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排序方式: 共有485条查询结果,搜索用时 15 毫秒
111.
Elena G. Govorunova Mustapha Moussaif Andrey Kullyev Ken C. Q. Nguyen Thomas V. McDonald David H. Hall Ji Y. Sze 《PloS one》2010,5(4)
The C. elegans eat-6 gene encodes a Na+, K+-ATPase α subunit and is a homolog of the familial hemiplegic migraine candidate gene FHM2. Migraine is the most common neurological disorder linked to serotonergic dysfunction. We sought to study the pathophysiological mechanisms of migraine and their relation to serotonin (5-HT) signaling using C. elegans as a genetic model. In C. elegans, exogenous 5-HT inhibits paralysis induced by the acetylcholinesterase inhibitor aldicarb. We found that the eat-6(ad467) mutation or RNAi of eat-6 increases aldicarb sensitivity and causes complete resistance to 5-HT treatment, indicating that EAT-6 is a component of the pathway that couples 5-HT signaling and ACh neurotransmission. While a postsynaptic role of EAT-6 at the bodywall NMJs has been well established, we found that EAT-6 may in addition regulate presynaptic ACh neurotransmission. We show that eat-6 is expressed in ventral cord ACh motor neurons, and that cell-specific RNAi of eat-6 in the ACh neurons leads to hypersensitivity to aldicarb. Electron microscopy showed an increased number of synaptic vesicles in the ACh neurons in the eat-6(ad467) mutant. Genetic analyses suggest that EAT-6 interacts with EGL-30 Gαq, EGL-8 phospholipase C and SLO-1 BK channel signaling to modulate ACh neurotransmission and that either reduced or excessive EAT-6 function may lead to increased ACh neurotransmission. Study of the interaction between eat-6 and 5-HT receptors revealed both stimulatory and inhibitory 5-HT inputs to the NMJs. We show that the inhibitory and stimulatory 5-HT signals arise from distinct 5-HT neurons. The role of eat-6 in modulation of excitatory neurotransmission by 5-HT may provide a genetic explanation for the therapeutic effects of the drugs targeting 5-HT receptors in the treatment of migraine patients. 相似文献
112.
The permeability of inside-out and right-side-out vesicles from erythrocyte membranes to inorganic cations was determined quantitatively. Using 86Rb as a K analog, we have measured the rate constant of 86Rb efflux from vesicles under equilibrium exchange conditions, using a dialysis procedure. The permeability coefficients of the vesicles to Rb are only about an order of magnitude greater than that of whole erythrocytes. Furthermore, we have measured many of the specialized transport systems known to exist in erythrocytes and have shown that glucose, sulfate, ATP-dependent Ca and ATP-dependent Na transport activities are retained by the vesicle membranes. These results suggest that inside-out and right-side-out vesicles can be used effectively to study transport properties of erythrocyte membranes. 相似文献
113.
Identifying clusters of functionally related genes in genomes 总被引:4,自引:0,他引:4
MOTIVATION: An increasing body of literature shows that genomes of eukaryotes can contain clusters of functionally related genes. Most approaches to identify gene clusters utilize microarray data or metabolic pathway databases to find groups of genes on chromosomes that are linked by common attributes. A generalized method that can find gene clusters regardless of the mechanism of origin would provide researchers with an unbiased method for finding clusters and studying the evolutionary forces that give rise to them. RESULTS: We present an algorithm to identify gene clusters in eukaryotic genomes that utilizes functional categories defined in graph-based vocabularies such as the Gene Ontology (GO). Clusters identified in this manner need only have a common function and are not constrained by gene expression or other properties. We tested the algorithm by analyzing genomes of a representative set of species. We identified species-specific variation in percentage of clustered genes as well as in properties of gene clusters including size distribution and functional annotation. These properties may be diagnostic of the evolutionary forces that lead to the formation of gene clusters. AVAILABILITY: A software implementation of the algorithm and example output files are available at http://fcg.tamu.edu/C_Hunter/. 相似文献
114.
