bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunosuppressive therapy modulates T lymphocyte gene expression in patients with systemic lupus erythematosus
Authors: Pereira Elayne , Tamia‐Ferreira Márcia Cristina , Cardoso Renato Sousa , Mello Stephano Spanó , Sakamoto‐Hojo Elza Tiemi , Passos Geraldo A. S. , Donadi Eduardo Antonio 
Published: August 2004

SummaryTo evaluate the T‐cell large‐scale differential gene expression in systemic lupus erythematosus (SLE) patients presenting with glomerulonephritis we studied SLE patients before and after immunosuppressive treatment. Large‐scale gene expression of peripheral blood mononuclear T cells was evaluated using cDNA microarray nylon membranes containing 5184 cDNAs. Data were analysed using the SAM and Cluster and Treeview software. When untreated patients were compared to healthy individuals, 38 genes, most of them located on chromosomes 1, 3, 6, 17 and 19, were repressed, and when untreated patients were compared to treated ones, 154 genes, located on chromosomes 1, 6, 7, 12 and 17, were induced. In terms of biological function of coded proteins, the differentially expressed genes were associated with apoptosis, cell cycle, chromosomal scaffold, cytokine/chemokine, DNA repair/replication, Golgi/mitochondrial proteins, mRNA processing, signalling molecules and tumour suppressors. Two autoantigen genes related to RNA splicing (small nuclear riboprotein 70 000 MW‐U1 SNR, and splicing factor 3a, 60 000 MW), and the tetranectin‐plasminogen‐binding protein were repressed. The Fc fragment of immunoglobulin G low affinity IIb, apoptotic protease activating factor‐1, two subunits of cytochrome c, caspase 8, complement C5a, HLA‐DRA, HLA‐DQB1, transforming growth factor‐β receptor II, small nuclear ribonucleoprotein polypeptide N (Sm protein N) genes, heterogeneous nuclear riboprotein‐C, and argininosuccinate lyase genes, among others, were induced. A total of 10 genes were repressed in untreated patients and induced in treated ones, among them tumour necrosis factor (ligand) superfamily member 9, tumour protein p53, mannosidase alpha class IA, and CD22. Although some of these differentially expressed genes are typically expressed in B cells, CD22 and CD32 have also been reported in T cells and may provide regulatory signals to B cells. Assessment of differential gene expression may provide hybridization signatures that may identify susceptibility, diagnostic and prognostic markers of SLE.
TLR9−/− and TLR9+/+ mice display similar immune responses to a DNA vaccine
Authors: Babiuk Shawn , Mookherjee Neeloffer , Pontarollo Reno , Griebel Phillip , Van Drunen Littel‐Van Den Hurk Sylvia , Hecker Rolf , Babiuk Lorne 
Published: August 2004

SummaryPlasmid DNA continues to attract interest as a potential vaccine‐delivery vehicle. However, the mechanisms whereby immune responses are elicited by plasmids are not fully understood. Although there have been suggestions regarding the importance of CpG motifs in plasmid immunogenicity, the molecular mechanisms by which CpG motifs enhance immune responses to DNA vaccines are not well understood. As Toll‐like receptor 9‐deficient (TLR9−/−) mice fail to respond to the adjuvant effects of CpG oligonucleotides, we used these mice to determine the effect of CpG motifs in plasmids used for DNA immunization. In the study described below, we report that DNA immunization was as effective in eliciting antigen‐specific antibody and at stimulating antigen‐specific interferon‐γ (IFN‐γ)‐secreting cells in TLR9−/− mice as in TLR9+/+ mice. This study illustrates that DNA vaccines elicit immune responses by multiple mechanisms and demonstrates that TLR9 is not essential for the induction of immune responses following DNA immunization.
Asymptomatic parasitaemia as a risk factor for symptomatic malaria in a cohort of Ugandan children
Authors: Njama‐Meya Denise , Kamya Moses R. , Dorsey Grant 
Published: August 2004

