bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Stagonospora nodorum‐wheat pathosystem involves multiple proteinaceous host‐selective toxins and corresponding host sensitivity genes that interact in an inverse gene‐for‐gene manner
Authors: Friesen Timothy L. , Meinhardt Steven W. , Faris Justin D. 
Published: June 2007

SummaryWe recently showed that the wheat pathogen Stagonospora nodorum produces proteinaceous host‐selective toxins (HSTs). These toxins include SnTox1 as well as SnToxA, a HST first identified from Pyrenophora tritici‐repentis that was implicated in a very recent horizontal gene transfer event from S. nodorum to P. tritici‐repentis. Compelling evidence implicating SnToxA and SnTox1 in disease development has been obtained. Here, we report the partial purification and characterization of a third HST designated SnTox2, as well as the genetic characterization of the corresponding host‐sensitivity gene. SnTox2 was protease sensitive and is estimated between 7 and 10 kDa in size. Sensitivity to SnTox2 was conferred by a single dominant gene designated Snn2, which mapped to the short arm of wheat chromosome 2D. Genetic analysis of reaction to conidial inoculations in a segregating wheat population indicated that both the Snn2‐SnTox2 and the Tsn1‐SnToxA interactions were involved in disease development, and together they accounted for the majority of the phenotypic variation. Therefore, S. nodorum produces multiple toxins that rely on specific interactions with host gene products to cause disease. The identification of multiple HST–host gene interactions important for disease development and the availability of the S. nodorum whole genome sequence indicate the potential for this pathosystem to serve as a toxin‐based, inverse gene‐for‐gene model.
miR172 regulates stem cell fate and defines the inner boundary of APETALA3 and PISTILLATA expression domain in Arabidopsis floral meristems
Authors: Zhao Li , Kim YunJu , Dinh Theresa T. , Chen Xuemei 
Published: June 2007

SummaryIn Arabidopsis, two floral homeotic genes APETALA2 (AP2) and AGAMOUS (AG) specify the identities of perianth and reproductive organs, respectively, in flower development. The two genes act antagonistically to restrict each other to their proper domains of action within the floral meristem. In addition to AG, which antagonizes AP2, miR172, a microRNA, serves as a negative regulator of AP2. In this study, we showed that AG and miR172 have distinct functions in flower development and that they largely act independently in the negative regulation of AP2. We uncovered functions of miR172‐mediated repression of AP2 in the regulation of floral stem cells and in the delineation of the expression domain of another class of floral homeotic genes. Given the antiquity of miR172 in land plants, our findings have implications for the recruitment of a microRNA in the building of a flower in evolution.
Analysis of HLA class I–II haplotype frequency and segregation in a cohort of patients with advanced stage ovarian cancer
Authors: Gamzatova Z. , Villabona L. , Van Der Zanden H. , Haasnoot G. W. , Andersson E. , Kiessling R. , Seliger B. , Kanter L. , Dalianis T. , Bergfeldt K. , Masucci G. V. 
Published: June 2007

AbstractIn solid tumors, human leucocyte antigen (HLA)‐A2 has been suggested to be a risk factor and a negative prognostic factor. The HLA‐A2 allele in Scandinavia has a high prevalence; it decreases with latitude and also with ovarian cancer mortality in Europe. Furthermore, an association of the HLA‐A2 allele with severe prognosis in serous adenocarcinoma of the ovary in stages III–IV was found. Thirty‐two unrelated Swedish women with relapsing or progressive ovarian cancer were analysed for the genotypes at the HLA‐A, HLA‐B, HLA‐Cw, and HLA‐DRB1 loci by the polymerase chain reaction/sequence–specific primer method. The frequencies of HLA alleles of healthy Swedish bone marrow donors provided by the coordinating centre of the Bone Marrow Donors Worldwide Registries, Leiden, the Netherlands were used as controls. When this cohort of epithelial ovarian cancer patients was compared with healthy Swedish donors, the frequency of HLA‐A1 and HLA‐A2 gene/phenotype appears, although not statistically significant, to be increased in patients with ovarian carcinoma, while HLA‐A3 was decreased. HLA‐A2 homozygotes were twofold higher in patients. The A2‐B8 haplotype was significantly increased (corrected P value). A2–B5, A2–B15, A2–DRB1*03, A2–DRB1*04, A2–B15–Cw3, and A2–B8–DRB1*03 had odds ratio as well as the level of the lower confidence interval above 1 and significant P value only when considered as single, non‐corrected analysis. HLA‐B15 and HLA‐Cw3 were only present in HLA‐A2‐positive patients showing that the HLA‐A2–HLA‐Cw3 and HLA‐B15 haplotypes were segregated. In this selected cohort with advanced disease, there are indications of an unusual overrepresentation of HLA class I and II genes/haplotypes as well as segregation for the HLA‐A2–HLA‐Cw3 and HLA‐B15 haplotypes. These findings are presented as a descriptive analysis and need further investigations on a larger series of ovarian cancer patients to establish prognostic associations.
The MHC2TA−168A/G and +1614G/C polymorphisms and risk for multiple sclerosis or chronic inflammatory arthropathies
Authors: O’Doherty C. , Hawkins S. , Rooney M. , Vandenbroeck K. 
Published: June 2007

