RNA polymerase III transcription is repressed in response to the tumour suppressor ARF

The tumour suppressor protein ARF provides a defence mechanism against hyperproliferative stresses that can result from the aberrant activation of oncogenes. Accordingly, ARF is silenced or deleted in many human cancers. Activation of ARF can arrest growth and cell cycle progression, or trigger apoptosis. A principle mediator of these effects is p53, which ARF stabilizes by binding and inhibiting MDM2. However, ARF has additional targets and remains able to block growth in the absence of p53, albeit less efficiently. For example, ARF can suppress rRNA production in a p53-independent manner. We have found that the synthesis of tRNA by RNA polymerase III is also inhibited in response to ARF. However, in contrast to its effects on rRNA synthesis, ARF is unable to inhibit tRNA gene transcription when p53 is ablated. These results add to the growing list of cellular changes that can be triggered by ARF induction

Associations between pressure to breastfeed and depressive, anxiety, obsessive-compulsive, and eating disorder symptoms among postpartum women

BACKGROUND: Data from qualitative interviews indicate postpartum individuals feel pressure from their healthcare providers, the media, and their partners to breastfeed their infant(s). However, the link between pressure to breastfeed and maternal mental health symptoms has not been evaluated quantitatively. The goal of the current study was to evaluate the associations between perceived pressure to breastfeed from various sources and depressive, anxiety, obsessive-compulsive, and eating disorder symptoms among postpartum individuals. METHODS: Participants were 306 women, ages 18-39, who gave birth in the past 12 months in the United States (primarily in North Carolina). They completed an online survey about their health history (including mental health symptoms) and breastfeeding experiences. RESULTS: Results found postpartum women perceived more pressure to breastfeed from healthcare providers and from the media compared to pressure to breastfeed from their partners. Pressure from healthcare providers was associated with depressive, obsessive-compulsive, and eating disorder symptoms, but not with anxiety symptoms. Pressure from the media was associated with only depressive and eating disorder symptoms. Pressure from partners was not significantly associated with mental health symptoms. Above and beyond the other sources of pressure, pressure from healthcare providers explained a unique proportion of variance of obsessive-compulsive and eating disorder symptoms. LIMITATIONS: Limitations include the cross-sectional design (which limits causal interpretations), and the homogenous sample (87% identified as White). CONCLUSIONS: Messaging and information about breastfeeding (particularly from healthcare providers) should be reviewed to determine if there is language which could be perceived as "pressure." It is important to screen for a variety of mental health symptoms, including eating disorders, in perinatal populations when discussing breastfeeding

Asteroseismology of the open clusters NGC 6791, NGC 6811, and NGC 6819 from nineteen months of Kepler photometry

We studied solar-like oscillations in 115 red giants in the three open clusters NGC 6791, NGC 6811, and NGC 6819, based on photometric data covering more than 19 months with NASA's Kepler space telescope. We present the asteroseismic diagrams of the asymptotic parameters \delta\nu_02, \delta\nu_01 and \epsilon, which show clear correlation with fundamental stellar parameters such as mass and radius. When the stellar populations from the clusters are compared, we see evidence for a difference in mass of the red giant branch stars, and possibly a difference in structure of the red clump stars, from our measurements of the small separations \delta\nu_02 and \delta\nu_01. Ensemble \'{e}chelle diagrams and upper limits to the linewidths of l = 0 modes as a function of \Delta\nu of the clusters NGC 6791 and NGC 6819 are also shown, together with the correlation between the l = 0 ridge width and the T_eff of the stars. Lastly, we distinguish between red giant branch and red clump stars through the measurement of the period spacing of mixed dipole modes in 53 stars among all the three clusters to verify the stellar classification from the color-magnitude diagram. These seismic results also allow us to identify a number of special cases, including evolved blue stragglers and binaries, as well as stars in late He-core burning phases, which can be potentially interesting targets for detailed theoretical modeling.Comment: 30 pages, 15 figures, 1 table, accepted to Ap

HST/STIS Spectroscopy of the Lyman-Alpha Emission Line in the Central Dominant Galaxies in A426, A1795, and A2597: Constraints on Clouds in the Intracluster Medium

