur as soon as seeds germinate.
First Report of Phytophthora ramorum Causing Shoot Dieback on Bilberry (Vaccinium myrtillus) in Norway
Authors: Herrero M. L. , Toppe B. , Brurberg M. B.
Published: December 2010

In the annual Norwegian Phytophthora ramorum survey in 2009, wild bilberry samples, collected during September and October in a semimanaged park (arboretum) in the southwest coast of Norway, tested positive in a P. ramorum-specific real-time PCR test (1). Necrotic lesions were observed in shoot tips, branching points, and around leaf abscission scars. The lesions were of variable dimensions. In the samples collected in October, some lesions were confluent and completely covered some shoots. After direct detection on plant material, P. ramorum was isolated from necrotic lesions of the stems on semiselective media PARP (corn meal agar amended with pimaricin, ampicillin, rifampicin, and pentacloronitrobenzene) (2). The isolates were identified by the production of abundant chlamydospores on agar and deciduous, semipapillate sporangia that is characteristic of P. ramorum (3). Sexual structures were not observed. Three pure cultures obtained from different plant samples also tested positive for P. ramorum by the specific real-time PCR test (1). All positive samples were found in close vicinity of infected rhododendron plants. In this location, P. ramorum had already been detected on rhododendron in 2005. A pathogenicity test was performed with two isolates from bilberry and one from rhododendron. Wild asymptomatic bilberry plants were collected at the end of June in the forest around Oslo. Two shoot tips with 6 to 10 leaves each and one small part of a branch with several shoots and immature berries were used for testing each isolate. The inoculations were made by dipping the shoots in a zoospore suspension (2 to 3 × 104 zoospores ml–1) for 1 min. Inoculated material was placed in moist incubation chambers and incubated at room temperature (19 to 24°C). Controls were obtained by dipping shoots in sterile water. After 2 days, lesions were observed on leaf laminae from all the shoots inoculated with the three different isolates. After 4 days, severe petiole necroses were observed and leaves abscised easily from the stems. Symptoms on the stems were observed in the apical part or areas around the nodes. Some shoots were almost completely necrotic. Heavy sporulation was observed on the berries. P. ramorum was reisolated from leaves and stems of inoculated shoots for all the isolates. P. ramorum was not recovered from control plants. To our knowledge, this is the first report of P. ramorum on bilberry in Norway.

References: (1) K. L. Hughes et al. Phytopathology 96:975, 2006. (2) M. E. Kannwischer and D. J. Mitchell. Phytopathology 68:1760, 1978. (3) S. Werres et al. Mycol. Res.105:1155, 2001.
LSH and G9a/GLP complex are required for developmentally programmed DNA methylation
Authors: Myant Kevin , Termanis Ausma , Sundaram Arvind Y.M. , Boe Tristin , Li Chao , Merusi Cara , Burrage Joe , Heras Jose I. de Las , Stancheva Irina
Published: December 2010

LSH, a member of the SNF2 family of chromatin remodeling ATPases encoded by the Hells gene, is essential for normal levels of DNA methylation in the mammalian genome. While the role of LSH in the methylation of repetitive DNA sequences is well characterized, its contribution to the regulation of DNA methylation and the expression of protein-coding genes has not been studied in detail. In this report we investigate genome-wide patterns of DNA methylation at gene promoters in Hells−/− mouse embryonic fibroblasts (MEFs). We find that in the absence of LSH, DNA methylation is lost or significantly reduced at ∼20% of all normally methylated promoter sequences. As a consequence, a large number of genes are misexpressed in Hells−/− MEFs. Comparison of Hells−/− MEFs with wild-type MEFs and embryonic stem (ES) cells suggests that LSH is important for de novo DNA methylation events that accompany the establishment and differentiation of embryonic lineage cells. We further show that the generation of normal DNA methylation patterns and stable gene silencing at specific promoters require cooperation between LSH and the G9a/GLP complex of histone methylases. At such loci, G9a recruitment is compromised when LSH is absent or greatly reduced. Taken together, our data suggest a mechanism whereby LSH promotes binding of DNA methyltransferases and the G9a/GLP complex to specific loci and facilitates developmentally programmed DNA methylation and stable gene silencing during lineage commitment and differentiation.
Analysis of streptococcal CRISPRs from human saliva reveals substantial sequence diversity within and between subjects over time
Authors: Pride David T. , Sun Christine L. , Salzman Julia , Rao Nitya , Loomer Peter , Armitage Gary C. , Banfield Jillian F. , Relman David A.
Published: December 2010

