Theoretical aspects of motor protein induced filament depolymerisation

Many active processes in cells are driven by highly specialised motor proteins, which interact with the cytoskeleton: a network of filamentous structures, e.~g.~ actin filaments and microtubules, which organises intracellular transport and largely determines the cell shape. These motor proteins are able to transduce the chemical energy, stored in ATP molecules, to do mechanical work while interacting with a filament. Certain motor proteins, e.~g.~members of the KIN-13 kinesin subfamily, are able to interact specifically with filament ends and induce depolymerisation of the filament ends. One important role for KIN-13 family members is in the mitotic spindle, a microtubule structure that is formed in the process of cell division and is responsible for separation and distribution of the duplicated genetic material to the forming daughter cells. The aim of this work is to develop a theoretical framework capable of describing experimentally observed behaviour and shed light on underlying principles of motor induced filament depolymerisation. We use two different theoretical approaches to describe motor dynamics in this non- equilibrium situation: On the one hand we use phenomenological continuum equations which themselves are to a large extent independent of the underlying molecular details of the system. Molecular details of the system are incorporated in the equations through the specific values of macroscopic parameters which are determined by the underlying details. On the other hand, we use one- and two-dimensional discrete stochastic descriptions of motors on a filament. These kind of descriptions enable us to investigate the effects of different microscopic mechanisms of filament depolymerisation, and to investigate the role of fluctuations on the dynamic behaviour of motor proteins. We additionally discuss filament depolymerisation in the case where motors are not free to move but are fixed to a common anchoring point and depolymerise filaments under the influence of applied forces, mimicking the situation in the mitotic spindle. Our results can be related to recent experiments on members of the KIN-13 subfamily and predictions made in our theory can be tested by further experiments. Although motivated by experiments involving members of the KIN-13 subfamily, our theory is not restricted to these motors but applies in general to associated proteins which regulate dynamics of filament ends

Hydromethylthionine enhancement of central cholinergic signalling is blocked by rivastigmine and memantine

The present study was carried out with funds supplied by TauRx Therapeutic Ltd. We are grateful to Helene Lau for assistance with 182 |KONDAK etAl.the analytical determinations. Open access funding enabled and or-ganized by ProjektDEAL TauRx Therapeutics Ltd., Aberdeen, Grant/Award Number: R0154Peer reviewedPublisher PD

Proving the Absence of Microarchitectural Timing Channels

Microarchitectural timing channels are a major threat to computer security. A set of OS mechanisms called time protection was recently proposed as a principled way of preventing information leakage through such channels and prototyped in the seL4 microkernel. We formalise time protection and the underlying hardware mechanisms in a way that allows linking them to the information-flow proofs that showed the absence of storage channels in seL4.Comment: Scott Buckley and Robert Sison were joint lead author

Filament depolymerization by motor molecules

Motor proteins that specifically interact with the ends of cytoskeletal filaments can induce filament depolymerization. A phenomenological description of this process is presented. We show that under certain conditions motors dynamically accumulate at the filament ends. We compare simulations of two microscopic models to the phenomenological description. The depolymerization rate can exhibit maxima and dynamic instabilities as a function of the bulk motor density for processive depolymerization. We discuss our results in relation to experimental studies of Kin-13 family motor proteins

Mitochondrial Effects of Hydromethylthionine, Rivastigmine and Memantine in Tau-Transgenic Mice

Funding This study was sponsored by WisTa Laboratories Ltd., Singapore. (grant PAR1577).Peer reviewedPublisher PD

NEW ADAPTIVE ALGORITHM FOR DETECTING LOW-AND HIGH OHMIC FAULTS IN MESHED NETWORKS

ABSTRAC

Increased Cholinergic Response in α-Synuclein Transgenic Mice (h-α-synL62)

Peer reviewedPostprin