We report on HST/STIS spectra of the Lyman-alpha emission in the central dominant galaxies in three rich clusters of galaxies. We find evidence for a population of clouds in the intracluster medium.We detect 10 Ly-alpha absorption systems towards the nucleus of NGC1275 with columns of N(HI) 1E12-1E14 cm-2. The detected absorption features are most consistent with associated nuclear absorption systems. There is very little nuclear absorption at the systemic velocity in NGC1275. This implies that the large columns detected in the 21 cm line towards the parsec scale radio source avoid the line of sight to the nucleus. This gas may be located in a circumnuclear disk or torus. We detect at least one and possibly two absorption features towards the extended Ly-alpha in A426. We do not detect absorption towards the extended Ly-alpha emission in A1795, and A2597 with upper limits N(HI) 1E13 cm-2 for optically thin absorbers. Our data constrain the covering factor of any high column density gas in the ICM to be less than 25%. Our results suggest that the lack of observed intermediate temperature gas is not explained by obscuration. In addition, the low columns of gas on the 100 kpc scales in the ICM suggests that (1) the rate at which cold gas accumulates in the ICM on these scales is very low, and (2) the dense nebulae in the central 10 kpc must have cooled or been deposited in situ.Comment: 6 figure

Sustainable Agriculture Lesson for Middle School Classrooms

In this lesson, students will learn about sustainability, where farmers/agriculturists can meet the needs of food, fiber, and fuel for the growing population. Students learn about growing population, its growth rate, major food source, sustainability barrel, potential ripple effects of positive impacts as well as the food waste and its effects

Cardiac Troponin After Percutaneous Coronary Intervention and 1-Year Mortality in Non–ST-Segment Elevation Acute Coronary Syndrome Using Systematic Evaluation of Biomarker Trends

ObjectivesThis study sought to review cardiac troponin (cTn) trends during non–ST-segment elevation acute coronary syndrome (NSTE ACS) in patients undergoing percutaneous coronary intervention (PCI) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Non–ST-Segment Elevation Acute Coronary Syndromes) and SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors) studies and to study the relationship between post-PCI cTn and mortality.BackgroundThe prognostic value of cTn post-PCI is controversial. In patients with NSTE ACS, it is especially difficult to distinguish between cTn elevations due to PCI or index myocardial infarction (MI).MethodsTime and cTn (indexed by upper limit of normal [ULN]) data pairs were plotted for 10,199 patients and independently reviewed by 2 physicians to identify patients in whom post-PCI cTn elevation could be distinguished from that of index MI. Post-PCI cTn peak was identified for each plot, and its relationship with 1-year mortality was evaluated using Cox modeling, correcting for 15 clinical variables from the EARLY ACS 1-year mortality model (including baseline cTn). We used an identical methodology to assess the association between creatine kinase-myocardial band and 1-year mortality.ResultsPatients with cTn (re-)elevation post-PCI not evaluable were identified and excluded from further analysis (4,198 [41%] with cTn rising prior to PCI; 229 [2%] with missing cTn). Among the remainder (n = 5,772 [57%]), in the multivariable model, peak cTn post-PCI was associated with a 7% increase in mortality (hazard ratio [HR] for 10× ULN increase: 1.07, 95% confidence interval [CI]: 1.02 to 1.11; p = 0.0038). Peak post-PCI creatine kinase-myocardial band was significantly associated with 1-year mortality (HR for 1× ULN increase: 1.13, 95% CI: 1.05 to 1.21; p = 0.0013).ConclusionsWe used a methodology that differentiated post-PCI cTn (re-)elevation from that of presenting MI in more than one-half of patients with NSTE ACS undergoing PCI. This identified a highly significant relationship between post-PCI cTn and 1-year mortality, with implications for both incorporating a cTn post-PCI MI definition and preventing PCI-related myonecrosis

Strike-slip faulting during the 2014 Bároarbunga-Holuhraun dike intrusion, central Iceland

