90 research outputs found
Lipoarabinomannan from Mycobacterium tuberculosis promotes macrophage survival by phosphorylating bad through a phosphatidylinositol 3-kinase/Akt pathway
Efforts in prevention and control of tuberculosis suffer from the lack of detailed knowledge of the mechanisms used by pathogenic mycobacteria for survival within host cell macrophages. The exploitation of host cell signaling pathways to the benefit of the pathogen is a phenomenon that deserves to be looked into in detail. We have tested the hypothesis that lipoarabinomannan (LAM) from the virulent species of Mycobacterium tuberculosis possesses the ability to modulate signaling pathways linked to cell survival. The Bcl-2 family member Bad is a proapoptotic protein. Phosphorylation of Bad promotes cell survival in many cell types. We demonstrate that man-LAM stimulates Bad phosphorylation in a phosphatidylinositol 3-kinase (PI-3K)-dependent pathway in THP-1 cells. Man-LAM activated PI-3K. LAM-stimulated phosphorylation of Bad was abrogated in cells transfected with a dominant-negative mutant of PI-3K (Δp85), indicating that activation of PI-3K is sufficient to trigger phosphorylation of Bad by LAM. Since phosphorylation of Bad occurred at serine 136, the target of the serine/threonine kinase Akt, the effect of LAM on Akt kinase activity was tested. Man-LAM could activate Akt as evidenced from phosphorylation of Akt at Thr308 and by the phosphorylation of the exogenous substrate histone 2B. Akt activation was abrogated in cells transfected with Δp85. The phosphorylation of Bad by man-LAM was abrogated in cells transfected with a kinase-dead mutant of Akt. These results establish that LAM-mediated Bad phosphorylation occurs in a PI-3K/Akt-dependent manner. It is therefore the first demonstration of the ability of a mycobacterial virulence factor to up-regulate a signaling pathway involved in cell survival. This is likely to be one of a number of virulence-associated mechanisms by which bacilli control host cell apoptosis
Study of giant dipole resonance in hot rotating light mass nucleus P-31
An exclusive systematic study of the giant dipole resonance (GDR) parameters has been performed in very light mass nucleus (31)Pin the temperature range of similar to 0.8-2.1 MeV and average angular momentum of similar to 11-16 (h) over bar. The high-energy gamma rays from the decay of the GDR, evaporated neutrons and gamma-ray multiplicities have been measured. The angular distribution of high-energy gamma rays has also been measured at E-beam= 42 MeV. The GDR parameters, nuclear level density parameter and nuclear temperature were precisely determined by simultaneous statistical model analysis of high-energy gamma ray and evaporated neutron spectra. It is observed that the measured width remains roughly constant up to a temperature of similar to 1.6 MeV. Moreover, the thermal pairing plays no role in describing the GDR width in this open-shell light nucleus at the above-mentioned temperatures and angular momenta. The present measurements provide an excellent platform to extend the applicability of the existing theoretical models down to the very light mass nuclei.The PDMrelated calculations were performed on the RIKEN HOKUSAIGreatWave System and supported by the Vietnam National Foundation for Science and Technology Development under the Grant
No. 103.04-2017.69
Discussion on a possible neutrino detector located in India
We have identified some important and worthwhile physics opportunitites with
a possible neutrino detector located in India. Particular emphasis is placed on
the geographical advantage with a stress on the complimentary aspects with
respect to other neutrino detectors already in operation.Comment: 9 pages; arXiv copy of published proceedings contributio
UDP-Glucose Dehydrogenase from Capra Hircus Liver: Purification, Partial Characterization and Evaluation as a Coupling Enzyme in UDP-Galactose 4-Epimerase Assay
UDP-glucose dehydrogenase from Capra hircus has been purified to homogeneity by salt fractionations,
heat treatment and chromatographic steps. It is a homohexamer of about 300 kDa. Though the basic physical
and enzymatic properties of the caprine enzyme are comparable to those of the beef liver enzyme, it
has lower energy of activation and different entropy and enthalpy for the transition state during catalysis.
The caprine enzyme can act suitably as an auxiliary enzyme in the coupled assay system for UDP-galactose
4-epimeras
Factor V Activator from Daboia russelli russelli Venom Destabilizes �-Amyloid Aggregate, the Hallmark of Alzheimer Disease*
Formation of plaque by fibrils of �-amyloid (A�) peptide in
the brain is the characteristic feature of Alzheimer disease (AD).
Inhibition of the process of aggregate formation from A�-monomer
and destabilization of the aggregate could be useful for
prevention and propagation of the disease respectively. Russell’s
viper venom (RVV) contains protein(s) that destabilize A�
aggregates as revealed from the thioflavin T assay. The active
component was identified as factor V activator (RVV-V). Among
the possible mechanisms of destabilization, RVV-V-mediated proteolysis
was ruled out from mass spectrometric data and the thioflavinTassay.
The alternate hypothesis that small peptides derived
fromRVV-Vdestabilize the aggregate is better supported by experimental
results. Six small peptides were synthesized using RVV-V
as the template, and three unrelated peptides were synthesized to
serve as controls. Destabilization ofA� aggregate by these peptides
was studied using spectrofluorometric assays, atomic force
microscopy, transmission electron microscopy, and confocal
microscopy. Among the peptides, CTNIF and the mixture of
the six peptides were most potent in converting the aggregates
to the monomeric state and thus, preventing cytotoxicity
in SH-SY5Y human neuroblastoma cells. The control peptides
failed to show similar effects. Moreover, some of these
peptides are stable in blood for 24 h. Therefore, these venomderived
peptides offer an encouraging opportunity to prevent
amyloidosis and may provide information to combat A
Preservation of Natural Stability of Fruit “Bromelain” from Ananas Comosus (PINEAPPLE)
Pineapple extract, “bromelain,” is a rich source of proteases having
therapeutic benefits. The processed fruit does not show proteolytic activity
probably due to harsh conditions of sterilization. Storage of fresh fruit at -4C
without preservatives retained 75 � 5% proteolytic activity after 180 days
(with or without eight cycles of freeze–thawing in between) and was devoid of
microbial contamination. Peroxidase, acid phosphatase and amylase activities
were also retained by 75 � 5%. Immunomodulatory activity of the fresh
and the stored fruit was comparable. For industrial scale, g irradiation of
1–2 kGray is proposed to ensure sterility that does not affect enzyme activities.
Under these conditions, no signs of freeze burning are observed. The
ultraviolet-visible spectra of the fresh and stored fruit extracts are also indistinguishable.
The process is commercially viable and amply improves the
quality of processed pineapple in terms of active “bromelain.
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