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31.
Ushio-Fukai M Zuo L Ikeda S Tojo T Patrushev NA Alexander RW 《Circulation research》2005,97(8):829-836
Important output signals of the angiotensin subtype 1 receptor (AT1R) in vascular smooth muscle cells (VSMCs) are mediated by angiotensin II (Ang II)-stimulated transactivation of the epidermal growth factor receptor (EGF-R), which is critical for vascular hypertrophy. Ang II-induced EGF-R transactivation is mediated through cSrc, a proximal target of reactive oxygen species (ROS) derived from NAD(P)H oxidase (NOX) and is dependent on AT(1)R trafficking through caveolin1 (Cav1)-enriched lipid rafts. Underlying molecular mechanisms are incompletely understood. The nonreceptor tyrosine kinase, proto-oncogene cAbl is a substrate of Src and is a major mediator for ROS-dependent tyrosine phosphorylation of Cav1. We thus hypothesized that cAbl is important for ROS-, cSrc-, and Cav1-dependent growth-related AT1R signal transduction. Here we show that Ang II induces tyrosine phosphorylation of cAbl in rat VSMCs and mouse aorta, and that Ang II promotes association of cAbl with AT(1)R, both of which are Src-dependent. Pretreatment of rat VSMCs with the NOX inhibitor diphenylene iodonium or the antioxidants N-acetylcysteine or ebselen significantly inhibited Ang II-induced cAbl phosphorylation. Cell fractionation shows that both EGF-Rs and cAbl are found basally in Cav1-enriched membrane fractions. Knockdown of cAbl protein using small interference RNA inhibits Ang II-stimulated: (1) trafficking of AT1R into, and EGF-R out of, Cav1-enriched lipid rafts; (2) EGF-R transactivation; (3) appearance of the transactivated EGF-R and phospho-Cav1 at focal adhesions; and (4) vascular hypertrophy. These studies provide a novel role of cAbl in the spatial and temporal organization of growth-related AT1R signaling in VSMCs and suggest that cAbl may be generally important in signaling of G-protein coupled receptors. 相似文献
32.
Dokholyan NV Li L Ding F Shakhnovich EI 《Proceedings of the National Academy of Sciences of the United States of America》2002,99(13):8637-8641
The folding of many small proteins is kinetically a two-state process that represents overcoming the major free-energy barrier. A kinetic characteristic of a conformation, its probability to descend to the native state domain in the amount of time that represents a small fraction of total folding time, has been introduced to determine to which side of the free-energy barrier a conformation belongs. However, which features make a protein conformation on the folding pathway become committed to rapidly descending to the native state has been a mystery. Using two small, well characterized proteins, CI2 and C-Src SH3, we show how topological properties of protein conformations determine their kinetic ability to fold. We use a macroscopic measure of the protein contact network topology, the average graph connectivity, by constructing graphs that are based on the geometry of protein conformations. We find that the average connectivity is higher for conformations with a high folding probability than for those with a high probability to unfold. Other macroscopic measures of protein structural and energetic properties such as radius of gyration, rms distance, solvent-accessible surface area, contact order, and potential energy fail to serve as predictors of the probability of a given conformation to fold. 相似文献
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36.
Zhao Li Chao‐Hsiung Hsu Nikolay Dimitrov Dennis W. Hwang Hsin‐Wei Chang Lian‐Pin Hwang Yung‐Ya Lin 《Magnetic resonance in medicine》2015,73(1):spcone-spcone
This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade‐offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo‐continuous labeling, background suppression, a segmented three‐dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. Magn Reson Med 73:102–116, 2015. © 2014 Wiley Periodicals, Inc. 相似文献
37.
George E. A. Swann Virginia N. Panizzo Sebastiano Piccolroaz Vanessa Pashley Matthew S. A. Horstwood Sarah Roberts Elena Vologina Natalia Piotrowska Michael Sturm Andre Zhdanov Nikolay Granin Charlotte Norman Suzanne McGowan Anson W. Mackay 《Proceedings of the National Academy of Sciences of the United States of America》2020,117(44):27211
Lake Baikal, lying in a rift zone in southeastern Siberia, is the world''s oldest, deepest, and most voluminous lake that began to form over 30 million years ago. Cited as the “most outstanding example of a freshwater ecosystem” and designated a World Heritage Site in 1996 due to its high level of endemicity, the lake and its ecosystem have become increasingly threatened by both climate change and anthropogenic disturbance. Here, we present a record of nutrient cycling in the lake, derived from the silicon isotope composition of diatoms, which dominate aquatic primary productivity. Using historical records from the region, we assess the extent to which natural and anthropogenic factors have altered biogeochemical cycling in the lake over the last 2,000 y. We show that rates of nutrient supply from deep waters to the photic zone have dramatically increased since the mid-19th century in response to changing wind dynamics, reduced ice cover, and their associated impact on limnological processes in the lake. With stressors linked to untreated sewage and catchment development also now impacting the near-shore region of Lake Baikal, the resilience of the lake’s highly endemic ecosystem to ongoing and future disturbance is increasingly uncertain.Ancient lakes have long been associated with both high levels of biodiversity and endemicity. However, they are also being threatened by anthropogenic forcings that have led to impacts ranging from the warming of lake waters (1), hydrological modifications (2), increases in aquatic toxicity (3), and declining endemic populations due to introductions of nonnative species (4). With global populations increasingly reliant on large and ancient lakes for ecosystem services, the biodiversity (5) and value of aquatic systems to society (6), particularly in ancient lake systems (7), are at risk. Lake Baikal (Russia) is an exceptional example of an ancient lake (Fig. 1). In addition to containing ∼20% of global surface freshwater, the lake is characterized by its high degree of biodiversity with over 2,500 flora and fauna, the majority of which are endemic (8). This has been attributed to the lake’s age and fully oxygenated water column, driven by seasonal overturning and deep water renewal (9, 10) that sustains an almost completely endemic deep water fauna (8).Open in a separate windowFig. 