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101.
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103.
Purification and characterization of the respiratory nitrate reductase of Bacillus stearothermophilus 总被引:1,自引:0,他引:1
The reduced methylviolegen-nitrate reductase of the obligate thermophile, Bacillus stearothermophilus NCA strain 2184 (ATCC 12016), has been purified to electrophoretic homogeneity, 53-fold with a yield of 12,5%. The purification procedure involved solubilization with octyl glucoside, ammonium sulfate precipitation, ion-exchange, and molecular sieve chromatography. The molecular weight of the enzyme was estimated by polyacrylamide gel electrophoresis to be about 210,000. The enzyme possesses two subunits of 150,000 and 44,000 daltons in equimolar ratio, and no cytochrome. There are 6 atoms of nonheme iron and 12 mol of labile sulfide in 1 mol of the purified enzyme. The 44,000-dalton β subunit is the smallest of all the characterized bacterial nitrate reductases and is very close to the size of the β1 subunit of Escherichia coli. The various β components of other bacterial nitrate reductases are probably derived from this 44,000-dalton subunit. 相似文献
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105.
JB Parentes-Vieira PV Lopes-Costa CG Pires AR dos Santos JD Pereira-Filho BB da Silva 《International Seminars in Surgical Oncology : ISSO》2007,4(1):22
Background
The objective of this study was to evaluate angiogenesis according to CD34 antigen expression in estrogen receptor (ER)-positive and negative breast carcinomas.Methods
This study comprised 64 cases of infiltrating ductal carcinoma in postmenopausal women divided into two groups: Group A: ER-positive, n = 35; and Group B: ER-negative, n = 29. The anti-CD34 monoclonal antibody was used as a marker for endothelial cells. Microvessel count was carried out in 10 fields per slide using a 40× objective lens (magnification 400×). Statistical analysis of the data was performed using Student's t-test (p < 0.05).Results
The mean number of vessels stained with the anti-CD34 antibody in the estrogen receptor-positive and negative tumors was 23.51 ± 1.15 and 40.24 ± 0.42, respectively. The number of microvessels was significantly greater in the estrogen receptor-negative tumors (p < 0.001).Conclusion
ER-negative tumors have significantly greater CD34 antigen expression compared to ER-positive tumors.106.
Teng YK Verburg RJ Verpoort KN Diepenhorst GM Bajema IM van Tol MJ Jol-van der Zijde EC Toes RE Huizinga TW van Laar JM 《Arthritis research & therapy》2007,9(5):R106
In order to identify pathogenic correlates of refractory rheumatoid arthritis (RA), antibodies against anti-cyclic citrullinated
protein (ACPAs) were investigated in RA patients in whom the dysregulated immune system had been ablated by high-dose chemotherapy
(HDC) and autologous haematopoietic stem cell transplantation (HSCT). Six patients with refractory RA were extensively characterized
in terms of levels of total immunoglobulins, RA-specific autoantibodies (ACPAs and rheumatoid factor) and antibodies against
rubella, tetanus toxoid (TT) and phosphorylcholine before and after HDC plus HSCT. Additionally, the avidity of ACPAs was
measured before and after treatment and compared with the avidity of TT antibodies following repeated immunizations. Synovial
biopsies were obtained by arthroscopy before HDC plus HSCT, and analyzed by immunohistochemistry. In the three patients with
clinically long-lasting responses to HDC plus HSCT (median 423 days), significant reductions in ACPA-IgG levels after therapy
were observed (median level dropped from 215 to 34 arbitrary units/ml; P = 0.05). In contrast, stable ACPA-IgG levels were observed in three patients who relapsed shortly after HDC plus HSCT (median
of 67 days). Clinical responders had ACPA-IgG of lower avidity (r = 0.75; P = 0.08) and higher degree of inflammation histologically (r = 0.73; P = 0.09). Relapse (after 38 to 530 days) in all patients was preceded by rising levels of low avidity ACPA-IgG (after 30 to
388 days), in contrast to the stable titres of high avidity TT antibodies. In conclusion, humoral autoimmune responses were
differentially modulated by immunoablative therapy in patients with synovial inflammation and low avidity ACPA-IgG autoantibodies
as compared with patients with high levels of high avidity ACPA-IgG. The distinct clinical disease course after immunoablative
therapy based on levels and avidity of ACPA-IgG indicates that refractory RA is not a single disease entity. 相似文献
107.
