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Extracellular vesicles transfer nuclear Abl-dependent and radiation-induced miR-34c into unirradiated cells to cause bystander effects.
Ionizing radiation (IR) not only activates DNA damage response (DDR) in irradiated cells but also induces bystander effects (BE) in cells not directly targeted by radiation. How DDR pathways activated in irradiated cells stimulate BE is not well understood. We show here that extracellular vesicles secreted by irradiated cells (EV-IR), but not those from unirradiated controls (EV-C), inhibit colony formation in unirradiated cells by inducing reactive oxygen species (ROS). We found that µEV-IR from Abl nuclear localization signal-mutated ( Abl-µNLS) cells could not induce ROS, but expression of wild-type Abl restored that activity. Because nuclear Abl stimulates miR-34c biogenesis, we measured miR-34c in EV and found that its levels correlated with the ROS-inducing activity of EV. We then showed that EV from miR-34c minigene-transfected, but unirradiated cells induced ROS; and transfection with miR-34c-mimic, without radiation or EV addition, also induced ROS. Furthermore, EV-IR from miR34-family triple-knockout cells could not induce ROS, whereas EV-IR from wild-type cells could cause miR-34c increase and ROS induction in the miR-34 triple-knockout cells. These results establish a novel role for extracellular vesicles in transferring nuclear Abl-dependent and radiation-induced miR-34c into unirradiated cells to cause bystander oxidative stress
Spectral method for matching exterior and interior elliptic problems
A spectral method is described for solving coupled elliptic problems on an
interior and an exterior domain. The method is formulated and tested on the
two-dimensional interior Poisson and exterior Laplace problems, whose solutions
and their normal derivatives are required to be continuous across the
interface. A complete basis of homogeneous solutions for the interior and
exterior regions, corresponding to all possible Dirichlet boundary values at
the interface, are calculated in a preprocessing step. This basis is used to
construct the influence matrix which serves to transform the coupled boundary
conditions into conditions on the interior problem. Chebyshev approximations
are used to represent both the interior solutions and the boundary values. A
standard Chebyshev spectral method is used to calculate the interior solutions.
The exterior harmonic solutions are calculated as the convolution of the
free-space Green's function with a surface density; this surface density is
itself the solution to an integral equation which has an analytic solution when
the boundary values are given as a Chebyshev expansion. Properties of Chebyshev
approximations insure that the basis of exterior harmonic functions represents
the external near-boundary solutions uniformly. The method is tested by
calculating the electrostatic potential resulting from charge distributions in
a rectangle. The resulting influence matrix is well-conditioned and solutions
converge exponentially as the resolution is increased. The generalization of
this approach to three-dimensional problems is discussed, in particular the
magnetohydrodynamic equations in a finite cylindrical domain surrounded by a
vacuum
Exact eigenstate analysis of finite-frequency conductivity in graphene
We employ the exact eigenstate basis formalism to study electrical
conductivity in graphene, in the presence of short-range diagonal disorder and
inter-valley scattering. We find that for disorder strength, 5, the
density of states is flat. We, then, make connection, using the MRG approach,
with the work of Abrahams \textit{et al.} and find a very good agreement for
disorder strength, = 5. For low disorder strength, = 2, we plot the
energy-resolved current matrix elements squared for different locations of the
Fermi energy from the band centre. We find that the states close to the band
centre are more extended and falls of nearly as as we move away
from the band centre. Further studies of current matrix elements versus
disorder strength suggests a cross-over from weakly localized to a very weakly
localized system. We calculate conductivity using Kubo Greenwood formula and
show that, for low disorder strength, conductivity is in a good qualitative
agreement with the experiments, even for the on-site disorder. The intensity
plots of the eigenstates also reveal clear signatures of puddle formation for
very small carrier concentration. We also make comparison with square lattice
and find that graphene is more easily localized when subject to disorder.Comment: 11 pages,15 figure
Boesenbergia pandurata Attenuates Diet-Induced Obesity by Activating AMP-Activated Protein Kinase and Regulating Lipid Metabolism
Obesity, a chronic metabolic disorder, is characterized by enlarged fat mass and dysregulation of lipid metabolism. The medicinal plant, Boesenbergia pandurata (Roxb.) Schltr., has been reported to possess anti-oxidative and anti-inflammatory properties; however, its anti-obesity activity is unexplored. The present study was conducted to determine whether B. pandurata extract (BPE), prepared from its rhizome parts, attenuated high-fat diet (HFD)-induced obesity in C57BL/6J mice. The molecular mechanism was investigated in 3T3-L1 adipocytes and HepG2 human hepatoma cells. BPE treatment decreased triglyceride accumulation in both 3T3-L1 adipocytes and HepG2 hepatocytes by activating AMP-activated protein kinase (AMPK) signaling and regulating the expression of lipid metabolism-related proteins. In the animal model, oral administration of BPE (200 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides were suppressed by BPE administration. Fat pad masses were reduced in BPE-treated mice, as evidenced by reduced adipocyte size. Furthermore, BPE protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. BPE also activated AMPK signaling and altered the expression of lipid metabolism-related proteins in white adipose tissue and liver. Taken together, these findings indicate that BPE attenuates HFD-induced obesity by activating AMPK and regulating lipid metabolism, suggesting a potent anti-obesity agent
Mechanisms of MEOX1 and MEOX2 Regulation of the Cyclin Dependent Kinase Inhibitors p21CIP1/WAF1 and p16INK4a in Vascular Endothelial Cells
Senescence, the state of permanent cell cycle arrest, has been associated
with endothelial cell dysfunction and atherosclerosis. The cyclin dependent
kinase inhibitors p21CIP1/WAF1 and p16INK4a govern the
G1/S cell cycle checkpoint and are essential for determining whether
a cell enters into an arrested state. The homeodomain transcription factor
MEOX2 is an important regulator of vascular cell proliferation and is a direct
transcriptional activator of both p21CIP1/WAF1 and p16INK4a.
