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A new antibiotic traps lipopolysaccharide in its intermembrane transporter

Gram-negative bacteria are extraordinarily difficult to kill because their cytoplasmic membrane is surrounded by an outer membrane that blocks the entry of most antibiotics. The impenetrable nature of the outer membrane is due to the presence of a large, amphipathic glycolipid called lipopolysaccharide (LPS) in its outer leaflet1. Assembly of the outer membrane requires transport of LPS across a protein bridge that spans from the cytoplasmic membrane to the cell surface. Maintaining outer membrane integrity is essential for bacterial cell viability, and its disruption can increase susceptibility to other antibiotics2–6. Thus, inhibitors of the seven lipopolysaccharide transport (Lpt) proteins that form this transenvelope transporter have long been sought. A new class of antibiotics that targets the LPS transport machine in Acinetobacter was recently identified. Here, using structural, biochemical and genetic approaches, we show that these antibiotics trap a substrate-bou

Vitrobot markDurapore milliporePerkin elmerAnatrace maumeeGatan bioquantumFisher scientificGlobal phasingEnzo life sciencesThermo fisherAlfa aesarHycult biotechnologyNew england biolabsEton biosciencesSupplementary tablesOmplete protease inhibitor cocktailAmicon ultra

N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1,2. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3–5, but their effects on mRNA translation fidelity have not been fully explored. Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination. The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome

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Societal polarization regarding vaccinations found to be distorting accuracy of people s recall of pandemic

Societal polarization regarding vaccinations found to be distorting accuracy of people s recall of pandemic
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Cornelia betschPhilipp sprengholzLuca henkelUniversity of bambergSciencex networkResearch briefingUniversity of erfurtUniversity of viennaUniversity of chicagoExtended data tableNorthern hemisphere

Personal biases warp COVID-19 memories, posing a challenge for future pandemic policies

In a series of studies, researchers found that personal biases significantly influence how individuals remember the COVID-19 pandemic, which could potentially shape historical narratives and impact future pandemic policies. They suggest that recognizing these biases is crucial for developing long-term strategies that maintain societal trust and cohesion.

United statesUnited kingdomSouth koreaWorld health organizationExtended data tableCoronavirus disease covid 19Public health

Neural landscape diffusion resolves conflicts between needs across time

Animals perform flexible goal-directed behaviours to satisfy their basic physiological needs1–12. However, little is known about how unitary behaviours are chosen under conflicting needs. Here we reveal principles by which the brain resolves such conflicts between needs across time. We developed an experimental paradigm in which a hungry and thirsty mouse is given free choices between equidistant food and water. We found that mice collect need-appropriate rewards by structuring their choices into persistent bouts with stochastic transitions. High-density electrophysiological recordings during this behaviour revealed distributed single neuron and neuronal population correlates of a persistent internal goal state guiding future choices of the mouse. We captured these phenomena with a mathematical model describing a global need state that noisily diffuses across a shifting energy landscape. Model simulations successfully predicted behavioural and neural data, including population ne

Atlas ccfvNgai rxfpTprime karshJupyter ipythonAllen brain instituteElectron microscopy sciencesAllen institute ccfvAllen institute brain atlasThermo fisherNational institutes of healthAllen institute mouse brain atlasStanford universityAdministrative panelLaboratory animal careNational institutesWorld precision instruments