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991.
Ezhevskaya M Trandafir F Moens L Dewilde S Van Doorslaer S 《Journal of inorganic biochemistry》2011,105(9):1131-1137
The function of neuroglobin, a member of the vertebrate globin family, is still unknown. In human neuroglobin (NGB), the formation of a disulfide bridge between the CysCD7 and CysD5 is known to affect the heme environment and its ligand-binding kinetics. Here, we show by means of EPR that the PheB10 residue plays a key role in transmitting the structural information from the disulfide bridge to the heme-pocket region. While formation of a disulfide bridge in ferric wild-type NGB leads to a considerable change of its EPR parameters, only minor changes are observed in the case of ferric PheB10Leu NGB. Furthermore, wild-type NGB is found to be much more stable in the presence of H2O2 than its PheB10Leu or its HisE7Leu mutants. While tyrosyl radicals are induced in HisE7Leu NGB by the addition of H2O2, this is not the case for wild-type and PheB10Leu NGB. The results will be discussed in terms of the protein's putative functions. 相似文献
992.
Bacteria and archaea involved in anaerobic digestion of distillers grains with solubles 总被引:1,自引:0,他引:1
Ziganshin AM Schmidt T Scholwin F Il'inskaya ON Harms H Kleinsteuber S 《Applied microbiology and biotechnology》2011,89(6):2039-2052
Cereal distillers grains, a by-product from bioethanol industry, proved to be a suitable feedstock for biogas production in
laboratory scale anaerobic digesters. Five continuously stirred tank reactors were run under constant conditions and monitored
for biogas production and composition along with other process parameters. Iron additives for sulfide precipitation significantly
improved the process stability and efficiency, whereas aerobic pretreatment of the grains had no effect. The microbial communities
in the reactors were investigated for their phylogenetic composition by terminal restriction fragment length polymorphism
analysis and sequencing of 16S rRNA genes. The bacterial subcommunities were highly diverse, and their composition did not
show any correlation with reactor performance. The dominant phylotypes were affiliated to the Bacteroidetes. The archaeal
subcommunities were less diverse and correlated with the reactor performance. The well-performing reactors operated at lower
organic loading rates and amended with iron chloride were dominated by aceticlastic methanogens of the genus Methanosaeta. The well-performing reactor operated at a high organic loading rate and supplemented with iron hydroxide was dominated by
Methanosarcina ssp. The reactor without iron additives was characterized by propionate and acetate accumulation and high hydrogen sulfide
content and was dominated by hydrogenotrophic methanogens of the genus Methanoculleus. 相似文献
993.
Pandolfino JE Lin Z Roman S Kahrilas PJ 《American journal of physiology. Gastrointestinal and liver physiology》2011,301(4):G679-G683
Whereas conventional manometry depicts peristalsis as pressure variation over time, high-resolution manometry makes it equally feasible to depict pressure variation along the lumen (spatial pressure variation plots). This study analyzed the characteristics of spatial pressure variation plots during normal peristalsis. High-resolution manometry studies of 72 normal subjects were analyzed with custom MATLAB programs. A coordinate-based strategy was used to normalize both timing of peristalsis and esophageal length. A spatial pressure variation function was devised to localize the proximal (P) and the distal troughs (D) on each subject's composite pressure topography and track the length within the P-D segment contracting concurrently in the course of peristalsis. The timing at which this function peaked was compared with that of the contractile deceleration point (CDP). The length of concurrent contraction during normal peristalsis had an average span of 9.3 cm, encompassing 61% of the distal P-D length of the esophagus. The timing of the CDP position closely matched that of maximal length within the P-D segment contracting concurrently (r = 0.90, P < 0.001). The pressure morphology of the maximal concurrent contraction was that of a smooth curve, and it was extremely rare to see multiple peaks along the vertical axis (seen in 4 of 72 subjects). Concurrent contraction involving ~60% of the P-D span occurred with normal peristalsis. The segment of concurrent contraction progressively increased as peristalsis progressed, peaked at the CDP, and then progressively decreased. How abnormalities of the extent or timing of concurrent contraction relate to clinical syndromes requires further investigation. 相似文献
994.
995.
