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981.
Arbuckle W Baugh M Belshaw S Bennett DJ Bruin J Cai J Cameron KS Claxton C Dempster M Everett K Fradera X Hamilton W Jones PS Kinghorn E Long C Martin I Robinson J Westwood P 《Bioorganic & medicinal chemistry letters》2011,21(3):932-935
Based on the theoretical understanding of the in vivo lysosomotropism, by adjusting the pka of basic nitrogen containing cathepsin S inhibitors, a set of compounds with pka 6-8 were identified to have excellent cell based Lip10 activity, yet avoiding undesired sequestration in spleen. 相似文献
982.
For a monolayer sheet to migrate cohesively, it has long been suspected that each constituent cell must exert physical forces not only upon its extracellular matrix but also upon neighboring cells. The first comprehensive maps of these distinct force components reveal an unexpected physical picture. Rather than showing smooth and systematic variation within the monolayer, the distribution of physical forces is dominated by heterogeneity, both in space and in time, which emerges spontaneously, propagates over great distances, and cooperates over the span of many cell bodies. To explain the severe ruggedness of this force landscape and its role in collective cell guidance, the well known mechanisms of chemotaxis, durotaxis, haptotaxis are clearly insufficient. In a broad range of epithelial and endothelial cell sheets, collective cell migration is governed instead by a newly discovered emergent mechanism of innately collective cell guidance - plithotaxis. 相似文献
983.
Burchak ON Pihive EL Maigre L Guinchard X Bouhours P Jolivalt C Schneider D Maurin M Giglione C Meinnel T Paris JM Denis JN 《Bioorganic & medicinal chemistry》2011,19(10):3204-3215
A collection of 3-substituted indole derivatives was prepared using nucleophilic addition of indoles to nitrones. The compounds were then tested for their antibacterial activity against almost thirty bacterial strains representative of common human pathogens. Two types of indolic molecules inhibit the growth of Staphylococcus aureus, including MRSA and VISA strains, with MIC values ranging from 8 to 16 mg/L. 相似文献
984.
Lugari A Breuer S Coursindel T Opi S Restouin A Shi X Nazabal A Torbett BE Martinez J Collette Y Parrot I Arold ST Morelli X 《Bioorganic & medicinal chemistry》2011,19(24):7401-7406
The HIV-1 auxiliary protein Nef is required for the onset and progression of AIDS in HIV-1-infected persons. Here, we have deciphered the mode of action of a second-generation inhibitor of Nef, DLC27-14, presenting a competitive IC(50) of ~16 μM measured by MALDI-TOF experiments. Thermal protein denaturation experiments revealed a negative effect on stability of Nef in the presence of a saturating concentration of the inhibitor. The destabilizing action of DLC27-14 was confirmed by a HIV protease-based experiment, in which the protease sensitivity of DLC27-14-bound Nef was three times as high as that of apo Nef. The only compatible docking modes of action for DLC27-14 suggest that DLC27-14 promotes an opening of two α-helices that would destabilize the Nef core domain. DLC27-14 thus acts as a specific protein disorder catalyzer that destabilizes the folded conformation of the protein. Our results open novel avenues toward the development of next-generation Nef inhibitors. 相似文献
985.
Aicardi syndrome is a genetic disorder characterized by the triad of infantile spasm in flexion, callosal agenesis and ocular abnormalities (chorioretinal lacunae, coloboma of optic disc). We report a typical case of Aicardi syndrome with all the classical features. 相似文献
986.
987.
Ariella Alperovitch‐Lavy Itai Sharon Forest Rohwer Eva‐Mari Aro Fabian Glaser Ron Milo Nathan Nelson Oded Béjà 《Environmental microbiology》2011,13(1):24-32
Cyanobacteria play a key role in marine photosynthesis, which contributes to the global carbon cycle and to the world oxygen supply. Genes encoding the photosystem‐II (PSII) reaction centre are found in many cyanophage genomes, and it was suggested that the horizontal transfer of these genes might be involved in increasing phage fitness. Recently, evidence for the existence of phages carrying Photosystem‐I (PSI) genes was also reported. Here, using a combination of different marine metagenomic datasets and a unique crossing of the datasets, we now describe the finding of phages that, as in plants and cyanobacteria, contain both PSII and PSI genes. In addition, these phages also contain NADH dehydrogenase genes. The presence of modified PSII and PSI genes in the same viral entities in combination with electron transfer proteins like NAD(P)H dehydrogenase (NDH‐1) strongly points to a role in perturbation of the cyanobacterial host photosynthetic electron flow. We therefore suggest that, depending on the physiological condition of the infected cyanobacterial host, the viruses may use different options to maximize survival. The modified PSI may alternate between functioning with PSII in linear electron transfer and contributing to the production of both NADPH and ATP or functioning independently of PSII in cyclic mode via the NDH‐1 complex and thus producing only ATP. 相似文献
988.
Blocking IL-1 in patients with knee osteoarthritis is an attractive strategy. Cohen and colleagues report a randomised, placebo-controlled,
multiple-dose trial using a monoclonal antibody blocking IL-1 type 1 receptor. They failed to show any positive results in
terms of evolution of pain for up to 12 weeks, in line with the former trials using intraarticular injections of IL-1 receptor
antagonist. A trend was observed, however, in a subgroup of patients with high level of pain at baseline. Although these data
may suggest cessation of IL-1 therapy in osteoarthritis, other methods such as limited intraarticular anti-IL-1 delivery should
still be considered. 相似文献
989.
Milena R. Martelli Fran?ois Brygo Philippe Delaporte Xavier Rouau C??cile Barron 《Food biophysics》2011,6(4):433-439
During the wheat milling process, the bran fractionation is related to its mechanical properties, which are measured using
tensile tests on hand-isolated tissues. However, the dissection of wheat tissues implies a soaking stage in water that can
modify tissue properties. New methodologies are required to evaluate wheat tissue properties directly on native grains. The
aim of this work was to estimate wheat grain tissue cohesion by the ionization effectiveness via laser-induced breakdown spectroscopy
(LIBS) technique. Isolated bran tissues and wheat grains were submitted to LIBS analysis using a pulsed argon fluoride (193 nm,
15 ns, 1 Hz, 2 J cm−2) excimer laser and a compact optic fiber spectrometer (HR2000). The first approach was to correlate the ratios of ionic to
atomic emission lines (MgII/MgI and CaII/CaI) of isolated tissues to their mechanical measurements. The energy needed to rupture
the tissue was correlated to MgII/MgI (R
2 = 0.72). Secondly, native grains were irradiated and chemometrics was applied to discriminate tissue spectra. The aleurone
layer isolated after the soaking step presented a higher MgII/MgI than the aleurone layer from native grains, indicating a
possible water effect on the tissue cohesion. In conclusion, the LIBS technique may be a potential method for rapid structural
analysis of vegetal material allowing wheat population screening of both compositional and mechanical properties. 相似文献
990.