Biology subjects

Sato, T.

Publications and source records attributed to Sato, T..

8 recordsLinked to original sources

bioRxiv2018

Anti-tumor effects of antimicrobial peptides, targets of the innate immune system, against hematopoietic tumors in Drosophila mxc mutants

The innate immune response is the first line of defense against microbial infections. In Drosophila, three immune pathways induce the synthesis of antimicrobial peptides (AMPs) in the fat body. Recently, it has been reported that certain cationic AMPs exhibit selective cytotoxicity against human cancer cells. However, little is known about their anti-tumor effects. Drosophila mxcmbn1 mutants exhibit malignant hyperplasia in a larval hematopoietic organ called the lymph gland (LG). Here, using RNA-Seq analysis, we found that many immunoresponsive genes, including AMP genes, were up-regulated in the mutants. Down-regulation of these pathways by either a Toll or an imd mutation enhanced the tumor phenotype of the mxc mutants. Conversely, ectopic expression of each of five different AMPs in the fat body significantly suppressed the LG hyperplasia phenotype in the mutants. Thus, we propose that the Drosophila innate immune system can suppress progression of hematopoietic tumors by inducing AMP gene expression. Overexpression of any one of these five AMPs resulted in enhanced apoptosis in the mutant LGs, while no apoptosis signals were detected in controls. We observed that two AMPs, Drosomycin and Defensin, were taken up by circulating hemocyte-like cells, which were associated with LG regions showing reduced cell-to-cell adhesion in the mutants; another AMP, diptericin, was directly localized on the tumors without intermediating hemocytes. These results lead us to conclude that the AMPs have a specific cytotoxic effect that enhance apoptosis exclusively in the tumor cells.\n\nSummary statementAntimicrobial peptides can be associated with tumor cells generated in a hematopoietic tissue in Drosophila mxc mutants and have an anti-tumor effect in suppressing their growth.

developmental biology↗

bioRxiv2018

A transgenic mutant mouse line accompanied by the complete deletion of interleukin-33 showed insulin and leptin resistances

Interleukin (IL) -33 has been identified as a member of the IL-1 family. Members of the IL-1 family have been reported to be involved in the regulation of energy homeostasis and glucose metabolism. Homozygous transgenic mutant mice of FLP14 line, that we previously generated, unexpectedly developed mature-onset obesity and diabetes. Through genetic investigations, we found that insertion of the transgenes had resulted in complete deletion of the Il33 gene. These obese male homozygous mutant mice exhibited hyperphagia with hyperleptinemia and insulin resistance caused by increased hepatic gluconeogenesis and decreased glucose uptake in skeletal muscle. As a result of examining preobese male homozygous mutant mice to investigate with the exclusion of the effect of obesity, hyperphagia with hyperleptinemina and insulin resistance caused by decreased glucose uptake in skeletal muscle were already observed, but the increased hepatic glucose production was not. To investigate whether the insulin resistance was caused by deletion of the Il33 gene, we treated these preobese homozygous mutant mice with recombinant IL-33 protein and noted a significant improvement in insulin resistance. Thus, insulin resistance in these homozygous mutant mice was caused, at least in part, by IL-33 deficiency, suggesting a favorable role of IL-33 for glucose metabolism in the skeletal muscle.

molecular biology↗

bioRxiv2018

Narrowly confined and glomerulus-specific onset latencies of odor-evoked calcium transients in the periglomerular cells of the mouse main olfactory bulb

Odor information is transmitted from olfactory sensory neurons to principal neurons at the glomeruli of the olfactory bulb. The intraglomerular neuronal circuit also includes hundreds of GABAergic interneurons referred to as periglomerular (PG) cells. Stimulus selectivity is well correlated among PG cells that are associated with the same glomerulus, consistent with their highly homogeneous sensory inputs. However, much less is known about the temporal aspects of their activity, including the temporal coordination of their odor-evoked responses. As many PG cells within a glomerular module respond to the same stimulus, the extent to which their activity is temporally aligned will affect the temporal profile of their population inhibitory inputs. Using random-access high-speed two-photon microscopy, we recorded the odor-evoked calcium transients of mouse PG cells and compared the onset latency and rise time among neurons putatively associated with the same and different glomeruli. Whereas the overall onset latencies of odor-evoked transients were distributed across a ~150 ms time window, those from cells putatively associated with the same glomerulus were confined to a much narrower window of several tens of milliseconds. This result suggests that onset latency primarily depends on the associated glomerulus. We also observed glomerular specificity in the rise time. The glomerulus-specific temporal pattern of odor-evoked activity implies that the temporal patterns of inhibitory inputs are unique to individual glomerulus-odor pairs, which may contribute to efficient shaping of the temporal pattern of activity in the principal neurons.

neuroscience↗

bioRxiv2018

Skull base invasive low-grade meningiomas, a distinct genetic subgroup: A microarray gene expression profile analysis.

