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81.
Tepper AD Ruurs P Wiedmer T Sims PJ Borst J van Blitterswijk WJ 《The Journal of cell biology》2000,150(1):155-164
Apoptosis is generally accompanied by a late phase of ceramide (Cer) production, the significance of which is unknown. This study describes a previously unrecognized link between Cer accumulation and phosphatidylserine (PS) exposure at the cell surface, a characteristic of the execution phase of apoptosis resulting from a loss of plasma membrane phospholipid asymmetry. Using a fluorescent sphingomyelin (SM) analogue, N-(N-[6-[(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino]caproyl]-sphingosylphosphorylcholine (C(6)-NBD-SM), we show that Cer is derived from SM, initially located in the outer leaflet of the plasma membrane, which gains access to a cytosolic SMase by flipping to the inner leaflet in a process of lipid scrambling paralleling PS externalization. Lipid scrambling is both necessary and sufficient for SM conversion: Ca(2+) ionophore induces both PS exposure and SM hydrolysis, whereas scrambling-deficient Raji cells do not show PS exposure or Cer formation. Cer is not required for mitochondrial or nuclear apoptotic features since these are still observed in Raji cells. SM hydrolysis facilitates cholesterol efflux to methyl-beta-cyclodextrin, which is indicative of a loss of tight SM-cholesterol interaction in the plasma membrane. We provide evidence that these biophysical alterations in the lipid bilayer are essential for apoptotic membrane blebbing/vesiculation at the cell surface: Raji cells show aberrant apoptotic morphology, whereas replenishment of hydrolyzed SM by C(6)- NBD-SM inhibits blebbing in Jurkat cells. Thus, SM hydrolysis, during the execution phase of apoptosis, results from a loss of phospholipid asymmetry and contributes to structural changes at the plasma membrane. 相似文献
82.
Smith F Sims J 《BMJ (Clinical research ed.)》2000,320(7247):1471; author reply 1473-1471; author reply 1474
83.
Elevated CO2 concentration has independent effects on expansion rates and thickness of soybean leaves across light and nitrogen gradients 总被引:1,自引:0,他引:1
The rate and extent of leaf thickness and area development are important
determinants of whole plant photosynthetic capacity. The interactive
effects of photon flux density (PFD), nitrogen supply
and CO2 concentration on leaf expansion rate were measured as well as final
leaf size and thickness of soybean. Leaf thickness and final area were not
correlated with leaf relative expansion rate (RER)
suggesting that these parameters are controlled by different mechanisms and
that final leaf dimensions are determined by the duration rather than the
rate of leaf expansion. Carbohydrate supply did not explain the variation
in leaf RER since RER increased
with increasing CO2 concentration, but decreased with increasing
PFD. Leaf thickness and final area were related to
resource supply but not in a simple fashion. Both positive and negative
correlations between leaf thickness and carbohydrate and nitrogen
concentrations were obtained depending on the environmental variable
responsible for the variation. In contrast, there was a simple proportional
relationship between whole plant relative growth rate and a correlate of
leaf thickness (leaf water content per unit area), suggesting that leaf
thickness responds to the balanced supply of all resources, in the same
fashion as RGR, rather than to any individual
resource. 相似文献
84.
Polarized migration and spreading of epithelial sheets is important during many processes in vivo, including embryogenesis and wound healing. However, the signaling pathways that regulate epithelial migrations are poorly understood. To identify molecular components that regulate the spreading of epithelial sheets, we performed a screen for mutations that perturb epidermal cell migration during embryogenesis in Caenorhabditis elegans. We identified one mutant (jc5) as a weak mutation in itr-1, which encodes the single inositol 1,4,5-trisphosphate receptor (ITR) in C. elegans. During the migration of the embryonic epidermis, jc5 embryos display defects including misdirected migration or premature cessation of migration. Cells that halt their migration have disorganized F-actin and display reduced filopodial protrusive activity at their leading edge. Furthermore, some filopodia formed by epidermal cells in itr-1(jc5) embryos exhibit abnormally long lifetimes. Pharmacological studies with the inositol 1,4,5-trisphosphate antagonist xestospongin C phenocopy these defects, confirming that ITR function is important for proper epidermal migration. Our results provide the first molecular evidence that movements of embryonic epithelial cell sheets can be controlled by ITRs and suggest that such regulation may be a widespread mechanism for coordinating epithelial cell movements during embryogenesis. 相似文献
85.
