bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of plasma nucleosomes upon treatment with anti‐tumour necrosis factor‐α antibodies
Authors: D'Auria F. , Rovere‐Querini P. , Giazzon M. , Ajello P. , Baldissera E. , Manfredi A. A. , Sabbadini M. G. 
Published: December 2004

Abstract.Objective.  Patients undergoing anti‐tumour necrosis factor‐α (TNF‐α) treatment often develop autoantibodies. Apoptotic cell antigens are a potential initiating stimulus for autoantibodies. Our goal was to verify whether anti‐cytokine therapy causes the release of nucleosomes, a major autoantigen generated during cell death.Design.  Laboratory research study with comparison group.Setting.  Clinical Immunology Unit and Lab, H San Raffaele University Hospital, Italy.Subjects.  Eleven healthy controls and 87 rheumatic patients were studied, including 51 with rheumatoid arthritis (RA) and 33 patients with systemic lupus erythematosus (SLE).Interventions.  Vein blood samples were taken via the antecubital vein. Blood was retrieved from 11 patients before and after injection of anti‐TNF‐α humanized antibodies. Nucleosomes were measured with an enzyme‐linked immunosorbent assay. Cell death induced by anti‐TNF‐α antibodies and by the soluble cytokine was assessed in vitro.Main outcome measures.  Nucleosome level by treatment.Results.  Enzyme‐linked immunosorbent assay effectively detected nucleosomes either released by dying cells in vitro or circulating in the plasma. SLE but not RA patients had circulating nucleosomes at the steady state. Eight of 11 patients had significantly higher levels of plasma nucleosomes after infliximab. Minute amounts of TNF‐α enabled infliximab to induce cell death in vitro.Conclusions.  The accumulation of nucleosomes possibly fosters the development of autoantibodies in subjects with appropriate genetic backgrounds.
Extracellular role of HMGB1 in inflammation and sepsis
Authors: Wang H. , Yang H. , Tracey K. J. 
Published: December 2004

Abstract.High mobility group box 1 (HMGB1), a 30 kDa nuclear and cytosolic protein widely studied as a transcription factor and growth factor, has recently been identified as a cytokine mediator of lethal systemic inflammation (e.g. endotoxaemia and sepsis), arthritis and local inflammation. It is released by activated macrophages, and serum levels increase significantly during endotoxaemia, sepsis and arthritis with significant delayed kinetics in comparison with tumour necrosis factor (TNF) and interleukin‐1β. Recently identified biological activities of HMGB1 include activation of macrophages/monocytes to release proinflammatory cytokines, upregulation of endothelial adhesion molecules, stimulation of epithelial cell barrier failure, and mediation of fever and anorexia. Passive immunization with anti‐HMGB1 antibodies confers significant protection against lethal endotoxaemia, sepsis, arthritis and lipopolysaccharide‐induced acute lung injury, even when antibody administration is delayed until after the early TNF responses have resolved. Strategies to inhibit HMGB1 activity and release are being investigated in these and other preclinical models of acute and chronic inflammation.
The current biology of resistin
Authors: Steppan Claire M. , Lazar Mitchell A. 
Published: December 2004

Abstract.Obesity and noninsulin‐dependent diabetes mellitus are globally epidemic. Insulin resistance is a major contributor to the pathogenesis of type II diabetes and plays a role in numerous other metabolic disorders including hypertension, dyslipidaemia and atherosclerosis. Obesity, in particular visceral adiposity, is positively correlated with insulin resistance. Although this correlation between adiposity and insulin resistance is well established in human beings as well as in rodent models, the mechanisms involved in obesity‐related insulin resistance are not fully defined. One mechanism is that factors secreted from adipocytes can affect peripheral insulin resistance. One candidate for such a factor is resistin, an adipocyte‐secreted hormone that impairs glucose homeostasis and insulin action in the mouse. This review will summarize our current understanding of resistin and will attempt to provide a framework for future study of its role in rodent and human physiology.
Statistical issues in interpreting clinical trials
Authors: DeMets D. L. 
Published: December 2004

