The Evolution of Connectivity in Metabolic Networks

Processes in living cells are the result of interactions between biochemical compounds in highly complex biochemical networks. It is a major challenge in biology to understand causes and consequences of the specific design of these networks. A characteristic design feature of metabolic networks is the presence of hub metabolites such as ATP or NADH that are involved in a high number of reactions. To study the emergence of hub metabolites, we implemented computer simulations of a widely accepted scenario for the evolution of metabolic networks. Our simulations indicate that metabolic networks with a large number of highly specialized enzymes may evolve from a few multifunctional enzymes. During this process, enzymes duplicate and specialize, leading to a loss of biochemical reactions and intermediary metabolites. Complex features of metabolic networks such as the presence of hubs may result from selection of growth rate if essential biochemical mechanisms are considered. Specifically, our simulations indicate that group transfer reactions are essential for the emergence of hubs

The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening.

Cell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense and respond to remain unclear. Here we show that the rate of force application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic force regimes to cells through substrate stretching, optical tweezers, and atomic force microscopy, we find that increasing loading rates trigger talin-dependent mechanosensing, leading to adhesion growth and reinforcement, and YAP nuclear localization. However, above a given threshold the actin cytoskeleton softens, decreasing loading rates and preventing reinforcement. By stretching rat lungs in vivo, we show that a similar phenomenon may occur. Our results show that cell sensing of external forces and of passive mechanical parameters (like tissue stiffness) can be understood through the same mechanisms, driven by the properties under force of the mechanosensing molecules involved

ROSE:radiology, obstruction, symptoms and exposure - a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group

Introduction: The coexistence of chronic obstructive pulmonary disease (COPD) and bronchiectasis (BE) seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. // Methods: We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD-BE association”. A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and gender distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds. // Results: A-hundred-and-two (72.3%) out of 141 invited experts participated the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD-BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry (FEV1/FVC<0.7), (3) at least two characteristic symptoms (cough, expectoration, dyspnoea, fatigue, frequent infections) and (4) current or past exposure to smoke (≥10 pack-years) or other toxic agents (biomass, etc.)”. These criteria form the acronym “ROSE” (Radiology, Obstruction, Symptoms, Exposure). // Conclusions: The Delphi process formulated a European consensus definition of “COPD-BE association”. We hope this definition will have broad applicability across clinical practice and research in the future

Fractional Levy motion through path integrals

Fractional Levy motion (fLm) is the natural generalization of fractional Brownian motion in the context of self-similar stochastic processes and stable probability distributions. In this paper we give an explicit derivation of the propagator of fLm by using path integral methods. The propagators of Brownian motion and fractional Brownian motion are recovered as particular cases. The fractional diffusion equation corresponding to fLm is also obtained.Comment: 9 pages, minor changes, published versio

New evidence on housing wealth and consumption channels

This paper provides new evidence on the effect of housing wealth on consumption by focusing on the impact of home-equity extraction. We develop a household consumption decision model to illustrate the differential effect of home-equity extraction, relative to net home equity, on consumption. The home-equity extraction channel is also shown to vary with household-level borrowing constraints. Based on U.S. household survey data and an instrumental-variables approach, our empirical results validate model predictions. We find that the marginal propensity to consume is two times higher for the home-equity extraction channel relative to the conventional housing wealth effect. The consumption effect of home-equity extraction is more than 2.5 times greater for liquidity-constrained households than for unconstrained households. These results are even more pronounced in the case of durable goods consumption for constrained borrowers

