bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manipulation of systemic oxygen flux by acute exercise and normobaric hypoxia: implications for reactive oxygen species generation
Authors: Davison Gareth W. , Morgan Rhian M. , Hiscock Natalie , Garcia Juan M. , Grace Fergal , Boisseau Natalie , Davies Bruce , Castell Linda , McEneny Jane , Young Ian S. , Hullin David , Ashton Tony , Bailey Damian M. 
Published: December 2005

Maximal exercise in normoxia results in oxidative stress due to an increase in free radical production. However, the effect of a single bout of moderate aerobic exercise performed in either relative or absolute normobaric hypoxia on free radical production and lipid peroxidation remains unknown. To examine this, we randomly matched {according to their normobaric normoxic V̇O2peak [peak V̇O2 (oxygen uptake)]} and assigned 30 male subjects to a normoxia (n=10), a hypoxia relative (n=10) or a hypoxia absolute (n=10) group. Each group was required to exercise on a cycle ergometer at 55% of V̇O2peak for 2 h double-blinded to either a normoxic or hypoxic condition [FiO2 (inspired fraction of O2)=0.21 and 0.16 respectively]. ESR (electron spin resonance) spectroscopy in conjunction with ex vivo spin trapping was utilized for the direct detection of free radical species. The main findings show that moderate intensity exercise increased plasma-volume-corrected free radical and lipid hydroperoxide concentration (pooled rest compared with exercise data, P&lt;0.05); however, there were no selective differences between groups (state×group interaction, P&gt;0.05). The delta change in free radical concentration was moderately correlated with systemic V̇O2 (r2=0.48, P&lt;0.05). The hyperfine coupling constants recorded from the ESR spectra [aN=13.8 Gauss, and aHβ=1.9 Gauss; where 1 Gauss=10−4 T (telsa)] are suggestive of oxygen-centred free radical species formed via the decomposition of lipid hydroperoxides. Peripheral leucocyte and neutrophil cells and total CK (creatine kinase) activity all increased following sustained exercise (pooled rest compared with exercise data, P&lt;0.05), but no selective differences were observed between groups (state×group interaction, P&gt;0.05). We conclude that a single bout of moderate aerobic exercise increases secondary free radical species. There is also evidence of exercise-induced muscle damage, possibly caused by the increase in free radical generation.
A novel mutation in the cardiac myosin-binding protein C gene is responsible for hypertrophic cardiomyopathy with severe ventricular hypertrophy and sudden death
Authors: Konno Tetsuo , Shimizu Masami , Ino Hidekazu , Fujino Noboru , Uchiyama Katsuharu , Mabuchi Tomohito , Sakata Kenji , Kaneda Tomoya , Fujita Takashi , Masuta Eiichi , Mabuchi Hiroshi 
Published: December 2005

It has been demonstrated previously that clinical phenotypes of HCM (hypertrophic cardiomyopathy) caused by mutations in the cardiac MyBP-C (myosin-binding protein C) gene show late onset, low penetrance and favourable clinical course. However, we have encountered severe phenotypes in several carriers of the MyBP-C gene mutations. The aim of the present study was to screen novel MyBP-C gene mutations in patients with HCM and to investigate the genetic differences in affected subjects with severe phenotypes. The MyBP-C gene was screened in 292 Japanese probands with HCM, and a novel c.2067+1G→A mutation was present in 15 subjects in five families. Clinical phenotypes of carriers of the c.2067+1G→A mutation were compared with those of a previously identified Arg820Gln (Arg820→Gln) mutation in the MyBP-C gene. The disease penetrance in subjects aged ≥30 years was 90% in carriers of the c.2067+1G→A mutation and 61% in carriers of the Arg820Gln mutation. Sudden death occurred in four subjects from three families with the c.2067+1G→A mutation and in two subjects from one family with the Arg820Gln mutation. Two carriers of the c.2067+1G→A mutation had substantial hypertrophy (maximal wall thickness ≥30 mm). In contrast, two carriers of the Arg820Gln mutation had end-stage HCM. In conclusion, the c.2067+1G→A mutation is associated with HCM with substantial hypertrophy and moderate incidence of sudden death, whereas the Arg820Gln mutation is associated with end-stage HCM. These observations may provide important prognostic information regarding the clinical practice of HCM.
Quality classification of tandem mass spectrometry data
Authors: Salmi Jussi , Moulder Robert , Filén Jan-Jonas , Nevalainen Olli S. , Nyman Tuula A. , Lahesmaa Riitta , Aittokallio Tero 
Published: December 2005

