Determinants of emissions pathways in the coupled climate-social system.

The ambition and effectiveness of climate policies will be essential in determining greenhouse gas emissions and, as a consequence, the scale of climate change impacts1,2. However, the socio-politico-technical processes that will determine climate policy and emissions trajectories are treated as exogenous in almost all climate change modelling3,4. Here we identify relevant feedback processes documented across a range of disciplines and connect them in a stylized model of the climate-social system. An analysis of model behaviour reveals the potential for nonlinearities and tipping points that are particularly associated with connections across the individual, community, national and global scales represented. These connections can be decisive for determining policy and emissions outcomes. After partly constraining the model parameter space using observations, we simulate 100,000 possible future policy and emissions trajectories. These fall into 5 clusters with warming in 2100 ranging between 1.8 °C and 3.6 °C above the 1880-1910 average. Public perceptions of climate change, the future cost and effectiveness of mitigation technologies, and the responsiveness of political institutions emerge as important in explaining variation in emissions pathways and therefore the constraints on warming over the twenty-first century.

Comprehensive evidence implies a higher social cost of CO2.

The social cost of carbon dioxide (SC-CO2) measures the monetized value of the damages to society caused by an incremental metric tonne of CO2 emissions and is a key metric informing climate policy. Used by governments and other decision-makers in benefit-cost analysis for over a decade, SC-CO2 estimates draw on climate science, economics, demography and other disciplines. However, a 2017 report by the US National Academies of Sciences, Engineering, and Medicine1 (NASEM) highlighted that current SC-CO2 estimates no longer reflect the latest research. The report provided a series of recommendations for improving the scientific basis, transparency and uncertainty characterization of SC-CO2 estimates. Here we show that improved probabilistic socioeconomic projections, climate models, damage functions, and discounting methods that collectively reflect theoretically consistent valuation of risk, substantially increase estimates of the SC-CO2. Our preferred mean SC-CO2 estimate is $185 per tonne of CO2 ($44-$413 per tCO2: 5%-95% range, 2020 US dollars) at a near-term risk-free discount rate of 2%, a value 3.6 times higher than the US government's current value of $51 per tCO2. Our estimates incorporate updated scientific understanding throughout all components of SC-CO2 estimation in the new open-source Greenhouse Gas Impact Value Estimator (GIVE) model, in a manner fully responsive to the near-term NASEM recommendations. Our higher SC-CO2 values, compared with estimates currently used in policy evaluation, substantially increase the estimated benefits of greenhouse gas mitigation and thereby increase the expected net benefits of more stringent climate policies.

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo.

Chromatin remodelers such as the SWI/SNF complex coordinate metazoan development through broad regulation of chromatin accessibility and transcription, ensuring normal cell cycle control and cellular differentiation in a lineage-specific and temporally restricted manner. Mutations in genes encoding the structural subunits of chromatin, such as histone subunits, and chromatin regulating factors are associated with a variety of disease mechanisms including cancer metastasis, in which cancer co-opts cellular invasion programs functioning in healthy cells during development. Here we utilize Caenorhabditis elegans anchor cell (AC) invasion as an in vivo model to identify the suite of chromatin agents and chromatin regulating factors that promote cellular invasiveness. We demonstrate that the SWI/SNF ATP-dependent chromatin remodeling complex is a critical regulator of AC invasion, with pleiotropic effects on both G0 cell cycle arrest and activation of invasive machinery. Using targeted protein degradation and enhanced RNA interference (RNAi) vectors, we show that SWI/SNF contributes to AC invasion in a dose-dependent fashion, with lower levels of activity in the AC corresponding to aberrant cell cycle entry and increased loss of invasion. Our data specifically implicate the SWI/SNF BAF assembly in the regulation of the G0 cell cycle arrest in the AC, whereas the SWI/SNF PBAF assembly promotes AC invasion via cell cycle-independent mechanisms, including attachment to the basement membrane (BM) and activation of the pro-invasive fos-1/FOS gene. Together these findings demonstrate that the SWI/SNF complex is necessary for two essential components of AC invasion: arresting cell cycle progression and remodeling the BM. The work here provides valuable single-cell mechanistic insight into how the SWI/SNF assemblies differentially contribute to cellular invasion and how SWI/SNF subunit-specific disruptions may contribute to tumorigeneses and cancer metastasis.

Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell.

The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of C. elegans anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that normally exits the cell cycle and enters a post-mitotic state before initiating contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the set of negative cell cycle regulators that maintain the AC in this post-mitotic, invasive state. Our findings revealed a critical role for CKI-1 (p21CIP1/p27KIP1) in redundantly maintaining the post-mitotic state of the AC, as loss of CKI-1 in combination with other negative cell cycle regulators-including CKI-2 (p21CIP1/p27KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (ß-TrCP)-resulted in proliferating ACs. Remarkably, time-lapse imaging revealed that these ACs retain their ability to invade. Upon examination of a node in the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs do so by maintaining aspects of pro-invasive gene expression. We therefore report that the requirement for a post-mitotic state for invasive cell behavior can be bypassed following direct cell cycle perturbation.

