Buried and accessible surface area control intrinsic protein flexibility

Proteins experience a wide variety of conformational dynamics that can be crucial for facilitating their diverse functions. How is the intrinsic flexibility required for these motions encoded in their three-dimensional structures? Here, the overall flexibility of a protein is demonstrated to be tightly coupled to the total amount of surface area buried within its fold. A simple proxy for this, the relative solvent accessible surface area (Arel), therefore shows excellent agreement with independent measures of global protein flexibility derived from various experimental and computational methods. Application of Arel on a large scale demonstrates its utility by revealing unique sequence and structural properties associated with intrinsic flexibility. In particular, flexibility as measured by Arel shows little correspondence with intrinsic disorder, but instead tends to be associated with multiple domains and increased {\alpha}- helical structure. Furthermore, the apparent flexibility of monomeric proteins is found to be useful for identifying quaternary structure errors in published crystal structures. There is also a strong tendency for the crystal structures of more flexible proteins to be solved to lower resolutions. Finally, local solvent accessibility is shown to be a primary determinant of local residue flexibility. Overall this work provides both fundamental mechanistic insight into the origin of protein flexibility and a simple, practical method for predicting flexibility from protein structures.Comment: 36 pages, 11 figures, author's manuscript, accepted for publication in Journal of Molecular Biolog

Land Grant Application- Marsh, Joseph (Westminister)

Land grant application submitted to the Maine Land Office on behalf of Joseph Marsh for service in the Revolutionary War, by their widow Mary.https://digitalmaine.com/revolutionary_war_mass/1226/thumbnail.jp

Constraints on primordial magnetic fields from CMB distortions in the axiverse

Measuring spectral distortions of the cosmic microwave background (CMB) is attracting considerable attention as a probe of high energy particle physics in the cosmological context, since PIXIE and PRISM have recently been proposed. In this paper, CMB distortions due to resonant conversions between CMB photons and light axion like particles (ALPs) are investigated, motivated by the string axiverse scenario which suggests the presence of a plenitude of light axion particles. Since these resonant conversions depend on the strength of primordial magnetic fields, constraints on CMB distortions can provide an upper limit on the product of the photon-ALP coupling constant g and the comoving strength of primordial magnetic fields B. Potentially feasible constraints from PIXIE/PRISM can set a limit g B < 10^{-16} GeV^{-1} nG for ALP mass, m_\phi < 10^{-14} eV. Although this result is not a direct constraint on g and B, it is significantly tighter than the product of the current upper limits on g and B.Comment: 8 pages, 3 figure

Distributional Impacts of Country-of-Origin Labeling in the U.S. Meat Industry

Concerns about the negative effects of U.S. meat and livestock imports on domestic livestock prices have increased interest in country-of origin labeling (COOL) legislation. An equilibrium displacement model is used to estimate short-run and long-run changes in equilibrium prices and quantities of meat and livestock in the beef, pork, and poultry sectors resulting from the implementation of COOL. Retail beef and pork demand would have to experience a one-time, permanent increase of 4.05% and 4.45%, respectively, so that feeder cattle and hog producers do not lose producer surplus over a 10-year period.country-of-origin labeling, equilibrium displacement model, producer surplus, Agribusiness,

A 3.55 keV Photon Line and its Morphology from a 3.55 keV ALP Line

Galaxy clusters can efficiently convert axion-like particles (ALPs) to photons. We propose that the recently claimed detection of a 3.55--3.57 keV line in the stacked spectra of a large number of galaxy clusters and the Andromeda galaxy may originate from the decay of either a scalar or fermionic $7.1$ keV dark matter species into an axion-like particle (ALP) of mass $m_{a} \lesssim 6\cdot 10^{-11}~{\rm eV}$, which subsequently converts to a photon in the cluster magnetic field. In contrast to models in which the photon line arises directly from dark matter decay or annihilation, this can explain the anomalous line strength in the Perseus cluster. As axion-photon conversion scales as $B^2$ and cool core clusters have high central magnetic fields, this model can also explains the observed peaking of the line emission in the cool cores of the Perseus, Ophiuchus and Centaurus clusters, as opposed to the much larger dark matter halos. We describe distinctive predictions of this scenario for future observations.Comment: 6 page

Using deep mutational scanning to benchmark variant effect predictors and identify disease mutations

Abstract To deal with the huge number of novel protein‐coding variants identified by genome and exome sequencing studies, many computational variant effect predictors (VEPs) have been developed. Such predictors are often trained and evaluated using different variant data sets, making a direct comparison between VEPs difficult. In this study, we use 31 previously published deep mutational scanning (DMS) experiments, which provide quantitative, independent phenotypic measurements for large numbers of single amino acid substitutions, in order to benchmark and compare 46 different VEPs. We also evaluate the ability of DMS measurements and VEPs to discriminate between pathogenic and benign missense variants. We find that DMS experiments tend to be superior to the top‐ranking predictors, demonstrating the tremendous potential of DMS for identifying novel human disease mutations. Among the VEPs, DeepSequence clearly stood out, showing both the strongest correlations with DMS data and having the best ability to predict pathogenic mutations, which is especially remarkable given that it is an unsupervised method. We further recommend SNAP2, DEOGEN2, SNPs&GO, SuSPect and REVEL based upon their performance in these analyses

Galaxy UV-luminosity function and reionization constraints on axion dark matter

If the dark matter (DM) were composed of axions, then structure formation in the Universe would be suppressed below the axion Jeans scale. Using an analytic model for the halo mass function of a mixed DM model with axions and cold dark matter, combined with the abundance-matching technique, we construct the UV-luminosity function. Axions suppress high-$z$ galaxy formation and the UV-luminosity function is truncated at a faintest limiting magnitude. From the UV-luminosity function, we predict the reionization history of the universe and find that axion DM causes reionization to occur at lower redshift. We search for evidence of axions using the Hubble Ultra Deep Field UV-luminosity function in the redshift range $z=6$-$10$, and the optical depth to reionization, $\tau$, as measured from cosmic microwave background polarization. All probes we consider consistently exclude $m_a\lesssim 10^{-23}\text{ eV}$ from contributing more than half of the DM, with our strongest constraint ruling this model out at more than $8\sigma$ significance. In conservative models of reionization a dominant component of DM with $m_a=10^{-22}\text{ eV}$ is in $3\sigma$ tension with the measured value of $\tau$, putting pressure on an axion solution to the cusp-core problem. Tension is reduced to $2\sigma$ for the axion contributing only half of the DM. A future measurement of the UV-luminosity function in the range $z=10$-$13$ by JWST would provide further evidence for or against $m_a=10^{-22}\text{ eV}$. Probing still higher masses of $m_a=10^{-21}\text{ eV}$ will be possible using future measurements of the kinetic Sunyaev-Zel'dovich effect by Advanced ACTPol to constrain the time and duration of reionization.Comment: 17 pages, 8 figures, 2 tables. v2: Minor Changes. References added. Published in MNRA