Viruses may play an important role in the evolution of human microbial communities. Clustered regularly interspaced short palindromic repeats (CRISPRs) provide bacteria and archaea with adaptive immunity to previously encountered viruses. Little is known about CRISPR composition in members of human microbial communities, the relative rate of CRISPR locus change, or how CRISPR loci differ between the microbiota of different individuals. We collected saliva from four periodontally healthy human subjects over an 11- to 17-mo time period and analyzed CRISPR sequences with corresponding streptococcal repeats in order to improve our understanding of the predominant features of oral streptococcal adaptive immune repertoires. We analyzed a total of 6859 CRISPR bearing reads and 427,917 bacterial 16S rRNA gene sequences. We found a core (ranging from 7% to 22%) of shared CRISPR spacers that remained stable over time within each subject, but nearly a third of CRISPR spacers varied between time points. We document high spacer diversity within each subject, suggesting constant addition of new CRISPR spacers. No greater than 2% of CRISPR spacers were shared between subjects, suggesting that each individual was exposed to different virus populations. We detect changes in CRISPR spacer sequence diversity over time that may be attributable to locus diversification or to changes in streptococcal population structure, yet the composition of the populations within subjects remained relatively stable. The individual-specific and traceable character of CRISPR spacer complements could potentially open the way for expansion of the domain of personalized medicine to the oral microbiome, where lineages may be tracked as a function of health and other factors.
Allogeneic transplantation for Hodgkin’s lymphoma
Authors: Corradini Paolo , Sarina Barbara , Farina Lucia
Published: December 2010

Hodgkin’s lymphoma (HL) can be cured in most of the patients, but in case of refractory disease or relapse after autologous stem cell transplantation (SCT) the prognosis becomes very poor. In these patients a consensus about the standard approach has not been achieved so far and only allogeneic SCT has shown a long‐term disease control. The postulated graft‐versus‐Hodgkin’s lymphoma is a matter of controversy, but the clinical responses observed after donor lymphocyte infusions may explain the superiority of alloSCT over standard chemo‐radiotherapy. The results of conventional myeloablative alloSCT had a relevant non‐relapse mortality (NRM), discouraging its widespread application as salvage treatment. In the last 10 years, reduced intensity conditioning (RIC) significantly decreased the NRM, widening the application of alloSCT also to heavily pretreated patients. Taking into account all phase II studies, 20–30% of patients receiving RIC alloSCT are disease‐free and probably some of them are cured.
The multiple faces of indirect defences and their agents of natural selection
Authors: Kessler André , Heil Martin
Published: December 2010

1.Plants commonly attract predatory and parasitoid organisms, and may thereby increase resistance against antagonistic herbivores. Mechanisms for indirect resistance include the provision of resources (e.g. food and shelter) for predators as well as the provision of information (e.g. herbivore‐induce volatiles) on the location of hosts and prey that can facilitate the foraging behaviour of natural enemies of herbivores.

2.These ecologically divergent mechanisms for attracting bodyguards should also differ fundamentally in their evolution, particularly in how herbivores and their predators select on plant resistance traits. However, these different strategies are typically lumped together in theoretical discussions of indirect defences.

3.Here we highlight the fundamental differences between resource‐mediated and information‐mediated indirect resistance and discuss the relative evolutionary impacts of the interacting organisms as agents of natural selection in shaping indirect defence traits of plants.