Abstract
Motivation: Peptide identification by tandem mass spectrometry is an important tool in proteomic research. Powerful identification programs exist, such as SEQUEST, ProICAT and Mascot, which can relate experimental spectra to the theoretical ones derived from protein databases, thus removing much of the manual input needed in the identification process. However, the time-consuming validation of the peptide identifications is still the bottleneck of many proteomic studies. One way to further streamline this process is to remove those spectra that are unlikely to provide a confident or valid peptide identification, and in this way to reduce the labour from the validation phase.
Results: We propose a prefiltering scheme for evaluating the quality of spectra before the database search. The spectra are classified into two classes: spectra which contain valuable information for peptide identification and spectra that are not derived from peptides or contain insufficient information for interpretation. The different spectral features developed for the classification are tested on a real-life material originating from human lymphoblast samples and on a standard mixture of 9 proteins, both labelled with the ICAT-reagent. The results show that the prefiltering scheme efficiently separates the two spectra classes.
Availability: The software tools are available on request from the authors.
Contact: jussi.salmi@it.utu.fi
Supplementary information: The Mascot ion score distributions and the C4.5 classification rules can be found at address
Effects of culling on badger Meles meles spatial organization: implications for the control of bovine tuberculosis
Authors: WOODROFFE ROSIE , DONNELLY CHRISTL A. , COX D. R. , BOURNE F. JOHN , CHEESEMAN C. L. , DELAHAY R. J. , GETTINBY GEORGE , MCINERNEY JOHN P. , MORRISON W. IVAN 
Published: December 2005

Summary

The incidence of bovine tuberculosis (TB) in British cattle has risen markedly over the last two decades. Failure to control the disease in cattle has been linked to the persistence of a reservoir of infection in European badgers Meles meles, a nationally protected species. Although badger culling has formed a component of British TB control policy for many years, a recent large‐scale randomized field experiment found that TB incidence in cattle was no lower in areas subject to localized badger culling than in nearby areas where no experimental culls occurred. Indeed, analyses indicated that cattle incidence was higher in culled areas.
One hypothesis advanced to explain this pattern is that localized culling disrupted badgers’ territorial behaviour, potentially increasing the rate of contact between cattle and infected badgers. This study evaluated this hypothesis by investigating badger activity and spatial organization in 13 study areas subjected to different levels of culling. Badger home ranges were mapped by feeding colour‐marked baits at badger dens and measuring the geographical area in which colour‐marked faeces were retrieved.
Badger home ranges were consistently larger in culling areas. Moreover, in areas not subjected to culling, home range sizes increased with proximity to the culling area boundary. Patterns of overlap between home ranges were also influenced by culling.
Synthesis and applications. This study demonstrates that culling badgers profoundly alters their spatial organization as well as their population density. These changes have the potential to influence contact rates between cattle and badgers, both where culls occur and on adjoining land. These results may help to explain why localized badger culling appears to have failed to control cattle TB, and should be taken into account in determining what role, if any, badger culling should play in future control strategies.
Regulating immunity to malaria
Authors: RILEY E. M. , WAHL S. , PERKINS D. J. , SCHOFIELD L. 
Published: December 2005

SUMMARY The optimal outcome of a malaria infection is that parasitized cells are killed and degraded without inducing significant pathology. Since much of the pathology of malaria infection can be immune‐mediated, this implies that immune responses have to be carefully regulated. The mechanisms by which anti‐malarial immune responses are believed to be regulated were discussed at the recent Malaria Immunology Workshop (Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; February 2005). Potential regulatory mechanisms include regulatory T cells, which have been shown to significantly modify cellular immune responses to various protozoan infections, including leishmania and malaria; neutralising antibodies to pro‐inflammatory malarial toxins such as glycosylphosphatidylinositol and haemozoin; and self‐regulating networks of effector molecules. Innate and adaptive immune responses are further moderated by the broader immunological environment, which is influenced by both the genetic background of the host and by co‐infection with other pathogens. A detailed understanding of the interplay between these different immunoregulatory processes may facilitate the rationale design of vaccines and novel therapeutics.
Inhibitory effects on HLA‐DR1‐specific T‐cell activation by influenza virus haemagglutinin‐derived peptides
Authors: Li X , Li R , Li Z. 
Published: December 2005

