Mitochondrial H2O2 release does not directly cause damage to chromosomal DNA.

Reactive Oxygen Species (ROS) derived from mitochondrial respiration are frequently cited as a major source of chromosomal DNA mutations that contribute to cancer development and aging. However, experimental evidence showing that ROS released by mitochondria can directly damage nuclear DNA is largely lacking. In this study, we investigated the effects of H2O2 released by mitochondria or produced at the nucleosomes using a titratable chemogenetic approach. This enabled us to precisely investigate to what extent DNA damage occurs downstream of near- and supraphysiological amounts of localized H2O2. Nuclear H2O2 gives rise to DNA damage and mutations and a subsequent p53 dependent cell cycle arrest. Mitochondrial H2O2 release shows none of these effects, even at levels that are orders of magnitude higher than what mitochondria normally produce. We conclude that H2O2 released from mitochondria is unlikely to directly damage nuclear genomic DNA, limiting its contribution to oncogenic transformation and aging.

Identified senescence endotypes in aged cartilage are reflected in the blood metabolome.

Heterogeneous accumulation of senescent cells expressing the senescence-associated secretory phenotype (SASP) affects tissue homeostasis which leads to diseases, such as osteoarthritis (OA). In this study, we set out to characterize heterogeneity of cellular senescence within aged articular cartilage and explored the presence of corresponding metabolic profiles in blood that could function as representative biomarkers. Hereto, we set out to perform cluster analyses, using a gene-set of 131 senescence genes (N = 57) in a previously established RNA sequencing dataset of aged articular cartilage and a generated metabolic dataset in overlapping blood samples. Using unsupervised hierarchical clustering and pathway analysis, we identified two robust cellular senescent endotypes. Endotype-1 was enriched for cell proliferating pathways, expressing forkhead box protein O4 (FOXO4), RB transcriptional corepressor like 2 (RBL2), and cyclin-dependent kinase inhibitor 1B (CDKN1B); the FOXO mediated cell cycle was identified as possible target for endotype-1 patients. Endotype-2 showed enriched inflammation-associated pathways, expressed by interleukin 6 (IL6), matrix metallopeptidase (MMP)1/3, and vascular endothelial growth factor (VEGF)C and SASP pathways were identified as possible targets for endotype-2 patients. Notably, plasma-based metabolic profiles in overlapping blood samples (N = 21) showed two corresponding metabolic clusters in blood. These non-invasive metabolic profiles could function as biomarkers for patient-tailored targeting of senescence in OA.

Calcium promotes persistent soil organic matter by altering microbial transformation of plant litter.

Calcium (Ca) can contribute to soil organic carbon (SOC) persistence by mediating physico-chemical interactions between organic compounds and minerals. Yet, Ca is also crucial for microbial adhesion, potentially affecting colonization of plant and mineral surfaces. The importance of Ca as a mediator of microbe-mineral-organic matter interactions and resulting SOC transformation has been largely overlooked. We incubated 44Ca labeled soils with 13C15N labeled leaf litter to study how Ca affects microbial transformation of litter and formation of mineral associated organic matter. Here we show that Ca additions promote hyphae-forming bacteria, which often specialize in colonizing surfaces, and increase incorporation of litter into microbial biomass and carbon use efficiency by approximately 45% each. Ca additions reduce cumulative CO2 production by 4%, while promoting associations between minerals and microbial byproducts of plant litter. These findings expand the role of Ca in SOC persistence from solely a driver of physico-chemical reactions to a mediator of coupled abiotic-biotic cycling of SOC.

Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease mainly affecting upper and lower motoneurons. Several functionally heterogeneous genes have been associated with the familial form of this disorder (fALS), depicting an extremely complex pathogenic landscape. This heterogeneity has limited the identification of an effective therapy, and this bleak prognosis will only improve with a greater understanding of convergent disease mechanisms. Recent evidence from human post-mortem material and diverse model systems has highlighted the synapse as a crucial structure actively involved in disease progression, suggesting that synaptic aberrations might represent a shared pathological feature across the ALS spectrum. To test this hypothesis, we performed the first comprehensive analysis of the synaptic proteome from post-mortem spinal cord and human iPSC-derived motoneurons carrying mutations in the major ALS genes. This integrated approach highlighted perturbations in the molecular machinery controlling vesicle release as a shared pathomechanism in ALS. Mechanistically, phosphoproteomic analysis linked the presynaptic vesicular phenotype to an accumulation of cytotoxic protein aggregates and to the pro-apoptotic activation of the transcription factor c-Jun, providing detailed insights into the shared pathobiochemistry in ALS. Notably, sub-chronic treatment of our iPSC-derived motoneurons with the fatty acid docosahexaenoic acid exerted a neuroprotective effect by efficiently rescuing the alterations revealed by our multidisciplinary approach. Together, this study provides strong evidence for the central and convergent role played by the synaptic microenvironment within the ALS spinal cord and highlights a potential therapeutic target that counteracts degeneration in a heterogeneous cohort of human motoneuron cultures.

Decomposition decreases molecular diversity and ecosystem similarity of soil organic matter.

Soil organic matter (SOM) is comprised of a diverse array of reactive carbon molecules, including hydrophilic and hydrophobic compounds, that impact rates of SOM formation and persistence. Despite clear importance to ecosystem science, little is known about broad-scale controls on SOM diversity and variability in soil. Here, we show that microbial decomposition drives significant variability in the molecular richness and diversity of SOM between soil horizons and across a continental-scale gradient in climate and ecosystem type (arid shrubs, coniferous, deciduous, and mixed forests, grasslands, and tundra sedges). The molecular dissimilarity of SOM was strongly influenced by ecosystem type (hydrophilic compounds: 17%, P < 0.001; hydrophobic compounds: 10% P < 0.001) and soil horizon (hydrophilic compounds: 17%, P < 0.001; hydrophobic compounds: 21%, P < 0.001), as assessed using metabolomic analysis of hydrophilic and hydrophobic metabolites. While the proportion of shared molecular features was significantly higher in the litter layer than subsoil C horizons across ecosystems (12 times and 4 times higher for hydrophilic and hydrophobic compounds, respectively), the proportion of site-specific molecular features nearly doubled from the litter layer to the subsoil horizon, suggesting greater differentiation of compounds after microbial decomposition within each ecosystem. Together, these results suggest that microbial decomposition of plant litter leads to a decrease in SOM α-molecular diversity, yet an increase in ß-molecular diversity across ecosystems. The degree of microbial degradation, determined by the position in the soil profile, exerts a greater control on SOM molecular diversity than environmental factors, such as soil texture, moisture, and ecosystem type.

Microbial carbon use efficiency promotes global soil carbon storage.

Soils store more carbon than other terrestrial ecosystems1,2. How soil organic carbon (SOC) forms and persists remains uncertain1,3, which makes it challenging to understand how it will respond to climatic change3,4. It has been suggested that soil microorganisms play an important role in SOC formation, preservation and loss5-7. Although microorganisms affect the accumulation and loss of soil organic matter through many pathways4,6,8-11, microbial carbon use efficiency (CUE) is an integrative metric that can capture the balance of these processes12,13. Although CUE has the potential to act as a predictor of variation in SOC storage, the role of CUE in SOC persistence remains unresolved7,14,15. Here we examine the relationship between CUE and the preservation of SOC, and interactions with climate, vegetation and edaphic properties, using a combination of global-scale datasets, a microbial-process explicit model, data assimilation, deep learning and meta-analysis. We find that CUE is at least four times as important as other evaluated factors, such as carbon input, decomposition or vertical transport, in determining SOC storage and its spatial variation across the globe. In addition, CUE shows a positive correlation with SOC content. Our findings point to microbial CUE as a major determinant of global SOC storage. Understanding the microbial processes underlying CUE and their environmental dependence may help the prediction of SOC feedback to a changing climate.