4.We review clear evidence for a defensive function of resource‐mediated indirect resistance, and recognize a significant lack of evidence for an adaptive function of information‐mediated traits. A comparison of the underlying factors driving coevolution in each category of indirect defences, suggests that information‐mediated indirect resistance is less likely to be subject to coevolution between plants and the third trophic level.
Cell wall integrity is linked to mitochondria and phospholipid homeostasis in Candida albicans through the activity of the post‐transcriptional regulator Ccr4‐Pop2
Authors: Dagley Michael J. , Gentle Ian E. , Beilharz Traude H. , Pettolino Filomena A. , Djordjevic Julianne T. , Lo Tricia L. , Uwamahoro Nathalie , Rupasinghe Thusitha , Tull Dedreja L. , McConville Malcolm , Beaurepaire Cecile , Nantel André , Lithgow Trevor , Mitchell Aaron P. , Traven Ana
Published: December 2010

The cell wall is essential for viability of fungi and is an effective drug target in pathogens such as Candida albicans. The contribution of post‐transcriptional gene regulators to cell wall integrity in C. albicans is unknown. We show that the C. albicans Ccr4‐Pop2 mRNA deadenylase, a regulator of mRNA stability and translation, is required for cell wall integrity. The ccr4/pop2 mutants display reduced wall β‐glucans and sensitivity to the echinocandin caspofungin. Moreover, the deadenylase mutants are compromised for filamentation and virulence. We demonstrate that defective cell walls in the ccr4/pop2 mutants are linked to dysfunctional mitochondria and phospholipid imbalance. To further understand mitochondrial function in cell wall integrity, we screened a Saccharomyces cerevisiae collection of mitochondrial mutants. We identify several mitochondrial proteins required for caspofungin tolerance and find a connection between mitochondrial phospholipid homeostasis and caspofungin sensitivity. We focus on the mitochondrial outer membrane SAM complex subunit Sam37, demonstrating that it is required for both trafficking of phospholipids between the ER and mitochondria and cell wall integrity. Moreover, in C. albicans also Sam37 is essential for caspofungin tolerance. Our study provides the basis for an integrative view of mitochondrial function in fungal cell wall biogenesis and resistance to echinocandin antifungal drugs.
RatA (YfjG), an Escherichia coli toxin, inhibits 70S ribosome association to block translation initiation
Authors: Zhang Yonglong , Inouye Masayori
Published: December 2010

RatA (YfjG) is a toxin encoded by the ratA–ratB (yfjG–yfjF) operon on the Escherichia coli genome. Induction of RatA led to the inhibition of protein synthesis, while DNA and RNA synthesis was not affected. The stability of mRNAs was also unchanged as judged by in vivo primer extension experiments and by Northern blotting analysis. The ribosome profile of the cells overexpressing RatA showed that 70S ribosomes as well as polysomes significantly decreased with concomitant increase of 50S and 30S subunits. The addition of purified RatA to a cell‐free system inhibited the formation of 70S ribosomes even in the presence of 6 mM Mg2+. RatA was specifically associated with 50S subunits, indicating that it binds to 50S subunits to block its association with 30S subunits leading to the inhibition of formation of 70S ribosomes. However, RatA did not cause dissociation of 70S ribosomes and its anti‐association activity was blocked by paromomycin, an inhibitor for IF3, an essential initiation factor, having 21% sequence homology with RatA. Here we demonstrate that RatA is a new E. coli toxin, which effectively blocks the translation initiation step. We propose that this toxin of previously unknown function be renamed as RatA (Ribosome association toxin A).
Leptospira immunoglobulin‐like protein B (LigB) binding to the C‐terminal fibrinogen αC domain inhibits fibrin clot formation, platelet adhesion and aggregation
Authors: Lin Yi‐Pin , McDonough Sean P. , Sharma Yogendra , Chang Yung‐Fu
Published: December 2010