Abstract.Randomized clinical trial is an important research tool in evaluating new therapeutic agents, devices and procedures. In order to obtain reliable and unbiased results, careful consideration must be given in the design and conduct of the trial. However, bias can be introduced in the analysis of the final data if certain principles are not followed. Several issues are described that make interpretation of analyses challenging. These include the intent‐to‐treat principle, the use of surrogate outcome measures, subgroup analyses, missing data and noninferiority trials.
Rapid Emergency Medicine score: a new prognostic tool for in‐hospital mortality in nonsurgical emergency department patients
Authors: Olsson T. , Terent A. , Lind L. 
Published: December 2004

Abstract.Objectives.  To evaluate the predictive accuracy of the scoring system Rapid Acute Physiology score (RAPS) in nonsurgical patients attending the emergency department (ED) regarding in‐hospital mortality and length of stay in hospital (LOS), and to investigate whether the predictive ability of RAPS could be improved by extending the system.Design.  Prospective cohort study.Setting.  An adult ED of a 1200‐bed university hospital.Subjects.  A total of 12 006 nonsurgical patients presenting to the ED during 12 consecutive months.Methods.  For all entries to the ED, RAPS (including blood pressure, respiratory rate, pulse rate and Glasgow coma scale) was calculated. The RAPS system was extended by including the peripheral oxygen saturation and patient age (Rapid Emergency Medicine score, REMS) and this new score was calculated for each patient. The statistical associations between the two scoring systems and in‐hospital mortality as well as LOS in hospital were examined.Results.  The REMS was superior to RAPS in predicting in‐hospital mortality [area under receiver operating characteristic (ROC) curve 0.852 ± 0.014 SEM for REMS compared with 0.652 ± 0.019 for RAPS, P < 0.05]. An increase of 1‐point in the 26‐point REMS scale was associated with an OR of 1.40 for in‐hospital death (95% CI: 1.36–1.45, P < 0.0001). Similar results were obtained in the major patient groups (chest pain, stroke, coma, dyspnoea and diabetes), in all age groups and in both sexes. The association between REMS and LOS was modest (r = 0.47, P = 0.0001).Conclusions.  The REMS was a powerful predictor of in‐hospital mortality in patients attending the ED over a wide range of common nonsurgical disorders.
Highly elevated serum phyto‐oestrogen concentrations in patients with diabetic nephropathy
Authors: Von Hertzen L. , Forsblom C. , Stumpf K. , Pettersson‐Fernholm K. , Adlercreutz H. , Groop P.‐H. ,   on behalf of the FinnDiane Study Group
Published: December 2004

Abstract.Background and objectives.  Phyto‐oestrogens, naturally occurring phenolic, hormone‐like compounds, have raised considerable interest due to their anticarcinogenic, antiatherogenic and antioxidative potential. Oxidative stress may be one of the key factors in the development of vascular complications in patients with type 1 diabetes. Here, we tested the hypothesis that high concentrations of phyto‐oestrogens in serum may be associated with lower occurrence of vascular complications in these patients.Subjects.  A total of 400 patients, recruited consecutively from the participant register of the nationwide FinnDiane study of type 1 diabetes and divided into four parallel groups according to the severity of their renal disease with 100 patients to each group: (i) normoalbuminuric patients, (ii) microalbuminuric patients, (iii) macroalbuminuric patients, and (iv) patients with end‐stage renal disease (ESRD).Main outcome  measures.  Phyto‐oestrogen concentrations in serum (enterolactone, daidzein, genistein and equol) and urine (enterolactone), assessed by time‐resolved fluoroimmunoassay.Results.  Highly elevated serum concentrations of phyto‐oestrogens were measured amongst patients with diabetic nephropathy, and low concentrations amongst patients without diabetic complications. The pattern was similar for all phyto‐oestrogens measured, although the increase in mean serum concentrations along with the increasing severity of renal disease was steepest for enterolactone, ranging from 13 nmol L−1 amongst women and 18 nmol L−1 amongst men in normoalbuminuric patients to 181 and 206 nmol L−1 in women and men, respectively, in patients with ESRD (P < 0.001 for both genders between the groups). A strong correlation between serum enterolactone and creatinine concentration was found (r = 0.60, P < 0.001).Conclusions.  The serum concentration of phyto‐oestrogens and the severity of diabetic renal disease showed a close positive association, suggesting that phyto‐oestrogens are unable to provide any major protective effect, through antioxidative or other mechanisms, on the development of diabetic renal and cardiovascular complications.
Metapopulation models for historical inference
Authors: Wakeley John 
Published: December 2004

