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1.
ß-Crystallins are structural lens proteins with aconserved two-domain structure and variable N- and C-terminalextensions. These extensions are assumed to be involved in quaternaryinteractions within the ß-crystallin oligomers orwith other lens proteins. Therefore, the production of ßA3-and ßAl-crystallin from the single ßA3/A1mRNA by dual translation initiation is of interest. These crystallinsare identical, except that ßAl has a much shorterN-terminal extension than ßA3. This rare mechanismhas been conserved for over 250 million years during the evolutionof the ßA3/A1 gene, suggesting that the generationof different N-terminal extensions confers a selective advantage.We therefore compared the stability and association behaviourof recombinant ßA3- and ßAl-crystallin.Both proteins are equally stable in urea- and pH-induced denaturationexperiments. Gel filtration and analytical ultracentrifugationestablished that ßA3 and ßA1 both form homodimers.In the water-soluble proteins of bovine lens, ßA3and ßA1 are present in the same molecular weight fractions,indicating that they oligomerize equally with other ß-crystallins.1H-NMR spectroscopy showed that residues Met1 to Asn22 of theN-terminal extension of ßA3 have great flexibilityand are solvent exposed, excluding them from protein interactionsin the homodimer. These results indicate that the differentN-terminal extensions of ßA3 and ßA1 donot affect their homo- or heteromeric interactions.  相似文献   

2.
Ageratina adenophora is one of the major invasive weeds that causes instability of the ecosystem. Research has reported that A. adenophora produces allelochemicals that inhibit the growth and development of food crops, and also contain some toxic compounds that cause toxicity to animals that consume it. Over the past decades, studies on the identification of major toxic compounds of A. adenophora and their toxic molecular mechanisms have been reported. In addition, weed control interventions, such as herbicides application, was employed to reduce the spread of A. adenophora. However, the development of therapeutic and prophylactic measures to treat the various A. adenophora—induced toxicities, such as hepatotoxicity, splenotoxicity and other related disorders, have not been established to date. The main toxic pathogenesis of A. adenophora is oxidative stress and inflammation. However, numerous studies have verified that some extracts and secondary metabolites isolated from A. adenophora possess anti-oxidation and anti-inflammation activities, which implies that these extracts can relieve toxicity and aid in the development of drug or feed supplements to treat poisoning-related disorders caused by A. adenophora. Furthermore, beneficial bacteria isolated from rumen microbes and A. adenophora can degrade major toxic compounds in A. adenophora so as to be developed into microbial feed additives to help ameliorate toxicity mediated by A. adenophora. This review presents an overview of the toxic mechanisms of A. adenophora, provides possible therapeutic strategies that are available to mitigate the toxicity of A. adenophora and introduces relevant information on identifying novel prophylactic and therapeutic measures against A. adenophora—induced toxicity.  相似文献   

3.
The transmission of T-2 toxin and its metabolites into the edible tissues of poultry has potential effects on human health. We report that T-2 toxin significantly induces CYP1A4 and CYP1A5 expression in chicken embryonic hepatocyte cells. The enzyme activity assays of CYP1A4 and CYP1A5 heterologously expressed in HeLa cells indicate that only CYP1A5 metabolizes T-2 to 3′OH-T-2 by the 3′-hydroxylation of isovaleryl groups. In vitro enzyme assays of recombinant CYP1A5 expressed in DH5α further confirm that CYP1A5 can convert T-2 into TC-1 (3′OH-T-2). Therefore, CYP1A5 is critical for the metabolism of trichothecene mycotoxin in chickens.  相似文献   

