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Recent studies of microbial biogeography have revealed the global distribution of cosmopolitans and dispersal of regional endemics, but little is known about how these processes are affected by microbial evolution. Here, we compared DNA sequences from snow/glacier algae found in an 8000-year-old ice from a glacier in central Asia with those from modern snow samples collected at 34 snow samples from globally distributed sites at the poles and mid-latitudes, to determine the evolutionary relationship between cosmopolitan and endemic phylotypes of snow algae. We further applied a coalescent theory–based demographic model to the DNA sequences. We found that the genus Raphidonema (Trebouxiophyceae) was distributed over both poles and mid-latitude regions and was detected in different ice core layers, corresponding to distinct time periods. Our results indicate that the modern cosmopolitan phylotypes belonging to Raphidonema were persistently present long before the last glacial period. Furthermore, endemic phylotypes originated from ancestral cosmopolitan phylotypes, suggesting that modern regional diversity of snow algae in the cryosphere is a product of microevolution. These findings suggest that the cosmopolitans dispersed across the world and then derived new localized endemics, which thus improves our understanding of microbial community formation by microevolution in natural environments.

Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is an Epstein-Barr virus-positive, aggressive lymphoma with a heterogeneous cell of origin and variable clinical course. Several clinical prognostic indices have been proposed for ENKTL; however, there are few pathological biomarkers. This multi-institutional study sought to identify histologically assessable prognostic factors. We investigated mutation profiles by targeted next-generation sequencing (NGS) and immunohistochemical assessments of expression of MYC, Tyr705-phosphorylated (p-)STAT3, and CD30 in 71 ENKTL samples. The median age of the patients was 66 years (range, 6-100). The most frequent mutations were in STAT3 (27%), JAK3 (4%), KMT2D (19%), TP53 (13%), BCOR (10%), and DDX3X (7%). Immunohistochemistry (IHC) revealed that ENKTLs with STAT3 mutations exhibited higher expression of pSTAT3 and CD30. BCOR mutations were associated with increased MYC expression. Univariate analysis in the entire cohort showed that stage (II, III, or IV), BCOR mutations, TP53 mutations, and high MYC expression (defined as ≥40% positive neoplastic cells) were associated with reduced overall survival (OS). Multivariate modeling identified stage (II, III, or IV) and high MYC expression as independent adverse prognostic factors. In a subgroup analysis of patients treated with anthracycline (AC)-free chemotherapy and/or radiotherapy (RT) with curative intent, BCOR but not high MYC expression was an independent adverse prognostic factor. In conclusion, activating STAT3 mutations are common in ENKTLs and are associated with increased CD30 expression. MYC overexpression is, at least in part, associated with deleterious BCOR mutations, and this BCOR–MYC linkage may have prognostic significance, underscoring the potential utility of IHC for MYC in risk stratification of patients with ENKTL.

The brown bear is one of the few surviving megafauna species that made it through the Late Quaternary megafaunal extinctions. It is widely distributed and has become a model organism for studying biogeographic patterns across Eurasia and North America. However, to date, most studies have focused on the mitochondrial genome with nuclear genomes only being used for evolutionary studies within the Ursusidae family or local population studies. Here we present novel genomic data from two Late Pleistocene brown bears from Japan and Siberia, and combine them with modern and ancient published genomes from across the Holarctic range, to investigate the species’ genomic evolutionary history. We uncovered four differentiated populations corresponding to Europe, Siberia, Japan, and North America which all diverged ~100 kya. Palaeogenomic data reveals population continuity in all populations apart from in Europe where Late Pleistocene European individuals cluster with Siberia rather than contemporary/mid-late Holocene European individuals. We propose a replacement around the Pleistocene-Holocene transition in Europe, supported by results of a recent population expansion in modern European individuals. Population continuity in Japan and North America contrasts mitochondrial suggestions of multiple migration events. However, the rapid population diversification and increased likelihood of gene flow and incomplete lineage may have biased mitochondrial results. Demographic results show similar effective population declines in all populations ~50 kya which we suggest is due to the geographic dispersal of the newly diversified populations and a decrease of gene flow between populations.

