Gene activation precedes DNA demethylation in response to infection in human dendritic cells

DNA methylation is considered to be a relatively stable epigenetic mark. However, a growing body of evidence indicates that DNA methylation levels can change rapidly; for example, in innate immune cells facing an infectious agent. Nevertheless, the causal relationship between changes in DNA methylation and gene expression during infection remains to be elucidated. Here, we generated time-course data on DNA methylation, gene expression, and chromatin accessibility patterns during infection of human dendritic cells with Mycobacterium tuberculosis. We found that the immune response to infection is accompanied by active demethylation of thousands of CpG sites overlapping distal enhancer elements. However, virtually all changes in gene expression in response to infection occur before detectable changes in DNA methylation, indicating that the observed losses in methylation are a downstream consequence of transcriptional activation. Footprinting analysis revealed that immune-related transcription factors (TFs), such as NF-κB/Rel, are recruited to enhancer elements before the observed losses in methylation, suggesting that DNA demethylation is mediated by TF binding to cis-acting elements. Collectively, our results show that DNA demethylation plays a limited role to the establishment of the core regulatory program engaged upon infection

Mitochondrial cyclophilin D promotes disease tolerance by licensing NK cell development and IL-22 production against influenza virus

Severity of pulmonary viral infections, including influenza A virus (IAV), is linked to excessive immunopathology, which impairs lung function. Thus, the same immune responses that limit viral replication can concomitantly cause lung damage that must be countered by largely uncharacterized disease tolerance mechanisms. Here, we show that mitochondrial cyclophilin D (CypD) protects against IAV via disease tolerance. Cyp

Devotions for Advent 2023 Return & Rebuild The Temple of God An Advent & Christmastide Devotional

Greetings in the name of Christ! Across two seminaries, across several states, and across this Advent and Christmastide, we have gathered devotions from several students- both at CTSFW and CSL- to guide us in our consideration of this season. As new theologians and workers in the Church, we have a chance to encourage our brothers and sisters and stir each other up to look to Christ. So who is this Christ? He is the culmination of the entire Scriptures, and so we find Him everywhere. The books of Ezra and Haggai are center stage in the Advent portion: God provides a way to return, to contribute to the presence of God among His people by building His Temple. Yes, Advent is a penitential season, a season of recognizing our vocations and how we have fallen short- but also how Christ comes among us nevertheless. We all have a part to play in rebuilding the body of Christ, the true Temple of God. Let not fear of our persecutors rule over us, because God will shame them and vindicate those who wait for Him! In the joy of Christmastide, enjoy the season with a smattering of texts and devotions (as well as 3 sermons!) on the fulfillment of God’s Temple, the incarnate God! What Zerubabbel sought to accomplish, Christ has fulfilled, and He will not let us go without a reminder of our duties to the Church. His body is worthy of every gift we can bring! The Church is now God’s Temple, and even our individual bodies. How great a stewardship that we have, to build up the Body of the crucified, risen, and ascended Lord! Indeed, God’s manifold word, both Law and Gospel, have much to say to us this season. Thank you to all who contributed your wisdom and meditations for the communities’ use- and may God bless your reading and prayer.https://scholar.csl.edu/osp/1024/thumbnail.jp

Pacific Portraits: The People Behind the Scenes at Pacific University (Volume One)

When a dormitory toilet is clogged, who’s the guy charged with fixing it? Who assures that benefits and work-study monies are paid and accounted for on time? And who is tasked with ensuring Luau goes off without a hitch or that students from Saudi Arabia know how to navigate the cultural idiosyncrasies of an American university? Meet the people who work behind the scenes at Pacific University—the community of staff and faculty—as captured by Pacific’s own creative writing and photography students. Their jobs and lives are varied, but their dedication to ensuring a dynamic educational experience in all its varieties is common between them. This book strives to capture and share their stories through the creative efforts of the students their work serves.https://commons.pacificu.edu/beetree/1001/thumbnail.jp

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Genome of Diuraphis noxia, a global aphid pest of small grains

