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991.
Michael. J. Smith Keely M. Ough Michael P. Scroggie E. Sabine G. Schreiber Michele Kohout 《Aquatic Botany》2009
Bayesian modeling techniques (which accounted for imperfect detection) were used to assess changes in macrophyte assemblages in 58 wetlands along a typical salinity gradient in Western Victoria, Australia. By incorporating detectability into our predictions, an unbiased estimate was made of the relationship between salinity and both individual species occupancy and the expected number of species. When compared to the freshest wetlands, macrophyte species number was predicted to decrease by as much as 60–70% at conductivities of around 6.0 mS cm−1 (11% seawater), a value often considered the upper salinity tolerance for many freshwater aquatic plants. The model also predicted a 40–50% drop in species number at conductivities of around 1.5 mS cm−1 (3% seawater). It was also found that 25 out of 76 freshwater species were unlikely to occur at conductivities above 1.0 mS cm−1. Consequently, secondary salinisation of fresh non-riverine wetlands is highly likely to markedly and negatively impact upon non-riverine wetland macrophyte assemblages. 相似文献
992.
Nicolas Lvy Maren Oehlmann Franois Delalande Heinz Peter Nasheuer Alain Van Dorsselaer Valrie Schreiber Gilbert de Murcia Josiane Mnissier-de Murcia Domenico Maiorano Anne Bresson 《Nucleic acids research》2009,37(10):3177-3188
Repair of single-stranded DNA breaks before DNA replication is critical in maintaining genomic stability; however, how cells deal with these lesions during S phase is not clear. Using combined approaches of proteomics and in vitro and in vivo protein–protein interaction, we identified the p58 subunit of DNA Pol α-primase as a new binding partner of XRCC1, a key protein of the single strand break repair (SSBR) complex. In vitro experiments reveal that the binding of poly(ADP-ribose) to p58 inhibits primase activity by competition with its DNA binding property. Overexpression of the XRCC1-BRCT1 domain in HeLa cells induces poly(ADP-ribose) synthesis, PARP-1 and XRCC1-BRCT1 poly(ADP-ribosyl)ation and a strong S phase delay in the presence of DNA damage. Addition of recombinant XRCC1-BRCT1 to Xenopus egg extracts slows down DNA synthesis and inhibits the binding of PCNA, but not MCM2 to alkylated chromatin, thus indicating interference with the assembly of functional replication forks. Altogether these results suggest a critical role for XRCC1 in connecting the SSBR machinery with the replication fork to halt DNA synthesis in response to DNA damage. 相似文献
993.
Wurzenberger C Koelzer VH Schreiber S Anz D Vollmar AM Schnurr M Endres S Bourquin C 《Cancer immunology, immunotherapy : CII》2009,58(6):901-913
Dendritic cell (DC) vaccines have emerged as a promising strategy to induce antitumoral cytotoxic T cells for the immunotherapy
of cancer. The maturation state of DC is of critical importance for the success of vaccination, but the most effective mode
of maturation is still a matter of debate. Whereas immature DC carry the risk of inducing tolerance, extensive stimulation
of DC may lead to DC unresponsiveness and exhaustion. In this study, we investigated how short-term versus long-term DC activation
with a Toll-like receptor 9 agonist influences DC phenotype and function. Murine DC were generated in the presence of the
hematopoietic factor Flt3L (FL-DC) to obtain both myeloid and plasmacytoid DC subsets. Short activation of FL-DC for as little
as 4 h induced fully functional DC that rapidly secreted IL-12p70 and IFN-α, expressed high levels of costimulatory and MHC
molecules and efficiently presented antigen to CD4 and CD8 T cells. Furthermore, short-term activated FL-DC overcame immune
suppression by regulatory T cells and acquired high migratory potential toward the chemokine CCL21 necessary for DC recruitment
to lymph nodes. In addition, vaccination with short-term activated DC induced a strong cytotoxic T-cell response in vivo and
led to the eradication of tumors. Thus, short-term activation of DC generates fully functional DC for tumor immunotherapy.
These results may guide the design of new protocols for DC generation in order to develop more efficient DC-based tumor vaccines. 相似文献
994.
Trevor D. Lawley Simon Clare Alan W. Walker Mark D. Stares Thomas R. Connor Claire Raisen David Goulding Roland Rad Fernanda Schreiber Cordelia Brandt Laura J. Deakin Derek J. Pickard Sylvia H. Duncan Harry J. Flint Taane G. Clark Julian Parkhill Gordon Dougan 《PLoS pathogens》2012,8(10)
Relapsing C. difficile disease in humans is linked to a pathological imbalance within the intestinal microbiota, termed dysbiosis, which remains poorly understood. We show that mice infected with epidemic C. difficile (genotype 027/BI) develop highly contagious, chronic intestinal disease and persistent dysbiosis characterized by a distinct, simplified microbiota containing opportunistic pathogens and altered metabolite production. Chronic C. difficile 027/BI infection was refractory to vancomycin treatment leading to relapsing disease. In contrast, treatment of C. difficile 027/BI infected mice with feces from healthy mice rapidly restored a diverse, healthy microbiota and resolved C. difficile disease and contagiousness. We used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis. 相似文献
995.
996.
