Reconciling biodiversity conservation and flood risk reduction : The new strategy for freshwater protected areas

Aim: Natural disaster risk reduction (DRR) is becoming a more important function of protected area (PAs) for current and future global warming. However, biodiversity conservation and DRR have been handled separately and their interrelationship has not been explicitly addressed. This is mainly because, due of prevailing strategies and criteria for PA placement, a large proportion of PAs are currently located far from human-occupied areas, and habitats in human-occupied areas have been largely ignored as potential sites for conservation despite their high biodiversity. If intensely developed lowland areas with high flooding risk overlap with important sites for biodiversity conservation, it would be reasonable to try to harmonize biodiversity conservation and human development in human-inhabited lowland areas. Here, we examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and whether human-inhabited lowland flood risk management sites might be suitable to designate as freshwater protected areas (FPAs). Location: Across Japan. Methods: We examined whether extant PAs can conserve macroinvertebrate and freshwater fish biodiversity and analysed the relationship between candidate sites for new FPAs and flood disaster risk and land use intensity at a national scale across Japan based on distribution data for 131 freshwater fish species and 1395 macroinvertebrate species. Results: We found that extant PAs overlapped with approximately 30% of conservation-priority grid cells (1 km2) for both taxa. Particularly for red-listed species, only one species of freshwater fish and three species of macroinvertebrate achieved the representation target within extant PAs. Moreover, more than 40% of candidate conservation-priority grid cells were located in flood risk and human-occupied areas for both taxa. Main conclusions: Floodplain conservation provides suitable habitat for many freshwater organisms and helps control floodwaters, so establishing new FPAs in areas with high flood risk could be a win-win strategy for conserving freshwater biodiversity and enhancing ecosystem-based DRR (eco-DRR)

Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype

Cellular senescence, a state of irreversible cell-cycle arrest caused by a variety of cellular stresses, is critically involved in age-related tissue dysfunction in various organs. However, the features of cells in the central nervous system that undergo senescence and their role in neural impairment are not well understood as yet. Here, through comprehensive investigations utilising single-cell transcriptome analysis and various mouse models, we show that microglia, particularly in the white matter, undergo cellular senescence in the brain and spinal cord during ageing and in disease models involving demyelination. Microglial senescence is predominantly detected in disease-associated microglia, which appear in ageing and neurodegenerative diseases. We also find that commensal bacteria promote the accumulation of senescent microglia and disease-associated microglia during ageing. Furthermore, knockout of p16 INK4a, a key senescence inducer, ameliorates the neuroinflammatory phenotype in damaged spinal cords in mice. These results advance our understanding of the role of cellular senescence in the central nervous system and open up possibilities for the treatment of age-related neural disorders.Matsudaira T., Nakano S., Konishi Y., et al. Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype. Communications Biology 6, 665 (2023); https://doi.org/10.1038/s42003-023-05027-2

Ex vivo reconstitution of fetal oocyte development in humans and cynomolgus monkeys

ヒト・サルの胎児卵巣から原始卵胞を体外で作出することに成功. 京都大学プレスリリース. 2022-08-01.New egg recipe to boost fertility research. 京都大学プレスリリース. 2022-08-14.In vitro oogenesis is key to elucidating the mechanism of human female germ-cell development and its anomalies. Accordingly, pluripotent stem cells have been induced into primordial germ cell-like cells and into oogonia with epigenetic reprogramming, yet further reconstitutions remain a challenge. Here, we demonstrate ex vivo reconstitution of fetal oocyte development in both humans and cynomolgus monkeys (Macaca fascicularis). With an optimized culture of fetal ovary reaggregates over three months, human and monkey oogonia enter and complete the first meiotic prophase to differentiate into diplotene oocytes that form primordial follicles, the source for oogenesis in adults. The cytological and transcriptomic progressions of fetal oocyte development in vitro closely recapitulate those in vivo. A comparison of single-cell transcriptomes among humans, monkeys, and mice unravels primate-specific and conserved programs driving fetal oocyte development, the former including a distinct transcriptomic transformation upon oogonia-to-oocyte transition and the latter including two active X chromosomes with little X-chromosome upregulation. Our study provides a critical step forward for realizing human in vitro oogenesis and uncovers salient characteristics of fetal oocyte development in primates

Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model

Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors

GATA-3 is required for early T lineage progenitor development

Most T lymphocytes appear to arise from very rare early T lineage progenitors (ETPs) in the thymus, but the transcriptional programs that specify ETP generation are not completely known. The transcription factor GATA-3 is required for the development of T lymphocytes at multiple late differentiation steps as well as for the development of thymic natural killer cells. However, a role for GATA-3 before the double-negative (DN) 3 stage of T cell development has to date been obscured both by the developmental heterogeneity of DN1 thymocytes and the paucity of ETPs. We provide multiple lines of in vivo evidence through the analysis of T cell development in Gata3 hypomorphic mutant embryos, in irradiated mice reconstituted with Gata3 mutant hematopoietic cells, and in mice conditionally ablated for the Gata3 gene to show that GATA-3 is required for ETP generation. We further show that Gata3 loss does not affect hematopoietic stem cells or multipotent hematopoietic progenitors. Finally, we demonstrate that Gata3 mutant lymphoid progenitors exhibit neither increased apoptosis nor diminished cell-cycle progression. Thus, GATA-3 is required for the cell-autonomous development of the earliest characterized thymic T cell progenitors

