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RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity
No full textIn all domains of life, tRNAs mediate the transfer of genetic information from mRNAs to proteins. As their depletion suppresses translation and, consequently, viral replication, tRNAs represent long-standing and increasingly recognized targets of innate immunity1,2,3,4,5. Here we report Cas12a3 effector nucleases from type V CRISPR–Cas adaptive immune systems in bacteria that preferentially cleave tRNAs after recognition of target RNA. Cas12a3 orthologues belong to one of two previously unreported nuclease clades that exhibit RNA-mediated cleavage of non-target RNA, and are distinct from all other known type V systems. Through cell-based and biochemical assays and direct RNA sequencing, we demonstrate that recognition of a complementary target RNA by the CRISPR RNA triggers Cas12a3 to cleave the conserved 5′-CCA-3′ tail of diverse tRNAs to drive growth arrest and anti-phage defence. Cryogenic electron microscopy structures further revealed a distinct tRNA-loading domain that positions the tRNA tail in the RuvC active site of the nuclease. By designing synthetic reporters that mimic the tRNA acceptor stem and tail, we expanded the capacity of current CRISPR-based diagnostics for multiplexed RNA detection. Overall, these findings reveal widespread tRNA inactivation as a previously unrecognized CRISPR-based immune strategy that broadens the application space of the existing CRISPR toolbox
Neuroscience: What doesn’t kill you makes you stronger
No full textSmall amounts of stress are thought to have beneficial effects. A new study reports a mechanism by which the psychedelic drug, psilocybin, causes acute release of stress hormones, despite its known long-term anti-anxiety effects
Variational structures for the Fokker-Planck equation with general Dirichlet boundary conditions
No full textWe prove the convergence of a modified Jordan–Kinderlehrer–Otto scheme to a solution
to the Fokker–Planck equation in Ω e R^d with general—strictly positive and temporally
constant—Dirichlet boundary conditions. We work under mild assumptions on the domain,
the drift, and the initial datum. In the special case where Ω is an interval in R1, we prove
that such a solution is a gradient flow—curve of maximal slope—within a suitable space of
measures, endowed with a modified Wasserstein distance. Our discrete scheme and modified
distance draw inspiration from contributions by A. Figalli and N. Gigli [J. Math. Pures
Appl. 94, (2010), pp. 107–130], and J. Morales [J. Math. Pures Appl. 112, (2018), pp. 41–88]
on an optimal-transport approach to evolution equations with Dirichlet boundary conditions.
Similarly to these works, we allow the mass to flow from/to the boundary ∂Ω throughout
the evolution. However, our leading idea is to also keep track of the mass at the boundary
by working with measures defined on the whole closure Ω . The driving functional is a
modification of the classical relative entropy that also makes use of the information at the
boundary. As an intermediate result, when Ω is an interval in R1, we find a formula for the
descending slope of this geodesically nonconvex functional
Limitation of time promotes cooperation in structured collaboration systems
No full textTemporal networks are obtained from time-dependent interactions among individuals, whereas the interactions can be emails, phone calls, face-to-face meetings, or work collaboration. In this article, a temporal game framework is established, in which interactions among rational individuals are embedded into two-player games in a time-dependent manner. This allows studying the time-dependent complexity and variability of interactions, and the way they affect prosocial behaviors. Based on this simple mathematical model, it is found that the level of cooperation is promoted when the time of collaboration is equally limited for every individual. This observation is confirmed by a series of systematic human experiments on over 1,400 subjects, forming a foundation for comprehensively describing human temporal interactions in collaboration. The research results reveal an important incentive for human cooperation, leading to a better understanding of a fascinating aspect of human nature in society