Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

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A Molecular Switching Mechanism in Differentiation

Abstract. The selection of polarity in cells of the cambium in higher plants is a regulated process of development which results in horizontally or vertically oriented cells. A set of mathematical equations suggestive of this developmental dichotomy is given a new biologic interpretation. As a result, a molecular scheme capable of acting as a biochemical switch is suggested. The model features two structural protein monomers whose synthesis is controlled autogenously by feedback repression. The implications of this and similar mechanisms to other differentiating systems is discussed.     

Public perspectives on genetic biocontrol technologies for controlling invasive fish

Understanding people’s knowledge, attitudes, and concerns about genetic biocontrol can help researchers understand the challenges and opportunities that may be encountered during development of these technologies. This study conducted eight focus groups in the United States Great Lakes and Lake Champlain region to assess different stakeholders’ views about genetic biocontrol technology, factors affecting whether or not they support its use, and recommendations on how to proceed with its development. Stakeholders were excited about having a new invasive species control tool, but they were deeply concerned about potential unintended consequences. The primary concerns relate to ecological impacts, along with the cost of development and the possibility that such efforts will distract from other, ongoing control work. Participants made a number of recommendations to genetic biocontrol developers, including setting up regulatory systems, conducting independent cost benefit analyses and risk assessments, and engaging stakeholders throughout the development process.     

The XcpR protein of Pseudomonas aeruginosa dimerizes via its N-terminus

Extracellular protein secretion by the main terminal branch of the general secretory pathway in Pseudomonas aeruginosa requires a secretion machinery comprising the products of at least 12 genes. One of the components of this machinery, the XcpR protein, belongs to a large family of related proteins distinguished by the presence of a highly conserved nucleotide binding domain (Walker box A). The XcpR protein is essential for the process of extracellular secretion and amino acid substitutions within the Walker A sequence result in inactive XcpR. The same mutations exert a dominant negative effect on protein secretion when expressed in wild-type bacteria. Transdominance of XcpR mutants suggests that this protein is involved in interactions with other components of the secretion machinery or that it functions as a multimer. In this study, the amino-terminal portion of the cI repressor protein of phage λ was used as a reporter of dimerization in Escherichia coli following fusion to full-length as well as a truncated form of XcpR. The cI–XcpR hybrid proteins were able to dimerize, as demonstrated by the immunity of bacteria expressing them to killing by λ phage. The full-length XcpR as well as several deletion mutants of XcpR were able to disrupt the dimerization of the chimeric cI–XcpR protein. The disruption of cI–XcpR dimers using the deletion mutants of XcpR, combined with the analysis of their dominant negative effects on protein secretion, was used to map the minimal dimerization domain of XcpR, which is located within an 85 amino acid region in its N-terminal domain. Taken together, the data presented in this paper suggest that the XcpR protein dimerizes via its N-terminus and that this dimerization is essential for extracellular protein secretion.     

Models for contact-mediated pattern formation: cells that form parallel arrays

Kinetic continuum models are derived for cells that crawl over a 2D substrate, undergo random reorientation, and turn in response to contact with a neighbor. The integro-partial differential equations account for changes in the distribution of orientations in the population. It is found that behavior depends on parameters such as total mass, random motility, adherence, and sloughing rates, as well as on broad aspects of the contact response. Linear stability analysis, and numerical, and cellular automata simulations reveal that as parameters are varied, a bifurcation leads to loss of stability of a uniform (isotropic) steady state, in favor of an (anisotropic) patterned state in which cells are aligned in parallel arrays.     

Uptake and tissue distribution of manganese in the white sucker (Catostomus commersoni) under conditions of low pH

Concentrations of manganese were determined in the liver, kidney, muscle and bone of white suckers (Catostomus commersoni) from five acid (pH < 5.8), and two circumneutral lakes in south-central Ontario. Manganese tissue concentrations were greater in fish captured from the most acidified lakes with the greatest concentrations of dissolved manganese. These fish had increased concentrations of manganese in the liver, as indicated by a comparison of liver:kidney manganese concentration ratios among the seven fish populations. Tissue concentrations of manganese from all populations either were negatively correlated (P < 0.05) or remained constant with fish size indicating homeostatic regulation of this metal. Manganese concentrations of the benthic fauna were positively correlated to sediment concentrations (R=0.30). Lake sediment manganese concentrations were significantly correlated to maximum lake depth (R=0.80, P < 0.03), with the concentrations in the top 0–1 cm dependent on the redox conditions in the seven lakes. Based on the seven lakes studied, manganese concentrations in the benthic-feeding white sucker correlated better with dissolved manganese, than with either the concentrations in food or surficial sediments.     

A mathematical theory of size distributions in tissue culture

A model for growth of a tissue culture consisting of cell clumps is given. A set of equations for following the size distribution of clumps is used to determine total biomass accumulation. Existence and uniqueness of a solution to the equations is proved, and estimates of the biomass growth is given in a number of situations.     

Activation of m1 Muscarinic Acetylcholine Receptor Regulates τ Phosphorylation in Transfected PC12 Cells

Abstract: Hyperphosphorylated τ proteins are the principal fibrous component of the neurofibrillary tangle pathology in Alzheimer's disease. The possibility that τ phosphorylation is controlled by cell surface neurotransmitter receptors was examined in PC12 cells transfected with the gene for the rat m₁ muscarinic acetylcholine receptor. Stimulation of m₁ receptor in these cells with two acetylcholine agonists, carbachol and AF102B, decreased τ phosphorylation, as indicated by specific τ monoclonal antibodies that recognize phosphorylation-dependent epitopes and by alkaline phosphatase treatment. The muscarinic effect was both time and dose dependent. In addition, a synergistic effect on τ phosphorylation was found between treatments with muscarinic agonists and nerve growth factor. These studies provide the first evidence for a link between the cholinergic signal transduction system and the neuronal cytoskeleton that can be mediated by regulated phosphorylation of τ microtubule-associated protein.