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Separate Pathways (separate + pathway)
Selected AbstractsPak1 and Pak2 are activated in recurrent respiratory papillomas, contributing to one pathway of Rac1-mediated COX-2 expressionINTERNATIONAL JOURNAL OF CANCER, Issue 9 2010Rong Wu Abstract Recurrent respiratory papillomas are premalignant tumors of the airway caused by human papillomaviruses (HPVs), primarily Types 6 and 11. We had reported that respiratory papillomas overexpress the epidermal growth factor receptor (EGFR), the small GTPase Rac1 and cyclooxygenase-2 (COX-2), and have enhanced nuclear factor-,B (NF,B) activation with decreased levels of I,B-, but not I,B-,. We also showed that EGFR-activated Rac1 mediates expression of COX-2 through activation of p38 mitogen-activated protein kinase. We have now asked whether the p21-activated kinases Pak1 or Pak2 mediate activation of p38 by Rac1 in papilloma cells. Pak1 and Pak2 were constitutively activated in vivo in papilloma tissue compared with normal epithelium, and Rac1 siRNA reduced the level of both phospho-Pak1 and phospho-Pak2 in cultured papilloma cells. Reduction in Pak1 and Pak2 with siRNA decreased the COX-2 expression in papilloma cells, increased the levels of I,B-, and reduced the nuclear localization of NF-,B, but had no effect on p38 phosphorylation. Our studies suggest that Rac1 , Pak1/Pak2 , NF,B is a separate pathway that contributes to the expression of COX-2 in HPV-induced papillomas, independently of the previously described Rac1 , p38 , COX-2 pathway. [source] The VERNALIZATION INDEPENDENCE 4 gene encodes a novel regulator of FLOWERING LOCUS CTHE PLANT JOURNAL, Issue 5 2002Hua Zhang Summary The late-flowering, vernalization-responsive habit of many Arabidopsis ecotypes is mediated predominantly through repression of the floral programme by the FLOWERING LOCUS C (FLC) gene. To better understand this repressive mechanism, we have taken a genetic approach to identify novel genes that positively regulate FLC expression. We identified recessive mutations in a gene designated VERNALIZATION INDEPENDENCE 4 (VIP4), that confer early flowering and loss of FLC expression in the absence of cold. We cloned the VIP4 gene and found that it encodes a highly hydrophilic protein with similarity to proteins from yeasts, Drosophila, and Caenorhabditis elegans. Consistent with a proposed role as a direct activator of FLC, VIP4 is expressed throughout the plant in a pattern similar to that of FLC. However, unlike FLC, VIP4 RNA expression is not down-regulated in vernalized plants, suggesting that VIP4 is probably not sufficient to activate FLC, and that VIP4 is probably not directly involved in a vernalization mechanism. Epistasis analysis suggests that VIP4 could act in a separate pathway from previously identified FLC regulators, including FRIGIDA and the autonomous flowering promotion pathway gene LUMINIDEPENDENS. Mutants lacking detectable VIP4 expression flower earlier than FLC null mutants, suggesting that VIP4 regulates flowering-time genes in addition to FLC. Floral morphology is also disrupted in vip4 mutants; thus, VIP4 has multiple roles in development. [source] Symbolically speaking: a connectionist model of sentence productionCOGNITIVE SCIENCE - A MULTIDISCIPLINARY JOURNAL, Issue 5 2002Franklin Chang Abstract The ability to combine words into novel sentences has been used to argue that humans have symbolic language production abilities. Critiques of connectionist models of language often center on the inability of these models to generalize symbolically (Fodor & Pylyshyn, 1988; Marcus, 1998). To address these issues, a connectionist model of sentence production was developed. The model had variables (role-concept bindings) that were inspired by spatial representations (Landau & Jackendoff, 1993). In order to take advantage of these variables, a novel dual-pathway architecture with event semantics is proposed and shown to be better at symbolic generalization than several variants. This architecture has one pathway for mapping message content to words and a separate pathway that enforces sequencing constraints. Analysis of the model's hidden units demonstrated that the model learned different types of information in each pathway, and that the model's compositional behavior arose from the combination of these two pathways. The model's ability to balance symbolic and statistical behavior in syntax acquisition and to model aphasic double dissociations provided independent support for the dual-pathway architecture. [source] Genetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retinaDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2008Ann C. Morris Abstract Development of therapies to treat visual system dystrophies resulting from the degeneration of rod and cone photoreceptors may directly benefit from studies of animal models, such as the zebrafish, that display continuous retinal neurogenesis and the capacity for injury-induced regeneration. Previous studies of retinal regeneration in fish have been conducted on adult animals and have relied on methods that cause acute damage to both rods and cones, as well as other retinal cell types. We report here the use of a genetic approach to study progenitor cell responses to photoreceptor degeneration in the larval and adult zebrafish retina. We have compared the responses to selective rod or cone degeneration using, respectively, the XOPS-mCFP transgenic line and zebrafish with a null mutation in the pde6c gene. Notably, rod degeneration induces increased proliferation of progenitors in the outer nuclear layer (ONL) and is not associated with proliferation or reactive gliosis in the inner nuclear layer (INL). Molecular characterization of the rod progenitor cells demonstrated that they are committed to the rod photoreceptor fate while they are still mitotic. In contrast, cone degeneration induces both Müller cell proliferation and reactive gliosis, with little change in proliferation in the ONL. We found that in both lines, proliferative responses to photoreceptor degeneration can be observed as 7 days post fertilization (dpf). These two genetic models therefore offer new opportunities for investigating the molecular mechanisms of selective degeneration and regeneration of rods and cones. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008. [source] Degradation of nonylphenol ethoxylates in estuarine sediment under aerobic and anaerobic conditionsENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2003P. Lee Ferguson Abstract Nonylphenol ethoxylate (NPEO) surfactants and their metabolites are ubiquitous contaminants of the aquatic environment. Despite considerable interest in the environmental fate of these compounds due to concerns over toxicity and estrogenic activity, the pathways of NPEO degradation in sediments have not previously been reported, in spite of the fact that sediment appears to be an important sink for these compounds in the environment. In the present work, we have examined the rates and pathways of NPEO degradation in batch sediment slurry experiments using radiolabeled NPEO mixtures. Results suggest that NPEOs are more persistent in sediments under anaerobic conditions than in the presence of oxygen. In addition, it was illustrated that NPEO degradation proceeds via separate pathways in oxic and anoxic sediment. Discernible metabolites were identified and an overall mass balance for NPEO degradation in oxic and anoxic sediment was achieved. In contrast with previous studies, no evidence was observed for net production of nonylphenol from NPEOs during aerobic or anaerobic degradation. The observed relative rates at which NPEO ethoxymers disappeared in the sediment slurry experiments were consistent with previous reports for these compounds in sediment and other environmental media, although the absolute rates measured were somewhat faster than those reported for field sediments. [source] Chemosensory and steroid-responsive regions of the medial amygdala regulate distinct aspects of opposite-sex odor preference in male Syrian hamstersEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Pamela M. Maras Abstract In rodent species, such as the Syrian hamster, the expression of sexual preference requires neural integration of social chemosensory signals and steroid hormone cues. Although anatomical data suggest that separate pathways within the nervous system process these two signals, the functional significance of this separation is not well understood. Specifically, within the medial amygdala, the anterior region (MEa) receives input from the olfactory bulbs and other chemosensory areas, whereas the posterodorsal region (MEpd) contains a dense population of steroid receptors and receives less substantial chemosensory input. Consequently, the MEa may subserve a primarily discriminative function, whereas the MEpd may mediate the permissive effects of sex steroids on sexual preference. To test these hypotheses, we measured preference and attraction to female and male odors in males with lesions of either the MEa or MEpd. In Experiment 1, lesions of either region eliminated opposite-sex odor preferences. Importantly, MEpd-lesioned males displayed decreased attraction toward female odors, suggesting decreased sexual motivation. In contrast, MEa-lesioned males displayed high levels of investigation of both male and female odors, suggesting an inability to categorize the relevance of the odor stimuli. In Experiment 2, we verified that both MEa- and MEpd-lesioned males could discriminate between female and male odors, thereby eliminating the possibility that the observed lack of preference reflected a sensory deficit. Taken together, these results suggest that both the MEa and MEpd are critical for the expression of opposite-sex odor preference, although they appear to mediate distinct aspects of this behavior. [source] LPL polymorphism predicts stroke risk in menGENETIC EPIDEMIOLOGY, Issue 3 2002Alanna C. Morrison Abstract Variation in lipid levels has been associated with atherosclerotic vascular disease, including stroke. Genes contributing to interindividual variation in lipid levels may play a role in the etiology of stroke, either through their effects on lipid synthesis and metabolism or through separate pathways. For this reason, we sought to examine the association between polymorphisms in the lipoprotein lipase (LPL) and apolipoprotein E (APOE) genes and subclinical and clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study. Subclinical stroke was determined by cerebral magnetic resonance imaging (MRI). Subclinical cerebral infarct cases (n = 197) were compared to a stratified random sample identified from individuals participating in the MRI examination (n = 200). Incidence of clinical ischemic stroke was determined by following the ARIC cohort for an average of 7.5 years for potential cerebrovascular events; 218 validated clinical ischemic strokes were identified. A stratified random sample of the ARIC cohort (CRS, n = 964) was used as the