bluuebunny/crossref_metadata_2025 huggingface dataset:
Marek's disease virus Meq transforms chicken cells via the v-Jun transcriptional cascade: A converging transforming pathway for avian oncoviruses
Authors: Levy Alon M. , Gilad Oren , Xia Liang , Izumiya Yoshihiro , Choi Jonathan , Tsalenko Anya , Yakhini Zohar , Witter Richard , Lee Lucy , Cardona Carol J. , Kung Hsing-Jien
Published: October 2005

Marek's disease virus (MDV) is a highly pathogenic and oncogenic herpesvirus of chickens. MDV encodes a basic leucine zipper (bZIP) protein, Meq (MDV EcoQ). The bZIP domain of Meq shares homology with Jun/Fos, whereas the transactivation/repressor domain is entirely different. Increasing evidence suggests that Meq is the oncoprotein of MDV. Direct evidence that Meq transforms chicken cells and the underlying mechanism, however, remain completely unknown. Taking advantage of the DF-1 chicken embryo fibroblast transformation system, a well established model for studying avian sarcoma and leukemia oncogenes, we probed the transformation properties and pathways of Meq. We found that Meq transforms DF-1, with a cell morphology akin to v-Jun and v-Ski transformed cells, and protects DF-1 from apoptosis, and the transformed cells are tumorigenic in chorioallantoic membrane assay. Significantly, using microarray and RT-PCR analyses, we have identified up-regulated genes such as JTAP-1, JAC, and HB-EGF, which belong to the v-Jun transforming pathway. In addition, c-Jun was found to form stable dimers with Meq and colocalize with it in the transformed cells. RNA interference to Meq and c-Jun down-modulated the expression of these genes and reduced the growth of the transformed DF-1, suggesting that Meq transforms chicken cells by pirating the Jun pathway. These data suggest that avian herpesvirus and retrovirus oncogenes use a similar strategy in transformation and oncogenesis.
EVOPRINTER, a multigenomic comparative tool for rapid identification of functionally important DNA
Authors: Odenwald Ward F. , Rasband Wayne , Kuzin Alexander , Brody Thomas
Published: October 2005

Here, we describe a multigenomic DNA sequence-analysis tool,
evoprinter
, that facilitates the rapid identification of evolutionary conserved sequences within the context of a single species. The
evoprinter
output identifies multispecies-conserved DNA sequences as they exist in a reference DNA. This identification is accomplished by superimposing multiple reference DNA vs. test-genome pairwise
blat
(
blast
-like alignment tool) readouts of the reference DNA to identify conserved nucleotides that are shared by all orthologous DNAs.
evoprinter
analysis of well characterized genes reveals that most, if not all, of the conserved sequences are essential for gene function. For example, analysis of orthologous genes that are shared by many vertebrates identifies conserved DNA in both protein-encoding sequences and noncoding cis
-
regulatory regions, including enhancers and mRNA microRNA binding sites. In
Drosophila
, the combined mutational histories of five or more species affords near-base pair resolution of conserved transcription factor DNA-binding sites, and essential amino acids are revealed by the nucleotide flexibility of their codon-wobble position(s). Conserved small peptide-encoding genes, which had been undetected by conventional gene-prediction algorithms, are identified by the codon-wobble signatures of invariant amino acids. Also,
evoprinter
allows one to assess the degree of evolutionary divergence between orthologous DNAs by highlighting differences between a selected species and the other test species.
Corroboration of
in vivo
cartilage pressures with implications for synovial joint tribology and osteoarthritis causation
Authors: Morrell Kjirste C. , Hodge W. Andrew , Krebs David E. , Mann Robert W.
Published: October 2005

Pressures on normal human acetabular cartilage have been collected from two implanted instrumented femoral head hemipros-theses. Despite significant differences in subjects' gender, morphology, mobility, and coordination,
in vivo
pressure measurements from both subjects covered similar ranges, with maximums of 5-6 MPa in gait, and as high as 18 MPa in other movements. Normalized for subject weight and height (nMPa), for free-speed walking the maximum pressure values were 25.2 for the female subject and 24.5 for the male subject. The overall maximum nMPa values were 76.2 for the female subject during rising from a chair at 11 months postoperative and 82.3 for the male subject while descending steps at 9 months postoperative. These unique
in vivo
data are consistent with corresponding cadaver experiments and model analyses. The collective results,
in vitro
data, model studies, and now corroborating
in vivo
data support the self-pressurizing “weeping” theory of synovial joint lubrication and provide unique information to evaluate the influence of
in vivo
pressure regimes on osteoarthritis causation and the efficacy of augmentations to, and substitutions for, natural cartilage.
Inhibition of hypothalamic fatty acid synthase triggers rapid activation of fatty acid oxidation in skeletal muscle
Authors: Cha Seung Hun , Hu Zhiyuan , Chohnan Shigeru , Lane M. Daniel
Published: October 2005

