Biology subjects

Konishi, T.

Publications and source records attributed to Konishi, T..

14 recordsLinked to original sources

bioRxiv2026

Tumor-associated tissue-resident macrophages drive pancreatic cancer progression through IGF1-IGF1R signaling

The specific contribution of tissue-resident macrophages (TRMs) to pancreatic ductal adenocarcinoma (PDAC) progression remains unclear. Here, we found that a high abundance of TRM-derived tumor-associated macrophages (TRM-TAMs) is an independent indicator of poor prognosis in patients with PDAC. To elucidate the underlying mechanism, we established an advanced organoid platform (iMac-FPCO), which incorporates macrophages derived from human induced pluripotent stem cells to reflect the differentiation process of TRMs. Single-cell transcriptomic analysis revealed this model recapitulates the transcriptional identity of TRM-TAMs in patient tissue. We demonstrated that TRM-TAMs drive cancer cell proliferation, while maintaining chemoresistance, and identified TRM-derived insulin-like growth factor 1 (IGF1) as the critical mediator. This result provides a rationale for why previous trials targeting IGF1 receptor (IGF1R) failed to improve survival in unselected patient populations. We hypothesize that stratifying patients by TRM-TAM abundance could help identify a responsive subgroup, thereby reviving IGF1R-targeted therapy as a viable treatment for PDAC.

cancer biology↗

bioRxiv2025

What makes a society dead: accumulation of uric acid increases infectious disease risk in termites

In social insect colonies, the high reproductive output of kings and queens is supported by non-reproductive castes, a division of labour that allows for the rapid recovery of individuals, often including those of the reproductive castes. However, these seemingly permanent colonies eventually face collapse. Studying the mechanisms of colony death is crucial for understanding the maintenance of insect social systems. Here, we show that the accumulation of uric acid (a major product of nitrogen metabolism) in workers increases their infectious disease risk in the Japanese subterranean termite Reticulitermes speratus. In this species, king replacement has been associated with colony demise, and we found that king replacement increases the uric acid contents in worker bodies in the field. Uric acid, which has antioxidant activity, was shown to reduce in vivo levels of reactive oxygen species (ROS), a key player in innate immunity. Workers with decreased ROS levels were more susceptible than those with normal ROS levels to an opportunistic pathogen that causes disease to immunocompromised termites. Our results indicate that regulating the individual oxidant/antioxidant balance through the interactions among colony members plays a pivotal role in the immunity of social insects.

ecology↗

bioRxiv2024

Afadin-deficient retinas exhibit severe neuronal lamination defects but preserve visual functions

Neural lamination is a common feature of the central nervous system (CNS), with several subcellular structures, such as adherens junctions (AJs), playing a role in this process. The retina is also heavily laminated, but it remains unclear how laminar formation impacts retinal cell morphology, synapse integrity, and overall retinal function. In this study, we demonstrate that the loss of afadin, a key component of AJs, in mice leads to significant pathological changes. These include the disruption of outer retinal lamination and a notable decrease as well as mislocalization of photoreceptors, their outer segments, and photoreceptor synapses. Interestingly, despite these severe impairments, we recorded small local field potentials, including the a- and b-waves. We also classified retinal ganglion cells (RGCs) into ON, ON-OFF, and OFF types based on their firing patterns in response to light stimuli. Additionally, we successfully characterized the receptive fields of certain RGCs. Overall, these findings provide evidence that retinal circuit function can be partially preserved even when there are significant disruptions in both retinal lamination and photoreceptor synapses. Our results indicate that retinas with severely altered morphology still retain some capacity to process light stimuli.

neuroscience↗

bioRxiv2023

Why do some fungi want to be sterile? The role of dysfunctional Pro1 in the rice blast fungus

