Cryptic diploid lineage of Betula ermanii at its southern boundary populations in Japan.

Polyploidy is thought to enable species diversification and adaptation to extreme environments. Resolving the ecological differences between a taxon's ploidy levels would therefore provide important insights into local adaptation and speciation. The genus Betula includes many polyploids, but estimates of their phylogenetic relationships and evolutionary history are uncertain because of cryptic lineages and species. As one of the southern boundary populations of Betula ermanii in Japan has been shown to have distinctive genetic characteristics and traits, the differences in ploidy levels between three southern boundary and various other Japanese B. ermanii populations were investigated using flow cytometry. Leaf and seed morphologies were also compared. Apart from individuals in southern boundary populations, all those sampled were tetraploid. Individuals from the southern boundary populations were mostly diploid, apart from a few from lower altitude Shikoku populations, which were tetraploid. Leaf and seed morphologies differed between tetraploids and diploids. Diploid individuals were characterized by leaves with a heart-shaped base and many leaf teeth, and seeds with relatively longer wings. The diploid populations could be considered a cryptic relict lineage of B. ermanii, and there is a possibility that this lineage is a diploid ancestor of B. ermanii and a relict population of the Sohayaki element. Further investigation of the Japanese Betula phylogenetic relationships would enable an informed discussion of taxonomic revisions.

Response of stomatal density and size in Betula ermanii to contrasting climate conditions: The contributions of genetic and environmental factors.

As plant distribution and performance are determined by both environmental and genetic factors, clarifying the contribution of these two factors is a key for understanding plant adaptation and predicting their distribution under ongoing global warming. Betula ermanii is an ideal species for such research because of its wide distribution across diverse environments. Stomatal density and size are crucial traits that plants undergo changes in to adapt to different environments as these traits directly influence plant photosynthesis and transpiration. In this study, we conducted a multi-location common garden experiment using B. ermanii to (1) clarify the contribution of both environmental and genetic factors to the variation in stomatal density and size of B. ermanii, (2) demonstrate the differences in the plasticity of stomatal density and size among B. ermanii populations, and (3) understand how stomatal density and size of B. ermanii would respond to increased temperature and changing precipitation patterns. Genetic factors played a more significant role in stomatal size than environmental factors, suggesting that B. ermanii struggles to adjust its stomatal size in response to a changing environment. Our results also revealed a positive correlation between stomatal size plasticity and original habitat suitability, indicating that in B. ermanii populations in harsh environments exhibit lower adaptability to environmental shifts. Although stomatal density and size of B. ermanii showed the significant responses to increased temperature and shifting precipitation patterns, the response ranges of stomatal density and size to the environmental factors varied among populations. Our findings highlighted the interplay between genetic and environmental factors in determining the intraspecific variation in stomatal density and size in B. ermanii. This indicated that certain populations of B. ermanii exhibit limited stomatal plasticity and adaptability, which could directly affect photosynthesis and transpiration, suggesting potential population-specific fitness implications for B. ermanii under future climate change.

Divergent mechanisms of reduced growth performance in Betula ermanii saplings from high-altitude and low-latitude range edges.

The reduced growth performance of individuals from range edges is a common phenomenon in various taxa, and considered to be an evolutionary factor that limits the species' range. However, most studies did not distinguish between two mechanisms that can lead to this reduction: genetic load and adaptive selection to harsh conditions. To address this lack of understanding, we investigated the climatic and genetic factors underlying the growth performance of Betula ermanii saplings transplanted from 11 populations including high-altitude edge and low-latitude edge population. We estimated the climatic position of the populations within the overall B. ermanii's distribution, and the genetic composition and diversity using restriction-site associated DNA sequencing, and measured survival, growth rates and individual size of the saplings. The high-altitude edge population (APW) was located below the 95% significance interval for the mean annual temperature range, but did not show any distinctive genetic characteristics. In contrast, the low-latitude edge population (SHK) exhibited a high level of linkage disequilibrium, low genetic diversity, a distinct genetic composition from the other populations, and a high relatedness coefficient. Both APW and SHK saplings displayed lower survival rates, heights and diameters, while SHK saplings also exhibited lower growth rates than the other populations' saplings. The low heights and diameters of APW saplings was likely the result of adaptive selection to harsh conditions, while the low survival and growth rates of SHK saplings was likely the result of genetic load. Our findings shed light on the mechanisms underlying the reduced growth performance of range-edge populations.

Epidemiology of Coronavirus Disease 2019 in Yamagata Prefecture, Japan, January-May 2020: the Importance of Retrospective Contact Tracing.

