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At least 163 records · Page 9

Comparative MicroRNA Expression Patterns in Fibroblasts after Low and High Doses of Low-LET Radiation Exposure

Exposure to ionizing radiation causes DNA damage to cells, and provokes a plethora of cellular responses controlled by unique gene-directed signaling pathways. MicroRNAs (miRNAs) are small (~22-nucleotide), non-coding RNAs which functionally silence gene expression by either degrading the messages or inhibiting translation. Here we investigate radiation-dependent changes in these negative regulators by comparing the expression patterns of all 462 known human miRNAs in fibroblasts, after exposure to low (0.1 Gy) or high (2 Gy) doses of X-rays at 30 min, 2, 6 and 24 hrs post-treatment. The expression patterns of microRNAs after low and high doses of radiation show a similar qualitative down-regulation trend at early (0.5 hr) and late (24 hr) time points, with a quantitatively steeper slope following the 2 Gy exposures. Interestingly, an interruption of this downward trend is observed after the 2 Gy exposure, i.e. a significant up-regulation of microRNAs at 2 hrs, then reverting to the downward trend by 6 hrs; this interruption at the intermediate time point was not observed with the 0.1 Gy exposure. At the early time point (0.5 hr), candidate gene targets of selected down-regulated microRNAs, common to both 0.1 and 2 Gy exposures, were those functioning in chromatin remodeling. Candidate target genes of unique up-regulated microRNAs seen at a 2 hr intermediate time point, after the 2 Gy exposure only, are those involved in cell death signaling. Finally, putative target genes of down-regulated microRNAs seen at the late (24 hr) time point after either doses of radiation are those involved in the up-regulation of DNA repair, cell signaling and homeostasis. Thus we hypothesize that after radiation exposure, microRNAs acting as hub negative regulators for unique signaling pathways needed to be down-regulated so as to de-repress their target genes for the proper cellular responses, including DNA repair and cell maintenance. The unique microRNAs up-regulated at 2 hr after 2 Gy suggest the cellular response to functionally suppress the apoptotic death signaling reflex after exposure to high dose radiation. Further analyses with transcriptome and global proteomic profiling will validate the reciprocal expression of signature microRNAs selected in our radiation-exposed cells, and their candidate target gene families, and test our hypothesis that unique radiation-specific microRNAs are keys in governing signaling responses for damage control of this environmental hazard.

Maes, Olivier C.↗

Let's Roll! Rolling Out or Deploying SEPG Assets

The topics covered in this slide presentation are: the general approach to software quality improvement (SQI) at Jet Propulsion Institute, the SQI deployment process, and lessons learned in regard to SQI. The Software Engineering Process Group (SEPG) is the group charged with SQI. The initial focus of the Software Quality Improvement (SQI) Project is on mission-critical software for flight projects, their spacecraft and instrument systems, and their ground systems.

process improvements↗

System Re-set: High LET Radiation or Transient Musculoskeletal Disuse Cause Lasting Changes in Oxidative Defense Pathways Within Bone

Six months post-IR, there were no notable changes in skeletal expression of 84 principal genes in the p53 signaling pathway due to low dose IR (0.5Gy), HU, or both. In contrast, numerous genes relevant to oxidative stress were regulated by the treatments, typically in a direction indicative of increased oxidative stress and impaired defense. IR and HU independently reduced (between 0.46 to 0.88 fold) expression levels of Noxa1, Gpx3, Prdx2, Prdx3, and Zmynd17. Surprisingly, transient HU alone (sham-irradiated) decreased expression of several redox-related genes (Gpx1,Gstk1, Prdx1, Txnrd2), which were not affected significantly by IR alone. Irradiation increased (1.13 fold) expression of a gene responsible for production of superoxides by neutrophils (NCF2). Of interest, only combined treatment with HU and IR led to increased expression levels of Ercc2, (1.19 fold), a DNA excision repair enzyme. Differences in gene expression levels may reflect a change in gene expression on a per cell basis, a shift in the repertoire of specific cell types within the tissue, or both. Serum nitrite/nitrate levels were elevated to comparable levels (1.6-fold) due to IR, HU or both, indicative of elevated systemic nitrosyl stress. CONCLUSIONS The magnitude of changes in skeletal expression of oxidative stress-related genes six months after irradiation and/or transient unloading tended to be relatively modest (0.46-1.15 fold), whereas the p53 pathway was not affected. The finding that many different oxidative stress-related genes differed from controls at this late time point implicates a generalized impairment of oxidative defense within skeletal tissue, which coincides with both profound radiation damage to osteoprogenitors/stem cells in bone marrow and impaired remodeling of mineralized tissue.

