CD160Ig Fusion Protein Targets a Novel Costimulatory Pathway and Prolongs Allograft Survival

CD160 is a cell surface molecule expressed by most NK cells and approximately 50% of CD8⁺ cytotoxic T lymphocytes. Engagement of CD160 by MHC class-I directly triggers a costimulatory signal to TCR-induced proliferation, cytokine production and cytotoxic effector functions. The role of CD160 in alloimmunity is unknown. Using a newly generated CD160 fusion protein (CD160Ig) we examined the role of the novel costimulatory molecule CD160 in mediating CD4⁺ or CD8⁺ T cell driven allograft rejection. CD160Ig inhibits alloreactive CD8⁺ T cell proliferation and IFN-γ production in vitro, in particular in the absence of CD28 costimulation. Consequently CD160Ig prolongs fully mismatched cardiac allograft survival in CD4^−/−, CD28^−/− knockout and CTLA4Ig treated WT recipients, but not in WT or CD8^−/− knockout recipients. The prolonged cardiac allograft survival is associated with reduced alloreactive CD8⁺ T cell proliferation, effector/memory responses and alloreactive IFN-γ production. Thus, CD160 signaling is particularly important in CD28-independent effector/memory CD8⁺ alloreactive T cell activation in vivo and therefore may serve as a novel target for prevention of allograft rejection.     

Induction of localized auxin response during spontaneous nodule development in Lotus japonicus

In leguminous plants, rhizobial infection of the epidermis triggers proliferation of cortical cells to form a nodule primordium. Recent studies have demonstrated that two classic phytohormones, cytokinin and auxin, have important functions in nodulation. The identification of these functions in Lotus japonicus was facilitated by use of the spontaneous nodule formation 2 (snf2) mutation of the putative cytokinin receptor LOTUS HISTIDINE KINASE 1 (LHK1). Analyses using snf2 demonstrated that constitutive activation of cytokinin signaling causes formation of spontaneous nodule-like structures in the absence of rhizobia and that auxin responses are induced in proliferating cortical cells during such spontaneous nodule development. Thus, cytokinin signaling positively regulates the auxin response. In the present study, we further investigated the induction of the auxin response using a gain-of-function mutation of Ca²⁺/calmodulin-dependent protein kinase (CCaMK) that causes spontaneous nodule formation. We demonstrate that CCaMK^T265D-mediated spontaneous nodule development is accompanied by a localized auxin response. Thus, a localized auxin response at the site of an incipient nodule primordium is essential for nodule organogenesis.     

Characteristic Cerebrospinal Fluid Cytokine/Chemokine Profiles in Neuromyelitis Optica,Relapsing Remitting or Primary Progressive Multiple Sclerosis

Background

Differences in cytokine/chemokine profiles among patients with neuromyelitis optica (NMO), relapsing remitting multiple sclerosis (RRMS), and primary progressive MS (PPMS), and the relationships of these profiles with clinical and neuroimaging features are unclear. A greater understanding of these profiles may help in differential diagnosis.

Methods/Principal Findings

We measured 27 cytokines/chemokines and growth factors in CSF collected from 20 patients with NMO, 26 with RRMS, nine with PPMS, and 18 with other non-inflammatory neurological diseases (OND) by multiplexed fluorescent bead-based immunoassay. Interleukin (IL)-17A, IL-6, CXCL8 and CXCL10 levels were significantly higher in NMO patients than in OND and RRMS patients at relapse, while granulocyte-colony stimulating factor (G-CSF) and CCL4 levels were significantly higher in NMO patients than in OND patients. In NMO patients, IL-6 and CXCL8 levels were positively correlated with disability and CSF protein concentration while IL-6, CXCL8, G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IFN-γ were positively correlated with CSF neutrophil counts at the time of sample collection. In RRMS patients, IL-6 levels were significantly higher than in OND patients at the relapse phase while CSF cell counts were negatively correlated with the levels of CCL2. Correlation coefficients of cytokines/chemokines in the relapse phase were significantly different in three combinations, IL-6 and GM-CSF, G-CSF and GM-CSF, and GM-CSF and IFN-γ, between RRMS and NMO/NMOSD patients. In PPMS patients, CCL4 and CXCL10 levels were significantly higher than in OND patients.

Conclusions

Our findings suggest distinct cytokine/chemokine alterations in CSF exist among NMO, RRMS and PPMS. In NMO, over-expression of a cluster of Th17- and Th1-related proinflammatory cytokines/chemokines is characteristic, while in PPMS, increased CCL4 and CXCL10 levels may reflect on-going low grade T cell and macrophage/microglia inflammation in the central nervous system. In RRMS, only a mild elevation of proinflammatory cytokines/chemokines was detectable at relapse.     