SummaryObjectives  To assess the prevalence of asymptomatic parasitaemia, determine its association with symptomatic malaria, and identify independent predictors of asymptomatic parasitaemia in a cohort of children from Kampala, Uganda.Methods  A total of 316 children aged 6 months to 5 years were recruited from the community. The prevalence of asymptomatic parasitaemia was assessed at enrolment and approximately every 30 days during follow‐up. Participants received all of their health care in our clinic, including a standardized approach to the diagnosis and treatment of symptomatic malaria.Results  A total of 283 (90%) subjects completed the full 1‐year follow‐up and were included in this study, yielding 2557 routine smears. The prevalence of asymptomatic parasitaemia was 17% at enrolment, but 5–8% for the remainder of the study. The risk of developing symptomatic malaria within 30 days was significantly higher in those with a positive routine than in those with a negative one (50%vs. 9%, P < 0.001). Higher parasite densities were associated with increased odds of developing symptomatic malaria within 30 days (P = 0.003). Only 11% of episodes of asymptomatic parasitaemia, involving 6% of subjects, arose and cleared without therapy. In multivariate analysis the only significant risk factor for asymptomatic parasitaemia was whether a child had any episode of symptomatic malaria during the course of the study (OR = 3.0, P = 0.02).Conclusion  In our cohort of children from an urban meso‐endemic environment, asymptomatic parasitaemia was uncommon and frequently followed by symptomatic malaria. This suggests that presumptive treatment of asymptomatic parasitaemia in such settings would be an efficient means of preventing symptomatic malaria.
Investigational use of ribavirin in the treatment of severe acute respiratory syndrome, Singapore, 2003
Authors: Leong Hoe‐Nam , Ang Brenda , Earnest Arul , Teoh Cindy , Xu Wei , Leo Yee‐Sin 
Published: August 2004

SummaryObjective  Ribavirin is a broad spectrum nucleoside analogue efficacious in the treatment of several viral infections. In the recent severe acute respiratory syndrome (SARS) outbreak, ribavirin was used in various countries against this novel coronavirus. We conducted a retrospective analysis to assess the efficacy of ribavirin in the treatment of SARS in Singapore.Methods  A total of 229 cases were analysed. Ninety‐seven (42.4%) patients received ribavirin at a mean of 6.4 days of illness. Clinical and laboratory parameters taken at the start of ribavirin treatment were compared with day 5, 6 or 7 parameters of those patients not on treatment. The two groups were compared using Fisher's exact test and Student's t‐test. Multivariate analysis was performed using Cox regression model with death as the outcome of interest.Results  The treatment group had younger women with more symptoms of myalgia (P < 0.001). The crude death rate was 12.9% in the control and 10.3% (P = 0.679) in the treatment group. After correction for age, male sex, lactate dehydrogenase levels and steroid use, the hazard ratio was 1.03 (95% CI: 0.44–2.41, P = 0.939).Conclusion  In this retrospective, uncontrolled cohort analysis, use of ribavirin did not appear to confer any benefit for patients with SARS.
Additional health and development activities for community‐directed distributors of ivermectin: threat or opportunity for onchocerciasis control?
Authors: Okeibunor Joseph C. , Ogungbemi Michael K. , Sama Martin , Gbeleou Sesso C. , Oyene Ukam , Remme Jan H. F. 
Published: August 2004

SummaryWe studied the involvement of community‐directed distributors (CDDs) of ivermectin for onchocerciasis control in other health and development activities in Nigeria, Togo and Cameroon. Most CDDs (82%) were involved in additional activities, especially EPI, water and sanitation and community development projects. These activities did not take up much time and were not considered an important burden. Ivermectin treatment coverage did not decline with increasing number of additional activities. Other health programmes are interested in building on the experiences and structures of community‐directed treatment with ivermectin and involving CDDs in their health programmes. Some, such as EPI, provide financial incentives. Incentives by other programmes may enhance the performance of CDDs when they are selected on the basis of their CDD status. CDDs, health personnel and community members have very positive attitudes towards greater involvement of CDDs in additional health and development activities. We conclude that additional activities for CDDs do not pose a threat to but rather provide an opportunity to strengthen sustainability and effectiveness of ivermectin treatment.
Effective antiplatelet therapy does not prolong transgenic pig to baboon cardiac xenograft survival
Authors: Schirmer Johannes M. , Fass David N. , Byrne Guerard W. , Tazelaar Henry D. , Logan John S. , McGregor Christopher G. A. 
Published: August 2004

