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Ribosome biogenesis is a cellular process critical for protein homeostasis during cell growth and multiplication. Our previous study confirmed up-regulation of ribosome biogenesis during endometriosis progression and malignant transition, thus anti-ribosome biogenesis may be effective for treating endometriosis and the associated complications. A mouse model with human endometriosis features was established and treated with three different drugs that can block ribosome biogenesis, including inhibitors against mTOR/PI3K (GSK2126458) and RNA polymerase I (CX5461 and BMH21). The average lesion numbers and disease frequencies were significantly reduced in treated mice as compared to controls treated with vehicle. Flow cytometry analyses confirmed the reduction of small peritoneal macrophage and neutrophil populations with increased large versus small macrophage ratios, suggesting inflammation suppression by drug treatments. Lesions in treated mice also showed lower nerve fiber density which can support the finding of pain-relief by behavioral studies. Our study therefore suggested ribosome biogenesis as a potential therapeutic target for treating endometriosis.

[1] The Taiwan mountain belt is composed of a Cenozoic slate belt (Hsuehshan Range units, HR, and Backbone Slates, BS) and of accreted polymetamorphic basement rocks (Tananao Complex, TC). Ongoing crustal shortening has resulted from the collision between the Chinese continental margin and the Luzon volcanic arc, which initiated ~6.5 Ma ago. The grade and age of metamorphism and exhumation are a key record of the development of the orogenic wedge. Because the Taiwan mountain belt is mostly composed by accreted sediments lacking metamorphic index minerals, quantitative constraints on metamorphism are sparse. By contrast, these rocks are rich in carbonaceaous material (CM) and are therefore particularly appropriate for RSCM (Raman Spectroscopy of CM) thermometry. We apply this technique in addition to (U-Th)/He thermochronology on detrital zircons to assess peak metamorphic temperatures (T) and the late exhumational history respectively, along different transects in central and southern Taiwan. In the case of the HR units, we find evidence for high metamorphic T of at least 340[degrees]350 [degrees]C and locally up to 475[degrees]C, and for relative rapid exhumation with zircon (U-Th)/He ages in the range of 1.5-2 Ma. Farther east, the BS were only slightly metamorphosed (T < 330 [degrees]C), and zircons are not reset for (U-Th)/He. From the eastern BS to the inner TC schists, T gradually increases from ~350[degrees]C up to ~500[degrees]C following an inverted metamorphic gradient. Available geochronological constraints and the continuous thermal gradient from the BS to the basement rocks of the TC suggest that the high RSCM T of the TC were most probably acquired during the last orogeny, and were not inherited from a previous thermal event. Zircons yield (U-Th)/He ages of ~0.5-1.2 Ma. Peak metamorphic T and the timing of exhumation do not show along-strike variations over the TC in the studied area. In contrast, exhumation is laterally diachronous and decreases southward in the case of the HR units. In particular, our data imply that the HR units have been exhumed by a minimum of 15 km over the last few Ma. In the case of the BS, they show far less cumulated exhumation and much slower cooling rates. We propose that most of the deformation and exhumation of the Taiwan mountain belt is sustained through two underplating windows located beneath the Hsuehshan Range and the TC. Our data show significant departures from the predictions of the prevailing model in Taiwan, which assumes a homogeneous critical wedge with dominant frontal accretion. Our study sheds new light on how the mountain belt has grown as a possible result of underplating mostly. doi: 10.1029/2006TC002064.

Geodetic evidence for slow slip recurrence changed by stress perturbations was rare, especially from afterslip following a nearby large earthquake. The first observed slow slip events in the southernmost Ryukyu subduction had occurred in 2005, 2009, and 2015 following the nearby 2002 March 31 Mw 7.1 Hualien offshore earthquake. To investigate whether the Mw 7.1 earthquake had influenced the occurrence times of the slow slip, we calculated the coseismic slip distribution and afterslip distribution using the surface displacements from onshore Global Navigation Satellite System observations. The stress perturbation on the slow-slip regions caused by the coseismic slip was quantified using the Coulomb failure criteria. We also examined the aftershock distribution and the evolution with time to clarify the stress perturbations from the afterslip offshore. Our results show that the primary afterslip distribution may have overlapped the 2009 and 2015 slow-slip patch at the downdip of the earthquake. The coseismic stress perturbation may have influenced the SSEs area directly by a Coulomb stress increase of probably 0.10 MPa. However, the 2005 SSE patch in the updip depths had only a little coseismic slip and afterslip with the Coulomb stress increase of approximately 0.06 MPa. We find that most of the aftershocks had occurred in the 2009 and 2015 slow-slip region that evolved into a typical aftershock sequence at least 2.5 years after the earthquake. The surface geodetic displacements reveal that the afterslip may have lasted longer than 4.5 years after the earthquake. The evidence for the afterslip proves that the 2009 and 2015 slow-slip patch was influenced by the afterslip directly for years. We suggest that the ongoing afterslip may have modulated the coseismic stress perturbation. It may explain the delay of the 2009 slow slip occurrence compared with the recurrence interval between the 2009 and 2015 slow slip events. [ABSTRACT FROM AUTHOR]

Structural data from two transects across the active Taiwan arc-continent collision indicate that normal faulting is an important mechanism in the exhumation of the hinterland. The normal faulting extends to at least the brittle-ductile transition, records extension at a high angle to the topographic grain of the orogenic belt, and is responsible for the regional-scale rotation of ductile fabrics. These results are supported by a recent GPS survey of southern Taiwan that reveals extension in the hinterland contemporaneous with shortening in the foreland and collided arc.