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101.
102.
103.
Two transactivation mechanisms cooperate for the bulk of HIF-1-responsive gene expression 总被引:6,自引:0,他引:6
Kasper LH Boussouar F Boyd K Xu W Biesen M Rehg J Baudino TA Cleveland JL Brindle PK 《The EMBO journal》2005,24(22):3846-3858
104.
Fish track wastewater pollution to estuaries 总被引:1,自引:0,他引:1
Excess nitrogen is a forceful agent of ecological change in coastal waters, and wastewater is a prominent source of nitrogen.
In catchments where multiple sources of nitrogen pollution co-exist, biological indicators are needed to gauge the degree
to which wastewater-N can propagate through the receiving food webs. The purpose of this study was to test whether estuarine
fish are suitable as indicators of sewage-N pollution. Fish were analysed from three estuaries within a 100-km strip on the
Australian East Coast. The estuaries differ substantially in wastewater loading: (1) the Maroochy Estuary receives a large
fraction of the local shire’s treated sewage, (2) the Mooloolah Estuary has no licensed treated wastewater outfalls but marinas/harbours
and stormwater may contribute nitrogen, and (3) the Noosa Estuary which neither receives licensed discharges nor has suspected
wastewater loads. Sampling for fish included both high rainfall (‘wet’ season) and low rainfall (‘dry’ season) periods. Muscle-δ15N was the variable predicted to respond to treated wastewater loading, reflecting the relative enrichment in 15N resulting from the treatment process and distinguishing it from alternative N sources such as fertiliser and natural nitrogen
inputs (both 15N-depleted). Of the 19 fish species occurring in all three estuaries, those from the Maroochy Estuary had significantly elevated
δ15N values (up to 9.9‰), and inter-estuarine differences in fish-δ15N were consistent across seasons. Furthermore, not only did all fish from the estuary receiving treated wastewater carry a
very distinctive sewage-N tissue signal, but enriched muscle-δ15N was also evident in all species sampled from the one estuary in which sewage contamination was previously only suspected (i.e. the Mooloolah Estuary: 0.2–4.8‰ enrichment over fish from reference system). Thus, fish-δ15N is a suitable indicator of wastewater-N not only in systems that receive large loads, but also for the detection of more
subtle nitrogen inputs. Arguably, fish may be preferred indicators of sewage-N contamination because they: (1) integrate nitrogen
inputs over long time periods, (2) have an element of ‘ecological relevance’ because fish muscle-δ15N reflect movement of sewage-N through the food chain, and (3) pollution assessments can usually be based on evidence from
multiple species. 相似文献
105.
106.
The competition between protein folding and aggregation: off-lattice minimalist model studies 总被引:2,自引:0,他引:2
Protein aggregation has been associated with a number of human diseases, and is a serious problem in the manufacture of recombinant proteins. Of particular interest to the biotechnology industry is deleterious aggregation that occurs during the refolding of proteins from inclusion bodies. As a complement to experimental efforts, computer simulations of multi-chain systems have emerged as a powerful tool to investigate the competition between folding and aggregation. Here we report results from Langevin dynamics simulations of minimalist model proteins. Order parameters are developed to follow both folding and aggregation. By mapping natural units to real units, the simulations are shown to be carried out under experimentally relevant conditions. Data pertaining to the contacts formed during the association process show that multiple mechanisms for aggregation exist, but certain pathways are statistically preferred. Kinetic data show that there are multiple time scales for aggregation, although most association events take place at times much shorter than those required for folding. Last, we discuss results presented here as a basis for future work aimed at rational design of mutations to reduce aggregation propensity, as well as for development of small-molecular weight refolding enhancers. 相似文献
107.
Ghannam G Takeda A Camarata T Moore MA Viale A Yaseen NR 《The Journal of biological chemistry》2004,279(2):866-875
108.
