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221.
Oral tolerance induction is thought to depend on special antigen presenting cells in the gut. A new report in the previous issue of Arthritis Research & Therapy supports this idea by demonstrating that indoleamine 2,3-dioxygenase-expressing dendritic cells in Peyer's patches from orally tolerized mice suppress T-cell responses via the generation of CD4+CD25+ regulatory T cells. This finding provides novel input into the mechanisms of oral tolerance that could further facilitate its use for the treatment of autoimmunity and chronic inflammatory reactions. 相似文献
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223.
Background
The relatively recent introduction of a highly efficient mosquito vector and an avian pathogen (Plasmodium relictum) to an isolated island ecosystem with naïve, highly susceptible avian hosts provides a unique opportunity to investigate evolution of virulence in a natural system. Mixed infections can significantly contribute to the uncertainty in host-pathogen dynamics with direct impacts on virulence. Toward further understanding of how host-parasite and parasite-parasite relationships may impact virulence, this study characterizes within-host diversity of malaria parasite populations based on genetic analysis of the trap (thrombospondin-related anonymous protein) gene in isolates originating from Hawaii, Maui and Kauai Islands.Methods
A total of 397 clones were produced by nested PCR amplification and cloning of a 1664 bp fragment of the trap gene from two malarial isolates, K1 (Kauai) and KV115 (Hawaii) that have been used for experimental studies, and from additional isolates from wild birds on Kauai, Maui and Hawaii Islands. Diversity of clones was evaluated initially by RFLP-based screening, followed by complete sequencing of 33 selected clones.Results
RFLP analysis of trap revealed a minimum of 28 distinct RFLP haplotypes among the 397 clones from 18 birds. Multiple trap haplotypes were detected in every bird evaluated, with an average of 5.9 haplotypes per bird. Overall diversity did not differ between the experimental isolates, however, a greater number of unique haplotypes were detected in K1 than in KV115. We detected high levels of clonal diversity with clear delineation between isolates K1 and KV115 in a haplotype network. The patterns of within-host haplotype clustering are consistent with the possibility of a clonal genetic structure and rapid within-host mutation after infection.Conclusion
Avian malaria (P. relictum) and Avipoxvirus are the significant infectious diseases currently affecting the native Hawaiian avifauna. This study shows that clonal diversity of Hawaiian isolates of P. relictum is much higher than previously recognized. Mixed infections can significantly contribute to the uncertainty in host-pathogen dynamics with direct implications for host demographics, disease management strategies, and evolution of virulence. The results of this study indicate a widespread presence of multiple-genotype malaria infections with high clonal diversity in native birds of Hawaii, which when coupled with concurrent infection with Avipoxvirus, may significantly influence evolution of virulence.Reviewers
This article was reviewed by Joseph Schall (nominated by Laura Landweber), Daniel Jeffares (nominated by Anthony Poole) and Susan Perkins (nominated by Eugene Koonin).224.
Kimberly Wolzak Anna Nlle Margherita Farina Truus EM Abbink Marjo S van der Knaap Matthijs Verhage Wiep Scheper 《The EMBO journal》2022,41(16)
Proteostasis is essential for cellular survival and particularly important for highly specialised post‐mitotic cells such as neurons. Transient reduction in protein synthesis by protein kinase R‐like endoplasmic reticulum (ER) kinase (PERK)‐mediated phosphorylation of eukaryotic translation initiation factor 2α (p‐eIF2α) is a major proteostatic survival response during ER stress. Paradoxically, neurons are remarkably tolerant to PERK dysfunction, which suggests the existence of cell type‐specific mechanisms that secure proteostatic stress resilience. Here, we demonstrate that PERK‐deficient neurons, unlike other cell types, fully retain the capacity to control translation during ER stress. We observe rescaling of the ATF4 response, while the reduction in protein synthesis is fully retained. We identify two molecular pathways that jointly drive translational control in PERK‐deficient neurons. Haem‐regulated inhibitor (HRI) mediates p‐eIF2α and the ATF4 response and is complemented by the tRNA cleaving RNase angiogenin (ANG) to reduce protein synthesis. Overall, our study elucidates an intricate back‐up mechanism to ascertain translational control during ER stress in neurons that provides a mechanistic explanation for the thus far unresolved observation of neuronal resilience to proteostatic stress. 相似文献
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226.
