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Kawamura, K.

Publications and source records attributed to Kawamura, K..

17 recordsLinked to original sources

Distinct associative learning abilities for colour and odour in the flower-feeding Drosophila elegans and the fruit-feeding Drosophila melanogaster

Animal behaviour is both innately constrained and shaped by learning. This mosaic organization has evolved in response to species-specific ecological demands and may differ between sensory modalities. Flower-visiting animals are a particularly useful system for investigating the relationship between sensory ecology and learning because they rely on multiple floral cues, particularly odour and colour, to locate food sources. However, it remains largely unexplored whether specialization on floral resources entails divergence in learning abilities across sensory modalities. Drosophila elegans is a flower-feeding species that depends heavily on floral resources throughout its life; adults spend much of their time on flowers and larvae develop on fallen flower leaves. Here, we compared odour-reward and colour-reward associative learning between the flower-feeding D. elegans and the fruit-feeding D. melanogaster. We found that, under conditions of equilibrated motivation, odour- and colour-preference, and using the same sugar reward, D. elegans exhibited poorer odour-reward learning performance but better colour-reward learning performance than D. melanogaster. These results suggest that the modality-specific eligibility of sensory information to enter into associations, known as the 'Garcia-effect' in experimental psychology, can evolve oppositely between species. This highlights the relationship between ecological specialization and mnemonic processing, and shows that biological 'intelligence' is not general.

evolutionary biology↗

Lid speculum as effective active and reference electrodes for electroretinography recording in normal rabbits

PurposeAlthough electroretinography (ERG) is vital for evaluating retinal function, conventional corneal electrodes slide or detach in animals. This study aimed to investigate the effectiveness of a novel approach to ERG recording using a metal eyelid speculum for both active and reference electrodes in conjunction with a skin electrode-based ERG device. MethodsWe tested a stainless-steel eyelid speculum as both active and reference electrodes with a skin-electrode ERG system (HE-2000vet) in six healthy Japanese White rabbits. Dark-adapted rod and maximal responses and light-adapted cone and 30 Hz flicker ERGs were recorded in three weekly sessions. ResultsReproducible waveforms with identifiable a- and b-waves were obtained in every eye; rod b-waves reached 50-90 {micro}V and cone b-waves 40-55 {micro}V. Intraclass correlation coefficients revealed substantial interocular agreement and moderate-to-substantial inter-session reproducibility for b-wave amplitude and implicit time, whereas a-wave metrics were less reliable owing to lower amplitudes. The advantages of speculum electrode over corneal electrodes are that it requires no fur shaving, maintains stable contact regardless of globe orientation, and allows real-time observation. ConclusionsThis study demonstrated that an eyelid-speculum electrode is a practical, non-invasive alternative for veterinary and experimental ERG recordings, producing signal quality sufficient for longitudinal and interocular analyses while avoiding cosmetic and technical drawbacks of conventional methods.

neuroscience↗

Peristaltic contractions drive gut anisotropic growth through collective cell rearrangements

The gut is the longest organ in the body, and its length is essential for efficient absorption of nutrient in adults. It is known that the gut undergoes massive elongation during prenatal/embryonic stages1,2, in which anisotropic growth takes place. But how this characteristic organ growth is achieved remains unknown. We here demonstrate an unprecedented role of peristaltic movements in the embryonic gut elongation using a caecum as a novel model in chicken embryos. Inhibition of the peristaltic movements by chemical drugs impedes the elongation of caecum. The elongation-halted caecum restores its longitudinal growth by optogenetically introduced peristaltic movements. At the cellular level, we have found that circular smooth muscle cells divide along the circumferential axis in a peristalsis-independent manner, which would otherwise serve as an engine for the radial growth. However, with peristaltic stimulation, the cells expand collectively their distribution along the gut longitudinal axis leading to the elongation of this organ. Thus, peristaltic activity biases circumferentially proliferating smooth muscle cells toward longitudinal rearrangement. This two-step model offers a novel way to identify the peristaltic activity as a critical growth signal for the gut elongation, and also to parsimoniously explain the anisotropic growth of the gut, which undergoes the elongation while retaining its thickness.

developmental biology↗

Resilience and restoration from fasting-refeeding mediated by a nutrient-regulated linker histone

