Synergistic induction of avian immune gene expression by sirtuin modulators and histone methyltransferase inhibitors

With the parallel increase in the global demand for poultry production and rise in the threat of antimicrobial resistance, the development of novel antibiotic alternatives is integral to the security of the food-animal industry and public health. Recently, the induction of host defense peptides (HDPs) of the innate immune system has emerged as a host-directed therapeutic approach to simultaneously mitigate poultry infections and disease resistance. This study is focused on comparing the capacity for several epigenetic compounds, specifically four sirtuin modulators and a known histone methyltransferase inhibitor (BIX01294), to induce the avian innate immune response. To evaluate the in vitro response, chicken macrophage cells were treated with each compound (resveratrol, SRT2104, sirtinol, and EX527) with or without BIX01294 at variable timepoints (12, 24, 48 h). Following optimized treatment, RNA isolation, reverse transcription, and qPCR analysis of select innate immune genes (AvBD3, AvBD9, AvBD10, CLDN1, IL-1B, and MUC2) were performed to profile the avian immune response. Despite the hypothesized upregulation of the innate response strictly from sirtuin inhibitors, both the sirtuin inhibitors and activators synergized with BIX01294 to induce a significant avian HDP response with minimized inflammation. Although no further expression of mucosal or tight junction barrier protective genes was induced by any of the four modulators, this study furthers the need to understand sirtuin modulator epigenetic activity with future studies of histone profiling. Despite the unknown mechanisms of sirtuin modulators, the significant synergy response to these treatments validates the promising potential for these compounds to be actively explored as antibiotic alternatives.Lew Wentz FoundationBiochemistry and Molecular BiologyAnimal and Food Science

Epigenetic modulation of avian host defense peptide synthesis

The threat of antibiotic resistance has catalyzed the demand for novel antibiotic alternatives in veterinary and human medicine. In response, the activation of the innate immune system has become a promising alternative against resistant microbial infections.Host defense peptides (HDPs) are immunomodulatory peptides innately produced by mucosal epithelial cells along the gastrointestinal, respiratory, and urogenital tracts. These small-chain peptides utilize their dual hydrophobic and hydrophilic regions and cationic charges to electrostatically interfere with protein and nucleic acid synthesis in bacteria, fungi, protozoa, and cancer cells. HDPs recruit neutrophils, monocytes, and reduce the proinflammatory response, making them key modulators to the innate immune system.This study analyzes the potential for two epigenetic modulators, S-adenosylhomocysteine (SAH) and all-trans retinoic acid (ATRA), to induce HDP synthesis in chicken macrophage cell lines (HTC). It was hypothesized that SAH and ATRA would upregulate HDP gene expression independently and in combination with butyrate, a short-chain fatty acid known to induce HDPs.Independent trials were conducted to determine the ideal 24-hour treatment dosage of SAH and ATRA for HTC cells. Additionally, combination trials were conducted to analyze the synergy between each modulator and butyrate. Following treatment, RNA was isolated, subjected to reverse transcription, and gene expression was quantified by analyzing AvBD9 expression, a known avian HDP, normalized against GAPDH.Current results suggest that SAH and ATRA induce AvBD9 expression at optimal concentrations of 10 _M and 1 _M, respectively. However, neither compound induces statistically significant HDP expression independently or in synergy with butyrate. Further studies will be continued to confirm ATRA and SAH concentrations and avian HDP response.Lew Wentz FoundationBiochemistry and Molecular BiologyAnimal Scienc

Mercury Pollution History in Tropical and Subtropical American Lakes: Multiple Impacts and the Possible Relationship with Climate Change

Sediment cores obtained from 11 tropical and subtropical American lakes revealed that local human activities significantly increased mercury (Hg) inputs and pollution levels. Remote lakes also have been contaminated by anthropogenic Hg through atmospheric depositions. Long-term sediment-core profiles revealed an approximately 3-fold increase in Hg fluxes to sediments from c. 1850 to 2000. Generalized additive models indicate that c. 3-fold increases in Hg fluxes also occurred since 2000 in the remote sites, while Hg emissions from anthropogenic sources have remained relatively stable. The tropical and subtropical Americas are vulnerable to extreme weather events. Air temperatures in this region have shown a marked increase since the 1990s, and extreme weather events arising from climate change have increased. When comparing Hg fluxes to recent (1950-2016) climatic changes, results show marked increases in Hg fluxes to sediments during dry periods. The Standardized Precipitation-Evapotranspiration Index (SPEI) time series indicate a tendency toward more extreme drier conditions across the study region since the mid-1990s, suggesting that instabilities in catchment surfaces caused by climate change are responsible for the elevated Hg flux rates. Drier conditions since c. 2000 appear to be promoting Hg fluxes from catchments to lakes, a process that will likely be exacerbated under future climate-change scenarios

