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911.
Subunits of the endosomal sorting complex required for transport (ESCRT) were identified as components of a molecular machinery that sorts ubiquitinated membrane proteins into the intraluminal vesicles (ILVs) of multivesicular endosomes (MVEs) for subsequent delivery to the lumen of lysosomes or related organelles. As many of the membrane proteins that undergo ESCRT-mediated sorting are signalling receptors that are ubiquitinated in response to ligand binding, ESCRT subunits have been hypothesized to play a crucial role in attenuation of cell signalling by mediating ligand-induced receptor degradation. Here we discuss this concept based on the examples from loss-of-function studies in model organisms and cell lines. The emerging picture is that ESCRTs are indeed involved in downregulation of receptor signalling pathways associated with cell survival, proliferation and polarity. In addition, the recent discovery of a positive role for the ESCRT pathway in Wnt signalling through sequestration of an inhibitory cytosolic component into MVEs illustrates that ESCRTs may also control signalling in ways that are independent of degradative receptor sorting. 相似文献
912.
Arabidopsis DEMETER-LIKE proteins DML2 and DML3 are required for appropriate distribution of DNA methylation marks 总被引:2,自引:0,他引:2
Ortega-Galisteo AP Morales-Ruiz T Ariza RR Roldán-Arjona T 《Plant molecular biology》2008,67(6):671-681
Cytosine DNA methylation is a stable epigenetic mark for maintenance of gene silencing across cellular divisions, but it is a reversible modification. Genetic and biochemical studies have revealed that the Arabidopsis DNA glycosylase domain-containing proteins ROS1 (REPRESSOR OF SILENCING 1) and DME (DEMETER) initiate erasure of 5-methylcytosine through a base excision repair process. The Arabidopsis genome encodes two paralogs of ROS1 and DME, referred to as DEMETER-LIKE proteins DML2 and DML3. We have found that DML2 and DML3 are 5-methylcytosine DNA glycosylases that are expressed in a wide range of plant organs. We analyzed the distribution of methylation marks at two methylated loci in wild-type and dml mutant plants. Mutations in DML2 and/or DML3 lead to hypermethylation of cytosine residues that are unmethylated or weakly methylated in wild-type plants. In contrast, sites that are heavily methylated in wild-type plants are hypomethylated in mutants. These results suggest that DML2 and DML3 are required not only for removing DNA methylation marks from improperly-methylated cytosines, but also for maintenance of high methylation levels in properly targeted sites. 相似文献
913.
Vanessa B. Fortes Júlio César Bicca-Marques 《International journal of primatology》2008,29(3):717-722
We located 4 brown howlers (1 adult male, 2 adult females, and 1 juvenile male) showing abnormally lighter pelage in 3 social
groups comprising 5, 6, and 9 individuals in a 20 ha-forest fragment in the State of Rio Grande do Sul, Brazil. Two additional
groups composed only of normally colored individuals also live in the fragment, which is isolated from nearby fragments by
267–1009 m. They were the only brown howlers with abnormal pelage color out of a total of 386 individuals belonging to 67
groups in 21 fragments in the 5876-ha study area. The isolation of the forest fragment, its high howler density (2.2 individuals⁄ha),
and large group size (8.8 ± 2.4 individuals) may decrease the likelihood of successful immigration into the population, leading
to an increased probability of inbreeding that may facilitate the expression of rare alleles. 相似文献
914.
Huber J Fürnkranz A Bochkov VN Patricia MK Lee H Hedrick CC Berliner JA Binder BR Leitinger N 《Journal of lipid research》2006,47(5):1054-1062
Oxidized phospholipids stimulate endothelial cells to bind monocytes, but not neutrophils, an initiating event in atherogenesis. Here, we investigate intracellular signaling events induced by oxidized phospholipids in human umbilical vein endothelial cells (HUVECs) that lead to specific monocyte adhesion. In a static adhesion assay, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine and one of its components, 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine, stimulated HUVECs to bind U937 cells and human peripheral blood monocytes but not HL-60 cells or blood neutrophils. Monocyte adhesion was dependent on protein kinases A and C, extracellular signal-regulated kinase 1/2, p38 mitogen activated protein kinases (MAPKs), and cytosolic phospholipase A(2) (cPLA(2)). Inhibition of 12-lipoxygenase (12-LOX), but not cyclooxygenases, blocked monocyte adhesion, and addition of 12-hydroxyeicosatetraenoic acid (12-HETE) mimicked the effects of oxidized phospholipids. Peroxisome proliferator-activated receptor alpha (PPARalpha) was excluded as a possible target for 12-HETE, because monocyte adhesion was still induced in endothelial cells from PPARalpha null mice. Together, our results suggest that oxidized phospholipids stimulate HUVECs to specifically bind monocytes involving MAPK pathways, which lead to the activation of cPLA(2) and 12-LOX. Further analysis of signaling pathways induced by oxidized phospholipids that lead to specific monocyte adhesion should ultimately lead to the development of novel therapeutic approaches against chronic inflammatory diseases. 相似文献
915.