Malonyl-CoA functions as a mediator in the hypothalamic sensing of energy balance and regulates the neural physiology that governs feeding behavior and energy expenditure. The central administration of C75, a potent inhibitor of the fatty acid synthase (FAS), increases malonyl-CoA concentration in the hypothalamus and suppresses food intake while activating fatty acid oxidation in skeletal muscle. Closely correlated with the increase in muscle fatty acid oxidation is the phosphorylation/inactivation of acetyl-CoA carboxylase, which leads to reduced malonyl-CoA concentration. Lowering muscle malonyl-CoA, a potent inhibitor of carnitine/palmitoyl-CoA transferase 1 (CPT1), releases CPT1 from inhibitory constraint, facilitating the entry of fatty acids into mitochondria for β oxidation. Also correlated with these events are C75-induced increases in the expression of skeletal muscle peroxisome proliferator-activated receptor α (PPARα), a transcriptional activator of fatty acid oxidizing enzymes, and uncoupling protein 3 (UCP3), a thermogenic mitochondrial uncoupling protein. Phentolamine, an α-adrenergic blocking agent, prevents the C75-induced increases of skeletal muscle UCP3 and whole body fatty acid oxidation and C75-induced decrease of skeletal muscle malonyl-CoA. Thus, the sympathetic nervous system is implicated in the transmission of the “malonyl-CoA signal” from brain to skeletal muscle. Consistent with the up-regulation of UCP3 and PPARα is the concomitant increase in the expression of PGC1α, transcriptional coactivator of the UCP3 and PPARα-activated genes. These findings clarify the mechanism by which the hypothalamic malonyl-CoA signal is communicated to metabolic systems in skeletal muscle that regulate fatty acid oxidation and energy expenditure.
Natural killer cell and macrophage cooperation in MyD88-dependent innate responses to
Plasmodium falciparum
Authors: Baratin Myriam , Roetynck Sophie , Lépolard Catherine , Falk Christine , Sawadogo Serge , Uematsu Satoshi , Akira Shizuo , Ryffel Bernhard , Tiraby Jean-Gérard , Alexopoulou Lena , Kirschning Carsten J. , Gysin Jürg , Vivier Eric , Ugolini Sophie
Published: October 2005

IFN-γ secretion by natural killer (NK) cells is pivotal to several tumor and viral immune responses, during which NK and dendritic cells cooperation is required. We show here that macrophages are mandatory for NK cell IFN-γ secretion in response to erythrocytes infected with
Plasmodium falciparum
(
Pf
), a causative agent of human malaria. In addition, direct sensing of
Pf
infection by NK cells induces their production of the proinflammatory chemokine CXCL8, without triggering their granule-mediated cytolytic programs. Despite their reported role in
Pf
recognition, Toll-like receptor (TLR) 2, TLR9, and TLR11 are individually dispensable for NK cell activation induced by
Pf
-infected erythrocytes. However, IL-18R expression on NK cells, IL-18 production by macrophages, and MyD88 on both cell types are essential components of this previously undescribed pathway of NK cell activation in response to a parasite infection.
Condensation of the plasma membrane at the site of T lymphocyte activation
Authors: Gaus Katharina , Chklovskaia Elena , Fazekas de St. Groth Barbara , Jessup Wendy , Harder Thomas
Published: October 2005

After activation, T lymphocytes restructure their cell surface to form membrane domains at T cell receptor (TCR)–signaling foci and immunological synapses (ISs). To address whether these rearrangements involve alteration in the structure of the plasma membrane bilayer, we used the fluorescent probe Laurdan to visualize its lipid order. We observed a condensation of the plasma membrane at TCR activation sites. The formation of ordered domains depends on the presence of the transmembrane protein linker for the activation of T cells and Src kinase activity. Moreover, these ordered domains are stabilized by the actin cytoskeleton. Membrane condensation occurs upon TCR stimulation alone but is prolonged by CD28 costimulation with TCR. In ISs, which are formed by conjugates of TCR transgenic T lymphocytes and cognate antigen-presenting cells, similar condensed membrane phases form first in central regions and later at the periphery of synapses. The formation of condensed membrane domains at T cell activation sites biophysically reflects membrane raft accumulation, which has potential implications for signaling at ISs.
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease
Authors: Yu W. Haung , Cuervo Ana Maria , Kumar Asok , Peterhoff Corrinne M. , Schmidt Stephen D. , Lee Ju-Hyun , Mohan Panaiyur S. , Mercken Marc , Farmery Mark R. , Tjernberg Lars O. , Jiang Ying , Duff Karen , Uchiyama Yasuo , Näslund Jan , Mathews Paul M. , Cataldo Anne M. , Nixon Ralph A.
Published: October 2005

Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before β-amyloid (Aβ) deposits extracellularly in the presenilin (PS) 1/Aβ precursor protein (APP) mouse model of β-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Aβ. Purified AVs contain APP and β-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent γ-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Aβ production. Our results, therefore, link β-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.
Effect of Ingestion of Cow's Milk Protein Hydrolysate Formulas on α‐Casein‐Specific Immunoglobulin E and G1 Antibody Responses in Naïve and Sensitized Mice
Authors: Peng Ho‐Jen , Su Song‐Nan , Wu Keh‐Gong , Ho Chi‐Kuan , Kuo Hsiang‐Lan
Published: October 2005

Objectives:

Cow's milk protein hydrolysate formulas are widely used for genetically predisposed atopic infants. Whether hydrolysate formulas can induce oral tolerance to α‐casein was studied for the first time in naive and sensitized mice.

Methods:

Using immunoblotting, residual antigenicity to α‐casein was examined for in animals fed hydrolysate formulas. Naïve mice fed hydrolysate formulas for 1 to 4 weeks were later sensitized with α‐casein. Another group of mice sensitized first with α‐casein were then fed hydrolysate formulas continually for 12 weeks.

Results:

Oral tolerance measured by immunoglobulin (Ig)E and IgG1 antibody responses to α‐casein was induced in naïve mice fed NAN for 1 week or NAN‐HA for 4 weeks. IgE responses to α‐casein were suppressed in mice fed NAN‐HA for 1 week or Neoangelac FL for 4 weeks. In contrast, mice fed Alfare, Pepti‐Junior, or Pregestimil for 1 to 4 weeks did not develop tolerance to α‐casein. Antibody responses to α‐casein were not significantly suppressed in sensitized mice fed NAN or hydrolysate formulas for 12 weeks.