AbstractThe −168A‐G polymorphism has been shown to influence transcription of the MHC2TA gene and has been implicated in several inflammatory/autoimmune disorders. Attempts to reproduce these findings have been inconclusive. We investigated the role of this promoter single nucleotide polymorphism (SNP) in 440 multiple sclerosis (MS), 293 rheumatoid arthritis (RA), 74 juvenile idiopathic arthritis (JIA) patients and 316 healthy controls from Northern Ireland. We also genotyped a non‐synonymous SNP in exon 11, +1614G/C. There was no significant difference in the −168G allele frequencies and carriage rates in the separate RA, JIA, or MS collections compared with the control group [odds ratio (OR) = 1.1, 95% confidence intervals (CI) = 0.86–1.44; OR = 1.1, 95% CI = 0.75–1.68; OR = 1.1, 95% CI = 0.84–1.35, respectively]. Assessment of the common phenotype (chronic inflammatory disease; n = 807 vs 316 controls) was negative as well. Carriage of +1614C was protective against JIA (OR = 0.6, 95% CI = 0.3–1.0) and showed a similar trend in RA and MS (OR = 0.7, 95% CI = 0.5–1.0; OR = 0.8, 95% CI = 0.6–1.0, respectively). The common phenotype (chronic inflammatory disease) was also significant (OR = 0.7, 95% CI = 0.6–1.0).
Analysis of the HFE gene (C282Y, H63D and S65C) mutations in a general Chinese Han population
Authors: Lin A. , Yan W. H. , Xu H. H. , Zhu M. , Zhou M. Y. 
Published: June 2007

AbstractHereditary hemochromatosis (HH) is one of the most common autosomal recessive genetic disorders of iron metabolism in white populations, which leads to inappropriately high iron absorption. C282Y, H63D, and S65C are three major missense mutations of the hemochromatosis gene (HFE). In the present study, C282Y, H63D, and S65C mutations in 395 normal Chinese Han populations from Zhejiang province were investigated. No C282Y, S65C mutations, and H63D homozygote was observed, while the genotype frequency of H63D heterozygote was 4.6% and the allelic frequency 2.3% in this population. This was the first report to analyze the prevalence of C282Y, H63D, and S65C mutations in the HFE gene in a Chinese Han population. Low incidence of the HFE gene mutations could be a reason for the rarity of HH in the Chinese Han population studied.
HLA‐associated genetic resistance and susceptibility to type I diabetes in French North Africans and French natives
Authors: Guérin V. , Léniaud L. , Pédron B. , Guilmin‐Crépon S. , Tubiana‐Rufi N. , Sterkers G. 
Published: June 2007

AbstractThe distribution of human leukocyte antigen (HLA)‐DRB1–DQA1–DQB1 haplotypes was analyzed separately in two distinct French ethnic groups with type I diabetes (T1D), i.e. French North African migrants (n= 64, mean age at diagnosis = 8.25 years) and ancient French natives (n= 60, mean age at diagnosis = 7.42 years). HLA associations were determined by calculating odds ratios (ORs) between patients and two ethnic‐matched control populations. Results show highly similar ORs for the conservative DRB1*0301–DQA1*0501–DQB1*0201 haplotype of susceptibility (OR: 3.22 and 3.93 in migrants and natives, respectively) and the DRB1*1501–DQA1*0102–DQB1*0602 haplotype of resistance (OR: 0.05 and 0.03, respectively). In contrast, among the more variable DRB1*04–DQB1*0302 haplotypes of susceptibility, the DRB1*0402 (OR: 3.10 and 32.84) and 0405 (OR: 5.90 and 16.25, respectively) were associated with T1D in migrants and natives, whereas an increase of DRB1*0401, a rare allele in migrants, was significant in natives only. Also, among the DRB1*11–DQA1*0505–DQB1*0301 haplotypes of resistance, the OR observed for DRB1*1104–DQA1*0505–DQB1*0301, common in migrants, was lower (OR: 0.08) than for DRB1*1101–DQA1*0505–DQB1*0301 (OR: 0.32), common in natives. How DRB1*11 subtypes might affect differently the risk conferred by DQA1*0505–DQB1*0301 will be discussed.
Analysis of BTNL2 genetic polymorphisms in British and Dutch patients with sarcoidosis
Authors: Spagnolo P. , Sato H. , Grutters J. C. , Renzoni E. A. , Marshall S. E. , Ruven H. J. T. , Wells A. U. , Tzouvelekis A. , Van Moorsel C. H. M. , Van Den Bosch J. M. M. , Du Bois R. M. , Welsh K. I. 
Published: June 2007

