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231.
232.
Fischer DS Chander SK Woo LW Fenton JC Purohit A Reed MJ Potter BV 《The Journal of steroid biochemistry and molecular biology》2003,84(2-3):343-349
In pursuit of novel steroid sulfatase (STS) inhibitors devoid of estrogenicity, several D-ring modified steroid derivatives were synthesised. In vitro evaluation of the compounds identified two highly potent inhibitors, 4a and 4b, which were 18 times more active than estrone-3-O-sulfamate (EMATE), both having IC(50) values of ca. 1nM. These 16,17-seco-estra-1,3,5(10)-triene-16,17-imide derivatives were synthesised from estrone, via the intermediate 1, which was easily alkylated, deprotected and sulfamoylated affording the final compounds in high yields. In order to assess their biological profile, the selected inhibitors were tested for their in vivo inhibitory potency and estrogenicity in ovariectomised rats. After an oral dose of 10mg/kg per day for 5 days, 4a and 4b were found to inhibit rat liver steroid sulfatase by 99%. They were also devoid of estrogenic activity in the uterine weight gain assay, indicating that these two leads have therapeutic potential for the treatment of hormone-dependent breast cancer. 相似文献
233.
Filaments under distributed loads are common in biological systems. In this paper, we study the thermo-mechanical properties of an extensible thermally fluctuating elastic filament under distributed forces. The ground state of the filament is solved first, followed by an investigation of the thermal fluctuations around the ground state. We first consider a special case where the tangential component of the distributed force tau is uniform along the filament. For the force-extension relation in this case, we show that the filament is equivalent to one under end-to-end applied force F = tauL0/2 where L0 is the length of the filament. To study the thermal fluctuations under more general distributed loadings, the filament is first discretized into segments, and its energy is approximated up to quadratic order. Then the partition function of the discretized filament, or chain, is evaluated using multi-dimensional Gaussian integrals, from which free energy and other properties of the filament are derived. We show that a filament under distributed loads suffers larger thermal fluctuations than one with the end loads of the same magnitude. We also show that our results for a discretized filament agree with continuum theory for a continuous rod. Finally, we give some applications of our ideas to the stretching and fluctuation of DNA in non-uniform microfluidic channels. 相似文献
234.
Patrick Martin Benjamin AS Van Mooy Abigail Heithoff Sonya T Dyhrman 《The ISME journal》2011,5(6):1057-1060
In low-phosphorus (P) marine systems, phytoplankton replace membrane phospholipids with non-phosphorus lipids, but it is not known how rapidly this substitution occurs. Here, when cells of the model diatom Thalassiosira pseudonana were transferred from P-replete medium to P-free medium, the phospholipid content of the cells rapidly declined within 48 h from 45±0.9 to 21±4.5% of the total membrane lipids; the difference was made up by non-phosphorus lipids. Conversely, when P-limited T. pseudonana were resupplied with P, cells reduced the percentage of their total membrane lipids contributed by a non-phosphorus lipid from 43±1.5 to 7.3±0.9% within 24 h, whereas the contribution by phospholipids rose from 2.2±0.1 to 44±3%. This dynamic phospholipid reservoir contained sufficient P to synthesize multiple haploid genomes, suggesting that phospholipid turnover could be an important P source for cells. Field observations of phytoplankton lipid content may thus reflect short-term changes in P supply and cellular physiology, rather than simply long-term adjustment to the environment. 相似文献
235.
We measure the thermal fluctuation of the internal segments of a piece of DNA confined in a nanochannel about 50-100 nm wide. This local thermodynamic property is key to accurate measurement of distances in genomic analysis. For DNA in ~100 nm channels, we observe a critical length scale ~10 m for the mean extension of internal segments, below which the de Gennes' theory describes the fluctuations with no fitting parameters, and above which the fluctuation data falls into Odijk's deflection theory regime. By analyzing the probability distributions of the extensions of the internal segments, we infer that folded structures of length 150-250 nm, separated by ~10 m exist in the confined DNA during the transition between the two regimes. For ~50 nm channels we find that the fluctuation is significantly reduced since the Odijk regime appears earlier. This is critical for genomic analysis. We further propose a more detailed theory based on small fluctuations and incorporating the effects of confinement to explicitly calculate the statistical properties of the internal fluctuations. Our theory is applicable to polymers with heterogeneous mechanical properties confined in non-uniform channels. We show that existing theories for the end-to-end extension/fluctuation of polymers can be used to study the internal fluctuations only when the contour length of the polymer is many times larger than its persistence length. Finally, our results suggest that introducing nicks in the DNA will not change its fluctuation behavior when the nick density is below 1 nick per kbp DNA. 相似文献
236.
