Bcl-xS and Bad potentiate the death suppressing activities of Bcl-xL, Bcl-2, and A1 in yeast

Members of the Bcl-2 family can be grouped into three classes based upon their effects on cell death. The first class suppresses death and includes Bcl-2. A second group, which includes Bax, is lethal, whereas a third class, including Bcl-xS, potentiates killing, although the members are not lethal by themselves. The proteins in the last class are proposed to exert their activity by binding to anti-apoptotic family members, thereby making the cell more susceptible to killing by another agent. To test this hypothesis, an inducible yeast expression system is reported that permits the functional analysis of three Bcl-2 family members. In yeast, Bax is lethal, and this activity is suppressed by Bcl-xL, Bcl-2, and A1. Co-expression of Bcl-xS did not diminish the ability of any of the anti-apoptotic members to antagonize Bax. Rather, co-expression of Bcl-xS potentiated the anti-death activity of all three proteins. This effect was not the result of changes in either the levels or integrity of Bax or anti-apoptotic proteins. Thus, Bcl-xS can bind to anti-apoptotic family members, but this association does not result in loss of biological activity. Therefore, Bcl-xS may act downstream of Bax and in a pathway that is conserved in yeast.     

A new design of the esophageal Wallstent endoprosthesis resistant to distal migration

OBJECTIVE: Because plastic-covered metallic stents used in the palliation of patients with unresectable esophageal cancer are associated with significant rates of migration, particularly when the lower end of the stent projects into the gastric fundus, the purpose of this study was to establish whether two new prototype designs of the Wallstent esophageal endoprosthesis are prone to migration. SUBJECTS AND METHODS: A cylindrical stent and a conical stent were studied. Both designs included plastic covering inside the metallic mesh. In addition, the conical device incorporated a variation in the braiding angle between the upper and lower parts of the endoprosthesis. Ten conical stents and eight cylindrical stents were inserted in 18 patients with tumors involving the gastroesophageal junction who were followed up with esophagography and endoscopy. RESULTS: All insertions of stents were successful. Two cylindrical stents (25%) migrated distally. Two conical stents (20%) migrated proximally. One perforation occurred that was associated with distal migration of a cylindrical stent. CONCLUSION: The frequency of distal migration of cylindrical stents is unacceptably high. Conical stents are resistant to distal migration, although improvements in design are required to deal with the problem of proximal migration.     

Acute inhalation toxicity of neutralized chemical agent identification sets (CAIS) containing agent in chloroform

Basic fibroblast growth factor (bFGF) exerts angiogenic and mitogenic properties in human tissue. Since changes in ion currents modulate essential Ca2+-dependent intracellular pathways in endothelial cells, we have investigated a possible contribution of Ca2+-activated K+ channels (BKCa) on bFGF-induced endothelial cell proliferation. The patch-clamp technique was used to identify BKCa and to study their modulation by bFGF in cultured endothelial cells of human umbilical cord veins (HUVEC). Cell counts of HUVEC were carried out on different days to analyze bFGF-induced cell proliferation and its influence by the specific BKCa blocker iberiotoxin (IBX). Using single-channel recordings, we found characteristic BKCa with a single-channel slope conductance of 170.3 +/- 2.1 pS (n = 7), half-maximal activation at internal pCa = 5.7 (n = 5; test potential: 80 mV), and dose-dependent block by IBX (25-100 nmol/l). In cell-attached patches bFGF (50 ng/ml) caused a significant increase in the open-state probability (NPo) after 6 min at test potentials of 80 and 100 mV (n = 28; p < 0.001), respectively, which lasted up to 30 min. After preincubation with pertussis toxin (100 ng/ml; 4 h) bFGF superfusion did not cause a significant increase in BKCa activity until 25 min had passed (n = 20; p < 0.01). Addition of 100 nmol/l IBX to the pipette solution caused a total block of BKCa within 2 min in cell-attached patches, whereas bFGF (50 ng/ml) was not able to activate BKCa. When incubated with IBX (25-100 nmol/l) every 2 days, bFGF-induced proliferation of HUVEC was significantly decreased by 50 (-41%) and 100 nmol/l (-50%) IBX (n = 5; p < 0.001) after 7 days. We conclude that activation of BKCa by bFGF may play an important role in bFGF-induced proliferation of human endothelial cells and thus might be important in the process of angiogenesis and vascular remodelling.     

Why was my major professor so busy? Establishing an academic career while pursuing applied work.

How do newly appointed academic psychologists with applied interests navigate the diverse and unique challenges of establishing themselves as academicians while pursuing clinical interests? Based on the experience of 4 new professionals, this article highlights the adjustments that must be made when making the transition from trainee to professional, the challenges encountered as a new faculty member, and the pursuit of applied interests as a junior faculty member. Strategies for avoiding the pitfalls that one may encounter when attempting to combine academic with applied interests are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low cost miniature thermoelectric generator

A low-cost thermoelectric generator realised using integrated circuit technology is described. The thermopile comprises polycrystalline silicon thermoelements on a quartz substrate and employs a design previously reported by the authors for a silicon on sapphire device. An approximate 10 fold decrease in the substrate thermal conductivity is achieved. Results of output measurements are presented and compared with those of previous work highlighting the advantages of the new approach.<>     

The internal architecture of anaerobic sludge granules

The structural characteristics of well-formed anaerobic granular sludges were examined using scanning electron microscopy and light microscopy of thin sections. Transverse sections were found to consist of randomly orientated filaments of Methanothrix soehngenii. These were tightly packed with little space between the individual filament sheaths, revealing a ‘honeycomb’ appearance. Sections cut from wax-embedded granules were stained using a number of histochemical procedures. Detailed examination of the overall structure of the granules was possible, revealing the presence of filamentous bundles of Methanothrix surrounded by a matrix found to be carbohydrate in nature. Interpretation of serial sections through the depth of the granule allowed for the construction of a diagrammatic illustration of the internal structure. A relationship between the measured diameter of these microcolonies of Methanothrix and the distance from the centre of the granule was established. Together these results enabled a proposal to be made as to the possible mechanisms involved in the growth of granules. This supports previous suggestions relating to the involvement of Methanothrix and bacterial polymers.     

New Cubic Structure in the Ca-Si-O-N System

Subsolidus-phase studies in the calcium-silicon-oxygen-nitrogen system have been conducted using the reactive precursors calcium nitride, calcium oxide, and silicon nitride. A new structure has been isolated with a large, face-centered cubic lattice, a=1.4864 nm, which coexists with several new CaSiON phases as well as Ca₃Si₂O₄N₂ and the unknown "D' phase, reported previously by other workers. The new structure is not isotypic with any known mineral oxide. The highest degree of phase purity has been obtained using a 1.1 calcium nitride:silicon nitride starting mixture. Structural and approximate compositional analyses were conducted by X-ray diffraction and TEM energy dispersive spectroscopy.