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排序方式: 共有156条查询结果,搜索用时 15 毫秒
1.
Eugene D. Day Don D. Mickey Lewis C. Rigsbee Hans Meier 《Developmental neurobiology》1972,3(4):325-338
Zonal centrifuge and flotation–fractionation profile analysis of neonatal mouse brain homogenates in iso-osmotic Ficoll–sucrose density–gradients demonstrates the presence of four light density fractions. In msd neurological mutant mice with a myelin-synthesizing deficiency syndrome, the bands appear to be relatively normal until after the 10th day of postnatal brain development. With the onset of visible neurological symptoms after the 11th day, the four density bands begin to disappear from the zonal profiles and are all but absent at the time of death at about the 21st postnatal day. In normal littermates of the mutants, the bands persist with age and intensify. Although their identities remain unknown, the top three identify by their density with adult myelin and the fourth with the lighter of two adult synaptosome fractions. Mixtures of brain homogenates between mutant and normal littermates give rise to zonal and banding profiles intermediate between the separate profiles but somewhat less than their average in intensity. 相似文献
2.
Thomas Horn Brian D. Warner Joyce A. Running Kristi Downing Jennifer Clyne Mickey S. Urdea 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):875-877
Abstract Branched oligonucleotides have been synthesized using phosphoramidite derivatives with two protected hydroxyl functions. These molecules are employed for a label amplification strategy used in DNA probe diagnostics. 相似文献
3.
Marta Rodriguez-Garcia Nabanita Biswas Mickey V. Patel Fiona D. Barr Sarah G. Crist Christina Ochsenbauer John V. Fahey Charles R. Wira 《PloS one》2013,8(4)
The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described to influence HIV infection in epidemiological studies and regulate different immune responses that may affect HIV infection, the direct role that female sex hormones play in altering the susceptibility of target cells to HIV-infection is largely unknown. Here we evaluated the direct effect of 17-β-estradiol (E2) and ethinyl estradiol (EE) in HIV-infection of CD4+ T-cells and macrophages. Purified CD4+ T-cells and monocyte-derived macrophages were generated in vitro from peripheral blood and infected with R5 and X4 viruses. Treatment of CD4+ T-cells and macrophages with E2 prior to viral challenge reduced their susceptibility to HIV infection in a dose-dependent manner. Addition of E2 2 h after viral challenge however did not result in reduced infection. In contrast, EE reduced infection in macrophages to a lesser extent than E2 and had no effect on CD4+ T-cell infection. Reduction of HIV-infection induced by E2 in CD4+ T-cells was not due to CCR5 down-regulation, but was an entry-mediated mechanism since infection with VSV-G pseudotyped HIV was not modified by E2. In macrophages, despite the lack of an effect of E2 on CCR5 expression, E2–treatment reduced viral entry 2 h after challenge and increased MIP-1β secretion. These results demonstrate the direct effect of E2 on susceptibility of HIV-target cells to infection and indicate that inhibition of target cell infection involves cell-entry related mechanisms. 相似文献
4.
5.
Wilson Lim Bertrand Nyuykonge Kimberly Eadie Mickey Konings Juli Smeets Ahmed Fahal Alexandro Bonifaz Matthew Todd Benjamin Perry Kirandeep Samby Jeremy Burrows Annelies Verbon Wendy van de Sande 《PLoS neglected tropical diseases》2022,16(2)
Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common causative agents produce black grains and belong to the fungal orders Sordariales and Pleosporales. The current antifungal agents used to treat eumycetoma are itraconazole or terbinafine, however, their cure rates are low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from the Pandemic Response Box against common eumycetoma causative agents as part of the Open Source Mycetoma initiative (MycetOS). 26 compounds were able to inhibit the growth of Madurella mycetomatis, Madurella pseudomycetomatis and Madurella tropicana, 26 compounds inhibited Falciformispora senegalensis and seven inhibited growth of Medicopsis romeroi in vitro. Four compounds were able to inhibit the growth of all five species of fungi tested. They are the benzimidazole carbamates fenbendazole and carbendazim, the 8-aminoquinolone derivative tafenoquine and MMV1578570. Minimal inhibitory concentrations were then determined for the compounds active against M. mycetomatis. Compounds showing potent activity in vitro were further tested in vivo. Fenbendazole, MMV1782387, ravuconazole and olorofim were able to significantly prolong Galleria mellonella larvae survival and are promising candidates to explore in mycetoma treatment and to also serve as scaffolds for medicinal chemistry optimisation in the search for novel antifungals to treat eumycetoma. 相似文献
6.
Evaluation of procedures for amplification of small-size samples for hybridization on microarrays 总被引:3,自引:0,他引:3
Various approaches have been developed for the preparation of samples for gene expression monitoring. For Affymetrix chips, a standard protocol is widely used; however, this is inefficient for small samples such as laser capture microdissections. Several amplification procedures for such samples already exist, and our goal was to test two of them: the first is based on random PCR amplification, and the second, linear amplification, involves performing the standard protocol twice. We analyzed a dilution of a commercially available mouse brain total RNA preparation and microdissections from mouse hippocampus and striatum. We evaluated the quality of microarray data by analyzing several chip parameters and performing multiple comparisons. At the biological level, brain microdissections prepared with either method gave similar expression results. At the technical level, analysis of the commercial sample showed that random PCR amplification is more reproducible, requires smaller RNA input, and generates cRNA of higher quality than linear amplification. 相似文献
7.