Assessing the materiality of nature-related financial risks for the UK

•At least half of global GDP is moderately or highly directly dependent on nature, and ultimately there is no economy without its critical services, including clean and abundant water, clean air and food. Nature across most of the globe has now been significantly altered by multiple human drivers, such as land-use change, pollution, extraction of minerals, abstraction of water and climate change. Statistics on the current state of biodiversity loss and environmental degradation are alarming: the extent and condition of ecosystems has declined in 50% of natural ecosystems, including more than 85% of wetland area lost, and 25% of species are at risk of extinction (IPBES, 2019). The 2019 Global Assessment Report of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) concluded that fourteen of the eighteen ecosystem services that were assessed had declined since the 1970s. The United Kingdom is no exception. The percentage of UK habitats ‘in favourable or improving conservation status’ has been deteriorating since 2007, exacerbating impacts on our soils, pollinators, air and environmental pollution, water and flood protection. Our analyses show that 75% of the United Kingdom is covered by at least one hotspot of natural capital depletion, and 25% is covered by two or more hotspots of natural capital depletion. The UK, with its globally interconnected economy, is also exposed to significant global emerging risks. •The erosion of UK and global natural capital generates significant and long-term risks to society and the UK economy and financial sector. Studies by Central Banks around the world have highlighted the high degree of dependence on nature and the exposure of financial portfolios to nature-related risks. What is not yet clear, is the extent to which this is a material risk to financial stability, on a par with other risks on the radar of Central Banks, and if so, on what timescales this risk could emerge and where it might ‘fall through the cracks’ of current supervision and regulation. •The objective of this project was to assess the materiality of nature-related risks to the UK financial sector both in the near-term and the longer-term. To address this, we develop six innovations: 1.The first Nature-Related Risk Inventory for the UK (UK-NRRI), equivalent in format to the National Risk Register or Climate Change Risk Assessment (CCRA). 2.Dependency analysis with spatial information to track dependencies on international supply and the nature risks therein, alongside transition risk exposures for the seven largest banks. 3.Development of sector-specific nature-related Value at Risk (nVaR) scores. 4.Co-development of three benchmark scenarios of nature-related risks, following the approach outlined by the Taskforce on Nature-Related Financial Disclosures (TNFD 2023). 5.Macroeconomic modelling to gauge the potential impacts on UK prosperity and resilience. 6.Preliminary financial ‘stress test’ for the domestic lending of the UK’s seven largest banks. The analyses focus on physical nature-related risks, with exposure analysis or transition risks. The findings demonstrate that biodiversity loss and environmental degradation create material risks for the UK economy and financial sector, in addition to their wider social and biodiversity impacts. These impacts are near and present. We find that the deterioration of our natural environment could slow economic growth and result in UK Gross Domestic Product (GDP) being 6% lower than it would have been otherwise by the 2030s under two scenarios (domestic and international) and 12% lower under an AMR-pandemic scenario. These are greater than the impact on GDP experienced in the Global Financial Crisis, in which UK GDP fell by around 4% to 6%, and - for the AMR-pandemic scenario – greater than the GDP impact of the COVID-19 pandemic when GDP fell 11% over 2020. While these findings are preliminary, all the evidence points to them being conservative. This study focussed on quantifying near- to medium-term risks, but the evidence clearly demonstrates these risks will increase over time with the potential for crossing tipping points. •The compounding impacts of climate and nature loss would have a very material impact on UK GDP; equivalent to several lost years of growth. It is not realistic to consider nature in isolation as climate change and environmental degradation are occurring in parallel and are interconnected. Environmental degradation increases the likelihood and severity of an acute climate or health shock, and the combined effect would have a very material impact on the economy. For this reason, we also draw upon the NGFS climate scenarios to explore the compounding impacts of climate and nature. We find that in our acute shock scenarios, these compounding impacts can lead to a UK GDP that is 8% lower than it would be otherwise, with a peak shock that wipes out around £200 billion from UK GDP and persists for several quarters, equivalent to 4 – 7 years of lost growth over the period. •The gradual impacts of environmental degradation on the economy are as detrimental or more so than climate change in the near-term - and the chronic year-to-year changes lead to losses that are as important as more sudden shocks. We find that the impact to GDP of chronic year-on-year environmental degradation is at least on par with that from physical climate change risks in the coming decade and for acute shocks, can be far greater than climate impacts alone. In effect, the impacts of environmental degradation are doubling or more the impact of climate change. Antimicrobial resistance (AMR) and zoonotic diseases are closely linked with deforestation and habitat destruction which can bring humans and wild animals into closer contact and have been shown to lead to greater abundance of antibiotic resistance genes in soil. Chronic nature-related risks associated with soil degradation, water provisioning, pollution and pollination services have material impacts on agriculture, manufacturing, construction, utilities and key supply chains. •Around half of UK nature-related risks come from overseas, through supply chains and financial exposures, pointing toward the importance of working internationally to close the gaps in disclosures and risk management. The four trillion GBP of financial assets assessed are dependent upon many trillions more of assets globally. Analyses of UK financial exposures suggest that 56% of the total upstream financial exposures have a High or Very High dependence on ecosystem services. Exposures to overseas risks are most material (in financial terms) for the services and manufacturing sectors, with highest risks related to water. The agricultural sector is most at risk in percentage terms, but the largest risks in monetary terms are to the services and manufacturing sectors. Agriculture can be impacted by disruption to several ecosystem services, with potential reductions in output (the nature-related value at risk – or nVaR) up to 15% of total annual production for disruption of any one service, albeit multiple ecosystem services at risk and impacts occur simultaneously, with risks to related to pollination services, soil quality and invasive species. Looking across the UK economy, we find that the nVaR associated with disruption to ecosystem services is in the hundreds of billions and equivalent to several percentage points of GDP; water risks alone are equivalent to around 13% UK GDP (for an extreme 1-in-100 year risk). The agricultural sector is also the most exposed to transition risks and opportunities. •Looking across the portfolios of the seven largest UK banks, the analyses indicate possible adjustments in