The intrinsic load-resisting capacity of kinesin

Conventional kinesin is a homodimeric motor protein that is capable of walking unidirectionally along a cytoskeletal filament. While previous experiments indicated unyielding unidirectionality against an opposing load up to the so-called stall force, recent experiments also observed limited processive backwalking under superstall loads. This theoretical study seeks to elucidate the molecular mechanical basis for kinesin's steps over the full range of external loads that can possibly be applied to the dimer. We found that kinesin's load-resisting capacity is largely determined by a synergic ratchet-and-pawl mechanism inherent in the dimer. Load susceptibility of this inner molecular mechanical mechanism underlies kinesin's response to various levels of external loads. Computational implementation of the mechanism enabled us to rationalize major trends observed experimentally in kinesin's stalemate and consecutive back steps. The study also predicts several distinct features of kinesin's load-affected motility, which are seemingly counterintuitive but readily verifiable by future experiment.Comment: 44 pages, 6 figure

The Case for Absolute Spontaneity in Kant’s Critique of Pure Reason

Kant describes the understanding as a faculty of spontaneity. What this means is that our capacity to judge what is true is responsible for its own exercises, which is to say that we issue our judgments for ourselves. To issue our judgments for ourselves is to be self-conscious – i.e., conscious of the grounds upon which we judge. To grasp the spontaneity of the understanding, then, we must grasp the self-consciousness of the understanding. I argue that what Kant requires for explaining spontaneity is a conception of judgment as an intrinsic self-consciousness of the total unity of possible knowledge. This excludes what have been called ‘relative’ accounts of the spontaneity of the understanding, according to which our judgments are issued through a capacity fixed by external conditions. If so, then Kant conceives of understanding as entirely active. Or, to put it another way, he conceives of this capacity as absolutely spontaneous

Designing stem cell niches for differentiation and self-renewal

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche. Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro. In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries