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排序方式: 共有420条查询结果,搜索用时 15 毫秒
1.
CRISPR-Cas9 Knockin Mice for Genome Editing and Cancer Modeling 总被引:2,自引:0,他引:2
Randall J. Platt Sidi Chen Yang Zhou Michael J. Yim Lukasz Swiech Hannah R. Kempton James E. Dahlman Oren Parnas Thomas M. Eisenhaure Marko Jovanovic Daniel B. Graham Siddharth Jhunjhunwala Matthias Heidenreich Ramnik J. Xavier Robert Langer Daniel G. Anderson Nir Hacohen Aviv Regev Guoping Feng Phillip A. Sharp Feng Zhang 《Cell》2014
2.
Hiwa Majed Tatiana Johnston Celine Kelso Enrico Monachino Slobodan Jergic Nicholas E. Dixon Eleftherios Mylonakis Michael J. Kelso 《Bioorganic & medicinal chemistry letters》2018,28(22):3526-3528
Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of serious hospital-acquired infections and is responsible for significant morbidity and mortality in residential care facilities. New agents against MRSA are needed to combat rising resistance to current antibiotics. We recently reported 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carbodithioate (HMPC) as a new bacteriostatic agent against MRSA that appears to act via a novel mechanism. Here, twenty nine analogs of HMPC were synthesized, their anti-MRSA structure-activity relationships evaluated and selectivity versus human HKC-8 cells determined. Minimum inhibitory concentrations (MIC) ranged from 0.5 to 64?μg/mL and up to 16-fold selectivity was achieved. The 4-carbodithioate function was found to be essential for activity but non-specific reactivity was ruled out as a contributor to antibacterial action. The study supports further work aimed at elucidating the molecular targets of this interesting new class of anti-MRSA agents. 相似文献
3.
4.
Slobodan V Jovanovic Debbie Clements Kent MacLeod 《Free radical biology & medicine》1998,25(9):1044-1048
There is convincing epidemiological and in vitro evidence of chronic oxidative stress in individuals with Down syndrome (DS). These individuals develop Alzheimer like changes in the brain in their 30s and 40s. The incidence of autoimmune diseases and cataracts is significantly increased, and the overall ageing process is accelerated. In vitro studies show that impaired viability of DS neurons may be amended by simple chemical antioxidants, such as vitamin E, BHT and propyl gallate, clearly indicative of oxyl radical involvement. However, because of the lack of in vivo experiments, the role of oxidative stress in DS remains controversial. We report here on the results of the chemical analyses of urine samples of 166 individuals, where DS subjects were matched by their siblings. The levels of 8-hydroxy-2′-deoxyguanosine (2.35 ± 1.69 in DS vs. 1.35 ± 1.04 in controls, P = 0.00011), a biomarker of oxidative damage to DNA, and malondialdehyde (0.255 ± 0.158 in DS vs. 0.204 ± 0.128 in controls, P = 0.033), a biomarker of lipid peroxidation, are significantly elevated in individuals with DS. Dietary influences failed to show any significant correlation with the oxidative stress biomarkers. These results provide direct evidence for increased oxidative stress in individuals with DS. 相似文献
5.
6.
Zoran Stanimirovic Jevrosima Stevanovic Slobodan Jovanovic Marko Andjelkovic 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2005,588(2):152-157
Apitol®, with cymiazole hydrochloride as the active ingredient, is used in bee-keeping against the ectoparasitic mite Varroa destructor. The preparation was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister chromatid exchange, the mitotic index and the cell proliferation index were determined for three experimental concentrations of Apitol® (0.001, 0.01 and 0.1 mg/ml). All concentrations significantly (p < 0.001) increased the mitotic index (MI = 7.35 ± 0.18%, 8.31 ± 0.20% and 12.33 ± 0.25%, respectively), the proliferative index (PI = 1.83 ± 0.01, 1.84 ± 0.01 and 1.88 ± 0.02, respectively) and the frequency of sister chromatid exchange (SCE = 8.19 ± 1.81, 8.78 ± 1.80 and 13.46 ± 1.88, respectively), suggesting that cymiazole hydrochloride has genotoxic potential. 相似文献
7.
Miroslav Novaković Miroslava Stanković Ivan Vučković Nina Todorović Snežana Trifunović Danijela Apostolović Boris Mandić Milan Veljić Petar Marin Vele Tešević Vlatka Vajs Slobodan Milosavljević 《化学与生物多样性》2014,11(6):872-885
Nine diarylheptanoids, 1 – 9 , catechin ( 11 ), and a phenolic glucoside, 10 , were isolated from the bark of green alder (Alnus viridis). Four of the isolated compounds, i.e., 2, 5, 8, 10 , are new. The structures of 1 – 11 were determined on the basis of spectroscopic data. All isolated compounds were evaluated for their in vitro protective effects on chromosome aberrations in peripheral human lymphocytes using cytokinesis‐block micronucleus (CBMN) assay. Almost all of them exerted a pronounced effect of decreasing DNA damage of human lymphocytes, acting stronger than the known synthetic protector amifostine. 相似文献
8.
Jeonghan Lee Michael T. Nelson Kirstin E. Rose Slobodan M. Todorovic 《Molecular neurobiology》2013,48(2):274-280
T-type calcium channels in the dorsal root ganglia (DRG) have a central function in tuning neuronal excitability and are implicated in sensory processing including pain. Previous studies have implicated redox agents in control of T-channel activity; however, the mechanisms involved are not completely understood. Here, we recorded T-type calcium currents from acutely dissociated DRG neurons from young rats and investigated the mechanisms of CaV3.2 T-type channel modulation by S-nitrosothiols (SNOs). We found that extracellular application of S-nitrosoglutathione (GSNO) and S-nitroso-N-acetyl-penicillamine rapidly reduced T-type current amplitudes. GSNO did not affect voltage dependence of steady-state inactivation and macroscopic current kinetics of T-type channels. The effects of GSNO were abolished by pretreatment of the cells with N-ethylmaleimide, an irreversible alkylating agent, but not by pretreatment with 1H-(1,2,4) oxadiazolo (4,3-a) quinoxalin-1-one, a specific soluble guanylyl cyclase inhibitor, suggesting a potential effect of GSNO on putative extracellular thiol residues on T-type channels. Expression of wild-type CaV3.2 channels or a quadruple Cys-Ala mutant in human embryonic kidney cells revealed that Cys residues in repeats I and II on the extracellular face of the channel were required for channel inhibition by GSNO. We propose that SNO-related molecules in vivo may lead to alterations of T-type channel-dependent neuronal excitability in sensory neurons and in the central nervous system in both physiological and pathological conditions such as neuronal ischemia/hypoxia. 相似文献
9.
Chromium uptake bySaccharomyces cerevisiae and isolation of glucose tolerance factor from yeast biomass 总被引:2,自引:0,他引:2
Vlatka Gulan Zetic Vesna Stehlik-Tomas Slobodan Grba Lavoslav Lutilsky Damir Kozlek 《Journal of biosciences》2001,26(2):217-223
Fermentations with yeastSaccharomyces cerevisiae in semiaerobic and in static conditions with the addition of chromic chloride into the used molasses medium were analysed.
It was proved that the addition of optimal amounts of CrCl3 into the basal medium enhanced the kinetics of alcohol fermentations. The addition of 200 mg/l CrCl3 into the medium stimulated both the yeast growth and the ethanol production in all experimental conditions. On the other
hand, the results showed that Cr3+ ions were incorporated into yeast cells during fermentation. Under these conditions the accumulation of Cr3+ ions was performed by yeast cells during the exponential growth phase, and with enriched amounts of 30–45 (μg/gd.m. of cells.
Yeast biomass enriched with chromium ions was extracted with 01 mol/l NH4OH assuming that the extracts had the glucose tolerance factor (GTF). Then the extracts were passed through a gel-filtration
column in order to isolate and purify the GTF. The presence of GTF in the purified fractions was determined by measuring the
absorbance at 260 nm.
It is evident from the obtained results that the added purified fractions enhanced the rates of CO2 production as well as the glucose utilization during alcoholic fermentation. As expected, the enhancement of both rates depended
on the amounts of extracts added to the fermentation substrate. Thus, it is evident that purified extracts contained the GTF
compound, and that Cr3+ ions were bonded to the protein molecule. 相似文献
10.
Jennifer A. Hayward Deborah A. O'Connell R. John Raison Andrew C. Warden Michael H. O'Connor Helen T. Murphy Trevor H. Booth Andrew L. Braid Debbie F. Crawford Alexander Herr Tom Jovanovic Michael L. Poole Di Prestwidge Nat Raisbeck‐Brown Lucas Rye 《Global Change Biology Bioenergy》2015,7(3):497-511
The airline industry has a strong interest in developing sustainable aviation fuels, in order to reduce their exposure to increasing oil prices and cost liability for greenhouse gas emissions. The feasibility and cost of producing sustainable biomass‐based jet fuels at a sufficient scale to materially address these issues is an enormous challenge. This paper builds directly on the biophysical study by H.T. Murphy, D.A. O'Connell, R.J. Raison, A.C. Warden, T.H. Booth, A. Herr, A.L. Braid, D.F. Crawford, J.A. Hayward, T. Javonovic, J.G. McIvor, M.H. O'Connor, M.L. Poole, D. Prestwidge, N. Raisbeck‐Brown & L. Rye, In review, which examined a 25 year scale‐up strategy to produce 5% of projected jet fuel demand in Australia in 2020 (470 mL) in the Fitzroy region of Queensland, Australia. The strategy was based on the use of a mixed ligno‐cellulosic biomass feedstock and assumed, for the sake of exploring and quantifying the scenario, a simplified two‐step conversion process – conversion of biomass to crude bio‐oil within the region, and upgrade to jet fuel at a central Brisbane facility. This paper provides details on the costs of production in this scenario, focusing on two different strategies for biomass utilization, and two types of novel small–medium scale conversion technologies. The cost analyses have taken into account technology learning curves, different economies of scale and key cost sensitivities. The cost of biomass‐based jet fuels is estimated to be between 0.70 and 1.90 The airline industry has a strong interest in developing sustainable aviation fuels, in order to reduce their exposure to increasing oil prices and cost liability for greenhouse gas emissions. The feasibility and cost of producing sustainable biomass‐based jet fuels at a sufficient scale to materially address these issues is an enormous challenge. This paper builds directly on the biophysical study by H.T. Murphy, D.A. O'Connell, R.J. Raison, A.C. Warden, T.H. Booth, A. Herr, A.L. Braid, D.F. Crawford, J.A. Hayward, T. Javonovic, J.G. McIvor, M.H. O'Connor, M.L. Poole, D. Prestwidge, N. Raisbeck‐Brown & L. Rye, In review, which examined a 25 year scale‐up strategy to produce 5% of projected jet fuel demand in Australia in 2020 (470 mL) in the Fitzroy region of Queensland, Australia. The strategy was based on the use of a mixed ligno‐cellulosic biomass feedstock and assumed, for the sake of exploring and quantifying the scenario, a simplified two‐step conversion process – conversion of biomass to crude bio‐oil within the region, and upgrade to jet fuel at a central Brisbane facility. This paper provides details on the costs of production in this scenario, focusing on two different strategies for biomass utilization, and two types of novel small–medium scale conversion technologies. The cost analyses have taken into account technology learning curves, different economies of scale and key cost sensitivities. The cost of biomass‐based jet fuels is estimated to be between 0.70 and 1.90 $ L?1 when the efficiency of conversion of biomass to biocrude and subsequently to aviation fuel is varied by ±10% of published values, with an average value of 1.10 $ L?1. This is within the range of the projected 2035 conventional jet fuel price of 1.50 $ L?1. Therefore, biomass‐based jet fuel has the potential to contribute to supply of Australia's jet fuel needs in the future. 相似文献