Association of serum Ly6/PLAUR domain-containing protein 1 levels with skin sclerosis in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by aberrant immune activation, vascular injury, and fibrosis of the skin and internal organs. Ly6/PLAUR domain-containing protein 1 (LYPD1) was reported to be secreted and to have various physiological functions such as anti-angiogenic effects. Here we investigated serum LYPD1 levels in SSc patients and the association of serum LYPD1 levels with clinical features of SSc. Serum samples were obtained from 75 SSc patients and 22 healthy individuals as controls. We measured serum LYPD1 levels using enzyme-linked immunosorbent assay kits. Then, the relationship between serum LYPD1 levels and clinical features of SSc was analyzed. Serum LYPD1 levels in diffuse cutaneous SSc (dcSSc) patients were significantly higher than those in the limited cutaneous SSc (lcSSc) patients (median [25-75th percentiles], 1693.43 [1086.61-1917.57] vs. 904.55 [714.356-1285.56] pg/mL), while there were no significant differences in the serum LYPD1 levels between lcSSc and healthy controls (904.55 [714.356-1285.56] vs. 750.71 pg/mL [544.00-912.14]). Further analysis revealed that serum LYPD1 levels in patients correlated with skin thickness scores and serum interleukin (IL)-6 levels, which were known to reflect the extent of skin thickening in SSc. Moreover, serum LYPD1 levels showed a decrease with improvement in skin thickness after treatment, along with a decrease in serum IL-6 levels. These results indicate that LYPD1 might be a potential marker for monitoring skin sclerosis and evaluating the efficacy of skin fibrosis treatment in SSc patients.

Keratinocyte proline-rich protein modulates immune and epidermal response in imiquimod-induced psoriatic skin inflammation.

Psoriasis is a persistent inflammatory skin disease thought to arise as a result of the infiltration of inflammatory cells and activation of keratinocytes. Recent advances in basic research and clinical experience revealed that the interleukin (IL)-23/IL-17 axis has been identified as a major immune pathway in psoriasis. However, it remains unclear how keratinocyte factors contribute to the pathology of psoriasis. Keratinocyte proline-rich protein (KPRP) is a proline-rich insoluble protein, which is present in the epidermis and is likely to be involved in the skin barrier function. Here, to investigate the potential roles of KPRP in psoriatic skin inflammation, Kprp-modified mice were applied in the imiquimod (IMQ)-induced skin inflammation model, which develops psoriasis-like epidermal hyperplasia and cutaneous inflammation features. Then, heterozygous knockout (Kprp+/- ) but not homozygous knockout (Kprp-/- ) mice displayed attenuated skin erythema compared to control wild-type mice. In addition, RNA sequencing, quantitative PCR and/or histological analysis detected changes in the expression of several molecules related to psoriatic inflammation or keratinocyte differentiation in Kprp+/- mice, but not Kprp-/- mice. Further analysis exhibited reduced IL-17-producing γδlow T cells and amplified epidermal hyperplasia in Kprp+/- mice, which were implied to be related to decreased expression of ß-defensins and increased expression of LPAR1 (Lysophosphatidic acid receptor 1), respectively. Thus, our results imply that KPRP has the potential as a therapeutic target in psoriatic skin inflammation.

Serum cold-inducible RNA-binding protein levels as a potential biomarker for systemic sclerosis-associated interstitial lung disease.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrotic, inflammatory, and vascular dysfunction. Danger-associated molecular patterns (DAMPs)-mediated inflammasome activation has been reported to be involved in the pathogenesis of SSc. Cold-inducible RNA-binding protein (CIRP) is newly identified as a DAMP. Here we examined the clinical significance of serum levels of CIRP in 60 patients with SSc and 20 healthy control patients (HCs) using an enzyme-linked immunosorbent assay. Serum CIRP levels in diffuse cutaneous SSc (dcSSc) patients were significantly increased compared with limited cutaneous SSc (lcSSc) patients or HCs. When examining the relationship with SSc-specific parameters, serum CIRP levels with the presence of interstitial lung disease (ILD) were higher than those without ILD. In detail, serum CIRP levels correlated negatively with the percent predicted diffusing capacity for carbon monoxide and positively with levels of Krebs von den Lungen-6. In addition, elevated serum CIRP levels declined along with decreased SSc-ILD activity in patients who received immunosuppressive therapy. These results suggest that CIRP may play a role in the development of ILD in SSc. Moreover, CIRP could serve as a useful serological marker of SSc-ILD in terms of disease activity and therapeutic effects.

Cascade palladium-catalyzed alkenyl aminocarbonylation/ intramolecular aryl amidation: an annulative synthesis of 2-quinolones.

Palladium-catalyzed intermolecular aminocarbonylation/intramolecular amidation cascade sequences can be used to convert a range of 2-(2-haloalkenyl)aryl halide substrates efficiently and selectively to the corresponding 2-quinolones. Delaying the introduction of the CO atmosphere allows an amination/carbonylation sequence and the preparation of an isoquinolone.

