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During meiosis, crossover recombination connects homologous chromosomes to direct their accurate segregation1. Defective crossing over causes infertility, miscarriage and congenital disease. Each pair of chromosomes attains at least one crossover via the formation and biased resolution of recombination intermediates known as double Holliday junctions2,3. A central principle of crossover resolution is that the two Holliday junctions are resolved in opposite planes by targeting nuclease incisions to specific DNA strands4. The endonuclease activity of the MutLγ complex has been implicated in the resolution of crossovers5-10, but the mechanisms that activate and direct strand-specific cleavage remain unknown. Here we show that the sliding clamp PCNA is important for crossover-biased resolution. In vitro assays with human enzymes show that PCNA and its loader RFC are sufficient to activate the MutLγ endonuclease. MutLγ is further stimulated by a co-dependent activity of the pro-crossover factors EXO1 and MutSγ, the latter of which binds Holliday junctions11. MutLγ also binds various branched DNAs, including Holliday junctions, but does not show canonical resolvase activity, implying that the endonuclease incises adjacent to junction branch points to achieve resolution. In vivo, RFC facilitates MutLγ-dependent crossing over in budding yeast. Furthermore, PCNA localizes to prospective crossover sites along synapsed chromosomes. These data highlight similarities between crossover resolution and the initiation steps of DNA mismatch repair12,13 and evoke a novel model for crossover-specific resolution of double Holliday junctions during meiosis.

Species often include multiple ecotypes that are adapted to different environments1. However, it is unclear how ecotypes arise and how their distinctive combinations of adaptive alleles are maintained despite hybridization with non-adapted populations2-4. Here, by resequencing 1,506 wild sunflowers from 3 species (Helianthus annuus, Helianthus petiolaris and Helianthus argophyllus), we identify 37 large (1-100 Mbp in size), non-recombining haplotype blocks that are associated with numerous ecologically relevant traits, as well as soil and climate characteristics. Limited recombination in these haplotype blocks keeps adaptive alleles together, and these regions differentiate sunflower ecotypes. For example, haplotype blocks control a 77-day difference in flowering between ecotypes of the silverleaf sunflower H. argophyllus (probably through deletion of a homologue of FLOWERING LOCUS T (FT)), and are associated with seed size, flowering time and soil fertility in dune-adapted sunflowers. These haplotypes are highly divergent, frequently associated with structural variants and often appear to represent introgressions from other-possibly now-extinct-congeners. These results highlight a pervasive role of structural variation in ecotypic adaptation.

The use of accelerated beams of electrons, protons or ions has furthered the development of nearly every scientific discipline. However, high-energy muon beams of equivalent quality have not yet been delivered. Muon beams can be created through the decay of pions produced by the interaction of a proton beam with a target. Such 'tertiary' beams have much lower brightness than those created by accelerating electrons, protons or ions. High-brightness muon beams comparable to those produced by state-of-the-art electron, proton and ion accelerators could facilitate the study of lepton-antilepton collisions at extremely high energies and provide well characterized neutrino beams1-6. Such muon beams could be realized using ionization cooling, which has been proposed to increase muon-beam brightness7,8. Here we report the realization of ionization cooling, which was confirmed by the observation of an increased number of low-amplitude muons after passage of the muon beam through an absorber, as well as an increase in the corresponding phase-space density. The simulated performance of the ionization cooling system is consistent with the measured data, validating designs of the ionization cooling channel in which the cooling process is repeated to produce a substantial cooling effect9-11. The results presented here are an important step towards achieving the muon-beam quality required to search for phenomena at energy scales beyond the reach of the Large Hadron Collider at a facility of equivalent or reduced footprint6.

Industry research funding is vastly eclipsing academia’s spend, but healthy development demands broad input. [ABSTRACT FROM AUTHOR]

Human genetic studies of common variants have provided substantial insight into the biological mechanisms that govern ovarian ageing1. Here we report analyses of rare protein-coding variants in 106,973 women from the UK Biobank study, implicating genes with effects around five times larger than previously found for common variants (ETAA1, ZNF518A, PNPLA8, PALB2 and SAMHD1). The SAMHD1 association reinforces the link between ovarian ageing and cancer susceptibility1, with damaging germline variants being associated with extended reproductive lifespan and increased all-cause cancer risk in both men and women. Protein-truncating variants in ZNF518A are associated with shorter reproductive lifespan—that is, earlier age at menopause (by 5.61 years) and later age at menarche (by 0.56 years). Finally, using 8,089 sequenced trios from the 100,000 Genomes Project (100kGP), we observe that common genetic variants associated with earlier ovarian ageing associate with an increased rate of maternally derived de novo mutations. Although we were unable to replicate the finding in independent samples from the deCODE study, it is consistent with the expected role of DNA damage response genes in maintaining the genetic integrity of germ cells. This study provides evidence of genetic links between age of menopause and cancer risk.Analyses focusing on protein-truncating variants from 106,973 women from in the UK Biobank identify variants in genes that reinforce the link between reproductive lifespan in women and cancer risk in both sexes. [ABSTRACT FROM AUTHOR]

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.

