7,351 research outputs found
Inferring the Rate-Length Law of Protein Folding
We investigate the rate-length scaling law of protein folding, a key
undetermined scaling law in the analytical theory of protein folding. We
demonstrate that chain length is a dominant factor determining folding times,
and that the unambiguous determination of the way chain length corre- lates
with folding times could provide key mechanistic insight into the folding
process. Four specific proposed laws (power law, exponential, and two stretched
exponentials) are tested against one an- other, and it is found that the power
law best explains the data. At the same time, the fit power law results in
rates that are very fast, nearly unreasonably so in a biological context. We
show that any of the proposed forms are viable, conclude that more data is
necessary to unequivocally infer the rate-length law, and that such data could
be obtained through a small number of protein folding experiments on large
protein domains
Intermolecular correlations are necessary to explain diffuse scattering from protein crystals
Conformational changes drive protein function, including catalysis,
allostery, and signaling. X-ray diffuse scattering from protein crystals has
frequently been cited as a probe of these correlated motions, with significant
potential to advance our understanding of biological dynamics. However, recent
work challenged this prevailing view, suggesting instead that diffuse
scattering primarily originates from rigid body motions and could therefore be
applied to improve structure determination. To investigate the nature of the
disorder giving rise to diffuse scattering, and thus the potential applications
of this signal, a diverse repertoire of disorder models was assessed for its
ability to reproduce the diffuse signal reconstructed from three protein
crystals. This comparison revealed that multiple models of intramolecular
conformational dynamics, including ensemble models inferred from the Bragg
data, could not explain the signal. Models of rigid body or short-range
liquid-like motions, in which dynamics are confined to the biological unit,
showed modest agreement with the diffuse maps, but were unable to reproduce
experimental features indicative of long-range correlations. Extending a model
of liquid-like motions to include disorder across neighboring proteins in the
crystal significantly improved agreement with all three systems and highlighted
the contribution of intermolecular correlations to the observed signal. These
findings anticipate a need to account for intermolecular disorder in order to
advance the interpretation of diffuse scattering to either extract biological
motions or aid structural inference.Comment: 12 pages, 5 figures (not including Supplementary Information
Tributes to Professor Cyril A. Fox, Jr.
Cy Fox often forgets that he was supposed to be “only” an academic. For three decades, as he helped thousands of law students through the intricacies of the Rule in Shelley’s Case, or watched them calculate a “life in being plus twenty one years” for the Rule Against Perpetuities, he failed to appreciate that law school was supposed to be an amalgam of theory and confusion, not the place for his teaching law students about helping real people solve real life problems
Direct radiative capture of p-wave neutrons
The neutron direct radiative capture (DRC) process is investigated,
highlighting the role of incident p-wave neutrons. A set of calculations is
shown for the 12-C(n,gamma) process at incoming neutron energies up to 500 keV,
a crucial region for astrophysics. The cross section for neutron capture
leading to loosely bound s, p and d orbits of 13-C is well reproduced by the
DRC model demonstrating the feasibility of using this reaction channel to study
the properties of nuclear wave functions on and outside the nuclear surface. A
sensitivity analysis of the results on the neutron-nucleus interaction is
performed for incident s- as well as p-waves. It turned out that the DRC cross
section for p-wave neutrons is insensitive to this interaction, contrary to the
case of incident s-wave neutrons.
PACS number(s): 25.40Lw,21.10Gv,23.40.HcComment: 16 pages, REVTeX file, PostScript file, .dvi fil
Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment.
Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b+ Ly6G+ neutrophils into the spinal cord. Targeting neutrophils resulted in a reduction in demyelination arguing for a role for these cells in myelin damage. Collectively, these findings emphasize that CXCL1-mediated attraction of neutrophils into the CNS augments demyelination suggesting that this signaling pathway may offer new targets for therapeutic intervention
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