Intermittent fasting and fasting-refeeding regimens can slow biological aging across taxa1. Shifts between fed and fasted states activate ancient nutrient-sensing pathways which alter cellular and epigenetic states to promote longevity2-4. Yet how biological age trajectories progress during fasting-refeeding, and how nutrient-sensing pathways reprogram epigenetic state remain largely unknown. Here we observe increases in predicted biological age of Caenorhabditis elegans during prolonged fasting in adult reproductive diapause, followed by extraordinary reduction of biological age during refeeding. We identify hil-1/H1-0 as an evolutionarily conserved nutrient-regulated linker histone which mediates adaptations to fasting and refeeding downstream of FOXO and TFEB transcription factors. In C. elegans and human cell culture, hil-1/H1-0 upregulation during low-nutrient states promotes long-term survival and subsequent refeeding-induced recovery. Restoration of C. elegans after prolonged fasting is improved by enhancing the natural downregulation of hil-1 specifically during refeeding. Our study identifies HIL-1/H1.0 as part of an ancestral epigenetic switch during fasting-refeeding that reprograms metabolic and cellular states underlying resilience and restoration.

genetics↗

Self-organized patterning of peristaltic waves by suppressive actions in a developing gut

Gut peristalsis is a wave-like movement of a local contraction along the gut, and plays important roles in nutrient digestion and absorption. When peristaltic waves emerge in embryonic guts, randomly distributed origins of peristaltic waves (OPWs) become progressively confined to specific sites. We have investigated how this random-to-organized positioning is achieved using the caecum as a model in chicken embryos. While prominent OPWs, recognized as active (spontaneous) contractions, are located at endpoints of the intact caecum, other regions are also found to possess latent rhythm unveiled by fragmentation of a caecum into pieces, showing that the latent rhythm is normally suppressed in the intact gut. Analyses with caecum fragments demonstrate that the latent rhythm is spatially patterned in an early gut, to which negative impact by primitive passing waves contributes; the more passing waves a region experiences to undergo forced/passive contractions, the slower latent rhythm this region acquires. This patterned latent rhythm underlies the final positioning of OPWs at later stages, where a site with faster latent rhythm dominates neighboring slower rhythm, surviving as a "winner" by macroscopic lateral inhibition. Thus, the random-to-organized patterning of OPWs proceeds by self-organization within the caecum, in which two distinct mechanisms, at least, are employed; suppressive actions by primitive waves followed by macroscopic lateral inhibition.

developmental biology↗

A primordial TFEB-TGFβ signaling axis systemically regulates diapause and stem cell longevity

Fasting/refeeding enhances animal health and lifespan across taxa. C. elegans can endure months of fasting in adult reproductive diapause (ARD) and upon refeeding, regenerate and reproduce. hlh-30/TFEB is an ARD master regulator whose mutants live mere days in ARD and dont recover with refeeding. Here we find that downregulation of TGF{beta} signaling bypasses hlh-30 collapse, and restores recovery, germline stem cell proliferation and reproductive competence. Upon fasting, HLH-30/TFEB(+) downregulates TGF{beta} in sensory neurons, to inhibit Notch and promote reproductive quiescence in the germline. Upon refeeding, these pathways are upregulated to activate stem cells and promote reproduction. hlh-30 loss induces a senescent-like DNA damage, immune and growth metabolic signature reversed by inhibiting TGF{beta} signaling. TFEBs role is conserved in mammalian diapause models, including mouse embryonic and human cancer diapause. Thus, TFEB-TGF{beta} axis relays systemic signals matching nutrient supply with growth signaling, to regulate stem cell longevity, senescence and regeneration across species.

cell biology↗

Wnt4a is indispensable for genital duct elongation but not for gonadal sex differentiation in the medaka Oryzias latipes

In most vertebrates, oviducts are derived from Mullerian ducts and sperm ducts from Wolffian ducts. In teleosts, however, Mullerian ducts are absent. Wolffian ducts function as nephric ducts in both sexes, and genital ducts are formed by posterior extension of either ovaries or testes. Whether genital ducts of teleosts are newly evolved organs or are a variant of the Mullerian ducts is an important question for evolutionary mechanisms of morphogenesis. One of the genes essential for Mullerian duct formation in mice, wnt4, is expressed in the mesenchyme and induces invagination of the coelomic epithelium and its posterior elongation. Here, we approached to the above question by examining genital duct development in mutants of two Wnt4 genes in medaka (wnt4a is orthologous to mouse wnt4 and wnt4b paralogous). The wnt4b mutants had short body but were fertile with normal genital ducts. In contrast, both male and female wnt4a mutants had posterior elongation of the gonads stopped within or just outside the coelom, depending on the mutated alleles. Genetic females of the scl mutants (unable to synthesize testosterone or estrogens) have gonads containing both previtellogenic oocytes and spermatogenic cysts. Their gonads do not have ovarian cavities or sperm duct primordia and are lacking genital ducts completely. The results suggest Wnt4a target organs are posterior parts of the ovarian cavities or the sperm duct primordia. Medaka wnt4a was expressed in the mesenchyme ventral to the genital ducts in both sexes. Thus, the aborted elongation of genital ducts in the wnt4a mutants, the ortholog of mouse wnt4, suggests strongly that mouse Mullerian ducts and teleost genital ducts share homologous developmental processes. To further demonstrate this possible homology, mechanisms of genital duct formation and possible roles of Wnt4 should be compared before and after the appearance of Mullerian ducts in vertebrate phylogeny, namely jawless fish and cartilaginous fish. Additionally, wnt4a and wnt4b single mutants or double mutants did not show sex-reversal, suggesting both genes are dispensable for gonadal sex differentiation in medaka. This is in contrast to indispensable function of Wnt4 in mammalian ovarian differentiation.

developmental biology↗

Viral proteins and virus-like particles of the LTR5_Hs endogenous retrovirus in human primordial germ cell-like cells

The hominoid-specific endogenous retrovirus LTR5_Hs is transcriptionally activated in human primordial germ cell-like cells (hPGCLCs), a pluripotent stem cell-derived cell culture model of PGCs. Here, taking the unique advantage of our novel cell culture method to obtain large amounts of pure hPGCLCs, we performed proteomics profiling of hPGCLCs and detected various viral proteins produced from the LTR5_Hs RNA via ribosomal frameshifting. We also present transmission electron microscopy images of 100-nm diameter virus-like particles (VLPs) assembled at the surface of hPGCLCs. Compared to hPGCLCs, expression of LTR5_Hs RNA is far weaker in human seminomas, the germ cell tumors resembling PGCs. Re-analysis of published single cell RNA-seq data of human embryos revealed strong activation of LTR5_Hs in migrating PGCs but suppressed in PGCs upon they reach the gonadal anlagen. In the microfluidics-supported polarized embryoids mimicking peri-implantation stages of human embryos, LTR5_Hs RNA was detected by RNA in situ hybridization in NANOG+/TFAP2C+/SOX17+ cells resembling freshly emerged PGCs. These results support that human germ cells produce LTR5_Hs proteins and VLPs during their earliest stages of normal development until their settlement in the gonadal anlagen. SUMMARY STATEMENTThe hominoid-specific endogenous retrovirus LTR5_Hs is activated in a cell culture model resembling early-stage human primordial germ cells, producing not only viral RNA but also retrovirus proteins and virus-like particles.

developmental biology↗

Population-specific association of Clock gene polymorphism with annual cycle timing in stonechats

Timing is essential for survival and reproduction of organisms across the tree of life. The core circadian clock gene Clk has been implicated in annual timing and shows highly conserved sequence homology across vertebrates except for one variable region of poly Glutamine repeats. Clk genotype varies in some species with latitude, seasonal timing and migration. However, findings are inconsistent, difficult to disentangle from environmental responses, and biased towards high latitudes. Here we combine field data with a common-garden set up to study associations of Clk with latitude, migration and annual-cycle timing within the stonechat species complex with trans-equatorial distribution range. Including 950 individuals from nine populations with diverse migratory strategies. Gene diversity was lowest in resident African and Canary Island populations and increased with latitude, independently of migration distance. Repeat length and annual-cycle timing was linked in a population-specific way. Specifically, equatorial African stonechats showed delayed timing with longer repeat length for all annual-cycle stages. Our data suggest that at low latitudes with constant photoperiod, Clk genotype might orchestrate a range of consistent, individual chronotypes. In contrast, the influence of Clk on annual-cycle timing at higher latitudes might be mediated by its interactions with genes involved in (circadian) photoperiodic pathways.

genetics↗

Serotonergic neural network related to behavioral inhibition system

Rationale The tendency to avoid punishment, called behavioral inhibition system, is an essential aspect of motivational behavior. Behavioral inhibition system is related to negative affect, such as anxiety, depression and pain, but its neural basis has not yet been clarified. Objectives To clarify the association between individual variations in behavioral inhibition system and brain 5-HT2A receptor availability and specify which brain networks were involved in healthy male subjects, using [18F]altanserin positron emission tomography and resting-state functional magnetic resonance imaging. Results Behavioral inhibition system score negatively correlated with 5-HT2A receptor availability in anterior cingulate cortex. A statistical model indicated that the behavioral inhibition system score was associated with 5-HT2A receptor availability, which was mediated by the functional connectivity between anterior cingulate cortex and left middle frontal gyrus, both of which involved in the cognitive control of negative information processing. Conclusions Individuals with high behavioral inhibition system displays low 5-HT2A receptor availability in anterior cingulate cortex and this cognitive control network links with prefrontal-cingulate integrity. These findings have implications for underlying the serotonergic basis of physiologies in aversion.