AbstractThe genealogical process for a sample from a metapopulation, in which local populations are connected by migration and can undergo extinction and subsequent recolonization, is shown to have a relatively simple structure in the limit as the number of populations in the metapopulation approaches infinity. The result, which is an approximation to the ancestral behaviour of samples from a metapopulation with a large number of populations, is the same as that previously described for other metapopulation models, namely that the genealogical process is closely related to Kingman's unstructured coalescent. The present work considers a more general class of models that includes two kinds of extinction and recolonization, and the possibility that gamete production precedes extinction. In addition, following other recent work, this result for a metapopulation divided into many populations is shown to hold both for finite population sizes and in the usual diffusion limit, which assumes that population sizes are large. Examples illustrate when the usual diffusion limit is appropriate and when it is not. Some shortcomings and extensions of the model are considered, and the relevance of such models to understanding human history is discussed.
Using genetic markers to estimate the pollen dispersal curve
Authors: Austerlitz Frederic , Dick Christopher W. , Dutech Cyril , Klein Etienne K. , Oddou‐Muratorio Sylvie , Smouse Peter E. , Sork Victoria L. 
Published: December 2004

AbstractPollen dispersal is a critical process that shapes genetic diversity in natural populations of plants. Estimating the pollen dispersal curve can provide insight into the evolutionary dynamics of populations and is essential background for making predictions about changes induced by perturbations. Specifically, we would like to know whether the dispersal curve is exponential, thin‐tailed (decreasing faster than exponential), or fat‐tailed (decreasing slower than the exponential). In the latter case, rare events of long‐distance dispersal will be much more likely. Here we generalize the previously developed twogener method, assuming that the pollen dispersal curve belongs to particular one‐ or two‐parameter families of dispersal curves and estimating simultaneously the parameters of the dispersal curve and the effective density of reproducing individuals in the population. We tested this method on simulated data, using an exponential power distribution, under thin‐tailed, exponential and fat‐tailed conditions. We find that even if our estimates show some bias and large mean squared error (MSE), we are able to estimate correctly the general trend of the curve — thin‐tailed or fat‐tailed — and the effective density. Moreover, the mean distance of dispersal can be correctly estimated with low bias and MSE, even if another family of dispersal curve is used for the estimation. Finally, we consider three case studies based on forest tree species. We find that dispersal is fat‐tailed in all cases, and that the effective density estimated by our model is below the measured density in two of the cases. This latter result may reflect the difficulty of estimating two parameters, or it may be a biological consequence of variance in reproductive success of males in the population. Both the simulated and empirical findings demonstrate the strong potential of twogener for evaluating the shape of the dispersal curve and the effective density of the population (de).
Identifying adaptive genetic divergence among populations from genome scans
Authors: Beaumont Mark A. , Balding David J. 
Published: December 2004

AbstractThe identification of signatures of natural selection in genomic surveys has become an area of intense research, stimulated by the increasing ease with which genetic markers can be typed. Loci identified as subject to selection may be functionally important, and hence (weak) candidates for involvement in disease causation. They can also be useful in determining the adaptive differentiation of populations, and exploring hypotheses about speciation. Adaptive differentiation has traditionally been identified from differences in allele frequencies among different populations, summarised by an estimate of FST. Low outliers relative to an appropriate neutral population‐genetics model indicate loci subject to balancing selection, whereas high outliers suggest adaptive (directional) selection. However, the problem of identifying statistically significant departures from neutrality is complicated by confounding effects on the distribution of FST estimates, and current methods have not yet been tested in large‐scale simulation experiments. Here, we simulate data from a structured population at many unlinked, diallelic loci that are predominantly neutral but with some loci subject to adaptive or balancing selection. We develop a hierarchical‐Bayesian method, implemented via Markov chain Monte Carlo (MCMC), and assess its performance in distinguishing the loci simulated under selection from the neutral loci. We also compare this performance with that of a frequentist method, based on moment‐based estimates of FST. We find that both methods can identify loci subject to adaptive selection when the selection coefficient is at least five times the migration rate. Neither method could reliably distinguish loci under balancing selection in our simulations, even when the selection coefficient is twenty times the migration rate.
Hidden biodiversity of the extremophilic Cyanidiales red algae
Authors: CINIGLIA CLAUDIA , YOON HWAN SU , POLLIO ANTONINO , PINTO GABRIELE , BHATTACHARYA DEBASHISH 
Published: December 2004

