eIF5A Promotes Translation Elongation, Polysome Disassembly and Stress Granule Assembly

Stress granules (SGs) are cytoplasmic foci at which untranslated mRNAs accumulate in cells exposed to environmental stress. We have identified ornithine decarboxylase (ODC), an enzyme required for polyamine synthesis, and eIF5A, a polyamine (hypusine)-modified translation factor, as proteins required for arsenite-induced SG assembly. Knockdown of deoxyhypusine synthase (DHS) or treatment with a deoxyhypusine synthase inhibitor (GC7) prevents hypusine modification of eIF5A as well as arsenite-induced polysome disassembly and stress granule assembly. Time-course analysis reveals that this is due to a slowing of stress-induced ribosome run-off in cells lacking hypusine-eIF5A. Whereas eIF5A only marginally affects protein synthesis under normal conditions, it is required for the rapid onset of stress-induced translational repression. Our results reveal that hypusine-eIF5A-facilitated translation elongation promotes arsenite-induced polysome disassembly and stress granule assembly in cells subjected to adverse environmental conditions

Associations between Polycyclic Aromatic Hydrocarbon–Related Exposures and p53 Mutations in Breast Tumors

Background: Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology. Objectives: We hypothesized that associations of PAH-related exposures with breast cancer would differ according to tumor p53 mutation status, effect, type, and number. Methods: We examined this possibility in a population-based case–control study using polytomous logistic regression. As previously reported, 151 p53 mutations among 859 tumors were identified using Surveyor nuclease and confirmed by sequencing. Results: We found that participants with p53 mutations were less likely to be exposed to PAHs (assessed by smoking status in 859 cases and 1,556 controls, grilled/smoked meat intake in 822 cases and 1,475 controls, and PAH–DNA adducts in peripheral mononuclear cells in 487 cases and 941 controls) than participants without p53 mutations. For example, active and passive smoking was associated with p53 mutation–negative [odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.11–2.15] but not p53 mutation–positive (OR = 0.77; 95% CI, 0.43–1.38) cancer (ratio of the ORs = 0.50, p < 0.05). However, frameshift mutations, mutation number, G:C→A:T transitions at CpG sites, and insertions/deletions were consistently elevated among exposed subjects. Conclusions: These findings suggest that PAHs may be associated with specific breast tumor p53 mutation subgroups rather than with overall p53 mutations and may also be related to breast cancer through mechanisms other than p53 mutation

Individual Differences in Sound-in-Noise Perception Are Related to the Strength of Short-Latency Neural Responses to Noise

Important sounds can be easily missed or misidentified in the presence of extraneous noise. We describe an auditory illusion in which a continuous ongoing tone becomes inaudible during a brief, non-masking noise burst more than one octave away, which is unexpected given the frequency resolution of human hearing. Participants strongly susceptible to this illusory discontinuity did not perceive illusory auditory continuity (in which a sound subjectively continues during a burst of masking noise) when the noises were short, yet did so at longer noise durations. Participants who were not prone to illusory discontinuity showed robust early electroencephalographic responses at 40–66 ms after noise burst onset, whereas those prone to the illusion lacked these early responses. These data suggest that short-latency neural responses to auditory scene components reflect subsequent individual differences in the parsing of auditory scenes

Computerized clinical decision support systems for chronic disease management: A decision-maker-researcher partnership systematic review

<p>Abstract</p> <p>Background</p> <p>The use of computerized clinical decision support systems (CCDSSs) may improve chronic disease management, which requires recurrent visits to multiple health professionals, ongoing disease and treatment monitoring, and patient behavior modification. The objective of this review was to determine if CCDSSs improve the processes of chronic care (such as diagnosis, treatment, and monitoring of disease) and associated patient outcomes (such as effects on biomarkers and clinical exacerbations).</p> <p>Methods</p> <p>We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews database, Inspec, and reference lists for potentially eligible articles published up to January 2010. We included randomized controlled trials that compared the use of CCDSSs to usual practice or non-CCDSS controls. Trials were eligible if at least one component of the CCDSS was designed to support chronic disease management. We considered studies 'positive' if they showed a statistically significant improvement in at least 50% of relevant outcomes.</p> <p>Results</p> <p>Of 55 included trials, 87% (n = 48) measured system impact on the process of care and 52% (n = 25) of those demonstrated statistically significant improvements. Sixty-five percent (36/55) of trials measured impact on, typically, non-major (surrogate) patient outcomes, and 31% (n = 11) of those demonstrated benefits. Factors of interest to decision makers, such as cost, user satisfaction, system interface and feature sets, unique design and deployment characteristics, and effects on user workflow were rarely investigated or reported.</p> <p>Conclusions</p> <p>A small majority (just over half) of CCDSSs improved care processes in chronic disease management and some improved patient health. Policy makers, healthcare administrators, and practitioners should be aware that the evidence of CCDSS effectiveness is limited, especially with respect to the small number and size of studies measuring patient outcomes.</p

Demography and Dispersal Ability of a Threatened Saproxylic Beetle: A Mark-Recapture Study of the Rosalia Longicorn (Rosalia alpina)

The Rosalia longicorn or Alpine longhorn (Coleoptera: Cerambycidae) is an endangered and strictly protected icon of European saproxylic biodiversity. Despite its popularity, lack of information on its demography and mobility may compromise adoption of suitable conservation strategies. The beetle experienced marked retreat from NW part of its range; its single population survives N of the Alps and W of the Carpathians. The population inhabits several small patches of old beech forest on hill-tops of the Ralska Upland, Czech Republic. We performed mark-recapture study of the population and assessed its distribution pattern. Our results demonstrate the high mobility of the beetle, including dispersal between hills (up to 1.6 km). The system is thus interconnected; it contained ∼2000 adult beetles in 2008. Estimated population densities were high, ranging between 42 and 84 adult beetles/hectare a year. The population survives at a former military-training ground despite long-term isolation and low cover of mature beech forest (∼1%). Its survival could be attributed to lack of forestry activities between the 1950s and 1990s, slow succession preventing canopy closure and undergrowth expansion, and probably also to the distribution of habitat patches on conspicuous hill-tops. In order to increase chances of the population for long term survival, we propose to stop clear-cuts of old beech forests, increase semi-open beech woodlands in areas currently covered by conifer plantations and active habitat management at inhabited sites and their wider environs

Variable Very High Energy Gamma-ray Emission from the Microquasar LS I +61 303

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and laboratories for elucidating the physics of relativistic jets. Here we report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I +61 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, suggesting the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or the absorption processes.Comment: 11 pages with 4 figure

Variable Very High Energy Gamma-ray Emission from the Microquasar LS I +61 303

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and laboratories for elucidating the physics of relativistic jets. Here we report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I +61 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, suggesting the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or the absorption processes.Comment: 11 pages with 4 figure