Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers

Chronic viral hepatitis is the most important risk factor for progression to hepatocellular carcinoma (HCC). To identify genetic risk factors for progression to HCC in individuals with chronic hepatitis C virus (HCV), we analyzed 467,538 SNPs in 212 Japanese individuals with chronic HCV with HCC and 765 individuals with chronic HCV without HCC. We identified one intronic SNP in the DEPDC5 locus on chromosome 22 associated with HCC risk and confirmed the association using an independent case-control population (710 cases and 1,625 controls). The association was highly significant when we analyzed the stages separately as well as together (rs1012068, P(combined) = 1.27 × 10(-13), odds ratio = 1.75). The significance level of the association further increased after adjustment for gender, age and platelet count (P = 1.35 × 10(-14), odds ratio = 1.96). Our findings suggest that common variants within the DEPDC5 locus affect susceptibility to HCC in Japanese individuals with chronic HCV infection.     

The core of the motor domain determines the direction of myosin movement

Myosins constitute a superfamily of at least 18 known classes of molecular motors that move along actin filaments. Myosins move towards the plus end of F-actin filaments; however, it was shown recently that a certain class of myosin, class VI myosin, moves towards the opposite end of F-actin, that is, in the minus direction. As there is a large, unique insertion in the myosin VI head domain between the motor domain and the light-chain-binding domain (the lever arm), it was thought that this insertion alters the angle of the lever-arm switch movement, thereby changing the direction of motility. Here we determine the direction of motility of chimaeric myosins that comprise the motor domain and the lever-arm domain (containing an insert) from myosins that have movement in the opposite direction. The results show that the motor core domain, but neither the large insert nor the converter domain, determines the direction of myosin motility.     

Superior cervical ganglionectomy in the Japanese quail

Résumé Les effets de l'ablation des ganglions cervicals supérieurs deCoturnix coturnix japonica font l'objet de cet exposé. Chez le mâle la gangliectomie bilatérale n'affecte pas l'activité testiculaire. Par contre chez les femelles la quantité d'ufs pondus est nettement réduite et l'interruption post-opératoire de la pondaison est prolongée; de plus la première ponte des jeunes femelles est retardée. LesCoturnix qui ont subi l'ablation des ganglions ont un taux de mortalité plus élevé lorsque les oiseaux sont exposés à des abaissements de température et des changements de photopériodisme.

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This work was supported in part by USPHS research grant No. NB 04171-83 and by NASA research grant No. NGR 05-004-028.     

Histamine sensitizing activity of lentinan,an antitumour polysaccharide

Riassunto E dimostrato che lentinan, polisaccaride antineoplastic, è capace di aumentare la sensibitità del topo contro istamina. La presomministrazione di lentinan invece non aumenta l'attività del fattore istamina sensibilizzante dellaBordetella pertussis. Lentinan non induce linfocitose nel topo.

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Acknowledgment: Thanks are due to Drs.G. Chihara andY. Y. Maeda, National Cancer Centre, Research Institute, Tokyo, for kindly supplying lentinan.     

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the “infection–inflammation–exacerbation” axis of COPD disease progression, and may represent promising targets for therapeutic intervention.     

A galaxy at a redshift z = 6.96

When galaxy formation started in the history of the Universe remains unclear. Studies of the cosmic microwave background indicate that the Universe, after initial cooling (following the Big Bang), was reheated and reionized by hot stars in newborn galaxies at a redshift in the range 6 < z < 14 (ref. 1). Though several candidate galaxies at redshift z > 7 have been identified photometrically, galaxies with spectroscopically confirmed redshifts have been confined to z < 6.6 (refs 4-8). Here we report a spectroscopic redshift of z = 6.96 (corresponding to just 750 Myr after the Big Bang) for a galaxy whose spectrum clearly shows Lyman-alpha emission at 9,682 A, indicating active star formation at a rate of approximately 10M(o) yr(-1), where M(o) is the mass of the Sun. This demonstrates that galaxy formation was under way when the Universe was only approximately 6 per cent of its present age. The number density of galaxies at z approximately 7 seems to be only 18-36 per cent of the density at z = 6.6.     

Pummerer-type Functionalization of Aryl and Alkenyl Selenoxides

Heteroatom-stabilized carbenium ions have been widely recognized as potential electrophilic reagents. However, in contrast with the extensive works on thionium ion series, the highly labile character of selenoxide functionalities has caused serious limitation in the synthetic use in spite of their wide potentiality as synthetic equivalents of electrophilic selonium ions. In this paper, novel generation of selonium ions and the synthetic uses of the species for Pummerer-type α-functionalization and for cycloaddition by using the novel dienophilic behavior of π-conjugated selonium cations.     

Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome

By exome sequencing, we found de novo SMARCB1 mutations in two of five individuals with typical Coffin-Siris syndrome (CSS), a rare autosomal dominant anomaly syndrome. As SMARCB1 encodes a subunit of the SWItch/Sucrose NonFermenting (SWI/SNF) complex, we screened 15 other genes encoding subunits of this complex in 23 individuals with CSS. Twenty affected individuals (87%) each had a germline mutation in one of six SWI/SNF subunit genes, including SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B.