AbstractCollagen (CII) 263‐272 peptide, an autoantigen in rheumatoid arthritis, is a specific human leukocyte antigen (HLA)‐DR1/4‐binding peptide recognized by T‐cell receptors (TCR). The affinity of influenza virus haemagglutinin (HA) 306‐318 peptide for the antigen‐binding groove of HLA‐DR1/4 molecules is higher than that of CII263‐272. The HLA‐DR1/4‐binding residues of HA306‐318 are located in the region 308‐317. Altered HA308‐317 peptides with substitutions of TCR‐contact residues may inhibit HLA‐DR1/4‐specific T‐cell activation by blocking the antigen‐binding site of HLA‐DR1/4 molecules. To evaluate the role of altered HA308‐317 peptides in HLA‐DR1‐restricted T‐cell activation, we synthesized three altered HA308‐317 peptides. The specific binding of altered HA308‐317 peptides to HLA‐DR1 molecules was examined using flow cytometry. Effects of altered HA308‐317 peptides on HLA‐DR1‐specific T‐cell hybridoma were studied by measuring T‐cell proliferation and surface expression of CD69 or CD25. The results showed that altered HA308‐317 peptides were able to bind to HLA‐DR1 molecules and competed with CII263‐272 or wildtype HA308‐317 peptide. Compared with wildtype CII263‐272 or HA308‐317, altered HA308‐317 peptides did not stimulate significant T‐cell proliferation and CD69 or CD25 expression. Furthermore, the altered HA308‐317 peptides inhibited HLA‐DR1‐specific T‐cell activation induced by CII263‐272 or wildtype HA308‐317 peptide, which may suggest an effective therapeutic strategy in inhibition of HLA‐DR1‐specific T‐cell responses in autoimmunity.
Monoclonal antibodies to native mouse angiotensin‐converting enzyme (CD143): ACE expression quantification, lung endothelial cell targeting and gene delivery
Authors: Balyasnikova I. V. , Sun Z.‐L. , Metzger R. , Taylor P. R. , Vicini E. , Muciaccia B. , Visintine D. J. , Berestetskaya Y. V. , McDonald T. D. , Danilov S. M. 
Published: December 2005

AbstractWe demonstrated previously that the monoclonal antibody 9B9 to angiotensin‐converting enzyme (ACE), which accumulates very selectively into the rat lung after systemic injection, is a powerful tool for immunotargeting of therapeutic agents or genes to the rat lung vascular bed. Bearing in mind a high research and therapeutic potential of lung targeting via ACE, we obtained a new set of rat monoclonal antibodies to different epitopes of mouse ACE in order to expand this approach to mice. Nine new monoclonal antibodies, recognizing epitopes on the N‐ and C‐domains of catalytically active mouse ACE, were obtained and examined for their efficacy to bind ACE bothin vitroandin vivo. This set of monoclonal antibodies was proved to be useful for ACE quantification (by flow cytometry and cell enzyme‐linked immunosorbent assay) on the surface of different mouse ACE‐expressing cells: endothelial cells, monocytes, macrophages, dendritic cells and spermatozoa. Moreover, gene delivery into mouse ACE‐expressing cells using adenoviruses increased 40‐fold after redirecting of these viruses to ACE (by coating these viruses with anti‐ACE monoclonal antibodies). Radiolabelled (I125) monoclonal antibodies specifically accumulated in the mouse lung after systemic injection. Monoclonal antibodies 3G8.17, 4B10.5 and 4B10.17 demonstrated the highest level of lung uptake, 40–50% of injected dose, and high selectivity of lung uptake. Influence of monoclonal antibodies on ACE shedding was negligible, except monoclonal antibody 1D10.11. None of the tested monoclonal antibodies inhibited ACE activityin vitro. In conclusion, a new set of rat monoclonal antibodies to mouse ACE was obtained suitable to study ACE biology in mice and for ACE expression quantification on mouse cells in particular. These monoclonal antibodies also demonstrated highly efficient and selective lung accumulation and thus has the potential for targeting drugs/genes to the pulmonary vasculature in different mouse models of human lung diseases, including numerous knockout models.
HLA‐A and HLA‐B distribution in Toto – a vanishing sub‐Himalayan tribe of India
Authors: Debnath M. , Chaudhuri T. K. 
Published: December 2005

AbstractThe frequency of HLA‐A and HLA‐B locus alleles was studied by using polymerase chain reaction‐based sequence‐specific primer method in a very primitive and vanishing sub‐Himalayan Indian Tribe, the Toto population of North Bengal. The Toto, a Mongoloid tribe with a population size of 1172 reside only in the Totopara of Jalpaiguri district of North Bengal. We studied 40 individuals and observed some high frequency alleles when compared to other Indian tribal, non‐tribal, and major world populations. Particularly, the frequency of HLA‐B14 was 32.5% in the Toto population, the highest known frequency reported in any population in the world. This indigenous tribal population may harbour novel HLA alleles and unique haplotypes which extensive HLA genotyping will help to reveal, and thus further our understanding of their genetic admixture and migration patterns.
Association of hypothyroid disease in Doberman Pinscher dogs with a rare major histocompatibility complex DLA class II haplotype
Authors: Kennedy L. J. , Huson H. J. , Leonard J. , Angles J. M. , Fox L. E. , Wojciechowski J. W. , Yuncker C. , Happ G. M. 
Published: December 2005