AbstractSarcoidosis is a heterogeneous disorder, both phenotypically and genetically. Two independent studies have recently shown that a functional polymorphism within butyrophilin‐like 2 (BTNL2) gene predisposes to sarcoidosis independently of the human leukocyte antigen (HLA)‐DRB1 alleles. However, in both studies, data analysis was not stratified by Löfgren’s syndrome, a clinically and genetically distinct sarcoidosis subset. BTNL2, potentially encoding an immune coreceptor, is adjacent and in linkage disequilibrium (LD) with HLA‐DRB1. We investigated six BTNL2 variants, including the functional rs2076530 (G > A), as well as HLA‐DRB1 alleles, by sequence‐specific primers–polymerase chain reaction, in 288 patients and 446 controls from two European countries. In the patient group as a whole, the HLA‐DRB1*14 [odds ratio (OR) = 3.1, Pc = 0.0003], DRB1*12 (OR = 2.5, Pc = 0.003), and BTNL2 rs2076530 A allele (OR = 1.49, Pc = 0.002) were all associated with disease susceptibility. However, after exclusion of patients presenting with Löfgren’s syndrome and after adjusting for HLA‐DRB1 alleles, the association between BTNL2 rs2076530 A and disease disappeared (P = 0.23). By contrast, both HLA‐DRB1*14 and DRB1*12 remained strongly significant (OR = 3.60, P < 0.0001 and OR = 3.03, P = 0.003, respectively). BTNL2 haplotype 4, tagged by the rs2076530 G allele, also remained associated with non‐Löfgren sarcoidosis after adjusting for HLA‐DRB1 alleles (OR 0.37, P = 0.016). In summary, HLA‐DRB1*14, DRB1*12, and BTNL2 haplotype 4 – but not rs2076530 A – are associated with non‐Löfgren sarcoidosis. However, the tight LD across the HLA complex makes it difficult to identify the precise location of the susceptibility locus/i. Larger sample sets from different ethnic groups, finer mapping, and more robust LD analyses across the HLA region are needed.
KIR3DL2: diversity in a hematopoietic stem cell transplant population
Authors: Gedil M. A. , Steiner N. K. , Hurley C. K. 
Published: June 2007

AbstractExons 2 through 9 of KIR3DL2 were amplified from genomic DNA from 79 bone marrow transplantation patients and their unrelated donors. Sequencing of heterozygotes and isolated alleles identified 9 of the 17 known alleles. The alleles provide confirmation of previously submitted sequences and are carried by transformed B‐cell lines that can be used as references for assay development. Alleles 3DL2*001, *002, *007 and *009 accounted for 111 of the total 144 possible alleles and were the only ones found in a homozygous state. New alleles (3DL2*017, *018, *019, *020, and *021) were found in seven transplant samples and one workshop cell. This study describes the development of reagents and protocols for sequencing of KIR3DL2 alleles from genomic DNA.
Analysis of interleukin‐23 receptor (IL23R) gene polymorphisms in systemic lupus erythematosus
Authors: Sánchez E. , Rueda B. , Callejas J. L. , Sabio J. M. , Ortego‐Centeno N. , Jimenez‐Alonso J. , López‐Nevot M. A. , Martín J. 
Published: June 2007