Gram-negative bacteria are surrounded by an inner cytoplasmic membrane and by an outer membrane, which serves as a protective barrier to limit entry of many antibiotics. The distinctive properties of the outer membrane are due to the presence of lipopolysaccharide.sup.1. This large glycolipid, which contains numerous sugars, is made in the cytoplasm; a complex of proteins forms a membrane-to-membrane bridge that mediates transport of lipopolysaccharide from the inner membrane to the cell surface.sup.1. The inner-membrane components of the protein bridge comprise an ATP-binding cassette transporter that powers transport, but how this transporter ensures unidirectional lipopolysaccharide movement across the bridge to the outer membrane is unknown.sup.2. Here we describe two crystal structures of a five-component inner-membrane complex that contains all the proteins required to extract lipopolysaccharide from the membrane and pass it to the protein bridge. Analysis of these structures, combined with biochemical and genetic experiments, identifies the path of lipopolysaccharide entry into the cavity of the transporter and up to the bridge. We also identify a protein gate that must open to allow movement of substrate from the cavity onto the bridge. Lipopolysaccharide entry into the cavity is ATP-independent, but ATP is required for lipopolysaccharide movement past the gate and onto the bridge. Our findings explain how the inner-membrane transport complex controls efficient unidirectional transport of lipopolysaccharide against its concentration gradient. Crystal structures of a five-protein complex comprising the inner-membrane components of the bacterial lipopolysaccharide transporter provide insight into the mechanism of extraction of lipopolysaccharide from the inner membrane and its transport to the outer membrane., Author(s): Tristan W. Owens [sup.1] , Rebecca J. Taylor [sup.1] , Karanbir S. Pahil [sup.1] , Blake R. Bertani [sup.2] , Natividad Ruiz [sup.2] , Andrew C. Kruse [sup.3] , [...]

Superconducting circuits are a competitive platform for quantum computation because they offer controllability, long coherence times and strong interactions--properties that are essential for the study of quantum materials comprising microwave photons. However, intrinsic photon losses in these circuits hinder the realization of quantum many-body phases. Here we use superconducting circuits to explore strongly correlated quantum matter by building a Bose-Hubbard lattice for photons in the strongly interacting regime. We develop a versatile method for dissipative preparation of incompressible many-body phases through reservoir engineering and apply it to our system to stabilize a Mott insulator of photons against losses. Site- and time-resolved readout of the lattice allows us to investigate the microscopic details of the thermalization process through the dynamics of defect propagation and removal in the Mott phase. Our experiments demonstrate the power of superconducting circuits for studying strongly correlated matter in both coherent and engineered dissipative settings. In conjunction with recently demonstrated superconducting microwave Chern insulators, we expect that our approach will enable the exploration of topologically ordered phases of matter.Engineered dissipation is used to stabilize a Mott-insulator phase of photons trapped in a superconducting circuit, providing insights into thermalization processes in strongly correlated quantum matter., Author(s): Ruichao Ma [sup.1] , Brendan Saxberg [sup.1] , Clai Owens [sup.1] , Nelson Leung [sup.1] , Yao Lu [sup.1] , Jonathan Simon [sup.1] , David I. Schuster [sup.1] Author [...]

Erratic funding for basic research, coupled with concerns that science has fallen down the priority list for politicians, has contributed to a shift in researchers' attitudes to lobbying. Erratic funding for basic research, coupled with concerns that science has fallen down the priority list for politicians, has contributed to a shift in researchers' attitudes to lobbying., Author(s): Brian Owens Author Affiliations: Demonstrators at a March for Science rally in Ottawa, Canada. [see PDF for image] Credit: David Kawai/Bloomberg/Getty Photo of demonstrators during the March for Science [...]

A small community of scientists has taken a do-it-yourself approach to microscopy: when the right tool for the job doesn't exist, make it. A small community of scientists has taken a do-it-yourself approach to microscopy: when the right tool for the job doesn't exist, make it., Author(s): Brian Owens Author Affiliations: The microscope makers Custom microscopes, such as the IsoView light-sheet microscope shown here, allow researchers to push beyond the limits of commercial systems. Credit: Raghav [...]

Author(s): Katherine Bourzac [1]; Neil Savage [2]; Brian Owens [3]; Andrew R Scott [4] Mosaic Materials: Capitalizing on carbon capture University of California, Berkeley Chemist Zoey Herm fills a balloon [...]

Researchers working with Indigenous partners are benefiting from traditional knowledge of the natural world. Researchers working with Indigenous partners are benefiting from traditional knowledge of the natural world., Author(s): Brian Owens Author Affiliations: First Nations communities bring expertise to Canada's scientific research Haley Shade (far left) and fellow students, Tanner Lockwood and Haley Allard, examine prairie plant species [...]

The buzz created by a 2017 national science review has faded, prompting calls for a renewed focus on innovation. The buzz created by a 2017 national science review has faded, prompting calls for a renewed focus on innovation., Author(s): Brian Owens Author Affiliations: Canada's researchers call for a return to stated science ambitions Monitoring activities in Ontario's IISD Experimental Lakes Area, an exceptional natural laboratory of 58 small [...]