270 research outputs found
Aurora kinase-C-T191D is constitutively active mutant
<p>Abstract</p> <p>Background</p> <p>Aurora kinases (Aurora-A, B and C) belong to a family of conserved serine/threonine kinases which are key regulators of cell cycle progression. Aurora-A and Aurora-B are expressed in somatic cells and involved in cell cycle regulation while aurora-C is meiotic chromosome passenger protein. As Aurora kinase C is rarely expressed in normal somatic cells and has been found over expressed in many cancer lines. It is suggested that Aurora-C-T191D is not hyperactive mutant.</p> <p>Result</p> <p>Aurora-C-T191D variant form was investigated and compared with wild type. The overexpression of Aurora-C-T191D was observed that it behaves like Aurora-C wild type (aurC-WT). Both Aurora-C-T191D and aurC-WT induce abnormal cell division resulting in centrosome amplification and multinucleation in transiently transfected cells as well as in stable cell lines. Similarly, Aurora-C-T191D and aurC-WT formed foci of colonies when grown on soft agar, indicating that a gain of Aurora-C activity is sufficient to transform cells. Furthermore, we reported that NIH-3 T3 stable cell lines overexpressing Aurora-C-T191D and its wild type partner induced tumour formation when injected into nude mice, demonstrating the oncogenic activity of enzymatically active Aurora kinase C. Interestingly enough tumour aggressiveness was positively correlated with the rate of kinase activity, making Aurora-C a potential anti-cancer therapeutic target.</p> <p>Conclusion</p> <p>These findings proved that Aurora C-T191D is not hyperactive but is constitutively active mutant.</p
Salinity effects on photosynthetic pigments, proline, biomass and nitric oxide in Salvinia auriculata Aubl.
Suboptimal Activation of Antigen-Specific CD4+ Effector Cells Enables Persistence of M. tuberculosis In Vivo
Adaptive immunity to Mycobacterium tuberculosis controls
progressive bacterial growth and disease but does not eradicate infection. Among
CD4+ T cells in the lungs of M.
tuberculosis-infected mice, we observed that few produced IFN-Îł
without ex vivo restimulation. Therefore, we hypothesized that one mechanism
whereby M. tuberculosis avoids elimination is by limiting
activation of CD4+ effector T cells at the site of infection in
the lungs. To test this hypothesis, we adoptively transferred Th1-polarized
CD4+ effector T cells specific for M.
tuberculosis Ag85B peptide 25 (P25TCRTh1 cells), which trafficked
to the lungs of infected mice and exhibited antigen-dependent IFN-Îł
production. During the early phase of infection, âŒ10% of P25TCRTh1
cells produced IFN-Îł in vivo; this declined to <1% as infection
progressed to chronic phase. Bacterial downregulation of fbpB
(encoding Ag85B) contributed to the decrease in effector T cell activation in
the lungs, as a strain of M. tuberculosis engineered to express
fbpB in the chronic phase stimulated P25TCRTh1 effector
cells at higher frequencies in vivo, and this resulted in CD4+ T
cell-dependent reduction of lung bacterial burdens and prolonged survival of
mice. Administration of synthetic peptide 25 alone also increased activation of
endogenous antigen-specific effector cells and reduced the bacterial burden in
the lungs without apparent host toxicity. These results indicate that
CD4+ effector T cells are activated at suboptimal
frequencies in tuberculosis, and that increasing effector T cell activation in
the lungs by providing one or more epitope peptides may be a successful strategy
for TB therapy
Identification and characterization of antibacterial compound(s) of cockroaches (Periplaneta americana)
Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic E. coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analyzed. Among hundreds of compounds, only a few homologous compounds were identified that contained isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole containing analogs, sulfonamides, furanones, flavanones, and known to possess broad-spectrum antimicrobial properties, and possess anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs
Putting the Lasts First: The Case for Community-Focused and Peer-Managed NGO Accountability Mechanisms
Galaxy Clusters Associated with Short GRBs. II. Predictions for the Rate of Short GRBs in Field and Cluster Early-Type Galaxies
We determine the relative rates of short GRBs in cluster and field early-type
galaxies as a function of the age probability distribution of their
progenitors, P(\tau) \propto \tau^n. This analysis takes advantage of the
difference in the growth of stellar mass in clusters and in the field, which
arises from the combined effects of the galaxy stellar mass function, the
early-type fraction, and the dependence of star formation history on mass and
environment. This approach complements the use of the early- to late-type host
galaxy ratio, with the added benefit that the star formation histories of
early-type galaxies are simpler than those of late-type galaxies, and any
systematic differences between progenitors in early- and late-type galaxies are
removed. We find that the ratio varies from R(cluster)/R(field) ~ 0.5 for n =
-2 to ~ 3 for n = 2. Current observations indicate a ratio of about 2,
corresponding to n ~ 0 - 1. This is similar to the value inferred from the
ratio of short GRBs in early- and late-type hosts, but it differs from the
value of n ~ -1 for NS binaries in the Milky Way. We stress that this general
approach can be easily modified with improved knowledge of the effects of
environment and mass on the build-up of stellar mass, as well as the effect of
globular clusters on the short GRB rate. It can also be used to assess the age
distribution of Type Ia supernova progenitors.Comment: ApJ accepted versio
- âŠ