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\"We all use language in different ways, depending on the situations we find ourselves in. In formal contexts we are usually expected to use a formal level of Standard English-the English codified in grammars, usage guides, and dictionaries. In May I Quote You on That? Stephen Spector offers a new approach to learning Standard English grammar and usage. The product of Spector's forty years of teaching courses on the English language, this book makes the conventions of formal writing and speech easier and more enjoyable to learn than traditional approaches usually do. Each lesson begins with humorous, interesting, or instructive illustrative quotations from writers, celebrities, and historical figures. Mark Twain appears alongside Winston Churchill, Yogi Berra, Woody Allen, Jerry Seinfeld, Stephen Colbert, Oprah, Lady Gaga, and many others. These quotations allow readers to infer the rules and word meanings from context. And if they stick in readers' memory, they can serve as models for the rules they exemplify. The lessons then offer short essays, written in a conversational style, on the history of the rules or the words being discussed. But because English is constantly changing, the essays offer not only the traditional rules of Standard English, but also the current opinions of usage panelists, stylists, and language specialists. When rules are controversial, Spector offers advice about stylistic choices. A companion website features a workbook with practice drills. This book will appeal to anyone who wants to write well. It's aimed at those who are applying to college, taking the SAT, or writing a job application, an essay, or anything else that requires clear and effective communication\"-- Provided by publisher.

Low vitamin D levels in human immunodeficiency virus type-1 (HIV) infected persons are associated with more rapid disease progression and increased risk for Mycobacterium tuberculosis infection. We have previously shown that 1α,25-dihydroxycholecalciferol (1,25D3), the active form of vitamin D, inhibits HIV replication in human macrophages through the induction of autophagy. In this study, we report that physiological concentrations of 1,25D3 induce the production of the human cathelicidin microbial peptide (CAMP) and autophagic flux in HIV and M. tuberculosis co-infected human macrophages which inhibits mycobacterial growth and the replication of HIV. Using RNA interference for Beclin-1 and the autophagy-related 5 homologue, combined with the chemical inhibitors of autophagic flux, bafilomycin A₁, an inhibitor of autophagosome-lysosome fusion and subsequent acidification, and SID 26681509 an inhibitor of the lysosome hydrolase cathepsin L, we show that the 1,25D3-mediated inhibition of HIV replication and mycobacterial growth during single infection or dual infection is dependent not only upon the induction of autophagy, but also through phagosomal maturation. Moreover, through the use of RNA interference for CAMP, we demonstrate that cathelicidin is essential for the 1,25D3 induced autophagic flux and inhibition of HIV replication and mycobacterial growth. The present findings provide a biological explanation for the benefits and importance of vitamin D sufficiency in HIV and M. tuberculosis-infected persons, and provide new insights into novel approaches to prevent and treat HIV infection and related opportunistic infections.

\" This book makes punctuation more fun and easier to learn than traditional approaches do. It teaches the natural way, by example: each lesson begins with quotes that exemplify good punctuation and sentence structure. Quotations are humorous and informative, drawn from the words of notable figures--Shakespeare, Mark Twain, Jerry Seinfeld, Taylor Swift, Beyoncé, Jennifer Lawrence, and many others. Short essays accompany each lesson, showing how each punctuation mark originated and how its use has altered over time. Correct punctuation is vital for clear, accurate, and natural writing. Anyone preparing a course assignment, applying for a job or for college admission, or doing any other formal writing needs to know the standard conventions of punctuation. Yet many people have never been taught how to punctuate. A necessary addition to any writer's bookshelf, this enjoyable book will teach readers to punctuate effectively and confidently--through over 500 memorable quotes and clear explanations of the rules. \"-- Provided by publisher.

HIV Nef acts as an anti-autophagic maturation factor through interaction with beclin-1 (BECN1). We report that exposure of macrophages to infectious or non-infectious purified HIV induces toll-like receptor 8 (TLR8) and BECN1 dependent dephosphorylation and nuclear translocation of TFEB and that this correlates with an increase in autophagy markers. RNA interference for ATG13, TFEB, TLR8, or BECN1 inhibits this HIV-induced autophagy. However, once HIV establishes a productive infection, TFEB phosphorylation and cytoplasmic sequestration are increased resulting in decreased autophagy markers. Moreover, by 7 d post-infection, autophagy levels are similar to mock infected controls. Conversely, although Nef deleted HIV similarly induces TFEB dephosphorylation and nuclear localization, and increases autophagy, these levels remain elevated during continued productive infection. Thus, the interaction between HIV and TLR8 serves as a signal for autophagy induction that is dependent upon the dephosphorylation and nuclear translocation of TFEB. During permissive infection, Nef binds BECN1 resulting in mammalian target of rapamycin (MTOR) activation, TFEB phosphorylation and cytosolic sequestration, and the inhibition of autophagy. To our knowledge, this is the first report of a virus modulating TFEB localization and helps to explain how HIV modulates autophagy to promote its own replication and cell survival.