Rapidly declining remarkability of temperature anomalies may obscure public perception of climate change.

The changing global climate is producing increasingly unusual weather relative to preindustrial conditions. In an absolute sense, these changing conditions constitute direct evidence of anthropogenic climate change. However, human evaluation of weather as either normal or abnormal will also be influenced by a range of factors including expectations, memory limitations, and cognitive biases. Here we show that experience of weather in recent years-rather than longer historical periods-determines the climatic baseline against which current weather is evaluated, potentially obscuring public recognition of anthropogenic climate change. We employ variation in decadal trends in temperature at weekly and county resolution over the continental United States, combined with discussion of the weather drawn from over 2 billion social media posts. These data indicate that the remarkability of particular temperatures changes rapidly with repeated exposure. Using sentiment analysis tools, we provide evidence for a "boiling frog" effect: The declining noteworthiness of historically extreme temperatures is not accompanied by a decline in the negative sentiment that they induce, indicating that social normalization of extreme conditions rather than adaptation is driving these results. Using climate model projections we show that, despite large increases in absolute temperature, anomalies relative to our empirically estimated shifting baseline are small and not clearly distinguishable from zero throughout the 21st century.

Mitotic Figures-Normal, Atypical, and Imposters: A Guide to Identification.

Counting mitotic figures (MF) in hematoxylin and eosin-stained histologic sections is an integral part of the diagnostic pathologist's tumor evaluation. The mitotic count (MC) is used alone or as part of a grading scheme for assessment of prognosis and clinical decisions. Determining MCs is subjective, somewhat laborious, and has interobserver variation. Proposals for standardizing this parameter in the veterinary field are limited to terminology (use of the term MC) and area (MC is counted in an area measuring 2.37 mm2). Digital imaging techniques are now commonplace and widely used among veterinary pathologists, and field of view area can be easily calculated with digital imaging software. In addition to standardizing the methods of counting MF, the morphologic characteristics of MF and distinguishing atypical mitotic figures (AMF) versus mitotic-like figures (MLF) need to be defined. This article provides morphologic criteria for MF identification and for distinguishing normal phases of MF from AMF and MLF. Pertinent features of digital microscopy and application of computational pathology (CPATH) methods are discussed. Correct identification of MF will improve MC consistency, reproducibility, and accuracy obtained from manual (glass slide or whole-slide imaging) and CPATH approaches.

International Guidelines for Veterinary Tumor Pathology: A Call to Action.

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as "living documents" on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.

Correlating Gastrointestinal Histopathologic Changes to Clinical Disease Activity in Dogs With Idiopathic Inflammatory Bowel Disease.

Prior studies have failed to detect a convincing association between histologic lesions of inflammation and clinical activity in dogs with inflammatory bowel disease (IBD). We hypothesized that use of a simplified histopathologic scoring system would improve the consistency of interpretation among pathologists when describing histologic lesions of gastrointestinal inflammation. Our aim was to evaluate the correlation of histopathologic changes to clinical activity in dogs with IBD using this new system. Forty-two dogs with IBD and 19 healthy control dogs were enrolled in this retrospective study. Endoscopic biopsies from the stomach, duodenum, ileum, and colon were independently scored by 8 pathologists. Clinical disease activity was scored using the Canine Inflammatory Bowel Disease Activity Index (CIBDAI) or the Canine Chronic Enteropathy Clinical Activity Index (CCECAI), depending on the individual study center. Summative histopathological scores and clinical activity were calculated for each tissue (stomach, duodenum, ileum, and colon) and each tissue histologic score (inflammatory/morphologic feature). The correlation between CCECAI/CIBDAI and summative histopathologic score was significant ( P < .05) for duodenum ( r = 0.42) and colon ( r = 0.33). In evaluating the relationship between histopathologic scores and clinical activity, significant ( P < .05) correlations were observed for crypt dilation ( r = 0.42), lamina propria (LP) lymphocytes ( r = 0.40), LP neutrophils ( r = 0.45), mucosal fibrosis ( r = 0.47), lacteal dilation ( r = 0.39), and villus stunting ( r = 0.43). Compared to earlier grading schemes, the simplified scoring system shows improved utility in correlating histopathologic features (both summative histology scores and select histologic scores) to IBD clinical activity.

The fingerprint of climate trends on European crop yields.