Socioecological effects of swidden management in traditional Maya agroforests in the Selva Lacandona of Chiapas, Mexico.

For millennia, Maya farmers (i.e., milperos) throughout Mesoamerica have managed milpa: sequential agroforests initiated by slashing and burning patches of secondary forest and then cultivating a diverse polyculture of trees and annual crops. To reduce greenhouse gas emissions associated with deforestation, the Mexican government and non-governmental organizations have urged milperos to cease burning. We collaborated with Maya milperos in several communities in the Montes Azules Biosphere Reserve region in Chiapas, Mexico to determine carbon retained as char in traditional milpas, carbon loss associated with burning, and effects of burning on soil quality. We found the carbon retention of char in Maya milpas (24 ± 6.5% of C in vegetation) is 4-1400% higher than other slash-and-burn agroecosystems reported in the literature. Burning resulted in significant carbon loss of 12.6 (±3.6) t C ha-1 yr-1, but this was partially mitigated by char production (3.0 [±0.6] t C ha-1 yr-1) and incomplete combustion of woody biomass. The effects of burning on soil were minimal, with the only significant changes observed being increases in pH, potassium availability, and cation exchange capacity (2, 100, and 7%, respectively). The mean residence times of charred materials were at least double that of uncharred biomass. While there is a risk that shortening fallow periods would undermine the sustainability of Maya swidden agroecology, proper management and secure land tenure can help maintain intensive production without enduring environmental degradation. The char produced in these swiddens and successional management could allow this agroforestry system to be a long-term carbon sink.

Magnesium-enriched poultry manure enhances phosphorus bioavailability in biochars.

Pyrolysis of calcium-rich feedstock (e.g., poultry manure) generates semi-crystalline and crystalline phosphorus (P) species, compromising its short-term availability to plants. However, enriching poultry manure with magnesium (Mg) before pyrolysis may improve the ability of biochar to supply P. This study investigated how increasing the Mg/Ca ratio and pyrolysis temperature of poultry manure affected its P availability and speciation. Mg enrichment by ∼2.1% increased P availability (extracted using 2% citric and formic acid) by 20% in Mg-biochar at pyrolysis temperatures up to 600 °C. Linear combination fitting of P K-edge XANES of biochar, and Mg/Ca stoichiometry, indicate that P species, mainly Ca-P and Mg-P, are altered after pyrolysis. At 300 °C, adding Mg as magnesium hydroxide [Mg(OH)2] created MgNH4PO4 (18%) and Mg3(PO4)2.8H2O (23%) in the biochar, while without addition of Mg Ca3(PO4)2 (11%) predominated, both differing only for pyrophosphate, 33 and 16%, respectively. Similarly, the P L2,3 edge XANES data of biochar made with Mg were indicative of either MgHPO4.3H2O or Mg3(PO4)2.8H2O, in comparison to CaHPO4.2H2O or Ca3(PO4)2 without Mg. More importantly, hydroxyapatite [Ca5(PO4)3(OH)] was not identified with Mg additions, while it was abundant in biochars produced without Mg both at 600 (12%) and 700 °C (32%). The presence of Mg formed Mg-P minerals that could enhance P mobility in soil more than Ca-P, and may have resulted in greater P availability in Mg-enriched biochars. Thus, a relatively low Mg enrichment can be an approach for designing and optimize biochar as a P fertilizer from P-rich excreta, with the potential to improve P availability and contribute to the sustainable use of organic residues.

Integrated biochar solutions can achieve carbon-neutral staple crop production.