Although sexual reproduction is widespread in eukaryotes, some fungal species can only reproduce asexually. Therefore, loss of sexual reproduction may confer survival advantages under certain conditions in certain species. In the rice blast fungus Pyricularia (Magnaporthe) oryzae, several isolates from the region of origin retain mating ability (female fertility), but most isolates are female sterile. Therefore, it is hypothesized that female fertility was lost during its spread from the origin to the rest of the world, and P. oryzae is an ideal biological model for studying the cause of the evolutionary shift in the reproductive mode. Here, we show that functional mutations of Pro1, a global transcriptional regulator of mating-related genes in filamentous fungi, is one cause of loss of female fertility in this fungus. Employing backcrossing between female-fertile and female-sterile field isolates, we identified the putative genomic region involved in female sterility by comparative genomics between the genomes of F4 female-fertile and -sterile progenies. Further genotyping, linkage, and functional analyses revealed that the functional mutation of Pro1 causes the loss of female fertility. RNA sequencing analysis showed that Pro1 regulates global gene expression, including that of several mating-related genes. The dysfunctional Pro1 did not affect the infection processes, such as conidial germination, appressorium formation, and penetration, but conidial release from conidiophores was increased. Furthermore, various types of mutations in Pro1 were detected in geographically distant P. oryzae, including pandemic isolates of wheat blast fungus. These results provide the first evidence that loss of female fertility may be advantageous to the life cycle of some plant pathogenic fungi. SignificanceMany pathogenic and industrial fungi are thought to have abdicated sexual reproduction, but the mechanisms and biological importance have been a long-standing mystery. Discovering why such fungi lost fertility is important to understand their survival strategies. Here, we revealed the genetic basis of how the rice blast fungus lost female fertility in nature and how this affects the life cycle. This has important implications for understanding evolution of blast pathogens and for developing an effective management strategy to control blast disease before a pandemic. Our findings also provide an additional perspective on advantages of asexual reproduction in some eukaryotes.

microbiology↗

bioRxiv2022

King- and queen-specific degradation of uric acid is the key to reproduction in termites

Caste-based reproductive division of labour in social insects is built on asymmetries in resource allocation within colonies. Kings and queens dominantly consume limited resources for reproduction, while non-reproductive castes such as workers and soldiers help reproductive castes. Studying the regulation of such asymmetries in resource allocation is crucial for understanding the maintenance of sociality in insects, although the molecular background is poorly understood. We focused on uric acid, which is reserved and utilized as a valuable nitrogen source in wood-eating termites. We found that king- and queen-specific degradation of uric acid is the key to reproduction in the subterranean termite Reticulitermes speratus. The urate oxidase gene (RsUAOX), which catalyses the first step of nitrogen recycling from stored uric acid, was highly expressed in mature kings and queens, and upregulated with differentiation into neotenic kings/queens. Suppression of uric acid degradation decreased the number of eggs laid per queen. Uric acid was shown to be provided by workers to reproductive castes. Our results suggest that the capacity to use nitrogen, which is essential for the protein synthesis required for reproduction, contributes to colony cohesion expressed as the reproductive monopoly held by kings and queens.

ecology↗

bioRxiv2022

Seasonal movement of royal chambers: where are the kings and queens of temperate termites in winter?

Overwintering is a critical part of the annual cycle for species that live in temperate, polar, and alpine regions. As a result, low-temperature biology is a key determinant of temperate species distribution. Termites distribute predominantly in tropical regions, and only a few species are found in the temperate zone. As with other social insects, termites are characterized by the division of labor between reproductive and non-reproductive castes in which the survival of reproductives is crucial to maintaining their society. Here, in the termite Reticulitermes speratus, we report the discovery of an underground royal chamber that kings and queens use to survive the winter, which is separate from the one they use during the warmer breeding season. Our investigation of field colonies indicates that in the spring the royals are localized in decayed logs on the ground, then move to their underground royal chamber located in the roots of stumps in the fall. The winter minimum temperature measured in the royal chamber was higher than the ground surface temperature. In overwintering termites, the kings and queens had higher cold tolerance than workers and soldiers. The kings and queens were at risk of mortality from -8 {degrees}C, compared to the workers and soldiers at -4 {degrees}C. Air temperatures dropped below this critical temperature of -8 {degrees}C multiple times, as evidenced from the past 140 years of weather records in Kyoto. This suggests that the underground movement of the royal chamber may contribute to avoiding the risk of overwintering mortality. These results demonstrate the social strategies implemented to overcome the environment met while living at the latitudinal limits. This study sheds light on one of the most important aspects of the biology of termites in terms of predicting their geographic distribution and spread by climate change. This work also helps further the understanding of the termites social system, seasonal phenology, long-term survivorship, and life cycle, and contributes to the development of pest control strategies.