neuroscience↗

Dissecting the clonality of I1 plasmids using ORF-based binarized structure network analysis of plasmids (OSNAp)

Phylogenetic relationship of 97 I1 plasmids harboring blaCTX-M genes encoding extended-spectrum beta-lactamase (ESBL) was analyzed using the ORF-based binarized structure network analysis of plasmids (OSNAp). The majority of plasmids carrying blaCTX-M-1 or blaCTX-M-8, ESBL genes primarily associated with domestic animals, were clonal. On the other hand, plasmids carrying blaCTX-M-14 or blaCTX-M-15, identified from both humans and domestic animals, were diverse in their contents. The findings suggest that circulation of I1 plasmids among humans and animals may contribute to their diversity.

microbiology↗

miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to affect muscle contractility upon proteotoxic challenge during ageing

Muscle function relies on the precise architecture of dynamic contractile elements, which must be fine-tuned to maintain motility throughout life. Muscle is also highly plastic, and remodelled in response to stress, growth, neural and metabolic inputs. The evolutionarily conserved muscle-enriched microRNA, miR-1, regulates distinct aspects of muscle biology during development, but whether it plays a role during ageing is unknown. Here we investigated the role of C. elegans miR-1 in muscle function in response to proteostatic stress during adulthood. mir-1 deletion results in improved mid-life muscle motility, pharyngeal pumping, and organismal longevity under conditions of polyglutamine repeat proteotoxic challenge. We identified multiple vacuolar ATPase subunits as subject to miR-1 control, and the regulatory subunit vha-13/ATP6VIA as a direct target downregulated via its 3UTR to mediate miR-1 physiology. miR-1 further regulates nuclear localization of lysosomal biogenesis factor HLH-30/TFEB and lysosomal acidification. In summary, our studies reveal that miR-1 coordinately regulates lysosomal v-ATPase and biogenesis to impact muscle function and health during ageing.

genetics↗

Massive occurrence of benthic plastic debris at the abyssal seafloor beneath the Kuroshio Extension, the North West Pacific

The deep-sea is considered to be an ultimate sink for marine plastic debris. The abyssal (3500-6500 m) covers the bulk of the deep ocean floor yet little is known about the extent of plastic debris on the abyssal seafloor. We undertook a quantitative assessment of debris presents on the abyssal seafloor (5700-5800 m depth) beneath the Kuroshio Extension current system in the Northwest Pacific, which is one of the major transit points for massive amounts of debris sourced from Asia that are entering the North Pacific Ocean. The dominant type of debris was single-use plastics-mainly bags and food packaging. The density of plastic debris (average 4561 items km-2) in the abyssal zone was the highest recorded for an abyssal plain, suggesting that the deep-sea basin of the Northwest Pacific is a significant reservoir of plastic debris.

ecology↗

Synthesis and preclinical evaluation of MTP38 as a novel PET ligand for phophodiesterase 7 in the brain

PurposePhosphodiesterase (PDE) 7 is a potential therapeutic target for neurological and inflammatory diseases, although in-vivo visualization of PDE7 has not been successful. In this study, we aimed to develop [11C]MTP38 as a novel positron emission tomography (PET) ligand for PDE7. Methods[11C]MTP38 was radiosynthesized by 11C-cyanation of a bromo precursor with [11C]HCN. PET scans of rat and rhesus monkey brains and in-vitro autoradiography of brain sections derived from these species were conducted with [11C]MTP38. In monkeys, dynamic PET data were analyzed with an arterial input function to calculate the total distribution volume (VT). The non-displaceable binding potential (BPND) in the striatum was also determined by a reference tissue model with cerebellar reference. Finally, striatal occupancy of PDE7 by an inhibitor was calculated in monkeys according to changes in BPND. Results[11C]MTP38 was synthesized with radiochemical purity [≥] 99.4% and molar activity of 38.6 {+/-} 12.6 GBq/mol. Autoradiography revealed high radioactivity in the striatum and its reduction by non-radiolabeled ligands, in contrast with unaltered autoradiographic signals in other regions. In-vivo PET after radioligand injection to rats and monkeys demonstrated that radioactivity was rapidly distributed to the brain and intensely accumulated in the striatum relative to the cerebellum. Correspondingly, estimated VT values in the monkey striatum and cerebellum were 3.59 and 2.69 mL/cm3, respectively. The cerebellar VT value was unchanged by pretreatment with unlabeled MTP38. Striatal BPND was reduced in a dose-dependent manner after pretreatment with MTP-X, a PDE7 inhibitor. Relationships between PDE7 occupancy by MTP-X and plasma MTP-X concentration could be described by Hills sigmoidal function. ConclusionWe have provided the first successful preclinical demonstration of in-vivo PDE7 imaging with a specific PET radioligand. [11C]MTP38 is a feasible radioligand for evaluating PDE7 in the brain and is currently being applied to a first-in-human PET study.