Conclusions:

Primary IgE responses to α‐casein are readily suppressed in naïve mice firts fed cow's milk formula or partially hydrolyzed formula for 1 week. Conversely, ongoing IgE, IgG1, and IgG antibody responses to α‐casein are poorly supressed in previously sensitized mice even after prolonged feeding of cow's milk formula or hydrolysate formulas.
Diagnostic and Therapeutic Endoscopic Retrograde Cholangiopancreatography in Children: A Large Series Report
Authors: Cheng Chi‐Liang , Fogel Evan L , Sherman Stuart , McHenry Lee , Watkins James L , Croffie Joseph M , Gupta Sandeep K , Fitzgerald Joseph F , Lazzell‐Pannell Laura , Schmidt Suzette , Lehman Glen A
Published: October 2005

Objectives:

Our goal is to evaluate the indications, findings, therapies, safety, and technical success of endoscopic retrograde cholangiopancreatography (ERCP) in children.

Methods:

Our database was searched for patients 17 years of age or younger undergoing ERCP between January 1994 and March 2003. Additional information was obtained by chart review. The safety and technical success of ERCP were examined. Complications were classified by the consensus criteria.

Results:

A total of 245 patients (95 M, 150 F; mean age 12.3 years) underwent 329 examinations. Indications included biliary pathology (n = 93), pancreatic pathology (n = 111), and chronic abdominal pain of suspected biliary or pancreatic origin (n = 41). The ERCP findings were bile duct stone(s) (n = 29), benign biliary stricture (n = 19), primary sclerosing cholangitis (n = 7), anomalous pancreaticobiliary union (n = 8), choledochal cyst (n = 5), bile duct leak (n = 6), malignant biliary stricture (n = 2), biliary atresia (n = 1), chronic pancreatitis (n = 44), pancreas divisum (n = 26), pancreatic duct stricture with (n = 6) or without (n = 9) leak, pancreatic tumor (n = 1), periampullary adenoma (n = 2), and sphincter of Oddi dysfunction (n = 65). Endoscopic therapies were performed in 71% of the procedures and included sphincterotomy, stone extraction, stricture dilation, endoprosthesis placement, snare papillectomy, and cystoduodenostomy. Thirty‐two (9.7%) post‐ERCP complications occurred and included cholangitis in 1 patient and pancreatitis in 31. The pancreatitis was graded mild in 24, moderate in 5, and severe in 2. No mortality related to ERCP occurred.

Conclusions:

Diagnostic and therapeutic ERCP results are similar in children and adults except for a lower incidence of malignant disease in children. Technical success rates are high. However, ERCP‐related pancreatitis is not uncommon, and the risk and benefits should be carefully reviewed before proceeding. Outcome data are necessary and is currently being accumulated at our institution.
Early Weaning Stimulates Intestinal Brush Border Enzyme Activities in Piglets, Mainly at the Posttranscriptional Level
Authors: Marion Julia , Petersen Yvette Miata , Romé Véronique , Thomas Françoise , Sangild Per Torp , Dividich Jean Le , Huërou‐Luron Isabelle Le
Published: October 2005

Backgrounds:

Weaning‐associated anorexia is the main factor responsible for structural alterations of the small intestine. However, whether weaning and the postweaning feed intake level affect disaccharidase and peptidase gene expression remains to be elucidated.

Methods:

Adaptation of the small intestine to early weaning at 7 days of age and the effects of postweaning feed intake were investigated on 56 pigs in two trials. Structural parameters and gene expression and activities of intestinal lactase, maltase, sucrase, aminopeptidases A and N, and dipeptidyl peptidase IV were determined along the small intestine.

Results:

Within 3 days, weaning induced increases in maltase, sucrase, and peptidase specific activities (P < 0.05) and a decrease in lactase activity and villous height (P < 0.05). Only for maltase activity were the weaning‐induced changes closely correlated with corresponding mRNA levels. In weaned piglets, aminopeptidase N activity was consistently stimulated and dipeptidyl peptidase IV depressed by high level of feed intake but without effects on the corresponding mRNA levels. Furthermore, the longitudinal distribution of enzyme activities along the small intestine showed poor correlation with the corresponding mRNA levels.

Conclusion:

Early weaning in pigs is associated with a remarkable capacity of the small intestine to rapidly increase the activity of key brush border enzymes. This adaptation, largely independent on feed intake for intestinal enzyme mRNAs and disaccharidase activities, occurred at the posttranscriptional rather than at the transcriptional level of enzyme biosynthesis (except for maltase). The length of the postweaning anorexia period did not affect the subsequent intestinal capacity for villous elongation but may postpone maturation of peptidase activities.
Early effects of climate change: do they include changes in vector-borne disease?
Authors: Kovats R. S. , Campbell-Lendrum D. H. , McMichel A. J. , Woodward A. , Cox J. St H.
Published: October 2005

The world's climate appears now to be changing at an unprecedented rate. Shifts in the distribution and behaviour of insect and bird species indicate that biological systems are already responding to this change. It is well established that climate is an important determinant of the spatial and temporal distribution of vectors and pathogens. In theory, a change in climate would be expected to cause changes in the geographical range, seasonality (intra–annual variability), and in the incidence rate (with or without changes in geographical or seasonal patterns). The detection and then attribution of such changes to climate change is an emerging task for scientists. We discuss the evidence required to attribute changes in disease and vectors to the early effects of anthropogenic climate change. The literature to date indicates that there is a lack of strong evidence of the impact of climate change on vector–borne diseases (i.e. malaria, dengue, leishmaniasis, tick–borne diseases). New approaches to monitoring, such as frequent and long–term sampling along transects to monitor the full latitudinal and altitudinal range of specific vector species, are necessary in order to provide convincing direct evidence of climate change effects. There is a need to reassess the appropriate levels of evidence, including dealing with the uncertainties attached to detecting the health impacts of global change.
Language rights: Moving the debate forward
Authors: May Stephen
Published: October 2005