Background
Dihydroartemisinin (DHA), a powerful anti-malarial drug, has been used as monotherapy and artemisinin-based combination therapy (ACT) for more than decades. So far, however, the tissue distribution and metabolic profile of DHA data are not available from animal and humans.Methods
Pharmacokinetics, tissue distribution, mass balance, and elimination of [14C] DHA have been studieded in rats following a single intravenous administration. Protein binding was performed with rat and human plasma. Drug concentrations were obtained up to 192 hr from measurements of total radioactivity and drug concentration to determine the contribution by the parent and metabolites to the total dose of drug injected from whole blood, plasma, urine and faecal samples.Results
Drug was widely distributed after 1 hr and rapidly declined at 24 hr in all tissues except spleen until 96 hrs. Only 0.81% of the total radioactivity was detected in rat brain tissue. DHA revealed a high binding capacity with both rat and human plasma proteins (76–82%). The concentration of total radioactivity in the plasma fraction was less than 25% of that in blood total. Metabolism of DHA was observed with high excretion via bile into intestines and approximately 89–95% dose of all conjugations were accounted for in blood, urine and faeces. However, the majority of elimination of [14C] DHA was through urinary excretion (52% dose). The mean terminal half-lives of plasma and blood radioactivity (75.57–122.13 h) were significantly prolonged compared with that of unchanged DHA (1.03 h).Conclusion
In rat brain, the total concentration of [14C] was 2-fold higher than that in plasma, indicating the radioactivity could easily penetrate the brain-blood barrier. Total radioactivity distributed in RBC was about three- to four-fold higher than that in plasma, suggesting that the powerful anti-malarial potency of DHA in the treatment of blood stage malaria may relate to the high RBC binding. Biliary excretion and multiple concentration peaks of DHA have been demonstrated with high urinary excretion due to a most likely drug re-absorption in the intestines (enterohepatic circulation). The long lasting metabolites of DHA (> 192 hr) in the rats may be also related to the enterohepatic circulation. 相似文献916.
The influence of depth,site exposure and season on the intensity of iceberg scouring in nearshore Antarctic waters 总被引:2,自引:3,他引:2
Ice scour disturbance has a significant effect on the physical and biological characteristics of polar benthos. A series of
grids, each consisting of 25 markers, were deployed along depth transects and replicated at two contrasting study sites at
Adelaide Island, West Antarctic Peninsula. Markers were surveyed and replaced every 3 months for 2 years in order to assess
the frequency and intensity of iceberg impacts. Depth, site, season and year were all highly significant factors influencing
ice scouring frequency. We observed a high variation in the duration of winter fast ice between sites and years, which had
a marked effect on ice scouring frequency. The ecological effects of the disturbance regime are likely to include depth zonation
of benthic assemblages, patchiness of communities at varying stages of recovery and the near denudation of sessile fauna in
the shallow subtidal.
相似文献
Dan A. SmaleEmail: |
917.
Takashi Haramura 《Journal of Ethology》2007,25(1):3-7
Microhabitat selection is particularly important to increase the survival rate and reproductive success of animals inhabiting
heterogeneous environments. I investigated microhabitat selection of Buergeria
japonica tadpoles inhabiting the stream in a coastal area to reveal how animals select their appropriate habitat under heterogeneous
and unstable environments on the subtropical Okinawa Island of Japan. Tadpoles are sensitive to subtle environmental changes,
and the mouths of streams in coastal areas that have intense environmental fluctuations such as desiccation and sudden changes
in current velocity would be risky habitat for tadpoles. Tadpoles of B. japonica can inhabit both lotic and lentic systems. Field observations showed that, among six physical factors (water depth, water
temperature, salinity, pH, current velocity, and substrate), current velocity and water temperature were key factors in microhabitat
selection by tadpoles. It is likely that tadpoles stay at low current velocity sites to reduce the probability of being washed
out to the sea by a sudden squall and that selection of warmer sites would accelerate development of tadpoles so as to escape
the heterogeneous aquatic habitat sooner. 相似文献
918.
