Search results for "Positive"
showing 10 items of 1875 documents
HEXIM1 Diffusion in the Nucleus Is Regulated by Its Interactions with Both 7SK and P-TEFb
2019
International audience; How nuclear proteins diffuse and find their targets remains a key question in the transcription field. Dynamic proteins in the nucleus are classically subdiffusive and undergo anomalous diffusion, yet the underlying physical mechanisms are still debated. In this study, we explore the contribution of interactions to the generation of anomalous diffusion by the means of fluorescence spectroscopy and simulation. Using interaction-deficient mutants, our study indicates that HEXIM1 interactions with both 7SK RNA and positive transcription elongation factor b are critical for HEXIM1 subdiffusion and thus provides evidence of the effects of protein-RNA interaction on molecu…
Picomolar inhibition of cholera toxin by a pentavalent ganglioside GM1os-calix[5]arene
2013
Cholera toxin (CT), the causative agent of cholera, displays a pentavalent binding domain that targets the oligosaccharide of ganglioside GM1 (GM1os) on the periphery of human abdominal epithelial cells. Here, we report the first GM1os-based CT inhibitor that matches the valency of the CT binding domain (CTB). This pentavalent inhibitor contains five GM1os moieties linked to a calix[5]arene scaffold. When evaluated by an inhibition assay, it achieved a picomolar inhibition potency (IC50 = 450 pM) for CTB. This represents a significant multivalency effect, with a relative inhibitory potency of 100000 compared to a monovalent GM1os derivative, making GM1os-calix[5]arene one of the most potent…
Pore formation by Vibrio cholerae cytolysin follows the same archetypical mode as beta-barrel toxins from gram-positive organisms.
2009
Vibrio cholerae cytolysin (VCC) forms SDS-stable heptameric beta-barrel transmembrane pores in mammalian cell membranes. In contrast to structurally related pore formers of gram-positive organisms, no oligomeric prepore stage of assembly has been detected to date. In the present study, disulfide bonds were engineered to tie the pore-forming amino acid sequence to adjacent domains. In their nonreduced form, mutants were able to bind to rabbit erythrocytes and to native erythrocyte membranes suspended in PBS solution and form SDS-labile oligomers. These remained nonfunctional and represented the long-sought VCC prepores. Disulfide bond reduction in these oligomers released the pore-forming se…
A Positive Definite Advection Scheme for Use in Long Range Transport Models: Extension to Monotonicity
1992
Numerical modeling of atmospheric transport processes requires the solution of the continuity equation for prognostic variables such as momentum, heat, water vapor, liquid water or chemical species of the atmosphere. Although in the literature many advection schemes are known to solve this problem (Lax and Wendroff 1964, Crowley 1968, Tremback et al. 1987, Bott 1989a,b), these algorithms show different disadvantages, which sometimes yield undesirably poor numerical results. For instance, the upstream method is known to produce large numerical diffusion. The higher order versions of the advection schemes of Tremback et al. (1987) are much less diffusive. Unfortunately, the schemes are not po…
Vuorovaikutus osana opettajan arviointiosaamista (VOPA) -toimintamallin vaiheittaiset kuvaukset
2021
Vuorovaikutus osana opettajan arviointiosaamista (VOPA) -toimintamallin vaiheittaiset kuvaukset edesauttavat opetustilanteisiin liittyvän vuorovaikutuksen systemaattista havainnointia ja reflektointia sekä tarjoavat yhteistä sanastoa teeman käsittelyyn. Tarkastelemalla ryhmän vuorovaikutusta eri vaiheiden kautta, tuetaan ajatusta opettajan vuorovaikutusosaamisen kehittyvästä luonteesta. Opettajaopiskelijat ja opettajat voivat hyödyntää vaiheittaisia kuvauksia oman opetuksensa suunnittelussa, toteutuksessa ja reflektoinnissa. Opettajankouluttajat voivat hyödyntää vaiheittaisia kuvauksia opiskelijoiden opetusharjoittelun tutkimusperustaisessa havainnoinnissa ja ohjaamisessa. Learning interact…
Bleomycin Exerts Ambivalent Antitumor Immune Effect by Triggering Both Immunogenic Cell Death and Proliferation of Regulatory T Cells
2013
International audience; Bleomycin (BLM) is an anticancer drug currently used for the treatment of testis cancer and Hodgkin lymphoma. This drug triggers cancer cell death via its capacity to generate radical oxygen species (ROS). However, the putative contribution of anticancer immune responses to the efficacy of BLM has not been evaluated. We make here the observation that BLM induces immunogenic cell death. In particular, BLM is able to induce ROS-mediated reticulum stress and autophagy, which result in the surface exposure of chaperones, including calreticulin and ERp57, and liberation of HMBG1 and ATP. BLM induces anti-tumor immunity which relies on calreticulin, CD8(+) T cells and inte…
Antibiotic susceptibility of cocultures in polymicrobial infections such as peri-implantitis or periodontitis: an in vitro model.
2011
Although polymicrobial infections, such as peri-implantitis or periodontitis, were postulated in the literature to be caused by synergistic effects of bacteria, these effects remain unclear looking at antibiotic susceptibility. The aim of this study is to compare the antibiotic susceptibilities of pure cultures and definite cocultures.Laboratory strains of Aggregatibacter actinomycetemcomitans (Aa) (previously Actinobacillus actinomycetemcomitans), Capnocytophaga ochracea (Co), and Parvimonas micra (Pm) (previously Peptostreptococcus micros) were cultivated under anaerobic conditions, and their susceptibilities to 10 antibiotics (benzylpenicillin G, ampicillin, amoxicillin, ampicillin/sulba…
New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-ox…
2014
The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compounds, enantiomers separation and absolute configuration assignment. Experimental determination of the antibacterial activity of the designed (S)-1-((3-(4-(3-methyl-1,2,4-oxadiazol-5- yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea and (S)-1-((3-(3-fluoro-4-(3-methyl-1,2,4- oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea against multidrug resistan…
Unraveling the T-B tangle in anti-CD20 multiple sclerosis therapy.
2019
Significance Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. CD8+ T cells have been strongly implicated in MS pathogenesis, but it is unclear whether myelin is a CD8+ T cell autoantigenic target in MS. This study demonstrated that while myelin-specific CD8+ T cells are present at similar frequencies in untreated MS patients and healthy subjects, the proportion of memory and CD20-expressing myelin-specific CD8+ T cells was increased in MS patients, suggesting prior antigen encounter. This activated phenotype was reversible as the memory and CD20-expressing populations of certain myelin-specific CD8+ T cells were reduced following anti-CD20 trea…
Association between climate and new daily diagnoses of COVID-19
2020
AbstractBackgroundAlthough evidence is accumulating that climate conditions may positively or negatively influence the scale of coronavirus disease 2019 (COVID-19) outbreaks, uncertainty remains concerning the real impact of climate factors on viral transmission. Methods. The number of new daily cases of COVID-19 diagnosed in Verona (Italy) was retrieved from the official website of Veneto Region, while information on daily weather parameters in the same area was downloaded from IlMeteo website, a renowned Italian technological company specialized in weather forecasts. The search period ranged between March 1 to November 11, 2020. The number of new daily COVID-19 cases and meteorological da…