Leptospira immunoglobulin‐like (Lig) proteins including LigA and LigB are adhesins that bind to fibronectin, collagen, laminin and elastin. In addition, Lig proteins are fibrinogen (Fg)‐binding proteins, although the physiological role of the Lig–Fg interaction is unclear. In this study, a previously identified Fg‐binding region, LigBCen2 (amino acids 1014–1165 of LigB), has been further localized to LigBCen2R, which consists of the partial 11th and entire 12th Ig‐like domain (amino acids 1014–1119). LigBCen2R was found to bind to the C‐terminal αC domain of Fg (FgαCC; amino acids 392–644 in Fg α chain; isothermal titration calorimetry, KD = 0.375 µM; fluorescence spectrometry, KD = 0.364 µM). The quenching and blue shift observed for the maximum wavelength intensities of the tryptophan fluorescence spectra for FgαCCY570W upon LigBCen2RW1073C binding suggested an RGD motif close to the sole tryptophan on FgαCCY570W was buried in LigBCen2R upon saturation with FgαCC. A conformational change in LigBCen2R when bound to the FgαCC RGD motif blocked further binding to integrin αIIbβ3 on platelets, thus preventing their aggregation. LigBCen2R binding to FgαCC reduced clot formation but did not affect plasminogen and tissue‐type plasminogen activator interactions with FgαCC. This study is the first to report that a spirochaetal protein binds to the C‐terminal αC domain of Fg, which regulates thrombosis and fibrinolysis, and may help explain the pulmonary haemorrhage and thrombocytopenia seen in clinical cases of leptospirosis.
Regulation of HLA class II expression prevents allogeneic T‐cell responses
Authors: Jaimes Y. , Seltsam A. , Eiz‐Vesper B. , Blasczyk R. , Figueiredo C.
Published: December 2010

Human leukocyte antigen (HLA) class II molecules are polymorphic heterodimers that present peptides to CD4+ T‐cells. The HLA‐DM molecule contributes to assemble HLA class II‐peptide complexes. We investigated the effect of silencing either HLA‐DR or HLA‐DM expression in the allogeneic T‐cell responses.

The delivery of HLA‐DR‐ or HLA‐DM‐specific short hairpin RNAs (shRNAs) in a monocytic cell line caused a decrease by up to 85% and 75% at the respective mRNA level. Allogeneic T‐cells stimulated with HLA‐DM‐silenced monocytes decreased to 30% granzyme B mRNA and interferon gamma (IFN‐γ) production in comparison with T‐cells stimulated with monocytes expressing a non‐specific shRNA. By contrast, HLA‐DR‐silenced monocytes did not induce proliferation, up‐regulation of granzyme B mRNA levels or high IFN‐γ secretion by allogeneic T‐cells vs HLA‐DR expressing cells.

Direct targeting of HLA‐DR expression prevented more efficiently an allogeneic T‐cell response in comparison with the knockdown of the expression of HLA‐DM molecules. Silencing the expression of HLA‐DR molecules might contribute to the development of new allogeneic cell‐based therapeutic approaches.
Desensitization: achieving immune detente
Authors: Zachary A. A. , Eng H. S.
Published: December 2010