AbstractThe Cyanidiales is a group of asexual, unicellular red algae, which thrive in acidic and high temperature conditions around hot springs. These unicellular taxa have a relatively simple morphology and are currently classified into three genera, Cyanidium, Cyanidioschyzon and Galdieria. Little is known, however, about the biodiversity of Cyanidiales, their population structure and their phylogenetic relationships. Here we used a taxonomically broadly sampled three‐gene data set of plastid sequences to infer a robust phylogenetic framework for the Cyanidiales. The phylogenetic analyses support the existence of at least four distinct Cyanidiales lineages: the Galdieria spp. lineage (excluding Galdieria maxima), the Cyanidium caldarium lineage, a novel monophyletic lineage of mesophilic Cyanidium spp. and the Cyanidioschyzon merolae plus Galdieria maxima lineage. Our analyses do not support the notion of a mesophilic ancestry of the Cyanidiales and suggest that these algae were ancestrally thermo‐acidotolerant. We also used environmental polymerase chain reaction (PCR) for the rbcL gene to sample Cyanidiales biodiversity at five ecologically distinct sites at Pisciarelli in the Phlegrean Fields in Italy. This analysis showed a high level of sequence divergence among Cyanidiales species and the partitioning of taxa based on environmental conditions. Our research revealed an unexpected level of genetic diversity among Cyanidiales that revises current thinking about the phylogeny and biodiversity of this group. We predict that future environmental PCR studies will significantly augment known biodiversity that we have discovered and demonstrate the Cyanidiales to be a species‐rich branch of red algal evolution.
Effects of variation at the flower‐colour A locus on mating system parameters in Ipomoea purpurea
Authors: Fehr Carla , Rausher Mark D. 
Published: December 2004

AbstractAlthough alleles at both the W and A loci in the common morning glory, Ipomoea purpurea, produce similar white‐flowered phenotypes, these alleles differ by over an order of magnitude in average frequency. In this initial attempt to determine the causes of this difference, we employed artificial arrays of plants to estimate mating system characteristics (total siring success, selfing rates and contribution to the outcross pollen pool) for the homozygous pigmented and white‐flowered genotypes at the A locus. This experiment demonstrates that: (1) at both low and high frequencies, white‐flowered plants were visited by pollinators at the same rate as plants with pigmented flowers; (2) at both frequencies, the a allele exhibited a greater total siring success (self and outcross pollen) than the A allele; (3) individuals of both genotypes contributed equally to the outcross pollen pool; and (4) aa plants may have a higher selfing rate than AA plants. Coupled with minimal inbreeding depression in I. purpurea, these observations indicate that the allele producing white flowers enjoys a transmission advantage that would tend to cause this allele to increase in frequency. This transmission advantage is very similar to that shown previously to be operating on the white‐flowered allele at the W locus, although the specific causes of the advantage appear to differ between loci. The frequency difference between the two alleles is thus not likely to be due to differences in the effect of flower‐colour variation on transmission. Rather, substantially greater deleterious pleiotropic effects associated with the white‐flower a allele is likely to be the primary cause of the frequency difference.
Assessment of prey overlap between a native (Polistes humilis) and an introduced (Vespula germanica) social wasp using morphology and phylogenetic analyses of 16S rDNA
Authors: Kasper Marta L. , Reeson Andrew F. , Cooper Steven J. B. , Perry Kym D. , Austin Andrew D. 
Published: December 2004

