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51.
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Photosynthetic organisms are responsible for converting sunlight into organic matter, and they are therefore seen as a resource for the renewable fuel industry. Ethanol and esterified fatty acids (biodiesel) are the most common fuel products derived from these photosynthetic organisms. The potential of algae as producers of biodiesel precursor (or triacylglycerols (TAGs)) has yet to be realized because of the limited knowledge of the underlying biochemistry, cell biology and genetics. Well-characterized pathways from fungi and land plants have been used to identify algal homologs of key enzymes in TAG synthesis, including diacylglcyerol acyltransferases, phospholipid diacylglycerol acyltransferase and phosphatidate phosphatases. Many laboratories have adopted Chlamydomonas reinhardtii as a reference organism for discovery of algal-specific adaptations of TAG metabolism. Stressed Chlamydomonas cells, grown either photoautotrophically or photoheterotrophically, accumulate TAG in plastid and cytoplasmic lipid bodies, reaching 46-65% of dry weight in starch accumulation (sta) mutants. State of the art genomic technologies including expression profiling and proteomics have identified new proteins, including key components of lipid droplets, candidate regulators and lipid/TAG degrading activities. By analogy with crop plants, it is expected that advances in algal breeding and genome engineering may facilitate realizing the potential in algae. 相似文献
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Sack BK Merchant S Markusic DM Nathwani AC Davidoff AM Byrne BJ Herzog RW 《PloS one》2012,7(5):e37671
The major complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors) against factor VIII (FVIII). The current method for eradicating inhibitors, termed immune tolerance induction (ITI), is costly and protracted. Clinical protocols that prevent rather than treat inhibitors are not yet established. Liver-directed gene therapy hopes to achieve long-term correction of the disease while also inducing immune tolerance. We sought to investigate the use of adeno-associated viral (serotype 8) gene transfer to induce tolerance to human B domain deleted FVIII in hemophilia A mice. We administered an AAV8 vector with either human B domain deleted FVIII or a codon-optimized transgene, both under a liver-specific promoter to two strains of hemophilia A mice. Protein therapy or gene therapy was given either alone or in conjunction with anti-CD20 antibody-mediated B cell depletion. Gene therapy with a low-expressing vector resulted in sustained near-therapeutic expression. However, supplementary protein therapy revealed that gene transfer had sensitized mice to hFVIII in a high-responder strain but not in mice of a low-responding strain. This heightened response was ameliorated when gene therapy was delivered with anti-murine CD20 treatment. Transient B cell depletion prevented inhibitor formation in protein therapy, but failed to achieve a sustained hypo-responsiveness. Importantly, use of a codon-optimized hFVIII transgene resulted in sustained therapeutic expression and tolerance without a need for B cell depletion. Therefore, anti-CD20 may be beneficial in preventing vector-induced immune priming to FVIII, but higher levels of liver-restricted expression are preferred for tolerance. 相似文献
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Ingersoll SB Stoltzfus GP Merchant MH Ahmad S Edwards CR Ahmed A Oyer JL Finkler NJ Holloway RW Edwards JR 《Cytotherapy》2012,14(6):716-723
Background/AimsThe aim of this study was to compare the cytotoxic response against ovarian cancer (OC) cells elicited by different immune effector cells in combination with the cytokines interleukin (IL)-2 and interferon (IFN) α-2b.MethodsOC cells were co-cultured with peripheral blood mononuclear cells (PBMC) from normal donors or OC patients and IL-2 or IFN α-2b alone or in combination, in order to determine the cytotoxicity. T cells were isolated from healthy donors to determine T cell cytotoxic activity. PBMC from healthy donors and OC patients were expanded in an IL-2/IL-7/IL-12 cocktail with and without anti-CD3 antibody, and the cytotoxic activity measured. Flow cytometry was performed on primary, selected and expanded cells to determine T, B, and natural killer- (NK) cell percentages.ResultsHealthy donor PBMC elicited a significant cytotoxic response (59%) compared with OC patient PBMC (7%). T cells enriched from normal donors elicited a significant cytotoxic response (18%) compared with controls lacking effector cells (1.4%); however, the cytotoxicity observed was significantly less compared with unselected PBMC. Expanded effector cells consisted primarily of T cells (98%) and the fold-expansion was significantly higher in the presence of anti-CD3 (19- versus 132-fold). No significant difference in the expansion (either fold-expansion or cell type) was observed between OC patients and healthy donors. Expanded cells from both healthy donors and OC patients elicited a significant cytotoxic response in the presence of IL-2 (19% and 22%) compared with controls.ConclusionsPBMC from OC patients do not elicit a significant cytotoxic response; however, ex vivo-expanded cells from OC patients are capable of cytotoxic killing similar to unexpanded T cells isolated from normal donors. These data provide the groundwork for further development of cellular therapy against OC. 相似文献
