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Murakami, H.

Publications and source records attributed to Murakami, H..

At least 19 recordsLinked to original sources

Determination of effective meropenem and gentamicin doses in a silkworm infection model using a clinical Klebsiella aerogenes isolate

Klebsiella aerogenes, a member of the Enterobacteriaceae, is a causative agent of healthcare-associated infections, and outbreaks caused by drug-resistant K. aerogenes have been reported worldwide. The range of antimicrobial agents available for treating infections caused by carbapenem-resistant K. aerogenes is limited. While in vivo animal experiments using clinical K. aerogenes isolates to evaluate antimicrobial therapy could facilitate selection of the most effective treatment, conducting infection experiments involving large numbers of mammals such as mice is challenging due to ethical concerns related to animal welfare. Silkworms are invertebrates increasingly used as experimental models for infectious disease research to evaluate antimicrobial efficacy. In this study, we aimed to establish a silkworm infection model using a clinical K. aerogenes isolate to evaluate its utility for determining effective antimicrobial doses. K. aerogenes strains were isolated from a patient at a Japanese hospital, and a silkworm infection model was established using the clinical isolate. The non-metallo-beta-lactamase-producing strain K. aerogenes TUM25562, isolated from a patient with a complicated urinary tract infection, was susceptible to meropenem (MEPM) and gentamicin (GM) in vitro. During treatment, additional isolates with increased resistance to MEPM and subsequently to both MEPM and GM emerged. K. aerogenes TUM25562 caused dose-dependent mortality in silkworms. Treatment with clinically equivalent weight-based doses of MEPM or GM did not cure the infected silkworms. The median effective (ED50) doses of MEPM and GM were therefore investigated using the silkworm infection model. Administration of higher doses corresponding to four times the ED50 significantly prolonged the survival of infected silkworms. These results suggest that a silkworm infection model using clinical K. aerogenes isolates may provide a practical approach for evaluating antimicrobial efficacy and determining effective antimicrobial doses.

microbiology↗

Cohesin–axis interaction via a conserved Red1 motif promotes domain-specific DSB formation and Mek1 activation

Faithful chromosome segregation during meiosis I requires tight control of interhomolog recombination. In budding yeast, the meiotic chromosome axis, built on Rec8-containing cohesin together with Red1 and Hop1, acts as a central platform regulating meiotic recombination from programmed DNA double-strand break (DSB) formation to checkpoint signaling and chromosome segregation, yet how cohesin recruits axis proteins remains unclear. Here, we identified a conserved cohesin-interacting motif (CIM) in Red1 that directly binds Rec8. AlphaFold3 modeling predicted that Red1-CIM forms a short -helix that docks into a conserved hydrophobic pocket within the Rec8 C-terminal winged-helix domain, which we confirmed biochemically. Disruption of the Red1-CIM preferentially impaired Red1 recruitment to Rec8-dependent chromosomal regions, while relative enrichment in Rec8-independent domains was preserved, leading to reduced DSB formation in Rec8-dependent domains. The Red1-CIM mutation also reduced crossover formation, increased chromosome missegregation, and reduced spore viability. Notably, this spore lethality exceeded that predicted by the reduction in DSB formation. Consistently, red1-CIM mutants failed to activate the meiotic checkpoint kinase Mek1. Finally, we provide evolutionary, structural, and biochemical evidence that this Red1-Rec8 interaction is conserved across fungi and plants. Together, these findings define a direct molecular bridge linking cohesin to chromosome-axis organization, spatial DSB regulation, and checkpoint signaling during meiosis.

molecular biology↗

Running the distance: robustness of embodied distance measurement despite social interference in fiddler crabs

Path integration (PI) is an essential navigation strategy. Through PI, animals integrate their movements during foraging into a home vector" that allows direct return to the origin. In humans, feedback from body movement contributes to readout of the home vector: physical estimation by walking toward the origin improves peoples ability to identify the origin point. However, how such feedback affects home vector readout in other animals remains unclear. Here, we show that leg movement feedback contributes to a robust readout of the home vector despite social interference in fiddler crabs. We found that whereas the internal estimation of burrow location during the return path is subject to induced errors by social behavior, the physical estimation is not, and feedback from leg movement contributes to robust distance measurement. Our findings suggest that animals may have evolved complex navigational systems to handle the inevitable interplay between navigational cues and social behavior.