Antibodies to donor HLA (human leukocyte antigen) and/or ABO antigens were a contraindication to transplantation of most organs for decades. Desensitization protocols have shown the ability to produce reduction of such antibodies sufficient to achieve a successful transplantation. The two major protocols in use are high‐dose IVIg or plasmapheresis with low‐dose IVIg. The protocols differ in the basic treatment and, to some degree, in their application, but both use standard immunosuppressive agents as well as more recently developed adjunctive agents such as cell‐depleting antibodies. Graft and patient survival with both types of protocol are comparable to that of non‐sensitized patients, although desensitized patients do have a higher incidence of antibody‐mediated rejection (AMR). Antibodies to donor antigens may persist after transplantation, and while the initial antibody titer represents the level of difficulty for successful desensitization, the strength of antibodies that persist after transplantation reflects the risk of AMR. Current protocols do not eliminate B cell clones specific for donor HLA; therefore, desensitized patients remain at an increased risk of antibody rebound if patients experience pro‐inflammatory events. Therefore, ongoing antibody monitoring is crucial for early detection of antibody‐mediated graft injury. Importantly, the results of numerous programs show that ABOi‐ and HLA‐positive crossmatch renal transplantation, with proper desensitization, can be performed successfully. Further, in addition to increasing the rate of transplantation among sensitized patients, desensitization is providing insight into immunoregulatory processes and may provide information useful in diseases involving immune dysfunction.
Challenges in pediatric transplantation: The impact of chronic kidney disease and cardiovascular risk factors on long‐term outcomes and recommended management strategies
Authors: Filler Guido
Published: December 2010

Filler G. Challenges in pediatric transplantation: The impact of chronic kidney disease and cardiovascular risk factors on long‐term outcomes and recommended management strategies. Pediatr Transplantation 2011: 15:25–31. © 2010 John Wiley & Sons A/S.

Abstract:  Barriers to successful outcomes following pediatric transplantation have shifted from ischemic reperfusion injury and rejection to more long‐term complications. Of particular concern is the high prevalence of CKD owing to preexisting damage and nephrotoxicity, as well as other CV complications such as hypertension and cardiomyopathy. All of these contribute to graft loss and shortened life expectancy, thereby limiting the success story of solid‐organ transplantation. Managing CKD and related CV morbidity should be integral to the care of pediatric transplant patients, and timely detection of any irregularities would increase the chances of restoring lost kidney function. GFR is still the widely accepted indicator of renal function, and nuclear medicine techniques are the gold standard measurement methods. These methods are limited by costs, radiation exposure and substrate injection, and current practice still uses the Schwartz estimate, despite its well‐documented limitations. Newer endogenous markers of GFR, such as cystatin C clearance, give a more accurate measure of true GFR but have not been embraced in the management of pediatric transplant recipients. Furthermore, indirect markers (e.g., microalbuminuria and hypertension) could also aid early detection of renal damage. The effects of mainstay immunosuppressants on kidney and heart function are varied, with available data indicating favorable outcomes with tacrolimus compared with ciclosporin. There is a need for appropriately designed and powered randomized controlled trials to validate innovative concepts for tailored immunosuppression in the pediatric population. To date, very few studies have generated long‐term data in pediatric renal transplant patients – results of 1–4‐yr study favored tacrolimus over ciclosporin, but other immunosuppressive agents also need to be evaluated.
Pollen and stigma morphology of some Phaseoleae species (Leguminosae) with different pollinators
Authors: Basso‐Alves J. P. , Agostini K. , de Pádua Teixeira S.
Published: December 2010

Pollen transport to a receptive stigma can be facilitated through different pollinators, which submits the pollen to different selection pressures. This study aimed to associate pollen and stigma morphology with zoophily in species of the tribe Phaseoleae. Species of the genera Erythrina, Macroptilium and Mucuna with different pollinators were chosen. Pollen grains and stigmas were examined under light microscopy (anatomy), scanning electronic microscopy (surface analyses) and transmission electronic microscopy (ultrastructure). The three genera differ in terms of pollen wall ornamentation, pollen size, pollen aperture, thickness of the pollen wall, amount of pollenkitt, pollen hydration status and dominant reserves within the pollen grain, while species within each genus are very similar in most studied characteristics. Most of these features lack relationships to pollinator type, especially in Erythrina and Mucuna. Pollen reserves are discussed on a broad scale, according to the occurrence of protein in the pollen of invertebrate‐ or vertebrate‐pollinated species. Some pollen characteristics are more associated to semi‐dry stigma requirements. This apical, compact, cuticularised and secretory stigma occurs in all species investigated. We conclude that data on pollen and stigma structure should be included together with those on floral morphology and pollinator behaviour for the establishment of functional pollination classes.
Malignant myoepithelioma of the breast
Authors: Terada Tadashi
Published: December 2010

