Covariation of hot spring geochemistry with microbial genomic diversity, function, and evolution.

The geosphere and the microbial biosphere have co-evolved for ~3.8 Ga, with many lines of evidence suggesting a hydrothermal habitat for life's origin. However, the extent that contemporary thermophiles and their hydrothermal habitats reflect those that likely existed on early Earth remains unknown. To address this knowledge gap, 64 geochemical analytes were measured and 1022 metagenome-assembled-genomes (MAGs) were generated from 34 chemosynthetic high-temperature springs in Yellowstone National Park and analysed alongside 444 MAGs from 35 published metagenomes. We used these data to evaluate co-variation in MAG taxonomy, metabolism, and phylogeny as a function of hot spring geochemistry. We found that cohorts of MAGs and their functions are discretely distributed across pH gradients that reflect different geochemical provinces. Acidic or circumneutral/alkaline springs harbor MAGs that branched later and are enriched in sulfur- and arsenic-based O2-dependent metabolic pathways that are inconsistent with early Earth conditions. In contrast, moderately acidic springs sourced by volcanic gas harbor earlier-branching MAGs that are enriched in anaerobic, gas-dependent metabolisms (e.g. H2, CO2, CH4 metabolism) that have been hypothesized to support early microbial life. Our results provide insight into the influence of redox state in the eco-evolutionary feedbacks between thermophiles and their habitats and suggest moderately acidic springs as early Earth analogs.

Wood-Ljungdahl pathway encoding anaerobes facilitate low-cost primary production in hypersaline sediments at Great Salt Lake, Utah.

Little is known of primary production in dark hypersaline ecosystems despite the prevalence of such environments on Earth today and throughout its geologic history. Here, we generated and analyzed metagenome-assembled genomes (MAGs) organized as operational taxonomic units (OTUs) from three depth intervals along a 30-cm sediment core from the north arm of Great Salt Lake, Utah. The sediments and associated porewaters were saturated with NaCl, exhibited redox gradients with depth, and harbored nitrogen-depleted organic carbon. Metabolic predictions of MAGs representing 36 total OTUs recovered from the core indicated that communities transitioned from aerobic and heterotrophic at the surface to anaerobic and autotrophic at depth. Dark CO2 fixation was detected in sediments and the primary mode of autotrophy was predicted to be via the Wood-Ljungdahl pathway. This included novel hydrogenotrophic acetogens affiliated with the bacterial class Candidatus Bipolaricaulia. Minor populations were dependent on the Calvin cycle and the reverse tricarboxylic acid cycle, including in a novel Thermoplasmatota MAG. These results are interpreted to reflect the favorability of and selectability for populations that operate the lowest energy requiring CO2-fixation pathway known, the Wood-Ljungdahl pathway, in anoxic and hypersaline conditions that together impart a higher energy demand on cells.

Pathways from research to sustainable development: Insights from ten research projects in sustainability and resilience.

Drawing on collective experience from ten collaborative research projects focused on the Global South, we identify three major challenges that impede the translation of research on sustainability and resilience into better-informed choices by individuals and policy-makers that in turn can support transformation to a sustainable future. The three challenges comprise: (i) converting knowledge produced during research projects into successful knowledge application; (ii) scaling up knowledge in time when research projects are short-term and potential impacts are long-term; and (iii) scaling up knowledge across space, from local research sites to larger-scale or even global impact. Some potential pathways for funding agencies to overcome these challenges include providing targeted prolonged funding for dissemination and outreach, and facilitating collaboration and coordination across different sites, research teams, and partner organizations. By systematically documenting these challenges, we hope to pave the way for further innovations in the research cycle.

Evolutionary Divergence of Marinobacter Strains in Cryopeg Brines as Revealed by Pangenomics.

Marinobacter spp. are cosmopolitan in saline environments, displaying a diverse set of metabolisms that allow them to competitively occupy these environments, some of which can be extreme in both salinity and temperature. Here, we introduce a distinct cluster of Marinobacter genomes, composed of novel isolates and in silico assembled genomes obtained from subzero, hypersaline cryopeg brines, relic seawater-derived liquid habitats within permafrost sampled near Utqiagvik, Alaska. Using these new genomes and 45 representative publicly available genomes of Marinobacter spp. from other settings, we assembled a pangenome to examine how the new extremophile members fit evolutionarily and ecologically, based on genetic potential and environmental source. This first genus-wide genomic analysis revealed that Marinobacter spp. in general encode metabolic pathways that are thermodynamically favored at low temperature, cover a broad range of organic compounds, and optimize protein usage, e.g., the Entner-Doudoroff pathway, the glyoxylate shunt, and amino acid metabolism. The new isolates contributed to a distinct clade of subzero brine-dwelling Marinobacter spp. that diverged genotypically and phylogenetically from all other Marinobacter members. The subzero brine clade displays genomic characteristics that may explain competitive adaptations to the extreme environments they inhabit, including more abundant membrane transport systems (e.g., for organic substrates, compatible solutes, and ions) and stress-induced transcriptional regulatory mechanisms (e.g., for cold and salt stress) than in the other Marinobacter clades. We also identified more abundant signatures of potential horizontal transfer of genes involved in transcription, the mobilome, and a variety of metabolite exchange systems, which led to considering the importance of this evolutionary mechanism in an extreme environment where adaptation via vertical evolution is physiologically rate limited. Assessing these new extremophile genomes in a pangenomic context has provided a unique view into the ecological and evolutionary history of the genus Marinobacter, particularly with regard to its remarkable diversity and its opportunism in extremely cold and saline environments.

Integrating stakeholders' perspectives and spatial modelling to develop scenarios of future land use and land cover change in northern Tanzania.

