Modeling the effects of contact-tracing apps on the spread of the coronavirus disease: mechanisms, conditions, and efficiency

This study simulates the spread of the coronavirus disease (COVID-19) using a detailed agent-based model and the census data of Japan to provide a comprehensive analysis of the effects of contact-tracing apps. The results reveal some crucial characteristics of these apps. First, with regard to contacts of those diagnosed with COVID-19, the apps that require them to be quarantined upon receiving an alert are successful in achieving containment; however, the apps that require them to get tested have a limited curve-flattening effect. Second, the former category of apps perform better than the latter because they quarantine those who are infected but have not become infectious yet; these are individuals who cannot be detected by the current testing technology. Third, if the download rate of the apps is extremely high, the apps that require quarantine achieve containment with a small number of quarantined people, thereby indicating high efficiency. Finally, given a fixed download rate, increasing the number of tests per day enhances the effectiveness of the apps, although the degree of improved effectiveness is not proportional to the change in the number of tests

The effectiveness of mobility control, shortening of restaurants’ opening hours, and working from home in Japan

Since the occurrence of the first outbreak of COVID-19 in a year ago, various interventions have been implemented to prevent its spread across the globe. Using an agent-based model that describes the attributes and mobility of the Japanese population, the present research evaluates the effectiveness of mobility control, shortening of restaurants’ opening hours, and working from home. Results show that severe mobility control that restricts 90% of domestic travels on a national level decreases the peak cases by a half, compared to when no interventions are undertaken. The effectiveness of this strategy is more than 20% compared to all other types of contact restrictions. Therefore, mobility control thatonlylimitsmovementfromandtohighlypopulatedregionsisaseffectiveas nationwide travel restrictions. This finding rationalizes region-specific mobility control that does not restrict travel among less populated regions, which are less conducive to the spread of the virus. Furthermore, shortening of restaurants’ opening hours is the most effective of all interventions taken in a state of emergency, thus, it should be utilized even after the emergency is lifted. However, working from home has limited effects

Innate Invariant NKT Cells Recognize Mycobacterium tuberculosis–Infected Macrophages, Produce Interferon-γ, and Kill Intracellular Bacteria

Cellular immunity to Mycobacterium tuberculosis (Mtb) requires a coordinated response between the innate and adaptive arms of the immune system, resulting in a type 1 cytokine response, which is associated with control of infection. The contribution of innate lymphocytes to immunity against Mtb remains controversial. We established an in vitro system to study this question. Interferon-γ is produced when splenocytes from uninfected mice are cultured with Mtb-infected macrophages, and, under these conditions, bacterial replication is suppressed. This innate control of bacterial replication is dependent on CD1d-restricted invariant NKT (iNKT) cells, and their activation requires CD1d expression by infected macrophages as well as IL-12 and IL-18. We show that iNKT cells, even in limiting quantities, are sufficient to restrict Mtb replication. To determine whether iNKT cells contribute to host defense against tuberculosis in vivo, we adoptively transferred iNKT cells into mice. Primary splenic iNKT cells obtained from uninfected mice significantly reduce the bacterial burden in the lungs of mice infected with virulent Mtb by the aerosol route. Thus, iNKT cells have a direct bactericidal effect, even in the absence of synthetic ligands such as α-galactosylceramide. Our finding that iNKT cells protect mice against aerosol Mtb infection is the first evidence that CD1d-restricted NKT cells mediate protection against Mtb in vivo

Christopher Simpson The Division-Viol, or The Art of PLAYING Ex tempore upon a GROUND. EDITIO SECVNDA Part III "The Method of ordering Division to a Ground" (2)

本訳稿はChristopher Simpson (1605頃－1669) 著 The Division-Viol, or, The Art of PLAYING Ex tempore upon a GROUND. DIVIDED INTO THREE PARTS. EDITIO SECVNDA, London, 1665 のPart III "The Method of ordering Division to a Ground" より§7～§12(pp.42-56)の全訳である

Christopher Simpson The Division-Viol, or The Art of PLAYING Ex tempore upon a GROUND. EDITIO SECVNDA Part III "The Method of ordering Division to a Ground" (3)

本訳稿はChristopher Simpson (1605頃－1669) 著 The Division-Viol, or, The Art of PLAYING Ex tempore upon a GROUND. DIVIDED INTO THREE PARTS. EDITIO SECVNDA, London, 1665 のPart III "The Method of ordering Division to a Ground" より§13～§16(pp.57-61)の全訳である

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters

乳がんの再発を起こす原因細胞を解明. 京都大学プレスリリース. 2023-11-16.The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain–containing ion transport regulator 3 (FXYD3), a component of the Na⁺/K⁺ pump. Accordingly, FXYD3⁺ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3⁺ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3⁺ CSCs were sensitive to senolytic Na⁺/K⁺ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3⁺ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na⁺/K⁺ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis

Intergenerational Bubbles of Beliefs for Sustainability

We constructed a simple model of a dynamic economy in which the current generation chooses to excessively consume, thereby rendering society unsustainable. In such an economy, we assumed that a notional bubbly asset emerges, and its value grows if the current generation conserves adequate resources for future generations. Provided that the bubbly asset is considered valuable, the current generation chooses to conserve resources, rendering the economy sustainable. The condition for sustainability is that the value of this asset grows intergenerationally and indefinitely. The asset represents a belief system, such as a religious doctrine or a political ideology. Results imply that, to restore sustainability, a new intergenerational belief system must be identified, and its value grows indefinitely

Mucosal-Associated Invariant T Cells in Autoimmune Diseases

Mucosal-associated invariant T (MAIT) cells are innate T cells restricted by MHC-related molecule 1 (MR1). MAIT cells express semi-invariant T-cell receptors TRAV1-2-TRAJ33/12/20 in humans and TRAV1-TRAJ33 in mice. MAIT cells recognize vitamin B2 biosynthesis derivatives presented by MR1. Similar to other innate lymphocytes, MAIT cells are also activated by cytokines in the absence of exogenous antigens. MAIT cells have the capacity to produce cytokines, such as IFNγ, TNFα, and IL-17, and cytotoxic proteins, including perforin and granzyme B. MAIT cells were originally named after their preferential location in the mucosal tissue of the gut, but they are also abundant in other peripheral organs, including the liver and lungs. In humans, the frequency of MAIT cells is high in peripheral blood, and these cells constitute approximately 5% of circulating CD3+ cells. Their abundance in tissues and rapid activation following stimulation have led to great interest in their function in various types of immune diseases. In this review, first, we will briefly introduce key information of MAIT cell biology required for better understating their roles in immune responses, and then describe how MAIT cells are associated with autoimmune and other immune diseases in humans. Moreover, we will discuss their functions based on information from animal models of autoimmune and immunological diseases