SARS-CoV-2 variants of concern exhibit varying degrees of transmissibility and, in some cases, escape from infection- and vaccine-induced immunity. Much effort has been devoted to measuring these phenotypes, but predicting their impact on the course of the pandemic - especially that of immune escape - remains a challenge. Here, we use a mathematical model to simulate the dynamics of wildtype and variant strains of SARS-CoV-2 in the context of vaccine rollout and nonpharmaceutical interventions. ...
#1Yinghong Xiao(UCSF: University of California, San Francisco)H-Index: 8
#2Peter V. Lidsky(UCSF: University of California, San Francisco)H-Index: 12
Last. Raul Andino(UCSF: University of California, San Francisco)H-Index: 64
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Summary null null RNA viruses generate defective viral genomes (DVG) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral response, inhibits replication and protects mice from several RNA viruses, including enteroviruses, influenza and SARS-CoV-2. While eTIP...
The construction of the human nervous system is a distinctly complex although highly regulated process. Human tissue inaccessibility has impeded a molecular understanding of the developmental specializations from which our unique cognitive capacities arise. A confluence of recent technological advances in genomics and stem cell-based tissue modeling is laying the foundation for a new understanding of human neural development and dysfunction in neuropsychiatric disease. Here, we review recent pro...
#1Stefan Bittner(Johannes Gutenberg University of Mainz)H-Index: 32
#2Frauke Zipp(Johannes Gutenberg University of Mainz)H-Index: 80
Successful therapeutic options directly targeting disability progression in patients with multiple sclerosis (MS), a chronic inflammatory disorder of the central nervous system, are lacking. Now, a study published in Nature by Absinta and colleagues profiles a lymphocyte-glia connection at the edge of chronic active lesions that continuously drives neurodegenerative pathways.
The mitochondrial genome encodes proteins central to mitochondrial function; however, transcript-specific mechanistic studies of mitochondrial gene products have been difficult because of challenges in their experimental manipulation. Cruz-Zaragoza et al. provide a solution to this challenge, introducing an elegant system for efficient translational silencing of transcripts in human mitochondria.
Summary null The human mitochondrial genome encodes thirteen core subunits of the oxidative phosphorylation system, and defects in mitochondrial gene expression lead to severe neuromuscular disorders. However, the mechanisms of mitochondrial gene expression remain poorly understood due to a lack of experimental approaches to analyze these processes. Here, we present an in vitro system to silence translation in purified mitochondria. In vitro import of chemically synthesized precursor-morpholino ...
Summary null null Dynein-decorated doublet microtubules (DMTs) are critical components of the oscillatory molecular machine of cilia, the axoneme, and have luminal surfaces patterned periodically by microtubule inner proteins (MIPs). Here we present an atomic model of the 48-nm repeat of a mammalian DMT, derived from a cryoelectron microscopy (cryo-EM) map of the complex isolated from bovine respiratory cilia. The structure uncovers principles of doublet microtubule organization and features spe...
Last. Tevie Mehlman(Weizmann Institute of Science)H-Index: 14
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The cyclic pyrimidines 3',5'-cyclic cytidine monophosphate (cCMP) and 3',5'-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP...
Last. Daniel Mucida(Rockefeller University)H-Index: 45
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Summary null null The enteric nervous system (ENS) controls several intestinal functions including motility and nutrient handling, which can be disrupted by infection-induced neuropathies or neuronal cell death. We investigated possible tolerance mechanisms preventing neuronal loss and disruption in gut motility after pathogen exposure. We found that following enteric infections, muscularis macrophages (MMs) acquire a tissue-protective phenotype that prevents neuronal loss, dysmotility, and main...
Cyclic pyrimidines cCMP and cUMP were known to be present in a variety of organisms and cell types, but their biological roles remained mysterious. Tal et al. show that bacteria use cCMP and cUMP as second messengers that function in anti-phage defense.
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