Kumar, Akhilesh↗

Listen; There's a Hell of a Good Universe Next Door; Let's Go

Scientific research is key to our nation's technological and economic development. One can attempt to focus research toward specific applications, but science has a way of surprising us. Think for example of the "charge-couple device", which was originally invented for memory storage, but became the modern digital camera that is used everywhere from camera phones to the Hubble Space Telescope. Using digital cameras, Hubble has taken pictures that reach back 12 billion light-years into the past, when the Universe was only 1-2 billion years old. Such results would never have been possible with the film cameras Hubble was originally supposed to use. Over the past two decades, Hubble and other telescopes have shown us much about the Universe -- many of these results are shocking. Our galaxy is swarming with planets; most of the mass in the Universe is invisible; and our Universe is accelerating ever faster and faster for unknown reasons. Thus, we live in a "hell of a good universe", to quote e.e. cummings, that we fundamentally don't understand. This means that you, as young scientists, have many worlds to discover

Rigby, Jane R.↗

Global Precipitation Measurement Cold Season Precipitation Experiment (GCPEx): For Measurement Sake Let it Snow

As a component of the Earth's hydrologic cycle, and especially at higher latitudes,falling snow creates snow pack accumulation that in turn provides a large proportion of the fresh water resources required by many communities throughout the world. To assess the relationships between remotely sensed snow measurements with in situ measurements, a winter field project, termed the Global Precipitation Measurement (GPM) mission Cold Season Precipitation Experiment (GCPEx), was carried out in the winter of 2011-2012 in Ontario, Canada. Its goal was to provide information on the precipitation microphysics and processes associated with cold season precipitation to support GPM snowfall retrieval algorithms that make use of a dual-frequency precipitation radar and a passive microwave imager on board the GPM core satellite,and radiometers on constellation member satellites. Multi-parameter methods are required to be able to relate changes in the microphysical character of the snow to measureable parameters from which precipitation detection and estimation can be based. The data collection strategy was coordinated, stacked, high-altitude and in-situ cloud aircraft missions with three research aircraft sampling within a broader surface network of five ground sites taking in-situ and volumetric observations. During the field campaign 25 events were identified and classified according to their varied precipitation type, synoptic context, and precipitation amount. Herein, the GCPEx fieldcampaign is described and three illustrative cases detailed.

GCPEx↗

Fiat Lux, Let There Be Light!

Most of us think of light as helping us see things, but it is so much more important than that. Light is electromagnetic energy moving in waves through space, interacting with atoms and molecules as it goes. So are radio waves, microwaves, infrared light, ultraviolet, x-rays and gamma rays - all of them are electromagnetic energy, and the only real difference is the spacing between the wave crests. So light gives us communications with each other with radio and TV, and it gives us the ability to travel through the universe using telescopes and our imagination. But light also gives us access to scientific questions, such as: what holds the atoms and molecules together? How does the mysterious quantum mechanics work? And understanding all these, how can we build electronic devices for modern life? And if we are very ambitious, we build accelerators like the Large Hadron Collider, and particles collide and concentrate electromagnetic energy into tiny spaces, and according to Einstein's E equals mc squared, we turn energy into new particles to learn, perhaps what the universe was like when it was a tiny fraction of a second old.