Min L Isa SA Fam WN Sze SK Beretta O Mortellaro A Ruedl C 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(4):1789-1798
A simultaneous engagement of different pathogen recognition receptors provides a tailor-made adaptive immunity for an efficient defense against distinct pathogens. For example, cross-talk of TLR and C-type lectin signaling effectively shapes distinct gene expression patterns by integrating the signals at the level of NF-κB. In this study, we extend this principle to a strong synergism between the dectin-1 agonist curdlan and an inflammatory growth factor, GM-CSF. Both together act in synergy in inducing a strong inflammatory signature that converts immature dendritic cells (DCs) to potent effector DCs. A variety of cytokines (IL-1β, IL-6, TNF-α, IL-2, and IL-12p70), costimulatory molecules (CD80, CD86, CD40, and CD70), chemokines (CXCL1, CXCL2, CXCL3, CCL12, CCL17), as well as receptors and molecules involved in fugal recognition and immunity such as Mincle, dectin-1, dectin-2, and pentraxin 3 are strongly upregulated in DC treated simultaneously with curdlan and GM-CSF. The synergistic effect of both stimuli resulted in strong IκBα phosphorylation, its rapid degradation, and enhanced nuclear translocation of all NF-κB subunits. We further identified MAPK ERK as one possible integration site of both signals, because its phosphorylation was clearly augmented when curdlan was coapplied with GM-CSF. Our data demonstrate that the immunomodulatory activity of curdlan requires an additional signal provided by GM-CSF to successfully initiate a robust β-glucan-specific cytokine and chemokine response. The integration of both signals clearly prime and tailor a more effective innate and adaptive response against invading microbes and fungi. 相似文献
115.
Ramachandran U Manavalan A Sundaramurthi H Sze SK Feng ZW Hu JM Heese K 《Neurochemistry international》2012,60(8):827-836
Tianma (Rhizoma gastrodiae) is the dried rhizome of the plant Gastrodia elata Blume (Orchidaceae family). As a medicinal herb in traditional Chinese medicine (TCM) its functions are to control convulsions, pain, headache, dizziness, vertigo, seizure, epilepsy and others. In addition, tianma is frequently used for the treatment of neurodegenerative disorders though the mechanism of action is widely unknown. Accordingly, this study was designed to examine the effects of tianma on the proteome metabolism in differentiated human neuronal SH-SY5Y cells to explore its specific effects on neuronal signaling pathways. Using an iTRAQ (isobaric tags for relative and absolute quantitation)-based proteomics research approach, we identified 2390 modulated proteins, out of which 406 were found to be altered by tianma in differentiated human neuronal SH-SY5Y cells. Based on the observed data, we hypothesize that tianma promotes neuro-regenerative signaling cascades by controlling chaperone/proteasomal degradation pathways (e.g. CALR, FKBP3/4, HSP70/90) and mobilizing neuro-protective genes (such as AIP5) as well as modulating other proteins (RTN1/4, NCAM, PACSIN2, and PDLIM1/5) with various regenerative modalities and capacities related to neuro-synaptic plasticity. 相似文献
116.
Water as an Essential Resource: Orb Web Spiders Cannot Balance Their Water Budget by Prey Alone 总被引:1,自引:0,他引:1
André Walter Natasha Cadenhead Valerie Sze Weii Lee Charlie Dove Emma Milley Mark A. Elgar 《Ethology : formerly Zeitschrift fur Tierpsychologie》2012,118(6):534-542
Water is essential for all living organisms because it acts as a major solvent and reaction medium. Terrestrial animals may lose water through evaporation and excretion and consequently have evolved strategies to balance their water budget by either minimising losses or by gaining water. The major pathway to gain water is via food intake, although many animals additionally drink free water. Spiders acquire substantial amounts of water by ingesting enzymatically liquefied prey. However, this may not account for the water needs of some species. We tested whether drinking is essential for orb web spiders of the genus Argiope by experimentally manipulating the diet (flies or crickets) and water supply (no water or a daily shower) to females and then measuring their subsequent drinking behaviour. Individuals of Argiope trifasciata, which are typically found in dry habitats, increased their body mass when fed crickets but not when fed flies. However, spiders deprived of water subsequently ingested significantly more water than spiders that received water every day, regardless of their feeding regime. This pattern was replicated in Argiope aetherea, which is found in the tropics and perhaps less likely to be water deprived in natural populations. Our results reveal that drinking allows these spiders to realise their water balance independent from the nutritional status. We suggest that the spiders may need to drink fresh water to process ingested nutrients. 相似文献
117.
Lokireddy S Wijesoma IW Bonala S Wei M Sze SK McFarlane C Kambadur R Sharma M 《The Biochemical journal》2012,446(1):23-36
Humoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNFα (tumour necrosis factor α) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of information regarding the tumoral factors that contribute to the atrophy of muscle during cancer cachexia. Therefore, in the present study, we have characterized the secretome of C26 colon cancer cells to identify the tumoral factors involved in cancer-induced skeletal muscle wasting. In the present study, we show that myostatin, a procachectic TGFβ (transforming growth factor β) superfamily member, is abundantly secreted by C26 cells. Consistent with myostatin signalling during cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium) resulted in myotubular atrophy due to the up-regulation of muscle-specific E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced activity of the ubiquitin-proteasome pathway. Furthermore, the C26 CM also activated ActRIIB (activin receptor type?II B)/Smad and NF-κB (nuclear factor κB) signalling, and reduced the activity of the IGF-I (insulin-like growth factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular features of myostatin action in skeletal muscles. Antagonists to myostatin prevented C26 CM-induced wasting in muscle cell cultures, further confirming that tumoral myostatin may be a key contributor in the pathogenesis of cancer cachexia. Finally, we show that treatment with C26 CM induced the autophagy-lysosome pathway and reduced the number of mitochondria in myotubes. These two previously unreported observations were recapitulated in skeletal muscles collected from C26 tumour-bearing mice. 相似文献
118.
