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A minimal cell can be thought of as comprising informational, compartment-forming and metabolic subsystems. To imagine the abiotic assembly of such an overall system, however, places great demands on hypothetical prebiotic chemistry. The perceived differences and incompatibilities between these subsystems have led to the widely held assumption that one or other subsystem must have preceded the others. Here we experimentally investigate the validity of this assumption by examining the assembly of various biomolecular building blocks from prebiotically plausible intermediates and one-carbon feedstock molecules. We show that precursors of ribonucleotides, amino acids and lipids can all be derived by the reductive homologation of hydrogen cyanide and some of its derivatives, and thus that all the cellular subsystems could have arisen simultaneously through common chemistry. The key reaction steps are driven by ultraviolet light, use hydrogen sulfide as the reductant and can be accelerated by Cu( I )–Cu (II) photoredox cycling. A minimal cell — one that has all the minimum requirements for life — is still a complex entity comprising informational, compartment-forming and metabolic subsystems. Here it is shown that, contrary to previous assumptions, a common prebiotically plausible chemistry can give rise to building blocks for all the subsystems.

The Paris Agreement commits 197 countries to achieve climate stabilisation at a global average surface temperature less than 2 ∘C above pre-industrial times using nationally determined contributions (NDCs) to demonstrate progress. Numerous industrialised economies have targets to achieve territorial climate neutrality by 2050, primarily in the form of “net zero” greenhouse gas (GHG) emissions. However, particular uncertainty remains over the role of countries' agriculture, forestry, and other land use (AFOLU) sectors for reasons including the potential trade-offs between GHG mitigation and food security, a non-zero emission target for methane as a short-lived GHG, and the requirement for AFOLU to act as a net sink to offset residual emissions from other sectors. These issues are represented at a coarse level in integrated assessment models (IAMs) that indicate the role of AFOLU in global pathways towards climate stabilisation. However, there is an urgent need to determine appropriate AFOLU management strategies at a national level within NDCs. Here, we present a new model designed to evaluate detailed AFOLU scenarios at national scale using the example of Ireland, where approximately 40 % of national GHG emissions originate from AFOLU. GOBLIN (General Overview for a Backcasting approach of Livestock INtensification) is designed to run randomised scenarios of agricultural activities and land use combinations within biophysical constraints (e.g. available land area, livestock productivities, fertiliser-driven grass yields, and forest growth rates). Using AFOLU emission factors from national GHG inventory reporting, GOBLIN calculates annual GHG emissions out to the selected target year for each scenario (2050 in this case). The long-term dynamics of forestry are represented up to 2120 so that scenarios can also be evaluated against the Paris Agreement commitment to achieve a balance between emissions and removals over the second half of the 21st century. Filtering randomised scenarios according to compliance with specific biophysical definitions (GHG time series) of climate neutrality will provide scientific boundaries for appropriate long-term actions within NDCs. We outline the rationale and methodology behind the development of GOBLIN, with an emphasis on biophysical linkages across food production, GHG emissions, and carbon sinks at a national level. We then demonstrate how GOBLIN can be applied to evaluate different scenarios in relation to a few possible simple definitions of “climate neutrality”, discussing opportunities and limitations.

Agroforestry has potential for strengthening the climate change resilience of smallholder farmers in Southeast Asia. In Indonesia, the food security challenges faced by smallholders will likely worsen due to climate change impacts. Agroforestry provides and option for strengthening climate change resilience, while contributing to food access, income, health, and environmental stability. To evaluate the evidence for such benefits, this systematic review identifies 22 peer-reviewed articles published between 2000 and 2019 which assess agroforestry’s contributions to food security in Indonesia, mostly in Java or Sumatra. Analysis of the studies indicate that traditional and commercial agroforestry contribute to food security in diverse ways: for example, traditional homegardens offer 20% more dietary diversity than commercial counterparts, while commercial homegardens may contribute up to five times more income. Agri-silviculture contributions fall along a timber versus non-timber forest product continuum that displays a similar tradeoff between diversity and income. Those systems with a commercial focus may receive 54% of their income from a single commodity crop such as coffee, while traditional systems allow greater access to plants with medicinal benefits. Nearly all agroforestry systems offered indirect benefits for food security, such as allowing more off-farm work than traditional agriculture and contributing to environmental stability: users of agroforestry were found by one study to collect 83% less fuelwood from natural forests. One study highlighted that agroforestry options have up to 98% greater net present value (for periods over 30 years) compared to slash and burn style agriculture. However, very few studies of Indonesian agroforestry focused explicitly on financial analysis and food security, indicating the need for further research. Given the similar situations faced by many Southeast Asia countries, our findings contribute to emerging trends throughout the region regarding the relationship between agroforestry and food security.