86.
Peter J. Sims 《生物化学与生物物理学报:生物膜》1983,732(3):541-552
The number of membrane-bound terminal complement proteins (C5b-9) required to generate a functional pore in the human erythrocyte membrane ghost has been determined. Resealed erythrocyte ghost membranes (ghosts) were treated with human complement proteins C5b6, C7, 131I-C8, and 125I-C9 under non-lytic conditions. Following C5b-9 assembly, sucrose-permeant ghosts were separated from C5b-9 ghosts that remained impermeant to sucrose by centrifugation over density barriers formed of 43% (w/v) sucrose. Analysis of 131I-C8 and 125I-C9 bound to sucrose-permeant and sucrose-impermeant subpopulations of C5b-9 ghosts revealed: 1. Sucrose-permeant C5b-9 ghosts show increased uptake of both 131I-C8 and 125I-C9 as compared to ghosts that remain impermeant to sucrose. Ghosts with less than 300 molecules 131I-C8 bound remain impermeant to sucrose, irrespective of the total C9 input, or, the multiplicity of C9 uptake by membrane C5b-8. 2. In the presence of excess 125I-C9, the ratio of 125I-C9/131I-C8 bound to membrane C5b67 is 3.2 ± 0.8 (mean ± 2 S.D.), suggesting an average stoichiometry of 3 C9 per C5b-8. Under these conditions, the ratio of 125I-C9/131I-C8 bound to sucrose-permeant ghosts (3.3 ± 0.7) does not significantly differ from the ratio bound to sucrose-impermeant ghosts (2.9 ± 0.6). 3. With limiting C9 input, the threshold of total C5b-8 uptake required for sucrose permeability increases significantly above 300 per cell when the ratio of bound 125I-C9/131I-C8 is decreased below unity. In the complete absence of C9, 11 700 C5b-8 complexes are bound to sucrose-permeant ghosts. It is concluded that more than 300 C5b-9 complexes must bind to the human erythrocyte to form a sucrose-permeant lesion. Although the binding of one C9 per C5b-8 is critical to the pore-forming activity of these proteins, the binding of additional molecules of C9 to each complex (C9/C8 > 1) does not significantly alter the threshold of total C5b-9 uptake required for lesion formation. 相似文献
87.
Hyunwoo Park Steven Weier Fareha Razvi Pamela A. Peña Neil A. Sims Jennica Lowell Cory Hungate Karma Kissinger Gavin Key Paul Fraser Johnathan A. Napier Edgar B. Cahoon Tom E. Clemente 《Plant biotechnology journal》2017,15(2):227-236
Soya bean (Glycine max (L.) Merr.) is sought after for both its oil and protein components. Genetic approaches to add value to either component are ongoing efforts in soya bean breeding and molecular biology programmes. The former is the primary vegetable oil consumed in the world. Hence, its primary usage is in direct human consumption. As a means to increase its utility in feed applications, thereby expanding the market of soya bean coproducts, we investigated the simultaneous displacement of marine ingredients in aquafeeds with soya bean‐based protein and a high Omega‐3 fatty acid soya bean oil, enriched with alpha‐linolenic and stearidonic acids, in both steelhead trout (Oncorhynchus mykiss) and Kampachi (Seriola rivoliana). Communicated herein are aquafeed formulations with major reduction in marine ingredients that translates to more total Omega‐3 fatty acids in harvested flesh. Building off of these findings, subsequent efforts were directed towards a genetic strategy that would translate to a prototype design of an optimal identity‐preserved soya bean‐based feedstock for aquaculture, whereby a multigene stack approach for the targeted synthesis of two value‐added output traits, eicosapentaenoic acid and the ketocarotenoid, astaxanthin, were introduced into the crop. To this end, the systematic introduction of seven transgenic cassettes into soya bean, and the molecular and phenotypic evaluation of the derived novel events are described. 相似文献
88.