animal behavior and cognition↗

De novo chemo-optogenetics through rational small-molecule design and TRAP display

Optical control of biomolecules is a powerful technique for biological research, but current tools derived from natural proteins face significant limitations. Engineering these proteins to meet researchers needs remains challenging. In this study, we present a novel approach to the de novo creation of tailored chemo-optogenetic tools. This method combines the rational design of synthetic photo-switchable molecules with in vitro selection of artificial protein binders that specifically recognize a particular conformation of these molecules. We demonstrate the utility of this approach by generating artificial proteins that bind exclusively to the cis-form of designed azobenzene derivatives. The newly created pairs enable sustained protein activation with a single light pulse and allow for precise, reversible, and repeatable switching of cellular processes using two distinct wavelengths of light in mammalian cells. This de novo technique provides tailored synthetic photoswitch-protein binder pairs, expanding the potential for optical biomolecule manipulation.

synthetic biology↗

Salivary proteins in spider mites: dual roles in feeding and silk fiber coating

Spider mites are plant cell-sucking herbivores that spin nanoscale adhesive silk fibers released from their mouthpart appendages. Previous whole-genome sequencing predicted 17 silk genes in the two-spotted spider mite, Tetranychus urticae, while silk proteomics detected two candidates, Fibroin-1 and Fibroin-2. However, saliva proteomics also detected Fibroin-1, Fibroin-2, and sFibroin-1 (with high sequence similarity to Fibroin-1). We investigated whether these three proteins function in silk, saliva, or both. We found Fibroin-1, sFibroin-1, and Fibroin-2 genes expressed in the salivary glands but found no direct internal connection between salivary and silk glands. Our silk proteomics detected 8 silk proteins previously predicted and 66 salivary proteins, including Fibroin-1, sFibroin-1, and Fibroin-2. We detected a bead-on-a-string pattern formed by fluid (hypothesized to be saliva) on the silk fiber and a fluid patch that remains at the piercing site on the leaf surface after mite feeding. RNAi-mediated silencing of Fibroin-1 and sFibroin-1 genes reduced mite feeding duration, survival, and fecundity, and silencing of Fibroin-2 gene showed a tendency to reduce the thickness of individual silk fibers. These results suggest that Fibroin-1, sFibroin-1, and Fibroin-2 are secreted from the salivary glands and then adhere to silk fibers. Fibroin-1 and sFibroin-1 may assist mites to adhere the tip of the mouthparts to the leaf surface when sucking with their stylets, while Fibroin-2 may coat silk fibers. This study reveals the dual role of saliva in plant cell-sucking herbivorous mites, namely, stabilizing the mouthparts during feeding and coating silk fibers to provide them with adhesive properties. HighlightsThree salivary proteins of spider mites are abundantly detected in their silk fibers. Though the salivary glands and silk glands are not connected, saliva appears to adhere to silk fibers after secretion. Knockdown of two of the three salivary protein genes suppressed the feeding behavior of spider mites, resulting in reduced survival and fecundity. Knockdown of the remaining salivary protein gene showed a tendency to reduce the thickness of the silk filament.

molecular biology↗

Targeting fatty acid synthase suppresses tumor development in NF2/CDKN2A-deficient malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is an uncommon yet deadly cancer linked to asbestos exposure. The lack of effective early diagnosis and treatment leads to reduced life expectancy among patients with MPM. This study is aimed to identify a novel molecular target inhibitor to develop more effective therapeutics for MPM. Our drug screening assay showed that the fatty acid synthase (FASN) inhibitor cerulenin demonstrates strong and selective anti-proliferative properties against NF2/CDKN2A(p16)-deficient MPM cells, surpassing the effects of cisplatin or pemetrexed. FASN protein is frequently detected in NF2/p16-deficient MPM tumor-derived tissues (15/15, 100%), but rarely in NF2/p16-intact MPM tumors (8/25, 32%). Notably, cerulenin administration successfully reduced the growth of NF2/p16-deficient MPM tumors in xenografted mice. Cerulenin inhibits mitochondrial fission by targeting dynamin-related protein 1 (DRP1) in NF2/p16-deficient cells. Moreover, the disruption of the FASN gene leads to increased ubiquitination of DRP1. These findings suggest that FASN might play a role in the tumorigenesis of MPM cells through the regulation of mitochondrial dynamics. This research offers a novel perspective on the potential development of precision medicine for MPM.