Ratnam Wickneswari M. A. R. Bhuiyan Sabu Kalluvettankuzhy K. Li Sze Lim Michael J. Thomson Md. Kairudin Narimah Md. Zain Abdullah 《Plant Molecular Biology Reporter》2012,30(4):929-939
A backcross breeding strategy was used to identify quantitative trait loci (QTLs) associated with 14 traits in a BC2F2 population derived from a cross between MR219, an indica rice cultivar and an accession of Oryza rufipogon (IRGC 105491). A total of 261 lines were genotyped with 96 microsatellite markers and evaluated for plant morphology, yield components and growth period. The genetic linkage map generated for this population with an average interval size of 16.2?cM, spanning 1,553.4?cM (Kosambi) of the rice genome. Thirty-eight QTLs were identified with composite interval mapping (CIM), whereas simple interval mapping (SIM) resulted in 47 QTLs (LOD >3.0). The O. rufipogon allele was favourable for 59% of QTLs detected through CIM. Of 261 BC2F2 families, 26 advanced backcross breeding lines (BC2F5) were used for QTL validation. These lines were selected on the basis of the yield traits potentiality in BC2F3 and BC2F4 generations. The field trial was conducted at three different locations in Malaysia using randomized complete block design with three replications. Trait based marker analysis was done for QTL determination. Twenty-five QTLs were detected in BC2F5 generation whereas 29 QTLs were detected in BC2F2 generation of the same population. Two QTLs (qPL-1 and qSPL-7) were not considered for validation due to their low R 2 values and two QTLs (qPSS-3-2 and qGW-3-2) were not detected in the BC2F5 population. Fifteen QTLs showed the beneficial effect to enhance the trait value of the breeding lines. QTL validation aided to select the promising lines for further utilization. 相似文献
119.
Curcumin, an active constituent of turmeric, has been shown to possess inhibitory effect of cell proliferation and induction of apoptosis towards a board range of tumors. Cell inhibition activities of curcumin are behaved differently in various cell types. To investigate the mechanism basis for the cell inhibition of curcumin on breast cancer cell lines, we examine curcumin effect on NFκB, cell cycle regulatory proteins and matrix metalloproteinases (MMPs) in two breast cancer cell lines (MDA-MB-231 and BT-483). Cell proliferation was performed by water soluble tetrazolium WST-1 assay. The effect of curcumin's on the activity of matrix metalloproteinase-1, 3, 9 were analyzed by RT-PCR. Cell cycle regulatory protein including cyclin D1, CDK4 and p21 were examined by immunochemistry. The expressions of NFκB in breast cancer cells treated with curcumin were studied by immunochemistry and western blot. The results from WST-1 cell proliferation assay showed that curcumin exhibited the anti-proliferation effect on MDA-MB-231 and BT-483 cells in a time- and dose-dependent manner. In response to the treatment, while, the expression of cyclin D1 had declined in MDA-MB-231 and the expression of CDK4 in BT-483 had declined. MMP1 mRNA expression in BT-483 and MDA-MB-231 had significantly decreased in curcumin treatment group compared with control group. Our finding extrapolates the antitumor activity of curcumin in mediating the breast cancer cell proliferative rate and invasion by down-regulating the NFκB inducing genes. 相似文献
120.
Kim Hung Lam Roberto Gambari Marcus Chun Wah Yuen Chi Wai Kan Penni Chan Lijin Xu Weijun Tang Chung Hin Chui Gregory Yin Ming Cheng Raymond Siu Ming Wong Fung Yi Lau Cindy Sze Wai Tong Andrew Kit Wah Chan Paul Bo San Lai Stanton Hon Lung Kok Chor Hing Cheng Albert Sun Chi Chan Johnny Cheuk On Tang 《Bioorganic & medicinal chemistry letters》2009,19(8):2266-2269
A series of 2,6-dimethoxylpyridinyl phosphine oxides have been synthesized and examined for their antitumor activity. 2,6-Dimethoxy-3-phenyl-4-diphenylphosphinoylpyridine 2 has been employed as the lead compound for this study. We found out that the presence of phosphine oxide on the 2,6-dimethoxylpyridine ring is important for the antitumor activity; the presence of bromine on this core leads to a further enhancement of its antitumor activity. This is the first reported work on the antitumor activity of the 2,6-dimethoxy-3,5-dibromopyridinyl phosphine oxide 5b towards MDAMB-231 breast cancer and SKHep-1 hepatoma cell lines. 相似文献