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The volatility of an environment significantly impacts cooperative behavior. In environments where viability-threatening events occur on a shorter timescale than reproduction, it is reasonable to measure the costs and benefits of cooperation in terms of their direct effect on survival probability. Then, the number of offspring increases with lifespan. ML792 With such a model, is it possible for cooperation to be evolutionarily stable, and how does cooperation depend on the benefit and cost of such interactions, and the volatility of the environment? In this paper, we develop an N-player survivor's dilemma in which prisoner's dilemma payoffs in an iteration are survival rates, and expected lifespan is the measure of reproductive fitness. We investigate cost, benefit, and volatility parameter ranges where various cooperative behaviors may occur. We observe that free-riding results in indirect punishment as the cheated partner's early death leaves the defector vulnerable. For 2- and 3-player versions of the game, we identify parameter regions where the repeated game becomes equivalent to a Harmony, Stag Hunt, or Prisoner's Dilemma static game and discuss evolutionary stability. We find that with two individuals, the initial fraction of cooperators necessary for cooperation to be selected for decreases as the benefit to cost ratio increases and as environmental volatility decreases. With the presence of a third individual, there also exists a parameter region where cooperation can invade an initially all-defecting population.The ongoing global pandemic of infection disease COVID-19 caused by the 2019 novel coronavirus (SARS-COV-2, formerly 2019-nCoV) presents critical threats to public health and the economy. The genome of SARS-CoV-2 had been sequenced and structurally annotated, yet little is known of the intrinsic organization and evolution of the genome. To this end, we present a mathematical method for the genomic spectrum, a kind of barcode, of SARS-CoV-2 and common human coronaviruses. The genomic spectrum is constructed according to the periodic distributions of nucleotides and therefore reflects the unique characteristics of the genome. The results demonstrate that coronavirus SARS-CoV-2 exhibits predominant latent periodicity-2 regions of non-structural proteins 3, 4, 5, and 6. Further analysis of the latent periodicity-2 regions suggests that the dinucleotide imbalances are increased during evolution and may confer the evolutionary fitness of the virus. Especially, SARS-CoV-2 isolates have increased latent periodicity-2 and periodicity-3 during COVID-19 pandemic. The special strong periodicity-2 regions and the intensity of periodicity-2 in the SARS-CoV-2 whole genome may become diagnostic and pharmaceutical targets in monitoring and curing the COVID-19 disease.Systemic light chain (AL) amyloidosis is a fatal protein misfolding disease in which excessive secretion, misfolding, and subsequent aggregation of free antibody light chains eventually leads to deposition of amyloid plaques in various organs. Patient-specific mutations in the antibody VL domain are closely linked to the disease, but the molecular mechanisms by which certain mutations induce misfolding and amyloid aggregation of antibody domains are still poorly understood. Here, we compare a patient VL domain with its non-amyloidogenic germline counterpart and show that, out of the five mutations present, two of them strongly destabilize the protein and induce amyloid fibril formation. Surprisingly, the decisive, disease-causing mutations are located in the highly variable complementarity determining regions (CDRs) but exhibit a strong impact on the dynamics of conserved core regions of the patient VL domain. This effect seems to be based on a deviation from the canonical CDR structures of CDR2 and CDR3 induced by the substitutions. The amyloid-driving mutations are not necessarily involved in propagating fibril formation by providing specific side chain interactions within the fibril structure. Rather, they destabilize the VL domain in a specific way, increasing the dynamics of framework regions, which can then change their conformation to form the fibril core. These findings reveal unexpected influences of CDR-framework interactions on antibody architecture, stability, and amyloid propensity.β2-Microglobulin (β2m) is the causative protein of dialysis-related amyloidosis. Its unfolding mainly proceeds along the pathway of NC →UC ⇄ UT, whereas refolding follows the UT → IT (→NT) →NC pathway, in which N, I, and U are the native, intermediate, and unfolded states, respectively, with the Pro32 peptidyl-prolyl bond in cis or trans conformation as indicated by the subscript. It is noted that the IT state is a putative amyloidogenic precursor state. Several aggregation-prone variants of β2m have been reported to date. One of these variants is D76N β2m, which is a naturally occurring amyloidogenic mutant. To elucidate the molecular mechanisms contributing to the enhanced amyloidogenicity of the mutant, we investigated the equilibrium and kinetic transitions of pressure-induced folding/unfolding equilibria in the wild type and D76N mutant by monitoring intrinsic tryptophan and 1-anilino-8-naphthalene sulfonate fluorescence. An analysis of kinetic data revealed that the different folding/unfolding behaviors of the wild type and D76N mutant were due to differences in the activation energy between the unfolded and the intermediate states as well as stability of the native state, leading to more rapid accumulation of IT state for D76N in the refolding process. In addition, the IT state was found to assume more hydrophobic nature. These changes induced the enhanced amyloidogenicity of the D76N mutant and the distinct pathogenic symptoms of patients. Our results suggest that the stabilization of the native state will be an effective approach for suppressing amyloid fibril formation of this mutant.Members of the ADF/cofilin family of regulatory proteins bind actin filaments cooperatively, locally change actin subunit conformation and orientation, and sever filaments at 'boundaries' between bare and cofilin-occupied segments. A cluster of bound cofilin introduces two distinct classes of boundaries due to the intrinsic polarity of actin filaments, one at the 'pointed' end-side and the other at the 'barbed' end-side of the cluster; severing occurs more readily at the pointed end side of the cluster ('fast-severing' boundary) than the barbed end side ('slow-severing' boundary). A recent electron-cryomicroscopy (cryo-EM) model of the slow-severing boundary revealed structural 'defects' at the interface that potentially contribute to severing. However, the structure of the fast-severing boundary remains uncertain. Here, we use extensive molecular dynamics simulations to produce atomic resolution models of both severing boundaries. Our equilibrated simulation model of the slow-severing boundary is consistent with the cryo-EM structural model.
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