Xiao-Xia Duan Guan-Peng Zhang Xiao-Bin Wang Hua Yu Jia-Li Wu Ke-Zhi Liu Lin Wang Xiang Long 《Molecular neurobiology》2017,54(3):1677-1683
The aim of this study was to evaluate the prognostic value of serum and cerebrospinal fluid (CSF) free fatty acid (FFA) levels in a cohort of patients with an acute ischemic stroke (AIS). In a prospective study, FFA levels were measured using an enzyme cycling method on admission in serum and CSF of 252 consecutive patients with AIS. The prognostic value of FFA to predict the functional outcome and mortality within 90-day was compared with the National Institutes of Health Stroke Scale score and with other known outcome predictors. Serum and CSF levels of FFA increased with increasing severity of stroke as defined by the NIHSS score (all P?<?0.001). Patients with an unfavorable outcomes and non-survivors had significantly increased FFA serum and CSF levels on admission (all P?<?0.0001). Multivariate logistic regression analysis adjusted for common risk factors showed that serum FFA ≥0.71 mmol/L (third quarters) was an independent predictor of functional outcome (odds ratios (OR)?=?4.86; 95 % confidence interval (CI) 2.26–10.48) and mortality (OR?=?7.72; 95 % CI 3.01–21.48). The area under the receiver operating characteristic curve of serum FFA was 0.79 (95 % CI, 0.72–0.86) for functional outcome and 0.86 (95 % CI, 0.78–0.94) for mortality. Similarly, CSF FFA level also was an indicator for predicting of functional outcome and mortality. FFA levels in serum and CSF may serve as independent biomarkers in addition of the traditional methods for assessing the functional outcome and mortality of AIS. 相似文献
919.
Wen-Xiang Cao Ting Li Zheng-Hai Tang Le-Le Zhang Zhao-Yu Wang Xia Guo Min-Xia Su Xiuping Chen Jin-Jian Lu 《Apoptosis : an international journal on programmed cell death》2018,23(9-10):521-531
The pseudokinase mixed lineage kinase domain-like protein (MLKL) is a core effector of necroptosis, and its function in necroptosis is widely studied. However, the function of MLKL in apoptosis remains unclear. In the present study, the role of MLKL in chelerythrine (CHE)-promoted apoptosis was studied. A special band of MLKL (i.e., *MLKL) was observed after treatment with CHE. MLKL and *MLKL were accumulated in the nucleus upon treatment with CHE and MLKL silencing reversed the CHE-induced apoptosis. Blockade of CHE-triggered reactive oxygen species (ROS) generation or inhibition of CHE-activated protein kinase-like endoplasmic reticulum kinase (PERK)-eukaryotic initiation factor 2 α subunit (eIF2α) pathway reversed the apoptosis. A decreased ROS level inhibited CHE-mediated nuclear translocation of MLKL and *MLKL and the activation of eIF2α, whereas MLKL or eIF2α silencing did not affect the CHE-triggered ROS generation. Furthermore, MLKL silencing prevented the CHE-activated eIF2α signal, and eIF2α silencing blocked the CHE-induced nuclear translocation of MLKL and *MLKL. Our studies suggested that CHE possibly induces apoptosis through the nuclear translocation of MLKL and *MLKL, which is promoted by a mutual regulation between MLKL and PERK–eIF2α pathway in response to ROS formation. The present study clarified the new function of MLKL in apoptosis. 相似文献
920.
Random network models have been a popular tool for investigating cortical network dynamics. On the scale of roughly a cubic millimeter of cortex, containing about 100,000 neurons, cortical anatomy suggests a more realistic architecture. In this locally connected random network, the connection probability decreases in a Gaussian fashion with the distance between neurons. Here we present three main results from a simulation study of the activity dynamics in such networks. First, for a broad range of parameters these dynamics exhibit a stationary state of asynchronous network activity with irregular single-neuron spiking. This state can be used as a realistic model of ongoing network activity. Parametric dependence of this state and the nature of the network dynamics in other regimes are described. Second, a synchronous excitatory stimulus to a fraction of the neurons results in a strong activity response that easily dominates the network dynamics. And third, due to that activity response an embedding of a divergent-convergent feed-forward subnetwork (as in synfire chains) does not naturally lead to a stable propagation of synchronous activity in the subnetwork; this is in contrast to our earlier findings in isolated subnetworks of that type. Possible mechanisms for stabilizing the interplay of volleys of synchronous spikes and network dynamics by specific learning rules or generalizations of the subnetworks are discussed. 相似文献