Viruses have evolved multiple strategies to evade elimination by the immune system. Here we examined the contribution of host long noncoding RNAs (lncRNAs) in viral immune evasion. By functional screening of lncRNAs whose expression decreased upon viral infection of macrophages, we identified a lncRNA (lncRNA-GM, Gene Symbol AK189470.1) that promoted type I interferon (IFN-I) production and inhibited viral replication. Deficiency of lncRNA-GM in mice increased susceptibility to viral infection and impaired IFN-I production. Mechanistically, lncRNA-GM bound to glutathione S-transferase M1 (GSTM1) and blocked GSTM1 interaction with the kinase TBK1, reducing GSTM1-mediated S-glutathionylation of TBK1. Decreased S-glutathionylation enhanced TBK1 activity and downstream production of antiviral mediators. Viral infection reprogrammed intracellular glutathione metabolism and furthermore, an oxidized glutathione mimetic could inhibit TBK1 activity and promote viral replication. RBPJ Inhibitor-1 ic50 Our findings reveal regulation of TBK1 by S-glutathionylation and provide insight into the viral mediated metabolic changes that impact innate immunity and viral evasion.Activated B cells participate in either extrafollicular (EF) or germinal center (GC) responses. Canonical responses are composed of a short wave of plasmablasts (PBs) arising from EF sites, followed by GC producing somatically mutated memory B cells (MBC) and long-lived plasma cells. However, somatic hypermutation (SHM) and affinity maturation can take place at both sites, and a substantial fraction of MBC are produced prior to GC formation. Infection responses range from GC responses that persist for months to persistent EF responses with dominant suppression of GCs. Here, we review the current understanding of the functional output of EF and GC responses and the molecular switches promoting them. We discuss the signals that regulate the magnitude and duration of these responses, and outline gaps in knowledge and important areas of inquiry. Understanding such molecular switches will be critical for vaccine development, interpretation of vaccine efficacy and the treatment for autoimmune diseases.Bats harbor diverse viruses and manifest distinct antiviral immune responses. Recently in Cell Host & Microbe, Boys et al. demonstrated that bat receptor transporter protein 4 (RTP4) is an innate antiviral effector that inhibits flavivirus replication, revealing an evolutionary arms race between flaviviruses and their hosts.Tumors use active immunosuppressive mechanisms to evade immune recognition and shape the local inflammatory environment. In this issue of Immunity, Bonavita et al. report that tumor-derived PGE2 blocks early activation of natural killer cells and interferes with subsequent adaptive immune cell recruitment to the tumor.Although many immune cells can secrete TGF-β, whether all sources of TGF-β are functionally equivalent is unknown. In this issue, Turner et al. uncover the importance of T regulatory (Treg) cell-intrinsic Tgfb1 gene dose in the prevention of autoimmunity and allergic disease.In this issue of Immunity, Chopp et. al. use single-cell transcriptomics and epigenomics in mice and human samples to delineate developmental trajectories of αβ T cell subsets and refine the kinetic selection model of CD4+ and CD8+ T cell lineage commitment.EBF1 is a pioneer transcription factor involved in B lymphocyte specification. In this issue of Immunity, Wang et al. localize EBF1's pioneering activity to a prion-like domain that mediates recruitment of the nucleosome remodeler Brg1 and FUS-assisted liquid-liquid phase separation.Evidence from psycholinguistic research indicates that sentence processing is impaired in Primary Progressive Aphasia (PPA), and more so in individuals with agrammatic (PPA-G) than logopenic (PPA-L) subtypes. Studies have mostly focused on offline sentence production ability, reporting impaired production of verb morphology (e.g., tense, agreement) and verb-argument structure (VAS) in PPA-G, and mixed findings in PPA-L. However, little is known about real-time sentence comprehension in PPA. The present study is the first to compare real-time semantic, morphosyntactic and VAS processing in individuals with PPA (10 with PPA-G and 9 with PPA-L), and in two groups of healthy (22 young and 19 older) individuals, using event-related potentials (ERP). Participants were instructed to listen to sentences that were either well-formed (n = 150) or contained a violation of semantics (e.g., *Owen was mentoring pumpkins at the party, n = 50), morphosyntax (e.g., *The actors was singing in the theatre, n = 50) or VAS (*Ryane results indicate that on-line processing of VAS information may also be impaired in PPA-L, despite their near-normal accuracy on standardized language tests of argument structure production.The financial success of a radiology department is crucial to the well-being of both the hospital and the community it serves. Radiology trainees should therefore be conscious of how the department maintains its value within the health system. The purpose of this review is to provide a concise foundational resource for contemporary radiology residents and fellows to understand the basic financial operations of a hospital-based radiology department and to demonstrate its importance in supporting clinical activities. The radiology report is at the heart of reimbursement. Coders use this tool to assign International Classification of Diseases and Current Procedural Terminology codes to file reimbursement claims. Medicare, commanding the highest market share for third-party payers, sets algorithmic standards for compensation practices. Private insurers contract with hospitals, and providers use these systems or create their own contractual framework. Radiology leaders strategically balance these revenue streams with various departmental costs utilizing tools such as budgets and forecasts to ensure long-term organizational viability. Notably, payment practices in the United States are transforming from fee-for-service to value-based care. The roles of the radiologist and the radiology report are evolving with it. Examples of value-based payment models are accountable care organizations and bundled payments. Radiologists participating in these models are increasingly expected to be stewards of imaging utilization and effectively manage health care resources. Within this context of a globally changing incentive structure, trainees must reconceptualize their educational experience to equip themselves for both current and future types of clinical practice.RBPJ Inhibitor-1 ic50
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