Why does Daphne pseudomezereum drop its leaves in the summer? An adaptive alternative to surviving forest shade

Daphne pseudomezereum A. Gray (Dpm) appears to be the only woody species in the north temperate forest that sheds its leaves in the summer while remaining green over winter (i.e. wintergreen leaf habit). Yet, the reason for this odd leaf habit has not been explored. To this end, we examined the microclimatic settings and ecophysiological traits of Dpm and its three native congeners in a field study of eight natural populations. In addition, we conducted a common garden experiment using Dpm plants where potential carbon gain across the seasons was estimated, using actual field microclimate data. Together, these data tested the hypothesis that Dpm retained traits of an open-grown upland ancestor, unable to adapt to the deep summer shade, it survived by becoming summer dormant and wintergreen. Our hypothesis was supported by patterns of leaf ecophysiological traits and carbon gain simulations in Dpm, consistent with the energetic feasibility of a summer dormancy followed by an autumn leaf sprout. We also conclude that carbon deficit driven by low light and high respiration cost is the trigger for the leaf habit of Dpm and assert that its phenological strategy represents a rare but viable alternative strategy for persistence in the temperate understory.     

Analysis of the activity rhythm of the predatory bug Orius sauteri (Poppius) (Heteroptera: Anthocoridae) for optimizing its selective light attraction

Applied Entomology and Zoology - The minute pirate bug Orius sauteri (Poppius) (Heteroptera: Anthocoridae) is a major natural enemy of micro-pests and is expected to be an effective pest-control...     

Base composition and nucleosome density in exonic and intronic regions in genes of the filamentous ascomycetes Aspergillus nidulans and Aspergillus oryzae

We sequenced nucleosomal DNA fragments of the filamentous ascomycetes Aspergillus nidulans and Aspergillus oryzae and then mapped those sequences on their genomes. We compared the GC content and nucleosome density in the exonic and intronic regions in the genes of A. nidulans and A. oryzae. Although the GC content and nucleosome density in the exonic regions tended to be higher than those in the intronic regions, the difference in the distribution of the GC content was more notable than that of the nucleosome density. Next, we compared the GC content and nucleosome density in the exonic regions of 9616 orthologous gene pairs. In both Aspergillus species, the GC content did not correlate with the nucleosome density. In addition, the Spearman's rank correlation coefficient (ρ = 0.51) between the GC content of the exonic regions of the 9616 orthologous gene pairs was higher than that (ρ = 0.31) of the nucleosome densities of A. nidulans and A. oryzae. These results strongly suggest that the GC content in the exons of the orthologous gene pairs has been conserved during evolution but the nucleosome density has varied throughout.     

The SNP in the promoter region of the bovine ELOVL5 gene influences economic traits including subcutaneous fat thickness

Genetic analyses have contributed to improvements of economically important traits derived from adipose tissue such as fatty acid composition in beef. Elongation of very long chain fatty acids (ELOVL) genes encode for the enzymes that play an important role in elongation of long-chain fatty acids. In this study, we aimed to discover genetic polymorphisms of ELOVL gene family in cattle populations to develop genetic markers. As a result, five synonymous mutations were detected in the coding regions of the ELOVL1, ELOVL2, ELOVL3 and ELOVL5 genes. In addition, six mutations were identified in promoter region of the ELOVL5. Two of five mutations in the promoter region of ELOVL5 were expected to alter the ELOVL5 expression and influence the economic traits, because of the high synteny of the region which was essential for activation of Elovl5 in mouse. Therefore, we performed association analysis between the genotypes and traits and our result revealed that T allele of g.-110T>C in ELOVL5 gene promoter indicated significantly thinner subcutaneous fat thickness (TT, 2.39 cm; CT, 2.35 cm) than that of C allele (CC, 2.68 cm) in a Japanese Black population. Our results suggest that the g.-110T>C is a useful genetic marker for the breeding in beef cattle.     

Anti‐adhesive property of P‐selectin glycoprotein ligand‐1 (PSGL‐1) due to steric hindrance effect

P‐selectin glycoprotein ligand‐1 (PSGL‐1) is an adhesive molecule that is known to be a ligand for P‐selectin. An anti‐adhesive property of PSGL‐1 has not been previously reported. In this study, we show that PSGL‐1 expression is anti‐adhesive for adherent cells and we have elucidated the underlying mechanism. Overexpression of PSGL‐1 induced cell rounding and floating in HEK293T cells. Similar phenomena were demonstrated in other adherent cell lines with overexpression of PSGL‐1. PSGL‐1 overexpression inhibits access of antibodies to cell surface molecules such as integrins, HLA and CD25. Cells transfected with PSGL‐1 deletion mutants that lack a large part of the extracellular domain and chimeric construct expressing extracellular CD86 and intracellular PSGL‐1 only showed rounded morphology, but there are no floating cells. These results indicated that PSGL‐1 causes steric hindrance due to the extended structure of its extracellular domain that is highly O‐glycosylated, but intracellular domain also has some effect on cell rounding. This study implies that PSGL‐1 has Janus‐faced functions, being both adhesive and anti‐adhesive. J. Cell. Biochem. 114: 1271–1285, 2013. © 2013 Wiley Periodicals, Inc.