In this study, we show the changes in the wall of the middle cerebral artery of a subject who suffered multiple system atrophy with autonomic failure. An electron-immunocytochemical approach was employed to reveal the presence of endothelin-1. Our results demonstrate the presence of immunoreactive endothelin-1 in the endothelial cells of the intima, vascular smooth muscle cells and macrophages of the media and neointima, and perivascular nerves/axons varicosities at the adventitial-medial border of the artery. It is concluded that endothelin-1 may, therefore, play a number of roles within diseased cerebral artery. The finding of endothelin-1-positive varicosities of autonomic innervation to this artery suggests an influence of neural endothelin on vascular smooth muscle in multiple system atrophy with autonomic failure. However, the presence of features such as neointima formation, wall irregularities and foam cells suggest the coexistence of atherosclerosis. 相似文献
8.
Regulation of light-dependent Gqalpha translocation and morphological changes in fly photoreceptors 总被引:5,自引:0,他引:5
Kosloff M Elia N Joel-Almagor T Timberg R Zars TD Hyde DR Minke B Selinger Z 《The EMBO journal》2003,22(3):459-468
Heterotrimeric G-proteins relay signals between membrane-bound receptors and downstream effectors. Little is known, however, about the regulation of Galpha subunit localization within the natural endogenous environment of a specialized signaling cell. Here we show, using live Drosophila flies, that light causes massive and reversible translocation of the visual Gqalpha to the cytosol, associated with marked architectural changes in the signaling compartment. Molecular genetic dissection together with detailed kinetic analysis enabled us to characterize the translocation cycle and to unravel how signaling molecules that interact with Gqalpha affect these processes. Epistatic analysis showed that Gqalpha is necessary but not sufficient to bring about the morphological changes in the signaling organelle. Furthermore, mutant analysis indicated that Gqbeta is essential for targeting of Gqalpha to the membrane and suggested that Gqbeta is also needed for efficient activation of Gqalpha by rhodopsin. Our results support the 'two-signal model' hypothesis for membrane targeting in a living organism and characterize the regulation of both the activity-dependent Gq localization and the cellular architectural changes in Drosophila photoreceptors. 相似文献
9.
Wang YE Park A Lake M Pentecost M Torres B Yun TE Wolf MC Holbrook MR Freiberg AN Lee B 《PLoS pathogens》2010,6(11):e1001186
Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. Matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. Curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associated with this nuclear localization remains obscure. We report here that the nuclear-cytoplasmic trafficking of the Nipah virus matrix (NiV-M) protein and associated post-translational modification play a critical role in matrix-mediated virus budding. Nipah virus (NiV) is a highly pathogenic emerging paramyxovirus that causes fatal encephalitis in humans, and is classified as a Biosafety Level 4 (BSL4) pathogen. During live NiV infection, NiV-M was first detected in the nucleus at early stages of infection before subsequent localization to the cytoplasm and the plasma membrane. Mutations in the putative bipartite nuclear localization signal (NLS) and the leucine-rich nuclear export signal (NES) found in NiV-M impaired its nuclear-cytoplasmic trafficking and also abolished NiV-M budding. A highly conserved lysine residue in the NLS served dual functions: its positive charge was important for mediating nuclear import, and it was also a potential site for monoubiquitination which regulates nuclear export of the protein. Concordantly, overexpression of ubiquitin enhanced NiV-M budding whereas depletion of free ubiquitin in the cell (via proteasome inhibitors) resulted in nuclear retention of NiV-M and blocked viral budding. Live Nipah virus budding was exquisitely sensitive to proteasome inhibitors: bortezomib, an FDA-approved proteasome inhibitor for treating multiple myeloma, reduced viral titers with an IC(50) of 2.7 nM, which is 100-fold less than the peak plasma concentration that can be achieved in humans. This opens up the possibility of using an "off-the-shelf" therapeutic against acute NiV infection. 相似文献
10.
Mickey L. Wells Sandra O. Williams Ronald A. Sanftleben Samuel B. Balik Barry A. Evans 《AAPS PharmSciTech》2010,11(1):113-119
The Food and Drug Administration (FDA) approved the New Drug Application for Wellbutrin sustained release (SR) 100 mg tablets
on October 4, 1996. However, by 1998, the FDA expressed concern about the stability of this drug product based on an increase
in the dissolution profile on storage. Data submitted in the annual report showed that this drug product could not meet the
expiry of 18 months at the International Committee on Harmonization storage condition of 25°C/60% relative humidity. The FDA
mandated a 12-month expiry and GlaxoWellcome tightened this further by instituting an expiry of 9 months. The FDA also requested
a long-term solution to the stability of Wellbutrin SR 100 mg tablets. Investigations via colloidal solutions revealed that
the dissolution rate increase on storage occurred due to acid hydrolysis of the release controlling polymer. This drug product
was successfully reformulated by slowing the initial dissolution rate and having an increased ratio of release controlling
polymer to acid stabilizer. The reformulation used the same ingredients and manufacturing unit processes as the original formulation.
The reformulated drug product was approved by the FDA on October 11, 2000 with an 18-month shelf-life. The shelf-life was
extended to 36 months in an annual update to the FDA on December 1, 2005. 相似文献