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排序方式: 共有213条查询结果,搜索用时 62 毫秒
61.
Sehayek E Wang R Ono JG Zinchuk VS Duncan EM Shefer S Vance DE Ananthanarayanan M Chait BT Breslow JL 《Journal of lipid research》2003,44(9):1605-1613
To better understand the regulation of biliary phospholipid and cholesterol excretion, canalicular membranes were isolated from the livers of C57BL/6J mice and abundant proteins separated by SDS-PAGE and identified by matrix-assisted laser desorption/ionization mass spectrometry. A prominent protein revealed by this analysis was betaine homocysteine methyltransferase (BHMT). This enzyme catalyzes the first step in a three-enzyme pathway that promotes the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC). Immunoblotting confirmed the presence of BHMT on the canalicular membrane, failed to reveal the presence of the second enzyme in this pathway, methionine adenosyltransferase, and localized the third enzyme of the pathway, PE N-methyltransferase (PEMT). Furthermore, immunfluorescence microscopy unambiguously confirmed the localization of PEMT to the canalicular membrane. These findings indicate that a local mechanism exists in or around hepatocyte canalicular membranes to promote phosphatidylethnolamine methylation and PC biosynthesis. Finally, immunoblotting revealed the presence and immunofluorescence microscopy unambiguously localized the scavenger receptor class B type I (SR-BI) to the canalicular membrane. Therefore, SR-BI, which is known to play a role in cholesterol uptake at the hepatocyte basolateral membrane, may also be involved in biliary cholesterol excretion. Based on these findings, a model is proposed in which local canalicular membrane PC biosynthesis in concert with the phospholipid transporter mdr2 and SR-BI, promotes the excretion of phospholipid and cholesterol into the bile. 相似文献
62.
Emmanuel?GeretaEmail author Ephraim?Mwangomo Eric?Wolanski 《Wetlands Ecology and Management》2004,12(4):301-307
The distribution of temperature, salinity, visibility and dissolved oxygen was sampled from 1996 to 2002 at sites along the Seronera River. The minimum temperature decreased with distance upstream. The salinity increased up-river where occasionally hypersaline conditions prevailed. Dissolved oxygen was highly variable spatially and temporally, depending on both the level of eutrophication by animal dung and the presence of wetlands that help filter the excess nutrients. During the study period, fringing, freshwater wetlands have generally been degraded and in some cases destroyed, and this has been accompanied by significantly decreased oxygen levels, sometimes nearing anoxic conditions. Also during this period, saltwater wetlands have increased, and since wildlife impacted these wetlands little, dissolved oxygen levels remained high throughout. Visibility was highest in areas fringed by wetlands.This revised version wa published online in March 2005 with corrections to the issue cover date. 相似文献
63.
Immunotherapy of established tumors using bone marrow transplantation with antigen gene--modified hematopoietic stem cells 总被引:2,自引:0,他引:2
Cui Y Kelleher E Straley E Fuchs E Gorski K Levitsky H Borrello I Civin CI Schoenberger SP Cheng L Pardoll DM Whartenby KA 《Nature medicine》2003,9(7):952-958
A major focus of cancer immunotherapy is to develop strategies to induce T-cell responses through presentation of tumor antigens by dendritic cells (DCs). Current vaccines are limited in their ability to efficiently transfer antigens to DCs in vivo. Ex vivo-generated DCs can be efficiently loaded with antigen but after reinjection, few DCs traffic to secondary lymphoid organs, the critical sites for antigen presentation. To enhance efficiency and durability of antigen presentation by DCs, we transduced hematopoietic stem-progenitor cells (HSCs) with a model tumor antigen and then transplanted the gene-modified cells into irradiated recipient mice, which resulted in efficient expression of the transgene in a large proportion of donor derived DCs in lymphoid organs. The combination of bone marrow transplantation (BMT) using transduced HSCs, systemic agents that generate and activate DCs, and mature T-cell infusion resulted in substantial expansion and activation of antigen-specific T cells. This tripartite strategy provided potent antigen-specific immunotherapy for an aggressive established tumor. 相似文献
64.
65.
Abstract: Production and metabolism of platelet-activating factor (PAF) in the fetal rat brain under normal and under ischemic stress conditions were examined. Endogenous PAF levels, determined by a bioassay using PAF-stimulated platelet release of [3H]serotonin, averaged 2.32 ± 2.14 pg/mg in control brains and was reduced to 1.10 ± 1.06 pg/mg after 20 min of maternal-fetal blood flow occlusion. [3H]PAF administered intracranially into the fetuses in utero was removed in a biphasic, time-dependent manner: a rapid component with an estimated elimination rate constant of 0.067 min?1 and t1/2 of 10 min and a slower component with an elimination rate of 0.017 min?1 and t1/2 of 41 min. In fetal brains subjected to ischemia a delayed elimination of [3H]PAF was noticed in the slow component (t1/2 = 59 min), indicating a possible difference between the clearance of exogenous and endogenous PAF. The disappearance of [3H]PAF was accompanied by an increase in the radioactivity associated with lyso-PAF that reached a plateau after 2.5 min, possibly indicating the degradation of the fast component. A steady increase in the alkyl-acyl-glycerophosphorylcholine radioactivity commenced after 5 min and continued up to 30 min. The endogenous production of PAF and the rapid degradation due to maternal-fetal blood flow occlusion indicate an additional target for therapeutic intervention in the pathology of intrauterine ischemia. Addition of the calcium ionophore A23187 stimulated in vitro formation of PAF and lyso-PAF from [3H]-choline-labeled fetal brain phospholipids, suggesting that intracellular calcium may play a major stimulatory role in PAF production. Degradation of polyphosphoinositides by a phospholipase C may constitute a major target for PAF generated either by decapitation or after blood flow occlusion, as evident from the protective effect of the in vivo administered BN52021 PAF antagonist. 相似文献
66.