AbstractThe aim of this study was to evaluate the association between systemic lupus erythematosus (SLE) and polymorphisms in the interleukin‐23 receptor (IL23R) gene, which have been previously found to be associated with two autoimmune diseases: inflammatory bowel disease and psoriasis. Our study includes 224 SLE patients and 342 healthy controls. The genotyping of IL23R variants was carried out using a polymerase chain reaction system with predeveloped TaqMan allelic discrimination assays. No statistically significant differences were observed between SLE patients and healthy controls with any of the IL23R genetic variants. In addition, we did not find any significant differences when we stratified SLE patients according to their clinical and demographic features. These results suggest that IL23R polymorphisms do not appear to play an important role in the susceptibility or severity of SLE in the Spanish population.
No evidence of PERV infection in healthcare workers exposed to transgenic porcine liver extracorporeal support
Authors: Levy Marlon F. , Argaw Takele , Wilson Carolyn A. , Brooks James , Sandstrom Paul , Merks Harriet , Logan John , Klintmalm Goran 
Published: June 2007

Background:  Clinical xenotransplantation holds great promise by providing one solution to the shortage of human organs for transplantation, while also posing a potential public health threat by facilitating transmission of infectious disease from source animals to humans. One potential vector for infectious disease transmission is healthcare workers (HCW) who are involved in administering xenotransplantation procedures. Methods: In this study, we studied 49 healthcare workers involved in the care of two subjects who participated in a study of porcine liver perfusion as treatment of fulminant hepatic failure. We looked for serologic and virologic evidence of transmission of porcine endogenous retrovirus, and found that HCW had no evidence of infection. Conclusions: Results of our survey demonstrate that application of standard precautions may be sufficient to prevent transmission of porcine endogenous retrovirus, an agent of concern in ex vivo xenotransplantation products.
Effect of various immunosuppressive monotherapies on survival and histopathology of monkey islet xenografts in rats
Authors: Balamurugan A. N. , Nelson Everette J. R. , Ramakrishna Banumathi , Gunasekaran S. 
Published: June 2007

Abstract:  Background:  The isolation and testing of monkey islets after transplantation in small animal models provides basic information about their functional capacity. We describe the effect of cyclosporine A (CsA), tacrolimus (FK506) or prednisolone monotherapy on preventing monkey islet graft rejection after xenoTx in a rat model. Histopathological aspects are reported.Methods:  Indian bonnet monkey (Macaca radiata radiata) islets were isolated by a simple stationary digestion technique using collagenase. The islets were purified with dextran density gradients and were transplanted under the renal capsule of normal or diabetic rats. The rats received a daily dose of CsA, or FK506, or prednisolone, and the grafts were removed at different intervals to determine islet survival. The effect of discontinuation of CsA on islet graft survival was also monitored. Histological examination of islets transplanted into normal or streptozotocin‐induced diabetic rats was carried out. In diabetic rats, islet survival was determined by the graft’s ability to achieve euglycemia.Results: Reversal of diabetes was achieved in all transplanted diabetic rats, demonstrating the efficacy of the isolated monkey islets. Histological examination indicated that monkey islets survived in the presence of continuous high‐dose immunosuppressive monotherapy in rats. Various types of infiltrating cells were observed in the grafted area at varying times after transplantation, depending on the immunosuppressive treatment. After discontinuation of CsA, the grafts were protected for a short period.Conclusions:  This study provided evidence for monkey islet survival after transplantation into rats receiving immunosuppressive monotherapy. Basic information on infiltrating cell types may be important in the study of xenograft rejection.
Soluble Galα(1,3)Gal conjugate combined with hDAF preserves morphology and improves function of cardiac xenografts
Authors: Brandl Ulrike , Erhardt Matthias , Michel Sebastian , Jöckle Hannah , Burdorf Lars , Bittmann Iris , Rössle Matthias , Mordstein Volker , Brenner Paolo , Hammer Claus , Reichart Bruno , Schmoeckel Michael 
Published: June 2007

