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  • Articles  (194)
  • Springer  (194)
  • American Chemical Society (ACS)
  • American Geophysical Union
  • Institute of Electrical and Electronics Engineers (IEEE)
  • National Academy of Sciences
  • 2015-2019  (109)
  • 2005-2009  (85)
  • 1990-1994
  • 1980-1984
  • 2017  (109)
  • 2008  (85)
  • Immunogenetics  (25)
  • 1504
  • Medicine  (194)
Collection
  • Articles  (194)
Source
Publisher
  • Springer  (194)
  • American Chemical Society (ACS)
  • American Geophysical Union
  • Institute of Electrical and Electronics Engineers (IEEE)
  • National Academy of Sciences
Years
  • 2015-2019  (109)
  • 2005-2009  (85)
  • 1990-1994
  • 1980-1984
Year
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  • 1
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    Peptide-binding motifs of two common equine class I MHC molecules in Thoroughbred horses (2017)
    Springer
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    Publication Date: 2017-03-19
    Description: Quantitative peptide-binding motifs of MHC class I alleles provide a valuable tool to efficiently identify putative T cell epitopes. Detailed information on equine MHC class I alleles is still very limited, and to date, only a single equine MHC class I allele, Eqca-1*00101 (ELA-A3 haplotype), has been characterized. The present study extends the number of characterized ELA class I specificities in two additional haplotypes found commonly in the Thoroughbred breed. Accordingly, we here report quantitative binding motifs for the ELA-A2 allele Eqca-16*00101 and the ELA-A9 allele Eqca-1*00201. Utilizing analyses of endogenously bound and eluted ligands and the screening of positional scanning combinatorial libraries, detailed and quantitative peptide-binding motifs were derived for both alleles. Eqca-16*00101 preferentially binds peptides with aliphatic/hydrophobic residues in position 2 and at the C-terminus, and Eqca-1*00201 has a preference for peptides with arginine in position 2 and hydrophobic/aliphatic residues at the C-terminus. Interestingly, the Eqca-16*00101 motif resembles that of the human HLA A02-supertype, while the Eqca-1*00201 motif resembles that of the HLA B27-supertype and two macaque class I alleles. It is expected that the identified motifs will facilitate the selection of candidate epitopes for the study of immune responses in horses.
    Print ISSN: 0093-7711
    Electronic ISSN: 1432-1211
    Topics: Biology , Medicine
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  • 2
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    CXCL12a/CXCR4b acts to retain neutrophils in caudal hematopoietic tissue and to antagonize recruitment to an injury site in the zebrafish larva (2017)
    Springer
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    Publication Date: 2017-02-22
    Description: Neutrophils are a major component of the innate immune response and the most abundant circulating cell type in humans and zebrafish. The CXCL12/CXCR4 ligand receptor pair plays a key role in neutrophil homeostasis, controlling definitive hematopoiesis and neutrophil release into circulation. Neutrophils overexpressing CXCR4 respond by migrating towards sources of CXCL12, which is abundant in hematopoietic tissues. However, the physiological role of CXCL12/CXCR4 signaling during inflammatory responses remains unknown. Here, we show that zebrafish mutants lacking functional CXCL12a or CXCR4b show disrupted granulopoiesis in the kidney and increased number of circulating neutrophils. Additionally, CXCL12a and CXCR4b mutants display exacerbated recruitment of neutrophils to wounds and not to infections, and migrating neutrophils to wounds show increased directionality. Our results show that CXCL12a/CXCR4b signaling antagonizes wound-induced inflammatory signals by retaining neutrophils in hematopoietic tissues as a part of a balance between both inflammatory and anti-inflammatory cues, whose dynamic levels control neutrophils complex migratory behavior.
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  • 3
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    Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets (2017)
    Springer
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    Publication Date: 2017-03-01
    Description: Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1 , TNIP1 , and CD44 , not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6 , DNAJB3 , TTF1 , GRIN2B , MON2 , LATS2 , SNX6 , RBFOX1 , NCOA3 , and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.
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  • 4
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    A new ataxia-telangiectasia mutation in an 11-year-old female (2017)
    Springer
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    Publication Date: 2017-05-10
    Description: Ataxia-telangiectasia (A-T), a rare inherited disorder, usually affects the nervous and immune systems, and occasionally other organs. A-T is associated mainly with mutations in the ataxia telangiectasia mutated (ATM) gene, which encodes a protein kinase that has a major role in the cellular response to DNA damage. We report here a novel ATM mutation (c.3244_3245insG; p.His1082fs) in an 11-year old female. This subject presented with typical features, with the addition of chest manifestations including mediastinal lymphadenopathy and diffuse bilateral micronodular infiltration of the lungs, along with a high EBV titer. The subject died as a result of rapid B-cell lymphoma progression before chemotherapy could be initiated. This case highlights the need for the rapid diagnosis of A-T mutations and the detection of associated life-threatening outcomes such as cancers.