the valuations of domestic holdings (excluding finance) of up to 4 – 5% over the coming decade from physical nature-related risks. Depending on the bank, the most at-risk sectors include agriculture, utilities, real-estate and manufacturing. Preliminary analyses suggest that between 8% and 53% of the portfolios of the seven largest banks are exposed also to transition risks. Firms could also derive opportunities from the nature-positive transition; including new demand for nature-positive products and services. The findings of this study take us further than previous studies to-date by clearly demonstrating the materiality of nature-related risks and the potential for compounding risks with climate change. Further work is needed to assess the implications for regulation, policy and supervision. Based upon the findings presented here and elsewhere, we believe there is a case for action by Central Banks, regulators and governments to assess if and where nature may be falling through the cracks of current frameworks and where this could lead to financial stability risks that justify explicit changes to those frameworks. We make a series of arguments based on the evidence for why nature may present new challenges that necessitate action. It is clear, for example, from other work (e.g. GARP 2024 and TNFD 2023), that there are sizeable information asymmetries created by the lack of disclosures of nature-related risks and impacts that mean that risks are currently under-priced. This may lead to an accumulation of systemic risk that goes undetected. We also lay out how nature-related risks suffer from the same ‘tragedy of the horizon’ issue identified by Mark Carney in 2015, but also additional challenges of a ‘tragedy of scale’ and unique drivers and risk transmission channels that are not captured within current climate-related risk assessments. •This study adds further evidence to support the conclusion from the Dasgupta Review and others that an early orderly transition toward a nature-positive economy brings significant benefits for UK prosperity and financial stability, through reducing both transition and physical risks, as well as for people and planet. Actions that could be considered by regulators and supervisors to mitigate risks to financial stability include advancing disclosures, broadening supervisory statements on climate to explicitly include environmental risks and introducing a simple nature-risk scenario within exploratory scenario exercises. There are many low-regrets measures that could be taken now, including supporting capability building through fora such as the Climate Financial Risk Forum and working with the scientific community to advance a set of benchmark scenarios, building upon those developed here. Regulators should also take timely opportunities to incorporate nature alongside climate into emerging frameworks, for example on transition plans, ISSB standards and taxonomies. •For financial institutions, the findings should motivate action to assess and manage nature-related financial risks, build capability, and begin to incorporate nature into emerging transition plans. These preliminary results suggest that even in the short-term nature-related risk is not negligible, especially if the losses are considered in relative terms to specific fractions of a lending portfolio. Financial institutions can manage risks to their own portfolios through working with their clients to reduce risks through supporting their transition and resilience. Importantly the transition toward a nature-positive economy presents opportunities as well as risks. With early action, UK firms – both financial and real-economy – can capture these opportunities. •For government, the materiality of nature-related risks demonstrated in this study add additional urgency to put in place the mechanisms, domestically and globally, to meet the goals and targets of the Kunming-Montreal Global Biodiversity Framework (GBF), as well as domestic policies such as the Environmental Improvement Plan (2023). This includes engaging internationally to ensure that emerging sustainable finance frameworks incorporate nature and nature related, including the IFRS Foundation’s ISSB. There is also an urgent rationale for investment and closer working with the scientific community to improve data and analytics as a public good to underpin the UK's transition to a resilient, nature-positive economy. •To continue to advance this area, strengthening collaboration between financial institutions and the scientific community is essential. Nature-related financial risk assessment is in its infancy, but risks are significant. This study has revealed several gaps in knowledge and approaches that require further study. It has also produced a series of tools that can be advanced today: •A Nature-Related Risk Inventory (UK-NRRI) that includes 29 key risks to the UK, with zoonotic diseases and antimicrobial resistance, soil health decline and global repercussions of food insecurity emerging as highest risks in terms of likelihood and impacts. •A set of benchmark narrative and quantitative scenarios that could form the basis for the further co-development of a set of scenarios for financial institutions, through fora such as the Climate Financial Risk Forum and UK Integrating Finance and Biodiversity network. There is a need to build platforms for collaboration and an opportunity to build upon existing fora such as the Climate Financial Risk Forum. The new £7m UKRI Integrating Finance and Biodiversity network, bringing together 17 research institutions, provides a ready venue to deepen collaborations. •Finally, while our focus has been on nature-related risks, the findings have implications for climate change given the strong interconnections between climate and nature The findings suggest that incorporating nature-related risk amplifications in climate scenarios would double the estimated impact of climate change on the UK economy, beyond what is currently predicted by the NGFS

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The Human Phenotype Ontology project:linking molecular biology and disease through phenotype data

The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online

Atypical brain structures as a function of gray matter volume (GMV) and gray matter density (GMD) in young adults relating to autism spectrum traits

Individuals with autistic traits are those who present in the normal population with characteristics of social, communication, personality, and cognitive impairments but do not meet the clinical threshold for autism spectrum disorder (ASD). Most studies have focused on the abnormalities in ASD patients rather than on individuals with autistic traits. In this study, we focused on the behaviors of a large sample (N = 401) of Chinese individuals with different levels of autistic traits, measured using the Autism Spectrum Quotient, and applied voxel-based morphometry (VBM) to determine their association to differences in brain structure. The results mainly showed that the correlation between gray matter volume (GMV) and gray matter density of the brain and the Autism Spectrum Quotient was significant in these regions: the right middle frontal gyrus, which are involved in social processing and social reasoning; the left parahippocampal gyrus, which is involved in socioemotional behaviors and unconscious relational memory encoding; and the right superior parietal lobule, which are involved in cognitive control and the ability to show attention to detail. These findings reveal that people with autistic traits in the normal population have atypical development in GMV and gray matter density, which may affect their social functioning and communication ability