This study critically examines the use of ‘no additional warming’ approaches, such as temperature neutrality (TN), to determine national climate policy on agricultural methane (CH4). The reduced-complexity climate model MAGICC was used to quantify future national warming contributions for Ireland (a country with high per-capita CH4 emissions driven by large-scale dairy and beef production) under a business-as-usual pathway and three alternative scenarios: (1) TN, (2) a split-gas emission target, or (3) net-zero greenhouse gas emissions by 2050. TN implicitly ‘grandfathers’ CH4 emissions, ‘rewarding’ modest emission reductions even when per capita warming remains high, thereby shifting the mitigation burden and constraining the developmental space for low-income, food-insecure countries. Weaker CH4 emission reduction ambition, i.e. use of TN at the national level, is often justified on the basis of protecting global food security, because it can avoid ‘emission leakage’ from countries that export livestock products with below-average GHG intensities. However, this study demonstrates such justifications have little merit given that global trade in animal-sourced foods largely benefits wealthy markets, and often relies on imported feed, contributing to indirect land use change. The study concludes that the TN approach is not a robust basis for fair and effective national climate policy, and risks a potentially costly underestimation of both long-term CH4 mitigation and carbon dioxide removal in the context of national planning for an equitable, sustainable, food secure future.

This paper responds to a comment on our study of national “temperature neutrality” (TN) as a basis for climate policy, using Ireland as a case study. The comment mischaracterises our original analysis in several respects; we correct these mischaracterisations and engage with the substantive arguments raised. We demonstrate that the comment constructs a false dichotomy between national TN and net-zero greenhouse gas emissions (NZ-GHG), overlooking the split-gas compromise pathways explicitly evaluated in our original study. In addition, the EU effort-sharing framework is based on absolute GHG emissions reductions, not temperature contributions, and Ireland’s obligations under Regulation (EU) 2018/842 and the Paris Agreement require economy-wide absolute reductions. A national TN approach is therefore incompatible with these existing frameworks. We further show that widespread adoption of national TN would create a proliferation dynamic, a “race to the bottom”, in which the mitigation gap left by TN-adopting states increases pressure on remaining states, collectively undermining the EU and global mitigation effort. We also rebut the assertion that GWP100 lacks scientific rigour: it is grounded in the same physical climate modelling as TN-based approaches and benefits from a standardised, internationally accepted accounting protocol. Finally, we highlight the equity implications identified in our original study: national TN grandfathers disproportionately high per-capita agricultural CH 4 emissions in Ireland, appropriating emissions space needed by food-insecure developing countries. We conclude that TN is not an effective, fair, transparent, or robust basis for national climate policy.

BackgroundIntratumoral injection of cyclic dinucleotide (CDN) agonists of the stimulator of interferon genes (STING) pathway engages innate immune activation and priming of adaptive immune effectors to foster local and distal tumor clearance. Despite proven therapeutic efficacy in preclinical models, a thorough understanding of how CDNs reprogram suppressive myeloid stroma in mouse and man is lacking.MethodsHere, we perform deep transcript-level and protein-level profiling of myeloid-derived suppressor cells and M2 macrophages following stimulation with CDNs of ascending potency. Additionally, we leverage orthotopic Kras+/G12DTP53+/R172HPdx1-Cre (KPC) derived models of pancreatic adenocarcinoma (PDAC) to determine the capacity for locally administered CDNs to sensitize PDAC to immune checkpoint blockade. We use bioluminescent in vivo imaging and 30-parameter flow cytometry to profile growth kinetics and remodeling of the tumor stroma post-therapy.ResultsHighly potent synthetic STING agonists repolarize suppressive myeloid populations of human and murine origin in part through inhibition of Myc signaling, metabolic modulation, and antagonism of cell cycle. Surprisingly, high-potency synthetic agonists engage qualitatively unique pathways as compared with natural CDNs. Consistent with our mechanistic observations, we find that intratumoral injection of the highest activity STING agonist, IACS-8803, into orthotopic pancreatic adenocarcinoma lesions unmasks sensitivity to checkpoint blockade immunotherapy. Dimensionality reduction analyses of high parameter flow cytometry data reveals substantial contributions of both myeloid repolarization and T cell activation underlying the in vivo therapeutic benefit of this approach.ConclusionsThis study defines the molecular basis of STING-mediated myeloid reprogramming, revealing previously unappreciated and qualitatively unique pathways engaged by CDNs of ascending potency during functional repolarization. Furthermore, we demonstrate the potential for high potency CDNs to overcome immunotherapy resistance in an orthotopic, multifocal model of PDAC.