MEOX1 and MEOX2 have been shown to be partially functionally redundant during
development, suggesting that they regulate similar target genes in
vivo. We compared the ability of MEOX1 and MEOX2 to activate p21CIP1/WAF1
and p16INK4a expression and induce endothelial cell cycle arrest.
Our results demonstrate for the first time that MEOX1 regulates the MEOX2
target genes p21CIP1/WAF1 and p16INK4a. In addition,
increased expression of either of the MEOX homeodomain transcription factors
leads to cell cycle arrest and endothelial cell senescence. Furthermore, we
show that the mechanism of transcriptional activation of these cyclin dependent
kinase inhibitor genes by MEOX1 and MEOX2 is distinct. MEOX1 and MEOX2 activate
p16INK4a in a DNA binding dependent manner, whereas they induce
p21CIP1/WAF1 in a DNA binding independent manner
Emerging trends in government venture capital policies in smaller peripheral economies: lessons from Finland, New Zealand, and Estonia
Emerging trends from the developing venture capital industries of three smaller peripheral economies (Finland, New Zealand, and Estonia), demonstrate that government policy can overcome scale and distance barriers to assist in establishing venture capital to support innovative potential high growth ventures. Eight common policy themes for successful venture capital development are: new venture stimulation; dedicated finance policy institutions; stable, internationally harmonized tax and regulations; business angel development; inward investment; international venture capital fund development; smooth pipeline of investment; effective investment exit market. Venture capital policy development themes are interconnected, requiring a holistic ecosystem approach. A blueprint for successful small peripheral economy venture capital development requires an initial phase of new venture demand stimulation and ensuing simultaneity of policies to engineer venture capital development
Genome-wide scans identify known and novel regions associated with prolificacy and reproduction traits in a sub-Saharan African indigenous sheep (Ovis aries)
Maximizing the number of offspring born per female is a key functionality trait in commercial- and/or subsistence-oriented livestock enterprises. Although the number of offspring born is closely associated with female fertility and reproductive success, the genetic control of these traits remains poorly understood in sub-Saharan Africa livestock. Using selection signature analysis performed on Ovine HD BeadChip data from the prolific Bonga sheep in Ethiopia, 41 candidate regions under selection were identified. The analysis revealed one strong selection signature on a candidate region on chromosome X spanning BMP15, suggesting this to be the primary candidate prolificacy gene in the breed. The analysis also identified several candidate regions spanning genes not reported before in prolific sheep but underlying fertility and reproduction in other species. The genes associated with female reproduction traits included SPOCK1 (age at first oestrus), GPR173 (mediator of ovarian cyclicity), HB-EGF (signalling early pregnancy success) and SMARCAL1 and HMGN3a (regulate gene expression during embryogenesis). The genes involved in male reproduction were FOXJ1 (sperm function and successful fertilization) and NME5 (spermatogenesis). We also observed genes such as PKD2L2, MAGED1 and KDM3B, which have been associated with diverse fertility traits in both sexes of other species. The results confirm the complexity of the genetic mechanisms underlying reproduction while suggesting that prolificacy in the Bonga sheep, and possibly African indigenous sheep is partly under the control of BMP15 while other genes that enhance male and female fertility are essential for reproductive fitness
3D bioactive composite scaffolds for bone tissue engineering
Bone is the second most commonly transplanted tissue worldwide, with over four million operations using bone grafts or bone substitute materials annually to treat bone defects. However, significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma, cancer, infection and arthritis. Developing bioactive three-dimensional (3D) scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering (BTE). A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts. However, individual groups of materials including polymers, ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone. Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds. This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers, hydrogels, metals, ceramics and bio-glasses in BTE. Scaffold fabrication methodology, mechanical performance, biocompatibility, bioactivity, and potential clinical translations will be discussed
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