Site-selective modification of peptides using rhodium and palladium catalysis: complementary electrophilic and nucleophilic arylation.

The site-selective modification of peptides containing dehydroalanine, tyrosine and tryptophan residues has been achieved using rhodium catalysed conjugate additions or palladium catalysed aryl-amination and -etherification reactions.

Characterization of the soybean genome using EST-derived microsatellite markers.

We generated a high-density genetic linkage map of soybean using expressed sequence tag (EST)-derived microsatellite markers. A total of 6920 primer pairs (10.9%) were designed to amplify simple sequence repeats (SSRs) from 63,676 publicly available non-redundant soybean ESTs. The polymorphism of two parent plants, the Japanese cultivar 'Misuzudaizu' and the Chinese line 'Moshidou Gong 503', were examined using 10% polyacrylamide gel electrophoresis. Primer pairs showing polymorphism were then used for genotyping 94 recombinant inbred lines (RILs) derived from a cross between the parents. In addition to previously reported markers, 680 EST-derived microsatellite markers were selected and subjected to linkage analysis. As a result, 935 marker loci were mapped successfully onto 20 linkage groups, which totaled 2700.3 cM in length; 693 loci were detected using the 668 EST-derived microsatellite markers developed in this study, the other 242 loci were detected with 105 RFLP markers, 136 genome-derived microsatellite markers, and one phenotypic marker. We examined allelic variation among 23 soybean cultivars/lines and a wild soybean line using 668 mapped EST-derived microsatellite markers (corresponding to 686 marker loci), in order to determine the transferability of the markers among soybean germplasms. A limited degree of macrosynteny was observed at the segmental level between the genomes of soybean and the model legume Lotus japonicus, which suggests that considerable genome shuffling occurred after separation of the species and during establishment of the paleopolyploid soybean genome.

Complete genome structure of Gloeobacter violaceus PCC 7421, a cyanobacterium that lacks thylakoids.

The nucleotide sequence of the entire genome of a cyanobacterium Gloeobacter violaceus PCC 7421 was determined. The genome of G. violaceus was a single circular chromosome 4,659,019 bp long with an average GC content of 62%. No plasmid was detected. The chromosome comprises 4430 potential protein-encoding genes, one set of rRNA genes, 45 tRNA genes representing 44 tRNA species and genes for tmRNA, B subunit of RNase P, SRP RNA and 6Sa RNA. Forty-one percent of the potential protein-encoding genes showed sequence similarity to genes of known function, 37% to hypothetical genes, and the remaining 22% had no apparent similarity to reported genes. Comparison of the assigned gene components with those of other cyanobacteria has unveiled distinctive features of the G. violaceus genome. Genes for PsaI, PsaJ, PsaK, and PsaX for Photosystem I and PsbY, PsbZ and Psb27 for Photosystem II were missing, and those for PsaF, PsbO, PsbU, and PsbV were poorly conserved. cpcG for a rod core linker peptide for phycobilisomes and nblA related to the degradation of phycobilisomes were also missing. Potential signal peptides of the presumptive products of petJ and petE for soluble electron transfer catalysts were less conserved than the remaining portions. These observations may be related to the fact that photosynthesis in G. violaceus takes place not in thylakoid membranes but in the cytoplasmic membrane. A large number of genes for sigma factors and transcription factors in the LuxR, LysR, PadR, TetR, and MarR families could be identified, while those for major elements for circadian clock, kaiABC were not found. These differences may reflect the phylogenetic distance between G. violaceus and other cyanobacteria.

Complete genome structure of the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1.

The entire genome of a thermophilic unicellular cyanobacterium, Thermosynechococcus elongatus BP-1, was sequenced. The genome consisted of a circular chromosome 2,593,857 bp long, and no plasmid was detected. A total of 2475 potential protein-encoding genes, one set of rRNA genes, 42 tRNA genes representing 42 tRNA species and 4 genes for small structural RNAs were assigned to the chromosome by similarity search and computer prediction. The translated products of 56% of the potential protein-encoding genes showed sequence similarity to experimentally identified and predicted proteins of known function, and the products of 34% of these genes showed sequence similarity to the translated products of hypothetical genes. The remaining 10% lacked significant similarity to genes for predicted proteins in the public DNA databases. Sixty-three percent of the T. elongatus genes showed significant sequence similarity to those of both Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120, while 22% of the genes were unique to this species, indicating a high degree of divergence of the gene information among cyanobacterial strains. The lack of genes for typical fatty acid desaturases and the presence of more genes for heat-shock proteins in comparison with other mesophilic cyanobacteria may be genomic features of thermophilic strains. A remarkable feature of the genome is the presence of 28 copies of group II introns, 8 of which contained a presumptive gene for maturase/reverse transcriptase. A trace of genome rearrangement mediated by the group II introns was also observed.