This article provides an overview of the current issues and challenges facing the nascent paradigm of minority language rights (MLR). It focuses on the theoretical points of dispute and tension with respect to MLR, as well as the challenges attendant upon their implementation in complex, multiethnic and multilingual contexts. The article acknowledges, but also responds to, key critiques of MLR to date. These include debates about linguistic modernisation, linguistic identities and essentialism, language and social mobility, and macro and micro language practices. In light of these debates, the article speculates about possible ways forward for the MLR paradigm.
Situating language rights:  English and Swahili in Tanzania revisited1
Authors: Blommaert Jan
Published: October 2005

This paper argues for an ethnographic‐sociolinguistic approach to the issue of linguistic rights. In much of the literature on linguistic rights, a fundamentally flawed set of assumptions about language and society is being used, leading to assessments of language situations that are empirically not sustainable. An alternative set of assumptions is offered, grounded in ethnography and focused on language use as oriented towards centering institutions that attribute indexicalities – function and value – to linguistic resources. Such centers are invariably multiple but stratified, and the state occupies a crucial place in these systems, between the world system and local forces. This model is applied to the Tanzanian sociolinguistic situation, where a strong state appeared to be caught between pressures that were both transnational and local. This gave rise to a pattern of distribution of linguistic resources, including English and Swahili, that offered semiotic opportunities to speakers to construct deeply ‘local’ meanings. The languages were not in themselves agents of inequality, but the way in which they were distributed nationally and in relation to transnational hierarchies is the key to understanding inequality. Discussions of linguistic rights should start from assessments of the real potential and constraints of linguistic resources, not from idealized and static conceptions of language and society and predefined scenarios of their interaction.
Adenosine and deoxyadenosine induces apoptosis in oestrogen receptor‐positive and ‐negative human breast cancer cells via the intrinsic pathway
Authors: Hashemi M. , Karami‐Tehrani F. , Ghavami S. , Maddika S. , Los M.
Published: October 2005

Abstract.  In this study we have examined the cytotoxic effects of different concentrations of adenosine (Ado) and deoxyadenosine (dAdo) on human breast cancer cell lines. Ado and dAdo alone had little effect on cell cytotoxicity. However, in the presence of adenosine deaminase (ADA) inhibitor, EHNA, adenosine and deoxyadenosine led to significant growth inhibition of cells of the lines tested. Ado/EHNA and dAdo/EHNA‐induced cell death was significantly inhibited by NBTI, an inhibitor of nucleoside transport, and 5′‐amino‐5′‐deoxyadenosine, an inhibitor of adenosine kinase, but the effects were not affected by 8‐phenyltheophylline, a broad inhibitor of adenosine receptors. The Ado/EHNA combination brought about morphological changes consistent with apoptosis. Caspase‐9 activation was observed in MCF‐7 and MDA‐MB468 human breast cancer cell lines on treatment with Ado/EHNA or dAdo/EHNA, but, as expected, caspase‐3 activation was only observed in MDA‐MB468 cells. The results of the study, thus, suggest that extracellular adenosine and deoxyadenosine induce apoptosis in both oestrogen receptor‐positive (MCF‐7) and also oestrogen receptor‐negative (MDA‐MB468) human breast cancer cells by its uptake into the cells and conversion to AMP (dAMP) followed by activation of nucleoside kinase, and finally by the activation of the mitochondrial/intrinsic apoptotic pathway.
Enhanced matrix degradation after withdrawal of TGF‐β1 triggers hepatocytes from apoptosis to proliferation and regeneration
Authors: Arendt E. , Ueberham U. , Bittner R. , Gebhardt R. , Ueberham E.
Published: October 2005

Abstract. TGF‐β1 is a profibrogenic cytokine participating in deposition of extracellular matrix in fibrotic disorders. In liver, its anti‐proliferative/apoptotic effect on hepatocytes promotes fibrosis. The tetracycline‐controlled double‐transgenic TALAP−2/ptetTGF‐β1 mouse provides a model for reversible liver fibrosis. In livers of TGF‐β1‐expressing mice, hepatocytes showed synchronous apoptosis detected by DNA laddering and active caspase‐3 staining that disappeared when expression of transgenic TGF‐β1 was switched off. In these ‘off’ mice, perisinusoidal liver fibrosis resolved within 21 days accompanied by elevated proliferation of hepatocytes. Here, we have specified the intermediary stages (2–3 days off and 6 days off) in terms of (i) proliferation (by immunohistochemical staining of proliferating cell nuclear antigen and expression of cyclin D1 mRNA) and (ii) extracellular matrix remodelling processes (by measuring mRNA expression of matrix metalloproteinases‐2 and ‐13 (mmp‐2 and mmp‐13) and tissue inhibitor of matrix metalloproteinases 1 (timp‐1) and quantitative morphometric analysis. In summary, we show a rapidly declining timp‐1 mRNA level together with lastingly high mmp‐2 and mmp‐13 mRNA levels after 2–3 days, suggesting that high matrix‐degrading potential represents a prerequisite for the markedly enhanced proliferation of hepatocytes in the early stages after switching off transgenic TGF‐β1.
Genetic divergence does not predict change in ornament expression among populations of stalk‐eyed flies
Authors: SWALLOW JOHN G. , WALLACE LISA E. , CHRISTIANSON SARAH J. , JOHNS PHILIP M. , WILKINSON GERALD S.
Published: October 2005