cancer biology↗

Meiotic DNA break resection and recombination rely on chromatin remodeler Fun30

DNA double-strand breaks (DSBs) are nucleolytically processed to generate single-stranded DNA tails for homologous recombination. In Saccharomyces cerevisiae meiosis, this 5-to-3 resection involves initial nicking by the Mre11-Rad50-Xrs2 complex (MRX) plus Sae2, then exonucleolytic digestion by Exo1. Chromatin remodeling adjacent to meiotic DSBs is thought to be necessary for resection, but the relevant remodeling activity was unknown. Here we show that the SWI/SNF-like ATPase Fun30 plays a major, non-redundant role in resecting meiotic DSBs. A fun30 null mutation shortened resection tract lengths almost as severely as an exo1-nd (nuclease-dead) mutation, and resection was further shortened in the fun30 exo1-nd double mutant. Fun30 associates with chromatin in response to meiotic DSBs, and the constitutive positioning of nucleosomes governs resection endpoint locations in the absence of Fun30. We infer that Fun30 directly promotes both the MRX- and Exo1-dependent steps in resection, possibly by removing nucleosomes from broken chromatids. Moreover, we found that the extremely short resection in the fun30 exo1-nd double mutant is accompanied by compromised interhomolog recombination bias, leading to defects in recombination and chromosome segregation. Thus, this study also provides insight about the minimal resection lengths needed for robust recombination.

molecular biology↗

Characterization of sediment and granite hosted deep underground research laboratories reveals diverse microbiome functions, limited temporal variation and substantial genomic conservation

Underground research laboratories (URLs) provide a window on the deep biosphere and enable investigation of potential microbial impacts on nuclear waste, CO2 and H2 stored in the subsurface. We carried out the first multi-year study of groundwater microbiomes sampled from defined intervals between 140 and 400 m below the surface of the Horonobe and Mizunami URLs, Japan. We reconstructed draft genomes for >90% of all organisms detected over a four year period. The Horonobe and Mizunami microbiomes are dissimilar, likely because the Mizunami URL is hosted in granitic rock and the Horonobe URL in sedimentary rock. Despite this, hydrogen metabolism, rubisco-based CO2 fixation, reduction of nitrogen compounds and sulfate reduction are well represented functions in microbiomes from both URLs, although methane metabolism is more prevalent at the organic- and CO2-rich Horonobe URL. High fluid flow zones and proximity to subsurface tunnels select for candidate phyla radiation bacteria in the Mizunami URL. We detected near-identical genotypes for approximately one third of all genomically defined organisms at multiple depths within the Horonobe URL. This cannot be explained by inactivity, as in situ growth was detected for some bacteria, albeit at slow rates. Given the current low hydraulic conductivity and groundwater compositional heterogeneity, ongoing inter-site strain dispersal seems unlikely. Alternatively, the Horonobe URL microbiome homogeneity may be explained by higher groundwater mobility during the last glacial period. Genotypically-defined species closely related to those detected in the URLs were identified in three other subsurface environments in the USA. Thus, dispersal rates between widely separated underground sites may be fast enough relative to mutation rates to have precluded substantial divergence in species composition. Species overlaps between subsurface locations on different continents constrain expectations regarding the scale of global subsurface biodiversity. Overall, microbiome and geochemical stability over the study period has important implications for underground storage applications.

microbiology↗

Information structure of heterogeneous criticality in fish school

The integrated information theory (IIT) measures the degree of consciousness in living organisms from an information-theoretic perspective. This theory can be extended to general systems such as those measuring criticality. Herein, we applied the IIT to actual collective behaviour (Plecoglossus altivelis). We found that the group integrity (i.e., {Phi}) could be maximised in the critical state and that several levels of criticalities existed in a group as subgroups. Furthermore, these fragmented critical groups coexisted with traditional criticality as a whole. The distribution of high-criticality subgroups was heterogeneous in terms of time and space. In particular, the core fish in the high-criticality group tended to be unaffected by internal and external stimulation, in contrast to those in the low-criticality group. The results of this study are consistent with previous interpretations of critical phenomena and provide a new interpretation of the detailed dynamics of an empirical critical state.

animal behavior and cognition↗

A novel spawning survey: identifying spawning times and locations of jack mackerel in a semi-closed bay using environmental DNA analysis

