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Biology subjects

Hosoya, T.

Publications and source records attributed to Hosoya, T..

11 recordsLinked to original sources

Dermatomycosis associated with Nannizziopsis arthrosporioides in a breeding colony of gecko (Correlophus ciliatus and Rhacodactylus auriculatus).

This report describes lethal Nannizziopsis-associated dermatomycosis in a breeding colony of the family Diplodactylidae (Correlophus ciliatus and Rhacodactylus auriculatus). After introducing one gecko from overseas, three with indirect contact history died due to severe skin lesions. Extensive lesions were observed on the toe pads and ventral surface, along with necrotic dermatitis and cellulitis associated with fungi forming hyphae. Subsequently, four geckos developed diarrhea, melena, emaciation, and fungal dermatitis of the toe pads and died. Histopathologically, the fungal morphologies observed in the skin lesions of the seven geckos were consistent, and Nannizziopsis arthrosporioides was isolated and identified in two of them. To our knowledge, this is the first report of a fatal outbreak of N. arthrosporioides in geckos.

pathology↗

DNA Specimen Preservation using DESS and DNA Extraction in Museum Collections: A Case Study Report

Recent advances in DNA research have increased the necessity for museums to preserve not only morphological specimens but also their DNA, leading us to maintain tissue samples linked to specimens at -80{degrees}C. DNA analysis has become an essential tool for taxonomic research and biodiversity assessment; however, freezer storage for all samples is impractical due to space limitations and operational costs. This creates a pressing need to develop more widely applicable DNA preservation methods. We investigated the comparative effects of traditional preservation methods versus DESS (DMSO/EDTA/saturated NaCl solution) preservation on both morphology and DNA integrity using museum specimens from various taxonomic groups. Our results demonstrated that DESS preservation maintained high-quality DNA fragments exceeding >15 kb at room temperature across all examined species, with nematode samples maintaining DNA integrity even after 10 years of storage. When preserving whole organisms, the optimal preservation solution conditions for maintaining both morphological features and DNA integrity varied among species. Notably, DNA integrity was maintained even after complete evaporation of the DESS solution. These findings suggest that DESS utilization for specimen DNA preservation is effective across many species, not only for long-term storage in environments without freezer facilities but also for temporary preservation until freezing. Simple SummaryRecent advances in DNA research have increased the necessity for museums to preserve not only morphological specimens but also their DNA, leading us to maintain tissue samples linked to specimens at -80{degrees}C. However, as freezer storage for all samples is impractical, there is a pressing need to develop more widely applicable DNA preservation methods. In this study, we investigated the effectiveness of traditional preservation methods versus DESS (DMSO/EDTA/saturated NaCl solution) preservation with regards to both morphology and DNA integrity using our museum specimens. Our results demonstrated that DESS preservation maintained high molecular weight DNA at room temperature across all examined species. When preserving whole organisms, the optimal preservation solution conditions for maintaining both morphological features and DNA integrity varied among species. Notably, DNA integrity was maintained even after complete evaporation of the DESS solution. These findings suggest that DESS utilization for specimen DNA preservation is effective across many species, not only for long-term storage in environments without freezer facilities but also for temporary preservation until freezing is possible.

zoology↗

First evidence of Clavicipitaceous fungus attacking a vertebrate

Metapochonia bulbillosa (Clavicipitaceae) was isolated as a causative agent of a new frog mycosis of Pelophylax porosus brevipodus, one of the endangered frogs in Japan. Analysis of spontaneous outbreaks and infection experiments confirmed that the fungus can lethally affect Pelophylax porosus brevipodus, as well as Dryophytes japonicus. This is the first evidence that a species of Clavicipitaceae, originally known as a plant pathogen, also affects vertebrates.

microbiology↗

Temperature vaulting: A method for screening selective, slow- and tight-binding inhibitors targeting kinases in their non-native state