Stalk‐eyed flies (Diptera: Diopsidae) possess eyes at the ends of elongated peduncles, and exhibit dramatic variation in eye span, relative to body length, among species. In some sexually dimorphic species, evidence indicates that eye span is under both intra‐ and intersexual selection. Theory predicts that isolated populations should evolve differences in sexually selected traits due to drift. To determine if eye span changes as a function of divergence time, 1370 flies from 10 populations of the sexually dimorphic species, Cyrtodiopsis dalmanni and Cyrtodiopsis whitei, and one population of the sexually monomorphic congener, Cyrtodiopsis quinqueguttata, were collected from Southeast Asia and measured. Genetic differentiation was used to assess divergence time by comparing mitochondrial (cytochrome oxidase II and 16S ribosomal RNA gene fragments) and nuclear (wingless gene fragment) DNA sequences for c. five individuals per population. Phylogenetic analyses indicate that most populations cluster as monophyletic units with up to 9% nucleotide substitutions between populations within a species. Analyses of molecular variance suggest a high degree of genetic structure within and among the populations; > 97% of the genetic variance occurs between populations and species while < 3% is distributed within populations, indicating that most populations have been isolated for thousands of years. Nevertheless, significant change in the allometric slope of male eye span on body length was detected for only one population of either dimorphic species. These results are not consistent with genetic drift. Rather, relative eye span appears to be under net stabilizing selection in most populations of stalk‐eyed flies. Given that one population exhibited dramatic evolutionary change, selection, rather than genetic variation, appears to constrain eye span evolution.
Eider females form non‐kin brood‐rearing coalitions
Authors: ÖST MARKUS , VITIKAINEN EMMA , WALDECK PETER , SUNDSTRÖM LISELOTTE , LINDSTRÖM KAI , HOLLMÉN TUULA , FRANSON J. CHRISTIAN , KILPI MIKAEL
Published: October 2005

Kin selection is a powerful tool for understanding cooperation among individuals, yet its role as the sole explanation of cooperative societies has recently been challenged on empirical grounds. These studies suggest that direct benefits of cooperation are often overlooked, and that partner choice may be a widespread mechanism of cooperation. Female eider ducks (Somateria mollissima) may rear broods alone, or they may pool their broods and share brood‐rearing. Females are philopatric, and it has been suggested that colonies may largely consist of related females, which could promote interactions among relatives. Alternatively, shared brood care could be random with respect to relatedness, either because brood amalgamations are accidental and nonadaptive, or through group augmentation, assuming that the fitness of all group members increases with group size. We tested these alternatives by measuring the relatedness of co‐tending eider females in enduring coalitions with microsatellite markers. Females formed enduring brood‐rearing coalitions with each other at random with respect to relatedness. However, based on previous data, partner choice is nonrandom and dependent on female body condition. We discuss potential mechanisms underlying eider communal brood‐rearing decisions, which may be driven by the specific ecological conditions under which sociality has evolved in this species.
Origin and diversification of the human parasite Schistosoma mansoni
Authors: MORGAN JESS A. T. , DEJONG RANDALL J. , ADEOYE GRACE O. , ANSA EBENEZER D. O. , BARBOSA CONSTANÇA S. , BRÉMOND PHILIPPE , CESARI ITALO M. , CHARBONNEL NATHALIE , CORRÊA LYGIA R. , COULIBALY GODEFROY , D’ANDREA PAULO SÉRGIO , DE SOUZA CECILIA PEREIRA , DOENHOFF MICHAEL J. , FILE SHARON , IDRIS MOHAMED A. , INCANI R. NINO , JARNE PHILIPPE , KARANJA DIANA M. S. , KAZIBWE FRANCIS , KPIKPI JOHN , LWAMBO NICHOLAS J. S. , MABAYE AMADOU , MAGALHÃES LUIZ A. , MAKUNDI ASANTELI , MONÉ HÉLÈNE , MOUAHID GABRIEL , MUCHEMI GERALD M. , MUNGAI BEN N. , SÉNE MARIAMA , SOUTHGATE VAUGHAN , TCHUENTÉ LOUIS ALBERT TCHUEM , THÉRON ANDRE , YOUSIF FOUAD , ZANOTTI‐MAGALHÃES ELIANA M. , MKOJI GERALD M. , LOKER ERIC S.
Published: October 2005

Schistosoma mansoni is the most widespread of the human‐infecting schistosomes, present in 54 countries, predominantly in Africa, but also in Madagascar, the Arabian Peninsula, and the Neotropics. Adult‐stage parasites that infect humans are also occasionally recovered from baboons, rodents, and other mammals. Larval stages of the parasite are dependent upon certain species of freshwater snails in the genus Biomphalaria, which largely determine the parasite's geographical range. How S. mansoni genetic diversity is distributed geographically and among isolates using different hosts has never been examined with DNA sequence data. Here we describe the global phylogeography of S. mansoni using more than 2500 bp of mitochondrial DNA (mtDNA) from 143 parasites collected in 53 geographically widespread localities. Considerable within‐species mtDNA diversity was found, with 85 unique haplotypes grouping into five distinct lineages. Geographical separation, and not host use, appears to be the most important factor in the diversification of the parasite. East African specimens showed a remarkable amount of variation, comprising three clades and basal members of a fourth, strongly suggesting an East African origin for the parasite 0.30–0.43 million years ago, a time frame that follows the arrival of its snail host. Less but still substantial variation was found in the rest of Africa. A recent colonization of the New World is supported by finding only seven closely related New World haplotypes which have West African affinities. All Brazilian isolates have nearly identical mtDNA haplotypes, suggesting a founder effect from the establishment and spread of the parasite in this large country.
Febrile nonhaemolytic transfusion reaction caused by antibodies against human platelet antigen 5a
Authors: Tazzari P. L. , Bontadini A. , Zamagni C. , Ricci F. , Fruet F. , Iannelli S. , Conte R.
Published: October 2005

summary.  Anti‐human platelet antigens (HPA) alloantibodies are seldom involved in febrile nonhaemolytic reactions (FNHTRs). We describe a case in which anti‐HPA‐5a alloantibodies are related to an FNHTR.

