15 research outputs found
Chemical Targeting of GAPDH Moonlighting Function in Cancer Cells Reveals Its Role in Tubulin Regulation
SummaryGlycolytic enzymes are attractive anticancer targets. They also carry out numerous, nonglycolytic “moonlighting” functions in cells. In this study, we investigated the anticancer activity of the triazine small molecule, GAPDS, that targets the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDS showed greater toxicity against cancer cells compared to a known GAPDH enzyme inhibitor. GAPDS also selectively inhibited cell migration and invasion. Our analysis showed that GAPDS treatment reduced GAPDH levels in the cytoplasm, which would modulate the secondary, moonlighting functions of this enzyme. We then used GAPDS as a probe to demonstrate that a moonlighting function of GAPDH is tubulin regulation, which may explain its anti-invasive properties. We also observed that GAPDS has potent anticancer activity in vivo. Our study indicates that strategies to target the secondary functions of anticancer candidates may yield potent therapeutics and useful chemical probes
Essential oil mixture on rumen fermentation and microbial community – an study
Objective The objective of this study was to investigate the effects of essential oil mixture (EOM) supplementation on rumen fermentation characteristics and microbial changes in an in vitro. Methods Three experimental treatments were used: control (CON, no additive), EOM 0.1 (supplementation of 1 g EOM/kg of substrate), and EOM 0.2 (supplementation of 2 g EOM/kg of substrate). An in vitro fermentation experiment was carried out using strained rumen fluid for 12 and 24 h incubation periods. At each time point, in vitro dry matter digestibility (IVDMD), neutral detergent fiber digestibility (IVNDFD), pH, ammonia nitrogen (NH3-N), and volatile fatty acid (VFA) concentrations, and relative microbial diversity were estimated. Results After 24 h incubation, treatments involving EOM supplementation led to significantly higher IVDMD (treatments and quadratic effect; p = 0.019 and 0.008) and IVNDFD (linear effect; p = 0.068) than did the CON treatment. The EOM 0.2 supplementation group had the highest NH3-N concentration (treatments; p = 0.032). Both EOM supplementations did not affect total VFA concentration and the proportion of individual VFAs; however, total VFA tended to increase in EOM supplementation groups, after 12 h incubation (linear; p = 0.071). Relative protozoa abundance significantly increased following EOM supplementation (treatments, p<0.001). Selenomonas ruminantium and Ruminococcus albus (treatments; p<0.001 and p = 0.005), abundance was higher in the EOM 0.1 treatment group than in CON. The abundance of Butyrivibrio fibrisolvens, fungi and Ruminococcus flavefaciens (treatments; p< 0.001, p<0.001, and p = 0.005) was higher following EOM 0.2 treatment. Conclusion The addition of newly developed EOM increased IVDMD, IVNDFD, and tended to increase total VFA indicating that it may be used as a feed additive to improve rumen fermentation by modulating rumen microbial communities. Further studies would be required to investigate the detailed metabolic mechanism underlying the effects of EOM supplementation
Slow Dynamics of Ring Polymer Melts by Asymmetric Interaction of Threading Configuration: Monte Carlo Study of a Dynamically Constrained Lattice Model
Abnormally slower diffusional processes than its internal structure relaxation have been observed in ring polymeric melt systems recently. A key structural feature in ring polymer melts is topological constraints which allow rings to assume a threading configuration in the melt phase. In this work, we constructed a lattice model under the assumption of asymmetric diffusivity between two threading rings, and investigated a link between the structural correlation and its dynamic behavior via Monte Carlo simulations. We discovered that the hierarchical threading configurations render the whole system to exhibit abnormally slow dynamics. By analyzing statistical distributions of timescales of threading configurations, we found that the decoupling between internal structure relaxation and diffusion is crucial to understand the threading effects on the dynamics of a ring melt. In particular, in the limit of small but threaded rings, scaling exponents of the diffusion coefficient D and timescale
τ
diff
with respect to the degree of polymerization N agree well with that of the annealed tree model as well as our mean-field analysis. As N increases, however, the ring diffusion abruptly slows down to the glassy behavior, which is supported by a breakdown of the Stokes–Einstein relation
Magnetic phase diagram of a 2-dimensional triangular lattice antiferromagnet NaBaMn(PO)
We report the magnetic phase transitions of a spin-5/2, 2-dimensional
triangular lattice antiferromagnet (AFM) NaBaMn(PO). From specific
heat measurements, we observe two magnetic transitions at temperatures 1.15 K
and 1.30 K at zero magnetic field. Detailed AC magnetic susceptibility
measurements reveal multiple phases including the
(up-up-down)-phase between 1.9 T and 2.9 T at
47 mK when magnetic field is applied along the axis, implying that
NaBaMn(PO) is a classical 2 TL Heisenberg AFM with easy-axis
anisotropy. However, it deviates from an ideal model as evidenced by a hump
region with hysteresis between the and
-phases and weak phase transitions. Our work provides another experimental
example to study frustrated magnetism in 2 TL AFM which also serves as a
reference to understand the possible quantum spin liquid behavior and anomalous
phase diagrams observed in sibling systems NaBa(PO) ( = Co,
Ni)
Chemical Targeting of GAPDH Moonlighting Function in Cancer Cells Reveals Its Role in Tubulin Regulation
Glycolytic enzymes are attractive anticancer targets. They also carry out numerous, nonglycolytic "moon-lighting" functions in cells. In this study, we investigated the anticancer activity of the triazine small molecule, GAPDS, that targets the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). GAPDS showed greater toxicity against cancer cells compared to a known GAPDH enzyme inhibitor. GAPDS also selectively inhibited cell migration and invasion. Our analysis showed that GAPDS treatment reduced GAPDH levels in the cytoplasm, which would modulate the secondary, moonlighting functions of this enzyme. We then used GAPDS as a probe to demonstrate that a moonlighting function of GAPDH is tubulin regulation, which may explain its anti-invasive properties. We also observed that GAPDS has potent anticancer activity in vivo. Our study indicates that strategies to target the secondary functions of anticancer candidates may yield potent therapeutics and useful chemical probes.1112sciescopu
Stochastic Photon Emission from Nonblinking Upconversion Nanoparticles
Because
of their well-known optical properties, upconversion nanoparticles
(UCNPs) are regarded as some of the most promising nanomaterials for
bioimaging, biosensors, and solar cells. The nonblinking nature of
their upconversion emissions has been a particularly beneficial advantage
for live-cell imaging. However, the origin of this unique property
has never been seriously investigated. We report, for the first time,
the observation of stochastic photon emission (SPEM) in core/shell
UCNPs (NaYF<sub>4</sub>:Yb<sup>3+</sup>,Er<sup>3+</sup>/NaYF<sub>4</sub>) on the microsecond and nanosecond time scales, even under continuous
irradiation at 980 nm. This SPEM was attributed to slow “upconversion
cycles”. We consider that the conventionally reported, nonblinking
nature of UCNP emissions can be attributed to the averaging of SPEMs
from multiple Er<sup>3+</sup> ions and the low temporal resolution
of previous observation. The off-time distribution, which possesses
kinetics information for the upconversion pathways, was well fitted
to a single exponential indicating involvement of a single rate-determining
step. The distinct behaviors of the green and red emissions confirm
their different photophysical pathways