Pathological and genetic correlates of apoptosis in the progression of colorectal neoplasia

Recent data indicate that dysphagia may occur following unilateral cortical stroke; however, the elucidation of specific cytoarchitectonic sites that produce deglutition disorders remains unclear. In a previous study of unilateral cortical stroke patients with dysphagia, Daniels et al. proposed that the insula may be important in swallowing as it was the most common lesion site in the patients studied. Therefore, 4 unilateral stroke patients with discrete lesions of the insular cortex were studied to further facilitate understanding of the role of the insula in swallowing. Dysphagia, as confirmed by videofluoroscopy, was evident in 3 of the 4 patients; all had lesions that involved the anterior insula, whereas the only patient without dysphagia had a lesion restricted to the posterior insula. These data suggest that the anterior insula may be an important cortical substrate in swallowing. The anterior insula has connections to the primary and supplementary motor cortices, the ventroposterior medial nucleus of the thalamus, and to the nucleus tractus solitarius, all of which are important regions in the mediation of oropharyngeal swallowing. Therefore, discrete lesions of the anterior insula may disrupt these connections and, thereby, produce dysphagia.     

A model of the pulmonary arterial bed in adults and infants

A microcomputer model based on an equivalent model of the systemic arterial circulation was used to simulate the pulmonary arterial circulation. The elements chosen to represent the physical properties of the pulmonary arterial bed were determined from the characteristic impedances and tme delays in the system. A terminal resistance that provided a reflection coefficient of 0.56 at a heart rate of 75 min-1 was chosen. The model simulated normal values for pressure and blood velocity in the main pulmonary artery and pulmonary capillary bed of adults and newborn infants. The results indicate that the relatively simple physical principles used to explain systemic hemodynamics are equally applicable to the pulmonary arterial circulation.     

Projection structure of frog rhodopsin in two crystal forms

Rhodopsin is the G protein-coupled receptor that upon light activation triggers the visual transduction cascade. Rod cell outer segment disc membranes were isolated from dark-adapted frog retinas and were extracted with Tween detergents to obtain two-dimensional rhodopsin crystals for electron crystallography. When Tween 80 was used, tubular structures with a p2 lattice (a = 32 A, b = 83 A, gamma = 91 degrees) were formed. The use of a Tween 80/Tween 20 mixture favored the formation of larger p22(1)2(1) lattices (a = 40 A, b = 146 A, gamma = 90 degrees). Micrographs from frozen hydrated frog rhodopsin crystals were processed, and projection structures to 7-A resolution for the p22(1)2(1) form and to 6-A resolution for the p2 form were calculated. The maps of frog rhodopsin in both crystal forms are very similar to the 9-A map obtained previously for bovine rhodopsin and show that the arrangement of the helices is the same. In a tentative topographic model, helices 4, 6, and 7 are nearly perpendicular to the plane of the membrane. In the higher-resolution projection maps of frog rhodopsin, helix 5 looks more tilted than it appeared previously. The quality of the two frog rhodopsin crystals suggests that they would be suitable to obtain a three-dimensional structure in which all helices would be resolved.     

Platelet and Erythrocyte Extravasation across Inflamed Corneal Venules Depend on CD18, Neutrophils,and Mast Cell Degranulation

Platelet extravasation during inflammation is under-appreciated. In wild-type (WT) mice, a central corneal epithelial abrasion initiates neutrophil (PMN) and platelet extravasation from peripheral limbal venules. The same injury in mice expressing low levels of the β₂-integrin, CD18 (CD18_hypo mice) shows reduced platelet extravasation with PMN extravasation apparently unaffected. To better define the role of CD18 on platelet extravasation, we focused on two relevant cell types expressing CD18: PMNs and mast cells. Following corneal abrasion in WT mice, we observed not only extravasated PMNs and platelets but also extravasated erythrocytes (RBCs). Ultrastructural observations of engorged limbal venules showed platelets and RBCs passing through endothelial pores. In contrast, injured CD18_hypo mice showed significantly less venule engorgement and markedly reduced platelet and RBC extravasation; mast cell degranulation was also reduced compared to WT mice. Corneal abrasion in mast cell-deficient (Kit^W-sh/W-sh) mice showed less venule engorgement, delayed PMN extravasation, reduced platelet and RBC extravasation and delayed wound healing compared to WT mice. Finally, antibody-induced depletion of circulating PMNs prior to corneal abrasion reduced mast cell degranulation, venule engorgement, and extravasation of PMNs, platelets, and RBCs. In summary, in the injured cornea, platelet and RBC extravasation depends on CD18, PMNs, and mast cell degranulation.     