4.
Oils from a selection ofAmaranthus caudatus, A. hypochondriacus andA. cruentus were extracted with hexane. The crude oils were analyzed for acid value, saponification and iodine number, and were included in basal casein diets for rat studies at 5 and 10% levels to replace equal amounts of refined cottonseed oil. The oils fromA. cruentus andA. hypochondriacus were similar in the oil properties studied and different fromA. caudatus. At either 5 or 10% food intake levels, weight gain and PER were not statistically different from values reported for cottonseed oil. True digestibility of amaranth oil was lower than that of cottonseed oil.A. cruentus oil gave the lowest digestibility. Oil levels induced statistical differences in food intake and digestibility. Oils fromA. caudatus, A. hypochondriacus and cottonseed induced similar serum cholesterol levels, while oil fromA. cruentus gave statistically higher values. Hemoglobin, hematocrit and serum proteins were similar among all groups. Microscopic analysis of the organs of the rats revealed some changes that were also found in cottonseed oil-fed rats. It was concluded that crude amaranth oil has lower digestibility than cottonseed oil, but that it is not responsible for growth-depressing effects when the seed is fed raw as compared to processed materials.  相似文献   

5.
S100A9, a Ca2+-binding protein, is tightly associated to neutrophil pro-inflammatory functions when forming a heterodimer with its S100A8 partner. Upon secretion into the extracellular environment, these proteins behave like damage-associated molecular pattern molecules, which actively participate in the amplification of the inflammation process by recruitment and activation of pro-inflammatory cells. Intracellular functions have also been attributed to the S100A8/A9 complex, notably its ability to regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. However, the complete functional spectrum of S100A8/A9 at the intracellular level is far from being understood. In this context, we here investigated the possibility that the absence of intracellular S100A8/A9 is involved in cytokine secretion. To overcome the difficulty of genetically modifying neutrophils, we used murine neutrophils derived from wild-type and S100A9−/− Hoxb8 immortalized myeloid progenitors. After confirming that differentiated Hoxb8 neutrophil-like cells are a suitable model to study neutrophil functions, our data show that absence of S100A8/A9 led to a dysregulation of cytokine secretion after lipopolysaccharide (LPS) stimulation. Furthermore, we demonstrate that S100A8/A9-induced cytokine secretion was regulated by the nuclear factor kappa B (NF-κB) pathway. These results were confirmed in human differentiated HL-60 cells, in which S100A9 was inhibited by shRNAs. Finally, our results indicate that the degranulation process could be involved in the regulation of cytokine secretion by S100A8/A9.  相似文献   

6.
Binary and ternary nanocomposites based on poly(vinylidene fluoride) (PVDF), poly(methyl methacrylate) (PMMA), and PVDF/PMMA blends were successfully prepared through a melt-mixing process, using a commercial organoclay (15A) as the nanofiller. The 15A was more finely dispersed (intercalated/partially exfoliated) within the PVDF matrix compared with the PMMA matrix. A higher PVDF content in the ternary composite essentially led to a superior degree of 15A dispersion. The 15A addition induced the polar β-form PVDF crystals, whereas the presence of PMMA in ternary composites reduced the efficiency in promoting β-form formation by 15A. Adding 15A also enhanced the nucleation of PVDF, but the enhancement was inferior while PMMA was present. Conversely, the crystal growth of PVDF was retarded with the existence of 15A, and the PVDF/15A binary composite exhibited the greatest retardation. The equilibrium melting temperature (Tm°) of PVDF in the neat state and in the blends increased after 15A addition. The PVDF/15A binary composite possessed an evidently higher β-form Tm° than the α-form Tm° of neat PVDF (~20.1 °C rise). Similar effects on the individual components, 15A declined the thermal stability of PVDF but increased that of PMMA in the ternary composites. Rheological property measurements revealed that the ternary composites performed in-between that of individual PVDF/15A and PMMA/15A binary composites. A percolation of 15A (pseudo)network structure was developed in the composites, and a more elastic behavior was observed with increasing PVDF content in the composites.  相似文献   

