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排序方式: 共有399条查询结果,搜索用时 31 毫秒
61.
Ellsworth BA Meng W Patel M Girotra RN Wu G Sher PM Hagan DL Obermeier MT Humphreys WG Robertson JG Wang A Han S Waldron TL Morgan NN Whaley JM Washburn WN 《Bioorganic & medicinal chemistry letters》2008,18(17):4770-4773
Inhibition of sodium-dependent glucose transporter 2 (SGLT2), the transporter that is responsible for renal re-uptake of glucose, leads to glucosuria in animals. SGLT-mediated glucosuria provides a mechanism to shed excess plasma glucose to ameliorate diabetes-related hyperglycemia and associated complications. The current study demonstrates that the proper relationship of a 4′-substituted benzyl group to a β-1C-phenylglucoside is important for potent and selective SGLT2 inhibition. The lead C-arylglucoside (7a) demonstrates superior metabolic stability to its O-arylglucoside counterpart (4) and it promotes glucosuria when administered in vivo. 相似文献
62.
Marlys Hammond David G. Washburn Tram H. Hoang Sharada Manns James S. Frazee Hiroko Nakamura Jaclyn R. Patterson Walter Trizna Charlene Wu Leonard M. Azzarano Rakesh Nagilla Melanie Nord Rebecca Trejo Martha S. Head Baoguang Zhao Angela M. Smallwood Kendra Hightower Nicholas J. Laping Christine G. Schnackenberg Scott K. Thompson 《Bioorganic & medicinal chemistry letters》2009,19(15):4441-4445
The lead serum and glucocorticoid-related kinase 1 (SGK1) inhibitors 4-(5-phenyl-1H-pyrrolo[2,3-b]pyridin-3-yl)benzoic acid (1) and {4-[5-(2-naphthalenyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]phenyl}acetic acid (2) suffer from low DNAUC values in rat, due in part to formation and excretion of glucuronic acid conjugates. These PK/glucuronidation issues were addressed either by incorporating a substituent on the 3-phenyl ring ortho to the key carboxylate functionality of 1 or by substituting on the group in between the carboxylate and phenyl ring of 2. Three of these analogs have been identified as having good SGK1 inhibition potency and have DNAUC values suitable for in vivo testing. 相似文献
63.
Sara L Goodacre Oliver Y Martin Dries Bonte Linda Hutchings Chris Woolley Kamal Ibrahim CF George Thomas Godfrey M Hewitt 《BMC biology》2009,7(1):32-8
Background
Dispersal plays a key role in shaping biological and ecological processes such as the distribution of spatially-structured populations or the pace and scale of invasion. Here we have studied the relationship between long-distance dispersal behaviour of a pest-controlling money spider,Erigone atra, and the distribution of maternally acquired endosymbionts within the wider meta-population. This spider persists in heterogeneous environments because of its ability to recolonise areas through active long-distance airborne dispersal using silk as a sail, in a process termed 'ballooning'. 相似文献64.
Analysis of the microbial proteome 总被引:11,自引:0,他引:11
Proteomics has begun to provide insight into the biology of microorganisms. The combination of proteomics with genetics, molecular biology, protein biochemistry and biophysics is particularly powerful, resulting in novel methods to analyse complex protein mixtures. Emerging proteomic technologies promise to increase the throughput of protein identifications from complex mixtures and allow for the quantification of protein expression levels. 相似文献
65.