Arrangement of rhodopsin transmembrane alpha-helices

Rhodopsins, the photoreceptors in rod cells, are G-protein-coupled receptors with seven hydrophobic segments containing characteristic conserved sequence patterns that define a large family. Members of the family are expected to share a conserved transmembrane structure. Direct evidence for the arrangement of seven alpha-helices was obtained from a 9A projection map of bovine rhodopsin. Structural constraints inferred from a comparison of G-protein-coupled receptor sequences were used to assign the seven hydrophobic stretches in the sequence to features in the projection map. A low-resolution three-dimensional structure of bovine rhodopsin and two projection structures of frog rhodopsin confirmed the position of the three least tilted helices, 4, 6 and 7. A more elongated peak of density for helix 5 indicated that it is tilted or bent, but helices 1, 2 and 3 were not resolved. Here we have used electron micrographs of frozen-hydrated two-dimensional frog rhodopsin crystals to determine the structure of frog rhodopsin. Seven rods of density in the map are used to estimate tilt angles for the seven helices. Density visible on the extracellular side of the membrane suggests a folded domain. Density extends from helix 6 on the intracellular side, and a short connection between helices 1 and 2, and possibly a part of the carboxy terminus, are visible.     

Capturing gas and particle motion in an idealised gas-granular flow

A model two-dimensional gas-granular flow, consisting of 4.76 mm-diameter nylon beads constrained to move between two glass plates, was investigated using particle image velocimetry (PIV) to measure the gas flow, and simultaneous image analysis to measure the motion of the bed particles. PIV confirmed that the deviations from the mean gas flow in the absence of large particles followed a Gaussian distribution, and clearly showed the motion of the gas around the large particles. The gas flow between two adjacent particles was seen to increase, and particles below one another were seen to reduce the gas flow around higher particles. No dependence of the gas flow on the direction of motion of the bed particles could be discerned, and the bed particles typically had speeds of around 1/10 of the gas speed.     

Accuracy of Doppler catheter measurements: effect of inhomogeneous beam power distribution on mean and peak velocity

ECT is an effective and rapidly acting treatment for certain major psychiatric disorders, even in patients with neurologic illness. Further, in some cases the neurologic illness itself also responds to ECT. Patients with some types of neurologic illness may be at increased risk of neurologic or cognitive side effects from ECT, but these risks can be lowered by careful pre-ECT evaluation and optimal ECT technique.     

Phosphorylation sites in bovine rhodopsin

Bovine rhodopsin has been phosphorylated in rod outer segments by ATP and endogenous rhodopsin kinase. Mono-, di-, and triphosphorylated rhodopsins have been prepared by chromatofocusing. Nearly all of the phosphate is found in peptide 330-348, formed by digestion of phosphorhodopsins with endoproteinase Asp-N. Sequence analysis of the phosphopeptides shows that monophosphorylated rhodopsin consists of a mixture containing rhodopsins phosphorylated at 338Ser and 343Ser. Diphosphorylated rhodopsin is phosphorylated at both 338Ser and 343Ser. When rhodopsin becomes triphosphorylated it does not become phosphorylated on 334Ser but appears to become phosphorylated on one or more of the four threonine residues: 335Thr, 336Thr, 340Thr, and 342Thr.     

Optical design of the atacama cosmology telescope and the millimeter bolometric array camera

The Atacama Cosmology Telescope is a 6 m telescope designed to map the cosmic microwave background simultaneously at 145, 215, and 280 GHz with arcminute resolution. Each frequency will have a 32 by 32 element focal plane array of transition edge sensor bolometers. The telescope and the cold reimaging optics are optimized for millimeter-wave observations with these sensitive detectors. The design of each is described.