Biology subjects

Hirose, A.

Publications and source records attributed to Hirose, A..

5 recordsLinked to original sources

bioRxiv2024

Cross-regulation of amino acid synthesis and catabolic electron transfer in bacteria

Amino acids are essential for life, serving primarily as the building blocks of proteins. Although the intracellular metabolic fate of amino acids is known, their roles in the global regulation of metabolic pathways are poorly characterized. Here, we investigated the function of amino acids as signaling molecules that modulate the catabolic activity of bacterial cells. Using the model bacterium Shewanella oneidensis MR-1, we showed that methionine activates catabolic processes, including extracellular electron transfer, at submillimolar concentrations. This regulation is mediated by MetR, a transcription factor that regulates methionine biosynthesis. In addition, the MetR-mediated regulation of catabolic electron transfer was observed in Aeromonas hydrophila. These findings reveal methionine-induced signaling cascades that cross-regulate amino acid biosynthesis and catabolism in bacteria. Our study highlights a novel physiological role for amino acids, suggesting their involvement in the coordinated regulation of anabolism and catabolism, particularly in bacteria that thrive in nutrient-limited habitats.

microbiology↗

bioRxiv2024

A Library of Custom PEG-Lipids reveals a Double-PEG-Lipid with Drastically Enhanced Paclitaxel Solubility and Human Cancer Cell Cytotoxicity when used in Fluid Micellar Nanoparticles

Paclitaxel (PTX) is one of the most widely utilized chemotherapeutics globally. However, the extremely poor water solubility of paclitaxel necessitates a mechanism of delivery within blood. Fluid lipid PTX nanocarriers (lipids in the chain-melted state) show promise as PTX delivery vectors, but remain limited by their solubility of PTX within the membrane. To improve pharmacokinetics, membrane surfaces are typically coated with polyethylene glycol (PEG). Recent work has demonstrated the generation of a population of micelles within fluid lipid formulations containing a 2kDa PEG-lipid at a 10 mol% ratio. Driven by the positive curvature of the PEG-lipid (i.e. area of head group > area of tails), micelle-containing formulations were found to exhibit significantly higher uptake in cancer cells, cytotoxicity, and in vivo antitumor efficacy compared to formulations containing solely liposomes. Here, we describe the custom synthesis of a library of high-curvature micelle-inducing PEG-lipids and examine the effects of PEG chain length, chain branching (single- or double-PEG-lipid), and cationic charge on PTX solubility and cytotoxicity. We examined PEG-lipids at standard (10 mol%) and high (100-x mol%, where x=PTX mol%) formulation ratios. Remarkably, all formulations containing the synthesized high-curvature PEG-lipids had improved PTX solubility over unPEGylated formulations and commercially available DOPE-5k. The highest PTX solubility was found within the 100-xO_SCPLOWPTXC_SCPLOW mol% PEG-lipid micellar formulations, with particles made from 2k2 (two PEG2k chains) encapsulating 13 mol% PTX for up to 24 h. The pancreatic cancer cell line PC3 exhibited higher sensitivity to formulations containing PEG-lipid at 100-xO_SCPLOWPTXC_SCPLOW mol%, the most potent of which being formulations made from 2k2 (IC50 = 14 nM). The work presented here suggests formulations employing high-curvature PEG-lipids, particularly the double-PEG-lipid 2k2, hold great potential as next-generation PTX delivery systems owing to their high PTX solubility, enhanced cell cytotoxicity, and ability for precision targeting by affixation of ligands to the PEG molecules.

bioengineering↗

bioRxiv2020

Oxicam-type NSAIDs enhance Agrobacterium-mediated transformation in plants

Agrobacterium-mediated transformation represents a key innovation for plant breeding and is routinely used in research and applied biology. However, for several species, the efficacy of transformation is limited. In this study, we discovered that oxicam-type nonsteroidal anti-inflammatory drugs (NSAIDs), including tenoxicam (TNX), enhance the efficiency of Agrobacterium-mediated transient transformation in the model species Arabidopsis thaliana via leaf infiltration and can be successfully applied in analyses of the subcellular localisation of fluorescent fusion proteins. TNX acts as an inhibitor of plant immune responses and lacks similar transient transformation efficiency in a dde2/ein2/pad4/sid2 quadruple mutant background, thereby indicating that TNX increases the efficiency of Agrobacterium infection via a transient shutdown of the immune system mediated by jasmonic acid, ethylene, and salicylic acid signalling. In addition, we found that TNX enhances the efficiency of stable transformation in crops of agricultural and economic importance, such as Jatropha and maize, indicating that TNX can enhance the integration of exogenous DNA into the plant genome via an increased introduction of DNA into plant cells. Given that treatment with oxicam compounds is simple, cost effective, and has broad utility, we anticipate that this discovery will contribute to accelerating genome-editing technologies in plants.

plant biology↗

bioRxiv2020

Visualization of seasonal shifts of phosphorus re-translocation and overwintering recycling in a shortened annual cycle system of the deciduous poplar tree (Populus alba L.).

Phosphorus (P) is an essential macronutrient for plant growth. In deciduous trees, P is remobilized from senescing leaves and stored in perennial tissues during winter for further growth. Annual internal recycling and accumulation of P is considered an important strategy to support vigorous growth of trees. However, the pathways of seasonal re-translocation of P and the molecular mechanisms of this transport have not been clarified. Here we show the seasonal P re-translocation route visualized using the real-time radioisotope imaging and the macro- and micro-autoradiography. We analyzed the seasonal re-translocation P in poplar (Populus alba. L) cultivated under "a shortened annual cycle system", which mimicked seasonal phenology in a laboratory. From growing to senescing season, sink tissues of 32P and/or 33P shifted from young leaves and the apex to the lower stem and roots. The radioisotope P re-translocated from a leaf was stored in phloem and xylem parenchyma cells and redistributed to new shoots after dormancy. Seasonal expression profile of phosphate transporters (PHT1, PHT5 and PHO1 family) was obtained in the same system. Our results reveal the seasonal P re-translocation routes at the organ and tissue levels and provide a foothold for elucidating its molecular mechanisms.

plant biology↗

bioRxiv2018

Microglial SIRPα regulates the emergence of CD11c+ microglia and demyelination damage in white matter

A characteristic subset of microglia expressing CD11c appears in response to brain damage. However, the functional role of CD11c+ microglia, as well as the mechanism of its induction, are poorly understood. Here we report that the genetic ablation of signal regulatory protein (SIRP), a membrane protein, induced CD11c+ microglia in the brain white matter. Mice lacking CD47, a physiological ligand of SIRP, and microglia-specific SIRP knockout mice exhibited the same phenotype, suggesting the interaction between microglial SIRP and CD47 on neighbouring cells suppressed the emergence of CD11c+ microglia. A lack of SIRP did not cause detectable damage in the white matter, but resulted in the increased expression of genes characteristic of the repair phase after demyelination. In addition, cuprizone-induced demyelination was alleviated by the microglia-specific ablation of SIRP. Thus, microglial SIRP suppresses the induction of CD11c+ microglia that have the potential to accelerate the repair of damaged white matter.

neuroscience↗