47 research outputs found

    Dimensional Reduction in Evolving Spin-Glass Model : Correlation of Phenotypic Responses to Environmental and Mutational Changes

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    The evolution of high-dimensional phenotypes is investigated using a statistical physics model consisting of interacting spins, in which phenotypes, genotypes, and environments are represented by spin configurations, interaction matrices, and external fields, respectively. We found that phenotypic changes upon diverse environmental change and genetic variation are highly correlated across all spins, consistent with recent experimental observations of biological systems. The dimension reduction in phenotypic changes is shown to be a result of the evolution of the robustness to thermal noise, achieved at the replica symmetric phase.UTokyo FOCUS Press releases "Limits on evolution revealed by statistical physics" https://www.u-tokyo.ac.jp/focus/en/press/z0508_00115.htm

    Replica symmetry breaking in an adiabatic spin-glass model of adaptive evolution

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    We study evolutionary canalization using a spin-glass model with replica theory, where spins and their interactions are dynamic variables whose configurations correspond to phenotypes and genotypes, respectively. The spins are updated under temperature T_S, and the genotypes evolve under temperature T_J, according to the evolutionary fitness. It is found that adaptation occurs at T_S < T_S^{RS}, and a replica symmetric phase emerges at T_S^{RSB} < T_S < T_S^{RS}. The replica symmetric phase implies canalization, and replica symmetry breaking at lower temperatures indicates loss of robustness.Comment: 5pages, 2 figure

    Funnel landscape and mutational robustness as a result of evolution under thermal noise

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    In biological systems, expression dynamics to shape a fitted phenotype for function has evolved through mutations to genes, as observed in the evolution of funnel landscape in protein. We study this evolutionary process with a statistical-mechanical model of interacting spins, where the fitted phenotype is represented by a configuration of a given set of "target spins" and interaction matrix J among spins is genotype evolving over generations. The expression dynamics is given by stochastic process with temperature T_S to decrease energy for a given set of J. The evolution of J is also stochastic with temperature T_J, following mutation in J and selection based on a fitness given by configurations of the target spins. Below a certain temperature T_S^{c2}, the highly adapted J evolves, whereasanother phase transition characterised by frustration occurs at T_S^{c1}<T_S^{c2}. At temperature lower than T_S^{c1}, the Hamiltonian exhibits a spin-glass like phase, where the dynamics requires long time steps to produce the fitted phenotype, and the fitness often decreases drastically by single mutation. In contrast, in the intermediate temperature phase between T_S^{c1} and T_S^{c2}, the evolved genotypes, that have no frustration around the target spins (we call "local Mattis state"), give a funnel-like rapid expression dynamics and are robust to mutation. These results imply that evolution under thermal noise beyond a certain level leads to funnel dynamics and mutational robustness. We will explain its mechanism with the statistical-mechanical method.Comment: 4pages, 4figure

    The astrocytic TRPA1 channel mediates an intrinsic protective response to vascular cognitive impairment via LIF production

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    認知症に対する新たな生体防御機構の発見 --アストロサイトのTRPA1活性化が、LIF産生を介して白質傷害や認知機能障害を防ぐ--. 京都大学プレスリリース. 2023-07-24.Vascular cognitive impairment (VCI) refers to cognitive alterations caused by vascular disease, which is associated with various types of dementia. Because chronic cerebral hypoperfusion (CCH) induces VCI, we used bilateral common carotid artery stenosis (BCAS) mice as a CCH-induced VCI model. Transient receptor potential ankyrin 1 (TRPA1), the most redox-sensitive TRP channel, is functionally expressed in the brain. Here, we investigated the pathophysiological role of TRPA1 in CCH-induced VCI. During early-stage CCH, cognitive impairment and white matter injury were induced by BCAS in TRPA1-knockout but not wild-type mice. TRPA1 stimulation with cinnamaldehyde ameliorated BCAS-induced outcomes. RNA sequencing analysis revealed that BCAS increased leukemia inhibitory factor (LIF) in astrocytes. Moreover, hydrogen peroxide-treated TRPA1-stimulated primary astrocyte cultures expressed LIF, and culture medium derived from these cells promoted oligodendrocyte precursor cell myelination. Overall, TRPA1 in astrocytes prevents CCH-induced VCI through LIF production. Therefore, TRPA1 stimulation may be a promising therapeutic approach for VCI