IntroductionMeningioma is the most common adult primary brain tumor originating from meningeal coverings of the brain and spinal cord. Commonly, World Health Organization (WHO) grade-I meningiomas are slowly growing and surgically curative, some present with clinically aggressive behavior, invading the skull base bone and soft tissues by extending into the extracranial spaces.\n\nMethodsTo detect the genetic background of the Skull Base Invasive Low-grade Meningioma (SBILM), we conducted a comprehensive analysis of gene expression was conducted on 32 meningioma samples.\n\nResultsThe cluster analysis of the gene expression profile demonstrated a distinctive clustering pattern of the SBILM. Based on the clinical behavior and the microarray findings, they might be a distinct subgroup of meningiomas.\n\nConclusionFurther studies on characterization of genes specifically expressed by the SBILM could lead to the development of diagnostic tools, differentiating it from other WHO grade-I meningiomas and assist in the appropriate management and follow-up strategy, and open the door for development of pharmacological therapies.

genomics↗

bioRxiv2018

Predation risk and resource abundance mediate foraging behaviour and intraspecific resource partitioning among consumers in dominance hierarchies

Dominance hierarchies and unequal resource partitioning among individuals are key mechanisms of population regulation. The strength of dominance hierarchies can be influenced by size dependent trade-offs between foraging and predator avoidance whereby competitively inferior subdominants can access a larger proportion of limiting resources by accepting higher predation risk. Foraging-predation risk trade-offs also depend on resource abundance. Yet, few studies have manipulated predation risk and resource abundance simultaneously; consequently, their joint effect on resource partitioning within dominance hierarchies are not well understood. We addressed this gap by measuring behavioural responses of masu salmon to experimental manipulations of predation risk and resource abundance in a natural temperate forest stream. Responses to predation risk depended on body size such that larger dominants exhibited more risk-averse behaviour (e.g., lower foraging and appearance rates) relative to smaller subdominants after exposure to a simulated predator. The magnitude of this effect was lower when resources were elevated, indicating that dominant fish accepted a higher predation risk to forage on abundant resources. However, the influence of resource abundance did not extend to the population level, where predation risk altered the distribution of foraging attempts (a proxy for energy intake) from being skewed towards large individuals to being skewed towards small individuals after predator exposure. Our results imply that size dependent foraging-predation risk trade-offs can mediate the strength of dominance hierarchies by allowing competitively inferior subdominants to access resources that would otherwise be monopolized.\n\nAuthor ContributionsSN, TS, and RU designed the study and performed the fieldwork; SN analyzed the data and wrote the manuscript with input from all authors.

ecology↗

bioRxiv2018

A new targeted capture method using bacterial artificial chromosome (BAC) libraries as baits for sequencing relatively large genes

To analyze a specific genome region using next-generation sequencing technologies, the enrichment of DNA libraries with targeted capture methods has been standardized. For enrichment of mitochondrial genome, a previous study developed an original targeted capture method that use baits constructed from long-range polymerase chain reaction (PCR) amplicons, common laboratory reagents, and equipment. In this study, a new targeted capture method is presented, that of bacterial artificial chromosome (BAC) double capture (BDC), modifying the previous method, but using BAC libraries as baits for sequencing a relatively large gene. We applied the BDC approach for the 214 kb autosomal region, ring finger protein 213, which is the susceptibility gene of moyamoya disease (MMD). To evaluate the reliability of BDC, cost and data quality were compared with those of a commercial kit. While the ratio of duplicate reads was higher, the cost was less than that of the commercial kit. The data quality was sufficiently the same as that of the kit. Thus, BDC can be an easy, low-cost, and useful method for analyzing individual genome region with substantial length.

genomics↗

bioRxiv2017

Ultrasonic Neuromodulation Causes Widespread Cortical Activation via an Indirect Auditory Mechanism

Ultrasound has received widespread attention as an emerging technology for targeted, non-invasive neuromodulation based on its ability to evoke electrophysiological and motor responses in animals. However, little is known about the spatiotemporal pattern of ultrasound-induced brain activity that could drive these responses. Here, we address this question by combining focused ultrasound with wide-field optical imaging of calcium signals in transgenic mice. Surprisingly, we find cortical activity patterns consistent with indirect activation of auditory pathways rather than direct neuromodulation at the ultrasound focus. Ultrasound-induced activity is similar to that evoked by audible sound. Furthermore, both ultrasound and audible sound elicit motor responses consistent with a startle reflex, with both responses reduced by chemical deafening. These findings reveal an indirect auditory mechanism for ultrasound-induced cortical activity and movement requiring careful consideration in future development of ultrasonic neuromodulation as a tool in neuroscience research.

neuroscience↗

bioRxiv2017

Lipid-protein interplay in dimerization of the juxtamembrane domains of epidermal growth factor receptor

Transmembrane (TM) helix and juxtamembrane (JM) domains (TM-JM) bridge the extracellular and intracellular domains of single-pass membrane proteins, including epidermal growth factor receptor (EGFR). TM-JM dimerization plays a crucial role in regulation of EGFR kinase activity at the cytoplasmic side. Although the interaction of JM with membrane lipids is thought to be important to turn on EGF signaling and phosphorylation of Thr654 on JM leads to desensitization, the underlying kinetic mechanisms remain unclear. Especially, how Thr654 phosphorylation regulates EGFR activity is largely unknown. Here, combining single-pair FRET imaging and nanodisc techniques, we showed that phosphatidylinositol 4,5-bis phosphate (PIP2) facilitated JM dimerization effectively. We also found that Thr654 phosphorylation dissociated JM dimers in the membranes containing acidic lipids, suggesting that Thr654 phosphorylation electrostatically prevented the interaction with basic residues in JM and acidic lipids. Based on the single-molecule experiment, we clarified the kinetic pathways of monomer (inactive state) - dimer (active state) transition of JM domains and alteration in the pathways depending on the membrane lipid species and Thr654 phosphorylation.

biophysics↗