ecology↗

bioRxiv2022

Study of aging using circuit tests and parametric analysis

Mouse development and aging were investigated in 11 tests. The test data were parametrically analysed, normalized, and integrated using principal component analysis (PCA). Changes in the indexing items displayed two trends: power and accuracy in the trials. Power decreased monotonically with age, whereas accuracy peaked at 6 months. Features, such as fear or anxiety, could not have been measured. The noise level and sensitivity of each test were determined. In an open field test that involved a video recording of movement, the noise level was the lowest and the sensitivity was high. This test contributed the most to the PCA axes, and reproduced the two main directions. Significance StatementThe mathematical aspect may have been neglected in behavioural tests. Here, the circuit test data were objectively analysed by focusing on the data distributions during the aging of mice. The test results revealed two clear directions for the data: power, which was gradually reduced, and accuracy, which peaked at sixth months old. Compared with the open field test evaluated using video recordings, the other tests had higher noise levels and weaker signals. Other tests can be improved by using movie recordings and identifying appropriate items.

animal behavior and cognition↗

bioRxiv2020

SARS-CoV-2 mutations among minks show reduced lethality and infectivity to humans

SARS-CoV-2 infection in minks has become a serious problem, as the virus may mutate and reinfect humans; some countries have decided to cull minks. Here, the virus sequencing data in minks were analysed and compared to those of human-virus. Although the mink-virus maintained the characteristics of human-virus, some variants rapidly mutated, adapting to minks. Some mink-derived variants infected humans, which accounted for 40% of the total SARS-CoV-2 cases in the Netherlands. These variants appear to be less lethal and infective compared to those in humans. Variants that have mutated further among minks were not found in humans. Such mink-viruses might be suitable for vaccination for humans, such as in the case of the smallpox virus, which is less infective and toxic to humans.

microbiology↗

bioRxiv2020

Changes in SARS-CoV-2 before the peak in each country, producing unique variants.

The second and subsequent waves of coronavirus disease 2019 (COVID-19) have caused problems worldwide 1. Here, using an objective analytical method 2, we present the changes that occurred in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of COVID-19, over time. The virus has mutated in three major directions, resulting in three groups to date. Analysis of the basic structure of the group of viruses was completed by April and shared across all continents. However, the virus continued to mutate independently in each country after the borders were closed. In particular, the virus mutated before the occurrence of the second and subsequent peaks. It seems that the mutations conferred higher infectivity to the virus, because of which the virus overcame previously effective protection and caused second waves of the disease. Currently, each country may possess such a unique, stronger variant. Some of them slowly entered other countries and caused epidemics. These viruses could also serve as sources of further mutations by exchanging parts of the genome, which could create variants with superior infectivity.

microbiology↗

bioRxiv2020

Cell lines of the same anatomic site and histologic type show large variability in intrinsic radiosensitivity and relative biological effectiveness to protons and carbon ions

PurposeTo show that radiation response across cancer cell lines of the same anatomic site and histologic type varies remarkably for protons and carbon (C) ions. Materials and MethodsWe measured and obtained from the literature clonogenic survival of human cancer cell lines of the lung (n=18), brain (n=10) and pancreas (n=10) exposed to photons, protons, and C-ions to assess their variability in response. We also treated cancer cell lines with DNA repair inhibitors prior to irradiation to assess how DNA repair capacity affects their variability in response. We quantified the variability in response by calculating the relative range (range/mean) and the coefficient of variation (COV) of the dose at 10% survival fraction (D10%) and relative biological effectiveness (RBE10%). ResultsThe relative range of D10% for lung cancer cell lines varied from 55-92% for photons, protons, and C-ions, with the relative range in RBE varying from 16-45% for protons and C-ions. For brain and pancreatic cancer cell lines, the relative range of D10% varied from 95-112%, and 39-75%, respectively, with the relative range in RBE varying from 27-33% and 25-50%, respectively. However, the COVs in D10% were approximately equal across radiation qualities, varying from 0.24{+/-}0.07-0.35{+/-}0.10, 0.35{+/-}0.09-0.69{+/-}0.62 and 0.13{+/-}0.03- 0.21{+/-}0.04 for lung, brain and pancreatic cancer cell lines, respectively. Greater relative ranges in D10% were observed in the cell lines with inhibited DNA repair, varying from 108%-157% for photons, protons, and C-ions, with relative ranges in RBE varying from 29-67%. The COVs in the D10% were also greater for the cell lines treated with inhibitors of DNA repair, varying from 0.34{+/-}0.09-0.41{+/-}0.06. ConclusionCell lines of the same anatomic site and histologic type have a remarkable variability in response, not only to photons but also to protons and C-ions. We attributed this variability to differences in DNA repair capacity. CategoryBiological Physics and Response Prediction

biophysics↗

bioRxiv2020

An empirical model to predict survival curve and relative biological effectiveness after helium and carbon ion irradiation based solely on the cell survival after photon irradiation

