EGF signalling regulates cell invagination as well as cell migration during formation of tracheal system in Drosophila

 The Drosophila tracheal system is a network of epithelial tubes that arises from the tracheal placodes, lateral clusters of ectodermal cells in ten embryonic segments. The cells of each cluster invaginate and subsequent formation of the tracheal tree occurs by cell migration and fusion of tracheal branches, without cell division. The combined action of the Decapentaplegic (Dpp), Epidermal growth factor (EGF) and breathless/branchless pathways are thought to be responsible for the pattern of tracheal branches. We ask how these transduction pathways regulate cell migration and we analyse the consequences on cell behaviour of the Dpp and EGF pathways. We find that rhomboid (rho) mutant embryos display defects not only in tracheal cell migration but also in tracheal cell invagination unveiling a new role for EGF signalling in the formation of the tracheal system. These results indicate that the transduction pathways that control tracheal cell migration are active in different steps of tracheal formation, beginning at invagination. We discuss how the consecutive steps of tracheal morphogenesis might affect the final branching pattern. Received: 9 October 1998 / Accepted: 5 November 1998     

Activation of Focal Adhesion Kinase by Salmonella Suppresses Autophagy via an Akt/mTOR Signaling Pathway and Promotes Bacterial Survival in Macrophages

Autophagy has emerged as an important antimicrobial host defense mechanism that not only orchestrates the systemic immune response, but also functions in a cell autonomous manner to directly eliminate invading pathogens. Pathogenic bacteria such as Salmonella have evolved adaptations to protect themselves from autophagic elimination. Here we show that signaling through the non-receptor tyrosine kinase focal adhesion kinase (FAK) is actively manipulated by the Salmonella SPI-2 system in macrophages to promote intracellular survival. In wild-type macrophages, FAK is recruited to the surface of the Salmonella-containing vacuole (SCV), leading to amplified signaling through the Akt-mTOR axis and inhibition of the autophagic response. In FAK-deficient macrophages, Akt/mTOR signaling is attenuated and autophagic capture of intracellular bacteria is enhanced, resulting in reduced bacterial survival. We further demonstrate that enhanced autophagy in FAK^−/− macrophages requires the activity of Atg5 and ULK1 in a process that is distinct from LC3-assisted phagocytosis (LAP). In vivo, selective knockout of FAK in macrophages resulted in more rapid clearance of bacteria from tissues after oral infection with S. typhimurium. Clearance was correlated with reduced infiltration of inflammatory cell types into infected tissues and reduced tissue damage. Together, these data demonstrate that FAK is specifically targeted by S. typhimurium as a novel means of suppressing autophagy in macrophages, thereby enhancing their intracellular survival.     

Association between IFNA genotype and the risk of sarcoidosis

Sarcoidosis is known to be a systemic granulomatous disorder characterized by a cell-mediated Th1-type inflammatory response. To identify a key genetic factor in the pathogenesis of sarcoidosis, we investigated single nucleotide polymorphisms within 10 candidate genes involved in type 1 immune process (IFNA17, IFNB, IFNG, IFNGR1, IFNGR2, IL12B, IL12RB1, IL12RB2, ETA-1, and NRAMP1) in an association-based study of 102 Japanese patients with sarcoidosis, 114 with tuberculosis, and 110 control subjects. After correction for multiple testing, an IFNA17 polymorphism (551TG) was found to be associated with susceptibility to sarcoidosis (odds ratio 3.27 [95% CI: 1.44–7.46], P=0.004, P_c=0.04), but not to tuberculosis. We observed no significant associations with the other polymorphisms of the Th1-related genes. We further typed another IFNA polymorphism (IFNA10 60TA) and confirmed two major haplotypes of the IFNA gene, viz., allele 1: IFNA10 [60T]-IFNA17 [551T] and allele 2: IFNA10 [60A]-IFNA17 [551G], in the Japanese population. In healthy subjects, IFNA allele 2, which is over-represented in patients with sarcoidosis, was significantly associated with increased IFN- and IL-12p70 production induced by Sendai virus in vitro. This study suggests that possession of the IFNA allele with higher levels of IFN- significantly increases the risk of sarcoidosis.M. Akahoshi and M. Ishihara contributed equally to this work     

Chemical Variability of Xylopia quintasii Engl. & Diels Leaf Oil from Côte d'Ivoire

The chemical composition of 42 essential‐oil samples isolated from the leaves of Xylopia quintasii harvested in three Ivoirian forests was investigated by GC‐FID, including the determination of retention indices (RIs), and by ¹³C‐NMR analyses. In total, 36 components accounting for 91.9–92.6% of the oil composition were identified. The content of the main components varied drastically from sample to sample: (E)‐β‐caryophyllene (0.9–56.9%), (Z)‐β‐ocimene (0.3–54.6%), β‐pinene (0.8–27.9%), α‐pinene (0.1–22.8%), and furanoguaia‐1,4‐diene (0.0–17.6%). The 42 oil compositions were submitted to hierarchical cluster and principal components analysis, which allowed the distinction of three groups within the oil samples. The composition of the oils of the major group (22 samples) was dominated by (E)‐β‐caryophyllene. The oils of the second group (12 samples) contained β‐pinene and α‐pinene as the principal compounds, while the oils of the third group (8 samples) were dominated by (Z)‐β‐ocimene, germacrene D, (E)‐β‐ocimene, and furanoguaia‐1,4‐diene. The oil samples of Group I and II came from clay‐soil forests, while the oil samples belonging to Group III were isolated from leaves harvested in a sandy‐soil forest.