AbstractCanine hypothyroid disease is similar to Hashimoto's disease in humans, which has been shown to be associated with human major histocompatibility complex (MHC) genes. We have collected 27 Doberman Pinschers affected with primary hypothyroid disease and compared their MHC class II haplotypes with 129 unaffected Doberman Pinschers. Three dog‐leucocyte antigen (DLA) genes, DLA‐DRB1, DQA1 and DQB1, were characterized by sequence‐based typing and assigned to haplotypes for each dog. One rare haplotype was found at an increased frequency in the affected dogs compared to the unaffected dogs (Odds ratio = 2.43,P < 0.02). This haplotype has only been found in Doberman Pinschers and Labradors to date.
HLA‐A, HLA‐B, and HLA‐DRB1 alleles and haplotypes in Naxi and Han populations in southwestern China (Yunnan province)
Authors: Shi L. , Xu S. B. , Ohashi J. , Sun H. , Yu J. K. , Huang X. Q. , Tao Y. F. , Yu L. , Horai S. , Chu J. Y. , Tokunaga K. 
Published: December 2005

AbstractThe frequencies of the human leukocyte antigen alleles HLA‐A, HLA‐B, and HLA‐DRB1 and the A‐B‐DRB1, A‐B, and B‐DRB1 haplotypes were studied in Naxi and Yunnan Han populations using polymerase chain reaction (PCR)‐sequence‐specific amplification for alleles A and B and a PCR‐microtiter plate hybridization method for the DRB1 allele. A total of 8 A, 19 B, and 30 DRB1 alleles were found in the Naxi population, and 15 A, 21 B, and 36 DRB1 alleles were found in Yunnan Han population. The common A‐B‐DRB1 haplotypes in the Naxi population were A*24‐B*15‐DRB1*1202, A*11‐B*15‐DRB1*0405, A*11‐B*15‐DRB1*1202, A*11‐B*38‐DRB1*08032, and A*11‐B*55‐DRB1*0405; the common A‐B haplotypes were A*11‐B*15, A*11‐B*38, and A*24‐B*15; and the common B‐DRB1 haplotypes were B*15‐DRB1*1202, B*38‐DRB1*08032, and B*48‐DRB1*1201. In the Yunnan Han population, the common A‐B‐DRB1 haplotypes were A*24‐B*15‐DRB1*1501, A*24‐B*46‐DRB1*08032, and A*24‐B*15‐DRB1*1201; the common A‐B haplotypes were A*24‐B*15, A*24‐B*46, and A*34‐B*46; and the common B‐DRB1 haplotypes were B*15‐DRB1*1501, B*46‐DRB1*09012, and B*46‐DRB1*1401. Phylogenetic tree and principal component analyzes based on HLA‐A, HLA‐B, and DRB1 allele frequencies suggested that the Naxi ethnic group belongs to the southern Chinese groups, while the Yunnan Han population is a characteristic population located intermediate between northern and southern Chinese groups, although they live in the southwest of China.
HLA class I diversity among rural rainforest inhabitants in Cameroon: identification of A*2612‐B*4407 haplotype
Authors: Torimiro J. N. , Carr J. K. , Wolfe N. D. , Karacki P. , Martin M. P. , Gao X. , Tamoufe U. , Thomas A. , Ngole E. M. , Birx D. L. , McCutchan F. E. , Burke D. S. , Carrington M. 
Published: December 2005