7.
TMEM16A is a Ca2+-activated Cl channel that controls broad cellular processes ranging from mucus secretion to signal transduction and neuronal excitability. Recent studies have reported that membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an important cofactor that allosterically regulates TMEM16A channel activity. However, the detailed regulatory actions of PIP2 in splice variants of TMEM16A remain unclear. Here, we demonstrated that the attenuation of membrane phosphoinositide levels selectively inhibited the current amplitude of the TMEM16A(ac) isoform by decreasing the slow, but not instantaneous, Cl currents, which are independent of the membrane potential and specific to PI(4,5)P2 depletion. The attenuation of endogenous PI(4,5)P2 levels by the activation of Danio rerio voltage-sensitive phosphatase (Dr-VSP) decreased the Cl currents of TMEM16A(ac) but not the TMEM16A(a) isoform, which was abolished by the co-expression of PIP 5-kinase type-1γ (PIPKIγ). Using the rapamycin-inducible dimerization of exogenous phosphoinositide phosphatases, we further revealed that the stimulatory effects of phosphoinositide on TMEM16A(ac) channels were similar in various membrane potentials and specific to PI(4,5)P2, not PI4P and PI(3,4,5)P3. Finally, we also confirmed that PI(4,5)P2 resynthesis is essential for TMEM16A(ac) recovery from Dr-VSP-induced current inhibition. Our data demonstrate that membrane PI(4,5)P2 selectively modulates the gating of the TMEM16A(ac) channel in an agonistic manner, which leads to the upregulation of TMEM16A(ac) functions in physiological conditions.  相似文献   

8.
《Ceramics International》2016,42(3):3907-3915
Nanosized anatase TiO2 particles anchored on nanocarbon substrates have great potential for practical applications in high-performance lithium ion batteries and efficient photocatalysts. The synthesis of this material usually utilizes calcination to crystallize amorphous titania, which normally causes the formation of aggregates and some side effects. In this work, we demonstrated that sub-20 nm anatase particles uniformly anchored on graphene oxide and reduced graphene oxide nanosheets in aqueous solution at a temperature of 90 °C and atmospheric pressure, without further calcination. The photocatalytic oxidation activity and electrochemical properties of graphene oxide/anatase TiO2 (GO/A) and reduced graphene oxide/anatase TiO2 (RGO/A) were comparatively investigated. We found that GO/A showed higher photocatalytic oxidation activity than RGO/A under UV light irradiation. Graphene oxide accepted electrons and suffered reduction, which finally decreased GO/A’s photocatalytic oxidation activity to an extent similar to RGO/A. We also found that, as anode material for Li-ion battery, the specific capacity of RGO/A was nearly three times that of GO/A at the same current rate. This study will inspire better design of metal oxide/nanocarbon nanocomposites for high performance lithium ion battery and photocatalysis applications.  相似文献   

9.
Hypoxia in non-small cell lung cancer (NSCLC) affects cancer progression, metastasis and metabolism. We previously showed that FAM13A was induced by hypoxia in NSCLC but the biological function of this gene has not been fully elucidated. This study aimed to investigate the role of hypoxia-induced FAM13A in NSCLC progression and metastasis. Lentiviral shRNAs were used for FAM13A gene silencing in NSCLC cell lines (A549, CORL-105). MTS assay, cell tracking VPD540 dye, wound healing assay, invasion assay, BrdU assay and APC Annexin V staining assays were performed to examine cell proliferation ability, migration, invasion and apoptosis rate in NSCLC cells. The results of VPD540 dye and MTS assays showed a significant reduction in cell proliferation after FAM13A knockdown in A549 cells cultured under normal and hypoxia (1% O2) conditions (p < 0.05), while the effect of FAM13A downregulation on CORL-105 cells was observed after 96 h exposition to hypoxia. Moreover, FAM13A inhibition induced S phase cell cycle arrest in A549 cells under hypoxia conditions. Silencing of FAM13A significantly suppressed migration of A549 and CORL-105 cells in both oxygen conditions, especially after 72 and 96 h (p < 0.001 in normoxia, p < 0.01 after hypoxia). It was showed that FAM13A reduction resulted in disruption of the F-actin cytoskeleton altering A549 cell migration. Cell invasion rates were significantly decreased in A549 FAM13A depleted cells compared to controls (p < 0.05), mostly under hypoxia. FAM13A silencing had no effect on apoptosis induction in NSCLC cells. In the present study, we found that FAM13A silencing has a negative effect on proliferation, migration and invasion activity in NSCLC cells in normal and hypoxic conditions. Our data demonstrated that FAM13A depleted post-hypoxic cells have a decreased cell proliferation ability and metastatic potential, which indicates FAM13A as a potential therapeutic target in lung cancer.  相似文献   

