The genomic and cellular basis of biosynthetic innovation in rove beetles.

How evolution at the cellular level potentiates macroevolutionary change is central to understanding biological diversification. The >66,000 rove beetle species (Staphylinidae) form the largest metazoan family. Combining genomic and cell type transcriptomic insights spanning the largest clade, Aleocharinae, we retrace evolution of two cell types comprising a defensive gland-a putative catalyst behind staphylinid megadiversity. We identify molecular evolutionary steps leading to benzoquinone production by one cell type via a mechanism convergent with plant toxin release systems, and synthesis by the second cell type of a solvent that weaponizes the total secretion. This cooperative system has been conserved since the Early Cretaceous as Aleocharinae radiated into tens of thousands of lineages. Reprogramming each cell type yielded biochemical novelties enabling ecological specialization-most dramatically in symbionts that infiltrate social insect colonies via host-manipulating secretions. Our findings uncover cell type evolutionary processes underlying the origin and evolvability of a beetle chemical innovation.

Climate warming increases extreme daily wildfire growth risk in California.

California has experienced enhanced extreme wildfire behaviour in recent years1-3, leading to substantial loss of life and property4,5. Some portion of the change in wildfire behaviour is attributable to anthropogenic climate warming, but formally quantifying this contribution is difficult because of numerous confounding factors6,7 and because wildfires are below the grid scale of global climate models. Here we use machine learning to quantify empirical relationships between temperature (as well as the influence of temperature on aridity) and the risk of extreme daily wildfire growth (>10,000 acres) in California and find that the influence of temperature on the risk is primarily mediated through its influence on fuel moisture. We use the uncovered relationships to estimate the changes in extreme daily wildfire growth risk under anthropogenic warming by subjecting historical fires from 2003 to 2020 to differing background climatological temperatures and aridity conditions. We find that the influence of anthropogenic warming on the risk of extreme daily wildfire growth varies appreciably on a fire-by-fire and day-by-day basis, depending on whether or not climate warming pushes conditions over certain thresholds of aridity, such as 1.5 kPa of vapour-pressure deficit and 10% dead fuel moisture. So far, anthropogenic warming has enhanced the aggregate expected frequency of extreme daily wildfire growth by 25% (5-95 range of 14-36%), on average, relative to preindustrial conditions. But for some fires, there was approximately no change, and for other fires, the enhancement has been as much as 461%. When historical fires are subjected to a range of projected end-of-century conditions, the aggregate expected frequency of extreme daily wildfire growth events increases by 59% (5-95 range of 47-71%) under a low SSP1-2.6 emissions scenario compared with an increase of 172% (5-95 range of 156-188%) under a very high SSP5-8.5 emissions scenario, relative to preindustrial conditions.

Global and regional drivers of land-use emissions in 1961-2017.

Historically, human uses of land have transformed and fragmented ecosystems1,2, degraded biodiversity3,4, disrupted carbon and nitrogen cycles5,6 and added prodigious quantities of greenhouse gases (GHGs) to the atmosphere7,8. However, in contrast to fossil-fuel carbon dioxide (CO2) emissions, trends and drivers of GHG emissions from land management and land-use change (together referred to as 'land-use emissions') have not been as comprehensively and systematically assessed. Here we present country-, process-, GHG- and product-specific inventories of global land-use emissions from 1961 to 2017, we decompose key demographic, economic and technical drivers of emissions and we assess the uncertainties and the sensitivity of results to different accounting assumptions. Despite steady increases in population (+144 per cent) and agricultural production per capita (+58 per cent), as well as smaller increases in emissions per land area used (+8 per cent), decreases in land required per unit of agricultural production (-70 per cent) kept global annual land-use emissions relatively constant at about 11 gigatonnes CO2-equivalent until 2001. After 2001, driven by rising emissions per land area, emissions increased by 2.4 gigatonnes CO2-equivalent per decade to 14.6 gigatonnes CO2-equivalent in 2017 (about 25 per cent of total anthropogenic GHG emissions). Although emissions intensity decreased in all regions, large differences across regions persist over time. The three highest-emitting regions (Latin America, Southeast Asia and sub-Saharan Africa) dominate global emissions growth from 1961 to 2017, driven by rapid and extensive growth of agricultural production and related land-use change. In addition, disproportionate emissions are related to certain products: beef and a few other red meats supply only 1 per cent of calories worldwide, but account for 25 per cent of all land-use emissions. Even where land-use change emissions are negligible or negative, total per capita CO2-equivalent land-use emissions remain near 0.5 tonnes per capita, suggesting the current frontier of mitigation efforts. Our results are consistent with existing knowledge-for example, on the role of population and economic growth and dietary choice-but provide additional insight into regional and sectoral trends.

