896 research outputs found
The Effect of Honeybees on Native Bee Communities in Northeastern Illinois and Northwestern Indiana Tallgrass Prairie Restorations
The goal of this research is to determine if honeybees are competing with native bees in tallgrass prairie restorations in Illinois and Indiana. Honeybees are a non-native species and recently honey been hives have been introduced to restorations without a systematic measured approach and thorough research into their effects on native bee populations and ecosystems. To test for evidence of competition between honeybees and native bees, data was gathered that would help in determining: 1) if nectar resources are limiting; 2) native bees have decreased pollen loads; and 3) species composition and foraging heights of native bees differ in sites with an introduced honeybee hive vs. sites without honeybee hives. Only one field season’s worth of data has been collected, thus no conclusions can be drawn until the second field season is completed
HLA Class I and KIR Genes Do Not Protect Against HIV Type 1 Infection in Highly Exposed Uninfected Individuals With Hemophilia A
A recent genome-wide association study (GWAS) involving patients with hemophilia A who were exposed to but uninfected with human immunodeficiency virus type 1 (HIV-1) did not reveal genetic variants associated with resistance to HIV-1 infection, beyond homozygosity for CCR5-Δ32. Since variation in HLA class I and KIR genes is not well interrogated by standard GWAS techniques, we tested whether these 2 loci were involved in protection from HIV-1 infection in the same hemophilia cohort, using controls from the general population. Our data indicate that HLA class I alleles, presence or absence of KIR genes, and functionally relevant combinations of the HLA/KIR genotypes are not involved in resistance to parenterally transmitted HIV-1 infectio
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Association between CTL Precursor Frequency to HLA-C Mismatches and HLA-C Antigen Cell Surface Expression
Previous studies showed the relevance of the cytotoxic T-cell precursor (CTLp) frequency assay for prediction of the outcome of HLA mismatched hematopoietic cell transplantation (HCT). Recently, it has been shown that HLA-C cell surface expression is correlated with virus specific cytotoxic T-cell responses and viremia control in HIV patients. The aim of the current study was to investigate the association between HLA-C antigen expression and the CTLp frequency to the mismatched HLA-C antigen. In total 115 recipient–donor pairs, for whom a successful CTLp assay was performed, were evaluated for this pilot study. All donor–recipient pairs were matched at 9/10 alleles with a single mismatch at the HLA-C locus. Antigen expression level of the mismatched HLA-C allele for each recipient and donor was based on the mean fluorescence intensity (MFI) values as described by Apps et al. (1). The cell surface expression of recipient’s mismatched HLA-C antigen was significantly lower among CTLp negative (n = 59) compared to CTLp positive (n = 56) pairs (154 and 193 MFI units, respectively, p = 0.0031). This difference was more pronounced in donor–recipient pairs that were mismatched for amino-acid residue-116 located in the groove of the HLA-C antigen, suggesting that the importance of peptide binding in the allo-recognition. Furthermore, in the particular case of low expression of the recipient mismatched HLA-C antigen (MFI < 115), CTLp reactivity depended on HLA-C expression level in the donor, the median MFI of donor’s mismatched HLA-C antigen was 114 in CTLp negative cases (n = 26), while in CTLp positive cases (n = 15) the median MFI of donor’s HLA-C antigen was 193 (p = 0.0093). We conclude that the expression level of the donor and recipient mismatched HLA-C antigens affect CTLp outcome. HLA-C antigen expression levels in combination with the CTLp assay may prove useful for the prediction of the clinical outcome of HLA-C mismatched HCT
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Mechanisms of Copy Number Variation and Hybrid Gene Formation in the KIR Immune Gene Complex
The fine-scale structure of the majority of copy number variation (CNV) regions remains unknown. The killer immunoglobulin receptor (KIR) gene complex exhibits significant CNV. The evolutionary plasticity of the KIRs and their broad biomedical relevance makes it important to understand how these immune receptors evolve. In this paper, we describe haplotype re-arrangement creating novel loci at the KIR complex. We completely sequenced, after fosmid cloning, two rare contracted haplotypes. Evidence of frequent hybrid KIR genes in samples from many populations suggested that re-arrangements may be frequent and selectively advantageous. We propose mechanisms for formation of novel hybrid KIR genes, facilitated by protrusive non-B DNA structures at transposon recombination sites. The heightened propensity to generate novel hybrid KIR receptors may provide a proactive evolutionary measure, to militate against pathogen evasion or subversion. We propose that CNV in KIR is an evolutionary strategy, which KIR typing for disease association must take into account
Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo.