We studied the specificity of the alloantibodies by flow cytometry, ELISA and MACE. Typing of donors and the patient was performed by sequence‐specific polymerase chain reaction.

The alloantibodies were found reactive with HPA‐5a antigens. The patient was HPA‐5b/b, whereas the donor of the platelet apheresis involved in the FNHTR was HPA‐5a/a.

Despite the low frequency of anti‐HPA‐5a antibodies, they might be responsible for FNHTR.
A clue to the basis of allelic enhancement: occurrence of the Ax subgroup in the offspring of blood group O parents
Authors: Olsson M. L. , Michalewska B. , Hellberg Å. , Walaszczyk A. , Chester M. A.
Published: October 2005

summary.  Apparent deviation from Mendelian rules of blood group inheritance is rarely observed. Blood group O parents with children expressing weak A subgroups have occasionally been described but not explained. A detailed serological investigation of such a family is described here. The ABO locus was analysed by PCR‐ASP/restriction fragment length polymorphism genotyping and DNA sequencing.

The propositus' RBCs were very weakly agglutinated with monoclonal anti‐A but distinctly with polyclonal anti‐A,B, i.e. typical for Ax. Serum anti‐A1 (titre 4) and ‐B were present. Her parents' blood groups were both clearly O, with titres of serum anti‐A1, and ‐A at 16 and 4, respectively. Adsorption/ elution studies demonstrated A antigen on the daughter's cells only. The ABO genotypes were: mother, AxO1; father, O1vO2; and propositus, AxO2. The Ax allele was an A1‐O1v hybrid allele with a crossing‐over breakpoint between positions 235 and 446 in intron 6 (Ax‐4). Compared to the A1 glycosyltransferase, this allele predicts a protein with two amino acid substitutions (Phe216Ile and Met277Val) known to yield either weakly expressed or no A antigen on RBCs.

This study suggests that the nature of the ABO allele in trans can influence A antigen expression, a phenomenon previously described as allelic enhancement (or reinforcement). Potential mechanisms for this are discussed.
Endothelial cell protection and complement inhibition in xenotransplantation: a novel in vitro model using whole blood
Authors: Banz Yara , Cung Trinh , Korchagina Elena Y. , Bovin Nicolai V. , Haeberli André , Rieben Robert
Published: October 2005

Abstract: Background:  Studying the interactions between xenoreactive antibodies, complement and coagulation factors with the endothelium in hyperacute and acute vascular rejection usually necessitates the use of in vivo models. Conventional in vitro or ex vivo systems require either serum, plasma or anti‐coagulated whole blood, making analysis of coagulation‐mediated effects difficult. Here a novel in vitro microcarrier‐based system for the study of endothelial cell (EC) activation and damage, using non‐anticoagulated whole blood is described. Once established, the model was used to study the effect of the characterized complement‐ and coagulation inhibitor dextran sulfate (DXS, MW 5000) for its EC protective properties in a xenotransplantation setting.

Methods:  Porcine aortic endothelial cells (PAEC), grown to confluence on microcarrier beads, were incubated with non‐anticoagulated whole human blood until coagulation occurred or for a maximum of 90 min. PAEC‐beads were either pre‐ or co‐incubated with DXS. Phosphate buffered saline (PBS) experiments served as controls. Fluid phase and surface activation markers for complement and coagulation were analyzed as well as binding of DXS to PAEC‐beads.

Results:  Co‐ as well as pre‐incubation of DXS, followed by washing of the beads, significantly prolonged time to coagulation from 39 ± 12 min (PBS control) to 74 ± 23 and 77 ± 20 min, respectively (P < 0.005 vs. PBS). DXS treatment attenuated surface deposition of C1q, C4b/c, C3b/c and C5b‐9 without affecting IgG or IgM deposition. Endothelial integrity, expressed by positivity for von Willebrand Factor, was maintained longer with DXS treatment. Compared with PBS controls, both pre‐ and co‐incubation with DXS significantly prolonged activated partial thromboplastin time (>300 s, P < 0.05) and reduced production of thrombin‐antithrombin complexes and fibrinopeptide A. Whilst DXS co‐incubation completely blocked classical pathway complement activity (CH50 test) DXS pre‐incubation or PBS control experiments showed no inhibition. DXS bound to PAEC‐beads as visualized using fluorescein‐labeled DXS.

Conclusions:  This novel in vitro microcarrier model can be used to study EC damage and the complex interactions with whole blood as well as screen ‘‘endothelial protective’’ substances in a xenotransplantation setting. DXS provides EC protection in this in vitro setting, attenuating damage of ECs as seen in hyperacute xenograft rejection.
Pig islet xenotransplantation: activation of porcine endogenous retrovirus in the immediate post‐transplantation period
Authors: Schmidt Peter , Forsman Anna , Andersson Göran , Blomberg Jonas , Korsgren Olle
Published: October 2005

Abstract:  Background:  Porcine endogenous retroviruses (PERV) are considered as the main infectious barrier in islet xenotransplantation. PERV has been shown to infect, but not to cause symptomatic disease in mice after islet transplantation. In vivo activation of PERV have so far not been examined. Expression of PERV was examined in adult and fetal porcine islets with or without the presence of known retroviral inducers or after transplantation to rats.