PurposeTo develop an empirical model to predict radiosensitivity and relative biological effectiveness (RBE) after helium (He) and carbon (C) ion irradiation with or without DNA repair inhibitors. MethodsWe characterized survival in eight human cancer cell lines exposed to 6 MV photons and to He- and C-ions with linear energy transfer (LET) values of 2.2-60.5 keV/m to verify that the radiosensitivity parameters (D5%, D10%, D20%, D37%, D50% and SF2Gy) correlate linearly between photon and ion radiation with or without DNA-PKcs or ATR inhibitors. Then, we parameterized the LET response of the parameters governing these linear correlations up to LET values of 225 keV/m using the data in the Particle Irradiation Data Ensemble (PIDE) v3.2 database, creating a model that predicts a cells ion radiosensitivity, RBE and ion survival curve for a given LET on the basis of the cells photon radiosensitivity. We then trained this model using the PIDE database as a training dataset, and validated it by predicting the radiosensitivity of the cell lines we exposed to He- and C- ions with LET ranging from 2.2-60.5 keV/m. ResultsRadiosensitivity to ions depended linearly with radiosensitivity of photons in the range of investigated LET values and the slopes and intercepts of these linear relationships within the PIDE database vary exponentially and linearly, respectively. Our model predicted ion radiosensitivity (e.g., D10%) within 5.1-21.3%, RBED10% within 5.0-17.1%, and ion mean inactivation dose within 6.7-25.1% for He- and C-ion LET ranging from 2.2-60.5 keV/m. ConclusionsRadiosensitivity to He- and C-ions depend linearly with radiosensitivity to photons and can be used to predict ion radiosensitivity, RBE and cell survival curves for clinically relevant LET values from 2.2-60.5 keV/m, with or without drug treatment. SUMMARYWe present a new empirical model capable of predicting clonogenic cell survival of cell lines exposed to helium and carbon ion beams. Our model is based on an observed linear correlation between radiosensitivity to ions and photons across a wide range of LET values. This linear correlation can be used to predict ion RBE, radiosensitivity, and the cell survival curve for a given LET all based on a cells photon survival curve.

biophysics↗

bioRxiv2020

Coronavirus, as a source of pandemic pathogens.

The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence SummaryThe genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.

microbiology↗

bioRxiv2020

Linker histone H1 determines cell stiffness and differentiation

ABSTRACTThe flexibility or stiffness, one mechanical property of cells, is a promising label-free biomarker for underlying cytoskeletal or nuclear changes associated with various disease processes and changes in cell state. However, the molecular changes responsible for the whole-cell mechanical stiffness remain to be clarified. Recently, it was shown that the deterministic lateral displacement (DLD) microfluidic device, originally developed for size fractionation of some particles, might be applied to distinguish cells according to their stiffness. In this experiment, using the DLD device and various cell lines differentially expressing histone H1, a positively-charged protein localized in the linker region of chromatin, we found linear relationships between histone H1 quantity and cell stiffness. We also found that the histone H1 quantity affected cell size and even cell differentiation.

cell biology↗

bioRxiv2018

Principal Component Analysis applied directly to Sequence Matrix

Sequence data is now widely used to observe relationships among organisms. However, understanding structure of the qualitative data is challenging. Conventionally, the relationships are analyzed using a dendrogram that estimates a tree shape. This approach has difficulty in verifying the appropriateness of the tree shape; rather, horizontal gene transfers and mating can make the shape of the relationship as networks. As a connection-free approach, principal component analysis (PCA) is used to summarize the distance matrix, which records distances between each combination of samples. However, this approach is limited regarding the treatment of information of sequence motifs; distances caused by different motifs are mixed up. This hides clues to figure out how the samples are different. As any bases may change independently, sequence is multivariate data essentially. Hence, differences among samples and bases that contribute to the difference should be observed coincidentally. To archive this, the sequence matrix is transferred to boolean vector and directly analyzed by using PCA. The effects are confirmed in diversity of Asiatic lion and human as well as environmental DNA. Resolution of samples and robustness of calculation is improved. Relationship of a direction of difference and causative nucleotides has become obvious at a glance.

evolutionary biology↗