    Insulinoma with symptoms of suspected transient ischemic attack : A case report

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    We report the case of a67-year-old woman who had symptoms suggestive of a transient ischemic attack(TIA), such as lightheadedness and transient visual changes before meals for 4 months. She experienced altered consciousness before lunch and was taken to the emergency room2weeks ago. She had repeated hypoglycemia with a blood glucose level of 31 mg/dL. Insulin secretion was not suppressed, with an immunoreactive insulin level of 14.0 μU/mL and connecting peptide immunoreactivity of 1.83 ng/mL for occasional blood glucose levels of 49 mg/dL. Dynamic CT revealed a 17‐mm mass enhanced during the arterial phase in the pancreatic uncinate process, suggestive of a pancreatic neuroendocrine tumor. A selective arterial secretagogue(calcium)injection test revealed the localization of insulinoma in the head of the pancreas. Therefore, pancreatoduodenectomy was performed. Hyperglycemia occurred after the surgery, and it was judged that the insulinoma was resected. This case showed TIA-like symptoms without signs of sympathetic overdrive associated with hypoglycemia. Thus, the diagnosis was delayed. Insulinoma may present with symptoms of neuroglycopenia but not autonomic activity due to hypoglycemia. Insulinoma should be distinguished in patients with unknown neurological symptoms since neuroglycopenia caused by insulinoma is diverse

    A cross-sectional study on maternal anxiety levels after cytomegalovirus screening

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    Purpose: we aimed to estimate the anxiety levels of pregnant women following maternal serum screening for CMV infection. Materials and methods: In this case-control study conducted from April 2016 to June 2017, we enrolled all pregnant women referred to our hospital who were CMV immunoglobulin (Ig) M antibody positive (IgM-positive group, n = 51); further, those who were CMV IgG positive but IgM negative (IgM-negative group, n = 51) during the same period were included as study controls. Data were collected on patient characteristics, CMV IgM levels, and whether patients were accompanied by their partners during the first hospital visit after CMV IgM testing. The State-Trait Anxiety Inventory was used to assess anxiety levels. Results: Both groups were age matched [mean age (years): IgM-positive, 30 ± 4.2 and IgM-negative, 29.9 ± 4.6]. The mean state-anxiety score was higher in the IgM-positive group (53 ± 9.6) than in the IgM-negative group (38.5 ± 7.0, p < .05) with no between-group differences in trait-anxiety scores. Similarly, a higher number of women were accompanied by their partners in the IgM-positive group. The state-anxiety scores and CMV IgM levels were not correlated in the IgM-positive group. Conclusion: Counseling support is essential for IgM-positive pregnant women following serum screening, and the screening should be avoided if support systems are unavailable

    TRPM2 Contributes to Inflammatory and Neuropathic Pain through the Aggravation of Pronociceptive Inflammatory Responses in Mice.

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    慢性痛の原因となる神経炎症応答の増悪機構を解明-新しい鎮痛薬開発の可能性-. 京都大学プレスリリース. 2012-03-15.Accumulating evidence suggests that neuroimmune interactions contribute to pathological pain. Transient receptor potential melastatin 2 (TRPM2) is a nonselective Ca(2+)-permeable cation channel that acts as a sensor for reactive oxygen species. TRPM2 is expressed abundantly in immune cells and is important in inflammatory processes. The results of the present study show that TRPM2 plays a crucial role in inflammatory and neuropathic pain. While wild-type and TRPM2 knock-out mice showed no difference in their basal sensitivity to mechanical and thermal stimulation, nocifensive behaviors in the formalin test were reduced in TRPM2 knock-out mice. In carrageenan-induced inflammatory pain and sciatic nerve injury-induced neuropathic pain models, mechanical allodynia and thermal hyperalgesia were attenuated in TRPM2 knock-out mice. Carrageenan-induced inflammation and sciatic nerve injury increased the expression of TRPM2 mRNA in the inflamed paw and around the injured sciatic nerve, respectively. TRPM2 deficiency diminished the infiltration of neutrophils and the production of chemokine (C-X-C motif) ligand-2 (CXCL2), a major chemokine that recruits neutrophils, but did not alter the recruitment of F4/80-positive macrophages in the inflamed paw or around the injured sciatic nerve. Microglial activation after nerve injury was suppressed in the spinal cord of TRPM2 knock-out mice. Furthermore, CXCL2 production and inducible nitric oxide synthase induction were diminished in cultured macrophages and microglia derived from TRPM2 knock-out mice. Together, these results suggest that TRPM2 expressed in macrophages and microglia aggravates peripheral and spinal pronociceptive inflammatory responses and contributes to the pathogenesis of inflammatory and neuropathic pain
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