Cosmic Neutrino Pevatrons: A Brand New Pathway to Astronomy, Astrophysics, and Particle Physics

The announcement by the IceCube Collaboration of the observation of 28 cosmic neutrino candidates has been greeted with a great deal of justified excitement. The data reported so far depart by 4.3\sigma from the expected atmospheric neutrino background, which raises the obvious question: "Where in the Cosmos are these neutrinos coming from?" We review the many possibilities which have been explored in the literature to address this question, including origins at either Galactic or extragalactic celestial objects. For completeness, we also briefly discuss new physics processes which may either explain or be constrained by IceCube data.Comment: This is a review article solicited for the inaugural edition of Journal of High Energy Astrophysics (JHEAp). Matching version accepted for publicatio

In silico whole-genome screening for cancer-related single-nucleotide polymorphisms located in human mRNA untranslated regions

BACKGROUND: A promising application of the huge amounts of genetic data currently available lies in developing a better understanding of complex diseases, such as cancer. Analysis of publicly available databases can help identify potential candidates for genes or mutations specifically related to the cancer phenotype. In spite of their huge potential to affect gene function, no systematic attention has been paid so far to the changes that occur in untranslated regions of mRNA. RESULTS: In this study, we used Expressed Sequence Tag (EST) databases as a source for cancer-related sequence polymorphism discovery at the whole-genome level. Using a novel computational procedure, we focused on the identification of untranslated region (UTR)-localized non-coding Single Nucleotide Polymorphisms (UTR-SNPs) significantly associated with the tumoral state. To explore possible relationships between genetic mutation and phenotypic variation, bioinformatic tools were used to predict the potential impact of cancer-associated UTR-SNPs on mRNA secondary structure and UTR regulatory elements. We provide a comprehensive and unbiased description of cancer-associated UTR-SNPs that may be useful to define genotypic markers or to propose polymorphisms that can act to alter gene expression levels. Our results suggest that a fraction of cancer-associated UTR-SNPs may have functional consequences on mRNA stability and/or expression. CONCLUSION: We have undertaken a comprehensive effort to identify cancer-associated polymorphisms in untranslated regions of mRNA and to characterize putative functional UTR-SNPs. Alteration of translational control can change the expression of genes in tumor cells, causing an increase or decrease in the concentration of specific proteins. Through the description of testable candidates and the experimental validation of a number of UTR-SNPs discovered on the secreted protein acidic and rich in cysteine (SPARC) gene, this report illustrates the utility of a cross-talk between in silico transcriptomics and cancer genetics

The Gcn4 transcription factor reduces protein synthesis capacity and extends yeast lifespan

In Saccharomyces cerevisiae, deletion of large ribosomal subunit protein-encoding genes increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the messenger RNA and protein abundance, ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes, some encoding ribosomal proteins, that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations, including ribosomal protein gene deletions, calorie restriction, and rapamycin treatment, and provide an explanation for its role in longevity and stress response

Human‐mediated dispersal and disturbance shape the metapopulation dynamics of a long‐lived herb

As anthropogenic impacts on the natural world escalate, there is increasing interest in the role of humans in dispersing seeds. But the consequences of this Human‐Mediated Dispersal (HMD) on plant spatial dynamics are little studied. In this paper, we ask how secondary dispersal by HMD affects the dynamics of a natural plant metapopulation. In addition to dispersal between patches, we suggest within‐patch processes can be critical. To address this, we assess how variation in local population dynamics, caused by small‐scale disturbances, affects metapopulation size. We created an empirically based model with stochastic population dynamics and dispersal among patches, which represented a real‐world, cliff‐top metapopulation of wild cabbage Brassica oleracea. We collected demographic data from multiple populations by tagging plants over eight years. We assessed seed survival, and establishment and survival of seedlings in intact vegetation vs. small disturbances. We modeled primary dispersal by wind using field data and used experimental data on secondary HMD by hikers. We monitored occupancy patterns over a 14‐yr period in the real metapopulation. Disturbance had large effects on local population growth rates, by increasing seedling establishment and survival. This meant that the modeled metapopulation grew in size only when the area disturbed in each patch was above 35%. In these growing metapopulations, although only 0.2% of seeds underwent HMD, this greatly enhanced metapopulation growth rates. Similarly, HMD allowed more colonizations in declining metapopulations under low disturbance, and this slowed the rate of decline. The real metapopulation showed patterns of varying patch occupancy over the survey years, which were related to habitat quality, but also positively to human activity along the cliffs, hinting at beneficial effects of humans. These findings illustrate that realistic changes to dispersal or demography, specifically by humans, can have fundamental effects on the viability of a species at the landscape scale

Enhanced Hydrologic Connectivity and Solute Dynamics Following Wildfire and Drought in a Contaminated Temperate Peatland Catchment

Intact peatlands provide hydrological ecosystem services, such as regulating water regimes and immobilizing pollutants within catchments. Climate change impacts including drought and wildfire may impair their functioning, potentially impacting ecosystem service delivery. Here we investigate stream water quality changes following the combined impacts of a summer drought and wildfire in a peat‐dominated catchment in the UK during 2018. The study catchment stores legacy pollutants (i.e., metals) due to past industrial activity, thus making it particularly susceptible to pollutant release during wildfires. We quantified changes in water chemistry during five storm events over a 9‐month period following the wildfire. Concentration‐discharge (C‐Q) relationships for nine solutes were analyzed to explore changes in activation and connectivity of solute source zones. Hysteresis and flushing indices of C‐Q responses further described solute dynamics during storm events. We found that most nutrient and base cation concentrations in the stream discharge were highest in the immediate post‐fire storm events and decreased during subsequent autumn and spring storms. Metal concentrations increased during autumn and spring storms, indicating delayed mobilization from within‐peat or distal headwater sources. Our findings suggest that seasonal re‐wetting and hydrologic connectivity following disturbance influenced solute source zone activation and transport in the study catchment. Water quality responses associated with wildfire and drought were primarily observed in the months following the wildfire, suggesting mobilization of pollutants peaks shortly after fire. Our results contribute to a critical understanding of the future of water quality risks in temperate peatland catchments subject to disturbances exacerbated by climate change