Agricultural food production is a main driver of global greenhouse gas emissions, with unclear pathways towards carbon neutrality. Here, through a comprehensive life-cycle assessment using data from China, we show that an integrated biomass pyrolysis and electricity generation system coupled with commonly applied methane and nitrogen mitigation measures can help reduce staple crops' life-cycle greenhouse gas emissions from the current 666.5 to -37.9 Tg CO2-equivalent yr-1. Emission reductions would be achieved primarily through carbon sequestration from biochar application to the soil, and fossil fuel displacement by bio-energy produced from pyrolysis. We estimate that this integrated system can increase crop yield by 8.3%, decrease reactive nitrogen losses by 25.5%, lower air pollutant emissions by 125-2,483 Gg yr-1 and enhance net environmental and economic benefits by 36.2%. These results indicate that integrated biochar solutions could contribute to China's 2060 carbon neutrality objective while enhancing food security and environmental sustainability.

A study on motion reduction for suspended platforms used in gravitational wave detectors.

We report a reduction in motion for suspended seismic-isolation platforms in a gravitational wave detector prototype facility. We sense the distance between two seismic-isolation platforms with a suspension platform interferometer and the angular motion with two optical levers. Feedback control loops reduce the length changes between two platforms separated by [Formula: see text] to [Formula: see text] at [Formula: see text], and the angular motion of each platform is reduced to [Formula: see text] at [Formula: see text]. As a result, the length fluctuations in a suspended optical resonator on top of the platforms is reduced by three orders of magnitude. This result is of direct relevance to gravitational wave detectors that use similar suspended optics and seismic isolation platforms.

Inducing Inorganic Carbon Accrual in Subsoil through Biochar Application on Calcareous Topsoil.

Biochar amendments add persistent organic carbon to soil and can stabilize rhizodeposits and existing soil organic carbon (SOC), but effects of biochar on subsoil carbon stocks have been overlooked. We quantified changes in soil inorganic carbon (SIC) and SOC to 2 m depth 10 years after biochar application to calcareous soil. The total soil carbon (i.e., existing SOC, SIC, and biochar-C) increased by 71, 182, and 210% for B30, B60, and B90, respectively. Biochar application at 30, 60, and 90 t ha-1 rates significantly increased SIC by 10, 38, and 68 t ha-1, respectively, with accumulation mainly occurring in the subsoil (below 1 m). This huge increase of SIC (mainly CaCO3) is ∼100 times larger than the inorganic carbon present in the added biochar (0.3, 0.6, or 0.9 t ha-1). The benzene polycarboxylic acid method showed that the biochar-amended soil contained more black carbon particles (6.8 times higher than control soil) in the depth of 1.4-1.6 m, which provided the direct quantitative evidence for biochar migration into subsoil after a decade. Spectral and energy spectrum analysis also showed an obvious biochar structure in the biochar-amended subsoil, accompanied by a Ca/Mg carbonate cluster, which provided further evidence for downward migration of biochar after a decade. To explain SIC accumulation in subsoil with biochar amendment, the interacting mechanisms are proposed: (1) biochar amendment significantly increases subsoil pH (0.3-0.5 units) 10 years after biochar application, thus forming a favorable pH environment in the subsoil to precipitate HCO3-; and (2) the transported biochar in subsoil can act as nuclei to precipitate SIC. Biochar amendment enhanced SIC by up to 80%; thus, the effects on carbon stocks in subsoil must be understood to inform strategies for carbon dioxide removal through biochar application. Our study provided critical knowledge on the impact of biochar application to topsoil on carbon stocks in subsoil in the long term.

Multifactorial effects matter: Moving thermal adaptation into a real-world setting.

We often study climate change impact by isolating various drivers and manipulating them at ideal state, despite that in reality those drivers change independent of each other and may produce unexpected results due to possible complex interacting effects over time. Even though global change experiments that examine multiple interacting global change factors are becoming more common, few have been applied to studies on thermal compensatory response of microbial respiration. We propose future studies on thermal adaptation to include multifactorial experiments.

WNT/beta-catenin signalling interrupts a senescence-induction cascade in human mesenchymal stem cells that restricts their expansion.