10.
Queens and workers of five honeybee species (Apis mellifera A. cerana A. dorsata A. floreaand A. andreniformis) were analyzed for their mandibular gland components. In A. melliferathe queen mandibular pheromone consists of 9-hydroxy- and 9-keto-2(E)-decenoic acids. (9-HDA and ODA), methyl p-hydroxybenzoate (HOB), and 4-hydroxy-3-methoxyphenyl-ethanol (HVA), and is responsible for retinue attraction, among other functions. In retinue bioassays with workers of A. cerana (whose queens lack HVA), ODA, 9-HDA, and HOB were sufficient to elicit maximal retinue behavior. This suggests that the known queen mandibular pheromone components detected in mandibular glands of A. cerana queens constitute the functional queen mandibular pheromone in this species. Both castes of A. mellifera produce 10- and 8-carbon acids that are functionalized at the last position in the chain, and these are the predominant compounds found in worker mandibular glands. Workers of the other species also had these compounds, along with 9-HDA and ODA that are normally not present in A. mellifera worker glands. Queens and workers of each species had a unique combination of mandibular compounds. The aromatic compounds were characteristic of queens from the cavity-nesting speciesA. mellifera (HOB and HVA) and A. cerana (HOB). These two species also had more pronounced differences in the mandibular blends of queens and workers than the open-nesting speciesA. dorsata A. floreaand A. andreniformis. Our results indicate that the more derived cavity-nesting species of Apis have evolved greater caste-specific differences between queens and workers and a higher number of queen pheromone components, compared to the open-nesting species.  相似文献   

11.
Endothelin-1 (ET-1) autocrine and paracrine signaling modulate cell proliferation of tumor cells by activating its receptors, endothelin A receptor (ETAR) and endothelin B receptor (ETBR). Dysregulation of ETAR activation promotes tumor development and progression. The potential of ETAR antagonists and the dual-ETAR and ETBR antagonists as therapeutic approaches are under preclinical and clinical studies. Salvianolic acid A (Sal A) is a hydrophilic polyphenolic derivative isolated from Salvia miltiorrhiza Bunge (Danshen), which has been reported as an anti-cancer and cardio-protective herbal medicine. In this study, we demonstrate that Sal A inhibits ETAR activation induced by ET-1 in both recombinant and endogenous ETAR expression cell lines. The IC50 values were determined as 5.7 µM in the HEK293/ETAR cell line and 3.14 µM in HeLa cells, respectively. Furthermore, our results showed that Sal A suppressed cell proliferation and extended the doubling times of multiple cancer cells, including HeLa, DU145, H1975, and A549 cell lines. In addition, Sal A inhibited proliferation of DU145 cell lines stimulated by exogenous ET-1 treatment. Moreover, the cytotoxicity and cardio-toxicity of Sal A were assessed in human umbilical vein endothelial cells (HUVEC) and Human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which proved that Sal A demonstrates no cytotoxicity or cardiotoxicity. Collectively, our findings indicate that Sal A is a novel anti-cancer candidate through targeting ETAR.  相似文献   

12.
13.
Six mutants of human epidermal growth factor (EGF), which carry single point substitutions within a surface patch proposed to juxtapose the bound receptor, were prepared and characterized for receptor affinity and mitogenicity. Receptor affinities relative to EGF are G12Q > H16D > Y13W > Q43A approximately = H16A approximately = EGF >> L15A. Notably, the reduced receptor affinity of mutant L15A indicates that Leu15 probably contributes substantially to receptor binding whereas unaltered receptor affinities observed for analogs H16A and Q43A indicate that neither His16 nor Gln43 contributes significantly to this interaction. On the other hand, the observed enhanced receptor affinities of analogs G12Q, Y13W and H16D highlight surface loci where additional productive receptor-binding contacts can be introduced. Interestingly, at acidic pH analog H16A reveals substantially greater receptor affinity than that of EGF, a property which may offer enhanced therapeutic utility in acidic environments in vivo.   相似文献   