AbstractThe population distribution of alleles of the classical HLA class I loci in Cameroon has not been well studied but is of particular interest given the AIDS and malarial epidemics afflicting this population. We investigated the genetic diversity of HLA‐A, HLA‐B and HLA‐C alleles in remote populations of Cameroon. Subjects from seven small, isolated, indigenous populations (N = 274) in the rainforest of southern Cameroon were typed for HLA‐A, HLA‐B and HLA‐C alleles using a polymerase chain reaction/sequence‐specific oligonucleotide probe assay and sequence analysis. Multiple alleles of the HLA‐A (N = 28), HLA‐B (N = 41) and HLA‐C (N = 21) loci were identified, of which A*2301[allele frequency (AF) = 12.8%], B*5802 (AF = 10.9%) and Cw*0401 (AF = 16.6%) were the most frequent individual alleles and A*02 (AF = 19.0%), B*58 (AF = 15.9%) and Cw*07 (AF = 22.4%) the most common serologically defined groups of alleles. Twenty‐six (28.9%) alleles with a frequency of less than 1% (AF < 1%), 39 (43%) with a frequency of 2.0–15.0% (AF = 2.0–15.0%), three globally uncommon alleles [A*2612 (AF = 2.0%), B*4016 (AF = 0.7%) and B*4407 (AF = 1.4%)], and the A*2612‐Cw*0701/06/18‐B*4407 haplotype (haplotype frequency = 1.3%) were also identified. Heterozygosity values of 0.89, 0.92 and 0.89 were determined for HLA‐A, HLA‐B and HLA‐C, respectively. The extensive allelic and haplotypic diversity observed in this population may have resulted from varied natural selective pressures on the population, as well as intermingling of peoples from multiple origins. Thus, from an anthropologic perspective, these data highlight the challenges in T–cell‐based vaccine development, the identification of allogeneic transplant donors and the understanding of infectious disease patterns in different populations.
SOCS1: a potent and multifaceted regulator of cytokines and cell‐mediated inflammation
Authors: Davey G. M. , Heath W. R. , Starr R. 
Published: December 2005

AbstractSuppressor of cytokine signalling‐1 (SOCS1), as the name implies, is a protein that functions as a negative regulator of cytokine signalling. Initially characterized for its ability to inhibit JAK phosphorylation and function, SOCS1 also targets proteins for degradation by the proteosome machinery. The expression of SOCS1 can be regulated at the transcription, translation and protein level. Despite the broad spectrum of cytokines that can induce SOCS1 expression and/or be inhibited by SOCS1 in vitro, the use of genetically modified mice has revealed a more specific role for SOCS1 in vivo including a critical role in the regulation of IFNγ signalling. In addition, SOCS1 has a complex role in T cell activation, and studies have revealed significant roles for SOCS1 in the regulation of IL‐4, IL‐12 and IL‐15 in vivo. Interestingly, SOCS1 action is not limited to the regulation of the classical JAK/STAT‐signalling pathway, because SOCS1 also inhibits cytokines like insulin and toll‐like receptor signal transduction, neither of which activates the JAK/STAT pathway. Evidence is emerging for a role for aberrant SOCS1 expression in human disease, particularly in a number of malignancies.
One‐Year Mortality in Bordeaux Cohort: The Value of Syndrome Classification
Authors: Loiseau Pierre , Loiseau Jérôme , Picot Marie‐Christine 
Published: December 2005

Summary:  Purpose: To evaluate the usefulness of the International Classification of Epilepsy Syndromes for 1‐year mortality in a prospective incidence study of first epileptic seizures. Methods: Date and cause of death from the treating physician in an incidence study of first afebrile seizures collected 15 years ago in Southwest France. Cases were classified by epilepsy syndrome. A total of 804 patients were included: acute symptomatic (n = 277), unprovoked (n = 439), or unclassifiable (n = 88). Results: One hundred and fifty‐one patients died within the first year: none with idiopathic partial or generalized epilepsy, 16/104 with symptomatic (standardized mortality ratio (SMR) 6.4, 95% CI 3.6–10.3), 1/59 with cryptogenic (SMR 1.7, 95% CI 0.1–9.7 CI) partial epilepsy, 1/14 (SMR 28.1, 95% CI 0.4–156.6) with symptomatic/cryptogenic generalized epilepsy, 2/23 with undetermined epilepsy, 1/135 with isolated seizure (SMR 0.6, 95% CI 0.1–3.1), and 90/277 (SMR 10.3, 95% CI 8.3–12.7) with acute symptomatic seizures. Unclassifiable seizures could not be classified as acute symptomatic or unprovoked: associated with alcohol abuse (death: 3/32, SMR 7.7, 95% CI 1.6–22.6), brain tumors (death: 31/39, SMR 41.5, 95% CI 28.2–58.9), and dementia (death: 6/17, SMR 5.4, 95% CI 2.0–11.7). Most deaths were due to progression of underlying disease, only 5.9% were seizure‐related. Conclusions: Although a syndromic diagnosis is important for treatment decisions and some prognostic aspects of seizure disorders, its value in mortality studies is limited. Mortality can be calculated only at the first (partial, generalized, and undetermined epilepsies, and special syndromes) and the second (idiopathic vs. symptomatic or cryptogenic) levels of the International Classification of Epilepsies.