From soap bubbles to multicellular organisms: Unraveling the role of cell adhesion and physical constraints in tile pattern formation and tissue morphogenesis.

Tile patterns, in which numerous cells are arranged in a regular pattern, are found in a variety of multicellular organisms and play important functional roles. Such regular arrangements of cells are regulated by various cell adhesion molecules. On the other hand, cell shape is also known to be regulated by physical constraints similar to those of soap bubbles. In particular, circumference minimization plays an important role, and cell adhesion negatively affects this process, thereby regulating tissue morphogenesis based on physical properties. Here, we focus on the Drosophila compound eye and the mouse auditory epithelium, and summarize the mechanisms of tile pattern formation by cell adhesion molecules such as cadherins, Irre Cell Recognition Modules (IRMs), and nectins. Phenomena that cannot be explained by physical stability based on cortical tension alone have been reported in the tile pattern formation in the compound eye, suggesting that previously unexplored forces such as cellular concentric expansion force may play an important role. We would like to summarize perspectives for future research on the mechanisms of tissue morphogenesis.

Committed emissions from existing energy infrastructure jeopardize 1.5 °C climate target.

Net anthropogenic emissions of carbon dioxide (CO2) must approach zero by mid-century (2050) in order to stabilize the global mean temperature at the level targeted by international efforts1-5. Yet continued expansion of fossil-fuel-burning energy infrastructure implies already 'committed' future CO2 emissions6-13. Here we use detailed datasets of existing fossil-fuel energy infrastructure in 2018 to estimate regional and sectoral patterns of committed CO2 emissions, the sensitivity of such emissions to assumed operating lifetimes and schedules, and the economic value of the associated infrastructure. We estimate that, if operated as historically, existing infrastructure will cumulatively emit about 658 gigatonnes of CO2 (with a range of 226 to 1,479 gigatonnes CO2, depending on the lifetimes and utilization rates assumed). More than half of these emissions are predicted to come from the electricity sector; infrastructure in China, the USA and the 28 member states of the European Union represents approximately 41 per cent, 9 per cent and 7 per cent of the total, respectively. If built, proposed power plants (planned, permitted or under construction) would emit roughly an extra 188 (range 37-427) gigatonnes CO2. Committed emissions from existing and proposed energy infrastructure (about 846 gigatonnes CO2) thus represent more than the entire carbon budget that remains if mean warming is to be limited to 1.5 degrees Celsius (°C) with a probability of 66 to 50 per cent (420-580 gigatonnes CO2)5, and perhaps two-thirds of the remaining carbon budget if mean warming is to be limited to less than 2 °C (1,170-1,500 gigatonnes CO2)5. The remaining carbon budget estimates are varied and nuanced14,15, and depend on the climate target and the availability of large-scale negative emissions16. Nevertheless, our estimates suggest that little or no new CO2-emitting infrastructure can be commissioned, and that existing infrastructure may need to be retired early (or be retrofitted with carbon capture and storage technology) in order to meet the Paris Agreement climate goals17. Given the asset value per tonne of committed emissions, we suggest that the most cost-effective premature infrastructure retirements will be in the electricity and industry sectors, if non-emitting alternatives are available and affordable4,18.

Bridging the gap: viable reaction pathways from tetrahedrane to benzyne.

The addition of sp-carbon-containing molecules to polycyclic sp3 tetrahedrane (c-C4H4) results in the formation of both o-benzyne (c-C6H4) and benzene (c-C6H6). Since both c-C6H4 and c-C6H6 have been detected in the interstellar medium (ISM), providing additional pathways for their possible astrochemical formation mechanisms can lead to the discovery of other molecules, such as c-C4H4, benzvalyne, and vinylidene (:CCH2). Addition of diatomic carbon (C2), the ethynyl radical (C2H), vinylidene, and acetylene (HCCH) to c-C4H4 is undertaken in individual pathways through high-level quantum chemical computations at the CCSD(T)-F12b/cc-pVTZ-F12 level of theory. The resulting C2 addition pathway proceeds barrierlessly through benzvalyne as an intermediate and reaches a true minimum at c-C6H4, but no leaving groups are produced which is required to dissipate excess energy within an interstellar chemical scheme. Similarly, the C2H addition to c-C4H4 produces benzvalyne as well as its related isomers. This pathway allows for the loss of a hydrogen leaving group to dissipate the resulting energy. Lastly, the HCCH and :CCH2 addition pathways follow through both benzvalene and benzvalyne in order to reach c-C6H6 (benzene) and c-C6H4 (o-benzyne) as well as H2 as the required leaving group. Although there is a barrier to the HCCH addition, the :CCH2 addition presents the contrary with only submerged barriers. These proposed mechanisms provide alternative possibilities for the formation of complex organic molecules in space.

