Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. We sequenced and analyzed the whole genomes of 27 HCCs, 25 of which were associated with hepatitis B or C virus infections, including two sets of multicentric tumors. Although no common somatic mutations were identified in the multicentric tumor pairs, their whole-genome substitution patterns were similar, suggesting that these tumors developed from independent mutations, although their shared etiological backgrounds may have strongly influenced their somatic mutation patterns. Statistical and functional analyses yielded a list of recurrently mutated genes. Multiple chromatin regulators, including ARID1A, ARID1B, ARID2, MLL and MLL3, were mutated in ～50% of the tumors. Hepatitis B virus genome integration in the TERT locus was frequently observed in a high clonal proportion. Our whole-genome sequencing analysis of HCCs identified the influence of etiological background on somatic mutation patterns and subsequent carcinogenesis, as well as recurrent mutations in chromatin regulators in HCCs.     

An aspartic acid repeat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to osteoarthritis

Osteoarthritis is the most common form of human arthritis. We investigated the potential role of asporin, an extracellular matrix component expressed abundantly in the articular cartilage of individuals with osteoarthritis, in the pathogenesis of osteoarthritis. Here we report a significant association between a polymorphism in the aspartic acid (D) repeat of the gene encoding asporin (ASPN) and osteoarthritis. In two independent populations of individuals with knee osteoarthritis, the D14 allele of ASPN is over-represented relative to the common D13 allele, and its frequency increases with disease severity. The D14 allele is also over-represented in individuals with hip osteoarthritis. Asporin suppresses TGF-beta-mediated expression of the genes aggrecan (AGC1) and type II collagen (COL2A1) and reduced proteoglycan accumulation in an in vitro model of chondrogenesis. The effect on TGF-beta activity is allele-specific, with the D14 allele resulting in greater inhibition than other alleles. In vitro binding assays showed a direct interaction between asporin and TGF-beta. Taken together, these findings provide another functional link between extracellular matrix proteins, TGF-beta activity and disease, suggesting new therapeutic strategies for osteoarthritis.     

A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities

Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here we identify a SNP in the promoter region of FCRL3, a member of the Fc receptor-like family, that is associated with susceptibility to rheumatoid arthritis (odds ratio = 2.15, P = 0.00000085). This polymorphism alters the binding affinity of nuclear factor-kappaB and regulates FCRL3 expression. We observed high FCRL3 expression on B cells and augmented autoantibody production in individuals with the disease-susceptible genotype. We also found associations between the SNP and susceptibility to autoimmune thyroid disease and systemic lupus erythematosus. FCRL3 may therefore have a pivotal role in autoimmunity.     

Developmental change of EEG in rat from 4th to 16th week

Summary The development of EEG in 8 male rats from 4 to 16 weeks age were studied chronically. Theta band had the highest power at 5–16 weeks. Especially after 11 weeks, theta band presented a signigicantly higher peak than that of 4-week-old. In contrast to this, delta band, which had the highest power at 4 weeks, was markedly decreased.     

Autoradiographic studies on the experimental pulmonary fibrosis of rats after H3-proline injection

Zusammenfassung Mit einer 2-, 4-, 8- und 16-Wochenbehandlung wurde bei Ratten experimentell eine Lungenfibrose durch SiO₂ verursacht. Später wurde i.p. H³-Prolin injiziert und durch Autoradiographie die pulmonale Fibrose bewertet. In den Pneumokoniose-Herden wurde die Radioaktivität mit der Zeit am intensivsten, wobei die höchste Aktivität in den Kollagenfasern gemessen wurde.     

Origin of the direct cortical response as studied in vitro in thin cortical sections

Résumé Pour examiner l'origine de la réponse corticale par stimulation directe, le potentiel produit dans la mince section corticale a été étudié. Dans la tranche qui se compose seulement de la couche moleculaire, la configuration de la réponse a été la même que celle qui a été suscitée dans le cortex intact. La propriété du potentiel indique que non seulement les ondes initiales rapides mais aussi les ondes secondaires retardées ont atteint la portion éloignée des dendrites apicalaux.     

Hydrolysis of amino acidβ-naphthylamides by aminopeptidases in human parotid saliva and human serum

Zusammenfassung Die Aktivität der Aminopeptidasen im menschlichen Speichel von Ohrspeicheldrüsen wurde durch Fluoreszenzanalyse gemessen. Die Substratspezifität der Speichelaminopeptidasen war derjenigen der Serumenzyme ähnlich. Das Glycyl-Prolin -naphthylamidspaltende Enzym war jedoch im Speichel von Ohrspeicheldrüsen in relativ grösserer Menge vorhanden.     

Effects ofγ-amino-butyric acid on the potentials evoked in vitro in the superior colliculus

Résumé L'acide butyrique gamma-amino (GABA) en basse concentration a réduit le potentiel suscité in vitro dans une tranche deColliculus superior chez le cobaye. Cette action suppressive de GABA ne s'est pas produite dans un medium sans chlore ou avec de la strychnine. On en a conclu que GABA simule le transmetteur inhibitoire dans leC. superior.