14.
Olfactory receptors (ORs), which belong to the G-protein-coupled receptor family, have been widely studied as ectopically expressed receptors in various human tissues, including the skin. However, the physiological functions of only a few OR types have been elucidated in skin cells. All-trans retinoic acid (ATRA) is a well-known medication for various skin diseases. However, many studies have shown that ATRA can have adverse effects, resulting from the suppression of cell proliferation. Here, we investigated the involvement of OR7A17 in the ATRA-induced suppression of human keratinocyte (HaCaT) proliferation. We demonstrated that OR7A17 is expressed in HaCaT keratinocytes, and its expression was downregulated by ATRA. The ATRA-induced downregulation of OR7A17 was attenuated via RAR α or RAR γ antagonist treatment, indicating that the effects of ATRA on OR7A17 expression were mediated through nuclear retinoic acid receptor signaling. Moreover, we found that the overexpression of OR7A17 induced the proliferation of HaCaT cells while counteracting the antiproliferative effect of ATRA. Mechanistically, OR7A17 overexpression reversed the ATRA-induced attenuation of Ca2+ entry. Our findings indicated that ATRA suppresses cell proliferation through the downregulation of OR7A17 via RAR α- and γ-mediated retinoid signaling. Taken together, OR7A17 is a potential therapeutic target for ameliorating the anti-proliferative effects of ATRA.  相似文献   

15.
Iron doping 4A zeolite (Fe-4A) was prepared and demonstrated as ozone catalyst to enhance hydroxyl radical (HO·) pathway. Fe-4A composites with different iron load were characterized, and the catalytic effects were discussed dealing with para-chlorobenzoic acid (p-CBA), atrazine (ATZ), and oxalic acid (OA) as model compounds. Results showed that Fe-4A/ozone system promoted the production of HO·, which was in-line with the strength of Lewis acidity that might have accelerated ozone-to-HO· transformation. Modeled RCT value validated the enhanced HO· exposure during catalysis that was more evident for 4%-Fe-4A. The Fe-4A exhibited structural stability and allows repeated use after facile regeneration.  相似文献   

16.
Compatibility of graft copolymer compatibilized two incompatible homopolymer A and B blends was simulated by using Monte Carlo method in a two‐dimensional lattice model. The copolymers with various graft structures were introduced in order to study the effect of graft structure on the compatibility. Simulation results showed that incorporation of both A‐g‐B (A was backbone) and B‐g‐A (B was backbone) copolymers could much improve the compatibility of the blends. However, A‐g‐B copolymer was more effective to compatibilize the blend if homopolymer A formed dispersed phase. Furthermore, simulation results indicated that A‐g‐B copolymers tended to locate at the interface and anchor two immiscible components when the side chain is relatively long. However, most of A‐g‐B copolymers were likely to be dispersed into the dispersed homopolymer A phase domains if the side chains were relatively short. On the other hand, B‐g‐A copolymers tended to be dispersed into the matrix formed by homopolymer B. Moreover, it was found that more and more B‐g‐A copolymers were likely to form thin layers at the phase interface with decreasing the length of side chain. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007  相似文献   

17.
A PAN-4A composite ion exchanger containing about 80% 4A powder was prepared to remove strontium and cesium ions from acidic solution. The SEM image of the fracture of composite bead showed that zeolite 4A powder was dispersed homogenously and the pores were well formed. The mean pore size of composite bead was 0.14 μm and its porosity was about 74%, which is much higher in comparison with the existing inorganic adsorbent beads. The acid and radiation stability tests showed that PAN-4A was stable against acid solution higher than pH 2 and radiation dose less than 1.89×108 rad, respectively. Ion exchange tests showed that the PAN-4A was selective for Sr ion. The distribution coefficients of PAN-4A for Sr and Cs ions at pH 2 were 2×104 mL/g and 280 mL/g, respectively. The ion exchange capacities (qs) of PAN-4A for Sr and Cs ions at pH 2, which are modeled by Dubinin-Polanyi equation, were 3.92 meq/g and 2.47 meq/g, respectively.  相似文献   