AbstractIn newly invaded communities, interspecific competition is thought to play an important role in determining the success of the invader and its impact on the native community. In southern Australia, the native Polistes humilis was the predominant social wasp prior to the arrival of the exotic Vespula germanica (Hymenoptera: Vespidae). Both species forage for similar resources (water, pulp, carbohydrate and protein prey), and concerns have arisen about potential competition between them. The aim of this study was to identify the protein foods that these wasps feed on. As many prey items are masticated by these wasps to the degree that they cannot be identified using conventional means, morphological identification was complemented by sequencing fragments of the mitochondrial 16S rRNA gene. GenBank searches using blast and phylogenetic analyses were used to identify prey items to at least order level. The results were used to construct complete prey inventories for the two species. These indicate that while P. humilis is restricted to feeding on lepidopteran larvae, V. germanica collects a variety of prey of invertebrate and vertebrate origin. Calculated values of prey overlap between the two species are used to discuss the implications of V. germanica impacting on P. humilis. Results obtained are compared to those gained by solely ‘conventional’ methods, and the advantages of using DNA‐based taxonomy in ecological studies are emphasized.
Phylogeography of olive ridley turtles (Lepidochelys olivacea) on the east coast of India: implications for conservation theory
Authors: Shanker K. , Ramadevi J. , Choudhury B. C. , Singh L. , Aggarwal R. K. 
Published: December 2004

AbstractOrissa, on the east coast of India, is one of the three mass nesting sites in the world for olive ridley turtles (Lepidochelys olivacea). This population is currently under threat as a result of fishery‐related mortality; more than 100 000 olive ridleys have been counted dead in the last 10 years in Orissa. In general, the globally distributed olive ridley turtle has received significantly less conservation attention than its congener, the Kemp's ridley turtle (L. kempi), because the latter is recognized as a distinct species consisting of a single endangered population. Our study of mitochondrial DNA haplotypes suggests that the ridley population on the east coast of India is panmictic, but distinct from all other populations including Sri Lanka. About 96% of the Indian population consisted of a distinct ‘K’ clade with haplotypes not found in any other population. Nested clade analysis and conventional analysis both supported range expansions and/or long‐distance colonization from the Indian Ocean clades to other oceanic basins, which suggested that these are the ancestral source for contemporary global populations of olive ridley turtles. These data support the distinctiveness of the Indian Ocean ridleys, suggesting that conservation prioritization should be based on appropriate data and not solely on species designations.
North Atlantic phylogeography and large‐scale population differentiation of the seagrass Zostera marina L.
Authors: OLSEN JEANINE L. , STAM WYTZE T. , COYER JAMES A. , REUSCH THORSTEN B. H. , BILLINGHAM MARTIN , BOSTRÖM CHRISTOFFER , CALVERT ELIZABETH , CHRISTIE HARTVIG , GRANGER STEPHEN , LUMIÈRE RICHARD LA , MILCHAKOVA NATALIYA , OUDOT‐LE SECQ MARIE‐PIERRE , PROCACCINI GABRIELE , SANJABI BAHRAM , SERRÃO ESTER , VELDSINK JAN , WIDDICOMBE STEPHEN , WYLLIE‐ECHEVERRIA SANDY 
Published: December 2004

AbstractAs the most widespread seagrass in temperate waters of the Northern Hemisphere, Zostera marina provides a unique opportunity to investigate the extent to which the historical legacy of the last glacial maximum (LGM18 000–10 000 years bp) is detectable in modern population genetic structure. We used sequences from the nuclear rDNA–internal transcribed spacer (ITS) and chloroplast matK‐intron, and nine microsatellite loci to survey 49 populations (> 2000 individuals) from throughout the species’ range. Minimal sequence variation between Pacific and Atlantic populations combined with biogeographical groupings derived from the microsatellite data, suggest that the trans‐Arctic connection is currently open. The east Pacific and west Atlantic are more connected than either is to the east Atlantic. Allelic richness was almost two‐fold higher in the Pacific. Populations from putative Atlantic refugia now represent the southern edges of the distribution and are not genetically diverse. Unexpectedly, the highest allelic diversity was observed in the North Sea–Wadden Sea–southwest Baltic region. Except for the Mediterranean and Black Seas, significant isolation‐by‐distance was found from ~150 to 5000 km. A transition from weak to strong isolation‐by‐distance occurred at ~150 km among northern European populations suggesting this scale as the natural limit for dispersal within the metapopulation. Links between historical and contemporary processes are discussed in terms of the projected effects of climate change on coastal marine plants. The identification of a high genetic diversity hotspot in Northern Europe provides a basis for restoration decisions.