The planarian Dugesia japonica can regenerate a complete individual from a head, trunk or tail fragment via activation of somatic pluripotent stem cells. About a century ago, Thomas Hunt Morgan attempted to explain the extraordinary regenerative ability of planarians by positing two opposing morphogenetic gradients of formative "head stuff" and "tail stuff" along the anterior-posterior axis. However, Morgan's hypothesis remains open to debate. Here we show that extracellular signal-related kinase (ERK) and Wnt/β-catenin signalling pathways establish a solid framework for planarian regeneration. Our data suggest that ERK signalling forms a spatial gradient in the anterior region during regeneration. The fibroblast growth factor receptor-like gene nou-darake (which serves as an output of ERK signalling in the differentiating head) and posteriorly biased β-catenin activity negatively regulate ERK signalling along the anterior-posterior axis in distinct manners, and thereby posteriorize regenerating tissues outside the head region to reconstruct a complete head-to-tail axis. On the basis of this knowledge about D. japonica, we proposed that β-catenin signalling is responsible for the lack of head-regenerative ability of tail fragments in the planarian Phagocata kawakatsui, and our confirmation thereof supports the notion that posterior β-catenin signalling negatively modulates the ERK signalling involved in anteriorization across planarian species. These findings suggest that ERK signalling has a pivotal role in triggering globally dynamic differentiation of stem cells in a head-to-tail sequence through a default program that promotes head tissue specification in the absence of posteriorizing signals. Thus, we have confirmed the broad outline of Morgan's hypothesis, and refined it on the basis of our proposed default property of planarian stem cells.

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We established a laboratory clonal strain of freshwater planarian (Dugesia japonica) that was derived from a single individual and that continued to undergo autotomous asexual reproduction for more than 20 years, and we performed large-scale genome sequencing and transcriptome analysis on it. Despite the fact that a completely clonal strain of the planarian was used, an unusually large number of mutations were detected. To enable quantitative genetic analysis of such a unique organism, we developed a new model called the Reference Gene Model, and used it to conduct large-scale transcriptome analysis. The results revealed large numbers of mutations not only outside but also inside gene-coding regions. Non-synonymous SNPs were detected in 74% of the genes for which valid ORFs were predicted. Interestingly, the high-mutation genes, such as metabolism- and defense-related genes, were correlated with genes that were previously identified as diverse genes among different planarian species. Although a large number of amino acid substitutions were apparently accumulated during asexual reproduction over this long period of time, the planarian maintained normal body-shape, behaviors, and physiological functions. The results of the present study reveal a unique aspect of asexual reproduction.

Serological evaluation with SARS-CoV-2 specific IgG antibody will be an alternative way to know the pandemic of novel coronavirus disease (COVID-19) if the capacity for diagnostic PCR test is limited. The point-of-care test to detect SARS-CoV-2 specific IgG antibody in peripheral blood (n =202) was performed in two community clinics in Tokyo, Japan. The overall

Introduction: The primary care clinic plays a major role in triage for coronavirus disease 2019 (COVID-19), where seroprevalence in the setting of primary care clinic remains less clear. As a point-of-care immunodiagnostic test for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the serosurvey represents an alternative to the polymerase chain reaction (PCR) test to measure the magnitude of COVID-19 outbreak in the communities lacking sufficient diagnostic capability for PCR testing. Methods: We assessed seropositivity for the SARS-CoV-2 IgG between April 21 and May 20, 2020, at 2 primary care clinics in Tokyo, Japan. Results: The overall positive percentage of SARS-CoV-2 IgG was 3.83% (95% confidence interval [CI]: 2.76-5.16) for the entire cohort (n = 1071). The 23 special wards of central Tokyo exhibited a significantly higher prevalence compared with the other areas of Tokyo after classification by residence ( P = .02, 4.68% [3.08-6.79] vs 1.83 [0.68-3.95] in central and suburban Tokyo, respectively). In central Tokyo, the southern area showed the highest seroprevalence compared with the other areas (7.92% [3.48-15.01]), corresponding to the cumulative number of confirmed COVID-19 patients by PCR test reported by the Tokyo Metropolitan Government. Conclusion: The seroprevalence surveyed in this study was too low for herd immunity, suggesting the need for robust disease control and prevention. A regional-level approach, rather than state- or prefectural-level, could be of importance in ascertaining detailed profiles of the COVID-19 outbreak.

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Planarians have established a unique body pattern along the anterior-posterior (AP) axis, which consists of at least four distinct body regions arranged in an anterior to posterior sequence: head, prepharyngeal, pharyngeal (containing a pharynx), and tail regions, and possess high regenerative ability. How they reconstruct the regional continuity in a head-to-tail sequence after amputation still remains unknown. We use as a model planarian Dugesia japonica head regeneration from tail fragments, which involves dynamic rearrangement of the body regionality of preexisting tail tissues along the AP axis, and show here that RNA interference of the gene D. japonica mek kinase 1 (Djmekk1) caused a significant anterior shift in the position of pharynx regeneration at the expense of the prepharyngeal region, while keeping the head region relatively constant in size, and accordingly led to development of a relatively longer tail region. Our data suggest that DjMEKK1 regulates anterior extracellular signal-regulated kinase (ERK) and posterior β-catenin signaling pathways in a positive and negative manner, respectively, to establish a proper balance resulting in the regeneration of planarian's scale-invariant trunk-to-tail patterns across individuals. Furthermore, we demonstrated that DjMEKK1 negatively modulates planarian β-catenin activity via its serine/threonine kinase domain, but not its PHD/RING finger domain, by testing secondary axis formation in Xenopus embryos. The data suggest that Djmekk1 plays an instructive role in the coordination between the establishment of the prepharyngeal region and posteriorizing of pharynx formation by balancing the two opposing morphogenetic signals along the AP axis during planarian regeneration.

The serosurvey is an alternative way to know the magnitude of the population infected by coronavirus disease 2019 (COVID-19) since the expansion of capacity of the polymerase chain reaction (PCR) to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was delayed. We herein report seroprevalence of COVID-19 accessed in the two community clinics in Tokyo. The point-of-care immunodiagnostic test was implemented to detect the SARS-CoV-2 specific IgG antibody in the peripheral capillary blood. The overall positive percentage of SARS-CoV-2 IgG antibody is 3.83% (95% confidence interval: 2.76-5.16) for the entire cohort (n =1,071). The central Tokyo of 23 special wards exhibited a significantly higher prevalence compared to the other area of Tokyo (p =0.02, 4.68% [95%CI: 3.08-6.79] versus 1.83 [0.68-3.95] in central and suburban Tokyo, respectively). The seroprevalence of the cohort surveyed in this study is low for herd immunity, which suggests the need for robust disease control and prevention. A community-based approach, rather than state or prefectural levels, is of importance to figure out profiles of the SARS-COV-2 outbreak.