Enhancement of Both Long-Term Depression Induction and Optokinetic Response Adaptation in Mice Lacking Delphilin

In the cerebellum, Delphilin is expressed selectively in Purkinje cells (PCs) and is localized exclusively at parallel fiber (PF) synapses, where it interacts with glutamate receptor (GluR) δ2 that is essential for long-term depression (LTD), motor learning and cerebellar wiring. Delphilin ablation exerted little effect on the synaptic localization of GluRδ2. There were no detectable abnormalities in cerebellar histology, PC cytology and PC synapse formation in contrast to GluRδ2 mutant mice. However, LTD induction was facilitated at PF-PC synapses in Delphilin mutant mice. Intracellular Ca2+ required for the induction of LTD appeared to be reduced in the mutant mice, while Ca2+ influx through voltage-gated Ca2+ channels and metabotropic GluR1-mediated slow synaptic response were similar between wild-type and mutant mice. We further showed that the gain-increase adaptation of the optokinetic response (OKR) was enhanced in the mutant mice. These findings are compatible with the idea that LTD induction at PF-PC synapses is a crucial rate-limiting step in OKR gain-increase adaptation, a simple form of motor learning. As exemplified in this study, enhancing synaptic plasticity at a specific synaptic site of a neural network is a useful approach to understanding the roles of multiple plasticity mechanisms at various cerebellar synapses in motor control and learning

Primary Immunodeficiency Disease Mimicking Pediatric Bechet’s Disease

Behcet’s disease (BD) is a chronic inflammatory disease with multisystemic involvement. Its etiology is considered to involve complex environmental and genetic factors. Several susceptibility genes for BD, such as human leukocyte antigen (HLA)-A26, IL23R-IL12RB2, IL10 and ERAP1, in addition to the well-studied HLA-B51, were mainly identified by genome-wide association studies. A heterozygous mutation in TNFAIP3, which leads to A20 haploinsufficiency, was found to cause an early-onset autoinflammatory disease resembling BD in 2016. Several monogenic diseases associated with primary immunodeficiency disease and trisomy 8 have recently been reported to display BD-like phenotypes. Among the genes causing these diseases, TNFAIP3, NEMO, RELA, NFKB1 and TNFRSF1A are involved in the NF-κB (nuclear factor κ light-chain enhancer of activated B cells) signaling pathway, indicating that this pathway plays an important role in the pathogenesis of BD. Because appropriate treatment may vary depending on the disease, analyzing the genetic background of patients with such diseases is expected to help elucidate the etiology of pediatric BD and assist with its treatment. Here, we summarize recently emerging knowledge about genetic predisposition to BD

Holographic Local Operator Quenches in BCFTs

We present a gravity dual of local operator quench in a two-dimensional CFT with conformal boundaries. This is given by a massive excitation in a three-dimensional AdS space with the end of the world brane (EOW brane). Due to the gravitational backreaction, the EOW brane gets deformed in a nontrivial way. We show that the energy-momentum tensor and entanglement entropy computed from the gravity dual and from the BCFT in the large $c$ limit match perfectly. Interestingly, this comparison avoids the folding of the EOW brane in an elegant way.Comment: 48 pages, 18 figures; minor revision: comments added, references added (v2); a minor correction, published version in JHEP (v3

Management Assessment and Future Projections of Construction and Demolition Waste Generation in Hai Phong City, Vietnam

Along with economic development, urbanization will generate a large amount of solid waste and put pressure on the waste management systems in developing countries. Face-to-face interview methods were used to investigate the current status of construction and demolition waste (CDW) management (collection, transportation, treatment, and storage) as well as reveal attitudes of governmental agencies and enterprises towards CDW recycling and recycled material products in Hai Phong City, Vietnam. Waste generation rates (WGRs) of the works were also determined by site surveys and as-built drawings method of typical old buildings to be demolished and two licensed new construction works. WGRs of 34.5 kg/m2 and 758 kg/m2 were identified during the construction and demolition of small private houses, respectively, while WGRs at public house demolition sites were 1053 kg/m2. To effectively manage the CDW, the gross floor area of new construction work was estimated by a multiple regression equation with the population and gross region domestic product growth. Based on this model combining the investigation results, the amount of CDW increase in 5–30 years is also predicted. This data set will help management agencies plan storage yards as well as select the appropriate CDW treatment and recycling methods, contributing to building a sustainable and effective CDW management model for Hai Phong City as well as Vietnam in the future