The organic cation transporter (OCT, SLC22) family is a family of polyspecific transmembrane proteins that are responsible for the uptake or excretion of many cationic drugs, toxins, and endogenous metabolites in a variety of tissues. Many of the OCTs have been previously characterized, but there are a number of orphan genes whose functions remain unknown. In this study, two novel rat SLC22 genes, SLC22A17 (BOCT1) and SLC22A23 (BOCT2), were cloned and characterized. Northern blot analysis showed that BOCT1 and BOCT2 mRNA was expressed in a wide variety of tissues. BOCT1 was strongly expressed in brain, primary neurons and brain endothelial cells, with highest expression in choroid plexus. BOCT2 was also abundantly expressed in brain, as well as in liver. To characterize the products of these genes, BOCT1 cDNA was isolated from a rat blood-brain barrier cDNA library, and BOCT2 cDNA was isolated from rat brain capillary and from cultured neurons using PCR techniques. Plasmids expressing BOCT1 and BOCT2 were transfected into HEK-293 cells, as were control cDNAs for OCT1 and OCTN2. Recombinant cell surface protein was verified by western blot and fluorescence microscopy. Transport activity of BOCT1 and BOCT2 was evaluated using radioisotope uptake assays. The OCT1- and OCTN2-expressing cells transported the canonical substrates, 1-methyl-4-phenyl-pyridinium (MPP(+)) and carnitine, respectively. However, BOCT1 and BOCT2-expressing cells did not show transport activity for these substrates or a number of other SLC22 substrates. These novel family members have a nonconserved amino terminus, relative to other OCTs, that may preclude typical SLC22 transport function. 相似文献
996.
Edelmann B Bertsch U Tchikov V Winoto-Morbach S Perrotta C Jakob M Adam-Klages S Kabelitz D Schütze S 《The EMBO journal》2011,30(2):379-394
We previously demonstrated that tumour necrosis factor (TNF)-induced ceramide production by endosomal acid sphingomyelinase (A-SMase) couples to apoptosis signalling via activation of cathepsin D and cleavage of Bid, resulting in caspase-9 and caspase-3 activation. The mechanism of TNF-mediated A-SMase activation within the endolysosomal compartment is poorly defined. Here, we show that TNF-induced A-SMase activation depends on functional caspase-8 and caspase-7 expression. The active forms of all three enzymes, caspase-8, caspase-7 and A-SMase, but not caspase-3, colocalize in internalized TNF receptosomes. While caspase-8 and caspase-3 are unable to induce activation of purified pro-A-SMase, we found that caspase-7 mediates A-SMase activation by direct interaction resulting in proteolytic cleavage of the 72-kDa pro-A-SMase zymogen at the non-canonical cleavage site after aspartate 253, generating an active 57 kDa A-SMase molecule. Caspase-7 down modulation revealed the functional link between caspase-7 and A-SMase, confirming proteolytic cleavage as one further mode of A-SMase activation. Our data suggest a signalling cascade within TNF receptosomes involving sequential activation of caspase-8 and caspase-7 for induction of A-SMase activation by proteolytic cleavage of pro-A-SMase. 相似文献
997.
Elowe S 《Molecular and cellular biology》2011,31(15):3085-3093
The spindle checkpoint ensures genome fidelity by temporarily halting chromosome segregation and the ensuing mitotic exit until the last kinetochore is productively attached to the mitotic spindle. At the interface between proper chromosome attachment and the metaphase-to-anaphase transition are the mammalian spindle checkpoint kinases. Compelling evidence indicates that the checkpoint kinases Bub1 and BubR1 have the added task of regulating kinetochore-microtubule attachments. However, the debate on the requirement of kinase activity is in full swing. This minireview summarizes recent advances in our understanding of the core spindle checkpoint kinases Bub1 and BubR1 and considers evidence that supports and opposes the role of kinase activity in regulating their functions during mitosis. 相似文献
998.