Abstract:  Background:  Microvascular thrombosis is a prominent characteristic of delayed xenograft rejection, therefore the effects of antiplatelet therapy with aspirin and clopidogrel on long‐term cardiac xenograft function was investigated in a heterotopic pig‐to‐baboon cardiac transplant model.Methods:  Donor hearts from human CD46 transgenic pigs were transplanted heterotopically to baboons. The recipients received immunosuppression that included tacrolimus, sirolimus, corticosteroids, anti‐CD20 monoclonal antibody and TPC, an α‐galactosyl‐polyethylene glycol conjugate. In group 1 (n = 9) in addition to immunosuppression, the recipients received combination therapy consisting of aspirin (80 mg/day) and clopidogrel (75 mg/day) beginning 2 days after transplant and continuing until cessation of graft function. Antiaggregatory efficacy was evaluated by platelet aggregation assay. In group 2 (n = 9) antiplatelet drugs were not given.Results:  Functional assays confirmed inhibition of platelet aggregation in group 1 suggesting sufficient systemic effects of the treatment. However, anticoagulant therapy did not result in significant prolongation of xenograft function (group 1: median survival 22 days, range 15 to 30 days; group 2: median survival 15 days, range 4 to 53 days). Histologic analysis at rejection revealed no difference in the level of platelet containing thrombi between the groups.Conclusions:  Inhibition of platelet aggregation by a combination of aspirin and clopidogrel did not have a significant impact on the length of xenograft survival or on the development of microvascular thrombosis in this pig‐to‐primate model.
Does exposure to swine leukocyte antigens after pig‐to‐nonhuman primate xenotransplantation provoke antibodies that cross‐react with human leukocyte antigens?
Authors: Key Tim , Schuurman Henk‐Jan , Taylor Craig J. 
Published: August 2004

Abstract:  Background:  A potential concern of using pig kidney xenografts for human transplantation is that antibodies produced to swine leukocyte antigens (SLA) may cross‐react with human leukocyte antigens (HLA) and thereby limit the scope for a subsequent human organ donor transplant. We therefore investigated whether exposure to SLA after pig‐to‐nonhuman primate kidney xenotransplantation gives rise to HLA cross‐reactive antibodies.Methods:  Serum samples were obtained from 52 cynomolgus monkeys that received kidney transplants from human decay‐accelerating factor (hDAF) transgenic pigs. Samples were collected pre‐transplant and at time of autopsy (mean 20 days post‐transplantation, range 1 to 53 days) and analyzed for IgG HLA class I and HLA class II specific antibodies by enzyme‐linked immunosorbent assay (ELISA) against pooled purified HLA antigens. To ensure the ability of the HLA ELISA to detect cynomolgus monkey IgG binding, parallel experiments were performed to detect IgG Gal‐α‐1,3‐Gal‐specific antibodies known to be present in cynomolgus monkey serum.Results:  Analysis of both pre‐ and post‐transplantation serum samples by ELISA demonstrated no detectable IgG antibody binding to HLA class I or class II antigens. Using the same ELISA antibody detection reagents, IgG Gal‐α‐1,3‐Gal‐specific antibodies were identified in 13 of 38 (34%) sera obtained before transplantation and 21 of 52 (40%) sera collected post‐transplantation, confirming that the negativeHLA ELISA results were not due to a technical aspect of the assay.Conclusion:  This study suggests that exposure to SLA following transplantation of porcine kidneys in nonhuman primates does not give rise to antibodies that cross‐react with HLA.
Loss of complementation and the logic of two-step meiosis
Authors: Archetti M. 
Published: August 2004

