Center for Cardiovascular Sciences, Albany Medical College, Albany, New York
Submitted 12 April 2007
; accepted in final form 1 February 2008
The intermediate filament (IF) network is one of the ...three cytoskeletal systems in smooth muscle. The type III IF proteins vimentin and desmin are major constituents of the network in smooth muscle cells and tissues. Lack of vimentin or desmin impairs contractile ability of various smooth muscle preparations, implying their important role for smooth muscle force development. The IF framework has long been viewed as a fixed cytostructure that solely provides mechanical integrity for the cell. However, recent studies suggest that the IF cytoskeleton is dynamic in mammalian cells in response to various external stimulation. In this review, the structure and biological properties of IF proteins in smooth muscle are summarized. The role of IF proteins in the modulation of smooth muscle force development and redistribution/translocation of signaling partners (such as p130 Crk-associated substrate, CAS) is depicted. This review also summarizes our latest understanding on how the IF network may be regulated in smooth muscle.
cytoskeleton; force development; vimentin; desmin
Address for reprint requests and other correspondence: D. D. Tang, Center for Cardiovascular Sciences, Albany Medical College, 47 New Scotland Ave., MC-8, Albany, NY 12208 (e-mail: tangd{at}mail.amc.edu )
Autophagy, a tightly regulated lysosome-dependent catabolic pathway, is important in the regulation of cancer development and progression and in determining the response of tumor cells to anticancer ...therapy. However, the role of autophagy in leukemia still remains largely unknown. Here we show that high-mobility group box 1 (HMGB1), the best characterized damage-associated molecular pattern, was released from leukemia cell lines after chemotherapy-induced cytotoxicity and activated autophagy to protect against injury. Treatment with HMGB1-neutralizing antibodies increased the sensitivity of leukemia cells to chemotherapy; whereas, exogenous HMGB1 rendered these cells more resistant to drug-induced cytotoxicity. Moreover, exogenous HMGB1 increased autophagy as evaluated by increased expression of the autophagic marker microtubule-associated protein light chain 3-II, degradation of sequestosome 1 (p62) and autophagosome formation. Furthermore, knockdown or pharmacological inhibition of either phosphoinositide 3-kinase-III or extracellular signal-regulated kinase kinase mitogen-activated protein kinase kinase/extracellular signal-regulated protein kinase inhibited HMGB1-induced autophagy. Taken together, these results suggest that HMGB1 release after chemotherapy is a critical regulator of autophagy and a potential drug target for therapeutic interventions in leukemia.
An understanding of the relative permeability of gas and water in coal reservoirs is vital for coalbed methane (CBM) development. In this work, a prediction model for gas–water effective permeability ...is established to describe the permeability variation within coal reservoirs during production. The effective stress and matrix shrinkage effects are taken into account by introducing the Palmer and Mansoori (PM) absolute permeability model. The endpoint relative permeability is calibrated through experimentation instead of through the conventional Corey relative permeability model, which is traditionally employed for the simulation of petroleum reservoirs. In this framework, the absolute permeability model and the relative permeability model are comprehensively coupled under the same reservoir pressure and water saturation conditions through the material balance equation. Using the Qinshui Basin as an example, the differences between the actual curve that is measured with the steady-state method and the simulation curve are compared. The model indicates that the effective permeability is expressed as a function of reservoir pressure and that the curve shape is controlled by the production data. The results illustrate that the PM–Corey dynamic prediction model can accurately reflect the positive and negative effects of coal reservoirs. In particular, the model predicts the matrix shrinkage effect, which is important because it can improve the effective permeability of gas production and render the process more economically feasible.
•A model is established to describe the variation of permeability during production.•The dynamic changes of irreducible water extend the two-phase flow region.•The model can provide a basis for prediction of CBM production.
The lattice thermal conductivity (λL) of general purpose grade polyacrylonitrile (PAN)-based carbon fibers with a crystallite size (La) of several nanometers was examined. Using a modified 3ω method, ...the λL of the fibers with different heat-treatment temperatures were detected, and it was found that the λL was linearly dependent on −1/La. Based on phonon scattering theory, this observation can be attributed to the combined effect of boundary scattering and point-defect scattering. The constant for point-defect scattering (A) was evaluated and a formula was derived.