Abstract:  Background:  Cytotoxic anti‐Galα(1,3)Gal antibodies play a key role in the rejection of pig organs transplanted into primates. Regimens reducing anti‐Galα(1,3)Gal antibodies were associated with severe side effects unable to prevent antibody rebound until soluble synthetic oligosaccharides with terminal Galα(1,3)Gal inhibiting antigen binding became available. We displayed kinetics of anti‐pig and anti‐Galα(1,3)Gal IgM and IgG antibody levels using GAS914, a Galα(1,3)Gal trisaccharide conjugated to poly‐l‐lysine, and investigated corresponding changes of parameters of heart function. Methods:  Using a working heart model, hDAF pig hearts were perfused with human blood containing GAS914 (group 1). As controls hDAF pig hearts (group 2) and landrace pig hearts (group 3) were perfused with human blood only. Levels of anti‐Galα(1,3)Gal (IgM, IgG) and anti‐pig antibodies were assessed to prove the effectiveness of GAS914. As parameters of heart function, cardiac output (CO), stroke work index (SWI), coronary blood flow (CBF) and coronary resistance were measured. Creatine phosphokinases, lactate dehydrogenase and aspartate aminotransferase were evaluated as markers of myocardial damage. Histological and immunohistochemical investigations were performed at the end of perfusion. Results: In group 1 an immediate and extensive reduction in both IgM and IgG anti‐Galα(1,3)Gal was found. Anti‐pig antibodies were eliminated accordingly. Antibody binding to GAS914 was complete before the start of organ perfusion. Corresponding to rapid antibody elimination in group 1 GAS914 not only was able to significantly prolong the beating time of the heart in hDAF pigs, but also to clearly improve functional parameters. When switching to the working heart mode hDAF pig hearts perfused with human blood containing GAS914 (group 1) revealed a CO starting at a significantly higher level than hDAF (group 2) and non‐transgenic pig hearts (group 3) perfused with human blood only. Similarly, in group 1 SWI was significantly increased at the beginning of perfusion compared to that of group 2 and group 3. The increase in CBF during perfusion and the corresponding fall of coronary resistance occurred without significant differences between the groups revealing the independence of hDAF and GAS914. Conclusions: Due to an immediate and profound reduction in Galα(1,3)Gal‐specific antibodies, soluble Galα(1,3)Gal conjugates not only prolong survival, but also improve the hemodynamic performance of the heart in DAF pigs.
Sexual selection maintains whole‐body chiral dimorphism in snails
Authors: SCHILTHUIZEN M. , CRAZE P. G. , CABANBAN A. S. , DAVISON A. , STONE J. , GITTENBERGER E. , SCOTT B. J. 
Published: June 2007

AbstractAlthough the vast majority of higher animals are fixed for one chiral morph or another, the cause for this directionality is known in only a few cases. In snails, for example, rare individuals of the opposite coil are unable to mate with individuals of normal coil, so directionality is maintained by frequency‐dependent selection. The snail subgenus Amphidromus presents an unexplained exception, because dextral (D) and sinistral (S) individuals occur sympatrically in roughly equal proportions (so‐called ‘antisymmetry’) in most species. Here we show that in Amphidromus there is sexual selection for dimorphism, rather than selection for monomorphism. We found that matings between D and S individuals occur more frequently than expected by chance. Anatomical investigations showed that the chirality of the spermatophore and the female reproductive tract probably allow a greater fecundity in such inter‐chiral matings. Computer simulation confirms that under these circumstances, sustained dimorphism is the expected outcome.
The spread of apomixis and its effect on resident genetic variation
Authors: ADOLFSSON S. , BENGTSSON B. O. 
Published: June 2007

AbstractIn a simulation model we investigated how much of the initial genetic variation that is retained in a population after a dominant mutation has brought apomixis to fixation in it. A marker allele associated with the apomixis mutation is generally retained after the fixation of apomixis, particularly if the two alleles are closely linked. The spread of asexuality, however, normally leads to almost no loss of genetic variation, neither with respect to cytotypes nor with respect to genotypes. This holds for large populations and apomixis mutants with strong pollen production. In smaller populations, and with apomicts with reduced pollen production, the outcome is more variable, ranging from no genetic variation retained to only weakly reduced variability compared with the initial state. These results help explain the high genetic variability in many apomicts. They also imply that natural selection will have many genotypes to act on even after the spread of apomixis.
How to separate genetic and environmental causes of similarity between relatives
Authors: KRUUK L. E. B. , HADFIELD J. D. 
Published: June 2007

AbstractRelated individuals often have similar phenotypes, but this similarity may be due to the effects of shared environments as much as to the effects of shared genes. We consider here alternative approaches to separating the relative contributions of these two sources to phenotypic covariances, comparing experimental approaches such as cross‐fostering, traditional statistical techniques and more complex statistical models, specifically the ‘animal model’. Using both simulation studies and empirical data from wild populations, we demonstrate the ability of the animal model to reduce bias due to shared environment effects such as maternal or brood effects, especially where pedigrees contain multiple generations and immigration rates are low. However, where common environment effects are strong, a combination of both cross‐fostering and an animal model provides the best way to avoid bias. We illustrate ways of partitioning phenotypic variance into components of additive genetic, maternal genetic, maternal environment, common environment, permanent environment and temporal effects, but also show how substantial confounding between these different effects may occur. Whilst the flexibility of the mixed model approach is extremely useful for incorporating the spatial, temporal and social heterogeneity typical of natural populations, the advantages will inevitably be restricted by the quality of pedigree information and care needs to be taken in specifying models that are appropriate to the data.