A polypeptide folds into its protein tertiary structure in the native state through a folding intermediate in the non-native state. The transition between these states is thermodynamically driven. A folding intermediate of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) autophosphorylates intramolecularly, whereas DYRK1A in the native state no longer catalyzes this reaction. The alteration in substrate specificity suggests a conformational transition of DYRK1A during its folding process. Consistent with this hypothesis, we identified FINDY (1), which inhibits the intramolecular autophosphorylation but not the intermolecular phosphorylation, suggesting that the folding intermediate possesses an alternative inhibitor-binding site. Meanwhile, it remains an issue that the methods for approaching the alternative binding site require an intricate assay tailored to the individual target. Here we show a method, designated as "temperature vaulting," for screening the non-native-state-targeted inhibitors of DYRK1A. Transient heating of recombinant DYRK1A protein drove the reversible transition between the native state and the non-native state targeted by FINDY (1). At physiological temperature, FINDY (1) slowly bound to the DYRK1A protein. These results indicate that transient heating accelerates the slow-binding process by assisting the protein to overcome the high-energy barrier leading to the target non-native state. The energy barrier also slowed down the dissociation process, resulting in tight binding between DYRK1A and FINDY (1). Furthermore, this study suggests that the dissociation rate underlies the inhibition selectivity of FINDY (1) between DYRK1A and its family kinase DYRK1B. This method enables the identification of slow- and tight-binding inhibitors that have been missed in conventional assays. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/632643v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@be5661org.highwire.dtl.DTLVardef@1925beorg.highwire.dtl.DTLVardef@fceb5borg.highwire.dtl.DTLVardef@bfbf91_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSA temperature vaulting method facilitated the screening of a slow- and tight-binding inhibitor targeting DYRK1A in the non-native state. A structure-activity relationship study of FINDY (1) demonstrated that a slight alteration in chemical structure impacts the inhibition kinetics. A molecular dynamics simulation of DYRK1A revealed binding-ready conformations for FINDY (1). The dissociation rate may underlie the inhibition selectivity of FINDY (1) between DYRK1A and DYRK1B in cellular systems.

biophysics↗

Easy-to-set-up image analysis characterizes phenotypic diversity in the growth of mushroom-forming fungus Schizophyllum commune

Schizophyllum commune, a common wood-decay mushroom known for its extremely high genetic diversity and as a rare cause of human respiratory diseases, could be a promising model fungus contributing to both biology and medicine. To better understand its phenotypic diversity, we developed an image analysis system that quantifies whole morphological traits of mycelia in Petri dishes. This study evaluated growth of six wild and one clinical isolates of Japanese S. commune, subjected to different temperatures and glucose concentrations, including a condition mimicking the human respiratory environment. Our analysis revealed that combinations of two growth indices, area and whiteness, highlighted strain-specific responses, with profiling growth patterns using clustering algorithms. Notably, the clinical isolate exhibited the strongest whiteness under the respiratory-like condition. We also found that the growth rate was strongly determined by glucose concentration, while the effects of temperature on growth varied among the strains, suggesting that while glucose preference is common in this species, responses to temperature differ between strains. Our results suggest that the system possesses sufficient sensitivity to detect growth traits of mycelia. This study provides a key to unravelling unknown traits behind the high polymorphisms in S. commune, including the ability to colonize the human respiratory tract.

microbiology↗

CiDRE+ M2c macrophages hijacked by SARS-CoV-2 cause COVID-19 severity

Infection of the lungs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the angiotensin I converting enzyme 2 (ACE2) receptor induces a type of systemic inflammation known as a cytokine storm. However, the precise mechanisms involved in severe coronavirus disease 2019 (COVID-19) pneumonia are unknown. Here, we show that interleukin-10 (IL-10) changed normal alveolar macrophages into ACE2-expressing M2c-type macrophages that functioned as spreading vectors for SARS-CoV-2 infection. The depletion of alveolar macrophages and blockade of IL-10 attenuated SARS-CoV-2 pathogenicity. Furthermore, genome-wide association and quantitative trait locus analyses identified novel mRNA transcripts in human patients, COVID-19 infectivity enhancing dual receptor (CiDRE), which has unique synergistic effects within the IL-10-ACE2 system in M2c-type macrophages. Our results demonstrate that alveolar macrophages stimulated by IL-10 are key players in severe COVID-19. Collectively, CiDRE expression levels are potential risk factors that predict COVID-19 severity, and CiDRE inhibitors might be useful as COVID-19 therapies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=195 HEIGHT=200 SRC="FIGDIR/small/510331v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1e96c82org.highwire.dtl.DTLVardef@1d2dc32org.highwire.dtl.DTLVardef@7689d1org.highwire.dtl.DTLVardef@520d17_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

First report of emerging snake fungal disease caused by Ophidiomyces ophiodiicola from Asia in imported captive snakes in Japan

Snake fungal disease (SFD) (Ophidiomycosis) is an emerging infectious disease caused by the fungus Ophidiomyces ophiodiicola which has been affecting wild and captive snakes in North America, Europe, and Australia. We report the cases of 12 imported captive colubrid snakes in Japan suspected of having SFD. Pathological and microbiological examinations were performed, and the results confirmed the diagnosis of SFD in two snakes, which indicated that the remaining sympatrically raised snakes also had SFD since they exhibited similar lesions. The oral administration of ciprofloxacin in addition to itraconazole had a significant treatment effect. This is the first report of SFD in Asia caused by O. ophiodiicola. To prevent the expansion of SFD in the natural environment in Japan, there is a need to evaluate the SFD carrier status of imported snakes, the pathogenicity of the infection in native snakes, and the prevalence and distribution of SFD in wild and captive snakes. Measures also must be taken to prevent endemicity globally.

