The entry of diphtheria toxin into the mammalian cell cytoplasm: evidence for lysosomal involvement

Lysosomotropic amines, such as ammonium chloride, are known to protect cells from the cytotoxic effects of diphtheria toxin. These drugs are believed to inhibit the transport of the toxin from a receptor at the cell exterior into the cytoplasm where a fragment of the toxin arrests protein synthesis. We studied the effects of lysosomotropic agents on the cytotoxic process to better understand how the toxin enters the cytoplasm. The cytotoxic effects of diphtheria toxin were not inhibited by antitoxin when cells were preincubated at 37 degrees C with toxin and ammonium chloride, exposed to antitoxin at 4 degrees C, washed to relieve the ammonium chloride inhibition, and finally warmed to 37 degrees C. The antigenic determinants of the toxin were, therefore, either altered or sheltered. It is likely that the combination of ammonium chloride and a low temperature trapped the toxin in an intracellular vesicle from which the toxin could proceed to the cytoplasm. Because lysosomotropic amines raise the pH within acidic intracellular vesicles, such as lysosomes, they could trap the toxin within such a vesicle if an acidic environment were necessary for the toxin to penetrate into the cytoplasm. We simulated acidic conditions which the toxin might encounter by exposing cells with toxin bound to their surface to acidic medium. We then measured the effects of lysosomotropic amines on the activity of the toxin to see if the acidic environment substituted for the function normally inhibited by the drugs. The drugs no longer protected the cells. This suggests that exposing the toxin to an acidic environment, such as that found within lysosomes, is an important step in the penetration of diphtheria toxin into the cytoplasm

EVALUATION OF CURRENT SOIL CONSERVATION STRATEGIES

The paper is divided into four broad selections. The first section spells out the major reasons for public action in regard to soil conservation. The second section briefly discusses the current soil conservation investments both public and private. The third section evaluates the current strategies, ranging from cost-sharing to regulation, in terms of economic, political, and administration effectiveness. Finally, the concluding section suggest what we have learned from the evaluation and what needs to be done so that future evaluations will have a firmer analytic basis.Land Economics/Use,

Associated primes of local cohomology modules and of Frobenius powers

We construct normal hypersurfaces whose local cohomology modules have infinitely many associated primes. These include unique factorization domains of characteristic zero with rational singularities, as well as F-regular unique factorization domains of positive characteristic. As a consequence, we answer a question on the associated primes of Frobenius powers of ideals, which arose from the localization problem in tight closure theory

Deterministic Global Attitude Estimation

A deterministic attitude estimation problem for a rigid body in an attitude dependent potential field with bounded measurement errors is studied. An attitude estimation scheme that does not use generalized coordinate representations of the attitude is presented here. Assuming that the initial attitude, angular velocity and measurement noise lie within given ellipsoidal bounds, an uncertainty ellipsoid that bounds the attitude and the angular velocity of the rigid body is obtained. The center of the uncertainty ellipsoid provides point estimates, and its size gives the accuracy of the estimates. The point estimates and the uncertainty ellipsoids are propagated using a Lie group variational integrator and its linearization, respectively. The estimation scheme is optimal in the sense that the attitude estimation error and the size of the uncertainty ellipsoid is minimized at each measurement instant, and it is global since the attitude is represented by a rotation matrix.Comment: IEEE Conference on Decision and Control, 2006. 6 pages, 6 figure