Biology subjects

Kamada, M.

Publications and source records attributed to Kamada, M..

9 recordsLinked to original sources

bioRxiv2026

A Proof-of-Concept Study on Attached Spirulina Cultivation Under Microgravity and Partial Gravity Aboard the ISS

Microalgal attached cultivation circumvents gas-liquid separation issues of liquid-suspended cultivation, yet performance under reduced gravity remains unevaluated. As a proof-of-concept, we evaluated Arthrospira platensis (Spirulina) cultivation under artificial 1G, 1/6G, and microgravity ({micro}G) on the International Space Station. Spirulina expanded without cell detachment, medium floating, or component separation, with relative radial growth rates of 0.28%0.5 day-1 (1G), 0.22%0.5 day-1 (1/6G), and 0.17-0.21%0.5 day-1 ({micro}G), demonstrating feasibility in space.

bioengineering↗

bioRxiv2026

Effects of microgravity on the three-dimensional morphology of rhizoids in Physcomitrium patens

Rooting systems of plants perceive environmental stimuli and flexibly regulate their growth. Therefore, understanding stimulus perception and response mechanisms is essential for optimizing cultivation. During the transition from aquatic to terrestrial environments, land plants have acquired mechanisms to adapt to gravitational force on land. Thus, elucidating gravity responses of rhizoids in bryophytes, early diverging land plants, provides important insights into how gravity-response mechanisms were established during land plant evolution. Analyzing rhizoid morphology under microgravity, where gravitational effects are largely eliminated, provides an effective approach to examine the gravity-response mechanisms that evolved after terrestrialization. In this study, to elucidate microgravity effects on rhizoid growth of Physcomitrium patens, we analyzed 3D datasets obtained by refraction-contrast micro-CT using synchrotron radiation after fixation and embedding of samples from the Space Moss experiment conducted on the International Space Station. Because each CT volume contains numerous rhizoids, we optimized a WEKA-based machine-learning segmentation approach by improving preprocessing, training, and postprocessing steps, resulting in a significantly improved segmentation accuracy. Comparison of 3D morphological indices between manually segmented rhizoids and predicted results supported the validity of the proposed method for morphological analysis. Morphological analyses revealed that, compared with both ground and artificial 1 x g conditions, rhizoid elongation and gravitropic responses were suppressed under microgravity, leading to reduced vertical growth. These findings indicate that gravity plays a fundamental role in rhizoid morphogenesis, and their absence affects growth orientation and elongation. This study provides foundational data for research on the rooting systems of bryophytes in space.

plant biology↗

bioRxiv2023

The cadmium-hypertolerant fern, Athyrium yokoscense, exhibits two cadmium stress mitigation strategies in the roots and the aerial parts

Athyrium yokoscense is hypertolerant to cadmium (Cd) and can grow normally under a high Cd concentration despite Cd being a highly toxic heavy metal. To mitigate Cd stress in general plant species, Cd is promptly chelated with a thiol compound and is isolated into vacuoles. Generated active oxygen species (ROS) in the cytoplasm are removed by reduced glutathione. However, we found many differences in the countermeasures in A. yokoscense. Thiol compounds accumulated in the stele of the roots, although a long-term Cd exposure induced Cd accumulation in the aerial parts. Synchrotron radiation-based X-ray fluorescence (SR-XRF) analysis indicated that a large amount of Cd was localized in the cell walls of the roots. Overexpression of AyNramp5a, encoding a representative Fe and Mn transporter of A. yokoscense, increased both Cd uptake and iron and manganese uptake in rice calli under the Cd exposure conditions. Organic acids were abundantly detected in A. yokoscense roots. Investigating the chemical forms of the Cd molecules by X-ray absorption fine structure (XAFS) analysis detected many compounds with Cd-oxygen (Cd-O) binding in A. yokoscense roots, whereas in the aerial parts, the ratio of the compounds with Cd-sulfur (Cd-S) binding was increased. Together, our results imply that the strong Cd tolerance of A. yokoscense is an attribute of the following two mechanisms: Cd-O compound formation in the cell wall is a barrier to reduce Cd uptake into aerial parts. Thiol compounds in the region of root stele are involved in detoxication of Cd by formation of Cd-S compounds. Statements and DeclarationsNo potential conflict of interest was reported by the authors.

