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Takamura, N.

Publications and source records attributed to Takamura, N..

4 recordsLinked to original sources

Exploring the functions of JAKMIP1 in neuronal IL-6/STAT3 signaling and its relevance to chromosome 15q-duplication syndrome

Growing evidence supports neuroinflammation as a risk factor for neurodevelopmental and psychiatric disorders. Interleukin 6 (IL-6), a classical pro-inflammatory cytokine, has been associated with autism spectrum disorder (ASD)-related phenotypes. To better understand molecular factors that modify neuronal cytokine responses in ASD, we investigated potential roles for JAKMIP1, a gene linked to chromosome 15q-duplication syndrome (Dup15q; a form of syndromic ASD), in regulating IL-6/STAT3 signaling. We observe that JAKMIP1 deficiency impairs IL-6/STAT3 signaling and IL-6-induced neuritogenesis in SH-SY5Y cells; and discover that JAKMIP1 may regulate STAT3 expression via its C-terminus, which exhibits nucleoplasmic localization. Additionally, we find that IL-6/STAT3 signaling is altered in Dup15q hiPSCs-derived cortical neurons, which display heightened responsiveness to IL-6; though it is unclear whether and how JAKMIP1 contributes to this. Overall, our findings identify JAKMIP1 as a modulator of neuronal IL-6/STAT3 signaling and support that ASD-linked genetic variants can alter the inflammatory landscape of ASD.

neuroscience↗

Genetic differentiation of water penny beetles may be associated with the formation process of the ancient Lake Biwa.

BackgroundWater flow is one of several factors that determine the habitats of aquatic insects. The conversions of stagnant (lentic) and running (lotic) water are physiologically and ecologically constrained. In general, aquatic insect species only occur in one of these environments. Though Eubrianax ramicornis (Coleoptera: Psephenidae) usually resides in rivers, however, it is also known to occur near the shores of Lake Biwa in Japan. Here, we investigated the genetic differences between the two Eubrianax species of Lake Biwa and its inflowing rivers, and other regions of Japan for the first time. Lake Biwa is an ancient lake and about four million years old. Though over 60 endemic species were described from Lake Biwa, they are mostly fish and molluscs, with only two species of aquatic insects. There are few reports of endemic aquatic insects in other ancient lakes, too. Discussion of the endemism of Eubrianax and its promoting factors is expected to provide insights into the evolution of aquatic insects in ancient lakes. MethodsWe surveyed and morphologically identified psephenid larvae in Lake Biwa and its inflowing rivers during the summers of 2017 and 2018 (Hayashi, 2009: Hayashi & Sota, 2009). We conducted phylogenetic analyses of two regions of COI and estimated the ages of population divergence based on fossil records of Eubrianax beetles in Lake Biwa as well as those of previously reported populations in other regions. We also analyzed two COI regions of the E. ramicornis haplotypes in Lake Biwa. ResultsFour psephenid species were identified among the samples collected in Lake Biwa and its inflowing rivers. Of these, E. ramicornis was collected only at the Lake Biwa shore whereas its congeneric E. granicollis was collected only from the rivers inflowing the lake. The phylogenetic analyses showed that E. ramicornis of Lake Biwa were clearly differentiated from those in previously reported regions and this divergence was estimated to have occurred 1.40 MYA. At that time, there was no lake at the location of present-day Lake Biwa. It is thought that rivers and their dammed flood plains to the east, with gravel and sand supplied by the rising Suzuka Mountains further to the east. Such an environments is preferable for E. ramicornis and they were thought to have become isolated from the surrounding rivers during the formation of Lake Biwa. On the contrary, there was no genetic differentiation between the E. granicollis population at the Lake Biwa inflow rivers and those elsewhere. Hence, E. granicollis might have migrated to the Lake Biwa watershed later than E. ramicornis and maintained gene flow over a wide area. The genetic differentiation of E. ramicornis reported here for the first time suggests that a species with a wide distribution may rather be evolving endemic to Lake Biwa. Reports on the endemism of aquatic insects in ancient lakes are scarce. This study is expected to bring new perspectives to the study of insect evolution in ancient lakes.

ecology↗

Catalytic Promiscuity of Rice 2-Oxoglutarate/Fe(II)-Dependent Dioxygenases Supports Xenobiotic Metabolism

The rice 2-oxoglutarate/Fe(II)-dependent dioxygenase HIS1 mediates the catalytic inactivation of five distinct {beta}-triketone herbicides (bTHs). During a search for potential inhibitors of HIS1, we found that it mediates the hydroxylation of trinexapac-ethyl (TE) in the presence of Fe2+ and 2-oxoglutarate. TE is a plant growth regulator that blocks gibberellin biosynthesis, and we observed that its addition to culture medium induced growth retardation of rice seedlings in a concentration-dependent manner. Similar treatment with hydroxylated TE revealed that hydroxylation greatly attenuated the inhibitory effect of TE on plant growth. Forced expression of HIS1 in a rice his1 mutant also reduced its sensitivity to TE compared with that of the nontransformant. These results indicated that HIS1 metabolizes TE and thereby markedly reduces its ability to slow plant growth. Furthermore, testing of five HIS1-related proteins (HSLs) of rice revealed that OsHSL2 and OsHSL4 also metabolize TE in vitro. HSLs from wheat and barley also showed such activity. In contrast, OsHSL1, which shares the highest amino acid sequence identity with HIS1 and metabolizes the bTH tefuryltrione, did not manifest TE-metabolizing activity. Site-directed mutagenesis of OsHSL1 informed by structural models showed that substitution of three amino acids with the corresponding residues of HIS1 conferred TE-metabolizing activity similar to that of HIS1. Our results thus reveal a catalytic promiscuity of HIS1 and its related enzymes that supports xenobiotic metabolism in plants. One-sentence summaryThe rice 2-oxoglutarate/Fe(II)-dependent dioxygenase HIS1 and related enzymes show broad substrate specificity and mediate metabolism of the growth regulator trinexapac-ethyl as well as of herbicides.

plant biology↗

Combined impact of pesticides and other environmental stressors on taxonomic richness of freshwater animals in irrigation ponds

Rice paddy irrigation ponds can sustain surprisingly high taxonomic richness and make significant contributions to regional biodiversity. We evaluated the impacts of pesticides and other environmental stressors on the taxonomic richness of freshwater animals in 21 irrigation ponds in Japan. We sampled a wide range of freshwater animals (reptiles, amphibians, fishes, mollusks, crustaceans, insects, annelids, bryozoans, and sponges) and surveyed environmental variables related to pesticide contamination, eutrophication, decreased macrophyte coverage, physical habitat destruction, and invasive alien species. Statistical analyses comprised contraction of highly correlated environmental variables, best-subset model selection, stepwise model selection, and permutation tests. Results showed that: (i) probenazole (fungicide) was the unique significant stressor on fish (i.e., contamination with this compound had a significantly negative correlation with fish taxonomic richness), (ii) the interaction of BPMC (insecticide; also known as fenobucarb) and bluegill (invasive alien fish) was a significant stressor on a "large insect" category (Coleoptera, Ephemeroptera, Hemiptera, Lepidoptera, Odonata, and Trichoptera), (iii) the interaction of BPMC and concrete bank was a significant stressor on an "invertebrate" category, (iv) the combined impacts of BPMC and the other stressors on the invertebrate and large insect categories resulted in an estimated mean loss of taxonomic richness by 15% and 77%, respectively, in comparison with a hypothetical pond with preferable conditions.

ecology↗