The canonical Wnt/β-catenin pathway plays an important role in different developmental processes through the regulation of stem cell functions. In the activation of the canonical Wnt/β-catenin pathway, β-catenin protein is imported into the nucleus and activates transcription of target genes including cyclin D1 and c-myc. Aberrant activation of the Wnt/β-catenin pathway contributes to carcinogenesis and malignant behaviors, and Wnt signaling is essential for the maintenance of cancer stem cells. The canonical Wnt/β-catenin pathway has been investigated extensively as a target in cancer treatment and several specific inhibitors of this signaling pathway have been identified through high-throughput screening. In this review, the significance of the canonical Wnt/β-catenin pathway in hematological carcinogenesis and screening methods for specific inhibitors are discussed.
Objective. We have previously described anti-KS autoantibodies and provided evidence that they are directed against asparaginyl-transfer RNA (tRNA) synthetase (AsnRS). The aim of the present study was to identify patients with anti-AsnRS autoantibodies and elucidate the clinical significance of this sixth antisynthetase antibody. In particular, we studied whether it was associated with the syndrome of myositis (polymyositis or dermatomyositis [DM]), interstitial lung disease (ILD), arthritis, and other features that had been previously associated with the 5 other anti-aminoacyltRNA synthetase autoantibodies.Methods. More than 2,500 sera from patients with connective tissue disease (including myositis and ILD) and controls were examined for anti-AsnRS autoantibodies by immunoprecipitation (IP). Positive and control sera were tested for the ability to inhibit AsnRS by preincubation of the enzyme source with the serum. The HLA class II (DRB1, DQA1, DQB1, DPB1) alleles were identified from restriction fragment length polymorphism of polymerase chain reaction-amplified genomic DNA.Results. Anti-AsnRS antibodies were identified in the sera of 8 patients (5 Japanese, 1 American, 1 German, and 1 Korean) by IP of the same distinctive set of tRNA and protein that differed from those precipitated by the other 5 antisynthetases, and these antibodies showed specific inhibition of AsnRS activity. Two of these patients had DM, but 7 of 8 (88%) had ILD. Four patients (50%) had arthritis, and 1 had Raynaud's phenomenon. This antisynthetase was very rare among myositis patients (present in 0% of Japanese myositis patients), but it was found in 3% of Japanese ILD patients. Thus, most patients with anti-AsnRS had chronic ILD with or without features of connective tissue disease. Interestingly, all 4 Japanese patients tested had DR2 (DRB1*1501/1502), compared with 33% of healthy controls.Conclusion. These results indicate that antiAsnRS autoantibodies, like anti-alanyl-tRNA synthetase autoantibodies, have a stronger association with ILD than with myositis and may be associated with the DR2 phenotype.The aminoacyl-transfer RNA (aminoacyl-tRNA) synthetases are a family of cytoplasmic enzymes that catalyze the formation of aminoacyl-tRNA from a specific amino acid and its cognate tRNA and play a crucial role in protein synthesis. Autoantibodies to certain of these synthetases (histidyl-, threonyl-, alanyl-, isoleucyl-, and glycyl-tRNA synthetases) have been identified in patients with inflammatory myopathies (1-6). Among these "antisynthetase autoantibodies," the most common is anti-Jo-1 (anti-histidyl-tRNA synthetase [anti-HisRS]), found in 20% of patients with polymyositis/dermatomyositis (PM/DM) (7-11). Anti-PL-7 (anti-threonyl-tRNA synthetase [anti-ThrRS])
In Alzheimer disease (AD) patient brains, the accumulation of amyloid-β (Aβ) peptides is associated with activated microglia. Aβ is derived from the amyloid precursor protein; two major forms of Aβ, that is, Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), exist. We previously reported that rat microglia phagocytose Aβ42, and high mobility group box protein 1 (HMGB1), a chromosomal protein, inhibits phagocytosis. In the present study, we investigated the effects of exogenous HMGB1 on rat microglial Aβ40 phagocytosis. In the presence of exogenous HMGB1, Aβ40 markedly increased in microglial cytoplasm, and the reduction of extracellular Aβ40 was inhibited. During this period, HMGB1 was colocalized with Aβ40 in the cytoplasm. Furthermore, exogenous HMGB1 inhibited the degradation of Aβ40 induced by the rat microglial cytosolic fraction. Thus, extracellular HMGB1 may internalize with Aβ40 in the microglial cytoplasm and inhibit Aβ40 degradation by microglia. This may subsequently delay Aβ40 clearance. We further confirmed that in AD brains, the parts of senile plaques surrounded by activated microglia are composed of Aβ40, and extracellular HMGB1 is deposited on these plaques. Taken together, microglial Aβ phagocytosis dysfunction may be caused by HMGB1 that accumulates extracellularly on Aβ plaques, and it may be critically involved in the pathological progression of AD.
Thin film p–i–n junction solar cells incorporating hydrogenated microcrystalline Si1-xGex (µc-Si1-xGex:H) absorber i layers (1 µm) have been fabricated by plasma-enhanced chemical vapor deposition in the composition range of 0≤x≤0.35. By increasing Ge content from x=0 to 0.15–0.2, short-circuit current density increases by ∼5 mA/cm2 with spectral sensitivities extending into the infrared wavelengths (>600 nm). However, solar cell parameters for larger Ge contents (x>0.2) are lowered by the increased charge carrier recombination in the µc-Si1-xGex:H i layer. As a result, a 6.3% efficient solar cell is obtained at x=0.2, exhibiting infrared response even higher than that of double-thickness µc-Si:H solar cells. The solar cell shows excellent performance stability under prolonged light soaking.
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