Linda J. Beaumont Rachael V. Gallagher Paul O. Downey Wilfried Thuiller Michelle R. Leishman Lesley Hughes 《Ecography》2009,32(5):757-764
Anthropogenically-induced climate change is one of the most important global threats to biodiversity. Understanding its impact on the distribution of exotic plant species is critical for developing effective adaptation and management strategies. However, there is insufficient information currently available on the biodiversity at risk from 1) exotic plant invasions, 2) climate change, and 3) the interaction between these two major threats, to develop such strategies. We use ecological niche models as a first step to identify zones inside and outside Australian protected areas that may be most at risk from invasions of three species of Hieracium (hawkweeds) under current and future (2030 and 2070) climate scenarios, should current control and eradication methods fail. These perennial herbs are native to Europe and invasive to New Zealand and North America. Naturalised in Australia, hawkweeds threaten native tussock grasslands and the grazing industry, and have been placed on the National Alert List. Using eight ecological niche models currently available in the software package BIOMOD, we found that these species have yet to realize the extent of their climatic distribution under present day climate in Australia. As climate change accelerates, the climatic range of hawkweeds was projected to contract overall. However, much of the Australian Alps, which contain large contiguous tracts of reserves and many endemic species, will continue to retain climatically suitable areas for hawkweeds through to 2070. These results emphasise the need for ongoing monitoring as well as focused control to minimize the likelihood of hawkweeds realizing their invasive potential in protected areas and beyond. 相似文献
108.
Qin Wang Dhaarmini Rajshankar Donald R. Branch Katherine A. Siminovitch Maria Teresa Herrera Abreu Gregory P. Downey Christopher A. McCulloch 《The Journal of biological chemistry》2009,284(31):20763-20772
Calcium (Ca2+) signaling by the pro-inflammatory cytokine interleukin-1 (IL-1) is dependent on focal adhesions, which contain diverse structural and signaling proteins including protein phosphatases. We examined here the role of protein-tyrosine phosphatase (PTP) α in regulating IL-1-induced Ca2+ signaling in fibroblasts. IL-1 promoted recruitment of PTPα to focal adhesions and endoplasmic reticulum (ER) fractions, as well as tyrosine phosphorylation of the ER Ca2+ release channel IP3R. In response to IL-1, catalytically active PTPα was required for Ca2+ release from the ER, Src-dependent phosphorylation of IP3R1 and accumulation of IP3R1 in focal adhesions. In pulldown assays and immunoprecipitations PTPα was required for the association of PTPα with IP3R1 and c-Src, and this association was increased by IL-1. Collectively, these data indicate that PTPα acts as an adaptor to mediate functional links between focal adhesions and the ER that enable IL-1-induced Ca2+ signaling.The interleukin-1 (IL-1)3 family of pro-inflammatory cytokines mediates host responses to infection and injury. Impaired control of IL-1 signaling leads to chronic inflammation and destruction of extracellular matrices (1, 2), as seen in pathological conditions such as pulmonary fibrosis (3), rheumatoid arthritis (4, 5), and periodontitis (6). IL-1 elicits multiple signaling programs, some of which trigger Ca2+ release from the endoplasmic reticulum (ER) as well as expression of multiple cytokines and inflammatory factors including c-Fos and c-Jun (7, 8), and matrix metalloproteinases (9, 10), which mediate extracellular matrix degradation via mitogen-activated protein kinase-regulated pathways (11).In anchorage-dependent cells including fibroblasts and chondrocytes, focal adhesions (FAs) are required for IL-1-induced Ca2+ release from the ER and activation of ERK (12–14). FAs are actin-enriched adhesive domains composed of numerous (>50) scaffolding and signaling proteins (15–17). Many FA proteins are tyrosine-phosphorylated, including paxillin, focal adhesion kinase, and src family kinases, all of which are crucial for the assembly and disassembly of FAs (18–21). Protein-tyrosine phosphorylation plays a central role in regulating many cellular processes including adhesion (22, 23), motility (24), survival (25), and signal transduction (26–29). Phosphorylation of proteins by kinases is balanced by protein-tyrosine phosphatases (PTP), which can enhance or attenuate downstream signaling by dephosphorylation of tyrosine residues (30–32).PTPs can be divided into two main categories: receptor-like and intracellular