Malignant myoepithelioma of the breast is rare. A 50‐year‐old Japanese woman was admitted to our hospital because of a right breast tumor (11 × 10 × 5.5 cm). Core needle biopsy revealed malignant spindle cells. A mastectomy was performed. The tumor consisted of malignant spindle, round, pleomorphic and giant cells with many mitotic figures and necrotic areas. Tumor and osteoclast‐like giant cells were scattered. Much lymphovascular permeation was seen. In a few areas, particularly on the tumor periphery, there were merges between the tumor cells and myoepithelial cells of the non‐tumorous ducts, as if the tumor emanated from the duct myoepithelium. The tumor was invasive into the skin and pectoral muscle. Immunohistochemically, the tumor cells were diffusely positive for vimentin, CD10, α‐smooth muscle antigen, and Ki‐67 (labeling = 95%). The significant areas of the tumor were positive for S100 protein, p63, p53, CD68, caldesmon, desmin and TGFβ1. A few areas were positive for pancytokeratin (AE1/3), cytokeratin (CK) 5/6, and CK 34βE12. In contrast, the tumor cells were negative for pancytokeratins (WSS, CAM5.2), CK7, CK8, CK14, CK18, CK19, CK20, EMA, CEA, bcl‐2, myoglobin, CD34, CD56, CD45, HMB45, GFAP, α‐1‐antitrypsin, synaptophysin, estrogen receptor, progesterone receptor, HER2/neu, MUC1, MUC2, MUC5AC and MUC6. The author diagnosed the tumor as malignant myoepithelioma, as myoepithelial markers (C10, p63, S100 protein, α‐smooth muscle actin, caldesmon) were positive, and also because there was a transition between the tumor cells and myoepithelium of non‐tumorous ducts. The grade of the tumor was high. The patient was treated with chemoradiation and was free of disease 5 months after the operation.
Coagulation considerations for infants and children undergoing cardiopulmonary bypass
Authors: Eaton Michael P. , Iannoli Ellen M.
Published: December 2010

Cardiac surgery involving cardiopulmonary bypass imposes a significant pathophysiologic burden on patients. Pediatric patients are especially predisposed to the adverse effects of surgery and bypass on the coagulation system, with resultant bleeding, transfusion, and poor outcomes. These risks accrue to pediatric patients in inverse proportion to their weight and are attributable to hematologic immaturity, coagulation defects associated with congenital heart disease, bypass equipment, and the nature of congenital heart surgery. Standard anticoagulation does not completely inhibit thrombin generation, and continuous consumption of coagulation factor continues throughout bypass. Conventional measurements of anticoagulation during bypass poorly reflect this incomplete anticoagulation, and alternate methods may improve anticoagulant therapy. Emerging therapies for blocking the effects of bypass on the coagulation system hold promise for decreasing bleeding and related complications, and improving outcomes in congenital heart surgery.
Reconstituted blood reduces blood donor exposures in children undergoing craniofacial reconstruction surgery
Authors: Stricker Paul A. , Fiadjoe John E. , Davis Amanda R. , Sussman Emily , Burgess Beverly J. , Ciampa Brian , Mendelsohn Jared , Bartlett Scott P. , Sesok‐Pizzini Deborah A. , Jobes David R.
Published: December 2010

Objective/Aims:  To assess the effect of prophylactic administration of fresh‐frozen plasma (FFP) in the form of reconstituted blood in children undergoing craniofacial reconstruction. The outcomes of interest included immediate postoperative coagulation laboratory test results, postoperative surgical drain output, and the number of unique blood donor exposures incurred.

Background:  We recently changed our intraoperative transfusion strategy in children undergoing craniofacial reconstruction surgery to one in which blood loss is replaced with donor‐matched reconstituted blood rather than traditional blood component therapy.

