Systematic Evaluation of the Metabolic to Mitogenic Potency Ratio for B10-Substituted Insulin Analogues

Background: Insulin analogues comprising acidic amino acid substitutions at position B10 have previously been shown to display increased mitogenic potencies compared to human insulin and the underlying molecular mechanisms have been subject to much scrutiny and debate. However, B10 is still an attractive position for amino acid substitutions given its important role in hexamer formation. The aim of this study was to investigate the relationships between the receptor binding properties as well as the metabolic and mitogenic potencies of a series of insulin analogues with different amino acid substitutions at position B10 and to identify a B10-substituted insulin analogue without an increased mitogenic to metabolic potency ratio. Methodology/Principal Findings: A panel of ten singly-substituted B10 insulin analogues with different amino acid side chain characteristics were prepared and insulin receptor (both isoforms) and IGF-I receptor binding affinities using purified receptors, insulin receptor dissociation rates using BHK cells over-expressing the human insulin receptor, metabolic potencies by lipogenesis in isolated rat adipocytes, and mitogenic potencies using two different cell types predominantly expressing either the insulin or the IGF-I receptor were systematically investigated. Only analogues B10D and B10E with significantly increased insulin and IGF-I receptor affinities as well as decreased insulin receptor dissociation rates displayed enhanced mitogenic potencies in both cell types employed. For the remaining analogues with less pronounced changes i

Sea-level rise in Denmark: paleo context, recent projections and policy implications

We present the most recent Intergovernmental Panel on Climate Change Sixth Assessment Report (AR6) sea-level projections for four Danish cities (Aarhus, Copenhagen, Esbjerg and Hirtshals) under the Shared Socioeconomic Pathway (SSP) family of climate scenarios. These sea-level changes projected over the next century are up to an order of magnitude larger than those observed over the previous century. At these cities, year 2150 sea-level changes of between 29 and 55 cm are projected under the very low emissions scenario (SSP1-1.9), while changes of between 99 and 123 cm are projected under the very high emissions scenario (SSP5-8.5). These differences highlight the potentially significant impact of remaining opportunities for climate change mitigation. Due to this increase in mean sea level, the mean recurrence time between historically extreme events is expected to decrease. Under the very high emissions scenario, the historical 100-year storm flood event will become a 1- to 5-year event at most Danish harbours by 2100. There is considerable uncertainty associated with these sea-level projections, primarily driven by uncertainty in the future evolution of the Antarctic ice sheet and future sterodynamic changes in ocean volume. The AR6 characterises collapse of the West Antarctic ice sheet as a low-probability but high-impact event that could cause several metres of sea-level rise around Denmark by 2150. In climate adaptation policy, the scientific landscape is shifting fast. There has been a tremendous proliferation of diverse sea-level projections in recent years, with the most relevant planning target for Denmark increasing c. 50 cm in the past two decades. Translating sea-level rise projections into planning targets requires value judgments about acceptable sea-level risk that depend on local geography, planning timeline and climate pathway. This highlights the need for an overarching national sea-level adaptation plan to ensure municipal plans conform to risk and action standards

Healthy minds 0-100 years: Optimising the use of European brain imaging cohorts ("Lifebrain").

The main objective of "Lifebrain" is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.This research is funded by the EU Horizon 2020 Grant: ‘Healthy minds 0–100 years: Optimising the use of European brain imaging cohorts (“Lifebrain”)’. Grant agreement number: 732592. Call: Societal challenges: Health, demographic change and well-bein

Changes in the arabinoxylan fraction of wheat grain during 1 alcohol production

Laboratory produced DDGS samples were compared with commercial samples from a distillery and a biofuel plant. Changes in structure, solubility and content of arabinoxylan (AX) was determined. The distillation process results in a relative increase of AX content compared to the starting material. The heating and drying processes involved in the production of DDGS lead to an increased solubility and viscosity of water-extractable AX. Production of DDGS results in structural changes to the AX. There is a decrease in 2-and 3-linked arabinose oligosaccharides, that contributes to around a 50% reduction in arabinosylation in DDGS compared with the starting grains. The current study shows that laboratory-scale DDGS provide an accurate representation of the commercial scale and that the AX composition of DDGS is consistently uniform irrespective of starting material. The uniformity of DDGS and thin stillage makes them a good potential source of AX for production of prebiotics or other novel products

Marine invasive alien species in Europe: 9 years after the IAS Regulation

Biological invasions, resulting from human activities, exert substantial impacts on ecosystems worldwide. This review focuses on marine invasive alien species (IAS) in Europe, examining the current state, proposing strategies to address the problem, and offering recommendations for enhanced management. Effective management of biological invasions relies on accessible, accurate data to inform decision-making. Information systems such as the European Alien Species Information Network (EASIN), Aquatic Non-Indigenous and Cryptogenic Species (AquaNIS), and World Register of Introduced Marine Species (WriMS) provide comprehensive databases on IAS, but their sustainability requires long-term maintenance, continuous updates, and support. Most countries lack specific monitoring programs for marine IAS, and standardization and improvement of monitoring methods are needed. Port monitoring plays a vital role in the early detection of new arrivals, and recent advancements in molecular techniques show promise for effective IAS monitoring. Risk screening tools are commonly employed to rank taxa based on their invasiveness potential in European regions, but variations in protocols can yield inconsistent results. European impact assessments highlight resource competition, novel habitat creation, and predation as primary mechanisms for negative impacts on biodiversity, while the creation of novel habitats represents a key mechanism for positive impacts. Preventing IAS introductions is critical, and measures such as ballast water treatment systems are implemented to reduce the likelihood of marine introductions. However, understanding introduction pathways remains uncertain for many IAS. Eradication and control efforts for marine IAS have limited success, emphasizing the need for enhanced biosecurity measures. Climate change, especially ocean warming, can intensify IAS impacts on native species and ecosystems. In climate change hotspots, some tropical aliens may, however, compensate for the loss of thermally sensitive natives with similar traits. Therefore, it is imperative to consider the interactions between climate change and IAS in developing effective management and conservation strategies. Enhancing IAS management in Europe entails i) securing adequate funding, ii) expanding the list of IAS of Union Concern to adequately cover marine invasions, iii) learning from countries with successful biosecurity practices, iv) sustaining information systems, v) improving monitoring and early warning systems with innovative technologies, vi) enhancing prediction models, vii) conducting integrated impact assessments and mapping cumulative IAS impacts, and vii) considering the potential benefits of IAS in ecosystem functioning and services