Kinetics of Metastable Argon Optical Excitation and Gain in Ar/He Microplasmas.

The optically pumped rare-gas metastable laser is capable of high-intensity lasing on a broad range of near-infrared transitions for excited-state rare gas atoms (Ar*, Kr*, Ne*, Xe*) diluted in flowing He. The lasing action is generated by photoexcitation of the metastable atom to an upper state, followed by collisional energy transfer with He to a neighboring state and lasing back to the metastable state. The metastables are generated in a high-efficiency electric discharge at pressures of ∼0.4 to 1 atm. The diode-pumped rare-gas laser (DPRGL) is a chemically inert analogue to diode-pumped alkali laser (DPAL) systems, with similar optical and power scaling characteristics for high-energy laser applications. We used a continuous-wave linear microplasma array in Ar/He mixtures to produce Ar(1s5) (Paschen notation) metastables at number densities exceeding 1013 cm-3. The gain medium was optically pumped by both a narrow-line 1 W titanium-sapphire laser and a 30 W diode laser. Tunable diode laser absorption and gain spectroscopy determined Ar(1s5) number densities and small-signal gains up to ∼2.5 cm-1. Continuous-wave lasing was observed using the diode pump laser. The results were analyzed with a steady-state kinetics model relating the gain and the Ar(1s5) number density.

Transboundary health impacts of transported global air pollution and international trade.

Millions of people die every year from diseases caused by exposure to outdoor air pollution. Some studies have estimated premature mortality related to local sources of air pollution, but local air quality can also be affected by atmospheric transport of pollution from distant sources. International trade is contributing to the globalization of emission and pollution as a result of the production of goods (and their associated emissions) in one region for consumption in another region. The effects of international trade on air pollutant emissions, air quality and health have been investigated regionally, but a combined, global assessment of the health impacts related to international trade and the transport of atmospheric air pollution is lacking. Here we combine four global models to estimate premature mortality caused by fine particulate matter (PM2.5) pollution as a result of atmospheric transport and the production and consumption of goods and services in different world regions. We find that, of the 3.45 million premature deaths related to PM2.5 pollution in 2007 worldwide, about 12 per cent (411,100 deaths) were related to air pollutants emitted in a region of the world other than that in which the death occurred, and about 22 per cent (762,400 deaths) were associated with goods and services produced in one region for consumption in another. For example, PM2.5 pollution produced in China in 2007 is linked to more than 64,800 premature deaths in regions other than China, including more than 3,100 premature deaths in western Europe and the USA; on the other hand, consumption in western Europe and the USA is linked to more than 108,600 premature deaths in China. Our results reveal that the transboundary health impacts of PM2.5 pollution associated with international trade are greater than those associated with long-distance atmospheric pollutant transport.

Anti-Granulocyte-Macrophage Colony-Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial.

Rationale: GM-CSF (granulocyte-macrophage colony-stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). Objectives: We sought to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. Measurements and Main Results: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [-6 to 17]; P = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. Conclusions: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. Clinical trial registered with www.clinicaltrials.gov (NCT04351243).

Approach to anisocoria in the emergency department.

Anisocoria describes asymmetric pupillary diameter, which can result from traumatic, pharmacologic, inflammatory, or ischemic effects on the eye. In many cases, anisocoria represents a normal physiologic variant. Morbidity associated with anisocoria is directly related to the inciting cause and can vary from benign to life-threatening. A thorough understanding by emergency physicians of normal ocular neuroanatomy, and of common causes of pathologic anisocoria, including medication-induced anisocoria, can facilitate appropriate resource utilization and timely subspecialty consultation, and can help prevent irreversible ocular injury and patient morbidity. We describe a patient who presented to the emergency department with acute onset of blurry vision with anisocoria.

The thermal isomerization of benzvalyne to benzyne.

