The spectrum of diaphragmatic hernia

Diaphragmatic hernias are among the most common abnormalities of the gastrointestinal tract. Those with significant paraesophageal features may require surgical intervention to prevent potentially lethal complications. By contrast, 90% of patients with sliding hiatal hernias respond favorably to behavior modification and antisecretory drug therapy.     

The regulation of collagen in fetal skin wounds: mRNA localization and analysis

The deposition of collagen in fetal skin wounds has been shown in several animal models. The authors used a radiolabeled RNA antisense probe, complementary to the mRNA for the alpha-1 chain of human procollagen type I, to assess regulation of this collagen species in fetal and adult rabbit wounds. Dorsal skin wounds were placed on fetal and maternal animals at the beginning of the third trimester, and were harvested 3, 5, and 7 days later. In situ RNA/RNA hybridization was performed on suitable specimens, and morphometric analysis was carried out with a computerized LECO image analyzer. Fetal wounds exhibited an inflow of mesenchymal cells that produced collagen type I at levels higher than the surrounding tissue; this activity was highest on days 3 and 5 after wounding. Adult wounds had increased fibroblast presence by day 7, producing collagen type I at levels higher than those of adjacent unwounded tissue. Morphometric analysis of the signal produced by in situ hybridization and of the number of cells producing the signal in a given field showed that fetal wounds appear to produce collagen type I by an increase in the number of cells in the area of the wound--not by induction of the gene for procollagen type I. In contrast, adult wounds had both fibroblast migration and induction of procollagen type I mRNA synthesis. These findings imply multilevel regulation of collagen production in the adult and posttranslational regulation in the fetus.     

The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions

The Src protein tyrosine kinase plays a critical role in a variety of signal transduction pathways. Strict regulation of its activity is necessary for proper signalling. We present here the crystal structure of chicken Src which is phosphorylated at Tyr527 and represents its least active form. Our structure, similar to the recently reported human Hck and Src structures, contains the SH3, SH2 and the kinase domains and the C-terminal regulatory tail but not the N-terminal unique domain. The SH3 domain uses its hydrophobic surface to coordinate the SH2-kinase linker such that residues Gln251 and Leu255 specifically interact with side chains in the beta2-beta3 and the alphaC-beta4 loops of the N-terminal lobe opposite of the kinase active site. This position of the SH3 domain and the coordination of the SH2-kinase linker also optimally places the SH2 domain such that the phosphorylated Tyr527 in the C-terminal tail interacts with the SH2 binding pocket. Analogous to Cdk2 kinase, the position of the Src alphaC-helix in the N-terminal lobe is swung out disrupting the position of the active site residues. Superposition of other protein kinases including human Hck and Src onto chicken Src indicate that the alphaC-helix position is affected by the relative position of the N-terminal lobe with respect to the C-terminal lobe of the kinase and that the presence of the SH3/SH2-kinase linker/N-terminal lobe interactions restricts the kinase lobes and alphaC-helix access to the active conformation. These superpositions also suggest that the highly conserved alphaC-beta4 loop restricts the conformational freedom of the N-terminal lobe by anchoring it to the C-terminal lobe. Finally, based on sequence alignments and conservation of hydrophobic residues in the Src SH2-kinase linker as well as in the alphaC-beta4 and beta2-beta3 loops, we propose that the Src-related kinases, Abl, Btk and Csk, share the same quaternary structure.     

Extracellular cellulase system of a thermotolerant streptomycete: Streptomyces albaduncus

In this study we compared viewer-centered (VC) with object-centered (OC) mental exploration of an imagined clock drawn on the ground. An upper case F portrayed on a computer screen was to be imagined standing up in the center of the clock. In Expt. 1, an adjustment task was used to verify that the discrimination of clock directions rendered by this perspective drawing was quite accurate. Precision was not affected by the imaginary size of the clock. In Expt. 2, subjects either (1) indicated the clock location pointed by the F given their viewing position (VC condition), or (2) their location at the periphery of the clock given the location pointed by the F (OC condition). Response latencies were proportional to the explored imaginary distance and increased with the size of the imagined environment. We found an additional mean processing time of at least 2 s in the OC condition with respect to the VC condition. Results are interpreted within Kosslyn's (Kosslyn, S.M., A cognitive neuroscience of visual cognition: further developments. In: R.H. Logie and M. Denis (Eds.), Mental Images in Human Cognition, Elsevier Science Publishers, Amsterdam, 1991, pp. 351-381 [17]) framework of cognitive neuroscience.