M.J. Siegert A. Behar M. Bentley D. Blake S. Bowden P. Christoffersen C. Cockell H. Corr D. C. Cullen H. Edwards A. Ellery C. Ellis-Evans G. Griffiths R. Hindmarsh D. A. Hodgson E. King H. Lamb L. Lane K. Makinson M. Mowlem J. Parnell D. A. Pearce J. Priscu A. Rivera M. A. Sephton M. R. Sims A . M. Smith M. Tranter J. L. Wadham G. Wilson J. Woodward 《Reviews in Environmental Science and Biotechnology》2007,6(1-3):161-179
Antarctic subglacial lakes have, over the past few years, been hypothesised to house unique forms of life and hold detailed
sedimentary records of past climate change. Testing this hypothesis requires in situ examinations. The direct measurement
of subglacial lakes has been considered ever since the largest and best-known lake, named Lake Vostok, was identified as having
a deep water-column. The Subglacial Antarctic Lake Environments (SALE) programme, set up by the Scientific Committee on Antarctic
Research (SCAR) to oversee subglacial lakes research, state that prior exploration of smaller lakes would be a “prudent way
forward”. Over 145 subglacial lakes are known to exist in Antarctica, but one lake in West Antarctica, officially named Ellsworth
Subglacial Lake (referred to hereafter as Lake Ellsworth), stands out as a candidate for early exploration. A consortium of
over 20 scientists from seven countries and 14 institutions has been assembled to plan the exploration of Lake Ellsworth.
An eight-year programme is envisaged: 3 years for a geophysical survey, 2 years for equipment development and testing, 1 year
for field planning and operation, and 2 years for sample analysis and data interpretation. The science experiment is simple
in concept but complex in execution. Lake Ellsworth will be accessed using hot water drilling. Once lake access is achieved,
a probe will be lowered down the borehole and into the lake. The probe will contain a series of instruments to measure biological,
chemical and physical characteristics of the lake water and sediments, and will utilise a tether to the ice surface through
which power, communication and data will be transmitted. The probe will pass through the water column to the lake floor. The
probe will then be pulled up and out of the lake, measuring its environment continually as this is done. Once at the ice surface,
any water samples collected will be taken from the probe for laboratory analysis (to take place over subsequent years). The
duration of the science mission, from deployment of the probe to its retrieval, is likely to take between 24 and 36 h. Measurements
to be taken by the probe will provide data about the following: depth, pressure, conductivity and temperature; pH levels;
biomolecules (using life marker chips); anions (using a chemical analyzer); visualisation of the environment (using cameras
and light sources); dissolved gases (using chromatography); and morphology of the lake floor and sediment structures (using
sonar). After the probe has been retrieved, a sediment corer may be dropped into the lake to recover material from the lake
floor. Finally, if time permits, a thermistor string may be left in the lake water to take time-dependent measurements of
the lake’s water column over subsequent years. Given that the comprehensive geophysical survey of the lake will take place
in two seasons during 2007–2009, a two-year instrument and logistic development phase from 2008 (after the lake’s bathymetry
has been assessed) makes it possible that the exploration of Lake Ellsworth could take place at the beginning of the next
decade. 相似文献
89.
Jo Meagan Garner Meiyun Fan Chuan He Yang Ziyun Du Michelle Sims Andrew M. Davidoff Lawrence M. Pfeffer 《The Journal of biological chemistry》2013,288(36):26167-26176
Malignant gliomas are locally aggressive, highly vascular tumors that have a dismal prognosis, and present therapies provide little improvement in the disease course and outcome. Many types of malignancies, including glioblastoma, originate from a population of cancer stem cells (CSCs) that are able to initiate and maintain tumors. Although CSCs only represent a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance drives tumorigenesis. Therefore, it is imperative to identify pathways associated with CSCs to devise strategies to selectively target them. In this study, we describe a novel relationship between glioblastoma CSCs and the Notch pathway, which involves the constitutive activation of STAT3 and NF-κB signaling. Glioma CSCs were isolated and maintained in vitro using an adherent culture system, and the biological properties were compared with the traditional cultures of CSCs grown as multicellular spheres under nonadherent culture conditions. Interestingly, both adherent and spheroid glioma CSCs show constitutive activation of the STAT3/NF-κB signaling pathway and up-regulation of STAT3- and NF-κB-dependent genes. Gene expression profiling also identified components of the Notch pathway as being deregulated in glioma CSCs, and the deregulated expression of these genes was sensitive to treatment with STAT3 and NF-κB inhibitors. This finding is particularly important because Notch signaling appears to play a key role in CSCs in a variety of cancers and controls cell fate determination, survival, proliferation, and the maintenance of stem cells. The constitutive activation of STAT3 and NF-κB signaling pathways that leads to the regulation of Notch pathway genes in glioma CSCs identifies novel therapeutic targets for the treatment of glioma. 相似文献