The development of next-generation antimalarials that are efficacious against the human liver and asexual blood stages is recognized as one of the world’s most pressing public health challenges. In recent years, aminoacyl-tRNA synthetases, including prolyl-tRNA synthetase, have emerged as attractive targets for malaria chemotherapy. We describe the development of a single-step biochemical assay for Plasmodium and human prolyl-tRNA synthetases that overcomes critical…
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The antimicrobial resistance crisis requires the introduction of novel antibiotics. The use of conventional broad-spectrum compounds selects for resistance in off-target pathogens and harms the microbiome. This is especially true for Mycobacterium tuberculosis, where treatment requires a 6-month course of antibiotics. Here we show that a novel antimicrobial from Photorhabdus noenieputensis, which we named evybactin, is a potent and selective…
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The intestinal immune system can maintain tolerance to harmless stimuli such as commensal bacteria and food, while providing protective immunity against pathogens. Dysregulation of this balance can trigger overt inflammatory diseases such as inflammatory bowel diseases (IBD), food allergy, or increased susceptibility/reactivity to enteric pathogens.
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Microglia are specialized macrophages in the brain parenchyma that exist in multiple transcriptional states and reside within a wide range of neuronal environments1,2,3,4. However, how and where these states are generated remains poorly understood. Here, using the mouse somatosensory cortex, we demonstrate that microglia density and molecular state acquisition are determined by the local composition of pyramidal neuron classes. Using…
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This study was a collaboration between the laboratories of Dr. Christian C. Dibble and Dr. Alex Toker at Beth Israel Deaconess Medical Center and Harvard Medical School in Boston. The Dibble lab is focused on understanding how cellular metabolism, in particular Coenzyme A metabolism, is controlled by the major growth signaling pathways that are recurrently mutated in cancer. The Toker lab has a long history of discoveries concerning the role of the PI3K-AKT signaling pathway in breast cancer and in developing novel therapeutic strategies for targeting AKT in cancer.
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Intracellular Tau protein accumulation and spreading in the brain contribute to neurodegeneration and cognitive impairments in Alzheimer’s disease (AD). However, the mechanisms governing tau spreading are not fully elucidated. Here, Montal et al. analyzed tau-PET in two cohorts of cognitively normal elderly participants and first established the tau-PET network across cortical areas in the aging brain. Correlating the network with transcriptomic data,…
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Streptococcus pneumoniae is a major cause of disease in older adults, for which two vaccines, a polysaccharide vaccine (PPSV23) and a glycoconjugate vaccine (PCV13), are available. Both vaccines have shown efficacy but differ in their ability to protect against nasopharyngeal carriage and noninvasive pneumonia. Here, Davies et al. used systems serology to compare immune responses to the two vaccines head to head. They…
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Small intestinal neuroendocrine tumors (SI-NETs) are the most common neoplasms of the small bowel. The majority of tumors are located in the distal ileum with a high incidence of multiple synchronous primary tumors. Even though up to 50% of SI-NET patients are diagnosed with multifocal disease, the mechanisms underlying multiple synchronous lesions remain elusive.
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Like most human pathogens, the malaria parasite Plasmodium falciparum experiences strong selection pressure from public health interventions such as drug treatment. While most commonly studied in the context of drug targets and related pathways, parasite adaptation to control measures likely extends to phenotypes beyond drug resistance. Here, we use modeling to explore how control measures can reduce levels of within-host competition between P.…
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