An Analysis of Private School Closings

We add to the small literature on private school supply by exploring exits of K-12 private schools. We find that the closure of private schools is not an infrequent event, and use national survey data from the National Center for Education Statistics to study closures of private schools. We assume that the probability of an exit is a function of excess supply of private schools over the demand, as well as the school's characteristics such as age, size, and religious affiliation. Our empirical results generally support the implications of the model. Working Paper 07-0

High-quality and anti-inflammatory diets and a healthy lifestyle are associated with lower sleep apnea risk

Study Objectives: Most studies on diet and sleep apnea focus on calorie restriction. Here we investigate potential associations between dietary quality (Healthy Eating Index [HEI], Dietary Inflammatory Index [DII]) and overall healthy lifestyle with sleep apnea risk. Methods: National Health and Nutrition Examination Survey data (waves 2005-2008 and 2015-2018; n = 14,210) were used to determine HEI, DII, and their quintiles, with the fifth quintile indicating highest adherence to each dietary construct. A healthy lifestyle score was determined using diet, smoking, alcohol intake, and physical activity level. The STOP-BANG questionnaire was used to define sleep apnea risk. Generalized linear regression models with binomial family and logit link were used to investigate potential associations. The models were adjusted for socioeconomic status, lifestyle factors, and chronic conditions. Results: The prevalence of high sleep apnea risk was 25.1%. Higher DII was positively associated with sleep apnea (odds ratioQuintile 5 vs Quintile 1 = 1.55; 95% confidence interval, 1.24-1.94; P for trend < .001), whereas higher HEI was associated with reduced sleep apnea risk (odds ratioQuintile 5 vs Quintile 1 = 0.72; 95% confidence interval, 0.59-0.88; P for trend = .007). Higher healthy lifestyle score was also associated with decreased odds of sleep apnea (P for trend < .001). There was a significant interaction between healthy lifestyle and sex with sleep apnea risk (P for interaction = .049) whereby females with higher healthy lifestyle scores had a lower risk of sleep apnea compared to males. Conclusions: Higher-quality and anti-inflammatory diets and a healthier overall lifestyle are associated with lower sleep apnea risk. These findings underline the importance of strategies to improve overall diet quality and promote healthy behavior, not just calorie restriction, to reduce sleep apnea risk

Statistical Characterization of the Chandra Source Catalog

The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray sources in a total area of ~0.75% of the entire sky, using data from ~3,900 separate ACIS observations of a multitude of different types of X-ray sources. In order to maximize the scientific benefit of such a large, heterogeneous data-set, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Characterization efforts of other, large Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while informative, cannot serve this purpose, since the CSC analysis procedures are significantly different and the range of allowable data is much less restrictive. We describe here the characterization process for the CSC. This process includes both a comparison of real CSC results with those of other, deeper Chandra catalogs of the same targets and extensive simulations of blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig. 52 replaced with a version which astro-ph can convert to PDF without issues.

Metabolomic and Transcriptomic Insights into How Cotton Fiber Transitions to Secondary Wall Synthesis, Represses Lignification, and Prolongs Elongation

The morphogenesis of single-celled cotton fiber includes extreme elongation and staged cell wall differentiation. Designing strategies for improving cotton fiber for textiles and other uses relies on uncovering the related regulatory mechanisms. In this research we compared the transcriptomes and metabolomes of two Gossypium genotypes, Gossypium barbadense cv Phytogen 800 and G. hirsutum cv Deltapine 90. When grown in parallel, the two types of fiber developed similarly except for prolonged fiber elongation in the G. barbadense cultivar. The data were collected from isolated fibers between 10 to 28 days post anthesis (DPA) representing: primary wall synthesis to support elongation; transitional cell wall remodeling; and secondary wall cellulose synthesis, which was accompanied by continuing elongation only in G. barbadense fiber. Results: Of 206 identified fiber metabolites, 205 were held in common between the two genotypes. Approximately 38,000 transcripts were expressed in the fiber of each genotype, and these were mapped to the reference set and interpreted by homology to known genes. The developmental changes in the transcriptomes and the metabolomes were compared within and across genotypes with several novel implications. Transitional cell wall remodeling is a distinct stable developmental stage lasting at least four days (18 to 21 DPA). Expression of selected cell wall related transcripts was similar between genotypes, but cellulose synthase gene expression patterns were more complex than expected. Lignification was transcriptionally repressed in both genotypes. Oxidative stress was lower in the fiber of G. barbadense cv Phytogen 800 as compared to G. hirsutum cv Deltapine 90. Correspondingly, the G. barbadense cultivar had enhanced capacity for management of reactive oxygen species during its prolonged elongation period, as indicated by a 138-fold increase in ascorbate concentration at 28 DPA. Conclusions: The parallel data on deep-sequencing transcriptomics and non-targeted metabolomics for two genotypes of single-celled cotton fiber showed that a discrete developmental stage of transitional cell wall remodeling occurs before secondary wall cellulose synthesis begins. The data showed how lignification can be transcriptionally repressed during secondary cell wall synthesis, and they implicated enhanced capacity to manage reactive oxygen species through the ascorbate-glutathione cycle as a positive contributor to fiber length.National Science Foundation grant 1025947Cellular and Molecular Biolog