This paper presents a method for objective detection of long-term slow slip events with durations on the order of years, on the plate boundary along the Nankai Trough, relying on global navigation ...satellite system daily coordinate data. The Chugoku region of Japan was held fixed to remove common mode errors, and a displacement component was calculated relative to the direction of plate subduction. Correlations were then calculated between this displacement component and a 3-year ramp function with a 1-year slope. Nearly all periods of strong correlation coincide with periods of previously reported long-term slow slip events. A period of strong correlation around the Kii Channel in 2000–2002 is attributed to a previously undocumented long-term slow slip event beneath the Kii Channel and the eastern part of Shikoku Island with an equivalent moment magnitude of 6.6. This detection method reveals variation among long-term slow slip events along the Nankai Trough.
We present a long-term slow slip event from 1996 to 1997 in the Kii Channel along the Nankai Trough in southwestern Japan that has not been reported previously. The long-term slow slip event had a ...moment magnitude
Mw
6.7 and a duration of 1 to 1.5 years. The magnitude of the event was smaller than those of the Tokai (
Mw
7.1) and the Bungo Channel (
Mw
7.0 to 7.1) events along the Nankai Trough. The slip was located slightly shallower than the depth of the low-frequency earthquakes around the Kii Channel. Long-term slow slips have been identified in various regions along the Nankai Trough, except in the Kii Peninsula. Unveiling the history of long-term slow slips is expected to contribute to an understanding of plate boundary characteristics as well as to the prediction of large earthquakes along the Nankai Trough.
Whether kidney proximal tubule harbors a scattered population of epithelial stem cells is a major unsolved question. Lineage-tracing studies, histologic characterization, and ex vivo functional ...analysis results conflict. To address this controversy, we analyzed the lineage and clonal behavior of fully differentiated proximal tubule epithelial cells after injury. A CreER ᵀ² cassette was knocked into the sodium-dependent inorganic phosphate transporter SLC34a1 locus, which is expressed only in differentiated proximal tubule. Tamoxifen-dependent recombination was absolutely specific to proximal tubule. Clonal analysis after injury and repair showed that the bulk of labeled cells proliferate after injury with increased clone size after severe compared with mild injury. Injury to labeled proximal tubule epithelia induced expression of CD24, CD133, vimentin, and kidney-injury molecule-1, markers of putative epithelial stem cells in the human kidney. Similar results were observed in cultured proximal tubules, in which labeled clones proliferated and expressed dedifferentiation and injury markers. When mice with completely labeled kidneys were subject to injury and repair there was no dilution of fate marker despite substantial proliferation, indicating that unlabeled progenitors do not contribute to kidney repair. During nephrogenesis and early kidney growth, single proximal tubule clones expanded, suggesting that differentiated cells also contribute to tubule elongation. These findings provide no evidence for an intratubular stem-cell population, but rather indicate that terminally differentiated epithelia reexpress apparent stem-cell markers during injury-induced dedifferentiation and repair.
The activities of the transaminases (aminotransferases) alanine aminotransferase and aspartate aminotransferase in the blood (serum or plasma) are widely used as sensitive markers of possible tissue ...damage and, in particular for liver toxicity. On the other hand, an increase in transaminase activities is not always accompanied by findings suggestive of hepatotoxicity. Transaminases are some of the key enzymes in the gluconeogenesis and glycolysis pathways and exist in many organs and tissues which have high activities of the gluconeogenesis and glycolysis. The activities of transaminases are altered not only in the liver but also in other organs by modification of gluconeogenesis by nutritional or hormonal factors and this phenomenon leads to alteration of transaminase activity in the blood. Drugs, which are considered to directly or secondarily modify gluconeogenesis through lowering blood glucose levels or activating lipid metabolism, such as α-glucosidase inhibitors and fibrates, slightly increase transaminase activities in the blood but there is little evidence that the phenomenon is related to drug-induced liver injury (DILI). This type of elevations can be called pharmacology-related elevation. The pharmacology-related elevation of transaminase activities sometimes makes it difficult to assess precisely the potential hepatotoxicity of new investigational drugs. Considering the characteristic of transaminases, concomitant use of new biomarkers more specific to hepatic injury is needed in the assessment of DILI both in non-clinical and clinical studies. In this review, we will discuss the specificity of transaminases to DILI and future perspectives for transaminases in the estimation of risk of DILI.
Purpose of review
During embryogenesis, the kidney is mainly generated from three progenitor cells; nephron progenitors, ureteric bud progenitors and stromal progenitors. Mutual interactions of the ...all three progenitor populations are essential to form a functional kidney with the higher-order structure. Pluripotent stem cells have potential to differentiate into all cell types of the animal body, including the kidney. In this review, we will summarize recent advances in reconstructing kidney organoids from pluripotent stem cells.
Recent findings
In the past years, major advances were reported to induce nephron and ureteric bud progenitors from pluripotent stem cells in mice and humans, and to create kidney organoids of nephron and/or ureteric bud-derived collecting duct tissues in vitro. These kidney organoid technologies were applied to high-throughput genetic screenings and small chemical screenings to identify key factors for kidney development and disease. Furthermore, a novel method was established to induce stromal progenitors from pluripotent stem cells, leading to creation of kidney organoids with the higher-order structures completely derived from pluripotent stem cells.
Summary
These advances in kidney organoids from pluripotent stem cells should lay a foundation to establish a novel therapy for kidney disease, which ultimately eliminate the need of dialysis and kidney transplantation for patients with kidney disease in the future.