This is the peer reviewed version of the following article:Augusto, D. G., O'Connor, G. M., Lobo-Alves, S. C., Bass, S., Martin, M. P., Carrington, M., . . . Petzl-Erler, M. L. (2015). Pemphigus is associated with KIR3DL2 expression levels and provides evidence that KIR3DL2 may bind HLA-A3 and A11 in vivo. European Journal of Immunology, 45(7), 2052-2060, which has been published in final form at DOI: 10.1002/eji.201445324. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-ArchivingAlthough HLA-A3 and A11 have been reported to be ligands for KIR3DL2, evidence for any in vivo relevance of this interaction is still missing. To explore the functional importance of KIR3DL2 allelic variation, we analyzed the autoimmune disease pemphigus foliaceus, previously associated (lower risk) with activating KIR genes. KIR3DL2*001 was increased in patients (odds ratio (OR) = 2.04; p = 0.007). The risk was higher for the presence of both KIR3DL2*001 and HLA-A3 or A11 (OR = 3.76, p = 0.013), providing the first evidence that HLA-A3 and A11 may interact with KIR3DL2 in vivo. The nonsynonymous single nucleotide polymorphism 1190T (rs3745902) was associated with protection (OR = 0.52, p = 0.018). This SNP results in a threonine-to-methionine substitution. Individuals who have methionine in this position exhibit a lower percentage of KIR3DL2-positive natural killer (NK) cells and also lower intensity of KIR3DL2 on expressing natural killer cells; additionally, we show that the expression of KIR3DL2 is independent of other killer cell immunoglobulin-like receptors. Pemphigus foliaceus is a very unique complex disease strongly associated with immune-related genes. It is the only autoimmune disease known to be endemic, showing a strong correlation with environmental factors. Our data demonstrate that this relatively unknown autoimmune disease may facilitate understanding of the molecular mechanisms of KIR3DL2 ligand recognition
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IFNL3 (IL28B) favorable genotype escapes hepatitis C virus-induced microRNAs and mRNA decay
The IFNL3 (IL28B) gene has received immense attention in the hepatitis C virus (HCV) field as multiple independent genome-wide association studies identified a strong association between polymorphisms near the IFNL3 gene and HCV clearance. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) located in the 3′ untranslated region (3′ UTR) of the IFNL3 mRNA that dictates transcript stability. This polymorphism influences AU-rich element-mediated decay as well as the binding of HCV-induced microRNAs during infection. Together, these pathways mediate robust repression of the unfavorable IFNL3 genotype. These data reveal a novel mechanism by which HCV attenuates the antiviral response and uncover new potential therapeutic targets for HCV treatment
Victims in Restorative Justice at Post-sentencing level. A Manual
The content of this manual evolved from the research project ‘Restorative Justice at post-sentencing level; supporting and protecting victims’ carried out by an international European team from Belgium, Croatia, Germany, Portugal, Spain and the United Kingdom. This manual is one of several project publications. The target group of this manual consists of those who are, in the widest sense, related to the work with victims of crime but also those, who are interested in Restorative Justice. This manual describes how victims of crime and therewith offenders and the community can be supported in various different ways. Therefore, the awareness of their needs is central at the outset. Furthermore, it aims to provide understanding of the individual process of coping and may therefore also lead to more self-awareness. If the victim is interested and prepared, it is possible to carry out Restorative Justice procedures in all types of crime and at all levels of seriousness, as long as it fits the person’s needs. The different steps to gain understanding of the situation of a victim and to provide support, as well as to empower in order to deal with what has occurred, are described in this manual. The different phases, before, during and after a restorative process, will be outlined as well as various RJ-procedures, from indirect victim-offendermediation to conferencing and possible techniques to apply during these procedures. That an atmosphere of trust is essential during the whole process appears evident as it is a basic principle of all Restorative Justice procedures. In order to provide better orientation, each sub-section is initiated with a number of key issues, which are then elaborated in a short text and concluded with a precise recommendation for practitioners to apply in the work with victims. More experienced practitioners can use this manual as a book of reference and concentrate on the recommendation whereas those, who have had less contact with victims in their work, can use it as an additional guide. In the final section, some case studies from the project partners England, Schleswig-Holstein, Portugal and Croatia give an exemplary insight into the restorative work carried out, from the victim perspective only
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