1.Location of Lake Baikal and its catchment (gray) together with the location of World Meteorological Organization station in Irkutsk, major catchment rivers (brown), coring sites (BAIK13-1, BAIK13-4), and sites providing additional data used in this study (BAIK13-7).Concerns exist over the future health of this unique ecosystem, amid evidence of extensive shoreline eutrophication (11, 12) and climate-induced shifts in primary productivity (13, 14). Together, these changes have impacted organisms ranging from sponges and gastropods to ciliates, flagellates, and algal communities (15). Given the likelihood of future anthropogenic disturbance on Lake Baikal, further disrupting productivity exchanges through the lake’s food web, there is a need to place these contemporary observations into their historical setting. In Lake Baikal, we have evidence that algal communities have undergone rapid multidecadal to multicentennial timescale changes over the last 2,000 y (16). However, there is a need to also gain a clearer insight into how biogeochemical and nutrient cycling has altered over the same timescale, both to contextualize natural and anthropogenic drivers of change and to understand the susceptibility of the lake’s ecosystem to further alteration under different climate states (17). Annual primary productivity in Lake Baikal is ultimately regulated by photic zone nutrient availability, in addition to ice/snow cover, which regulates light availability for photosynthesis (10, 18). Here, by analyzing the silicon isotope composition of diatom silica (δ30Sidiatom), we show that nutrient supply to the surface waters of Lake Baikal has rapidly increased through the 20th and 21st centuries coincident with increased wind-driven Ekman transport and reduced ice cover. These changes in photic zone nutrient availability have the potential to alter resource competition and prey–predator interactions across the lake (15, 19). 相似文献
38.
Water treatment plant (WTP) sludge is actively used in building materials production. The object of this research was modifying additives for ceramic bricks from WTP aluminium-containing sludge. The research aim of this study was to determine the suitability of a million-plus population city’s WTP sludge as a burning-out additive in the production of structural ceramics and to establish the optimal conditions for obtaining products with the best characteristics. The raw water belongs to water belongs to the hydrocarbonate class, the calcium group, and it is of low turbidity (1.5–40 mg/L kaolin). Sludge, sourced from WTP sedimentation tanks, was dewatered by adding lime or by using the freezing-thawing method. The spray-dried WTP sludge is introduced into the clay in amounts of 5% to 20% by weight. The addition of 20% reduces the sensitivity of the clay to drying, reduces the density of ceramic by 20% and simultaneously increases its compressive strength from 7.0 to 10.2 MPa. The use of WTP sludge as a modifying additive, pretreated by the freezing-thawing method, makes it possible to obtain ceramic bricks with improved properties. The results can be used for WTP sludge containing aluminium obtained by treating water of medium turbidity and medium colour. 相似文献
39.
A lipid bilayer containing a ternary mixture of low- and high-melting lipids and cholesterol (Chol) can give rise to domain formation, referred to as lipid rafts. Low-frequency Raman spectroscopy at reduced temperatures allows detection of normal membrane mechanical vibrations. In this work, Raman spectra were obtained in the spectral range between 5 and 90 cm−1 for bilayers prepared from dioleoyl-glycero-phosphocholine (DOPC), dipalmitoyl-glycero-phosphocholine (DPPC) and Chol. A narrow peak detected between 13 and 16 cm−1 was attributed to the vibrational eigenmode of a lipid monolayer (a leaflet). For the equimolar DOPC/DPPC ratio, the Chol concentration dependence for the peak position, width and amplitude may be divided into three distinct ranges: below 9 mol%, the intermediate range between 9 mol% and 38 mol%, and above 38 mol%. In the intermediate range the peak position attains its minimum, and the peak width drops approximately by a factor of two as compared with the Chol-free bilayers. Meanwhile, this range is known for raft formation in a fluid state. The obtained results may be interpreted as evidence that bilayer structures in the raft-containing fluid state may be frozen at low temperatures. The drop of peak width indicates that at the spatial scale of the experiment (∼2.5 nm) the intermolecular bilayer structure with raft formation becomes more homogeneous and more cohesive.Upon lipid raft formation, the Raman peak corresponding to monolayer normal mechanical vibrations drops remarkably in position and width. 相似文献
40.
Janetta V. Korneva Svetlana A. Kornienko Vadim V. Kuklin Nikolay M. Pronin Malcolm K. Jones 《Parasitology research》2014,113(1):425-432
Uterine organization and interaction with developing eggs in Tetrabothrius erostris (Tetrabothriidea), Nippotaenia mogurndae (Nippotaeniidea), Arostrilepis tenuicirrosa, and Monocercus arionis (Cyclophyllidea), cestodes belonging to three different orders, were investigated by scanning electron microscopy. The interactions were traced from sexually mature to gravid proglottids for all species. Pieces of evidence of interactions among these species include specific tight contacts between microlamellae of the uterine epithelium and the egg capsule, networks of fibrils between eggs and uterus, or numerous branched diverticula of the uterine wall that surround eggs or combinations of these. The contacts between uterine epithelium and eggs take place in mature and post-mature proglottids, at a period of development when eggs are newly formed and the embryos are rapidly developing. The eggs grow and develop actively in tight contact with the uterine wall. The maximum diameter of eggs increases 1.5–2 times (or 3.5–4 times in M. arionis) during development. In all species, the intimate contacts between uterus and eggs have weakened or disappeared by the time the proglottids have become gravid. The association between uterus and eggs thus appears as strong evidence of active trophic interaction (or matrotrophy) between the parent organism and developing eggs. 相似文献