Rapid rates of land use and land cover change (LULCC) in eastern Africa and limited instances of genuinely equal partnerships involving scientists, communities and decision makers challenge the development of robust pathways toward future environmental and socioeconomic sustainability. We use a participatory modelling tool, Kesho, to assess the biophysical, socioeconomic, cultural and governance factors that influenced past (1959-1999) and present (2000-2018) LULCC in northern Tanzania and to simulate four scenarios of land cover change to the year 2030. Simulations of the scenarios used spatial modelling to integrate stakeholders' perceptions of future environmental change with social and environmental data on recent trends in LULCC. From stakeholders' perspectives, between 1959 and 2018, LULCC was influenced by climate variability, availability of natural resources, agriculture expansion, urbanization, tourism growth and legislation governing land access and natural resource management. Among other socio-environmental-political LULCC drivers, the stakeholders envisioned that from 2018 to 2030 LULCC will largely be influenced by land health, natural and economic capital, and political will in implementing land use plans and policies. The projected scenarios suggest that by 2030 agricultural land will have expanded by 8-20% under different scenarios and herbaceous vegetation and forest land cover will be reduced by 2.5-5% and 10-19% respectively. Stakeholder discussions further identified desirable futures in 2030 as those with improved infrastructure, restored degraded landscapes, effective wildlife conservation, and better farming techniques. The undesirable futures in 2030 were those characterized by land degradation, poverty, and cultural loss. Insights from our work identify the implications of future LULCC scenarios on wildlife and cultural conservation and in meeting the Sustainable Development Goals (SDGs) and targets by 2030. The Kesho approach capitalizes on knowledge exchanges among diverse stakeholders, and in the process promotes social learning, provides a sense of ownership of outputs generated, democratizes scientific understanding, and improves the quality and relevance of the outputs.

Pharmacoproteomics Identifies Kinase Pathways that Drive the Epithelial-Mesenchymal Transition and Drug Resistance in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a complex and deadly disease lacking druggable genetic mutations. The limited efficacy of systemic treatments for advanced HCC implies that predictive biomarkers and drug targets are urgently needed. Most HCC drugs target protein kinases, indicating that kinase-dependent signaling networks drive HCC progression. To identify HCC signaling networks that determine responses to kinase inhibitors (KIs), we apply a pharmacoproteomics approach integrating kinome activity in 17 HCC cell lines with their responses to 299 KIs, resulting in a comprehensive dataset of pathway-based drug response signatures. By profiling patient HCC samples, we identify signatures of clinical HCC drug responses in individual tumors. Our analyses reveal kinase networks promoting the epithelial-mesenchymal transition (EMT) and drug resistance, including a FZD2-AXL-NUAK1/2 signaling module, whose inhibition reverses the EMT and sensitizes HCC cells to drugs. Our approach identifies cancer drug targets and molecular signatures of drug response for personalized oncology.

Kinobead/LC-MS Phosphokinome Profiling Enables Rapid Analyses of Kinase-Dependent Cell Signaling Networks.

Kinase-catalyzed protein phosphorylation is fundamental to eukaryotic signal transduction, regulating most cellular processes. Kinases are frequently dysregulated in cancer, inflammation, and degenerative diseases, and because they can be inhibited with small molecules, they became important drug targets. Accordingly, analytical approaches that determine kinase activation states are critically important to understand kinase-dependent signal transduction and to identify novel drug targets and predictive biomarkers. Multiplexed inhibitor beads (MIBs or kinobeads) efficiently enrich kinases from cell lysates for liquid chromatography-mass spectrometry (LC-MS) analysis. When combined with phosphopeptide enrichment, kinobead/LC-MS can also quantify the phosphorylation state of kinases, which determines their activation state. However, an efficient kinobead/LC-MS kinase phospho-profiling protocol that allows routine analyses of cell lines and tissues has not yet been developed. Here, we present a facile workflow that quantifies the global phosphorylation state of kinases with unprecedented sensitivity. We also found that our kinobead/LC-MS protocol can measure changes in kinase complex composition and show how these changes can indicate kinase activity. We demonstrate the utility of our approach in specifying kinase signaling pathways that control the acute steroidogenic response in Leydig cells; this analysis establishes the first comprehensive framework for the post-translational control of steroid biosynthesis.

Anthropological contributions to historical ecology: 50 questions, infinite prospects.

This paper presents the results of a consensus-driven process identifying 50 priority research questions for historical ecology obtained through crowdsourcing, literature reviews, and in-person workshopping. A deliberative approach was designed to maximize discussion and debate with defined outcomes. Two in-person workshops (in Sweden and Canada) over the course of two years and online discussions were peer facilitated to define specific key questions for historical ecology from anthropological and archaeological perspectives. The aim of this research is to showcase the variety of questions that reflect the broad scope for historical-ecological research trajectories across scientific disciplines. Historical ecology encompasses research concerned with decadal, centennial, and millennial human-environmental interactions, and the consequences that those relationships have in the formation of contemporary landscapes. Six interrelated themes arose from our consensus-building workshop model: (1) climate and environmental change and variability; (2) multi-scalar, multi-disciplinary; (3) biodiversity and community ecology; (4) resource and environmental management and governance; (5) methods and applications; and (6) communication and policy. The 50 questions represented by these themes highlight meaningful trends in historical ecology that distill the field down to three explicit findings. First, historical ecology is fundamentally an applied research program. Second, this program seeks to understand long-term human-environment interactions with a focus on avoiding, mitigating, and reversing adverse ecological effects. Third, historical ecology is part of convergent trends toward transdisciplinary research science, which erodes scientific boundaries between the cultural and natural.