Oxidative protein folding in eukaryotes: mechanisms and consequences

The endoplasmic reticulum (ER) provides an environment that is highly optimized for oxidative protein folding. Rather than relying on small molecule oxidants like glutathione, it is now clear that disulfide formation is driven by a protein relay involving Ero1, a novel conserved FAD-dependent enzyme, and protein disulfide isomerase (PDI); Ero1 is oxidized by molecular oxygen and in turn acts as a specific oxidant of PDI, which then directly oxidizes disulfide bonds in folding proteins. While providing a robust driving force for disulfide formation, the use of molecular oxygen as the terminal electron acceptor can lead to oxidative stress through the production of reactive oxygen species and oxidized glutathione. How Ero1p distinguishes between the many different PDI-related proteins and how the cell minimizes the effects of oxidative damage from Ero1 remain important open questions

Non-Hausdorff Symmetries of C*-algebras

Symmetry groups or groupoids of C*-algebras associated to non-Hausdorff spaces are often non-Hausdorff as well. We describe such symmetries using crossed modules of groupoids. We define actions of crossed modules on C*-algebras and crossed products for such actions, and justify these definitions with some basic general results and examples.Comment: very minor changes. To appear in Math. An

Tu Weiming, Liberal Education, and the Dialogue of the Humanities

This chapter discusses aspects of the work of Tu Weiming in relation to the idea of a liberal education. It does this in the context of broader questions about the nature, problems, and possibilities of comparative philosophy. Dialogue emerges in Tu’s work both as a substantive topic and as integral to aspects of his approach to philosophy and to his commitment to the dissemination of Confucian thought. In spite of Tu’s obvious success in many respects, some problems with this engagement with and in dialogue are identified, and these in turn are related to his treatment of questions of language and translation – in particular to his somewhat negative attitude to philosophy’s linguistic turn. The comparison of Confucian approaches with the idea of a liberal education enables reconsideration of ideas that are central to education, and in so doing the discussion demonstrates the value of comparative approaches in the study of education

Spin 3/2 dimer model

We present a parent Hamiltonian for weakly dimerized valence bond solid states for arbitrary half-integral S. While the model reduces for S=1/2 to the Majumdar-Ghosh Hamiltonian we discuss this model and its properties for S=3/2. Its degenerate ground state is the most popular toy model state for discussing dimerization in spin 3/2 chains. In particular, it describes the impurity induced dimer phase in Cr8Ni as proposed recently. We point out that the explicit construction of the Hamiltonian and its main features apply to arbitrary half-integral spin S.Comment: 5+ pages, 6 figures; to appear in Europhysics Letter

Trypanosoma brucei PRMT1 Is a Nucleic Acid Binding Protein with a Role in Energy Metabolism and the Starvation Stress Response.

In Trypanosoma brucei and related kinetoplastid parasites, transcription of protein coding genes is largely unregulated. Rather, mRNA binding proteins, which impact processes such as transcript stability and translation efficiency, are the predominant regulators of gene expression. Arginine methylation is a posttranslational modification that preferentially targets RNA binding proteins and is, therefore, likely to have a substantial impact on T. brucei biology. The data presented here demonstrate that cells depleted of T. brucei PRMT1 (TbPRMT1), a major type I protein arginine methyltransferase, exhibit decreased virulence in an animal model. To understand the basis of this phenotype, quantitative global proteomics was employed to measure protein steady-state levels in cells lacking TbPRMT1. The approach revealed striking changes in proteins involved in energy metabolism. Most prominent were a decrease in glycolytic enzyme abundance and an increase in proline degradation pathway components, changes that resemble the metabolic remodeling that occurs during T. brucei life cycle progression. The work describes several RNA binding proteins whose association with mRNA was altered in TbPRMT1-depleted cells, and a large number of TbPRMT1-interacting proteins, thereby highlighting potential TbPRMT1 substrates. Many proteins involved in the T. brucei starvation stress response were found to interact with TbPRMT1, prompting analysis of the response of TbPRMT1-depleted cells to nutrient deprivation. Indeed, depletion of TbPRMT1 strongly hinders the ability of T. brucei to form cytoplasmic mRNA granules under starvation conditions. Finally, this work shows that TbPRMT1 itself binds nucleic acids in vitro and in vivo, a feature completely novel to protein arginine methyltransferases.IMPORTANCETrypanosoma brucei infection causes human African trypanosomiasis, also known as sleeping sickness, a disease with a nearly 100% fatality rate when untreated. Current drugs are expensive, toxic, and highly impractical to administer, prompting the community to explore various unique aspects of T. brucei biology in search of better treatments. In this study, we identified the protein arginine methyltransferase (PRMT), TbPRMT1, as a factor that modulates numerous aspects of T. brucei biology. These include glycolysis and life cycle progression signaling, both of which are being intensely researched toward identification of potential drug targets. Our data will aid research in those fields. Furthermore, we demonstrate for the first time a direct association of a PRMT with nucleic acids, a finding we believe could translate to other organisms, including humans, thereby impacting research in fields as distant as human cancer biology and immune response modulation. Copyright © 2018 Kafková et al