PTPs (33). Two receptor-like PTPs have been localized to FA (leukocyte common antigen-related molecule and PTPα). Leukocyte common antigen-related molecule can dephosphorylate and mediate degradation of p130cas, which ultimately leads to cell death (34, 35). PTPα contains a heavily glycosylated extracellular domain, a transmembrane domain, and two intracellular phosphatase domains (33, 36). The amino-terminal domain predominantly mediates catalytic activity, whereas the carboxyl-terminal domain serves a regulatory function (37, 38). PTPα is enriched in FA (23) and is instrumental in regulating FA dynamics (39) via activation of c-Src/Fyn kinases by dephosphorylating the inhibitory carboxyl tyrosine residue, namely Tyr529 (22, 40–42) and facilitation of integrin-dependent assembly of Src-FAK and Fyn-FAK complexes that regulate cell motility (43). Although PTPα has been implicated in formation and remodeling of FAs (44, 45), the role of PTPα in FA-dependent signaling is not defined.Ca2+ release from the ER is a critical step in integrin-dependent IL-1 signal transduction and is required for downstream activation of ERK (13, 46). The release of Ca2+ from the ER depends on the inositol 1,4,5-triphosphate receptor (IP3R), which is an IP3-gated Ca2+ channel (47). All of the IP3R subtypes (subtypes 1–3) have been localized to the ER, as well as other the plasma membrane and other endomembranes (48–50). Further, IP3R may associate with FAs, enabling the anchorage of the ER to FAs (51, 52). However, the molecule(s) that provide the structural link for this association has not been defined.FA-restricted, IL-1-triggered signal transduction in anchorage-dependent cells may rely on interacting proteins that are enriched in FAs and the ER (53). Here, we examined the possibility that PTPα associates with c-Src and IP3R to functionally link FAs to the ER, thereby enabling IL-1 signal transduction. 相似文献
109.
Alla Bondareva Charlene M. Downey Fabio Ayres Wei Liu Steven K. Boyd Benedikt Hallgrimsson Frank R. Jirik 《PloS one》2009,4(5)
Lysyl oxidase (LOX), an extracellular matrix remodeling enzyme, appears to have a role in promoting breast cancer cell motility and invasiveness. In addition, increased LOX expression has been correlated with decreases in both metastases-free, and overall survival in breast cancer patients. With this background, we studied the ability of β-aminopropionitrile (BAPN), an irreversible inhibitor of LOX, to regulate the metastatic colonization potential of the human breast cancer cell line, MDA-MB-231. BAPN was administered daily to mice starting either 1 day prior, on the same day as, or 7 days after intracardiac injection of luciferase expressing MDA-MB-231-Luc2 cells. Development of metastases was monitored by in vivo bioluminescence imaging, and tumor-induced osteolysis was assessed by micro-computed tomography (μCT). We found that BAPN administration was able to reduce the frequency of metastases. Thus, when BAPN treatment was initiated the day before, or on the same day as the intra-cardiac injection of tumor cells, the number of metastases was decreased by 44%, and 27%, and whole-body photon emission rates (reflective of total tumor burden) were diminished by 78%, and 45%, respectively. In contrast, BAPN had no effect on the growth of established metastases. Our findings suggest that LOX activity is required during extravasation and/or initial tissue colonization by circulating MDA-MB-231 cells, lending support to the idea that LOX inhibition might be useful in metastasis prevention. 相似文献
110.
James A. Poulter David F. Gilmour Hiroyuki Kondo David A. Mackey Lisa S. Kearns Jamie E. Craig Louise M. Downey Moin D. Mohamed Chris F. Inglehearn 《American journal of human genetics》2010,86(2):248-253
Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder of the retinal vascular system. Although mutations in three genes (LRP5, FZD4, and NDP) are known to cause FEVR, these account for only a fraction of FEVR cases. The proteins encoded by these FEVR genes form part of a signaling complex that activates the Norrin-β-catenin signaling pathway. Recently, through a large-scale reverse genetic screen in mice, Junge and colleagues identified an additional member of this signaling complex, Tspan12. Here, we report that mutations in TSPAN12 also cause autosomal-dominant FEVR. We describe seven mutations identified in a cohort of 70 FEVR patients in whom we had already excluded the known FEVR genes. This study provides further evidence for the importance of the Norrin-β-catenin signaling pathway in the development of the retinal vasculature and also indicates that more FEVR genes remain to be identified. 相似文献