Background, Factors responsible for myeloid-derived suppressor cell (MDSC) expansion and T-cell dysfunction during human immunodeficiency virus type 1 (HIV) infection are unknown. This study investigated the role of MDSCs during HIV infection. Methods. Peripheral blood mononuclear cells (PBMCs) were cultured with gpl20 and infectious or inactivated HIV, with or without anti-interleukin 6 (IL-6) antibody. CD33⁺, CD4⁺, and CD8⁺ cells were isolated from PBMCs and cocultured in the presence or absence of inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), and arginase 1 inhibitors. CD11b⁺ CD33⁺ CD14⁺ HLA-DR-/lo MDSCs, phosphorylated STAT3 (pSTAT3), and CD4⁺ CD25⁺ FoxP3⁺ cells were evaluated by flow cytometry. IL-6, interferon γ (IFN-γ), interleukin 10 (IL-10), and gp120 levels were quantified by an enzyme-linked immunosorbent assay. Results. MDSCs expanded when PBMCs were exposed to infectious or inactivated HIV. Exposure to gp120 led to MDSC expansion, with increases in IL-6 levels and pSTAT3 expression. Anti-IL-6 abrogated MDSC expansion and pSTAT3 expression. gp120-expanded CD33⁺ MDSCs inhibited IFN-γ release from autologous T cells, which was restored upon ROS and iNOS inhibition. gp120-expanded CD33⁺ MDSCs increased IL-10 and CD4⁺ CD25⁺ FoxP3⁺ regulatory T-cell levels in CD4⁺ T-cell cocultures. Finally, high frequencies of MDSCs were present in HIV-infected persons, compared with healthy controls. Conclusions. These findings demonstrate that HIV gp120 induces IL-6 and MDSC expansion, which contributes to immune suppression by modulating cytokine and cellular responses.

Officer Francis, vigilante joker \"The Infamous Black Tongue,\" and ace thief Tesseract are forced by a cold-blooded Baba Yaga into an illegal fight ring as part of her effort to placate a vicious monster from another dimension.

Toll-like receptors (TLR) are important in recognizing microbial pathogens and triggering host innate immune responses, including autophagy, and in the mediation of immune activation during human immunodeficiency virus type-1 (HIV) infection. We report here that TLR8 activation in human macrophages induces the expression of the human cathelicidin microbial peptide (CAMP), the vitamin D receptor (VDR) and cytochrome P450, family 27, subfamily B, polypeptide 1 (CYP27B1), which 1α-hydroxylates the inactive form of vitamin D, 25-hydroxycholecalciferol, into its biologically active metabolite. Moreover, we demonstrate using RNA interference, chemical inhibitors and vitamin D deficient media that TLR8 agonists inhibit HIV through a vitamin D and CAMP dependent autophagic mechanism. These data support an important role for vitamin D in the control of HIV infection, and provide a biological explanation for the benefits of vitamin D. These findings also provide new insights into potential novel targets to prevent and treat HIV infection.

The major challenge to human immunodeficiency virus (HIV) treatment is the development of strategies that lead to viral eradication. A roadblock to accomplishing this goal is the lack of an approach that would safely eliminate HIV from all resting/latent reservoirs, including macrophages. Macrophages are a key part of the innate immune system and are responsible for recognizing invading microbes and sending appropriate signals to other immune cells. Here, we found that HIV induces the upregulation of the protein TREM1 (triggering receptor expressed on myeloid cells 1), which signals an increase in the expression of antiapoptotic proteins, thus promoting survival of HIV-infected macrophages. Macrophages are a reservoir for latent human immunodeficiency type 1 (HIV) infection and a barrier to HIV eradication. In contrast to CD4 + T cells, macrophages are resistant to the cytopathic effects of acute HIV infection. Emerging data suggest a role for TREM1 (triggering receptor expressed on myeloid cells 1) in this resistance to HIV-mediated cytopathogenesis. Here, we show that upon HIV infection, macrophages increase the expression of BCL2, BCLXL, TREM1, mitofusin 1 (MFN1), and MFN2 and the translocation of BCL2L11 (BIM) to the mitochondria and decrease the expression of BCL2-associated agonist of cell death (BAD) and BAX while maintaining a 95% survival rate over 28 days. The HIV proteins Tat and gp120 and the GU-rich single-stranded RNA (ssRNA) (RNA40) from the HIV long terminal repeat region (and a natural Toll-like receptor 8 [TLR8] agonist) induced similar effects. TREM1 silencing in HIV-infected macrophages led to decreased expression of BCL2, BCLXL, MFN1, and MFN2 and increased expression of BAD and BAX. This correlated with a significant increase in apoptosis mediated by a disruption of the mitochondrial membrane potential (Δψm), leading to the release of cytochrome c and caspase 9 cleavage. Exposure of TREM1 -silenced macrophages to Tat, gp120, or RNA40 similarly resulted in the disruption of Δψm, cytochrome c release, caspase 9 cleavage, and apoptosis. Thus, our findings identify a mechanism whereby HIV promotes macrophage survival through TREM1-dependent upregulation of BCL2 family proteins and mitofusins that inhibits BCL2L11-mediated disruption of Δψm and subsequent apoptosis. These findings indicate that TREM1 can be a useful target for elimination of the HIV reservoir in macrophages. IMPORTANCE The major challenge to human immunodeficiency virus (HIV) treatment is the development of strategies that lead to viral eradication. A roadblock to accomplishing this goal is the lack of an approach that would safely eliminate HIV from all resting/latent reservoirs, including macrophages. Macrophages are a key part of the innate immune system and are responsible for recognizing invading microbes and sending appropriate signals to other immune cells. Here, we found that HIV induces the upregulation of the protein TREM1 (triggering receptor expressed on myeloid cells 1), which signals an increase in the expression of antiapoptotic proteins, thus promoting survival of HIV-infected macrophages.

Two injections of mRNA-1273, a lipid nanoparticle–encapsulated mRNA-based vaccine produced in collaboration with the NIAID that encodes the SARS-CoV-2 spike protein, conferred protection against Covid-19 illness in 94% of vaccinated patients. Adverse effects of the vaccine were mild, transient local reactions, and the incidence of systemic effects such as fever, headache, and fatigue was low.