Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs) in order to form myelin, which is required for the rapid propagation of action potentials in the vertebrate nervous system. In spite of the considerable clinical importance of myelination, little is known about the basic molecular mechanisms underlying OL differentiation and myelination. Here, we show that cyclin-dependent kinase (Cdk) 5 is activated following the induction of differentiation, and that the Cdk5 inhibitor roscovitine inhibits OL differentiation. The complexity of the OL processes is also diminished after knocking down endogenous Cdk5 using RNAi. We also show that the focal adhesion protein paxillin is directly phosphorylated at Ser244 by Cdk5. Transfection of a paxillin construct harboring a Ser244 to Ala mutation dramatically inhibits its morphological effects. Importantly, phosphorylation of paxillin at Ser244 reduces its interaction with focal adhesion kinase (FAK). Taken together, these results suggest that phosphorylation of paxillin by Cdk5 is a key mechanism in OL differentiation and may ultimately regulate myelination.

The Median Tectonic Line (MTL) active fault system is a 300-km-long, arc-parallel, right-lateral strike-slip fault related to oblique subduction of the Philippine Sea plate beneath the Eurasian plate at the Nankai trough, southwest Japan. The fault on Shikoku Island has a slip rate of 5-10 mm/yr, one of the highest in onshore Japan. We identified 12 geometric segments along the MTL separated by discontinuities such as en echelon steps, bends, changes in strike, and gaps in the surface trace. A chronology of latest Holocene surface faulting on the MTL was constructed based on previously published and new work including trenching, geomorphic mapping, and acoustic profiling and piston coring of the submarine extension of the fault zone. The MTL probably does not rupture along its entire length in a single earthquake but instead consists of multiple "earthquake segments" that rupture independently of one another. The recurrence interval and surficial offset for surface-rupturing earthquakes at four individual sites on the MTL in Shikoku Island are 1000-3000 years and 5-8 m, respectively. The relatively long recurrence interval and large surficial offset per earthquake suggest large seismic moment release during surface-mpturing earthquakes on the MTL, as commonly observed for Japanese moderate to large intraplate earthquakes. Because the predicted rupture lengths based on empirical relations between surface displacement and rupture length are considerably larger than those of individual segments, large earthquakes on the MTL probably rupture multiple geometrically defined segments. The fault was previously thought to be unruptured at least in the past 1000 years based on the absence of historical evidence for destructive earthquakes. However, trench excavations show that part of the MTL mptured most recently during or after the 16th century A.D. with at least 6.9 + 0.7 m of slip along the main fault trace. This rupture may be correlated to the 1596 Keicho-Kinki earthquake, but further geological and historical investigations are needed to confirm this hypothesis. Nevertheless, a detailed model of the rupture process of this earthquake based on inversion of geodetic, geologic, and Paper number 95JB01913. 0148.0227/96/95JB.01913505.00 seismographic data suggests that the two principal en echelon steps are related to retardation of the propagating ruptures [Wald and Heaton, 1994]. As we learn more about the dynamic rupture processes of modern earthquakes, we also need to look at historic and late Quaternary earthquakes for rupture patterns along a fault through multiple earthquake cycles. In this paper, we describe the late Holocene behavior of the Median Tectonic Line (MTL), a large strike-slip fault in southwest Japan. The MTL is an arc-parallel, right-lateral strike-slip fault (Figure 1) related to oblique subduction of the Philippine Sea plate beneath the Eurasian plate along the Nankai trough [Fitch, 1972]. Arc-parallel strike-slip faults are capable of generating moderate to large earthquakes such as the 1892 Tapa...

No abstract

The blood brain barrier (BBB) is formed by brain microvascular endothelial cells (BMECs) and tightly regulates the transport of molecules from blood to neural tissues. In vitro BBB models from human pluripotent stem cell (PSCs)-derived BMECs would be useful not only for the research on the BBB development and function but also for drug-screening for neurological diseases. However, little is known about the differentiation of human PSCs to BMECs. In the present study, human induced PSCs (iPSCs) were differentiated into endothelial cells (ECs), and further maturated to BMECs. Interestingly, C6 rat glioma cell-conditioned medium (C6CM), in addition to C6 co-culture, induced the differentiation of human iPSC-derived ECs (iPS-ECs) to BMEC-like cells, increase in the trans-endothelial electrical resistance, decreased in the dextran transport and up-regulation of gene expression of tight junction molecules in human iPS-ECs. Moreover, Wnt inhibitors attenuated the effects of C6CM. In summary, we have established a simple protocol of the generation of BMEC-like cells from human iPSCs, and have demonstrated that differentiation of iPS-ECs to BMEC-like cells is induced by C6CM-derived signals, including canonical Wnt signals.

[1] We combine surface mapping of fault and fold scarps that deform late Quaternary alluvial strata with interpretation of a high-resolution seismic reflection profile to develop a kinematic model and determine fault slip rates for an active blind wedge thrust system that underlies Kuwana anticline in central Japan. Surface fold scarps on Kuwana anticline are closely correlated with narrow fold limbs and angular hinges on the seismic profile that suggest at least $1.3 km of fault slip completely consumed by folding in the upper 4 km of the crust. The close coincidence and kinematic link between folded terraces and the underlying thrust geometry indicate that Kuwana anticline has accommodated slip at an average rate of 2.2 ± 0.5 mm/yr on a 27°, west dipping thrust fault since early-middle Pleistocene time. In contrast to classical fault bend folds the fault slip budget in the stacked wedge thrusts also indicates that (1) the fault tip propagated upward at a low rate relative to the accrual of fault slip and (2) fault slip is partly absorbed by numerous bedding plane flexural-slip faults above the tips of wedge thrusts. An historic earthquake that occurred on the Kuwana blind thrust system possibly in A.D. 1586 is shown to have produced coseismic surface deformation above the doubly vergent wedge tip. Structural analyses of Kuwana anticline coupled with tectonic geomorphology at 10 3 -10 5 years timescales illustrate the significance of active folds as indicators of slip on underlying blind thrust faults and thus their otherwise inaccessible seismic hazards.