Genome factor and gene pleiotropy hypotheses in protein evolution

<p>Abstract</p> <p/> <p>The debate of genomic correlations between sequence conservation, protein connectivity, gene essentiality and gene expression, has generated a number of new hypotheses that are challenging the classical framework of molecular evolution. For instance, the translational selection hypothesis claims that the determination of the rate of protein evolution is the protein stability to avoid the misfolding toxicity. In this short article, we propose that gene pleiotropy, the capacity for affecting multiple phenotypes, may play a vital role in molecular evolution. We discuss several approaches to testing this hypothesis.</p> <p>Reviewers</p> <p>This article was reviewed by Dr Eugene Koonin, Dr Arcady Mushegian and Dr Claus Wilke.</p

Modification of Transition-Metal Redox by Interstitial Water in Hexacyanometalate Electrodes for Sodium-Ion Batteries.

A sodium-ion battery (SIB) solution is attractive for grid-scale electrical energy storage. Low-cost hexacyanometalate is a promising electrode material for SIBs because of its easy synthesis and open framework. Most hexacyanometalate-based SIBs work with aqueous electrolyte, and interstitial water in the material has been found to strongly affect the electrochemical profile, but the mechanism remains elusive. Here we provide a comparative study of the transition-metal redox in hexacyanometalate electrodes with and without interstitial water based on soft X-ray absorption spectroscopy and theoretical calculations. We found distinct transition-metal redox sequences in hydrated and anhydrated NaxMnFe(CN)6·zH2O. The Fe and Mn redox in hydrated electrodes are separated and are at different potentials, leading to two voltage plateaus. On the contrary, mixed Fe and Mn redox in the same potential range is found in the anhydrated system. This work reveals for the first time how transition-metal redox in batteries is strongly affected by interstitial molecules that are seemingly spectators. The results suggest a fundamental mechanism based on three competing factors that determine the transition-metal redox potentials. Because most hexacyanometalate electrodes contain water, this work directly reveals the mechanism of how interstitial molecules could define the electrochemical profile, especially for electrodes based on transition-metal redox with well-defined spin states

Chiral-Flux-Phase-Based Topological Superconductivity in Kagome Systems with Mixed Edge Chiralities

Recent studies have attracted intense attention on the quasi-2D kagome superconductors $A\text{V}_3\text{Sb}_5$ ($A =$ K, Rb, and Cs) where the unexpected chiral flux phase (CFP) associates with the spontaneous time-reversal symmetry breaking in charge density wave (CDW) states. Here, commencing from the 2-by-2 CDW phases, we bridge the gap between topological superconductivity (TSC) and time-reversal asymmetric CFP in kagome systems. Several chiral TSC states featuring distinct Chern numbers emerge for an s-wave or a d-wave superconducting pairing symmetry. Importantly, these CFP-based TSC phases possess unique gapless edge modes with mixed chiralities (i.e., both positive and negative chiralities), but with the net chiralities consistent with the Bogoliubov-de Gennes Chern numbers. We further study the transport properties of a two-terminal junction, using Chern insulator or normal metal leads via atomic Green's function method with Landauer-B\"uttiker formalism. In both cases, the normal electron tunneling and the crossed Andreev reflection oscillate as the chemical potential changes, but together contribute to plateau transmissions (1 and 3/2, respectively). These behaviors can be regarded as the signature of a topological superconductor hosting edge states with mixed chiralities.Comment: 6 pages, 4 figure

Oxysterols and retinal degeneration

Retinal degeneration, characterised by the progressive death of retinal neurons, is the most common cause of visual impairment. Oxysterols are the cholesterol derivatives produced via enzymatic and/or free radical oxidation that regulate cholesterol homeostasis in the retina. Preclinical and clinical studies have suggested a connection between oxysterols and retinal degeneration. Here, we summarise early and recent work related to retina oxysterol-producing enzymes and the distribution of oxysterols in the retina. We examine the impact of loss of oxysterol-producing enzymes on retinal pathology and explore the molecular mechanisms associated with the toxic or protective roles of individual oxysterols in different types of retinal degeneration. We conclude that increased efforts to better understand the oxysterol-associated pathophysiology will help in the development of effective retinal degeneration therapies

Real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy

Purpose: To develop an algorithm for real-time volumetric image reconstruction and 3D tumor localization based on a single x-ray projection image for lung cancer radiotherapy. Methods: Given a set of volumetric images of a patient at N breathing phases as the training data, we perform deformable image registration between a reference phase and the other N-1 phases, resulting in N-1 deformation vector fields (DVFs). These DVFs can be represented efficiently by a few eigenvectors and coefficients obtained from principal component analysis (PCA). By varying the PCA coefficients, we can generate new DVFs, which, when applied on the reference image, lead to new volumetric images. We then can reconstruct a volumetric image from a single projection image by optimizing the PCA coefficients such that its computed projection matches the measured one. The 3D location of the tumor can be derived by applying the inverted DVF on its position in the reference image. Our algorithm was implemented on graphics processing units (GPUs) to achieve real-time efficiency. We generated the training data using a realistic and dynamic mathematical phantom with 10 breathing phases. The testing data were 360 cone beam projections corresponding to one gantry rotation, simulated using the same phantom with a 50% increase in breathing amplitude. Results: The average relative image intensity error of the reconstructed volumetric images is 6.9% +/- 2.4%. The average 3D tumor localization error is 0.8 mm +/- 0.5 mm. On an NVIDIA Tesla C1060 GPU card, the average computation time for reconstructing a volumetric image from each projection is 0.24 seconds (range: 0.17 and 0.35 seconds). Conclusions: We have shown the feasibility of reconstructing volumetric images and localizing tumor positions in 3D in near real-time from a single x-ray image.Comment: 8 pages, 3 figures, submitted to Medical Physics Lette