3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes…
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The authors showed that Tvax works by delivering antigens to lymphoid organs throughout the body where they transfer antigens to host dendritic cells that initiate the immune response. We could stimulate even more potent T cell responses to the antigen by combining the antigen with other inflammatory signals in the same Tvax cells, eventually having a version of the Tvax that contained antigens and the inflammatory molecules IL-12 and GM-CSF.
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Lead authors Frank Soveg and Johannes Schwerk identified a membrane-targeted gene, OAS1 p46, with strong pan-antiviral activity against a subset of viral pathogens. This protein is active against several positive-stranded RNA viruses including picornaviruses, flaviviruses, and SARS-CoV-2. Mechanistically, they show this protein is targeted to host subcellular membranes that the viruses use to hide their replication components. Using this trick, OAS1 p46 gains access to the virus and activates RNaseL that chews up viral RNA to restrict viral replication.
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In this work, we characterized the role of the redox-responsive transcriptional regulator Rex in Listeria monocytogenes growth and pathogenesis. We demonstrated that alleviation of Rex repression coordinates expression of genes necessary in the GI tract during infection, including fermentative metabolism and virulence determinants. Furthermore, we determined that Rex-dependent regulation was required for bacterial replication in peripheral organs, specifically within the gallbladder.
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Scientists only have accurate dosage advice for a small number of the most well-studied genetic variants. In a project conducted by the Dunham and Fowler labs, all possible mutations in CYP2C9 were made so that they would be able to predict the right dosage for anyone, even someone with a new gene sequence that no one has ever seen before. They hope their data can improve personalized medicine and help people avoid adverse drug reactions.
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Microglia maintain brain health and play important roles in disease and injury. Despite their known ability to proliferate, the precise nature of the population(s) capable of generating new microglia in the adult brain remains controversial. We identified Prominin-1 (CD133 or Prom1) as a putative cell surface marker of committed brain myeloid progenitor cells. We demonstrate that Prom1 expressing cells isolated…
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Most work on the development of malaria vaccines happens in laboratory or clinical trials, where people or experimental conditions are “malaria naïve” – meaning that they mimic the first time that a person is infected with malaria.  Unfortunately, this is not how things happen in the real world – in malaria-endemic areas, people are often infected by malaria many times a year, and thus harbor what we call “pre-existing immunity” to malaria infection.  In this publication, we explore how this pre-existing immunity might impact vaccination to malaria.  We show that pre-existing immunity can decrease how well vaccination works in a mouse model of malaria.
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CRISPR-based cancer dependency maps are accelerating advances in cancer precision medicine, but adequate functional maps are limited to the most common oncogenes. To identify opportunities for therapeutic intervention in other rarer subsets of cancer, we investigate the oncogene-specific dependencies conferred by the lung cancer oncogene, RIT1. Here, genome-wide CRISPR screening in KRAS, EGFR, and RIT1-mutant isogenic lung cancer cells identifies shared and unique vulnerabilities…
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3’3’-cyclic di-adenosine monophosphate (c-di-AMP) is an important nucleotide second messenger found throughout the bacterial domain of life. C-di-AMP is essential in many bacteria and regulates a diverse array of effector proteins controlling pathogenesis, cell wall homeostasis, osmoregulation, and central metabolism. Despite the ubiquity and importance of c-di-AMP, methods to detect this signaling molecule are limited, particularly at single cell resolution.…
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The lab focuses on analyzing cellular immune responses in the context of cancer and infectious disease. Although we mostly perform human studies, we also use mice for some of our studies such as this one. Our long-term goal is to identify novel biomarkers or therapeutic strategies based on the characteristics of disease-relevant immune cells. In addition to unbiased cellular analysis approaches, we focus particularly on antigen-specific cells where we can be more confident that these cells are...
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