18.
The small intestine is the initial site of glucose absorption and thus represents the first of a continuum of events that modulate normal systemic glucose homeostasis. A better understanding of the regulation of intestinal glucose transporters is therefore pertinent to our efforts in curbing metabolic disorders. Using molecular genetic approaches, we investigated the role of Drosophila Solute Carrier 5A5 (dSLC5A5) in regulating glucose homeostasis by mediating glucose uptake in the fly midgut. By genetically knocking down dSLC5A5 in flies, we found that systemic and circulating glucose and trehalose levels are significantly decreased, which correlates with an attenuation in glucose uptake in the enterocytes. Reciprocally, overexpression of dSLC5A5 significantly increases systemic and circulating glucose and trehalose levels and promotes glucose uptake in the enterocytes. We showed that dSLC5A5 undergoes apical endocytosis in a dynamin-dependent manner, which is essential for glucose uptake in the enterocytes. Furthermore, we showed that the dSLC5A5 level in the midgut is upregulated by glucose and that dSLC5A5 critically directs systemic glucose homeostasis on a high-sugar diet. Together, our studies have uncovered the first Drosophila glucose transporter in the midgut and revealed new mechanisms that regulate glucose transporter levels and activity in the enterocyte apical membrane.  相似文献   

19.
Ageratum conyzoides L. weed often invades cultivated fields and reduces crop productivity in Southeast Asia and South China. However, intercropping this weed in citrus orchards may increase the population of predatory mite Amblyseius newsami, an effective natural enemy of citrus red mite Panonychus citri, and keep the population of P. citri at low and noninjurious levels. This study showed that A. conyzoides produced and released volatile allelochemicals into the air in the intercropped citrus orchard, and these volatiles influenced the olfactory responses of A. newsami and P. citri. At test temperature (25°C), A. conyzoides fresh leaves, its essential oil, and major constituents, demethoxy-ageratochromene, β-caryophyllene, α-bisabolene, and E-β-farnesene, attracted A. newsami and slightly repelled P. citri. Field experiments demonstrated that spraying A. conyzoides essential oil emulsion in an A. conyzoides nonintercropped citrus orchard increased the population density of A. newsami from below 0.1 to over 0.3 individuals per leaf, reaching the same level as in an A. conyzoides intercropped citrus orchard. However, this effect could not be maintained beyond 48 hr because of the volatility of the essential oil. In contrast, in the A. conyzoides intercropped citrus orchard, A. conyzoides plants continuously produced and released volatile allelochemicals and maintained the A. newsami population for a long time. The results suggest that intercropping of A. conyzoides not only made the citrus orchard ecosystem more favorable for the predatory mite A. newsami, but also that the volatile allelochemicals released from A. conyzoides regulated the population of A. newsami and P. citri.  相似文献   

20.
Solid solutions of 12CaO·7Al2O3 (C12A7) and 12SrO·7Al2O3 (S12A7) crystals were synthesized under high pressure. X‐ray diffraction patterns revealed that the lattice constants of the synthesized samples depend linearly on the compositional ratio of C12A7 and S12A7. Electron‐probe X‐ray microanalyses show that the chemical compositions of the crystals are represented by xC12A7·(1?x)S12A7 (0<x<1). These results indicate that the variation in the lattice constants is originated from a difference in the ionic radii of Ca2+ and Sr2+ ions. From impedance measurements, it was found that S12A7 has the highest conductivity (~1 × 10?3 Scm?1 at 550°C) among the solid solutions in the C12A7–S12A7 system.  相似文献   

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