The isomerization of the highly strained benzvalyne structure to o-benzyne has been investigated using MCSCF and CCSD(T) levels of theory. Two reaction channels were modeled: the disrotatory one which leads directly to the benzyne product, and the conrotatory one which leads to an intermediate which can subsequently lead to the benzyne product. Energies at the MRMP2 level give 22.9 kcal mol-1 for the disrotatory channel and 21.7 and 1.4 kcal mol-1 for the two steps in the conrotatory one. However, the CCSD(T) energies give 19.3 and 14.2 kcal mol-1 for the two conrotatory steps. The first step of the conrotatory channel is significantly higher than the second so is rate determining for this channel. Comparison of the two separate channels shows that the conrotatory has just a slight energetic edge of 1.2 kcal mol-1 at the MRMP2 level. We did not compute the disrotatory channel at the CCSD(T) level due to the significant biradical nature of the wavefunction with natural orbital occupation numbers of 1.2 and 0.8 in the active space.

Benzvalyne: Real or imaginary?

Benzvalyne (C6H4) is a bicyclic structural isomer of o-benzyne that some typically trusted levels of theory do not report as a minimum on the potential energy surface (PES). The structure was found to be a C2v minimum at the MCSCF, MP2, coupled-cluster single double, coupled-cluster single double triple (CCSDT)-1b, and CCSDT-2 levels of theory. Density functionals at the B3LYP-D3, B2PLYP-D3, and M06-D3 levels also produced a minimum structure. On the other hand, the CCSD(T), CCSD(T)-F12, and CCSDT-1a methods produced a single imaginary frequency for benzvalyne. However, the increase in the correlation for the CCSDT-1b and CCSDT-2 methods implies that benzvalyne is, in fact, a true, if highly strained, minimum on the PES. The C-C≡C bond angle was found to be only 108°; this angle is 180° for an unstrained C-C≡C triple bond moiety. As a result, the strain energy is notably high at 159 kcal mol-1. Comparing the strain energy of the rest of the molecule gives a strain energy of 92 kcal mol-1 for this triple bond region alone. The computed harmonic frequencies contain normal modes consisting of two hindered rotations of the C≡C diatomic part of the molecule, suggesting that the dissociation of this diatomic from the bicylobutane moiety may be important in the chemistry of this molecule. Because the putative C2v minimum is predicted to have a significant dipole moment (2.6 D), benzvalyne may be detectable in TMC-1, where the related o-benzyne molecule has recently been observed by radio astronomy.

Economic carbon cycle feedbacks may offset additional warming from natural feedbacks.

As the Earth warms, carbon sinks on land and in the ocean will weaken, thereby increasing the rate of warming. Although natural mechanisms contributing to this positive climate-carbon feedback have been evaluated using Earth system models, analogous feedbacks involving human activities have not been systematically quantified. Here we conceptualize and estimate the magnitude of several economic mechanisms that generate a carbon-climate feedback, using the Kaya identity to separate a net economic feedback into components associated with population, GDP, heating and cooling, and the carbon intensity of energy production and transportation. We find that climate-driven decreases in economic activity (GDP) may in turn decrease human energy use and thus fossil fuel CO2 emissions. In a high radiative forcing scenario, such decreases in economic activity reduce fossil fuel emissions by 13% this century, lowering atmospheric CO2 by over 100 ppm in 2100. The natural carbon-climate feedback, in contrast, increases atmospheric CO2 over this period by a similar amount, and thus, the net effect including both feedbacks is nearly zero. Our work highlights the importance of improving the representation of climate-economic feedbacks in scenarios of future change. Although the effects of climate warming on the economy may offset weakening land and ocean carbon sinks, a loss of economic productivity will have high societal costs, potentially increasing wealth inequity and limiting resources available for effective adaptation.

Impacts of climate change on future air quality and human health in China.

In recent years, air pollution has caused more than 1 million deaths per year in China, making it a major focus of public health efforts. However, future climate change may exacerbate such human health impacts by increasing the frequency and duration of weather conditions that enhance air pollution exposure. Here, we use a combination of climate, air quality, and epidemiological models to assess future air pollution deaths in a changing climate under Representative Concentration Pathway 4.5 (RCP4.5). We find that, assuming pollution emissions and population are held constant at current levels, climate change would adversely affect future air quality for >85% of China's population (∼55% of land area) by the middle of the century, and would increase by 3% and 4% the population-weighted average concentrations of fine particulate matter (PM2.5) and ozone, respectively. As a result, we estimate an additional 12,100 and 8,900 Chinese (95% confidence interval: 10,300 to 13,800 and 2,300 to 14,700, respectively) will die per year from PM2.5 and ozone exposure, respectively. The important underlying climate mechanisms are changes in extreme conditions such as atmospheric stagnation and heat waves (contributing 39% and 6%, respectively, to the increase in mortality). Additionally, greater vulnerability of China's aging population will further increase the estimated deaths from PM2.5 and ozone in 2050 by factors of 1 and 3, respectively. Our results indicate that climate change and more intense extremes are likely to increase the risk of severe pollution events in China. Managing air quality in China in a changing climate will thus become more challenging.