The effect of amyloid (A), the major constituent of the Alzheimer's (AD) brain on lipid metabolism was investigated in cultured nerve cells and in a fetal rat brain model. Differentiated (NGF) and undifferentiated PC12 cells or primary cerebral cell cultures were incubated with [14C]acetate in the absence or presence of A1–40. Incorporation of label into lipid species was determined after lipid extraction and TLC separation. Phosphatidylcholine (PC) and phosphatidylserine (PS) synthesis was increased by A1–40, in a dose dependent manner, an effect which was more pronounced in differentiated PC12 cells. A significant proportion of radioactivity (5–6%) was released into the medium with a radioactivity distribution similar to that of the cellular lipids. Cholesterol and PC were the highest labeled medium lipids. Increasing A1–40 concentration up to 0.1 g/ml in cerebral cells but not in PC12 cells, caused a relative increase (1.5 fold) in release of PS, while that of PE decreased. Stimulation of PS release may possibly be associated with apoptotic cell death. A1–40 peptide (5 g) was administered intraperitonealy into rat fetuses (18 days gestation) along with [14C]acetate (2Ci/fetus). After 24 h, the maternal-fetal blood supply was occluded for 20 min (ischemia) followed by 15 min reperfusion. Fetuses were killed and liver and brain tissue subjected to lipid extraction and radioactivity determination after TLC. A1–40 peptide increased synthesis of different classes of lipids up to 20–40% in brain tissue compared to controls. Labeling of liver lipids was decreased by A1–40 by 20–30%. A general decrease in synthesis of lipids was observed after ischemia/reperfusion. Our data suggest that A1–40 peptide regulates normal lipid biosynthesis but under ischemia it compromises it. The latter finding may confirm the oxidative stress etiology in AD and suggests that A1–40 modulation of lipid metabolism may have Alzheimer's pathological relevance, particularly at high peptide concentrations. 相似文献
67.
Understanding animal movement and resource selection provides important information about the ecology of the animal, but an animal's movement and behavior are not typically constant in time. We present a velocity-based approach for modeling animal movement in space and time that allows for temporal heterogeneity in an animal's response to the environment, allows for temporal irregularity in telemetry data, and accounts for the uncertainty in the location information. Population-level inference on movement patterns and resource selection can then be made through cluster analysis of the parameters related to movement and behavior. We illustrate this approach through a study of northern fur seal (Callorhinus ursinus) movement in the Bering Sea, Alaska, USA. Results show sex differentiation, with female northern fur seals exhibiting stronger response to environmental variables. 相似文献
68.
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model 总被引:1,自引:0,他引:1
69.
Pete Smith Katherine Calvin Johnson Nkem Donovan Campbell Francesco Cherubini Giacomo Grassi Vladimir Korotkov Anh Le Hoang Shuaib Lwasa Pamela McElwee Ephraim Nkonya Nobuko Saigusa Jean‐Francois Soussana Miguel Angel Taboada Frances C. Manning Dorothy Nampanzira Cristina Arias‐Navarro Matteo Vizzarri Jo House Stephanie Roe Annette Cowie Mark Rounsevell Almut Arneth 《Global Change Biology》2020,26(3):1532-1575
There is a clear need for transformative change in the land management and food production sectors to address the global land challenges of climate change mitigation, climate change adaptation, combatting land degradation and desertification, and delivering food security (referred to hereafter as “land challenges”). We assess the potential for 40 practices to address these land challenges and find that: Nine options deliver medium to large benefits for all four land challenges. A further two options have no global estimates for adaptation, but have medium to large benefits for all other land challenges. Five options have large mitigation potential (>3 Gt CO2eq/year) without adverse impacts on the other land challenges. Five options have moderate mitigation potential, with no adverse impacts on the other land challenges. Sixteen practices have large adaptation potential (>25 million people benefit), without adverse side effects on other land challenges. Most practices can be applied without competing for available land. However, seven options could result in competition for land. A large number of practices do not require dedicated land, including several land management options, all value chain options, and all risk management options. Four options could greatly increase competition for land if applied at a large scale, though the impact is scale and context specific, highlighting the need for safeguards to ensure that expansion of land for mitigation does not impact natural systems and food security. A number of practices, such as increased food productivity, dietary change and reduced food loss and waste, can reduce demand for land conversion, thereby potentially freeing‐up land and creating opportunities for enhanced implementation of other practices, making them important components of portfolios of practices to address the combined land challenges. 相似文献
70.
The use of numerical simulation as a means to predict the outcome of transurethral microwave thermotherapy (TUMT) is set forth in detail. The simulation was carried out as a case study of a specific TUMT procedure. The selection of the case study was based on the availability of extensive medical records which documented an extraordinary application of TUMT. Predictions were made of the time-varying temperature patterns within the prostate, the bladder, the sphincter, the pelvic floor, and the fat and connective tissue which envelop these organs. These temperature patterns provided the basis of maps which highlighted those locations where necrosis occurred. An injury integral was used to predict the extent of the necrotic tissue produced by the therapy. It was found that, for the specific case being considered, necrosis occurred not only within the prostate but also extended to the neck of the bladder and to the fatty tissue. A special feature of the simulation was the accounting of the liquid-to-vapor phase change of the interstitial water. The vapor generated by the phase change is believed to significantly enlarge the region of necrosis. By the same token, the vapor pressure is expected to cause motion of the high-temperature liquid to deep-tissue regions. The damage predicted by the numerical simulation was compared, in detail, with post-operative medical examinations and found to be corroborated. 相似文献