Abstract
Meiosis is usually a two-step process: two divisions preceded by a duplication. One-step meiosis, a single division without prior replication, is a more logical way to produce haploid gametes; moreover, one-step meiosis leads to higher variabilty in the progeny than two-step meiosis. Yet one-step meiosis is very rare in nature, and may not even exist at all. I suggest that this is because one-step meiosis, in contrast to two-step meiosis, can be easily invaded and replaced by asexual reproduction. I discuss why other existing peculiar forms of division leading to the production of haploid gametes, but not one-step meiosis, have the same effect as two-step meiosis.
Natural selection, evolvability and bias due to environmental covariance in the field in an annual plant
Authors: Winn A. A. 
Published: August 2004

AbstractEstimates of the form and magnitude of natural selection based on phenotypic relationships between traits and fitness measures can be biased when environmental factors influence both relative fitness and phenotypic trait values. I quantified genetic variances and covariances, and estimated linear and quadratic selection coefficients, for seven traits of an annual plant grown in the field. For replicates of 50 paternal half-sib families, coefficients of selection were calculated both for individual phenotypic values of the traits and for half-sib family mean values. The potential for evolutionary response was supported by significant heritability and phenotypic directional selection for several traits but contradicted by the absence of significant genetic variation for fitness estimates and evidence of bias in phenotypic selection coefficients due to environmental covariance for at least two of the traits analysed. Only studies of a much wider range of organisms and traits will reveal the frequency and extent of such bias.
Evidence for a single median fin-fold and tail in the Lower Cambrian vertebrate, Haikouichthys ercaicunensis
Authors: Zhang X.-G. , Hou X.-G. 
Published: August 2004

Abstract
In this study, we illustrate an exceptionally well-preserved Haikouichthys ercaicunensis from the Lower Cambrian Chengjiang fauna that displays complete single dorsal, ventral and caudal fins. This 530-million-year old vertebrate is fish-shaped and characterized by a single median fin-fold, which is an essential trait of the initial vertebrate chordates. The radially orientated ray-like structures in its dorsal fin somewhat resemble but are probably not real radials seen in basal vertebrates, such as hagfishes and lampreys. The unique design of primitive fins and fin structures provides additional insights into the early evolution of vertebrates.
Diminishing returns in social evolution: the not-so-tragic commons
Authors: Foster K. R. 
Published: August 2004

Abstract
A challenge for evolutionary theory is to understand how cooperation can occur in the presence of competition and cheating, a problem known as the tragedy of commons. Here I examine how varying the fitness returns from reproductive competition or cooperation affects the negative impact of competition on a social group. Varying linear returns does not affect the impact of competition. However, diminishing returns, where additional investments in either competition or cooperation give smaller and smaller rewards, reduce the effects of competition on the group. I show that diminishing returns are common in many systems, including social vertebrates, microbes, social insects and mutualisms among species. This suggests that the tragedy of the commons is not so tragic and that the disruptive effects of competition upon social life will often be minor.
Local co-adaptation leading to a geographical mosaic of coevolution in a social parasite system
Authors: Fischer B. , Foitzik S. 
Published: August 2004

AbstractThe geographical mosaic theory of coevolution predicts differences in the advance or trajectory of the coevolutionary process between local communities due to their composition and the strength of ecological selection pressures through competition and resource availability. In this study, we investigate local co-adaptation in different populations of a social parasite. We conducted cross-fostering experiments to test for interpopulational differences in raiding efficiency between various populations of a slave-making ant and the defence abilities of local hosts. Here, we demonstrate that the success of raids strongly depends on the combination of populations of the parasite Harpagoxenus sublaevis and its host Leptothorax acervorum, indicating very localized coevolution. We found no absolute differences between slave-maker populations; the outcome of an encounter depended more on whether the two opponents occur in sympatry or allopatry. Furthermore, this study supports the results of our earlier work, that the unparasitized English L. acervorum population is most aggressive against the parasite.
Host ecology determines the relative fitness of virus genotypes in mixed-genotype nucleopolyhedrovirus infections
Authors: Hodgson D. J. , Hitchman R. B. , Vanbergen A. J. , Hails R. S. , Possee R. D. , Cory J. S. 
Published: August 2004