plant biology↗

bioRxiv2023

Network-based prediction approach for cancer-specific driver missense mutations using a graph neural network

BackgroundIn cancer genomic medicine, finding driver mutations involved in cancer development and tumor growth is crucial. Machine-learning methods to predict driver missense mutations have been developed because variants are frequently detected by genomic sequencing. However, even though the abnormalities in molecular networks are associated with cancer, many of these methods focus on individual variants and do not consider molecular networks. Here we propose a new network-based method, Net-DMPred, to predict driver missense mutations considering molecular networks. Net-DMPred consists of the graph part and the prediction part. In the graph part, molecular networks are learned by a graph neural network (GNN). The prediction part learns whether variants are driver variants using features of individual variants combined with the graph features learned in the graph part. ResultsNet-DMPred, which considers molecular networks, performed better than conventional methods. Furthermore, the prediction performance differed by the molecular network structure used in learning, suggesting that it is important to consider not only the local network related to cancer but also the large-scale network in living organisms. ConclusionsWe propose a network-based machine learning method, Net-DMPred, for predicting cancer driver missense mutations. Our method enables us to consider the entire graph architecture representing the molecular network because it uses GNN. Net-DMPred is expected to detect driver mutations from a lot of missense mutations that are not known to be associated with cancer.

bioinformatics↗

bioRxiv2022

Inhibition of the BMP pathway suppresses tumor growth via downregulation of EGFR in MEK/ERK-dependent colorectal cancer

The bone morphogenetic protein (BMP) pathway promotes differentiation and induces apoptosis in normal colorectal epithelial cells. However, the effect of the BMP pathway in colorectal cancer (CRC) is controversial; it can either be tumor promoting or tumor suppressing, depending on the study. In this study, we found that CRC cells reside in a BMP-rich environment based on RNA-sequencing database analysis. Suppression of BMP using a specific BMP inhibitor, LDN193189, suppresses the growth of organoids in some CRC cases. CRC organoids treated with LDN193189 exhibited a decrease in epidermal growth factor receptor, which was, at least in part, mediated by protein degradation induced by leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1). Among CRC organoid panels from 18 different patients, suppression of organoid growth by BMP inhibition correlated with the induction of LRIG1 gene expression. Notably, knockdown of LRIG1 in organoids diminished the growth-suppressive effect of LDN193189. Furthermore, simultaneous treatment with LDN192189 and trametinib, an FDA-approved MEK inhibitor, resulted in a combination effect in both in vivo and in vitro xenograft tumor treatment in CRC organoids, which are susceptible to growth suppression by LDN193189. Taken together, the simultaneous inhibition of BMP and MEK can be a novel treatment option in CRC cases, and evaluating in vitro growth suppression and LRIG1 induction by BMP inhibition using patient-derived organoids could offer functional biomarkers for predicting potential responders.

cancer biology↗

bioRxiv2022

Three-dimensional visualization of moss rhizoid system by refraction-contrast X-ray micro-computed tomography

Land plants have two types of shoot-supporting systems, root system and rhizoid system, in vascular plants and bryophytes. However, since the evolutionary origin of the systems are different, how much they exploit common systems or distinct systems to architect their structures are largely unknown. To understand the regulatory mechanism how bryophytes architect rhizoid system responding to an environmental factor, such as gravity, and compare it with the root system of vascular plants, we have developed the methodology to visualize and quantitatively analyze the rhizoid system of the moss, Physcomitrium patens in 3D. The rhizoids having the diameter of 21.3 m on the average were visualized by refraction-contrast X-ray micro-CT using coherent X-ray optics available at synchrotron radiation facility SPring-8. Three types of shape (ring-shape, line, black circle) observed in tomographic slices of specimens embedded in paraffin were confirmed to be the rhizoids by optical and electron microscopy. Comprehensive automatic segmentation of the rhizoids which appeared in different three form types in tomograms was tested by a method using Canny edge detector or machine learning. Accuracy of output images was evaluated by comparing with the manually-segmented ground truth images using measures such as F1 score and IoU, revealing that the automatic segmentation using the machine learning was more effective than that using Canny edge detector. Thus, machine learning-based skeletonized 3D model revealed quite dense distribution of rhizoids, which was similar to root system architecture in vascular plants. We successfully visualized the moss rhizoid system in 3D for the first time.

