Cells respond to physical stimuli, such as stiffness(1), fluid shear stress(2) and hydraulic pressure(3,4). Extracellular fluid viscosity is a key physical cue that varies under physiological and pathological conditions, such as cancer(5). However, its influence on cancer biology and the mechanism by which cells sense and respond to changes in viscosity are unknown. Here we demonstrate that elevated viscosity counterintuitively increases the motility of various cell types on two-dimensional surfaces and in confinement, and increases cell dissemination from three-dimensional tumour spheroids. Increased mechanical loading imposed by elevated viscosity induces an actin-related protein 2/3 (ARP2/3)-complex-dependent dense actin network, which enhances Na+/H+ exchanger 1 (NHE1) polarization through its actin-binding partner ezrin. NHE1 promotes cell swelling and increased membrane tension, which, in turn, activates transient receptor potential cation vanilloid 4 (TRPV4) and mediates calcium influx, leading to increased RHOA-dependent cell contractility. The coordinated action of actin remodelling/dynamics, NHE1-mediated swelling and RHOA-based contractility facilitates enhanced motility at elevated viscosities. Breast cancer cells pre-exposed to elevated viscosity acquire TRPV4-dependent mechanical memory through transcriptional control of the Hippo pathway, leading to increased migration in zebrafish, extravasation in chick embryos and lung colonization in mice. Cumulatively, extracellular viscosity is a physical cue that regulates both short- and long-term cellular processes with pathophysiological relevance to cancer biology.

Collocated crystal sizes and mineral identities are critical for interpreting textural relationships in rocks and testing geological hypotheses, but it has been previously impossible to unambiguously constrain these properties using in situ instruments on Mars rovers. Here, we demonstrate that diffracted and fluoresced x-rays detected by the PIXL instrument (an x-ray fluorescence microscope on the Perseverance rover) provide information about the presence or absence of coherent crystalline domains in various minerals. X-ray analysis and multispectral imaging of rocks from the Seitah formation on the floor of Jezero crater shows that they were emplaced as coarsely crystalline igneous phases. Olivine grains were then partially dissolved and filled by finely crystalline or amorphous secondary silicate, carbonate, sulfate, and chloride/oxychlorine minerals. These results support the hypothesis that Seitah formation rocks represent olivine cumulates altered by fluids far from chemical equilibrium at low water-rock ratios.

High-throughput RNA sequencing offers broad opportunities to explore the Earth RNA virome. Mining 5,150 diverse metatranscriptomes uncovered >2.5 million RNA virus contigs. Analysis of >330,000 RNA-dependent RNA polymerases (RdRPs) shows that this expansion corresponds to a 5-fold increase of the known RNA vi-rus diversity. Gene content analysis revealed multiple protein domains previously not found in RNA viruses and implicated in virus-host interactions. Extended RdRP phylogeny supports the monophyly of the five es-tablished phyla and reveals two putative additional bacteriophage phyla and numerous putative additional classes and orders. The dramatically expanded phylum Lenarviricota, consisting of bacterial and related eu-karyotic viruses, now accounts for a third of the RNA virome. Identification of CRISPR spacer matches and bacteriolytic proteins suggests that subsets of picobirnaviruses and partitiviruses, previously associated with eukaryotes, infect prokaryotic hosts.

The Perseverance rover landed in Jezero crater, Mars, in February 2021. We used the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument to perform deep-ultraviolet Raman and fluorescence spectroscopy of three rocks within the crater. We identify evidence for two distinct ancient aqueous environments at different times. Reactions with liquid water formed carbonates in an olivine-rich igneous rock. A sulfate-perchlorate mixture is present in the rocks, which probably formed by later modifications of the rocks by brine. Fluorescence signatures consistent with aromatic organic compounds occur throughout these rocks and are preserved in minerals related to both aqueous environments.

The nature of dark matter is one of the most important unsolved questions in science. Some darkf matter candidates do not have sufficient nongravitational interactions to be probed in laboratory or accelerator experiments. It is thus important to develop astrophysical probes which can constrain or lead to a discovery of such candidates. We illustrate this using state-of-the-art measurements of strong gravitationally lensed quasars to constrain four of the most popular sterile neutrino models, and also report the constraints for other independent methods that are comparable in procedure. First, we derive effective relations to describe the correspondence between the mass of a thermal relic warm dark matter particle and the mass of sterile neutrinos produced via Higgs decay and grand unified theory (GUT)-scale scenarios, in terms of large-scale structure and galaxy formation astrophysical effects. Second, we show that sterile neutrinos produced through the Higgs decay mechanism are allowed only for mass >26keV, and GUT-scale scenario >5.3keV. Third, we show that the single sterile neutrino model produced through active neutrino oscillations is allowed for mass >92keV, and the three sterile neutrino minimal standard model (nuMSM) for mass >16keV. These are the most stringent experimental limits on these models.