Public health interventions have played an important role in controlling coronavirus disease 2019 (COVID-19), which is a rapidly spreading infectious disease. To contribute to future COVID-19 countermeasures, we aimed to verify the results of the countermeasures employed by public health centers (PHCs) against the first wave of COVID-19 in Yamagata Prefecture, Japan (Yamagata). Between January and May 2020, 1,253 patients suspected of SARS-CoV-2 infection were invited for testing. Simultaneously, based on retrospective contact tracings, PHCs investigated the infection sources and transmission routes of laboratory-confirmed COVID-19 cases and tested 928 contacts. Consequently, 69 cases were confirmed between March 31 and May 4, 58 of whom were from among the contacts (84.1%; 95% confidence interval [CI] 75.5-92.7). The spread of infection was triggered in cases harboring epidemiological links outside Yamagata. Subsequently, the number of cases rapidly increased. However, PHCs identified epidemiological links in 61 (88.4%; 95% CI 80.8-96.0) of the 69 cases, and transmission chains up to the fifth generation. Finally, the spread of infection ended after approximately one month. Our results indicate that the identification of infection sources and active case finding from contacts based on retrospective contact tracing was likely to be an effective strategy in ending the first wave of COVID-19 in Yamagata.

A case of recurrent hemoptysis caused by pulmonary actinomycosis diagnosed using transbronchial lung biopsy after bronchial artery embolism and a brief review of the literature.

A 60-year-old man was admitted to our hospital because of massive hemoptysis with acute respiratory failure. Since six months ago, he noticed gradual worsening of hemoptysis and was transferred to our hospital. Chest computed tomography showed a nodular lesion with cavitation in the left upper lobe and surrounding ground-glass opacification. Initially, a hemostatic agent was administered, but we eventually performed bronchial artery embolization (BAE) by ourselves due to persistent hemoptysis. After achieving good hemostasis with BAE bronchoscopy was performed, which gave a diagnosis of pulmonary actinomycosis on histopathologic examination of the transbronchial biopsy specimen without the need for lung resection.

Oriented immobilization to nanoparticles enhanced the therapeutic efficacy of antibody drugs.

Antibody drugs have been important therapeutic agents for treating various diseases, such as cancer, rheumatism, and hypercholesterolemia, for the last three decades. Despite showing excellent therapeutic efficacy with good safety in vivo, they require high doses. We have developed a ∼30-nm bio-nanocapsule (ZZ-BNC) consisting of hepatitis B virus envelope L protein fused with the tandem form of protein A-derived IgG Fc-binding Z domain (ZZ-L protein), for tethering antibodies in an oriented immobilization manner. In this study, antibody drugs were spontaneously conjugated to ZZ-BNC, which displayed the IgG Fv regions outwardly. The anti-human epidermal growth factor receptor IgG conjugated to ZZ-BNC (α-hEGFR-ZZ-BNC) was endocytosed by the human epidermoid carcinoma A431 cells, with increases in cellular uptake by ∼1.5 fold, compared that of α-hEGFR IgG alone. The amount of α-hEGFR IgG in the late endosomes and lysosomes was increased from 4% to 33% by the conjugation to ZZ-BNC. The in vitro cytotoxicity of α-hEGFR-ZZ-BNC was higher by ∼10-fold than that of α-hEGFR IgG alone. Furthermore, in vivo tumor growth was significantly reduced by α-hEGFR-ZZ-BNC than by α-hEGFR IgG alone. Taken together, since endosomal EGFR, not cell surface EGFR, played a pivotal role in the EGFR-mediated signaling cascade, ZZ-BNC increased α-hEGFR IgG avidity by efficiently repressing the activation of hEGFR not only on the cell surface, but presumably also in the endosomes. These results strongly suggested that ZZ-BNC is a promising nano-scaffold for enhancing the therapeutic efficacy and reducing the dose of antibody drugs. STATEMENT OF SIGNIFICANCE: Antibody drugs are widely used for treating severe diseases, such as cancer, rheumatism, and hypercholesterolemia. These drugs are composed of naturally occurring biomaterials with low immunogenicity and toxicity, as well as long in vivo serum half-life. To achieve sufficient therapeutic efficacy, the dose of antibody drugs are unavoidably higher than those of conventional drugs. The present study shows an innovative way to reduce the dose of antibody drugs by using a nanocarrier-conjugated antibody. Oriented immobilization of the antibody enhanced its avidity, endocytosis efficiency, and therapeutic efficacy.