Christian F Szaszák M Friedl S Drewianka S Lorenz D Goncalves A Furkert J Vargas C Schmieder P Götz F Zühlke K Moutty M Göttert H Joshi M Reif B Haase H Morano I Grossmann S Klukovits A Verli J Gáspár R Noack C Bergmann M Kass R Hampel K Kashin D Genieser HG Herberg FW Willoughby D Cooper DM Baillie GS Houslay MD von Kries JP Zimmermann B Rosenthal W Klussmann E 《The Journal of biological chemistry》2011,286(11):9079-9096
A-kinase anchoring proteins (AKAPs) tether protein kinase A (PKA) and other signaling proteins to defined intracellular sites, thereby establishing compartmentalized cAMP signaling. AKAP-PKA interactions play key roles in various cellular processes, including the regulation of cardiac myocyte contractility. We discovered small molecules, 3,3'-diamino-4,4'-dihydroxydiphenylmethane (FMP-API-1) and its derivatives, which inhibit AKAP-PKA interactions in vitro and in cultured cardiac myocytes. The molecules bind to an allosteric site of regulatory subunits of PKA identifying a hitherto unrecognized region that controls AKAP-PKA interactions. FMP-API-1 also activates PKA. The net effect of FMP-API-1 is a selective interference with compartmentalized cAMP signaling. In cardiac myocytes, FMP-API-1 reveals a novel mechanism involved in terminating β-adrenoreceptor-induced cAMP synthesis. In addition, FMP-API-1 leads to an increase in contractility of cultured rat cardiac myocytes and intact hearts. Thus, FMP-API-1 represents not only a novel means to study compartmentalized cAMP/PKA signaling but, due to its effects on cardiac myocytes and intact hearts, provides the basis for a new concept in the treatment of chronic heart failure. 相似文献
999.
Tumor cell programmed death ligand 1-mediated T cell suppression is overcome by coexpression of CD80
Haile ST Bosch JJ Agu NI Zeender AM Somasundaram P Srivastava MK Britting S Wolf JB Ksander BR Ostrand-Rosenberg S 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(12):6822-6829
Programmed death ligand 1 (PDL1, or B7-H1) is expressed constitutively or is induced by IFN-γ on the cell surface of most human cancer cells and acts as a "molecular shield" by protecting tumor cells from T cell-mediated destruction. Using seven cell lines representing four histologically distinct solid tumors (lung adenocarcinoma, mammary carcinoma, cutaneous melanoma, and uveal melanoma), we demonstrate that transfection of human tumor cells with the gene encoding the costimulatory molecule CD80 prevents PDL1-mediated immune suppression by tumor cells and restores T cell activation. Mechanistically, CD80 mediates its effects through its extracellular domain, which blocks the cell surface expression of PDL1 but does not prevent intracellular expression of PDL1 protein. These studies demonstrate a new role for CD80 in facilitating antitumor immunity and suggest new therapeutic avenues for preventing tumor cell PDL1-induced immune suppression. 相似文献
1000.
Stary G Klein I Bauer W Koszik F Reininger B Kohlhofer S Gruber K Skvara H Jung T Stingl G 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(1):103-112
Although glucocorticosteroids (GCSs) have been used for many decades in transplantation and (auto)inflammatory diseases, the exact mechanisms responsible for their immunosuppressive properties are not fully understood. The purpose of this study was to characterize the effects of oral GCSs on the cutaneous immune response. We analyzed, by immunofluorescence staining and quantitative RT-PCR, residual skin biopsy material from a clinical study in which we had used oral GCS as positive control for determining the effects of candidate anti-inflammatory compounds on epicutaneous patch tests of Ni-allergic patients. Expectedly, oral GCS treatment led to a reduction of clinical symptoms and infiltrating leukocytes. Notably, we observed increased numbers of dermal FOXP3(+)CD25(+) T cells and epidermal Langerhans cells (LCs) that were associated with upregulated mRNA expression of TGF-β in lesions of GCS-treated Ni-allergic patients. To investigate this phenomenon further, we exposed purified LCs to GCS. They exhibited, in contrast to GCS-nonexposed LCs, 1) a more immature phenotype, 2) higher intracellular amounts of TGF-β, and 3) increased receptor activator for NF-κB expression, conditions that reportedly favor the expansion of regulatory T cells (Tregs). Indeed, we observed an enhancement of functionally suppressive FOXP3(+) T cells when CD3(+) cells were incubated with GCS-pretreated LCs. The expansion of Tregs was inhibited by TGF-β blockage alone, and their suppressive activity was neutralized by a combination of anti-TGF-β and anti-IL-10 Abs. Our data show that systemically applied GCSs endow LCs with Treg-promoting properties and thus shed new light on the mechanisms of GCS-mediated immunosuppression. 相似文献