Modern Galactic surveys have revealed an ancient merger that dominates the stellar halo of our galaxy (Gaia-Sausage-Enceladus, GSE). Using chemical abundances and kinematics from the H3 Survey, we identify 5559 halo stars from this merger in the radial range r (Gal) = 6-60kpc. We forward model the full selection function of H3 to infer the density profile of this accreted component of the stellar halo. We consider a general ellipsoid with principal axes allowed to rotate with respect to the galactocentric axes, coupled with a multiply broken power law. The best-fit model is a triaxial ellipsoid (axes ratios 10:8:7) tilted 25 degrees above the Galactic plane toward the Sun and a doubly broken power law with breaking radii at 12 kpc and 28 kpc. The doubly broken power law resolves a long-standing dichotomy in literature values of the halo breaking radius, being at either similar to 15 kpc or similar to 30 kpc assuming a singly broken power law. N-body simulations suggest that the breaking radii are connected to apocenter pile-ups of stellar orbits, and so the observed double-break provides new insight into the initial conditions and evolution of the GSE merger. Furthermore, the tilt and triaxiality of the stellar halo could imply that a fraction of the underlying dark matter halo is also tilted and triaxial. This has important implications for dynamical mass modeling of the galaxy as well as direct dark matter detection experiments.

At broad spatial scales, primary productivity in lakes is known to increase in concert with nutrients, and variables that may disrupt or modify the tight coupling of nutrients and algae are of increasing interest, particularly for those shifting with climate change. Storms may disrupt algae-nutrient relationships, but the expected effects differ between winter and summer seasons, particularly for seasonally ice-covered lakes. In winter, storms can dramatically change the under-ice light environment, creating light limitation that disrupts algae-nutrient relationships. Further, storms can bring both snow that blocks light and also wind that blows snow off of ice. In open water conditions, storms may promote turbulence and external nutrient loading. Here, we test the hypotheses that winter and summer storms differentially affect algae-nutrient relationships across 84 seasonally ice-covered lakes included in the Ecology Under Lake Ice dataset. While nutrients explained most of the variation in chlorophyll across these lakes, we found that secondary drivers differed between seasons. Under-ice chlorophyll was higher under a variety of precipitation and wind conditions that tend to promote snow-free clear ice, highlighting the importance of light as a limiting factor for algal growth during winter. In summer, higher water temperatures and storms corresponded with higher chlorophyll. Our study suggests that examining ice-covered lakes in a gradient from the perennial ice cover of the poles to the intermittent ice cover of lower latitudes would yield key information on the shifts in light and nutrient limitation that control algal biomass.

Viruses, including retroviruses, can be passed from mothers to their progeny during birth and breastfeeding. It is assumed that newborns may develop immune tolerance to milk-transmitted pathogens similarly to food antigens. I/LnJ mice are uniquely resistant to retroviruses acquired as newborns or as adults as they produce virus-neutralizing antibodies (Abs). A loss-of-function allele of H2-Ob (Ob), originally mapped within the virus infectivity controller 1 (vic1) locus, is responsible for production of antiretrovirus Abs in I/LnJ mice. Importantly, Ob-deficient and vic1 I/LnJ congenic mice on other genetic backgrounds produce antivirus Abs when infected as adults, but not as newborns. We report here that I/LnJ mice carry an additional genetic locus, virus infectivity controller 2 (vic2), that abrogates neonatal immune tolerance to retroviruses. Further genetic analysis mapped the vic2 locus to the telomeric end of chromosome 15. Identification of the vic2 gene and understanding of the related signaling pathways would make blocking of neonatal immune tolerance to retroviruses an achievable goal.

Previous studies have demonstrated that Pseudomonas putida strains are not only capable of growth on a wide range of organic substrates, but also chemotactic towards many of these compounds. However, in most cases the specific chemoreceptors that are involved have not been identified. The complete genome sequences of P. putida strains F1 and KT2440 revealed that each strain is predicted to encode 27 methyl-accepting chemotaxis proteins (MCPs) or MCP-like proteins, 25 of which are shared by both strains. It was expected that orthologous MCPs in closely related strains of the same species would be functionally equivalent. However, deletion of the gene encoding the P. putida F1 orthologue (locus tag Pput_4520, designated mcfS) of McpS, a known receptor for organic acids in P. putida KT2440, did not result in an obvious chemotaxis phenotype. Therefore, we constructed individual markerless MCP gene deletion mutants in P. putida F1 and screened for defective sensory responses to succinate, malate, fumarate and citrate. This screen resulted in the identification of a receptor, McfQ (locus tag Pput_4894), which responds to citrate and fumarate. An additional receptor, McfR (locus tag Pput_0339), which detects succinate, malate and fumarate, was found by individually expressing each of the 18 genes encoding canonical MCPs from strain F1 in a KT2440 mcpS-deletion mutant. Expression of mcfS in the same mcpS deletion mutant demonstrated that, like McfR, McfS responds to succinate, malate, citrate and fumarate. Therefore, at least three receptors, McfR, McfS, and McfQ, work in concert to detect organic acids in P. putida F1.