Methods:  We performed a query of our prospective craniofacial surgery perioperative registry for children who underwent fronto‐orbital advancement or posterior cranial vault reconstruction. Registry data from this query were compared to data from a historical cohort.

Results:  Data for 46 registry cases were compared to 150 historical cohort cases. The median number of unique donor exposures for the reconstituted blood group was 2 vs 3 in the historical cohort (P = 0.004). The reconstituted blood group had a decreased incidence of postoperative derangements in soluble clotting factor tests (fibrinogen, PT, or aPTT; 2% vs 24%, P = 0.001), while there was no evidence for a difference in the incidence of thrombocytopenia. There was no evidence for differences in postoperative surgical drain output in the reconstituted blood group and historical cohort over the first 12, 24, and 48 h.

Conclusions:  Prophylactic administration of FFP in the form of donor‐matched reconstituted blood in children undergoing craniofacial reconstruction was associated with improved postoperative coagulation parameters, reduced blood donor exposures, and unchanged postoperative surgical drain output.
Phase locking, the Moran effect and distance decay of synchrony: experimental tests in a model system
Authors: Fox Jeremy W. , Vasseur David A. , Hausch Stephen , Roberts Jodie
Published: December 2010

Ecology Letters (2011) 14: 163–168

Spatially separated populations of many species fluctuate synchronously. Synchrony typically decays with increasing interpopulation distance. Spatial synchrony, and its distance decay, might reflect distance decay of environmental synchrony (the Moran effect), and/or short‐distance dispersal. However, short‐distance dispersal can synchronize entire metapopulations if within‐patch dynamics are cyclic, a phenomenon known as phase locking. We manipulated the presence/absence of short‐distance dispersal and spatially decaying environmental synchrony and examined their separate and interactive effects on the synchrony of the protist prey species Tetrahymena pyriformis growing in spatial arrays of patches (laboratory microcosms). The protist predator Euplotes patella consumed Tetrahymena and generated predator–prey cycles. Dispersal increased prey synchrony uniformly over both short and long distances, and did so by entraining the phases of the predator–prey cycles. The Moran effect also increased prey synchrony, but only over short distances where environmental synchrony was strongest, and did so by increasing the synchrony of stochastic fluctuations superimposed on the predator–prey cycle. Our results provide the first experimental demonstration of distance decay of synchrony due to distance decay of the Moran effect. Distance decay of the Moran effect likely explains distance decay of synchrony in many natural systems. Our results also provide an experimental demonstration of long‐distance phase locking, and explain why cyclic populations provide many of the most dramatic examples of long‐distance spatial synchrony in nature.
Defence Policy under the Labour Government: Operational Dynamism and Strategic Inertia
Authors: Dyson Tom
Published: December 2010

This article examines the process and outcome of defence reform under the Labour government, with a particular focus on the structuring of military input to defence planning. It argues that UK defence reform has been characterised by dynamism at the tactical and operational levels but that organisational politics between the services has impacted upon decisions surrounding defence capability procurement and force posture. The core executive has been able to structure military input to defence planning effectively at the tactical and operational levels. However, the core executive's capacity to provide clear guidance on the balance to be struck between capabilities and force postures relevant to contemporary and future conflict scenarios has been impeded by the British electoral cycle. Neo-classical realism provides, therefore, compelling analytical leverage in conceptualising British defence reform.
The British Civil Service: Perspectives on ‘Decline’ and ‘Modernisation’
Authors: Pyper Robert , Burnham June
Published: December 2010

This article was stimulated by the contradiction between two predominant characterisations of the British civil service. Some analysts see it as in decline, possibly terminally, overwhelmed by the challenges posed by the reforms and the changes in its policy environment; others see it as in the vanguard by adopting modernising reforms and adapting to new public service values. After critically examining these opposing perspectives on civil service ‘decline’ and ‘modernisation’, we conclude that these contrasting analyses suffer from adopting too limited a view of the British civil service in its historical and international context. The British civil service has during its long history progressively modernised and in a progressive way—becoming less corrupt, more accountable, more pluralist, more responsive to citizens’ needs—often sceptical about reform, but nevertheless moving with the times.
Immigrants in Denmark: Access to Employment, Class Attainment and Earnings in a High‐Skilled Economy
Authors: Brodmann Stefanie , Polavieja Javier G.
Published: December 2010