Over a 13 day period magma propagated laterally from the subglacial Bárðarbunga volcano in the northern rift zone, Iceland. It created > 30,000 earthquakes at 5–7 km depth along a 48 km path before erupting on 29 August 2014. The seismicity, which tracked the dike propagation, advanced in short bursts at 0.3–4.7 km/h separated by pauses of up to 81 h. During each surge forward, seismicity behind the dike tip dropped. Moment tensor solutions from the leading edge show exclusively left-lateral strike-slip faulting subparallel to the advancing dike tip, releasing accumulated strain deficit in the brittle layer of the rift zone. Behind the leading edge, both left- and right-lateral strike-slip earthquakes are observed. The lack of non-double-couple earthquakes implies that the dike opening was aseismic.Seismometers were borrowed from the Natural Environment Research Council (NERC) SEIS-UK (loans 968 and 1022),with funding by research grants from the NERC and the European Community’s Seventh Framework Programme grant 308377 (Project FUTUREVOLC), and graduate studentships from the NERC and Shell. We thank Ágúst Þór Gunnlaugsson and others who assisted with fieldwork in Iceland and Nigel Woodcock for his helpful discussions. M.T. Gudmundsson, H. Reynolds, and Þ. Högnadóttir supplied ice cauldron coordinates. The Icelandic Meteorological Office, Chris Bean (University College Dublin), and the British Geological Survey kindly provided additional data from seismometers in northeast Iceland, data delivery from IMO seismic database 20151001/01. We thank the two anonymous reviewers for their constructive comments. Hypocenter locations in Figure 1 are listed in Tables S2 and S3. (Department of Earth Sciences, Cambridge contribution ESC3539).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/2015GL06742

Complete reannotation of the Arabidopsis genome: methods, tools, protocols and the final release

BACKGROUND: Since the initial publication of its complete genome sequence, Arabidopsis thaliana has become more important than ever as a model for plant research. However, the initial genome annotation was submitted by multiple centers using inconsistent methods, making the data difficult to use for many applications. RESULTS: Over the course of three years, TIGR has completed its effort to standardize the structural and functional annotation of the Arabidopsis genome. Using both manual and automated methods, Arabidopsis gene structures were refined and gene products were renamed and assigned to Gene Ontology categories. We present an overview of the methods employed, tools developed, and protocols followed, summarizing the contents of each data release with special emphasis on our final annotation release (version 5). CONCLUSION: Over the entire period, several thousand new genes and pseudogenes were added to the annotation. Approximately one third of the originally annotated gene models were significantly refined yielding improved gene structure annotations, and every protein-coding gene was manually inspected and classified using Gene Ontology terms

A cell based high-throughput screening approach for the discovery of new inhibitors of respiratory syncytial virus

Background: Human respiratory syncytial virus (hRSV) is a highly contagious pathogen and is the most common cause of bronchiolitis and pneumonia for infants and children under one year of age. Worldwide, greater than 33 million children under five years of age are affected by hRSV resulting in three million hospitalizations and 200,000 deaths. However, severe lower respiratory tract disease may occur at any age, especially among the elderly or those with compromised cardiac, pulmonary, or immune systems. There is no vaccine commercially available. Existing therapies for the acute infection are ribavirin and the prophylactic humanized monoclonal antibody (Synagis® from MedImmune) that is limited to use in high risk pediatric patients. Thus, the discovery of new inhibitors for hRSV would be clinically beneficial. Results: We have developed and validated a 384-well cell-based, high-throughput assay that measures the cytopathic effect of hRSV (strain Long) in HEp-2 cells using a luminescent-based detection system for signal endpoint (Cell Titer Glo®). The assay is sensitive and robust, with Z factors greater than 0.8, signal to background greater than 35, and signal to noise greater than 24. Utilizing this assay, 313,816 compounds from the Molecular Libraries Small Molecule Repository were screened at 10 μM. We identified 7,583 compounds that showed greater than 22% CPE inhibition in the primary screen. The top 2,500 compounds were selected for confirmation screening and 409 compounds showed at least 50% inhibition of CPE and were considered active. We selected fifty-one compounds, based on potency, selectivity and chemical tractability, for further evaluation in dose response and secondary assays Several compounds had SI50 values greater than 3, while the most active compound displayed an SI50 value of 58.9. Conclusions: A robust automated luminescent-based high throughput screen that measures the inhibition of hRSV-induced cytopathic effect in HEp-2 cells for the rapid identification of potential inhibitors from large compound libraries has been developed, optimized and validated. The active compounds identified in the screen represent different classes of molecules, including aryl sulfonylpyrrolidines which have not been previously identified as having anti-hRSV activity