Star Cluster Classification using Deep Transfer Learning with PHANGS-HST

Currently available star cluster catalogues from HST imaging of nearby galaxies heavily rely on visual inspection and classification of candidate clusters. The time-consuming nature of this process has limited the production of reliable catalogues and thus also post-observation analysis. To address this problem, deep transfer learning has recently been used to create neural network models which accurately classify star cluster morphologies at production scale for nearby spiral galaxies (D < 20 Mpc). Here, we use HST UV-optical imaging of over 20,000 sources in 23 galaxies from the Physics at High Angular Resolution in Nearby GalaxieS (PHANGS) survey to train and evaluate two new sets of models: i) distance-dependent models, based on cluster candidates binned by galaxy distance (9-12 Mpc, 14-18 Mpc, 18-24 Mpc), and ii) distance-independent models, based on the combined sample of candidates from all galaxies. We find that the overall accuracy of both sets of models is comparable to previous automated star cluster classification studies (~60-80 per cent) and show improvement by a factor of two in classifying asymmetric and multi-peaked clusters from PHANGS-HST. Somewhat surprisingly, while we observe a weak negative correlation between model accuracy and galactic distance, we find that training separate models for the three distance bins does not significantly improve classification accuracy. We also evaluate model accuracy as a function of cluster properties such as brightness, colour, and SED-fit age. Based on the success of these experiments, our models will provide classifications for the full set of PHANGS-HST candidate clusters (N ~ 200,000) for public release.Comment: 16 pages, 10 figure

Satori 2018

The Satori is a student literary publication that expresses the artistic spirit of the students of Winona State University. Student poetry, prose, and graphic art are published in the Satori every spring since 1970. The Satori 2018 editors are Sajda Omar (Editor-in-Chief), Kylie Hoff, Keyanna Hultman, Audrey Sitte, Elyse Hoffmann. Art Director and Designer by Elyse Hoffmann. The 2018 Faculty advisor is Dr. Elizabeth Oness, Professor of English.https://openriver.winona.edu/satori/1012/thumbnail.jp

PHANGS: Constraining Star Formation Timescales Using the Spatial Correlations of Star Clusters and Giant Molecular Clouds

In the hierarchical view of star formation, giant molecular gas clouds (GMCs) undergo fragmentation to form small-scale structures made up of stars and star clusters. Here we study the connection between young star clusters and cold gas across a range of extragalactic environments by combining the high resolution (1") PHANGS-ALMA catalogue of GMCs with the star cluster catalogues from PHANGS-HST. The star clusters are spatially matched with the GMCs across a sample of 11 nearby star-forming galaxies with a range of galactic environments (centres, bars, spiral arms, etc.). We find that after 4-6 Myr the star clusters are no longer associated with any gas clouds. Additionally, we measure the autocorrelation of the star clusters and GMCs as well as their cross-correlation to quantify the fractal nature of hierarchical star formation. Young ($\leq$ 10 Myr) star clusters are more strongly autocorrelated on kpc and smaller spatial scales than the >10 Myr stellar populations, indicating that the hierarchical structure dissolves over time.Comment: 15 pages, 11 figures, 4 tables. Accepted to MNRAS Sept 6 202

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Topical advances and recent studies in paleolimnological research.

Paleolimnology combines the disciplines of limnology, geology and ecology, but because of challenges that separate investigators from direct knowledge about past lake conditions, the field is multidisciplinary by necessity. As a result, paleolimnology is influenced continuously by advances in many disciplines. As with limnological studies in recent decades, paleolimnology has diverged largely from the ecological and theoretical focuses of early investigators, but recent studies demonstrate the need for more integration of ecological and paleolimnological research. This paper provides a brief overview of recent paleolimnological investigations that have addressed questions related to theoretical ecology, as well as applied lake-management and climate research issues. We examine the use of transfer function models for estimating past water-quality conditions, and important caveats expressed by investigators about limitations in the development and use of such models. Paleolimnological research has contributed new insights about biological, physical and chemical processes in lakes that have been subject to change because of climate drivers and anthropogenic influences. These findings are relevant to predicting how lakes will respond to climate change, and will require new management approaches in the future. As the range of paleolimnological studies expands, there will be greater need for basic limnological research in order for paleolimnological investigators to better understand how sediments reflect lake processes of those regions