Lamin A/C proteins are the major components of a thin proteinaceous filamentous meshwork, the lamina, that underlies the inner nuclear membrane. A few specific mutations in the lamin A/C gene cause a disease with remarkably different clinical features: FPLD, or familial partial lipodystrophy (Dunnigan-type), which mainly affects adipose tissue. Lamin A/C mutant R482W is the key variant that causes FPLD. Biomolecular interaction and molecular dynamics (MD) simulation analysis were performed to understand dynamic behavior of native and mutant structures at atomic level. Mutant lamin A/C (R482W) showed more interaction with its biological partners due to its expansion of interaction surface and flexible nature of binding residues than native lamin A/C. MD simulation clearly indicates that the flexibility of interacting residues of mutant are mainly due to less involvement in formation of inter and intramolecular hydrogen bonds. Our analysis of native and Mutant lamin A/C clearly shows that the structural and functional consequences of the mutation R482W causes FPLD. Because of the pivotal role of lamin A/C in maintaining dynamics of nuclear function, these differences likely contribute to or represent novel mechanisms in laminopathy development. 相似文献
237.
The identification of pathogenic bacteria in water is important for addressing preventive and treatment issues regarding health and safety. A highly sensitive and specific solid-phase sandwich ELISA procedure was developed for the detection of typhoid causing extremely lethal water borne pathogen Salmonella typhi (S. typhi) on modified isopore polycarbonate (PC) black membranes. PC membranes were chemically derivatized to generate amino groups on the surface maintaining their pysico-optico properties. Surface modified PC membranes were characterized by ATR-FTIR spectrometer, goniometer and scanning electron microscope. Polyclonal somatic 'O' type antibodies (Abs) against whole cell S. typhi were immobilized on them by following the amine glutaraldehyde chemistry. Antibody immobilized membranes captured S. typhi from buffer solution and this complex was detected colourimetrically using HRP labelled S. typhi Ab. A detection limit of 2×10(3)cells/ml of bacteria was achieved with the modified PC membranes without any pre-enrichment step as against 10(6)-10(7)CFU/ml of bacteria by typical ELISA method. The assay was demonstrated to be specific for the target bacteria when compared with other cross-reactant water borne pathogens. The intra- and inter-assay precision for 10(4) and 10(5)cells/ml was 5.3-7.4 and 10.3-19.7% respectively. The developed immunoassay for the detection of S. typhi is simple, easy to handle, sensitive specific, reproducible and cost effective in comparison with the commercially existing immunochromatographic assays. 相似文献
238.
Centrosomes are the key regulating element of cell cycle progression. Aberrations in their functional mechanism leads to several cancer related disorders. Although genomic studies in the field of centrosome have been extensively carried out, with the lack of structural conformation, the proteomic analysis of pathological genetic mutation is still a challenging task. Several computational algorithms and high range force fields are used to design the 3D structure conformation of proteins, which has now become the leading platform for in-silico drug discovery approaches. Application of these highly efficient platforms in centrosomics studies will be a novel approach to develop an efficient drug therapy for the treatment of their dysfunction disorders. 相似文献
239.
HUGO M. RAMÍREZ‐TOBÍAS CECILIA B. PEÑA‐VALDIVIA J. ROGELIO AGUIRRE R. J. ANTONIO REYES‐AGÜERO ADRIANA B. SÁNCHEZ‐URDANETA SALVADOR VALLE G. 《Plant Species Biology》2012,27(2):124-137
The genetic diversity of Agave plants is threatened by clonal commercial reproduction and climatic change. Sexual reproduction is uncommon and research on seed germination is scarce. The present study evaluated the seed germination of Agave lechuguilla, Agave striata, Agave americana var. marginata, Agave asperrima, Agave cupreata, Agave duranguesis, Agave angustifolia ssp. tequilana and Agave salmiana at constant temperatures (10, 15, 20, 25, 30, 35 and 40°C). Initial imbibition (after the first 12 h) was significantly variable among species, positively correlated with seed weight (r = 0.6560, P < 0.001) and increased with temperature (from 35% at 10°C to 66% at 40°C). Temperature affected maximum imbibition (83–150%) for A. asperrima, A. lechuguilla, A. salmiana and A. striata; other species averaged 110%. Most germination kinetics best fitted a logistic model, whereas only a few treatments fit a Weibull model. The time to germination onset diminished (P < 0.05) from 125–173 h at 15°C to 68–84 h at 25°C, and then ascended to 84–196 h at 35°C. The mean germination rate and seed germination percentage after 312 h peaked at 25°C (0.50–0.95% seeds/h and 85–99%, respectively) and fell (P < 0.05) to near zero at 10 and 40°C. Temperatures of 10, 35 and 40°C were partially lethal to A. asperrima, A. duranguensis and A. salmiana seeds. The time to germination onset, seed germination percentage after 312 h and mean germination rate are best described by a Gaussian distribution, with its optimum at approximately 25°C. Thus, optimum temperatures are related to the ecological characteristics of each species area. 相似文献