Abstract
Mixed-genotype infections are common in many natural host–parasite interactions. Classical kin-selection models predict that single-genotype infections can exploit host resources prudently to maximize fitness, but that selection favours rapid exploitation when co-infecting genotypes share limited host resources. However, theory has outpaced evidence: we require empirical studies of pathogen genotypes that naturally co-infect hosts. Do genotypes actually compete within hosts? Can host ecology affect the outcome of co-infection? We posed both questions by comparing traits of infections in which two baculovirus genotypes were fed to hosts alongside inocula of the same or a different genotype. The host, Panolis flammea, is a herbivore of Pinus sylvestris and Pi. contorta. The pathogen, PfNPV (a nucleopolyhedrovirus), occurs naturally as mixtures of genotypes that differ, when isolated, in pathogenicity, speed of kill and yield. Single-genotype infection traits failed to predict the ‘winning’ genotypes in co-infections. Co-infections infected and caused lethal disease in more hosts, and produced high yields, relative to single-genotype infections. The need to share with nonkin did not cause fitness costs to either genotype. In fact, in hosts feeding on Pi. sylvestris, one genotype gained increased yields in mixed-genotype infections. These results are discussed in relation to theory surrounding adaptive responses to competition with nonkin for limited resources.
Worker reproduction and policing in insect societies: an ESS analysis
Authors: Wenseleers T. , Helanterä H. , Hart A. , Ratnieks F. L. W. 
Published: August 2004

Abstract
Insect societies are vulnerable to exploitation by workers who reproduce selfishly rather than help to rear the queen's offspring. In most species, however, only a small proportion of the workers reproduce. Here, we develop an evolutionarily stable strategy (ESS) model to investigate factors that could explain these observed low levels of reproductive exploitation. Two key factors are identified: relatedness and policing. Relatedness affects the ESS proportion of reproductive workers because laying workers generally work less, leading to greater inclusive fitness costs when within-colony relatedness is higher. The second key factor is policing. In many species, worker-laid eggs are selectively removed or ‘policed’ by other workers or the queen. We show that policing not only prevents the rearing of worker-laid eggs but can also make it unprofitable for workers to lay eggs in the first place. This can explain why almost no workers reproduce in species with efficient policing, such as honeybees, Apis, and the common wasp, Vespula vulgaris, despite relatively low relatedness caused by multiple mating of the mother queen. Although our analyses focus on social insects, the conclusion that both relatedness and policing can reduce the incentive for cheating applies to other biological systems as well.
Comparing phylogenetic signal in intraspecific and interspecific body size datasets
Authors: Ashton K. G. 
Published: August 2004

Abstract
Phylogenetic comparative methods have become a standard statistical approach for analysing interspecific data, under the assumption that traits of species are more similar than expected by chance (i.e. phylogenetic signal is present). Here I test for phylogenetic signal in intraspecific body size datasets to evaluate whether intraspecific datasets may require phylogenetic analysis. I also compare amounts of phylogenetic signal in intraspecific and interspecific body size datasets. Some intraspecific body size datasets contain significant phylogenetic signal. Detection of significant phylogenetic signal was dependant upon the number of populations (n) and the amount of phylogenetic signal (K) for a given dataset. Amounts of phylogenetic signal do not differ between intraspecific and interspecific datasets. Further, relationships between significance of phylogenetic signal and sample size and amount of phylogenetic signal are similar for intraspecific and interspecific datasets. Thus, intraspecific body size datasets are similar to interspecific body size datasets with respect to phylogenetic signal. Whether these results are general for all characters requires further study.