323 research outputs found
Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues
Salen Mn complexes, including EUK-134, EUK-189 and a newer cyclized analog EUK-207, are synthetic SOD/catalase mimetics that have beneficial effects in many models of oxidative stress. As oxidative stress is implicated in some forms of delayed radiation injury, we are investigating whether these compounds can mitigate injury to normal tissues caused by ionizing radiation. This review describes some of this research, focusing on several tissues of therapeutic interest, namely kidney, lung, skin, and oral mucosa. These studies have demonstrated suppression of delayed radiation injury in animals treated with EUK-189 and/or EUK-207. While an antioxidant mechanism of action is postulated, it is likely that the mechanisms of radiation mitigation by these compounds in vivo are complex and may differ in the various target tissues. Indicators of oxidative stress are increased in lung and skin radiation injury models, and suppressed by salen Mn complexes. The role of oxidative stress in the renal injury model is unclear, though EUK-207 does mitigate. In certain experimental models, salen Mn complexes have shown âmito-protectiveâ properties, that is, attenuating mitochondrial injury. Consistent with this, EUK-134 suppresses effects of ionizing radiation on mitochondrial function in rat astrocyte cultures. In summary, salen Mn complexes could be useful to mitigate delayed radiation injury to normal tissues following radiation therapy, accidental exposure, or radiological terrorism. Optimization of their mode of delivery and other key pharmaceutical properties, and increasing understanding of their mechanism(s) of action as radiation mitigators, are key issues for future study
TCT-121 First Human Transcatheter Aortic Valve Implantation of the Colibri Heart Valve, A Pre-mounted, Pre-packaged, Low Profile Ready for Use, Dry Valve in a 14 French Delivery System. Six Months Follow up.
Pyruvate Kinase Inhibits Proliferation during Postnatal Cerebellar Neurogenesis and Suppresses Medulloblastoma Formation
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNP) and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation, and tumorigenesis. We observed a dichotomous pattern of PKM expression, in which postmitotic neurons throughout the brain expressed the constitutively active PKM1 isoform, while neural progenitors and medulloblastomas exclusively expressed the less active PKM2. Isoform-specific Pkm2 deletion in CGNPs blocked all Pkm expression. Pkm2-deleted CGNPs showed reduced lactate production and increased SHH-driven proliferation.13C-flux analysis showed that Pkm2 deletion reduced the flow of glucose carbons into lactate and glutamate without markedly increasing glucose-to-ribose flux. Pkm2 deletion accelerated tumor formation in medulloblastoma- prone ND2:SmoA1 mice, indicating the disrupting PKM releases CGNPs from a tumor-suppressive effect. These findings show that distal and proximal disruptions of glycolysis have opposite effects on proliferation, and that efforts to block the oncogenic effect of aerobic glycolysis must target reactions upstream of PKM
The Cyprinodon variegatus genome reveals gene expression changes underlying differences in skull morphology among closely related species
Genes in durophage intersection set at 15 dpf. This is a comma separated table of the genes in the 15 dpf durophage intersection set. Given are edgeR results for each pairwise comparison. Columns indicating whether a gene is included in the intersection set at a threshold of 1.5 or 2 fold are provided. (CSV 13ĂÂ kb
Detection of intrinsic source structure at ~3 Schwarzschild radii with Millimeter-VLBI observations of SAGITTARIUS A*
We report results from very long baseline interferometric (VLBI) observations
of the supermassive black hole in the Galactic center, Sgr A*, at 1.3 mm (230
GHz). The observations were performed in 2013 March using six VLBI stations in
Hawaii, California, Arizona, and Chile. Compared to earlier observations, the
addition of the APEX telescope in Chile almost doubles the longest baseline
length in the array, provides additional {\it uv} coverage in the N-S
direction, and leads to a spatial resolution of 30 as (3
Schwarzschild radii) for Sgr A*. The source is detected even at the longest
baselines with visibility amplitudes of 4-13% of the total flux density.
We argue that such flux densities cannot result from interstellar refractive
scattering alone, but indicate the presence of compact intrinsic source
structure on scales of 3 Schwarzschild radii. The measured nonzero
closure phases rule out point-symmetric emission. We discuss our results in the
context of simple geometric models that capture the basic characteristics and
brightness distributions of disk- and jet-dominated models and show that both
can reproduce the observed data. Common to these models are the brightness
asymmetry, the orientation, and characteristic sizes, which are comparable to
the expected size of the black hole shadow. Future 1.3 mm VLBI observations
with an expanded array and better sensitivity will allow a more detailed
imaging of the horizon-scale structure and bear the potential for a deep
insight into the physical processes at the black hole boundary.Comment: 11 pages, 5 figures, accepted to Ap
Molecular tools for bathing water assessment in Europe:Balancing social science research with a rapidly developing environmental science evidence-base
The use of molecular tools, principally qPCR, versus traditional culture-based methods for quantifying microbial parameters (e.g., Fecal Indicator Organisms) in bathing waters generates considerable ongoing debate at the science-policy interface. Advances in science have allowed the development and application of molecular biological methods for rapid (~2Â h) quantification of microbial pollution in bathing and recreational waters. In contrast, culture-based methods can take between 18 and 96Â h for sample processing. Thus, molecular tools offer an opportunity to provide a more meaningful statement of microbial risk to water-users by providing near-real-time information enabling potentially more informed decision-making with regard to water-based activities. However, complementary studies concerning the potential costs and benefits of adopting rapid methods as a regulatory tool are in short supply. We report on findings from an international Working Group that examined the breadth of social impacts, challenges, and research opportunities associated with the application of molecular tools to bathing water regulations
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