Astrocyte abnormalities have received great attention for their association with various diseases in the brain but not so much in the eye. Recent independent genome-wide association studies of glaucoma, optic neuropathy characterized by retinal ganglion cell (RGC) degeneration, and vision loss found that single-nucleotide polymorphisms near the ABCA1 locus were common risk factors. Here, we show that Abca1 loss in retinal astrocytes causes glaucoma-like optic neuropathy in aged mice. ABCA1 was highly expressed in retinal astrocytes in mice. Thus, we generated macroglia-specific Abca1 -deficient mice (Glia-KO) and found that aged Glia-KO mice had RGC degeneration and ocular dysfunction without affected intraocular pressure, a conventional risk factor for glaucoma. Single-cell RNA sequencing revealed that Abca1 deficiency in aged Glia-KO mice caused astrocyte-triggered inflammation and increased the susceptibility of certain RGC clusters to excitotoxicity. Together, astrocytes play a pivotal role in eye diseases, and loss of ABCA1 in astrocytes causes glaucoma-like neuropathy.

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuously emerging, highlighting the importance of regular surveillance of SARS-CoV-2 and other epidemiologically significant pathogenic viruses in the current context. Reverse transcription-quantitative PCR (RT-qPCR) is expensive, time-consuming, labor-intensive, requires a large reagent volume, and only tests a few targets in a single run. High-throughput qPCR (HT-qPCR) utilizing the Biomark HD system (Fluidigm) can be used as an alternative. This study applied an HT-qPCR to simultaneously detect SARS-CoV-2, SARS-CoV-2 nucleotide substituted RNA, and other pathogenic viruses in wastewater. Wastewater samples were collected from the coronavirus disease 2019 (COVID-19) quarantine facility between October 2020 and February 2021 (n = 4) and from the combined and separated sewer lines of a wastewater treatment plant (WWTP) in Yokkaichi, Mie Prefecture, Japan, between March and August 2021 (n = 23 each). The samples were analyzed by HT-qPCR using five SARS-CoV-2, nine SARS-CoV-2 spike gene nucleotide substitution-specific, five pathogenic viruses, and three process control assays. All samples from the quarantine facility tested positive for SARS-CoV-2 and the nucleotide substitutions N501Y and S69-70 del (Alpha variant) were detected in the December 2020 sample, coinciding with the first clinical case in Japan. Only three WWTP samples were positive when tested with a single SARS-CoV-2 assay, whereas more than eight samples were positive when tested with all assays, indicating that using multiple assays increases the likelihood of detection. The nucleotide substitution L452R (Delta variant) was detected in the WWTP samples of Mie Prefecture in April 2021, but the detection of Delta variant from patients had not been reported until May 2021. Aichi virus 1 and norovirus GII were prevalent in WWTP samples. This study demonstrated that HT-qPCR may be the most time- and cost-efficient method for tracking COVID-19 and broadly monitoring community health.

Migratory geese could influence the microbiological water quality; however, their impacts on pathogen dynamics remain largely unknown. In this study, we analyzed the population dynamics of Campylobacter and Arcobacter group bacteria (AGB) in a freshwater lake in Japan over two years. The bacteria were quantified by using both culture-dependent and -independent methods. The potential sources of these bacteria were examined by a high-throughput flaA sequencing approach. Campylobacter was abundantly detected both by culture-dependent and -independent methods in the lake, especially when migratory geese were present in the lake. High-throughput flaA sequencing suggests that geese were the likely source of Campylobacter in the lake. The viable population of Campylobacter exceeds the concentrations that can potentially cause 10

In-situ follicular neoplasia (ISFN) is a histologically recognizable neoplastic proliferation of follicular lymphoma (FL)-like B cells confined to the germinal centres. While some ISFNs are associated with overt FL, others are incidentally identified as isolated or pure forms in individuals without evidence of overt FL. The prevalence of incidentally found isolated ISFN is approximately 3% in Europe; however, no screening study has been conducted in Asia. To investigate the incidence and clinicopathological characteristics of ISFNs in the Japanese population, we conducted histopathological screening of the lymph nodes (LNs) resected for solid tumours or inflammatory conditions.We screened for ISFN in 5700 LNs from 340 individuals using immunohistochemistry for BCL2 and identified seven ISFNs, with an incidence of 2.1%. The median age of the individuals with ISFN was 67 years, none of whom developed overt FL, with a median follow-up of 59 months. Next-generation sequencing was performed in five ISFNs, and 10 variants in seven FL-associated genes were identified. The identified variants included HIST1H1E (n = 2), ARID1A (n = 2), KMT2D (n = 1), CARD11 (n = 1), BCL7A (n = 1), CREBBP (n = 1) and TNFRSF14 (n = 1).The incidence of isolated ISFN in the Japanese population is not significantly different from that in Europe, presumably reflecting the recent increase in FL in Japan. These incidentally found ISFNs have a low potential to transform into overt FL. Although mutations of FL-associated genes are already present in ISFNs, further molecular studies are needed to identify driver genes leading to the transformation of ISFN to overt FL.