plant biology↗

bioRxiv2022

A model for generating differences in microtubules between axonal branches depending on the distance from terminals

In the remodeling of axonal arbor, the growth and retraction of branches are differentially regulated within a single axon. Although cell-autonomously generated differences in microtubule (MT) turnover are thought to be involved in selective branch regulation, the cellular system whereby neurons generate differences of MTs between axonal branches has not been clarified. Because MT turnover tends to be slower in longer branches compared with neighboring shorter branches, feedback regulation depending on branch length is thought to be involved. In the present study, we generated a model of MT lifetime in axonal terminal branches by adapting a length-dependent model in which parameters for MT dynamics were constant in the arbor. The model predicted that differences in MT lifetime between neighboring branches could be generated depending on the distance from terminals. In addition, the following points were predicted. Firstly, destabilization of MTs throughout the arbor decreased the differences in MT lifetime between branches. Secondly, differences of MT lifetime existed even before MTs entered the branch point. In axonal MTs in primary neurons, treatment with a low concentration of nocodazole significantly decreased the differences of detyrosination (deTyr) and tyrosination (Tyr) of tubulins, indicators of MT turnover. Expansion microscopy of the axonal shaft before the branch point revealed differences in deTyr/Tyr modification on MTs. Our model recapitulates the differences in MT turnover between branches and provides a feedback mechanism for MT regulation that depends on the axonal arbor geometry.

neuroscience↗

bioRxiv2021

Distinct and interchangeable growing patterns in colorectal cancer stem-like cells are regulated by Musashi-1

The dynamic and heterogeneous features of cancer stem-like cells (CSCs) have been widely recognized, but their nongenetic cellular plasticity mechanisms remain elusive. By using colorectal cancer organoids, we phenotypically tracked their spheroid formation and growth capacity to a single-cell resolution, and we discovered that the spheroid-forming cells exhibit a heterogeneous growth pattern, consisting of slow- and fast-growing spheroids. The isolated fast-growing spheroids seem to preserve a dual-growing pattern through multiple passages, whereas the isolated slow-growing spheroids are restricted to a slow-growing pattern. Notably, the spheroids of both patterns were tumorigenic. Moreover, the expression of CSC markers varied among the subpopulations with different growth patterns. The isolated slow-growing spheroids adopted the dual-growing pattern by various extrinsic triggers, in which Musashi-1 plays a key role. The slow-growing fraction was resistant to chemotherapy, and its successful isolation can provide an in vitro platform allowing us to elucidate their role in drug resistance.

cancer biology↗

bioRxiv2021

Network-based pathogenicity prediction for variants of uncertain significance

While the number of genome sequences continues to increase, the functions of many detected gene variants remain to be identified. These variants of uncertain significance constitute a major barrier to precision medicine 1-3. Although many computational methods have been developed to predict the function of these variants, they all rely on individual gene features and do not consider complex molecular relationships. Here we develop PathoGN, a molecular network-based approach for predicting variant pathogenicity. PathoGN significantly outperforms existing methods using benchmark datasets. Moreover, PathoGN successfully predicts the pathogenicity of 3,994 variants of uncertain significance in the real-world database ClinVar and designates potential pathogenicity. This is the first computational method for the clinical interpretation of variants using biomolecular networks, and we anticipate our method to be broadly useful for the clinical interpretation of variants and for assigning biological function to unknown variants at the genomic scale.

genomics↗