Colony-stimulating factor 1 receptor (CSF1R) inhibition has been extensively adopted by many laboratories for the study of microglia, with the assumption that it does not cause significant effect on peripheral immune cells. The authors showed that, contrary to the accepted notion, PLX5622, a commonly used CSF1R inhibitor, does not affect only microglia but also leads to long-term changes in the myeloid and lymphoid compartments, and affects the number of tissue-resident and interstitial macrophages.
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Adoptive cell therapy with chimeric antigen receptor T cells (CAR-T) has become a standard treatment for patients with certain aggressive B cell malignancies and holds promise to improve the care of patients suffering from numerous other cancers in the future. However, the high manufacturing cost of CAR-T cell therapies poses a major barrier to their broader clinical application. Among the…
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Stimulator of interferon genes (STING) is a receptor in human cells that senses foreign cyclic dinucleotides released during bacterial infection and endogenous cyclic GMP–AMP signalling during viral infection and antitumour immunity1–5. STING shares no structural homology with other known signalling proteins6–9, limiting functional analysis and preventing explanation of the origin of cyclic dinucleotide signalling in mammalian innate immunity. Here we…
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression. Methods We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the…
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Transcription-translation coupling has long been considered a defining feature of the central dogma in bacteria. However, transcription-translation coupling has largely been characterized in E. coli and other related bacteria. The authors have demonstrated that coupling does not occur in the model gram-positive bacteria B. subtilis. Instead, in this bacterium, transcription is much faster than translation, allowing the RNA polymerase to ‘run away’ from the ribosome.
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B cell receptors (BCRs) display a combination of variable (V)-gene-encoded complementarity determining regions (CDRs) and adaptive/hypervariable CDR3 loops to engage antigens. It has long been proposed that the former tune for recognition of pathogens or groups of pathogens. To experimentally evaluate this within the human antibody repertoire, we perform immune challenges in transgenic mice that bear diverse human CDR3 and…
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Gene regulatory logic reflects the occupancy of cis elements by transcription factors and the configuration of promoters and enhancers. As the majority of genome-wide analyses have focused on adult cells, scant attention has been paid to embryonic cells, other than embryonic stem cells. Focusing on genome-wide comparative analyses of two stages of erythroblasts, we discovered that regulation of embryonic-specific genes is promoter-centric…
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The authors developed a convenient platform to conjugate molecules to Cas9, and using this platform they were able to enhance the knock-in efficiencies. By hijacking the insulin expression and secretion machinery, they used their conjugation platform to efficiently engineer beta cells to secrete a non-endogenous peptide in a glucose-responsive manner as is observed for insulin.
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Decreasing discovery rates and increasing resistance have underscored the need for novel therapeutic options to treat Mycobacterium tuberculosis infection. The authors screened extracts from previously uncultured soil microbes for specific activity against M. tuberculosis, identifying three novel compounds. They further define the mechanism of action of one compound, amycobactin.
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STING agonist – a cancer immunotherapeutic drug – could produce strong antitumor immune responses, but requires repeated injections directly into tumors over months to achieve efficacy. Such frequent injections causes difficulties for patients to comply, and increases risk of cancer metastasis, infections, and chronic injection pain. To solve these problems, we developed a biocompatible and biodegradable microparticle platform that could programmatically release scheduled doses of STING agonist with just one injection.
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