Joseph E. Donnelly Stephen D. Herrmann Kate Lambourne Amanda N. Szabo Jeffery J. Honas Richard A. Washburn 《PloS one》2014,9(1)
Background
The magnitude of the negative energy balance induced by exercise may be reduced due to compensatory increases in energy intake.Objective
To address the question: Does increased exercise or physical activity alter ad-libitum daily energy intake or macronutrient composition in healthy adults?Data Sources
PubMed and Embase were searched (January 1990–January 2013) for studies that presented data on energy and/or macronutrient intake by level of exercise, physical activity or change in response to exercise. Ninety-nine articles (103 studies) were included.Study Eligibility Criteria
Primary source articles published in English in peer-reviewed journals. Articles that presented data on energy and/or macronutrient intake by level of exercise or physical activity or changes in energy or macronutrient intake in response to acute exercise or exercise training in healthy (non-athlete) adults (mean age 18–64 years).Study Appraisal and Synthesis Methods
Articles were grouped by study design: cross-sectional, acute/short term, non-randomized, and randomized trials. Considerable heterogeneity existed within study groups for several important study parameters, therefore a meta-analysis was considered inappropriate. Results were synthesized and presented by study design.Results
No effect of physical activity, exercise or exercise training on energy intake was shown in 59% of cross-sectional studies (n = 17), 69% of acute (n = 40), 50% of short-term (n = 10), 92% of non-randomized (n = 12) and 75% of randomized trials (n = 24). Ninety-four percent of acute, 57% of short-term, 100% of non-randomized and 74% of randomized trials found no effect of exercise on macronutrient intake. Forty-six percent of cross-sectional trials found lower fat intake with increased physical activity.Limitations
The literature is limited by the lack of adequately powered trials of sufficient duration, which have prescribed and measured exercise energy expenditure, or employed adequate assessment methods for energy and macronutrient intake.Conclusions
We found no consistent evidence that increased physical activity or exercise effects energy or macronutrient intake. 相似文献66.
67.
The COMPASS family of H3K4 methylases in Drosophila 总被引:1,自引:0,他引:1
Mohan M Herz HM Smith ER Zhang Y Jackson J Washburn MP Florens L Eissenberg JC Shilatifard A 《Molecular and cellular biology》2011,31(21):4310-4318
Methylation of histone H3 lysine 4 (H3K4) in Saccharomyces cerevisiae is implemented by Set1/COMPASS, which was originally purified based on the similarity of yeast Set1 to human MLL1 and Drosophila melanogaster Trithorax (Trx). While humans have six COMPASS family members, Drosophila possesses a representative of the three subclasses within COMPASS-like complexes: dSet1 (human SET1A/SET1B), Trx (human MLL1/2), and Trr (human MLL3/4). Here, we report the biochemical purification and molecular characterization of the Drosophila COMPASS family. We observed a one-to-one similarity in subunit composition with their mammalian counterparts, with the exception of LPT (lost plant homeodomains [PHDs] of Trr), which copurifies with the Trr complex. LPT is a previously uncharacterized protein that is homologous to the multiple PHD fingers found in the N-terminal regions of mammalian MLL3/4 but not Drosophila Trr, indicating that Trr and LPT constitute a split gene of an MLL3/4 ancestor. Our study demonstrates that all three complexes in Drosophila are H3K4 methyltransferases; however, dSet1/COMPASS is the major monoubiquitination-dependent H3K4 di- and trimethylase in Drosophila. Taken together, this study provides a springboard for the functional dissection of the COMPASS family members and their role in the regulation of histone H3K4 methylation throughout development in Drosophila. 相似文献
68.
M R Falvo S Washburn R Superfine M Finch F P Brooks Jr V Chi R M Taylor nd 《Biophysical journal》1997,72(3):1396-1403
We present our results on the manipulation of individual viruses using an advanced interface for atomic force microscopes (AFMs). We show that the viruses can be dissected, rotated, and translated with great facility. We interpret the behavior of tobacco mosaic virus with a mechanical model that makes explicit the competition between sample-substrate lateral friction and the flexural rigidity of the manipulated object. The manipulation behavior of tobacco mosaic virus on graphite is shown to be consistent with values of lateral friction observed on similar interfaces and the flexural rigidity expected for macromolecular assemblies. The ability to manipulate individual samples broadens the scope of possible studies by providing a means for positioning samples at specific binding sites or predefined measuring devices. The mechanical model provides a framework for interpreting quantitative measurements of virus binding and mechanical properties and for understanding the constraints on the successful, nondestructive AFM manipulation of delicate samples. 相似文献
69.