Understanding spawning ecology is important for species/population management and conservation. However, conventional surveys are often time- and labour-consuming and invasive. To address these challenges, environmental DNA (eDNA) analysis has emerged as a promising method for spawning surveys. This study investigated the spawning season and diurnal changes in eDNA concentrations targeted Japanese jack mackerel in Maizuru Bay, Japan, to assess the potential of eDNA-based spawning surveys in the marine environment. First, to estimate the spawning season, eDNA concentrations at sunset and sunrise were compared monthly for one year at three sites. As Japanese jack mackerel are nocturnal spawners, eDNA concentration will increase at night during the spawning season. A significant increase in eDNA concentration was observed between sunset and sunrise in July, suggesting that this period corresponded to the spawning season. This was confirmed by egg collection surveys using a plankton net. Second, to investigate diurnal changes in eDNA concentrations during the spawning season, time-series sampling was conducted every three hours for 24 hours in July. The results indicated that eDNA concentration showed a significant diurnal change with a peak between 9 PM and midnight, which is suggested to be their spawning time window. This study successfully estimated the spawning season of Japanese jack mackerel and demonstrated the potential of eDNA-based spawning surveys for the first time in marine environments. These surveys are expected to contribute to the advancement of this field as a new approach to overcoming traditional challenges in marine spawning surveys. HighlightsO_LIThe potential of eDNA for spawning surveys was assessed in jack mackerel. C_LIO_LIMonthly morning and evening eDNA sampling identified spawning activity in July. C_LIO_LIEgg surveys using a plankton net confirmed the spawning event. C_LIO_LITime-series sampling showed a diurnal change in eDNA concentrations in July. C_LIO_LIeDNA analysis is thus applicable for detecting spawning in marine species. C_LI

ecology↗

Robust spatial self-organization in crowds of asynchronous pedestrians

Similar to other animal groups, human crowds exhibit a variety of self-organized collective behaviors. Spontaneous formation of unidirectional lanes in bidirectional pedestrian flows is one of the most striking examples of self-organization in human crowds. In addition, previous experimental studies have suggested that stepping among pedestrians is spontaneously synchronized over time. However, those studies have primarily focused on one-dimensional, single-file crowds, limiting our understanding of temporal stepping patterns in crowds with more freedom of movement and their relationship to spatial patterns of organization. Here, we conducted experiments of bidirectional pedestrian flows (24 pedestrians in each group) and investigated the relationship between collective footsteps and self-organized lane formation by tracking each individual trajectory as well as foot-stepping kinematics. We found that, unlike previous studies, pedestrians did not spontaneously align their steps unless there was an external auditory cue to follow. Moreover, we found that footstep synchronization generated by external cues disturbed the flexibility of pedestrians lateral movements, increased potential collision risks, and narrowed the formed lanes, suggesting structural instability in the spatial organization. These results imply that, without external cues, pedestrians marching out of step with each other can efficiently self-organize into robust structures. Understanding how asynchronous individuals contribute to ordered collective behavior has potential applications for promoting efficient crowd management and will inform theoretical models for human and other animal collective behavior with asynchronous positional updates.

animal behavior and cognition↗

Cdc48 and its co-factor Ufd1 segregate CENP-A from centromeric chromatin and can induce chromosome elimination in the fission yeast Schizosaccharomyces pombe.

CENP-A, a variant of histone H3, determines the identity of the centromere, a chromosome locus at which a microtubule attachment site termed kinetochore is assembled. Because the position and size of the centromere and its number per chromosome must be maintained for the faithful segregation of chromosomes, the distribution of CENP-A is strictly regulated. In this study, we have aimed to understand mechanisms to regulate the distribution of CENP-A by a genetic approach in the fission yeast Schizosaccharomyces pombe. A mutant of the ufd1+ gene (ufd1-73) encoding a cofactor of Cdc48 ATPase is sensitive to CENP-A expressed at a high level and allows mislocalization of CENP-A. ChIP analysis has revealed that the level of CENP-A in centromeric chromatin is increased in the ufd1-73 mutant even when CENP-A is expressed at a normal level. A preexisting mutant of the cdc48+ gene (cdc48-353) phenocopies the ufd1-73 mutant. We have also shown that Cdc48 and Ufd1 proteins physically interact with centromeric chromatin. Finally, Cdc48 ATPase with Ufd1 artificially recruited to the centromere of a mini-chromosome (Ch16) induce a loss of CENP-A from Ch16, resulting in an increased rate of chromosome loss. It appears that Cdc48 ATPase, together with its cofactor Ufd1 segregates excess CENP-A from chromatin, likely in a direct manner, to maintain proper distribution of CENP-A. This mechanism may play an important role in centromere disassembly, a process to eliminate CENP-A massively to inactivate the kinetochore function during development, differentiation, and stress response in other organisms. Significance statementMaintaining the proper distribution of CENP-A is crucial for centromere identity. This process involves accurate positioning of CENP-A and removal of excess CENP-A from chromatin. The Cdc48-Ufd1 complex is essential for this regulation as it acts as a segregase that directly eliminates surplus CENP-A from chromatin. These findings have therapeutic significance as targeting the Cdc48 complex can potentially correct abnormal karyotypes in disomic embryos and prevent trisomic disorders like Down syndrome. This research advances our understanding of centromeric chromatin regulation and its potential therapeutic applications.