microbiology↗

Interspike intervals within retinal spike bursts combinatorially encode multiple stimulus features

Neurons in various regions of the brain generate spike bursts. While the number of spikes within a burst has been shown to carry information, information coding by interspike intervals (ISIs) is less well understood. In particular, a burst with k spikes has k-1 intraburst ISIs, and these k-1 ISIs could theoretically encode k-1 independent values. In this study, we demonstrate that such combinatorial coding occurs for retinal bursts. By recording ganglion cell spikes from isolated salamander retinae, we found that intraburst ISIs encode oscillatory light sequences that are much faster than the light intensity modulation encoded by the number of spikes. When a burst has three spikes, the two intraburst ISIs combinatorially encode the amplitude and phase of the oscillatory sequence. Analysis of trial-to-trial variability suggested that intraburst ISIs are regulated by two independent mechanisms responding to orthogonal oscillatory components, one of which is common to bursts with different number of spikes. Therefore, the retina encodes multiple stimulus features by exploiting all degrees of freedom of burst spike patterns, i.e., the spike number and multiple intraburst ISIs. Author SummaryNeurons in various regions of the brain generate spike bursts. Bursts are typically composed of a few spikes generated within dozens of milliseconds, and individual bursts are separated by much longer periods of silence ([~]hundreds of milliseconds). Recent evidence indicates that the number of spikes in a burst, the interspike intervals (ISIs), and the overall duration of a burst, as well as the timing of burst onset, encode information. However, it remains unknown whether multiple ISIs within a single burst encode multiple independent information contents. Here we demonstrate that such combinatorial ISI coding occurs for spike bursts in the retina. We recorded ganglion cell spikes from isolated salamander retinae stimulated with computer-generated movies. Visual response analyses indicated that multiple ISIs within a single burst combinatorially encode the phase and amplitude of oscillatory light sequences, which are different from the stimulus feature encoded by the spike number. The result demonstrates that the retina encodes multiple stimulus features by exploiting all degrees of freedom of burst spike patterns, i.e., the spike number and multiple intraburst ISIs. Because synaptic transmission in the visual system is highly sensitive to ISIs, the combinatorial ISI coding must have a major impact on visual information processing.

neuroscience↗

BAP1 deubiquitinase is a potent repressor of fetal hemoglobin biosynthesis

Human globin gene production transcriptionally \"switches\" from fetal to adult synthesis shortly after birth, and is controlled by macromolecular complexes that enhance or suppress transcription by cis-elements scattered throughout the locus. The DRED repressor is recruited to the {varepsilon}- and {gamma}-globin promoters by the orphan nuclear receptors TR2 (NR2C1) and TR4 (NR2C2) to engender their silencing in adult erythroid cells. Here we found that nuclear receptor corepressor-1 (NCoR1) is a critical component of DRED that acts as a scaffold to unite the DNA binding and epigenetic enzyme components (e.g. DNMT1 and LSD1) that elicit DRED function. We also describe a potent new regulator of {gamma}-globin repression: the deubiquitinase BAP1 is a component of the repressor complex whose activity maintains NCoR1 at sites in the {beta}-globin locus, and BAP1 inhibition in erythroid cells massively induces {gamma}-globin synthesis. These data provide new mechanistic insights through the discovery of novel epigenetic enzymes that mediate {gamma}-globin gene repression.

developmental biology↗

High throughput single cell sequencing of both T-cell-receptor-beta alleles

Allelic exclusion is a vital mechanism for the generation of monospecificity to foreign antigens in B- and T-lymphocytes. Here we developed a high-throughput barcoded method to simultaneously analyze the VDJ recombination status of both mouse T cell receptor beta alleles in hundreds of single cells using Next Generation Sequencing.

immunology↗

The ash dieback invasion of Europe was founded by two individuals from a native population with huge adaptive potential

Accelerating international trade and climate change make pathogen spread an increasing concern. Hymenoscyphus fraxineus, the causal agent of ash dieback is one such pathogen, moving across continents and hosts from Asian to European ash. Most European common ash (Fraxinus excelsior) trees are highly susceptible to H. fraxineus although a small minority (~5%) evidently have partial resistance to dieback. We have assembled and annotated a draft of the H. fraxineus genome which approaches chromosome scale. Pathogen genetic diversity across Europe, and in Japan, reveals a tight bottleneck into Europe, though a signal of adaptive diversity remains in key host interaction genes (effectors). We find that the European population was founded by two divergent haploid individuals. Divergence between these haplotypes represents the 'shadow' of a large source population and subsequent introduction would greatly increase adaptive potential and the pathogen's threat. Thus, EU wide biological security measures remain an important part of the strategy to manage this disease.

genomics↗