Gerardo Gonzalez-Valencia † Guillermo I. Perez-Perez Ronald G. Washburn ‡ Martin J. Blaser§ 《Helicobacter》1996,1(1):28-33
Background. Human serum represents an important barrier to the entry of most mucosal organisms into tissues and to the systemic circulation. If at all present, Helicobacter pylori within gastric tissue is rare, and bacteremia for this organism has been described only once.
Methods. To assess the susceptibility of H. pylori to the bactericidal activity present in normal human serum (NHS), we examined 13 H. pylori isolates. To assess the contributions of the classical and alternative complement pathways to killing, we added either C2-deficient or factor B-deficient serum, respectively, to heat-inactivated NHS. Also we assessed the ability of the strains to bind125 I-C3.
Results. After incubation for 60 minutes at 37°C, all 13 H. pylori strains were killed by NHS; heating to 56°C for 30 minutes ablated killing, indicating complement dependence for this phenomenon. In the absence of an antibody source, there was no killing when either an alternative or classical complement pathway source was used. Adding B-deficient serum to heat-inactivated normal human serum did not restore killing, but adding C2-deficient serum permitted partial killing. All of the 13 strains bound125 I-C3. Although the kinetics varied from strain to strain, C3 bound was significantly correlated ( r = 0.61, p = 0.03) with serum susceptibility.
Conclusions. H. pylori are susceptible to complement, alternative pathway activation appears critical, and C3 binding is a major locus of variability. 相似文献
Methods. To assess the susceptibility of H. pylori to the bactericidal activity present in normal human serum (NHS), we examined 13 H. pylori isolates. To assess the contributions of the classical and alternative complement pathways to killing, we added either C2-deficient or factor B-deficient serum, respectively, to heat-inactivated NHS. Also we assessed the ability of the strains to bind
Results. After incubation for 60 minutes at 37°C, all 13 H. pylori strains were killed by NHS; heating to 56°C for 30 minutes ablated killing, indicating complement dependence for this phenomenon. In the absence of an antibody source, there was no killing when either an alternative or classical complement pathway source was used. Adding B-deficient serum to heat-inactivated normal human serum did not restore killing, but adding C2-deficient serum permitted partial killing. All of the 13 strains bound
Conclusions. H. pylori are susceptible to complement, alternative pathway activation appears critical, and C3 binding is a major locus of variability. 相似文献
70.
Aspergillus fumigatus arp1 modulates conidial pigmentation and complement deposition 总被引:1,自引:0,他引:1
Huei-Fung Tsai Ronald G. Washburn Yun C. Chang & K. J. Kwon-Chung 《Molecular microbiology》1997,26(1):175-183
Aspergillus fumigatus is an important pathogen causing invasive pulmonary aspergillosis in immunocompromised patients. The fungus propagates by conidia, which are the infectious structures inhaled by the human host. Opsonophagocytosis is thought to contribute to clearance of the inhaled conidia, a process that is facilitated by complement deposition on conidial surfaces. We now show that conidial colour mutants exhibit significant increases in C3 binding capacity compared with wild type. A reddish-pink mutation that led to enhanced C3 binding was complemented by a cosmid clone. A 3.3 kb DNA fragment from the subsequently rescued cosmid was sufficient to restore the bluish-green conidial pigment. The bluish-green transformant exhibited a level of C3 binding similar to that of the parental strain. A gene, designated arp1 , was responsible for the complementation. Comparison of the genomic and cDNA sequences of arp1 revealed that it has two introns and encodes a putative protein of 168 amino acids. Arp1 is very similar to scytalone dehydratase, an enzyme involved in 1,8-dihydroxynaphthalene-melanin synthesis in Colletotrichum lagenarium and Magnaporthe grisea . Northern hybridization analysis revealed that arp1 is developmentally regulated, being expressed during conidiation. Disruption of arp1 resulted in reddish-pink conidia and increased C3 binding. Our studies suggest that arp1 modulates the bluish-green pigmentation of conidia as well as complement deposition. 相似文献