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INTRODUCTION: The morphological and molecular changes associated with the degeneration of arterioles in cerebral amyloid angiopathy (CAA) are incompletely understood. METHODS: Post mortem brains from 26 patients with CAA or neurological controls were analyzed using light-sheet microscopy, and morphological features of microvascular degeneration were quantified using surface volume rendering. Vascular stiffness was analyzed using atomic force microscopy. RESULT: Vascular smooth muscle cells (VSMCs) volume was reduced by ≈ 55% inCAA. This loss of VSMC volume correlated with increased arteriolar diameter, variability in diameter, and the volume of amyloid beta (Aβ) deposition in the vessel. Vessels with CAA were > 300% stiffer than controls. The volume of extracellular matrix cross-linking enzyme lysyl oxidase (LOX) correlated closely with vascular degenerative features. DISCUSSION: Our findings provide valuable insights into the connections among LOX, Aβ deposition, and vascular stiffness in CAA. Restoration of physiologic extracellular matrix properties in penetrating arteries may yield a novel therapeutic strategy for CAA. 

The present topography of the northern Tibetan Plateau is characterized by the northwest-trending Eastern Kunlun Range, Qaidam Basin, and Qilian Shan, which figure importantly into the evolution and mechanism of Tibetan plateau development during Cenozoic Indo-Asian convergence. Understanding the Cenozoic deformation history and the source-to-sink relationship through time has significant implications for deciphering the growth history of the northern Tibetan Plateau. Despite decades of study, the timing, pattern, and mechanisms of deformation across the northern Tibetan Plateau are still vigorously debated. The North Qaidam thrust belt, located between the Qaidam Basin and Qilian Shan thrust belt, provides a valuable record of Cenozoic deformation in the northern Tibetan Plateau. Here, we present the results of new geologic mapping, structural and sedimentology analysis, and apatite fission track thermochronology to constrain the Cenozoic evolution history and reconstruct the paleogeomorphology of the eastern domain of the North Qaidam thrust belt and its foreland, the Wulan Basin. Our analyses reveal the North Qaidam thrust belt experienced multi-phase exhumation since the Cretaceous. A period of Eocene localized thrust-related uplift of the North Qaidam thrust belt initiated shortly after India-Asia collision, and lower erosion rates in the Oligocene allowed the thrust belt to expand along-strike eastward. Local uplift shed sediments to the southwest, directly into the Qaidam Basin. Reactivation of the proximal thrust faults and initiation of the northwest-striking right-slip Elashan fault at ca. 15−10 Ma drove the final accelerated mid-Miocene cooling and denudation to the surface. This phase of deformation established the overall framework morphology of the northeastern margin of the Tibetan Plateau, including the overall structure of the basins and ranges. 

Abstract Although the Cenozoic Indo-Asian collision is largely responsible for the formation of the Tibetan plateau, the role of pre-Cenozoic structures in controlling the timing and development of Cenozoic deformation remains poorly understood. In this study we address this problem by conducting an integrated investigation in the northern foreland of the Tibetan plateau, north of the Qilian Shan-Nan Shan thrust belt, NW China. The work involves field mapping, U-Pb detrital-zircon dating of Cretaceous strata in the northern foreland of the Tibetan plateau, examination of growth-strata relationships, and construction and restoration of balanced cross sections. Our field mapping reveals multiple phases of deformation in the area since the Early Cretaceous, which was expressed by northwest-trending folding and northwest-striking thrusting that occurred in the early stages of the Early Cretaceous. The compressional event was followed immediately by extension and kinematically linked right-slip faulting in the later stage of the Early Cretaceous. The area underwent gentle northwest-trending folding since the late Miocene. We estimate the magnitude of the Early Cretaceous crustal shortening to be ~35%, which we interpret to have resulted from a far-field response to the collision between the Lhasa and the Qiangtang terranes in the south. We suggest that the subsequent extension in the Early Cretaceous was induced by orogenic collapse. U-Pb dating of detrital zircons, sourced from Lower Cretaceous sedimentary clasts from the north and the south, implies that the current foreland region of the Tibetan plateau was a topographic depression between two highland regions in the Early Cretaceous. Our work also shows that the Miocene strata in the foreland region of the northern Tibetan plateau was dominantly sourced from the north, which implies that the rise of the Qilian Shan did not impact the sediment dispersal in the current foreland region of the Tibetan plateau where this study was conducted. 

Abstract Flowering plants have evolved numerous intraspecific and interspecific prezygotic reproductive barriers to prevent production of unfavourable offspring 1 . Within a species, self-incompatibility (SI) is a widely utilized mechanism that rejects self-pollen 2,3 to avoid inbreeding depression. Interspecific barriers restrain breeding between species and often follow the SI × self-compatible (SC) rule, that is, interspecific pollen is unilaterally incompatible (UI) on SI pistils but unilaterally compatible (UC) on SC pistils 1,4–6 . The molecular mechanisms underlying SI, UI, SC and UC and their interconnections in the Brassicaceae remain unclear. Here we demonstrate that the SI pollen determinant S -locus cysteine-rich protein/ S -locus protein 11 (SCR/SP11) 2,3 or a signal from UI pollen binds to the SI female determinant S -locus receptor kinase (SRK) 2,3 , recruits FERONIA (FER) 7–9 and activates FER-mediated reactive oxygen species production in SI stigmas 10,11 to reject incompatible pollen. For compatible responses, diverged pollen coat protein B-class 12–14 from SC and UC pollen differentially trigger nitric oxide, nitrosate FER to suppress reactive oxygen species in SC stigmas to facilitate pollen growth in an intraspecies-preferential manner, maintaining species integrity. Our results show that SRK and FER integrate mechanisms underlying intraspecific and interspecific barriers and offer paths to achieve distant breeding in Brassicaceae crops.