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  • 5
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    The synergistic effects of ω-3 fatty acids and nano-curcumin supplementation on tumor necrosis factor (TNF)-α gene expression and serum level in migraine patients (2017)
    Springer
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    Publication Date: 2017-05-08
    Description: Migraine is a destabilizing neuroinflammatory disorder characterized by recurrent headache attacks. Evidences show tumor necrosis factor (TNF)-α play a role in neuroimmunity pathogenesis of migraine. TNF-α increase prostanoid production, hyperexcitability of neurons, and nociceptor activation resulted in neuroinflammation and neurogenic pain. ω-3 fatty acids and curcumin exert neuroprotective and anti-inflammatory effects via several mechanisms including suppression of TNF-α gene expression and its serum levels. The aim of this study is an evaluation of synergistic effects of ω-3 fatty acids and nano-curcumin on TNF-α gene expression and serum levels in migraine patients. The present study performed as a clinical trial over a 2 month period included 74 episodic migraine patients in 4 groups and received ω-3 fatty acids, nano-curcumin, and combination of them or placebo. At the start and the end of the study, the gene expression of TNF-α and TNF-α serum levels was measured by real-time PCR and ELISA method, respectively. Our results showed that the combination of ω-3 fatty acids and nano-curcumin downregulated TNF-α messenger RNA (mRNA) significantly in a synergistic manner ( P  〈 0.05). As relative to gene expression, a significant greater reduction in serum levels of TNF-α were observed in the combination group, but no significant differences in other groups. Supplementation with ω-3 fatty acids or nano-curcumin alone did not show significant reduction either in mRNA or serum levels of TNF-α. In addition, a much greater reduction in attack frequency was found in the combination group ( P  〈 0.001). These findings indicated that ω-3 fatty acids and curcumin supplementation can be considered as a new promising approach in migraine management.
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  • 6
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    A new mutation site in the AIRE gene causes autoimmune polyendocrine syndrome type 1 (2017)
    Springer
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    Publication Date: 2017-05-25
    Description: Autoimmune polyendocrine syndrome type 1 (APS-1, OMIM 2403000) is a rare autosomal recessive disease that is caused by autoimmune regulator (AIRE). The main symptoms of APS-1 are chronic mucocutaneous candidiasis, autoimmune adrenocortical insufficiency (Addison’s disease) and hypoparathyroidism. We collected APS-1 cases and analysed them. The AIRE genes of the patient and his family members were sequenced to identify whether the APS-1 patient had an AIRE mutation. We discovered a mutation site (c.206A〉C) that had never before been reported in the AIRE gene located in exon 2 of the AIRE gene. This homogyzous mutation caused a substitution of the 69th amino acid of the AIRE protein from glutamine to proline (p.Q69P). A yeast two-hybrid assay, which was used to analyse the homodimerization properties of the mutant AIRE protein, showed that the mutant AIRE protein could not interact with the normal AIRE protein. Flow cytometry and RT-qPCR analyses indicated that the new mutation site could decrease the expression levels of the AIRE, glutamic acid decarboxylase 65 (GAD65) and tryptophan hydroxylase-1 (TPH1) proteins to affect central immune tolerance. In conclusion, our research has shown that the new mutation site (c.206A〉C) may influence the homodimerization and expression levels and other aspects of the AIRE protein. It may also impact the expression levels of tissue-restricted antigens (TRAs), leading to a series of autoimmune diseases.
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  • 7
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    Identification of innate lymphoid cells in single-cell RNA-Seq data (2017)
    Springer
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    Publication Date: 2017-05-23
    Description: Innate lymphoid cells (ILCs) consist of natural killer (NK) cells and non-cytotoxic ILCs that are broadly classified into ILC1, ILC2, and ILC3 subtypes. These cells recently emerged as important early effectors of innate immunity for their roles in tissue homeostasis and inflammation. Over the last few years, ILCs have been extensively studied in mouse and human at the functional and molecular level, including gene expression profiling. However, sorting ILCs with flow cytometry for gene expression analysis is a delicate and time-consuming process. Here we propose and validate a novel framework for studying ILCs at the transcriptomic level using single-cell RNA-Seq data. Our approach combines unsupervised clustering and a new cell type classifier trained on mouse ILC gene expression data. We show that this approach can accurately identify different ILCs, especially ILC2 cells, in human lymphocyte single-cell RNA-Seq data. Our new model relies only on genes conserved across vertebrates, thereby making it in principle applicable in any vertebrate species. Considering the rapid increase in throughput of single-cell RNA-Seq technology, our work provides a computational framework for studying ILC2 cells in single-cell transcriptomic data and may help exploring their conservation in distant vertebrate species.