Specificity of binding of three soluble rat lung lectins to substituted and unsubstituted mammalian beta-galactosides 总被引:21,自引:0,他引:21
Binding of a series of mammalian glycoconjugates to three soluble rat lung lectins was determined with a quantitative assay. The three lectins, RL-14.5, RL-18, and RL-29, had a similar apparent affinity for lactose and associated with the same critical determinants, which included positions 4 and 6 of Gal and part of Glc. Derivatization at position 3 of Glc in lactose markedly reduced reactivity with the three lectins. For RL-14.5 and RL-29 the determinant extended specifically to the 3-hydroxyl of Glc which must be equatorial. In contrast, the stereochemical requirements for RL-18 were less specific, and Gal beta 1-3GalNAc bound as well as lactose. For RL-29 activity was markedly enhanced by GalNAc alpha 1-3 substitution on Gal, a modification which had little effect with RL-18 and inhibited binding to RL-14.5. Combinations of these residues in larger oligosaccharides and glycopeptides did not substantially enhance binding above that which might be expected from the sum of the constituent beta-galactoside residues. Although these lectins showed overlapping specificities, their binding properties are sufficiently different to suggest selective interactions with naturally occurring mammalian glycoconjugates. 相似文献
227.
228.
Michael E. Breimer Gunnar C. Hansson Karl-Anders Karlsson Hakon Leffler 《Biochemical and biophysical research communications》1980,95(1):416-422
A total neutral (non-acid) glycolipid fraction has been isolated from rat small intestine. By silicic acid column chromatography of the acetylated glycolipid derivative, 7 different partly purified fractions were obtained. Thin-layer chromatography of both the acetylated and native glycolipid fractions revealed a highly complex pattern with at least 30 different glycolipid bands having a thin-layer mobility as for mono- to dodecaglycosylceramides. Mass spectrometry of the permethylated and permethylated-reduced (LiAlH4) derivatives showed the presence of several glycolipid species not known before, including olighexosylceramides with 4, 5, 6 and 7 sugar residues and a tetraglycosylceramide with a blood group A determinant. This is the first report on such a complex glycolipid composition of a single organ. 相似文献
229.
Background
Sixteen, spring-born, single suckled, castrated male calves of Limousin × Holstein-Friesian and Simmental × Holstein-Friesian dams respectively, were used to investigate the effect of weaning on total leukocyte and differential counts, neutrophil functional activity, lymphocyte immunophenotypes, and acute phase protein response. Calves grazed with their dams until the end of the grazing season when they were housed in a slatted floor shed. On the day of housing, calves were assigned to a treatment, (i) abruptly weaned (W: n = 8) or (ii) non-weaned (controls) (C: n = 8). Weaned calves were housed in pens without their dams, whereas non-weaned (control) calves were housed with their dams. Blood was collected on day -7, 0 (housing), 2, 7, and 14 to determine total leukocyte and differential counts and concentration of fibrinogen and haptoglobin. Lymphocyte immunophenotypes were characterised using selected surface antigens (CD4+, CD8+, WC1+ (γδ T cells), MHC Class II+ lymphocytes), and the functional activities of neutrophils (surface expression of L-selectin (CD62L), phagocytic and oxidative burst activity) were investigated using flow cytometry. 相似文献230.
Sara S Roscioni Loes EM Kistemaker Mark H Menzen Carolina RS Elzinga Reinoud Gosens Andrew J Halayko Herman Meurs Martina Schmidt 《Respiratory research》2009,10(1):1-17