telescopes↗

Let's Exploit Available Knowledge on Vegetation Fluorescence

The potential to measure vegetation fluorescence from space (1) and to derive from it direct information on the gross primary productivity (GPP) of terrestrial ecosystems is probably the most thrilling development in remote sensing and global ecology of recent years, as it moves Earth observation techniques from the detection of canopy biophysics (e.g., fraction of absorbed radiation) and biochemistry (chlorophyll and nitrogen content) to the realm of ecosystem function. The existence of a functional relationship between fluorescence and photosynthesis has been elucidated over the last decade by several laboratories, notably as part of the preliminary studies of the European Space Agency Fluorescence Explorer (FLEX) Earth Explorer Mission. The empirical observation presented by Guanter et al. (2) of a linear relationship between fluorescence radiance and GPP, however, provides the first experimental confirmation of the feasibility of the approach— already thoroughly tested at leaf level—at the desired scale, despite the confounding effects associated with the satellite detection of such a faint signal. A word of clarification is needed here. The use of fluorescence as a probe of leaf photochemistry has been a staple of plant ecophysiology for decades, rooted in a sound understanding of photosynthetic energy dissipation. However, most past studies had to rely for the interpretation of results on active (pulse-saturated) techniques, making them unsuitable for remote-sensing applications. Over recent years, however, novel process based models have been developed for the interpretation of steady-state, solar-induced fluorescence at the leaf to canopy scale (3). We are therefore in a position to move beyond the mere empirical observation of an association between GPP and fluorescence radiance. In particular, Guanter et al. (2) base their analysis on the assumption of a constant ratio between photosynthetic and fluorescence light use efficiencies (equation 3 in ref. 2).We know, however, that the ratio is not constant, but changes widely in response to light, CO2, stomatal limitations, and extreme stress (4, 5). What’s more, we can make sense of such changes, thus extracting valuable information from the very scatter that is apparent in their data. However, this process will require the availability of more tailored instruments, such as the one planned for the FLEX mission. As already stressed by Guanter et al. (2), the spatial resolution of the Global Ozone Monitoring Experiment-2 sensor (40 × 80 km) makes it difficult to compare meaningfully the fluorescence signal with ground measurements, when only 60–70% of the footprint consists of the desired land-cover type (table S1 in ref. 2), suggesting that this could be largely responsible for the low signals observed in European grasslands. Moreover, the overpass time of the MetOp-A satellite (9:30 AM) implies that fluorescence is generally measured under light-limiting conditions, when fluorescence is only marginally affected by stomatal closure even under stress conditions. This result could explain the seasonal mismatch with daily GPP observed in natural ecosystems in the absence of irrigation (figure 4 in ref. 2). We hope, therefore, that this welcome contribution to this fast-advancing field will help demonstrate the potential of the new technique, and pave the way for more refined studies under both a technological and scientific point of view.

Space↗

Let Our Powers Combine! Harnessing NASA's Earth Observatory Natural Event Tracker (EONET) in Worldview

Constellations of NASA Earth Observing System (EOS) satellites orbit the earth to collect images and data about the planet in near real-time. Within hours of satellite overpass, you can discover where the latest wildfires, severe storms, volcanic eruptions, and dust and haze events are occurring using NASA's Worldview web application. By harnessing a repository of curated natural event metadata from NASA Earth Observatory's Natural Event Tracker (EONET), Worldview has moved natural event discovery to the forefront and allows users to select events-of-interest from a curated list, zooms to the area, and adds the most relevant imagery layers for that type of natural event. This poster will highlight NASA Worldviews new natural event feed functionality.

earth science↗

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks – especially double-strand breaks (DSBs) – that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells [1]. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cells

Plante, Ianik↗

Predicting cell death and mutation frequency for a wide spectrum of LET and across cell lines from DNA break clustering inside repair domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks – especially double-strand breaks (DSBs) – that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cells.

Ianik Plante↗