molecular biology↗

Optineurin provides a mitophagy contact site for TBK1 activation

Tank-binding kinase 1 (TBK1) is a Ser/Thr kinase involved in many intracellular processes including innate immunity, cell cycle, and apoptosis. TBK1 is also important for phosphorylating autophagy adaptors critical in selective autophagic removal of damaged mitochondria (mitophagy). However, the mechanism by which TBK1 is activated by PINK1/Parkin-mediated mitophagy remains largely unknown. Here, we show that the autophagy adaptor OPTN provides a unique platform for TBK1 activation. The OPTN-ubiquitin and OPTN-autophagy machinery interaction axes facilitate assembly of the OPTN-TBK1 complex at a contact site between damaged mitochondria and the autophagosome formation site. This assembly point serves as a positive feedback loop for TBK1 activation by accelerating hetero-autophosphorylation of the protein. Furthermore, expression of monobodies engineered in this study against OPTN impaired assembly of OPTN at the contact sites as well as the subsequent activation of TBK1 and mitochondrial degradation. Taken together the findings reveal that a positive reciprocal relationship between OPTN and TBK1 initiates autophagosome biogenesis on damaged mitochondria.

cell biology↗

Spontaneous behavioral coordination between pedestrians emerges through mutual anticipation rather than mutual gaze

Human activities are often performed together between two or more persons, as if they are a complex dance. Threading through a crowd is a striking example of such coordinated actions. Behavioral coordination should help to reduce head-on collisions, smooth a pedestrians pathway through a crowd, and promote a self-organization process. Although mutual anticipation between pedestrians would be a candidate for underlying mechanisms of behavioral coordination, it remains largely unexplored, especially in terms of visual information. Here, we investigated the effects of mutual anticipation between a pair of pedestrians performing simple avoidance tasks using a combination of motion- and eye-tracking systems. We found that pedestrians in a baseline condition spontaneously coordinated their walking speed and angle until passing each other. Visually distracting one of the pedestrians decreased the level of behavioral coordination, indicating that spontaneous coordination emerges through mutual anticipation. Importantly, blocking the pedestrians gaze information alone did not alter their walking, clearly ruling out the assumption that mutual gaze impacts pedestrian anticipation behavior. Moreover, eye-movement analysis demonstrated that the direction of a pedestrians gaze changed depending on the uncertainty of the oncoming pedestrians motion and that pedestrians tend to look ahead toward the ultimate passing direction before they actually walked in that direction. We propose that body motion cues may be sufficient and available for implicit negotiation on potential future motions. Our findings should be useful in various fields, including research on improvisational motions, pedestrian transportation, and robotic navigation.

animal behavior and cognition↗

Comprehensive analysis of the effect of mRNA sequences on translation efficiency and accuracy

Messenger ribonucleic acid (mRNA) sequences influence the translation efficiency and accuracy. To increase our knowledge of how mRNA sequences affect ribosome translation and apply the obtained information to improve the mRNA display method, we conducted a comprehensive analysis of the effect of mRNA sequences on the translation. Translation efficiency depended strongly on the three codons following the start codon. Furthermore, the codons at the ribosomal E- and P-sites strongly influence the misreading of the A-site blank codon by near-cognate transfer RNA. The purine base after the blank codon also induced a higher misread rate than that with a pyrimidine base. Based on these findings, we demonstrated construction of highly diverse monobody and macrocyclic peptide libraries that would be useful in developing functional peptides and proteins in the future.