The Noto region in Japan has been experiencing earthquake swarm activity since mid-2018, with repeated rises and falls in activity. Crustal deformation (expansion and uplift) observed there since the ...end of 2020 has been connected to crustal fluids. Studies in other regions have suggested that tides are related to earthquake swarm activities associated with crustal fluids. Therefore, we investigated whether tides are also involved in the Noto earthquake swarm activity. Our results suggest a tidal correlation only at greater depths in the southern part of the analyzed area (‘region Sd’). There, we inferred that an increase in pore fluid pressure caused by the inflow of deep fluids may have led to a decrease in fault fracture strength, making the local seismicity relatively susceptible to the effects of tidal forces. The significantly high value in region Sd of the scaling parameter
b
of the Gutenberg–Richter law (describing the earthquake magnitude–frequency distribution) and observed crustal deformation are consistent with this interpretation.
Graphical Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease leading to renal failure, wherein multiple cysts form in renal tubules and collecting ducts derived ...from distinct precursors: the nephron progenitor and ureteric bud (UB), respectively. Recent progress in induced pluripotent stem cell (iPSC) biology has enabled cyst formation in nephron progenitor-derived human kidney organoids in which
or
, the major causative genes for ADPKD, are deleted. However, cysts have not been generated in UB organoids, despite the prevalence of collecting duct cysts in patients with ADPKD.
CRISPR-Cas9 technology deleted
in human iPSCs and the cells induced to differentiate along pathways leading to formation of either nephron progenitor or UB organoids. Cyst formation was investigated in both types of kidney organoid derived from
-deleted iPSCs and in UB organoids generated from iPSCs from a patient with ADPKD who had a missense mutation.
Cysts formed in UB organoids with homozygous
mutations upon cAMP stimulation and, to a lesser extent, in heterozygous mutant organoids. Furthermore, UB organoids generated from iPSCs from a patient with ADPKD who had a heterozygous missense mutation developed cysts upon cAMP stimulation.
Cysts form in
mutant UB organoids as well as in iPSCs derived from a patient with ADPKD. The organoids provide a robust model of the genesis of ADPKD.
Long-term slow slip events (SSEs), the largest events among slow earthquakes, occur repeatedly along the Nankai Trough, southwest Japan. Their locations, near the locked zones of the plate interface ...responsible for great megathrust earthquakes in the Nankai Trough, suggest that these events influence conditions in this critical seismogenic region. Characterizing the spatiotemporal changes of long-term SSEs is important for understanding changes in the locked portions of the plate interface before major earthquakes. Two decades of observations by the global navigation satellite system along the Nankai Trough have detected no long-term SSEs in a large area beneath the Kii Peninsula. We report details of a long-term SSE detected in satellite navigation data from the Shima Peninsula, the easternmost part of the Kii Peninsula, from spring 2017 to autumn 2018. The estimated moment release from this event is equivalent to an earthquake of magnitude 6.4.
Objective
To generate knockin mice that express a tamoxifen‐inducible Cre recombinase from the Prg4 locus (Prg4GFPCreERt2 mice) and to use these animals to fate‐map the progeny of Prg4‐positive ...articular cartilage cells at various ages.
Methods
We crossed Prg4GFPCreERt2 mice with Rosa26floxlacZ or Rosa26mTmG reporter strains, admin‐istered tamoxifen to the double heterozygous offspring at different ages, and assayed Cre‐mediated recom‐bination by histochemistry and/or fluorescence microscopy.
Results
In 1‐month‐old mice, the expression of the Prg4GFPCreERt2 allele mirrored the expression of endogenous Prg4 and, when tamoxifen was admin‐istered for 10 days, caused Cre‐mediated recombination in ∼70% of the superficial‐most chondrocytes. Prg4GFPCreERt2‐expressing cells were mostly confined to the top 3 cell layers of the articular cartilage in 1‐month‐old mice, but descendants of these cells were located in deeper regions of the articular cartilage in aged mice. On embryonic day 17.5, Prg4GFPCreERt2‐expressing cells were largely restricted to the superficial‐most cell layer of the forming joint, yet at ∼1 year, the progeny of these cells spanned the depth of the articular cartilage.
Conclusion
Our results suggest that Prg4‐expressing cells located at the joint surface in the embryo serve as a progenitor population for all deeper layers of the mature articular cartilage. Also, our findings indicate that Prg4GFPCreERt2 is expressed by superficial chondrocytes in young mice, but expands into deeper regions of the articular cartilage as the animals age. The Prg4GFPCreERt2 allele should be a useful tool for inducing efficient Cre‐mediated recombination of loxP‐flanked alleles at sites of Prg4 expression.
Organs consist of the parenchyma and stroma, the latter of which coordinates the generation of organotypic structures. Despite recent advances in organoid technology, induction of organ-specific ...stroma and recapitulation of complex organ configurations from pluripotent stem cells (PSCs) have remained challenging. By elucidating the in vivo molecular features of the renal stromal lineage at a single-cell resolution level, we herein establish an in vitro induction protocol for stromal progenitors (SPs) from mouse PSCs. When the induced SPs are assembled with two differentially induced parenchymal progenitors (nephron progenitors and ureteric buds), the completely PSC-derived organoids reproduce the complex kidney structure, with multiple types of stromal cells distributed along differentiating nephrons and branching ureteric buds. Thus, integration of PSC-derived lineage-specific stroma into parenchymal organoids will pave the way toward recapitulation of the organotypic architecture and functions.
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