Permeability-control on volcanic hydrothermal system: case study for Mt. Tokachidake, Japan, based on numerical simulation and field observation

We investigate a volcanic hydrothermal system by using numerical simulation with three key observables as reference: the magnetic total field, vent temperature, and heat flux. We model the shallow hydrothermal system of Mt. Tokachidake, central Hokkaido, Japan, as a case study. At this volcano, continuous demagnetization has been observed since at least 2008, suggesting heat accumulation beneath the active crater area. The surficial thermal manifestation has been waning since 2000. We perform numerical simulations of heat and mass flow within a modeled edifice at various conditions and calculate associated magnetic total field changes due to the thermomagnetic effect. We focus on the system’s response for up to a decade after permeability is reduced at a certain depth in the modeled conduit. Our numerical simulations reveal that (1) conduit obstruction (i.e., permeability reduction in the conduit) tends to bring about a decrease in vent temperature and heat flux, as well as heat accumulation below the level of the obstruction, (2) the recorded changes cannot be consistently explained by changing heat supply from depth, and (3) caprock structure plays a key role in controlling the location of heating and pressurization. Although conduit obstruction may be caused by either physical or chemical processes in general, the latter seems more likely in the case of Mt. Tokachidake

Glaucoma in a New Zealand White Rabbit Fed High-cholesterol Diet

Goniodysgenesis, malformation of the filtration angle, was observed in a New Zealand white rabbit supplied with 100 g/day rabbit chow containing 0.2% cholesterol for 10 months. Histopathology revealed cupping of the optic disc, atrophy of the retina and hyalinization of the ciliary body in the bilateral eyeballs. These findings corresponded with histopathological features caused by glaucoma. On the basis of these findings, we diagnosed this lesion as glaucoma, and classified it as primary glaucoma because of the presence of developmental defects of the filtration angle. In this case, hypercholesterolemia-induced changes, such as aggregation of lipid-laden macrophages and cholesterin clefts in the sclera or choroid, might cause deterioration of the lesions in glaucoma

Seismicity controlled by resistivity structure : the 2016 Kumamoto earthquakes, Kyushu Island, Japan

The M JMA 7.3 Kumamoto earthquake that occurred at 1:25 JST on April 16, 2016, not only triggered aftershocks in the vicinity of the epicenter, but also triggered earthquakes that were 50–100 km away from the epicenter of the main shock. The active seismicity can be divided into three regions: (1) the vicinity of the main faults, (2) the northern region of Aso volcano (50 km northeast of the mainshock epicenter), and (3) the regions around three volcanoes, Yufu, Tsurumi, and Garan (100 km northeast of the mainshock epicenter). Notably, the zones between these regions are distinctively seismically inactive. The electric resistivity structure estimated from one-dimensional analysis of the 247 broadband (0.005–3000 s) magnetotelluric and telluric observation sites clearly shows that the earthquakes occurred in resistive regions adjacent to conductive zones or resistive-conductive transition zones. In contrast, seismicity is quite low in electrically conductive zones, which are interpreted as regions of connected fluids. We suggest that the series of the earthquakes was induced by a local accumulated stress and/or fluid supply from conductive zones. Because the relationship between the earthquakes and the resistivity structure is consistent with previous studies, seismic hazard assessment generally can be improved by taking into account the resistivity structure. Following on from the 2016 Kumamoto earthquake series, we suggest that there are two zones that have a relatively high potential of earthquake generation along the western extension of the MTL

Therapeutic manipulation of IKBKAP mis-splicing with a small molecule to cure familial dysautonomia.

Approximately half of genetic disease-associated mutations cause aberrant splicing. However, a widely applicable therapeutic strategy to splicing diseases is yet to be developed. Here, we analyze the mechanism whereby IKBKAP-familial dysautonomia (FD) exon 20 inclusion is specifically promoted by a small molecule splice modulator, RECTAS, even though IKBKAP-FD exon 20 has a suboptimal 5' splice site due to the IVS20 + 6 T > C mutation. Knockdown experiments reveal that exon 20 inclusion is suppressed in the absence of serine/arginine-rich splicing factor 6 (SRSF6) binding to an intronic splicing enhancer in intron 20. We show that RECTAS directly interacts with CDC-like kinases (CLKs) and enhances SRSF6 phosphorylation. Consistently, exon 20 splicing is bidirectionally manipulated by targeting cellular CLK activity with RECTAS versus CLK inhibitors. The therapeutic potential of RECTAS is validated in multiple FD disease models. Our study indicates that small synthetic molecules affecting phosphorylation state of SRSFs is available as a new therapeutic modality for mechanism-oriented precision medicine of splicing diseases

ADAMTS-1: A metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function

金沢大学医薬保健研究域医学系A disintegrin and metalloproteinase (ADAM) represents a protein family possessing both metalloproteinase and disintegrin domains. ADAMTS-1, an ADAM family member cloned from cachexigenic colon adenocarcinoma, is unusual in that it contains thrombospondin type I motifs and anchors to the extracellular matrix. To elucidate the biological role of ADAMTS-1, we developed ADAMTS-1-null mice by gene targeting. Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation. Impaired female fertilization accompanied by histological changes in the uterus and ovaries also resulted. Furthermore, ADAMTS-1(-/-) mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation. ADAMTS-1 thus appears necessary for normal growth, fertility, and organ morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease

Magmatic–hydrothermal system of Aso Volcano, Japan, inferred from electrical resistivity structures

We investigated the magmatic–hydrothermal system of Aso Volcano, Japan, using broadband magnetotelluric (MT) data. To establish the nature of the shallow crust, a previous resistivity model based on data from 100 measurement sites in and around Aso volcano was revised using data from 9 additional sites near Naka-dake crater, which is located in the central part of the volcano. The components of MT impedance and the tipper vector were used to obtain the resistivity structure by three-dimensional inversion. The resistivity structure shows a subvertical low-resistivity (< 1 Ωm) column-shaped body beneath Naka-dake crater that extends from − 600 m to 10 km below sea level (BSL) and dips steeply to the north-northeast. The position of the upper part of the column is displaced eastward compared with the previous model and does not overlap the position of the presumed magma reservoir inferred previously from seismic and geodetic observations underneath the western side of Naka-dake crater at a depth of 5 km. We interpret this low-resistivity column to be a magmatic–hydrothermal system composed of brine and magma that were transported to Naka-dake crater from the main deep-seated magma reservoir. A horizontal low-resistivity (< 10 Ωm) layer occurs beneath post-caldera cones at the depths of 0–2 km BSL, and this layer extends laterally from the upper part of the low-resistivity column. We interpret this low-resistivity layer as representing a shallow hydrothermal system that has developed around the central column-shaped magmatic–hydrothermal system