comparison group for clinical cases. The LPL S291-carrying genotypes and APOE ,2- and ,4-carrying genotypes were not significantly associated with subclinical or clinical stroke. The LPL X447-containing genotypes were significantly associated with subclinical (odds ratio [OR], 4.32; 95% confidence interval [CI], 1.23,15.15; P = 0.020) and clinical stroke (hazard rate ratio [HRR], 2.57; 95% CI, 1.24,5.34; P = 0.01) in men, both by themselves and after adjustment for multiple stroke risk factors. The LPL S447X polymorphism is significantly associated with subclinical cerebral infarction and incident clinical ischemic stroke in men from a middle-aged American population. This association does not appear to be mediated by triglyceride, high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels, or additional stroke risk factors. Genet. Epidemiol. 22:233,242, 2002. © 2002 Wiley-Liss, Inc. [source] Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in StreptomycesMOLECULAR MICROBIOLOGY, Issue 4 2005Neil R. Williamson Summary The biosynthetic pathway of the red-pigmented antibiotic, prodigiosin, produced by Serratia sp. is known to involve separate pathways for the production of the monopyrrole, 2-methyl-3-n-amyl-pyrrole (MAP) and the bipyrrole, 4-methoxy-2,2,-bipyrrole-5-carbaldehyde (MBC) which are then coupled in the final condensation step. We have previously reported the cloning, sequencing and heterologous expression of the pig cluster responsible for prodigiosin biosynthesis in two Serratia sp. In this article we report the creation of in-frame deletions or insertions in every biosynthetic gene in the cluster from Serratia sp. ATCC 39006. The biosynthetic intermediates accumulating in each mutant have been analysed by LC-MS, cross-feeding and genetic complementation studies. Based on these results we assign specific roles in the biosynthesis of MBC to the following Pig proteins: PigI, PigG, PigA, PigJ, PigH, PigM, PigF and PigN. We report a novel pathway for the biosynthesis of MAP, involving PigD, PigE and PigB. We also report a new chemical synthesis of MAP and one of its precursors, 3-acetyloctanal. Finally, we identify the condensing enzyme as PigC. We reassess the existing literature and discuss the significance of the results for the biosynthesis of undecylprodigiosin by the Red cluster in Streptomyces coelicolor A3(2). [source] Expression analysis of genes induced in barley after chemical activation reveals distinct disease resistance pathwaysMOLECULAR PLANT PATHOLOGY, Issue 5 2000Katrin Beßer Salicylic acid (SA) and its synthetic mimics 2,6-dichloroisonicotinic acid (DCINA) and benzo(1,2,3)thiadiazole-7-carbothioic acid S-methyl ester (BTH), protect barley systemically against powdery mildew (Blumeria graminis f.sp. hordei, Bgh) infection by strengthening plant defence mechanisms that result in effective papillae and host cell death. Here, we describe the differential expression of a number of newly identified barley chemically induced (BCI) genes encoding a lipoxygenase (BCI-1), a thionin (BCI-2), an acid phosphatase (BCI-3), a Ca2+ -binding EF-hand protein (BCI-4), a serine proteinase inhibitor (BCI-7), a fatty acid desaturase (BCI-8) and several further proteins with as yet unknown function. Compared with SA, the chemicals DCINA and BTH were more potent inducers of both gene expression and resistance. Homologues of four BCI genes were detected in wheat and were also differentially regulated upon chemical activation of disease resistance. Except for BCI-4 and BCI-5 (unknown function), the genes were also induced by exogenous application of jasmonates, whereas treatments that raise endogenous jasmonates as well as wounding were less effective. The fact that BCI genes were not expressed during incompatible barley,Bgh interactions governed by gene-for-gene relationships suggests the presence of separate pathways leading to powdery mildew resistance. [source] Photoinhibition and loss of photosystem II reaction centre proteins during senescence of soybean leaves.PHYSIOLOGIA PLANTARUM, Issue 3 2002Enhancement of photoinhibition by the, stay-green' mutation cytG The ,stay-green' mutation cytG in soybean (Glycine max) partially inhibits the degradation of the light-harvesting complex II (LHCII) and the associated chlorophyll during monocarpic senescence. cytG did not alter the breakdown of the cytochrome b6/f complex, thylakoid ATP synthase or components of Photosystem I. In contrast, cytG accelerated the loss of oxygen evolution activity and PSII reaction-centre proteins. These data suggest that LHCII and other thylakoid components are degraded by separate pathways. In leaves induced to senesce by darkness, cytG inhibited the breakdown of LHCII and chlorophyll, but it did not enhance the loss of PSII-core components, indicating that the accelerated degradation of PSII reaction centre proteins in cytG was light dependent. Illumination of mature and senescent leaves of wild-type soybean in the presence of an inhibitor (lincomycin) of chloroplast protein synthesis revealed that senescence per se did not affect the rate of photoinhibition in leaves. Likewise, mature leaves of the cytG mutant did not show more photoinhibition than wild-type leaves. However, in senescent cytG leaves, photoinhibition proceeded more rapidly than in the wild-type. We conclude that the cytG mutation enhances photoinhibition in senescing leaves, and photoinhibition causes the rapid loss of PSII reaction-centre proteins during senescence in cytG. [source] | ||||||||||||||||||||||