Europe has experienced a stagnation of some crop yields since the early 1990s as well as statistically significant warming during the growing season. Although it has been argued that these two are causally connected, no previous studies have formally attributed long-term yield trends to a changing climate. Here, we present two statistical tests based on the distinctive spatial pattern of climate change impacts and adaptation, and explore their power under a range of parameter values. We show that statistical power for the identification of climate change impacts is high in many settings, but that power for identifying adaptation is almost always low. Applying these tests to European agriculture, we find evidence that long-term temperature and precipitation trends since 1989 have reduced continent-wide wheat and barley yields by 2.5% and 3.8%, respectively, and have slightly increased maize and sugar beet yields. These averages disguise large heterogeneity across the continent, with regions around the Mediterranean experiencing significant adverse impacts on most crops. This result means that climate trends can account for ∼ 10% of the stagnation in European wheat and barley yields, with likely explanations for the remainder including changes in agriculture and environmental policies.

Cell cycle perturbation uncouples mitotic progression and invasive behavior in a post-mitotic cell.

The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of C. elegans anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that normally exits the cell cycle and enters a post-mitotic state, initiating contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the set of negative cell cycle regulators that maintain the AC in this post-mitotic, invasive state. Our findings revealed a critical role for CKI-1 (p21CIP1/p27KIP1) in redundantly maintaining the post-mitotic state of the AC, as loss of CKI-1 in combination with other negative cell cycle regulators-including CKI-2 (p21CIP1/p27KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (ß-TrCP)-resulted in proliferating ACs. Remarkably, time-lapse imaging revealed that these ACs retain their ability to invade. Upon examination of a node in the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs do so by maintaining aspects of pro-invasive gene expression. We therefore report that the requirement for a post-mitotic state for invasive cell behavior can be bypassed following direct cell cycle perturbation.

Drought sensitivity in mesic forests heightens their vulnerability to climate change.

Climate change is shifting the structure and function of global forests, underscoring the critical need to predict which forests are most vulnerable to a hotter and drier future. We analyzed 6.6 million tree rings from 122 species to assess trees' sensitivity to water and energy availability. We found that trees growing in wetter portions of their range exhibit the greatest drought sensitivity. To test how these patterns of drought sensitivity influence vulnerability to climate change, we predicted tree growth through 2100. Our results suggest that drought adaptations in arid regions will partially buffer trees against climate change. By contrast, trees growing in the wetter, hotter portions of their climatic range may experience unexpectedly large adverse impacts under climate change.

Biodiversity mediates ecosystem sensitivity to climate variability.

A rich body of evidence from local-scale experiments and observational studies has revealed stabilizing effects of biodiversity on ecosystem functioning. However, whether these effects emerge across entire regions and continents remains largely overlooked. Here we combine data on the distribution of more than 57,500 plant species and remote-sensing observations throughout the entire Western Hemisphere to investigate the role of multiple facets of plant diversity (species richness, phylogenetic diversity, and functional diversity) in mediating the sensitivity of ecosystems to climate variability at the regional-scale over the past 20 years. We show that, across multiple biomes, regions of greater plant diversity exhibit lower sensitivity (more stable over time) to temperature variability at the interannual and seasonal-scales. While these areas can display lower sensitivity to interannual variability in precipitation, they emerge as highly sensitive to precipitation seasonality. Conserving landscapes of greater diversity may help stabilize ecosystem functioning under climate change, possibly securing the continuous provisions of productivity-related ecosystem service to people.

Incorporating human behaviour into Earth system modelling.

Climate change and other challenges to the stability and functioning of natural and managed environmental systems are driven by increasing anthropogenic domination of the Earth. Models to forecast the trajectory of climate change and to identify pathways to sustainability require representation of human behaviour and its feedbacks with the climate system. Social climate models (SCMs) are an emerging class of models that embed human behaviour in climate models. We survey existing SCMs and make recommendations for how to integrate models of human behaviour and climate. We suggest a framework for representing human behaviour that consists of cognition, contagion and a behavioural response. Cognition represents the human processing of information around climate change; contagion represents the spread of information, beliefs and behaviour through social networks; and response is the resultant behaviour or action. This framework allows for biases, habituation and other cognitive processes that shape human perception of climate change as well as the influence of social norms, social learning and other social processes on the spread of information and factors that shape decision-making and behaviour. SCMs move beyond the inclusion of human activities in climate models to the representation of human behaviour that determines the magnitude, sign and character of these activities. The development of SCMs is a challenging but important next step in the evolution of Earth system models.

Land-use emissions embodied in international trade.

International trade separates consumption of goods from related environmental impacts, including greenhouse gas emissions from agriculture and land-use change (together referred to as "land-use emissions"). Through use of new emissions estimates and a multiregional input-output model, we evaluated land-use emissions embodied in global trade from 2004 to 2017. Annually, 27% of land-use emissions and 22% of agricultural land are related to agricultural products ultimately consumed in a different region from where they were produced. Roughly three-quarters of embodied emissions are from land-use change, with the largest transfers from lower-income countries such as Brazil, Indonesia, and Argentina to more industrialized regions such as Europe, the United States, and China. Mitigation of global land-use emissions and sustainable development may thus depend on improving the transparency of supply chains.