Reema Zeineldin Menake E Piyasena Troy S Bergstedt Larry A Sklar David Whitten Gabriel P Lopez 《Cytometry. Part A》2006,69(5):335-341
BACKGROUND: Fluorescent conjugated polymers display high fluorescence quantum yields and enhanced sensitivity to quenching (superquenching) by oppositely charged quenchers through energy or electron transfer. Fluorescent polymers and their quenchers are used in bead-based biosensor applications where the polymers are coated on particles. In this work, we investigate a detection method that utilizes superquenching on microspheres, which can be used for flow cytometric assays. METHODS: Microspheres were coated with the fluorescent cationic polyelectrolyte poly(p-phenylene-ethynylene) (PPE), and its superquenching by 9,10-anthraquinone-2,6-disulfonic acid (AQS) was examined by fluorometric methods in presence and in absence of a barrier to superquenching in the form of an anionic lipid bilayer. RESULTS: Flow cytometry detected superquenching of PPE on microspheres (MS-PPE) by AQS where high levels of reduction in fluorescence were observed. Adding different concentrations of AQS to MS-PPE yielded a Stern-Volmer quenching constant of 0.8x10(6) M-1. While forming an anionic lipid bilayer around the MS-PPE acted as a barrier to superquenching by AQS, disrupting the lipid bilayer allowed superquenching to take place. CONCLUSIONS: The sensitivity of flow cytometry in detecting fluorescence of microspheres and the amplified quenching sensitivity of fluorescent conjugated polymers both offer advantages over other fluorometric methods and conventional quenching detection. This study used superquenching of fluorescent polymers as a new tool in flow cytometry, thus combining the advantages offered by both method and detector. In addition, we employed the formation and the disruption of a supported lipid bilayer in mediating superquenching to offer new biosensing applications. 相似文献
109.
Zhang LM St Croix C Cao R Wasserloos K Watkins SC Stevens T Li S Tyurin V Kagan VE Pitt BR 《Experimental biology and medicine (Maywood, N.J.)》2006,231(9):1507-1515
S-nitrosation of the metal binding protein, metallothionein (MT) appears to be a critical link in affecting endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO)-induced changes in cytoplasmic and nuclear labile zinc, respectively. Although low molecular weight S-nitrosothiols also appear to affect this signaling system, less is known about the ability of extracellular protein nitrosothiols to transnitrosate MT. Accordingly, we synthesized fluorescently labeled S-nitroso-albumin (SNO-albumin, a major protein S-nitrosothiol in plasma) and determined, via confocal microscopy in fixed tissue, that it is transported into cultured rat pulmonary vascular endothelial cells in a temperature sensitive fashion. The cells were transfected with an expression vector that encodes human MT-IIa cDNA sandwiched between enhanced cyan (donor) and yellow (acceptor) fluorescent proteins (FRET-MT) that can detect conformational changes in MT through fluorescence resonance energy transfer (FRET). SNO-albumin and the membrane-permeant low molecular weight S-nitroso-l-cysteine ethyl ester (l-SNCEE) caused a conformational change in FRET-MT as ascertained by full spectral laser scanning confocal microscopy in live rat pulmonary vascular endothelial cells, a result which is consistent with transnitrosation of the reporter molecule. Transnitrosation of FRET-MT by SNO-albumin, but not l-SNCEE, was sensitive to antisense oligonucleotide-mediated inhibition of the expression of cell surface protein disulfide isomerase (csPDI). These results extend the original observations of Ramachandran et al. (Ramachandran N, Root P, Jiang XM, Hogg PJ, Mutus B. Proc Natl Acad Sci U S A 98: 9539-9544, 2001) and suggest that csPDI-mediated denitrosation helps to regulate the ability of the major plasma NO carrier (SNO-albumin) to transnitrosate endothelial cell molecular targets (e.g. MT). 相似文献
110.
Roepke TA Chang ES Cherr GN 《Journal of experimental zoology. Part A, Comparative experimental biology》2006,305(10):830-841
Endocrine disrupting compounds (EDCs) are known to affect reproduction and development in marine invertebrates. In previous work, we have shown that developing sea urchin embryos were sensitive to estradiol and estrogenic EDCs at environmentally relevant concentrations in a tamoxifen-sensitive manner (Roepke et al. 2005. Aquat Toxicol 71:155-173). In this study, we report the effects of maternal exposure to EDCs on embryo sensitivity and regulation of an orphan steroid receptor in sea urchin eggs. Maternal exposures were conducted by injecting female Strongylocentrotus purpuratus sea urchins initiating oogenesis with two concentrations of estradiol, octylphenol, tributyltin and o, p-DDD for 8 weeks with an induced spawning before and after the injection cycle. Developing embryos were less sensitive to estradiol following maternal exposure to estradiol, octylphenol and DDD. The steroidogenesis inhibitor, spironolactone, and the aromatase inhibitor, formestane, affected normal sea urchin development with EC50 values of 18 and 2 microM, respectively. Binding of estradiol was demonstrated in homogenates supernatants of sea urchin embryos by filtration centrifugation and column chromatography, but saturation was not reached until 4-6 hr and was highly variable. Analysis of eggs from pre- and post-injection spawns using real-time Q-PCR for the mRNA of an orphan steroid receptor, SpSHR2, shows that receptor mRNA increased in eggs with estradiol, octylphenol and tributyltin but decreased with DDD. RIA showed that estradiol may be present during gastrulation. In summary, maternal exposure to estradiol and EDCs alters embryo sensitivity and regulates the expression of an orphan steroid receptor in the egg. 相似文献