Endothelium- targeted overexpression of Krüppel- like factor 11 protects the blood- brain barrier function after ischemic brain injury

Microvascular endothelial cell (EC) injury and the subsequent blood- brain barrier (BBB) breakdown are frequently seen in many neurological disorders, including stroke. We have previously documented that peroxisome proliferator- activated receptor gamma (PPARγ)- mediated cerebral protection during ischemic insults needs Krüppel- like factor 11 (KLF11) as a critical coactivator. However, the role of endothelial KLF11 in cerebrovascular function and stroke outcome is unclear. This study is aimed at investigating the regulatory role of endothelial KLF11 in BBB preservation and neurovascular protection after ischemic stroke. EC- targeted overexpression of KLF11 significantly mitigated BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and infiltration of peripheral immune cells, and less brain water content. Endothelial cell- selective KLF11 transgenic (EC- KLF11 Tg) mice also exhibited smaller brain infarct and improved neurological function in response to ischemic insults. Furthermore, EC- targeted transgenic overexpression of KLF11 preserved cerebral tight junction (TJ) levels and attenuated the expression of pro- inflammatory factors in mice after ischemic stroke. Mechanistically, we demonstrated that KLF11 directly binds to the promoter of major endothelial TJ proteins including occludin and ZO- 1 to promote their activities. Our data indicate that KLF11 functions at the EC level to preserve BBB structural and functional integrity, and therefore, confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke and other neurological conditions involving BBB breakdown and neuroinflammation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155919/1/bpa12831_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155919/2/bpa12831.pd

A Comparison of Murine Smooth Muscle Cells Generated from Embryonic versus Induced Pluripotent Stem Cells

Smooth muscle cell (SMC) differentiation and dedifferentiation play a critical role in the pathogenesis of cardiovascular diseases. The lack of a good and simple in vitro SMC differentiation system has hampered the progress of SMC field for years. The generation of such an in vitro system would be invaluable for exploring molecular mechanisms of SMC differentiation and dedifferentiation. Recently, the establishment of induced pluripotent stem (iPS) cells has offered a novel therapeutic strategy to generate patient-specific stem cell lines. Here we have investigated whether iPS cells are able to differentiate into SMCs in vitro. Mouse iPS cell (O9 and TT025) monolayers were treated with 105 mol/L all-trans retinoid acid (RA). After 8 days of RA treatment, we found that >40% of the O9 iPS cells expressed the SMC-markers including SMα-actin and SM myosin heavy chain. Also, we documented that iPS-derived SMCs acquired SMC functional characteristics including contraction and calcium influx in response to stimuli. Moreover, our results indicated that there were differences in SMC-specific gene expression patterns between SMCs derived from O9 and TT025 iPS as well as normal embryonic stem cells. These differences might be due to disparity in the current iPS technology. Taken together, our data have established a simple iPS-SMC system to generate SMCs in vitro, which has tremendous potential to generate individualized SMCs for vascular tissue engineering and personalized drug screening.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78153/1/scd.2008.0179.pd

Formation of the black-hole binary M33 X-7 via mass-exchange in a tight massive system

M33 X-7 is among the most massive X-Ray binary stellar systems known, hosting a rapidly spinning 15.65 Msun black hole orbiting an underluminous 70 Msun Main Sequence companion in a slightly eccentric 3.45 day orbit. Although post-main-sequence mass transfer explains the masses and tight orbit, it leaves unexplained the observed X-Ray luminosity, star's underluminosity, black hole's spin, and eccentricity. A common envelope phase, or rotational mixing, could explain the orbit, but the former would lead to a merger and the latter to an overluminous companion. A merger would also ensue if mass transfer to the black hole were invoked for its spin-up. Here we report that, if M33 X-7 started as a primary of 85-99 Msun and a secondary of 28-32 Msun, in a 2.8-3.1 day orbit, its observed properties can be consistently explained. In this model, the Main Sequence primary transferred part of its envelope to the secondary and lost the rest in a wind; it ended its life as a ~16 Msun He star with a Fe-Ni core which collapsed to a black hole (with or without an accompanying supernova). The release of binding energy and, possibly, collapse asymmetries "kicked" the nascent black hole into an eccentric orbit. Wind accretion explains the X-Ray luminosity, while the black hole spin can be natal.Comment: Manuscript: 18 pages, 2 tables, 2 figure. Supplementary Information: 34 pages, 6 figures. Advance Online Publication (AOP) on http://www.nature.com/nature on October 20, 2010. To Appear in Nature on November 4, 201

The mini-JPAS: A study of the wavelength dependence of the photon response nonuniformity of the JPAS-pathfinder camera

Understanding the origins of small-scale flats of CCDs and their wavelength-dependent variations plays an important role in high-precision photometric, astrometric, and shape measurements of astronomical objects. Based on the unique flat data of 47 narrowband filters provided by JPAS-Pathfinder, we analyze the variations of small-scale flats as a function of wavelength. We find moderate variations (from about 1.0% at 390 nm to 0.3% at 890 nm) of small-scale flats among different filters, increasing toward shorter wavelengths. Small-scale flats of two filters close in central wavelengths are strongly correlated. We then use a simple physical model to reproduce the observed variations to a precision of about ±0.14% by considering the variations of charge collection efficiencies, effective areas, and thicknesses between CCD pixels. We find that the wavelength-dependent variations of the small-scale flats of the JPAS-Pathfinder camera originate from inhomogeneities of the quantum efficiency (particularly charge collection efficiency), as well as the effective area and thickness of CCD pixels. The former dominates the variations in short wavelengths, while the latter two dominate at longer wavelengths. The effects on proper flat-fielding, as well as on photometric/flux calibrations for photometric/slitless spectroscopic surveys, are discussed, particularly in blue filters/wavelengths. We also find that different model parameters are sensitive to flats of different wavelengths, depending on the relations between the electron absorption depth, photon absorption length, and CCD thickness. In order to model the wavelength-dependent variations of small-scale flats, a small number (around 10) of small-scale flats with well-selected wavelengths are sufficient to reconstruct small-scale flats in other wavelengths. © 2021. The American Astronomical Society. All rights reserved.he PRNU model adopted in this work was developed as part of Mr. Baocun Chen's undergraduate thesis work under the supervision of H.Z. This work is supported by the National Natural Science Foundation of China through projects NSFC 12173007 and 11603002, the National Key Basic R&D Program of China via 2019YFA0405503, and Beijing Normal University grant No. 310232102. We acknowledge the science research grants from the China Manned Space Project with Nos. CMS-CSST-2021-A08 and CMS-CSST2021-A09. Based on observations made with the JST/T250 telescope and JPCam at the Observatorio Astrofisico de Javalambre (OAJ) in Teruel, owned, managed, and operated by the Centro de Estudios de Fisica del Cosmos de Aragon (CEFCA). We acknowledge the OAJ Data Processing and Archiving Unit (UPAD) for reducing and calibrating the OAJ data used in this work. Funding for the JPAS Project has been provided by the Governments of Spain and Aragon through the Fondo de Inversion de Teruel, European FEDER funding, and the Spanish Ministry of Science, Innovation and Universities, as well as by the Brazilian agencies FINEP, FAPESP, and FAPERJ and the National Observatory of Brazil. Additional funding was also provided by the Tartu Observatory and the JPAS Chinese Astronomical Consortium. With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709