Prolonged alterations of cardiomyocyte gene expression following low dose high charge and energy particle radiation--implications for future deep space travel

INTRODUCTION: Space exploration is ultra-hazardous and unpredictably dangerous. One area of significant concern is the exposure of astronauts to deep space radiation and the development of deleterious health effects. Earth's magnetic field and atmosphere both act to deflect the majority of deep space radiation, protecting humans on the surface of earth as well as astronauts in low Earth orbit missions. Because this type of radiation is not encountered terrestrially, very limited evidence exists in regards to the effects on the well-being. Deep space radiation, which consists of high charge and energy (HZE) particles, may be experimentally reproduced for studies using a particle accelerator. The long-term degenerative effects of cosmic irradiation on the cardiovascular system are vastly unknown. Detailing the molecular response within cardiomyocytes after exposure to HZE irradiation will provide needed knowledge for scientists to accurately assess the cardiovascular risks associated with deep space radiation exposure. OBJECTIVE: The primary objective of this study is to characterize the molecular alterations of gene expression within murine cardiomyocytes following exposure to two different types of HZE. METHODS: Wild type C57B1/6NT (Taconic) mice were exposed to either 90 cGy, 1 GeV proton (1H) or 15 cGy, 1 GeV/nucleon iron (56Fe) HZE particle-radiation. Radiation exposure was performed at the NASA Space Radiation Laboratory located at the Brookhaven National Laboratory (Upton, NY). Biological samples were taken and transcriptome profiling was performed at various time points following irradiation (1, 3, 7, 14, and 28 days). RESULTS: Samples exposed to 56Fe-IR displayed significant levels of gene modulation, while proton-irradiation failed to elicit significant alterations in cardiomyocyte gene transcription compared to sham-irradiated samples. Network pathway analysis of iron-irradiated samples identified multiple biological pathways being significantly modulated. These biological pathways included cell death and survival, free radical scavenging, and inflammatory processes. Multiple points of upstream transcription regulation were identified as key nodes for regulating downstream expression. Validation of the signal transduction network by protein analysis showed that particle-IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of transcription factors GATA-4, STAT-3 and NF-B as key regulators. CONCLUSIONS: The molecular response to 56Fe-IR is unique and induces long-term modulations of gene expression in cardiomyocytes that last up to at least 28 days following radiation exposure. However, exposure to 1H-IR failed to elicit significantly robust alterations in gene expression in cardiomyocytes. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a significant role in the molecular response following HZE particle radiation. This study may have multiple implications for NASA's efforts to develop cardio-degenerative risk estimates for astronauts participating in future deep space missions. By identifying molecular mechanisms and potential molecular markers, scientists can begin to assess excess relative risks and develop strategies to mitigate risks of developing physiological changes which may compromise future missions. This study may also have major safety implications for the increasing number of patients receiving conventional and particle radiotherapy

FDG-PET Lacks Sufficient Sensitivity to Detect Myxoid Liposarcoma Spinal Metastases Detected by MRI

Purpose. To document a case of myxoid liposarcoma in which PET scan was less sensitive than MRI in detecting spinal metastasis. Materials and Methods. The case of a 65-year-old female with a history of myxoid liposarcoma (MLS) of the thigh resected 5 years previously and now presenting with low back pain is presented. Her medical oncologist ordered an FDG-PET scan to evaluate distant recurrence. Subsequently, an MRI of her spine was obtained by her surgeon. Results. The FDG-PET scan was obtained 1 week prior to the MRI, and it did not show increased glucose uptake in the spine. Her MRI did show increased signal intensity in her lumbar spine. CT needle biopsy confirmed the lesion to be metastatic MLS. Conclusion. FDG-PET scans are utilized to detect distant recurrence of cancerous lesions. Myxoid liposarcoma has a unique propensity to metastasize to the spine. Previous reports have documented the unreliability of bone scintigraphy to diagnose these metastases. Our report demonstrates that FDG-PET may also lack the sensitivity needed to detect these lesions. We advocate total spine MRI when screening for metastases in this population when they present with back pain

The Costs of Wrongful-Discharge Laws

We estimate the effects on employment and wages of wrongful-discharge protections in the United States. Over the last three decades, most U.S. state courts have adopted one or more common law wrongful discharge doctrines that limit employers' discretion to terminate workers at-will. Using this cross-state variation with a difference-in-difference framework, we find robust evidence of a modest negative impact ( 0.8 to 1.6 percentage points) of one wrongful-discharge doctrine, the implied-contract exception, on employment to population rates in state labor markets. The short-term impact is most pronounced for female, younger, and less-skilled workers, while the longer term costs appear to be borne by older and more-educated workers those most likely to litigate under this doctrine. We find no robust employment or wage effects of two other widely recognized wrongful-discharge laws: the public -policy and good-faith exceptions. Published findings in the literature range from no effect to very large negative effects. We reanalyze the two leading studies and find the discrepancies can be explained by methodological shortcomings in the one case and limitations in the coding of key court decisions in the other.