Soroka J Wandinger SK Mäusbacher N Schreiber T Richter K Daub H Buchner J 《Molecular cell》2012,45(4):517-528
Hsp90 is an essential molecular chaperone in the eukaryotic cytosol. Its function is modulated by cochaperones and posttranslational modifications. Importantly, the phosphatase Ppt1 is a dedicated regulator of the Hsp90 chaperone system. Little is known about Ppt1-dependent phosphorylation sites and how these affect Hsp90 activity. Here, we identified the major phosphorylation sites of yeast Hsp90 in its middle or the C-terminal domain and determined the subset regulated by Ppt1. In general, phosphorylation decelerates the Hsp90 machinery, reduces chaperone function in vivo, sensitizes yeast cells to Hsp90 inhibition and affects DNA repair processes. Modification of one particular site (S485) is lethal, whereas others modulate Hsp90 activity via distinct mechanisms affecting the ATPase activity, cochaperone binding and manipulating conformational transitions in Hsp90. Our mechanistic analysis reveals that phosphorylation of Hsp90 permits a regulation of the conformational cycle at distinct steps by targeting switch points for the communication of remote regions within Hsp90. 相似文献
997.
McCracken JA Custer EE Schreiber DT Tsang PC Keator CS Arosh JA 《Prostaglandins & other lipid mediators》2012,97(3-4):90-96
A new in vivo model for studying luteolysis was developed in sheep to provide a convenient method for collecting corpora lutea for molecular, biochemical, and histological analysis during a procedure that mimics natural luteolysis. It was found that the infusion of prostaglandin F(2α) (PGF(2α)) at 20 μg/min/h into the systemic circulation during the mid luteal phase of the cycle allowed sufficient PGF(2α) to escape across the lungs and thus mimic the transient 40% decline in the concentration of progesterone in peripheral plasma seen at the onset of natural luteolysis in sheep. Additional 1h-long systemic infusions of PGF(2α), given at physiological intervals, indicated that two infusions were not sufficient to induce luteolysis. However, an early onset of luteolysis and estrus was induced in one out of three sheep with three infusions, two out of three sheep with four infusions, and three out of three sheep with five infusions. Reducing the duration of each systemic infusion of PGF(2α) from 1h to 30 min failed to induce luteolysis and estrus even after six systemic infusions indicating that, not only are the amplitude and frequency of PGF(2α) pulses essential for luteolysis, but the actual duration of each pulse is also critical. We conclude that a minimum of five systemic pulses of PGF(2α), given in an appropriate amount and at a physiological frequency and duration, are required to mimic luteolysis consistently in all sheep. The five pulse regimen thus provides a new accurate in vivo model for studying molecular mechanisms of luteolysis. 相似文献
998.
Lukas Vaclavik Andre Schreiber Ondrej Lacina Tomas Cajka Jana Hajslova 《Metabolomics : Official journal of the Metabolomic Society》2012,8(5):793-803
High performance liquid chromatography?Cmass spectrometry (HPLC?CMS) technique, employing a hybrid triple quadrupole/linear ion trap (QqQ/LIT) mass analyzer, was used for comprehensive metabolomic fingerprinting of several fruit juices types, prepared from expensive (orange) or relatively low-priced (apple, grapefruit) fruits. Following the automated data mining and pre-treatment step, the suitability of the multivariate HPLC?CMS metabolomic data for authentication, i.e., classification of fruit juice and adulteration detection, was assessed with the use of advanced chemometric tools (principal component analysis, PCA, and linear discrimination analysis, LDA). The LDA classification model, constructed and validated employing a highly variable samples set, was able to reliably detect 15% addition of apple or grapefruit juice to orange juice. In the final stage of this study, high performance liquid chromatography?Cquadrupole?Cquadrupole-time-of-flight mass spectrometry (HPLC?CQqTOFMS) measurements were performed in order to obtain data for identification of pre-selected marker compounds using elemental formula calculation and online databases search. 相似文献
999.
1000.
C Ruiz JR Martins F Rudin S Schneider T Dietsche CA Fischer L Tornillo LM Terracciano R Schreiber L Bubendorf K Kunzelmann 《PloS one》2012,7(8):e43265
Head and neck squamous cell carcinoma (HNSCC) has the potential for early metastasis and is associated with poor survival. Ano1 (Dog1) is an established and sensitive marker for the diagnosis of gastrointestinal stromal tumors (GIST) and has recently been identified as a Ca(2+) activated Cl(-) channel. Although the ANO1 gene is located on the 11q13 locus, a region which is known to be amplified in different types of human carcinomas, a detailed analysis of Ano1 amplification and expression in HNSCC has not been performed. It is thus still unclear how Ano1 contributes to malignancy in HNSCC. We analyzed genomic amplification of the 11q13 locus and Ano1 together with Ano1-protein expression in a large collection of HNSCC samples. We detected a highly significant correlation between amplification and expression of Ano1 and showed that HNSCC patients with Ano1 protein expression have a poor overall survival. We further analyzed the expression of the Ano1 protein in more than 4'000 human samples from 80 different tumor types and 76 normal tissue types and detected that besides HNSCC and GISTs, Ano1 was rarely expressed in other tumor samples or healthy human tissues. In HNSCC cell lines, expression of Ano1 caused Ca(2+) activated Cl(-) currents, which induced cell motility and cell migration in wound healing and in real time migration assays, respectively. In contrast, knockdown of Ano1 did not affect intracellular Ca(2+) signaling and surprisingly did not reduce cell proliferation in BHY cells. Further, expression and activity of Ano1 strongly correlated with the ability of HNSCC cells to regulate their volume. Thus, poor survival in HNSCC patients is correlated with the presence of Ano1. Our results further suggest that Ano1 facilitates regulation of the cell volume and causes cell migration, which both can contribute to metastatic progression in HNSCC. 相似文献