This study examines employment access, class attainment, and earnings among native‐born and first‐generation immigrants in Denmark using Danish administrative data from 2002. Results suggest large gaps in employment access between native‐born Danes and immigrants, as well as among immigrant groups by country of origin and time of arrival. Non‐Western immigrants and those arriving after 1984 are at a particular disadvantage compared to other immigrants, a finding not explained by education differences. Immigrants are more likely to be employed in unskilled manual jobs and less likely to be employed in professional and intermediate‐level positions than native‐born Danes, although the likelihood of obtaining higher‐level positions increases as immigrants’ time in Denmark lengthens. Class attainment and accumulated work experience explain a significant portion of native‐immigrant gaps in earnings, but work experience reduces native‐immigrant gaps in class attainment for lower‐level positions only. The Danish “flexicurity” model and its implications for immigrants living in Denmark are discussed.
Differential susceptibility of astrocytic and neuronal function to 3‐chloropropanediol in the rat inferior colliculus
Authors: Brown Angus M. , Skamarauskas John , Lister Timothy , Madjd Ameneh , Ray David E.
Published: December 2010

J. Neurochem. (2011) 116, 996–1004.

We have previously shown that systemic administration of S(+)3‐chloropropanediol (3‐CPD) produces a morphological loss of astrocytes in specific nuclei of the rodent brain that precedes loss of both neurones and endothelial tight junctions. Here, we have evaluated the differential susceptibility of neuronal and astrocytic function to 3‐CPD, in order to see if this parallels the morphological selectivity. To do this, we have developed an in vivo method for monitoring astrocyte function over time by giving hourly 20‐min bolus challenge exposures to ammonia via an implanted microdialysis probe and measuring the resulting transient increases in the extracellular glutamine : glutamate ratio. These challenge ammonia exposures evoked a stable response for at least 5 h when the probe was implanted in the rat inferior colliculus, but caused no behavioural response or morphological damage. Although 3‐CPD produced a rapid and sustained abolition of the ammonia response within 2 h, the field potential response of inferior collicular neurones to sound fell significantly to 75.0 ± 3.9% pre‐dose at up to 8 h but then fell markedly, reaching 20.5 ± 3.7% at 2 days. Blood flow in the inferior colliculus also showed only late changes, increasing substantially at 2 days. Astrocyte damage at the EM level was seen from 3 h, followed by loss of astrocytes from 18 h to a minimum of 7 ± 10% control at 3 days. The rapid abolition of the ammonia response suggests that in addition to selective astrocyte death, 3‐CPD also produces an earlier impairment of astrocyte function that precedes loss of neuronal function. This initial functional selectivity of 3‐CPD provides a potential investigative tool in neurochemical studies of astrocyte‐neuronal interactions.
Determination of light transmission through multiple sheets of cellulose triacetate using ordinary absorption spectroscopy
Authors: Annis Patricia A , Campbell Jacqueline H , Knopp James A , King Jr Allen D
Published: December 2010

Ordinary optical absorption spectroscopy is used to assess the effects of reflection, scattering and optical absorption on light beams passing through sheets of cellulose triacetate fabric. The attenuation of light transmitted through multiple sheets of undyed fabric is analysed using a model that incorporates the concepts of reflection and turbidity. The attenuation of light by sheets of dyed fabric under conditions of significant light scattering is analysed using the model cited above. The results obtained under conditions of significant light scattering yield optical absorbance values for dye molecules incorporated in the fabric that correspond exactly with the absorbance values measured under conditions of total transparency, which is achieved using matching index of refraction spectroscopy.