RNA language models predict mutations that improve RNA function.

Structured RNA lies at the heart of many central biological processes, from gene expression to catalysis. RNA structure prediction is not yet possible due to a lack of high-quality reference data associated with organismal phenotypes that could inform RNA function. We present GARNET (Gtdb Acquired RNa with Environmental Temperatures), a new database for RNA structural and functional analysis anchored to the Genome Taxonomy Database (GTDB).

Structure-guided discovery of ancestral CRISPR-Cas13 ribonucleases.

The RNA-guided ribonuclease CRISPR-Cas13 enables adaptive immunity in bacteria and programmable RNA manipulation in heterologous systems. Cas13s share limited sequence similarity, hindering discovery of related or ancestral systems. To address this, we developed an automated structural-search pipeline to identify an ancestral clade of Cas13 (Cas13an) and further trace Cas13 origins to defense-associated ribonucleases.

The extracellular matrix integrates mitochondrial homeostasis.

Cellular homeostasis is intricately influenced by stimuli from the microenvironment, including signaling molecules, metabolites, and pathogens. Functioning as a signaling hub within the cell, mitochondria integrate information from various intracellular compartments to regulate cellular signaling and metabolism. Multiple studies have shown that mitochondria may respond to various extracellular signaling events.

Rapid DNA unwinding accelerates genome editing by engineered CRISPR-Cas9.

Thermostable clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas9) enzymes could improve genome-editing efficiency and delivery due to extended protein lifetimes. However, initial experimentation demonstrated Geobacillus stearothermophilus Cas9 (GeoCas9) to be virtually inactive when used in cultured human cells. Laboratory-evolved variants of GeoCas9 overcome this natural limitation by acquiring mutations in the wedge (WED) domain that produce >100-fold-higher genome-editing levels.

Non-Thermal Solar Wind Electron Velocity Distribution Function.

The quiet-time solar wind electrons feature non-thermal characteristics when viewed from the perspective of their velocity distribution functions. They typically have an appearance of being composed of a denser thermal "core" population plus a tenuous energetic "halo" population. At first, such a feature was empirically fitted with the kappa velocity space distribution function, but ever since the ground-breaking work by Tsallis, the space physics community has embraced the potential implication of the kappa distribution as reflecting the non-extensive nature of the space plasma.

Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes.

RNA-guided endonucleases form the crux of diverse biological processes and technologies, including adaptive immunity, transposition, and genome editing. Some of these enzymes are components of insertion sequences (IS) in the IS200/IS605 and IS607 transposon families. Both IS families encode a TnpA transposase and a TnpB nuclease, an RNA-guided enzyme ancestral to CRISPR-Cas12s.

CasPEDIA Database: a functional classification system for class 2 CRISPR-Cas enzymes.

CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities.

Eukaryotic RNA-guided endonucleases evolved from a unique clade of bacterial enzymes.

RNA-guided endonucleases form the crux of diverse biological processes and technologies, including adaptive immunity, transposition, and genome editing. Some of these enzymes are components of insertion sequences (IS) in the IS200/IS605 and IS607 transposon families. Both IS families encode a TnpA transposase and TnpB nuclease, an RNA-guided enzyme ancestral to CRISPR-Cas12.

The hypothalamus predates the origin of vertebrates.

The hypothalamus coordinates neuroendocrine functions in vertebrates. To explore its evolutionary origin, we describe integrated transcriptome/connectome brain maps for swimming tadpoles of , which serves as an approximation of the ancestral proto-vertebrate. This map features several cell types related to different regions of the vertebrate hypothalamus, including the mammillary nucleus, the arcuate nucleus, and magnocellular neurons.

The Effects of Upper-Hybrid Waves on Energy Dissipation in the Electron Diffusion Region.

Using a two-dimensional particle-in-cell simulation, we investigate the effects and roles of upper-hybrid waves (UHW) near the electron diffusion region (EDR). The energy dissipation via the wave-particle interaction in our simulation agrees with  ·  measured by magnetospheric multiscale (MMS) spacecraft. It means that UHW contributes to the local energy dissipation.

High-Frequency Waves Driven by Agyrotropic Electrons Near the Electron Diffusion Region.

National Aeronautics and Space Administration's Magnetosphere Multiscale mission reveals that agyrotropic electrons and intense waves are prevalently present in the electron diffusion region. Prompted by two distinct Magnetosphere Multiscale observations, this letter investigates by theoretical means and the properties of agyrotropic electron beam-plasma instability and explains the origin of different structures in the wave spectra. The difference is owing to the fact that in one instance, a continuous beam mode is excited, while in the other, discrete Bernstein modes are excited, and the excitation of one mode versus the other depends on physical input parameters, which are consistent with observations.

High-Frequency Wave Generation in Magnetotail Reconnection: Nonlinear Harmonics of Upper Hybrid Waves.

MMS3 spacecraft passed the vicinity of the electron diffusion region of magnetotail reconnection on 3 July 2017, observing discrepancies between perpendicular electron bulk velocities and drift, and agyrotropic electron crescent distributions. Analyzing linear wave dispersions, Burch et al. (2019, https://doi.

Comprehensive single-cell transcriptome lineages of a proto-vertebrate.

Ascidian embryos highlight the importance of cell lineages in animal development. As simple proto-vertebrates, they also provide insights into the evolutionary origins of cell types such as cranial placodes and neural crest cells. Here we have determined single-cell transcriptomes for more than 90,000 cells that span the entirety of development-from the onset of gastrulation to swimming tadpoles-in Ciona intestinalis.

Solar-wind proton anisotropy versus beta relation.

The present Letter puts forth a possible explanation for the outstanding problem of measured proton temperature anisotropy in the solar wind at 1 AU apparently being regulated by the mirror and oblique fire-hose instabilities. Making use of the fact that the local magnetic field intensity near 1 AU undergoes intermediate-scale temporal variations, the present Letter carries out the quasilinear analysis of the temperature anisotropy-driven instabilities with a time-varying local B field, assuming arbitrary initial temperature ratios and parallel betas. It is found that the saturated states in (β(∥), T(⊥)/T(∥)) space are bounded by the mirror and oblique fire-hose instabilities, which is superficially similar to the observation.

Self-consistent generation of superthermal electrons by beam-plasma interaction.

It has been known since the early days of plasma physics research that superthermal electrons are generated during beam-plasma laboratory experiments. Superthermal electrons (the kappa distribution) are also ubiquitously observed in space. To explain such a feature, various particle acceleration mechanisms have been proposed.

Exact energy principle in magnetic reconnection for current-sheet models.

On the basis of an exact nonlinear energy principle, it is shown that the change in magnetic topology (i.e., reconnection) in a finite-domain system leads to the conversion of magnetic field energy to particle energy.

Unified formulation for inhomogeneity-driven instabilities in the lower-hybrid range.

A local dispersion relation that describes inhomogeneity-driven instabilities in the lower-hybrid range is derived following a procedure that correctly describes energy exchange between waves and particles in inhomogeneous media, correcting some inherent ambiguities associated with the standard formalism found in the literature. Numerical solutions of this improved dispersion relation show that it constitutes a unified formulation for the instabilities in the lower-hybrid range, describing the so-called modified two-stream instability, excited by the ion cross-field drift, including the ion Weibel instability, and also describing the lower-hybrid drift instability, which is due to inhomogeneity effects on the electron population.