Bluetongue virus serotype 12 enters Australia - a further incursion of novel western lineage genome segments.

Bluetongue virus (BTV) is an arbovirus (genus: Orbivirus) that occurs worldwide. It infects domestic and wild ruminant species and can cause disease in livestock, producing high economic impact. Recently, it gained extra prominence throughout Europe, with disease occurring in regions traditionally free of BTV. BTV enters Australia from Southeast Asia via wind-borne infected Culicoides spp. The first Australian isolation was 1975 (BTV-20) and further serotypes were isolated between 1979-86 (BTV-1, -3, -9, -15, -16, -21, -23). Despite increased, more sensitive, monitoring, no more were detected in over two decades, implying a stable BTV episystem of eastern ancestry. Isolations of BTV-2, -7 and -5 then occurred between 2007-15, with the latter two possessing genome segments with high sequence identity to western isolates. We report on the first isolation and genomic characterization of BTV-12, which revealed that three more novel western topotype gene segments have entered northern Australia.

Integration of energy systems.

Abstract: This article in MRS Bulletin and the framework set out in the introductory article articulate a scenario of renewable electrons and electrification of end use appliances and industrial processes as a plausible paradigm to realize a carbon-free energy economy. The subsequent articles cover specific sectoral or chemical applications of those renewable electrons (e.g., for hydrogen, transportation, building use, electrochemical storage, and within the chemical industry). This article addresses the intersections among and across those sectors. We describe the importance of considering integrated systems and systems of systems as we consider pathways to a decarbonized energy economy. Further, we review and summarize key insights into the innovation challenges that reside at the particular integration interfaces among sectors, and highlight the opportunity for advances in materials and processes that will be critical to successful achievement of economy-wide, low-carbon energy systems.

The urban-adapted underground mosquito Culex pipiens form molestus maintains exogenously influenceable circadian rhythms.

Genes known to affect circadian rhythms (i.e. 'clock genes') also influence the photoperiodic induction of overwintering reproductive diapause in the northern house mosquito, Culex pipiens f. pipiens. This suggests that molecular changes in one or more clock genes could contribute to the inability to diapause in a second form of this mosquito, Culex pipiens f. molestus. Temperate populations of Cx. pipiens f. molestus inhabit underground locations generally devoid of predictable photoperiods. For this reason, there could be limited fitness consequences if the hypothesized molecular changes to its clock genes also eliminated this mosquito's ability to regulate circadian rhythms in response to photoperiod variation. Here, we demonstrate that in contrast to this prediction, underground derived Cx. pipiens f. molestus retain exogenously influenceable circadian rhythms. Nonetheless, our genetic analyses indicate that the gene Helicase domino (dom) has a nine-nucleotide, in-frame deletion specific to Cx. pipiens f. molestus. Previous work has shown that splice variants in this gene differentially influence circadian behavior in Drosophila melanogaster. We also find derived, non-synonymous single nucleotide polymorphisms (SNPs) in eight genes that may also affect circadian rhythms and/or diapause induction in Cx. pipiens f. molestus. Finally, four putative circadian genes were found to have no quantifiable expression during any examined life stage, suggesting potential regulatory effects. Collectively, our findings indicate that the distinct, but molecularly interconnected life-history traits of diapause induction and circadian rhythms are decoupled in Cx. pipiens f. molestus and suggest this taxon may be a valuable tool for exploring exogenously influenced phenotypes in mosquitoes more broadly.

Atmospheric methane removal: a research agenda.

Atmospheric methane removal (e.g. in situ methane oxidation to carbon dioxide) may be needed to offset continued methane release and limit the global warming contribution of this potent greenhouse gas. Because mitigating most anthropogenic emissions of methane is uncertain this century, and sudden methane releases from the Arctic or elsewhere cannot be excluded, technologies for methane removal or oxidation may be required. Carbon dioxide removal has an increasingly well-established research agenda and technological foundation. No similar framework exists for methane removal. We believe that a research agenda for negative methane emissions-'removal' or atmospheric methane oxidation-is needed. We outline some considerations for such an agenda here, including a proposed Methane Removal Model Intercomparison Project (MR-MIP). This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.