Anti-inflammatory effects of olanexidine gluconate on oral epithelial cells

Background: Periodontitis is a biofilm-induced chronic inflammatory condition of the periodontium. Chemokines produced by the innate and acquired immune responses play a significant role in disease progression. Reducing biofilm formation and inflammatory response caused by chemokines is vital for preventing and treating periodontitis. Previously, we observed that treatment with 0.1% olanexidine gluconate (OLG) inhibited biofilm formation on saliva-coated hydroxyapatite. This study aimed to evaluate the antiinflammatory effect of OLG on oral epithelial cells. Methods: We examined if OLG could inhibit the inflammatory responses caused by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and heat-killed P. gingivalis in immortalized human oral keratinocytes (RT7). Results: Treatment of RT7 with non-cytotoxic OLG concentrations significantly inhibited the production of inflammatory chemokines such as interleukin 8 (IL-8), C-C motif ligand 20 (CCL20), and growth-related oncogene protein-α (GRO-α), which are stimulated by P. gingivalis LPS in a concentration-dependent manner. Moreover, the inhibitory effects were observed regardless of the treatment time with P. gingivalis LPS (6, 12, or 24 h). OLG also significantly inhibited chemokine production stimulated by heat-killed P. gingivalis. Conclusions: The findings of this study suggest that treatment with OLG inhibits chronic inflammatory reactions in oral mucosal cells, such as periodontitis, caused by oral bacteria

A single ‘weight-lifting’ game covers all kinds of games

Game theory has been studied extensively to answer why cooperation is promoted in human and animal societies. All games are classified into five games: the Prisoner’s Dilemma, chicken game (including hawk?dove game), stag hunt game and two trivial games of either all cooperation or all defect, which are studied separately. Here, we propose a new game that covers all five game categories: the weight-lifting game. The player choose either to (1) carry a weight (cooperate: pay a cost) or (2) pretend to carry it (defect: pay no cost). The probability of success in carrying the weight depends on the number of cooperators, and the players either gain the success reward or pay the failure penalty. All five game categories appear in this game depending on the success probabilities for the number of cooperators. We prove that this game is exactly equivalent to the combination of all five games in terms of a pay-off matrix. This game thus provides a unified framework for studying all five types of games

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Bankruptcy is an inevitable fate of repeated investments with leverage

Due to the globalization and computerization of financial and economic activities, numerous repetitive leveraged investments have become possible in stock markets and currency exchanges. In reality, repeated leveraged investments up to 100 times/day are possible via online access. With computer-aided programs, this repetition number may easily increase 1000 times/day. The possibility of bankruptcy in repeated leveraged investments has never been considered in actual practices because the probability of bankruptcy in a single investment trial is almost negligible. Here, we show that the extremely numerous repetitions have a considerable chance of bankruptcy overall, even if the probability of bankruptcy for a single investment is extremely close to zero. The exact relationship between the repetitions and the probability of bankruptcy is approximated well by n(0.63)?=?m, where 10n is the number of repetitions, 10-m is the bankruptcy probability of a single investment, and n(0.63) is the 63% chance of bankruptcy. Thus, extremely rare events can always lead to bankruptcy in continuously repeated investment, even if the possibility of such an event is almost null. We suggest that the avoidance measure of bankruptcy is necessary in numerous repeated investments even if a single trial is almost certain to win

A single ‘weight-lifting’ game covers all kinds of games

Game theory has been studied extensively to answer why cooperation is promoted in human and animal societies. All games are classified into five games: the Prisoner’s Dilemma, chicken game (including hawk–dove game), stag hunt game and two trivial games of either all cooperation or all defect, which are studied separately. Here, we propose a new game that covers all five game categories: the weight-lifting game. The player choose either to (1) carry a weight (cooperate: pay a cost) or (2) pretend to carry it (defect: pay no cost). The probability of success in carrying the weight depends on the number of cooperators, and the players either gain the success reward or pay the failure penalty. All five game categories appear in this game depending on the success probabilities for the number of cooperators. We prove that this game is exactly equivalent to the combination of all five games in terms of a pay-off matrix. This game thus provides a unified framework for studying all five types of games

Energetic requirements of the transition from solitary to group living

Synergy is known to be vital for the group collaboration among non-kin individuals. In order to evaluate the condition of synergy that initiates group living, we build a model of food intake based on three types of functional response. We show that type III functional response is prerequisite for synergy to allow group living.The optimal number of gathering individuals can be also evaluated from Type III functional response curve. Type III functional response consists of terms depending linearly and bilinearly on the number of individuals and the bilinear term represents synergy. For a fixed value of the linear coefficient, there are upper and lower boundaries of the bilinear coefficient for synergistic collaboration. The dilution effect can be incorporated into the model through the functional response of the predator. Thus, the functional response of the predator as well as that of the prey contribute to the group living of the prey. Our model shows that group livings can be categorized into three types, namely those due to (1) synergy effect of the own group, (2) dilution effect against predators, and (3) both effects contributing together. The predator\u27s functional response plays a decisive role in the last two types, where the predator response should be of anti-Type III (i.e., Type II)

Tankyrase Regulates Neurite Outgrowth through Poly(ADP-ribosyl)ation-Dependent Activation of β-Catenin Signaling

Poly(ADP-ribosyl)ation is a post-translational modification of proteins by transferring poly(ADP-ribose) (PAR) to acceptor proteins by the action of poly(ADP-ribose) polymerase (PARP). Two tankyrase (TNKS) isoforms, TNK1 and TNK2 (TNKS1/2), are ubiquitously expressed in mammalian cells and participate in diverse cellular functions, including wnt/β-catenin signaling, telomere maintenance, glucose metabolism and mitosis regulation. For wnt/β-catenin signaling, TNKS1/2 catalyze poly(ADP-ribosyl)ation of Axin, a key component of the β-catenin degradation complex, which allows Axin’s ubiquitination and subsequent degradation, thereby activating β-catenin signaling. In the present study, we focused on the functions of TNKS1/2 in neuronal development. In primary hippocampal neurons, TNKS1/2 were detected in the soma and neurites, where they co-localized with PAR signals. Treatment with XAV939, a selective TNKS1/2 inhibitor, suppressed neurite outgrowth and synapse formation. In addition, XAV939 also suppressed norepinephrine uptake in PC12 cells, a rat pheochromocytoma cell line. These effects likely resulted from the inhibition of β-catenin signaling through the stabilization of Axin, which suggests TNKS1/2 enhance Axin degradation by modifying its poly(ADP-ribosyl)ation, thereby stabilizing wnt/β-catenin signaling and, in turn, promoting neurite outgrowth and synapse formation