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Nanopore sensors have attracted considerable interest for high-throughput sensing of individual nucleic acids and proteins without the need for chemical labels or complex optics. A prevailing problem in nanopore applications is that the transport kinetics of single biomolecules are often faster than the measurement time resolution. Methods to slow down biomolecular transport can be troublesome and are at odds with the natural goal of high-throughput sensing. Here we introduce a low-noise measurement platform that integrates a complementary metal-oxide semiconductor (CMOS) preamplifier with solid-state nanopores in thin silicon nitride membranes. With this platform we achieved a signal-to-noise ratio exceeding five at a bandwidth of 1 MHz, which to our knowledge is the highest bandwidth nanopore recording to date. We demonstrate transient signals as brief as 1 μs from short DNA molecules as well as current signatures during molecular passage events that shed light on submolecular DNA configurations in small nanopores. 相似文献
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Comparison of proteins expressed on secretory vesicle membranes and plasma membranes of human neutrophils 总被引:1,自引:0,他引:1
Uriarte SM Powell DW Luerman GC Merchant ML Cummins TD Jog NR Ward RA McLeish KR 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(8):5575-5581
Secretory vesicles are neutrophil intracellular storage granules formed by endocytosis. Understanding the functional consequences of secretory vesicle exocytosis requires knowledge of their membrane proteins. The current study was designed to use proteomic technologies to develop a more complete catalog of secretory vesicle membrane proteins and to compare the proteomes of secretory vesicle and plasma membranes. A total of 1118 proteins were identified, 573 (51%) were present only in plasma membrane-enriched fractions, 418 (37%) only in secretory vesicle-enriched membrane fractions, and 127 (11%) in both fractions. Gene Ontology categorized 373 of these proteins as integral membrane proteins. Proteins typically associated with other intracellular organelles, including nuclei, mitochondria, and ribosomes, were identified in both membrane fractions. Ingenuity Pathway Knowledge Base analysis determined that the majority of canonical and functional pathways were significantly associated with proteins from both plasma membrane-enriched and secretory vesicle-enriched fractions. There were, however, some canonical signaling pathways that involved proteins only from plasma membranes or secretory vesicles. In conclusion, a number of proteins were identified that may elucidate mechanisms and functional consequences of secretory vesicle exocytosis. The small number of common proteins suggests that the hypothesis that secretory vesicles are formed from plasma membranes by endocytosis requires more critical evaluation. 相似文献
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This study investigated the role of quercitol in osmotic adjustment in field-grown Eucalyptus astringens Maiden subject to seasonal drought stress over the course of 1 year. The trees grew in a native woodland and a farm plantation in the semi-arid wheatbelt region of south Western Australia. Plantation trees allocated relatively more biomass to leaves than woodland trees, but they suffered greater drought stress over summer, as indicated by lower water potentials, CO2 assimilation rates and stomatal conductances. In contrast, woodland trees had relatively fewer leaves and suffered less drought stress. Plantation trees under drought stress engaged in osmotic adjustment, but woodland trees did not. Quercitol made a significant contribution to osmotic adjustment in drought-stressed trees (25% of total solutes), and substantially more quercitol was measured in the leaves of plantation trees (5% dry matter) than in the leaves of woodland trees (2% dry matter). We found no evidence that quercitol was used as a carbon storage compound while starch reserves were depleted under drought stress. Differences in stomatal conductance, biomass allocation and quercitol production clearly indicate that E. astringens is both morphologically and physiologically 'plastic' in response to growth environment, and that osmotic adjustment is only one part of a complex strategy employed by this species to tolerate drought. 相似文献