Methods:  Isolated adult and fetal porcine islets were cultured under normal conditions or in the presence of dexamethasone or 5‐azacytidine and 5‐iodo‐2‐deoxyuridine. PERV mRNA content was analyzed by real‐time quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) and culture supernatants were analyzed for the presence of retroviral RT. Also, fetal islets were transplanted under the kidney capsule of immunocompetent or nude athymic rats. Expression of PERV mRNA in the grafts was evaluated by real‐time quantitative RT‐PCR. Infiltration of immunocompetent cells were evaluated by immunohistochemistry.

Results:  Both fetal and adult islets in culture produced small or even undetectable amounts of PERV mRNA and retroviral RT. PERV expression was not enhanced by retroviral inducers. In contrast, activation of PERV expression was observed the first day after transplantation of fetal islet‐like cell clusters in both athymic and normal rats. PERV expression peaked after 1 to 3 days and was then rapidly returned to background levels. PERV expression neither correlated with the innate immune response seen in athymic rats nor with the specific process of rejection in normal rats.

Conclusion:  Both fetal and adult islets produce low amounts of PERV mRNA in culture. After transplantation PERV expression is induced, seemingly independent of both the unspecific inflammatory response and the specific T‐cell‐mediated rejection process. It is speculated that PERV expression is correlated with the level of hypoxia in the islet xenograft.
Continuous sciatic block for leg and foot surgery in 160 children
Authors: VAS LAKSHMI
Published: October 2005

Background:  The aim of this study was to assess the safety and efficacy of continuous sciatic block for lower limb surgery in children.

Methods:  A total of 160 pediatric patients aged 4 months to 12 years weighing 3.5–50 kg, were given continuous sciatic block plus single shot 3‐in‐1 block for leg and foot surgery. After general anesthesia, the sciatic nerve was located by using loss of resistance to saline by the mid‐thigh approach. An 18 gauge epidural needle was introduced at the junction of the proximal two‐third with the distal one‐third of a line extending from the apex of popliteal triangle to the midpoint of the line joining the greater trochanter and the ischial tuberosity. A 20 g catheter was threaded through the needle for 5–10 cm and 0.25% bupivacaine 0.75 ml·kg−1 was injected. A single shot 3‐in‐1 block was also given to facilitate the use of a tourniquet with 0.25% bupivacaine 0.25 ml. In 20 patients a nerve stimulator was used in addition to loss of resistance. The intraoperative sedation comprised propofol and ketamine infusions and 50% nitrous oxide in oxygen by LMA.

Results:  Eight‐two percent of patients showed no response to surgery; 14% patients showed some response to the medial incision over the ankle and needed additional bolus doses of ketamine and propofol. Block was considered to have failed in 4% who required an increase in propofol and ketamine infusions. A total of 154 patients had good postoperative pain relief for 72 h with continuous infusion of 0.05% bupivacaine. The other six were given oral codeine and diclofenac. There were no complications attributable to sciatic block in any patient.

Conclusions:  Sciatic block with a single shot 3‐in‐1 block for tourniquet pain and light general anesthesia provides good intraoperative conditions for leg and foot surgery and adequate postoperative pain relief. Additional sedation to minimize the discomfort of a cast may be a consideration in the first 24 h.
Caudal block complication in a patient with trisomy 13
Authors: COHEN IRA TODD
Published: October 2005

In this report we describe a complication of a caudal block in a 4‐year‐old child with trisomy 13. The patient's history was remarkable for microcephaly, developmental delay, seizures, apnea, and prolonged emergence times. Induction of anesthesia and tracheal intubation were uneventful. A caudal block was aborted after positive aspiration of cerebrospinal fluid. A radiogram suggestive of spinal dysraphism, found on subsequent review, was confirmed by a magnetic resonance imaging scan consistent with tethered cord and dural ectasia. Congenital abnormalities associated with trisomy 13 and cutaneous signs suggestive of spinal abnormalities are reviewed. Avoidance of neuraxial regional anesthesia in these patients is recommended.
Clonidine added to bupivacaine in neonatal spinal anesthesia: a prospective comparison in 124 preterm and term infants
Authors: ROCHETTE ALAIN , TRONCIN RACHEL , RAUX OLIVIER , DADURE CHRISTOPHE , LUBRANO JEAN‐FRANÇOIS , BARBOTTE ERIC , CAPDEVILA XAVIER
Published: October 2005

Background:  Spinal anesthesia (SA) remains the ‘gold standard’ in neonatal anesthesia for inguinal herniorrhaphy but its short duration impedes its usefulness. We previously demonstrated that clonidine prolongs neonatal SA without immediate side effects.

Methods:  We conducted a prospective observational study of 124 infants undergoing herniorrhaphy under SA with bupivacaine and clonidine. Two cohorts, term (n = 57) and former preterm (n = 67) infants, were evaluated and compared with regard to episodes of apnea, desaturation, and bradycardia within 24 h of SA.

Results:  In both groups, postoperative desaturation episodes were unchanged after SA, compared with the 12 preoperative hours, despite significantly increased apnea (P < 0.003 and <0.011 respectively). Transient bradycardias occurred in former preterm infants (P < 0.014): they spontaneously resolved in all cases. Mean arterial pressure did not vary during the study. Upper sensory level of SA, sedation on entering the postanesthesia care unit (PACU) and duration of stay in the PACU were similar in both groups.