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  • 8
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    Characterization of MHC class I in a long distance migratory wader, the Icelandic black-tailed godwit (2017)
    Springer
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    Publication Date: 2017-05-24
    Description: The major histocompatibility complex (MHC) encodes proteins that are central for antigen presentation and pathogen elimination. MHC class I (MHC-I) genes have attracted a great deal of interest among researchers in ecology and evolution and have been partly characterized in a wide range of bird species. So far, the main focus has been on species within the bird orders Galliformes and Passeriformes, while Charadriiformes remain vastly underrepresented with only two species studied to date. These two Charadriiformes species exhibit striking differences in MHC-I characteristics and MHC-I diversity. We therefore set out to study a third species within Charadriiformes, the Icelandic subspecies of black-tailed godwits ( Limosa limosa islandica ). This subspecies is normally confined to parasite-poor environments, and we hence expected low MHC diversity. MHC-I was partially characterized first using Sanger sequencing and then using high-throughput sequencing (MiSeq) in 84 individuals. We verified 47 nucleotide alleles in open reading frame with classical MHC-I characteristics, and each individual godwit had two to seven putatively classical MHC alleles. However, in contrast to previous MHC-I data within Charadriiformes, we did not find any evidence of alleles with low sequence diversity, believed to represent non-classical MHC genes. The diversity and divergence of the godwits MHC-I genes to a large extent fell between the previous estimates within Charadriiformes. However, the MHC genes of the migratory godwits had few sites subject to positive selection, and one possible explanation could be a low exposure to pathogens.
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  • 9
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    Genetic variation of major histocompatibility complex genes in the endangered red-crowned crane (2017)
    Springer
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    Publication Date: 2017-05-15
    Description: Populations that have drastically decreased in the past often have low genetic variation, which may increase the risk of extinction. The genes of major histocompatibility complex (MHC) play an important role in the adaptive immune response of jawed vertebrates. Maintenance of adaptive genetic diversity such as that of MHC genes is important for wildlife conservation. Here, we determined genotypes of exon 3 of MHC class IA genes (MHCIA) and exon 2 of MHC class IIB genes (MHCIIB) to evaluate genetic variation of the endangered red-crowned crane population on Hokkaido Island, Japan, which experienced severe population decline in the past. We identified 16 and 6 alleles of MHCIA and MHCIIB, respectively, from 152 individuals. We found evidence of a positive selection at the antigen-binding sites in MHCIA exon 3 and MHCIIB exon 2. The phylogenetic analyses indicated evidence of trans-species polymorphism among the crane MHC genes. The genetic variability in both classes of MHC genes at the population level was low. No geographic structure was found based on the genetic diversity of microsatellite and MHC genes. Our study provides useful data for the optimal management of the red-crowned crane population in Hokkaido and can contribute to future studies on MHC genes of the continental populations of the red-crowned crane and other crane species.
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  • 10
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    Association of ulcerative colitis with transcobalamin II gene polymorphisms and serum homocysteine, vitamin B 12 , and folate levels in Chinese patients (2017)
    Springer
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    Publication Date: 2017-05-21
    Description: It has been reported that abnormal elevation of homocysteine is quite prevalent in ulcerative colitis (UC) patients. We attempted to explore the relationship of UC with transcobalamin II (TCN2) gene polymorphisms and serum homocysteine, vitamin B 12 , and folate levels in Chinese patients. TCN2 (rs1801198, rs9606756) genotypes were detected by the improved multiple ligase detection reaction (iMLDR) technique in 527 UC patients and 574 controls. Moreover, 128 UC patients and 138 controls were randomly selected for the measurement of homocysteine, vitamin B 12 , and folate levels by enzymatic cycling assay or chemiluminescence immunoassay. For TCN2 (rs1801198), the frequency of allele G and combined frequencies of CG and GG genotypes were increased in patients with mild, moderate, and severe UC compared with those with remission UC (all P  〈 0.001). The average homocysteine level was elevated (10.78 ± 3.33 vs 9.91 ± 2.88 μmol/L, P  = 0.024), whereas the average vitamin B 12 and folate levels were reduced (408.66 ± 185.00 vs 457.42 ± 206.47 pg/mL, P  = 0.044; 6.81 ± 3.06 vs 8.17 ± 2.58 ng/mL, P  〈 0.001, respectively) in UC patients than in controls. Compared with controls, the prevalence of hyperhomocysteinemia (HHcy 〉15.0 μmol/L), vitamin B 12 deficiency (〈203.0 pg/mL), and folate deficiency (〈4.0 ng/mL) was higher in UC patients (all P  〈 0.05). Both HHcy and folate deficiency were shown to be independent risk factors for UC (95% CI  = 1.206–12.293, P  = 0.023; 95% CI  = 1.910–11.129, P  = 0.001, respectively). TCN2 (rs1801198, rs9606756) mutations might aggravate the severity of UC. HHcy and folate deficiency are independent risk factors for UC.
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