Continuous Production of Prions after Infectious Particles Are Eliminated: Implications for Alzheimer’s Disease

Rat septal cells, induced to enter a terminal differentiation-like state by temperature shift, produce prion protein (PrP) levels 7x higher than their proliferative counterparts. Host PrP accumulates on the plasma membrane, newly elaborated nanotubes, and cell-to-cell junctions, important conduits for viral spread. To find if elevated PrP increased susceptibility to FU-CJD infection, we determined agent titers under both proliferating and arresting conditions. A short 5 day arrest and a prolonged 140 day arrest increased infectivity by 5x and 122x (>2 logs) respectively as compared to proliferating cells. Total PrP rapidly increased 7x and was even more elevated in proliferating cells that escaped chronic arrest conditions. Amyloid generating PrP (PrP-res), the “infectious prion” form, present at ∼100,000 copies per infectious particle, also increased proportionately by 140 days. However, when these highly infectious cells were switched back to proliferative conditions for 60 days, abundant PrP-res continued to be generated even though 4 logs of titer was lost. An identical 4 log loss was found with maximal PrP and PrP-res production in parallel cells under arresting conditions. While host PrP is essential for TSE agent spread and replication, excessive production of all forms of PrP can be inappropriately perpetuated by living cells, even after the initiating infectious agent is eliminated. Host PrP changes can start as a protective innate immune response that ultimately escapes control. A subset of other neurodegenerative and amyloid diseases, including non-transmissible AD, may be initiated by environmental infectious agents that are no longer present

Euler, Jacobi, and Missions to Comets and Asteroids

Whenever a freely spinning body is found in a complex rotational state, this means that either the body is a recent victim of an impact or a tidal interaction, or is a fragment of a recently disrupted progenitor. Another factor (relevant for comets) is outgassing. Due to impacts, tidal forces and outgassing, the asteroidal and cometary precession must be a generic phenomenon: while some rotators are in the state of visible tumbling, a much larger amount of objects must be performing narrow-cone precession not so easily observable from the Earth. The internal dissipation in a freely precessing top leads to relaxation (gradual damping of the precession) and sometimes to spontaneous changes in the rotation axis. Recently developed theory of dissipative precession of a rigid body reveals that this is a highly nonlinear process: while the body is precessing at an angular rate $\omega$, the precession-caused stresses and strains in the body contain components oscillating at other frequencies. Dependent upon the spin state, those frequencies may be higher or, most remarkably, lower than the precession rate. In many states dissipation at the harmonics is comparable to or even exceeds that at the principal frequency. For this and other reasons, in many spin states the damping of asteroidal and cometary wobble happens faster, by several orders, than believed previously. This makes it possible to measure the precession-damping rate. The narrowing of the precession cone through the period of about a year can be registered by the currently available spacecraft-based observational means. However, in the near-separatrix spin states a precessing rotator can considerably slow down its relaxation.Comment: 21 pages, 1 figur

Ultrasonic Characterization of Microspherical Inclusions in Zirconia and Crystallized Glass

In high performance ceramic materials the critical flaw size is ≃ 10 µm. Not all inclusions are equally detrimental to the structural properties. Therefore it is necessary to determine their size and composition.</p

Rapid chemical decontamination of infectious CJD and scrapie particles parallels treatments known to disrupt microbes and biofilms

232 hlm.; 21 cm

Sketch of North River, Mass.

Topographical survey made under the direction of H.L. Whiting...by O.H. Tittman.https://digitalcommons.salemstate.edu/maps_massachusetts/1004/thumbnail.jp