Senescence, the irreversible cell cycle arrest of damaged cells, is accompanied by a deleterious pro-inflammatory senescence-associated secretory phenotype (SASP). Senescence and the SASP are major factors in aging, cancer, and degenerative diseases, and interfere with the expansion of adult cells in vitro, yet little is known about how to counteract their induction and deleterious effects. Paracrine signals are increasingly recognized as important senescence triggers and understanding their regulation and mode of action may provide novel opportunities to reduce senescence-induced inflammation and improve cell-based therapies. Here, we show that the signalling protein WNT3A counteracts the induction of paracrine senescence in cultured human adult mesenchymal stem cells (MSCs). We find that entry into senescence in a small subpopulation of MSCs triggers a secretome that causes a feed-forward signalling cascade that with increasing speed induces healthy cells into senescence. WNT signals interrupt this cascade by repressing cytokines that mediate this induction of senescence. Inhibition of those mediators by interference with NF-κB or interleukin 6 signalling reduced paracrine senescence in absence of WNT3A and promoted the expansion of MSCs. Our work reveals how WNT signals can antagonize senescence and has relevance not only for expansion of adult cells but can also provide new insights into senescence-associated inflammatory and degenerative diseases.

Land-based measures to mitigate climate change: Potential and feasibility by country.

Land-based climate mitigation measures have gained significant attention and importance in public and private sector climate policies. Building on previous studies, we refine and update the mitigation potentials for 20 land-based measures in >200 countries and five regions, comparing "bottom-up" sectoral estimates with integrated assessment models (IAMs). We also assess implementation feasibility at the country level. Cost-effective (available up to $100/tCO2 eq) land-based mitigation is 8-13.8 GtCO2 eq yr-1 between 2020 and 2050, with the bottom end of this range representing the IAM median and the upper end representing the sectoral estimate. The cost-effective sectoral estimate is about 40% of available technical potential and is in line with achieving a 1.5°C pathway in 2050. Compared to technical potentials, cost-effective estimates represent a more realistic and actionable target for policy. The cost-effective potential is approximately 50% from forests and other ecosystems, 35% from agriculture, and 15% from demand-side measures. The potential varies sixfold across the five regions assessed (0.75-4.8 GtCO2eq yr-1 ) and the top 15 countries account for about 60% of the global potential. Protection of forests and other ecosystems and demand-side measures present particularly high mitigation efficiency, high provision of co-benefits, and relatively lower costs. The feasibility assessment suggests that governance, economic investment, and socio-cultural conditions influence the likelihood that land-based mitigation potentials are realized. A substantial portion of potential (80%) is in developing countries and LDCs, where feasibility barriers are of greatest concern. Assisting countries to overcome barriers may result in significant quantities of near-term, low-cost mitigation while locally achieving important climate adaptation and development benefits. Opportunities among countries vary widely depending on types of land-based measures available, their potential co-benefits and risks, and their feasibility. Enhanced investments and country-specific plans that accommodate this complexity are urgently needed to realize the large global potential from improved land stewardship.

Greenhouse Gas Inventory Model for Biochar Additions to Soil.

Stabilizing the global climate within safe bounds will require greenhouse gas (GHG) emissions to reach net zero within a few decades. Achieving this is expected to require removal of CO2 from the atmosphere to offset some hard-to-eliminate emissions. There is, therefore, a clear need for GHG accounting protocols that quantify the mitigation impact of CO2 removal practices, such as biochar sequestration, that have the potential to be deployed at scale. Here, we have developed a GHG accounting methodology for biochar application to mineral soils using simple parameterizations and readily accessible activity data that can be applied at a range of scales including farm, supply chain, national, or global. The method is grounded in a comprehensive analysis of current empirical data, making it a robust method that can be used for many applications including national inventories and voluntary and compliance carbon markets, among others. We show that the carbon content of biochar varies with feedstock and production conditions from as low as 7% (gasification of biosolids) to 79% (pyrolysis of wood at above 600 °C). Of this initial carbon, 63-82% will remain unmineralized in soil after 100 years at the global mean annual cropland-temperature of 14.9 °C. With this method, researchers and managers can address the long-term sequestration of C through biochar that is blended with soils through assessments such as GHG inventories and life cycle analyses.