The Treatment of Anxiety

Rational therapy requires accurate diagnosis. When we apply this precept to anxiety a fundamental question arises. Is anxiety an illness in terms of the now berated medical model which holds that an illness has a cause, a natural history, and hopefully a cure? Or is anxiety a basic aspect of the human condition, an innate pattern of response which becomes pathological when stress, induced by physiologic and social forces, is magnified out of proportion to the original stimulus? If the latter is true, then stress and social interactions are the causative factors, the anxiety only a reaction. Logically then, the condition of anxiety can be modified by alleviating stress or changing the social environment. Although there is no definitive answer to this major question concerning the nature of anxiety, we would like to present briefly some of the present knowledge about it

The Corn Belt Multi-State Corn Nitrogen Rate Calculator: Not Reliable for Kentucky Corn Producers

Because of the rising price of nitrogen (N) fertilizer, university personnel across the country are in the process of fine tuning N recommendations for com. Historically, each state has had different N recommendations based on research results obtained in different production systems and growing environments across each state. Some states in the Com Belt have used a yield potential (yield goal) approach to N recommendations. The expected yield is multiplied by a factor (usually 1.2) and then N credits for previous crop, manure, etc. are subtracted. One problem with this method is that as com yields increase N recommendations also increase. While this might seem logical, some studies show that N requirements are rising at a much slower pace than com yield. This simply means the com plant is becoming a more efficient user of N. States using the yield goal approach are realizing that, with time, their recommendations are increasingly exceeding the needs of the crop. For this reason, they are considering alternatives to the yield goal approach

Molecular manipulation of keratin 8/18 intermediate filaments: modulators of FAS-mediated death signaling in human ovarian granulosa tumor cells

Background: Granulosa cell tumors (GCT) are a rare ovarian neoplasm but prognosis is poor following recurrence. Keratin intermediate filaments expressed in these tumors are a diagnostic marker, yet paradoxically, may also constitute a target for therapeutic intervention. In the current study, we evaluated keratin 8/18 (K8/18) filament expression as a mechanism of resistance to apoptosis in GCT, specifically focusing on regulation of the cell surface death receptor, Fas (FAS). Methods: The GCT cell line, KGN, was transiently transfected with siRNA to KRT8 and KRT18 to reduce K8/18 filament expression. Expression of K8/18, FAS, and apoptotic proteins (PARP, cleaved PARP) were evaluated by fluorescence microscopy, flow cytometric analysis, and immunoblotting, respectively. The incidence of FAS-mediated apoptosis in KGN cells was measured by caspase 3/7 activity. All experiments were performed independently three to six times, using a fresh aliquot of KGN cells for each experiment. Quantitative data were analyzed by one- or two-way analysis of variance (ANOVA), followed by a Tukey’s post-test for multiple comparisons; differences among means were considered statistically significant at P \u3c 0.05. Results: Control cultures of KGN cells exhibited abundant K8/18 filament expression (~90 % of cells), and minimal expression of FAS (\u3c25 % of cells). These cells were resistant to FAS-activating antibody (FasAb)-induced apoptosis, as determined by detection of cleaved PARP and measurement of caspase 3/7 activity. Conversely, siRNA-mediated knock-down of K8/18 filament expression enhanced FAS expression (\u3e 70 % of cells) and facilitated FasAb-induced apoptosis, evident by increased caspase 3/7 activity (P \u3c 0.05). Additional experiments revealed that inhibition of protein synthesis, but not MEK1/2 or PI3K signaling, also prompted FasAb-induced apoptosis. Conclusions: The results demonstrated that K8/18 filaments provide resistance to apoptosis in GCT by impairing FAS expression. The abundance of keratin filaments in these cells and their role in apoptotic resistance provides a greater mechanistic understanding of ovarian tumorgenicity, specifically GCT, as well as a clinically-relevant target for potential therapeutic intervention

Consumer Purchases of Biotech Sweet Corn: Results from a Market Experiment

In the increasingly consumer-driven food system, consumer preferences toward agricultural biotechnology have the potential to influence decisions about development and adoption of biotech crop varieties. Current knowledge about consumer attitudes toward biotech foods is largely based on a number of consumer surveys and a growing body of experimental auctions. This paper reports results of a market experiment designed to isolate the effect of the use of biotechnology on consumer choices between two otherwise identical products. Two related varieties of fresh-market sweet corn were grown, labeled, and sold side-by-side in nine participating grocery stores in the Philadelphia area. Sales data indicate a market share of biotech corn of about 45 percent, with store-specific shares varying between 10 and 80 percent. Over 700 surveys were collected in stores. Surprisingly, only 65 percent of respondents noticed that there were two types of corn for sale despite the labeling and merchandising, and 87 percent of the sample spent one minute or less choosing their corn. About half of the respondents had heard of biotechnology before, and 16 percent volunteered the biotechnology trait as an influence on their purchase decision. Approximately 40 percent of the sample purchased some of the biotech variety, with several respondents purchasing some of each.Institutional and Behavioral Economics,