A novel membrane-based lateral-flow immunodipstick assay was developed for the fast screening of aflatoxin B2 (AFB2) as a model compound in food samples. The detector reagent consisted of magnetic ...nanogold microspheres (MnGMs) with nano-Fe2O3 particles as core and gold nanoparticles as shell, and bio-functionalized with monoclonal anti-AFB2 antibodies. Manually spotted AFB2–bovine serum albumin conjugates (AFB2–BSA) and goat anti-mouse IgG on nitrocellulose membrane were used as test and control lines, respectively. As the major advantage, experimental results indicated that the visual detection limit (cutoff value) of the MnGM-based dipstick immunoassay with 0.9ng/ml AFB2 was about threefold lower compared to a conventional immunodipstick test using gold nanoparticles as detection reagent. Qualitative results (yes/no) could be obtained within 15min without expensive equipment. The assay was evaluated with AFB2 spiked or naturally contaminated samples (n=8), including peanuts, hazelnuts, pistacia and almonds, receiving excellent correspondance with results from high performance liquid chromatography (HPLC). Most importantly, the assay gave no false negative results. By controlling the target antibody this assay can be easily extended for use with other food relevant toxins and thus represents a versatile detection method.
Maize (Zea mays L.) is a globally important staple food crop prone to contamination by aflatoxin, a carcinogenic secondary metabolite produced by the fungus Aspergillus flavus. An efficient approach ...to reduce accumulation of aflatoxin is the development of germplasm resistant to colonization and toxin production by A. flavus. Lipoxygenases (LOXs) are a group of non-heme iron containing dioxygenase enzymes that catalyze oxygenation of polyunsaturated fatty acids (PUFAs). LOX derived oxylipins play critical roles in plant defense against pathogens including A. flavus. The objectives of this study were to summarize sequence diversity and expression patterns for all LOX genes in the maize genome, and map their effect on aflatoxin accumulation via linkage and association mapping. In total, 13 LOX genes were identified, characterized, and mapped. The sequence of one gene, ZmLOX10, is reported from 5 inbred lines. Genes ZmLOX1/2, 5, 8, 9, 10 and 12 (GRMZM2G156861, or V4 numbers ZM00001D042541 and Zm00001D042540, GRMZM2G102760, GRMZM2G104843, GRMZM2G017616, GRMZM2G015419, and GRMZM2G106748, respectively) fell under previously published QTL in one or more mapping populations and are linked to a measurable reduction of aflatoxin in maize grains. Association mapping results found 28 of the 726 SNPs tested were associated with reduced aflatoxin levels at p ≤ 9.71 x 10-4 according to association statistics. These fell within or near nine of the ZmLOX genes. This work confirms the importance of some lipoxygenases for resistance to aflatoxin accumulation and may be used to direct future genetic selection in maize.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Raf-MEK-ERK pathway is commonly activated in human cancers, largely attributable to the extracellular signal-regulated kinases (ERKs) being a common downstream target of growth factor receptors, ...Ras, and Raf. Elevation of these up-stream signals occurs frequently in a variety of malignancies and ERK kinases play critical roles in promoting cell proliferation. Therefore, inhibition of MEK-mediated ERK activation is very appealing in cancer therapy. Consequently, numerous MEK inhibitors have been developed over the years. However, clinical trials have yet to produce overwhelming support for using MEK inhibitors in cancer therapy. Although complex reasons may have contributed to this outcome, an alternative possibility is that the MEK-ERK pathway may not solely provide proliferation signals to malignancies, the central scientific rationale in developing MEK inhibitors for cancer therapy. Recent developments may support this alternative possibility. Accumulating evidence now demonstrated that the MEK-ERK pathway contributes to the proper execution of cellular DNA damage response (DDR), a major pathway of tumor suppression. During DDR, the MEK-ERK pathway is commonly activated, which facilitates the proper activation of DDR checkpoints to prevent cell division. Inhibition of MEK-mediated ERK activation, therefore, compromises checkpoint activation. As a result, cells may continue to proliferate in the presence of DNA lesions, leading to the accumulation of mutations and thereby promoting tumorigenesis. Alternatively, reduction in checkpoint activation may prevent efficient repair of DNA damages, which may cause apoptosis or cell catastrophe, thereby enhancing chemotherapy's efficacy. This review summarizes our current understanding of the participation of the ERK kinases in DDR.
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