Conclusions:  The clinical significance of short apneas, recovering spontaneously without desaturation, remains debatable. It is concluded that addition of clonidine to neonatal SA results in acceptable side effects. Side effects must be compared with the potential advantages before future recommendations.
CSF pressure measurement during anesthesia: an unreliable technique
Authors: EIDLITZ‐MARKUS TAL , STIEBEL‐KALISH HADAS , RUBIN YEHOSHUA , SHUPER AVINOAM
Published: October 2005

Background:  The measurement of cerebrospinal fluid (CSF) pressure is necessary for many clinical indications. Its accuracy may be compromized in frightened or uncooperative children who find it difficult to relax sufficiently. The aim of the present study was to evaluate possible effects of general anesthesia on CSF pressure values.

Methods:  Lumbar puncture was performed under general anesthesia in 15 patients aged 4.5–20 years for the evaluation of headaches associated with a swollen optic nerve. Cerebrospinal fluid pressure was measured with a manometer when the patient was fully anesthetized (opening pressure) and then continuously recorded until the patient regained consciousness. The opening pressure was compared with the lowest pressure measured at the termination of the procedure (end‐measurement pressure).

Results:  Seventeen pressure measurements were performed in 15 patients. In all but two measurements, differences were noted between the opening and end pressure, ranging from 5 to 13 cmH2O. The opening pressure was abnormally high in 16 measurements, and the end pressure was abnormally high in seven. The difference between the two measurements was highly significant (P < 0.001).

Conclusions:  Lumbar puncture performed under general anesthesia may yield two pressure measurements. Many factors, such as hypercarbia and the anesthetic agent used, may influence the results. Owing to the dynamic changes in CSF pressure, measurements made under anesthesia may be unreliable.
Integrating Software into PRA: A Test‐Based Approach
Authors: Li Bin , Li Ming , Smidts Carol
Published: October 2005

Probabilistic risk assessment (PRA) is a methodology to assess the probability of failure or success of a system's operation. PRA has been proved to be a systematic, logical, and comprehensive technique for risk assessment. Software plays an increasing role in modern safety critical systems. A significant number of failures can be attributed to software failures. Unfortunately, current probabilistic risk assessment concentrates on representing the behavior of hardware systems, humans, and their contributions (to a limited extent) to risk but neglects the contributions of software due to a lack of understanding of software failure phenomena. It is thus imperative to consider and model the impact of software to reflect the risk in current and future systems. The objective of our research is to develop a methodology to account for the impact of software on system failure that can be used in the classical PRA analysis process. A test‐based approach for integrating software into PRA is discussed in this article. This approach includes identification of software functions to be modeled in the PRA, modeling of the software contributions in the ESD, and fault tree. The approach also introduces the concepts of input tree and output tree and proposes a quantification strategy that uses a software safety testing technique. The method is applied to an example system, PACS.
Benchmark Dose of Lead Inducing Anemia at the Workplace
Authors: Karita Kanae , Yano Eiji , Dakeishi Miwako , Iwata Toyoto , Murata Katsuyuki
Published: October 2005

To estimate the critical dose of lead inducing anemia in humans, the effects of lead on hemoglobin (Hb) and hematocrit (Hct) levels and red blood cell (RBC) count were examined in 388 male lead‐exposed workers with blood lead (BPb) levels of 0.05–5.5 (mean 1.3) μmol/L by using the benchmark dose (BMD) approach. The BPb level was significantly related to Hb (regression coefficient β=–0.276), RBC (β=–11.35), and Hct (β=–0.563) among the workers (p < 0.001) when controlling for age and working status. The average BPb levels were significantly higher in the workers with anemia (1.85 μmol/L), based on the WHO criteria, than in those without anemia (1.26 μmol/L). The benchmark dose levels of BPb (i.e., lower 95% confidence limits of BMD), calculated from the K‐power model set at an abnormal probability of 5% in unexposed workers and an excess risk of 5% in exposed workers were estimated to be 0.94 μmol/L (19.5 μg/dl) for Hb, 0.94 μmol/L (19.4 μg/dl) for RBC, and 1.43 μmol/L (29.6 μg/dl) for Hct. These findings suggest that reduction in hematopoietic indicators may be initiated at BPbs below the level currently considered without effect.
Information Specificity and Hazard Risk Potential as Moderators of Trust Asymmetry
Authors: White Mathew P. , Richard Eiser J.
Published: October 2005

Trust in risk managers appears to be an important antecedent of public acceptance for many hazards. However, such trust may be fragile since research suggests that negative performance information has a greater impact than positive performance information (Slovic, 1993). Closer examination of these findings suggests two potential moderators of this valence‐related asymmetry—information specificity and hazard risk potential. First, we predicted that the asymmetry would be less evident for low versus high specificity information (risk management policies vs. concrete events). Second, we predicted that it would also be less evident for a low‐ versus high‐risk hazard (pharmaceutical vs. nuclear industry). Study 1 reanalyzed Slovic's original trust asymmetry data for the nuclear industry. In line with Prediction 1, trust asymmetry was less evident for policy than event‐related information. Using a new set of items with more clearly defined levels of specificity, Study 2 replicated and extended these findings for the high‐risk hazard (nuclear power). In line with Prediction 2, trust asymmetry was even less evident for the low‐risk hazard (pharmaceuticals). Positive policies in this industry actually had a greater impact on trust than negative ones, in contrast to previous findings. Results support an information diagnosticity account of earlier findings and suggest that trust in risk managers may be more robust than previously believed.