Transcriptomics profiling of Indian mustard (Brassica juncea) under arsenate stress identifies key candidate genes and regulatory pathways

© 2015 Srivastava, Srivastava, Sablok, Deshpande and Suprasanna. Arsenic (As) is a non-essential element, a groundwater pollutant, whose uptake by plants produces toxic effects. The use of As-contaminated groundwater for irrigation can affect the crop productivity. Realizing the importance of the Brassica juncea as a crop plant in terms of oil-yield, there is a need to unravel mechanistic details of response to As stress and identify key functional genes and pathways. In this research, we studied time-dependent (4–96 h) transcriptome changes in roots and shoots of B. juncea under arsenate [As(V)] stress using Agilent platform. Among the whole transcriptome profiled genes, a total of 1,285 genes showed significant change in expression pattern upon As(V) exposure. The differentially expressed genes were categorized to various signaling pathways including hormones (jasmonate, abscisic acid, auxin, and ethylene) and kinases. Significant effects were also noticed on genes related to sulfur, nitrogen, CHO, and lipid metabolisms along with photosynthesis. Biochemical assays were conducted using specific inhibitors of glutathione and jasmonate biosynthesis, and kinases. The inhibitor studies revealed interconnection among sulfur metabolism, jasmonate, and kinase signaling pathways. In addition, various transposons also constituted a part of the altered transcriptome. Lastly, we profiled a set of key functional up- and down-regulated genes using real-time RT-PCR, which could act as an early indicators of the As stress

Front Stability in Mean Field Models of Diffusion Limited Growth

We present calculations of the stability of planar fronts in two mean field models of diffusion limited growth. The steady state solution for the front can exist for a continuous family of velocities, we show that the selected velocity is given by marginal stability theory. We find that naive mean field theory has no instability to transverse perturbations, while a threshold mean field theory has such a Mullins-Sekerka instability. These results place on firm theoretical ground the observed lack of the dendritic morphology in naive mean field theory and its presence in threshold models. The existence of a Mullins-Sekerka instability is related to the behavior of the mean field theories in the zero-undercooling limit.Comment: 26 pp. revtex, 7 uuencoded ps figures. submitted to PR

2D and 3D cubic monocrystalline and polycrystalline materials: their stability and mechanical properties

We consider 2- and 3-dimensional cubic monocrystalline and polycrystalline materials. Expressions for Young's and shear moduli and Poisson's ratio are expressed in terms of eigenvalues of the stiffness tensor. Such a form is well suited for studying properties of these mechanical characteristics on sides of the stability triangles. For crystalline high-symmetry directions lines of vanishing Poisson's ratio are found. These lines demarcate regions of the stability triangle into areas of various auxeticity properties. The simplest model of polycrystalline 2D and 3D cubic materials is considered. In polycrystalline phases the region of complete auxetics is larger than for monocrystalline materials.Comment: 9 pages, 3 figures, in proceedings of the Tenth International School on Theoretical Physics, Symmetry and Structural Properties of Condensed Matter, Myczkowce 200