The recent synthesis of pyrimidine ribonucleoside-2′,3′-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of ribonucleic acid (RNA) at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3′,5′-linked RNA polymers of extant biochemistry has been lacking (previous attempts led only to short oligomers with mixed linkages). Here we show that the 2′-hydroxyl group of oligoribonucleotide-3′-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, which allows rapid and efficient template-directed ligation. The 2′- O -acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers that possess either 2′- or 3′-terminal phosphates is selective for the 2′-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2′,3′-cyclic phosphates to predominantly 3′,5′-linked RNA via partially 2′- O -acetylated RNA. One theory for the abiogenesis of RNA involves ligation of shorter oligomers that are observed after dry-state condensation of mononucleotides. Here, the chemo- and regioselective acetylation of (oligo)nucleotides in water under prebiotically plausible conditions is described. This remarkable selectivity permits the rapid template-directed ligation of oligomers to favour extant 3′,5′-linkages.

The declining availability of grazing land and the increasing prices of commercial dairy feed threaten the sustainability of traditional smallholder livestock farmer (SLF) practices across sub-Saharan Africa. Fodder tree technology (FTT), an agroforestry approach that entails the cultivation of multipurpose fodder trees on farmlands, could help address such challenges. However, the adoption rate of FTT has been low, especially in Malawi, where dairy processing plants usually operate at 20% capacity and milk consumption is less than half the African average. This paper investigates the role of 20 possible determinants of FTT adoption. It uses binary logistic regression to analyze primary data collected through two extensive household surveys conducted during the Agroforestry Food Security Program (AFSP) in different regions of Malawi. This data is complemented with qualitative information extracted through in-depth interviews with SLF. The general lack of knowledge regarding FTT was identified as the largest constraint to adoption. It was further confounded by other factors such as the lack of market access, inconsistent emphasis of training organizations during extension efforts, gender disparities, poor land quality, and issues of land tenure. The “extension environment” created by the AFSP influenced the perceptions of SLF for some adoption determinants. In particular it reduced the influence of sociological and geographic factors such as relationships with lead farmers, and shifted financial focus from the cost and availability of inputs, to the means of capitalizing on outputs (such as market access). This improved FTT adoption by 53% overall. Some suggestions for future extension efforts on how to improve the perceptions of the expected utility of FTT include the careful evaluation of farmer-led extension models, assurance of seed supply, and the consideration of institutional/sociological factors in project design. Examples of such factors include divorce rates, conflicts between formal and customary laws/rules, and infrastructure.

The identification of agriculture and land use configurations that achieve net zero (NZ) greenhouse gas emissions is critical to inform appropriate land use and food policy, yet national NZ targets lack consistent definitions. Here, 3000 randomised scenarios projecting future agricultural production and compatible land use combinations in Ireland were screened using ten NZ definitions. When aggregating carbon dioxide, methane, and nitrous oxide emissions using various methods, 1–85% of scenarios met NZ criteria. Despite considerable variation, common actions emerged across definitions, including high rates of afforestation, organic soil re-wetting, and cattle destocking. Ambitious technical abatement of agricultural emissions moderated, but could not substitute, these actions. With abatement, 95th percentile milk output varied from 11–91% of 2021 output, but was associated with reductions of up to 98% in suckler-beef production, and a 47–387% increase in forest cover. Achieving NZ will thus require transformation of Ireland’s land sector. Lagging land use change effects require urgent action, but sustaining a just transition will require visioning of future NZ land use combinations supporting a sustainable and resilient food system, alongside an expanding circular bioeconomy. We provide new insight into the sensitivity of such visioning to NZ definitions, pointing to an urgent need for international consensus on the accounting of methane emissions in NZ targets.

Bioenergy with carbon capture and storage (BECCS) is a key component of pathways to net zero, yet potential interactions with forest carbon dynamics, cascading wood strategies, and progressive decarbonisation and CCS deployment are poorly represented in assessments. Here, using dynamic life cycle assessment, we explore these factors for sawmill residue-derived BECCS value chains over long, yet flexible, time-horizons. BECCS improves the climate performance of bioenergy and consistently delivers long-term global cooling, even in a fully decarbonised economy where substitution benefits cease, provided forest carbon stocks are maintained. Cascading wood use delivers greater near-term cooling via product substitutions compared to direct diversion to bioenergy, and provides temporary carbon storage complementing later deployment of permanent carbon storage via BECCS. Without cascading use, unharvested forests can deliver stronger near-term cooling than direct diversion to bioenergy, even with full BECCS deployment. However, the sink strength diminishes as forests mature, and sequestered carbon may be vulnerable to disturbances such as wildfire. Crossover points highlight the critical role of cascading wood use coupled with BECCS to ensure continuous and enduring cooling effects. Transferring biogenic carbon from forests to geological stores, via multiple uses, is likely to enhance the longevity and resilience of carbon dioxide removal in a rapidly warming world. Using wood in cascading applications provides stronger near-term cooling benefits through material substitution than sending it directly to bioenergy, while also offering temporary carbon storage according to a dynamic life cycle analysis