Background: The Russian wheat aphid, Diuraphis noxia Kurdjumov, is one of the most important pests of small grains throughout the temperate regions of the world. This phytotoxic aphid causes severe systemic damage symptoms in wheat, barley, and other small grains as a direct result of the salivary proteins it injects into the plant while feeding.Results: We sequenced and de novo assembled the genome of D. noxia Biotype 2, the strain most virulent to resistance genes in wheat. The assembled genomic scaffolds span 393 MB, equivalent to 93% of its 421 MB genome, and contains 19,097 genes. D. noxia has the most AT-rich insect genome sequenced to date (70.9%), with a bimodal CpG(O/E) distribution and a complete set of methylation related genes. The D. noxia genome displays a widespread, extensive reduction in the number of genes per ortholog group, including defensive, detoxification, chemosensory, and sugar transporter groups in comparison to the Acyrthosiphon pisum genome, including a 65% reduction in chemoreceptor genes. Thirty of 34 known D. noxia salivary genes were found in this assembly. These genes exhibited less homology with those salivary genes commonly expressed in insect saliva, such as glucose dehydrogenase and trehalase, yet greater conservation among genes that are expressed in D. noxia saliva but not detected in the saliva of other insects. Genes involved in insecticide activity and endosymbiont-derived genes were also found, as well as genes involved in virus transmission, although D. noxia is not a viral vector.Conclusions: This genome is the second sequenced aphid genome, and the first of a phytotoxic insect. D. noxia's reduced gene content of may reflect the influence of phytotoxic feeding in shaping the D. noxia genome, and in turn in broadening its host range. The presence of methylation-related genes, including cytosine methylation, is consistent with other parthenogenetic and polyphenic insects. The D. noxia genome will provide an important contrast to the A. pisum genome and advance functional and comparative genomics of insects and other organisms.Peer reviewedBiochemistry and Molecular Biolog

Common Genetic Variation Influences the Immune Response to Viral Infections in Human Populations

Humans show remarkable differences in susceptibility to many infectious diseases, and in part, this heterogeneity arises from variation in the immune response following infection. The immune response to infection is a complex, dynamic process that involves the coordinated action of multiple cell types to recognize and eliminate a pathogen. Genome-wide association studies and expression quantitative trait loci (eQTL) mapping studies in immune cells have shown that certain polymorphisms drive variation in the response to viruses in specific contexts. Yet, little is known about how genetic ancestry and genetic variation affect the immune response to viral infection more broadly. We generated single-cell RNA-sequencing data in multiple disease contexts, including in vitro infection with influenza A virus and in vivo infection with SARS-CoV-2, and mapped eQTL to study the genetic architecture of gene expression in these various settings. Following influenza infection, we showed that genetic ancestry effects on gene expression were common, highly cell type-specific, and often explained by cis-eQTL. Among hospitalized COVID-19 patients, we demonstrated that a substantial proportion of all cis-eQTL identified showed a significant gene-environment interaction effect: either they were observed only in monocytes of SARS-CoV-2-infected individuals or were associated with functional cell state. Together, our findings establish common cis-regulatory variants as key determinants of the response to viral infection, highlight the ubiquitous nature of gene-environment interactions in the framework of an immune response, and underscore the need to study regulatory processes in relevant cell types and disease states

Reproductive biology of the Texas ghost crab, Ocypode albicans Bosc (Decapoda: Ocypodidae)

Certain brachyura exhibit homing instincts which appear entirely equivalent to those of purely terrestrial forms. Cowles (1908) observed that O. arenaria returns directly to its burrow when in danger, even when some distance away. Hiatt (1948) presented other examples of this behavior, which is another expression of the fossorial habit. O. albicans appears to behave in this manner. These and other criteria have been presented (Hiatt, 1948) as evidence for a transition from a purely aquatic to a purely terrestrial mode of life. On the basis of these requirements, O. albicans is a near-terrestrial species. However, in its life history, this crab has a swimming zoea larval stage which is absolutely dependent upon the sea for survival. These characteristics are particularly attractive to the embryologist interested in adaptive reproduction and the ghost crab presents an opportunity to study reproductive and developmental adaptations in an animal in evolutionary flux between two vastly divergent environments. This attraction led me to investigate the reproductive biology of the Texas ghost crab. My original intent had been to include an account of the pre-larval embryology in order to provide a basis for an analysis of brachyuran development. At the outset I was awakened to the paucity of published information which might serve as a foundation for an embryological study. In the time available to me, I was able only to provide the framework for the ultimate study of embryological adaptations to the terrestrial habitat. At the beginning of each portion of this study, I have provided a brief historical introduction to that aspect of the problem. I have endeavored to present data in a manner most convenient to workers in each of the areas of investigation. Finally, I have presented my conclusions in the form of a summary, which, I believe, is the most useful technique in this form of studyEcology, Evolution and Behavio