biochemistry↗

Analysis of the persistence and particle size distributional shift of sperm-derived environmental DNA to monitor Jack Mackerel spawning activity

Environmental DNA (eDNA) analysis holds great promises as an efficient and noninvasive method to monitor not only the presence and biomass of organisms but also their spawning activity. In eDNA analysis-based monitoring of spawning activity, the detection of sperm-derived eDNA is a key point; however, its characteristics and dynamics are completely unknown. The present study focuses on the persistence and particle size distribution (PSD) of eDNA derived from the sperm of Japanese jack mackerel. First, we investigated the time-dependent degradation and the PSD of sperm-derived eDNA by artificially adding sperm to fish eDNA-free seawater. Next, we kept fish in tanks and examined the changes in DNA concentration and PSD before and after spawning. The data obtained from the two experiments showed that the degradation of sperm-derived eDNA proceeded rapidly, with PSD shifting to a smaller size, regardless of the DNA region (Cyt b or ITS1). Additionally, it was shown that the nuclei and mitochondria released from sperm through degradation had a size distribution that was not simply dependent on each organelle size. The results of this study will contribute to elucidating the characteristics and dynamics of eDNA specifically during the spawning season and to further developing eDNA analysis as a powerful tool for the monitoring of spawning activity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/483695v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@15a91e8org.highwire.dtl.DTLVardef@1212566org.highwire.dtl.DTLVardef@11e5e95org.highwire.dtl.DTLVardef@d39a36_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

An efficient early-pooling protocol for environmental DNA metabarcoding

Environmental DNA (eDNA) metabarcoding, a method that applies high-throughput sequencing and universal primer sets to eDNA analysis, has been a promising approach for efficient, comprehensive biodiversity monitoring. However, significant money-, labor-, and time-costs are still required for performing eDNA metabarcoding. In the present study, we assessed the performance of an "early-pooling" protocol (a protocol based on the 1st PCR indexing) to reduce the experimental costs of the library preparation for eDNA metabarcoding. Specifically, we performed three experiments to test the effects of 1st PCR and 2nd PCR indexing protocols on the community composition revealed by eDNA metabarcoding, of post-1st-PCR exonuclease purification on index-hopping, and of the number of PCR replicates and eDNA template volume on the number of detected OTUs. By analyzing 204 eDNA libraries from 3 natural aquatic ecosystems and 1 mock eDNA sample, we show that (i) the 1st PCR indexing does not cause clear biases in the outcomes of eDNA metabarcoding, (ii) post-1st-PCR exonuclease purification reduces the risk of index-hopping, and (iii) increasing the eDNA template volume can increase the number of detected OTUs and reduce the variations in detected community compositions, as can increasing the number of the 1st PCR replicates. Our results show that an early-pooling protocol with post-1st-PCR exonuclease purification and an increased amount of DNA template will reduce the risk of index-hopping, the costs for consumables and reagents, and the handling time in the library preparation, and that it produces comparable results to a 2nd-PCR-indexing protocol. Therefore, once a target metabarcoding region is determined and a set of indexed-1st-PCR primers is prepared, the early-pooling protocol provides a cost-, labor-, and time-efficient way to process a large number of samples.

ecology↗

Biogenic action of Lactobacillus plantarum SBT2227 promotes sleep in Drosophila melanogaster

Lactic acid bacteria (LAB) influence multiple aspects of host brain function via the production of active metabolites in the gut, which is known as the pre/pro-biotic action. However, little is known about the biogenic effects of LAB on host brain function. Here, we reported that the Lactobacillus plantarum SBT2227 promoted sleep in Drosophila melanogaster. Administration of SBT2227 primarily increased the amount of sleep and decreased sleep latency at the beginning of night-time. The sleep-promoting effects of SBT2227 were independent of the existing gut flora. Furthermore, heat treatment or mechanical crushing of SBT2227 did not suppress the sleep-promoting effects, indicative of biogenic action. Transcriptome analysis, and RNAi mini-screening for gut-derived peptide hormones revealed the requirement of neuropeptide F, a homologue of the mammalian neuropeptide Y, for the action of SBT2227. These biogenic effects of SBT2227 on the host sleep provide new insights into the interaction between the brain and gut bacteria.

animal behavior and cognition↗