neuroscience↗

Class I histone deacetylase HDA-3 is required for full maintenance of locomotor ability in Caenorhabditis elegans

Locomotor ability declines with old age. A persons capacity to maintain locomotor ability depends on genetic and environmental factors. Currently, the specific genetic factors that work to maintain locomotor ability are not well understood. Here we report the involvement of hda-3, encoding a class I histone deacetylase, as a specific genetic factor that contributes to the maintenance of locomotor ability in C. elegans. From a forward genetic approach, we identified a missense mutation in HDA-3 as the causative mutation for progressive decline in locomotor ability in one of the isolated strains. From transcriptome analysis, we found downregulated expression of two clusters of genes on Chromosome II and IV in this strain. Genes carrying CUB-like domains and genes carrying BATH domains were found on Chromosome II and IV, respectively. Knockdown of CUB-like genes, K08D8.5 and dod-17, and BATH genes, bath-1, bath-21 and bath-24 led to a progressive decline in locomotor ability. Our study identifies specific genetic factors that work to maintain locomotor ability and reveals potential targets for delaying age-related locomotor decline.

genetics↗

The Elongator Complex is Required to Maintain Locomotor Healthspan in Caenorhabditis elegans

An inherited mutation is not always immediately toxic. Some mutations cause symptoms during youth, while other mutations cause symptoms during adulthood. Mutant animals that show delayed onset of disease symptoms may provide insights into mechanisms that maintain functional capacities during adulthood. Here, we take advantage of the relatively short lifespan of the nematode Caenorhabditis elegans and develop a novel screening procedure to collect mutants with locomotor deficits that become apparent in adulthood. After ethyl methanesulfonate mutagenesis, we isolated five C. elegans mutant strains that progressively lose adult locomotor activity. In one of the mutant strains, a nonsense mutation in Elongator Complex Protein Component 2 (elpc-2) causes a progressive decline in locomotor function. Other C. elegans elpc mutants were also unable to maintain locomotor function during adulthood, indicating that the Elongator complex plays a critical role in maintaining locomotor healthspan in C. elegans.\n\nSignificance StatementTwo people with the same lifespan do not necessarily have the same healthspan. One person may retain locomotor and cognitive functions until the end of life, while another person may lose them during adulthood. Currently, the network of genes that regulate healthspan is largely unknown. Unbiased searches for genes that work to maintain functional capacities during adulthood may uncover key regulators of healthspan. Here we isolated five Caenorhabditis elegans mutant strains that progressively lose their locomotor function in adulthood. Mutant analysis suggests that the Elongator complex regulates locomotor healthspan. Mutants and mutations identified in the present screen may provide insights into mechanisms of age-related locomotor impairment and may provide clues for improving healthspan.

genetics↗

A high-quality sequence of Rosa chinensis to elucidate genome structure and ornamental traits

Rose is the worlds most important ornamental plant with economic, cultural and symbolic value. Roses are cultivated worldwide and sold as garden roses, cut flowers and potted plants. Rose has a complex genome with high heterozygosity and various ploidy levels. Our objectives were (i) to develop the first high-quality reference genome sequence for the genus Rosa by sequencing a doubled haploid, combining long and short read sequencing, and anchoring to a high-density genetic map and (ii) to study the genome structure and the genetic basis of major ornamental traits.\n\nWe produced a haploid rose line from R. chinensis Old Blush and generated the first rose genome sequence at the pseudo-molecule scale (512 Mbp with N50 of 3.4 Mb and L75 of 97). The sequence was validated using high-density diploid and tetraploid genetic maps. We delineated hallmark chromosomal features including the pericentromeric regions through annotation of TE families and positioned centromeric repeats using FISH. Genetic diversity was analysed by resequencing eight Rosa species. Combining genetic and genomic approaches, we identified potential genetic regulators of key ornamental traits, including prickle density and number of flower petals. A rose APETALA2 homologue is proposed to be the major regulator of petals number in rose. This reference sequence is an important resource for studying polyploidisation, meiosis and developmental processes as we demonstrated for flower and prickle development. This reference sequence will also accelerate breeding through the development of molecular markers linked to traits, the identification of the genes underlying them and the exploitation of synteny across Rosaceae.

genomics↗