Neutron diffraction reveals sequence-specific membrane insertion of pre-fibrillar islet amyloid polypeptide and inhibition by rifampicin

AbstractHuman islet amyloid polypeptide (hIAPP) forms amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM). Pre-fibrillar hIAPP oligomers (in contrast to monomeric IAPP or mature fibrils) increase membrane permeability, suggesting an important role in the disease. In the first structural study of membrane-associated hIAPP, lamellar neutron diffraction shows that oligomeric hIAPP inserts into phospholipid bilayers, and extends across the membrane. Rifampicin, which inhibits hIAPP-induced membrane permeabilisation in functional studies, prevents membrane insertion. In contrast, rat IAPP (84% identical to hIAPP, but non-amyloidogenic) does not insert into bilayers. Our findings are consistent with the hypothesis that membrane-active pre-fibrillar hIAPP oligomers insert into beta cell membranes in NIDDM

Quantifying non-CO2 contributions to remaining carbon budgets

The IPCC Special Report on 1.5 °C concluded that anthropogenic global warming is determined by cumulative anthropogenic CO2 emissions and the non-CO2 radiative forcing level in the decades prior to peak warming. We quantify this using CO2-forcing-equivalent (CO2-fe) emissions. We produce an observationally constrained estimate of the Transient Climate Response to cumulative carbon Emissions (TCRE), giving a 90% confidence interval of 0.26–0.78 °C/TtCO2, implying a remaining total CO2-fe budget from 2020 to 1.5 °C of 350–1040 GtCO2-fe, where non-CO2 forcing changes take up 50 to 300 GtCO2-fe. Using a central non-CO2 forcing estimate, the remaining CO2 budgets are 640, 545, 455 GtCO2 for a 33, 50 or 66% chance of limiting warming to 1.5 °C. We discuss the impact of GMST revisions and the contribution of non-CO2 mitigation to remaining budgets, determining that reporting budgets in CO2-fe for alternative definitions of GMST, displaying CO2 and non-CO2 contributions using a two-dimensional presentation, offers the most transparent approach

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Climate Science Special Report: Fourth National Climate Assessment (NCA4), Volume I

New observations and new research have increased our understanding of past, current, and future climate change since the Third U.S. National Climate Assessment (NCA3) was published in May 2014. This Climate Science Special Report (CSSR) is designed to capture that new information and build on the existing body of science in order to summarize the current state of knowledge and provide the scientific foundation for the Fourth National Climate Assessment (NCA4)

Indicators of Global Climate Change 2023: annual update of key indicators of the state of the climate system and human influence

Intergovernmental Panel on Climate Change (IPCC) assessments are the trusted source of scientific evidence for climate negotiations taking place under the United Nations Framework Convention on Climate Change (UNFCCC). Evidence-based decision-making needs to be informed by up-to-date and timely information on key indicators of the state of the climate system and of the human influence on the global climate system. However, successive IPCC reports are published at intervals of 5–10 years, creating potential for an information gap between report cycles. We follow methods as close as possible to those used in the IPCC Sixth Assessment Report (AR6) Working Group One (WGI) report. We compile monitoring datasets to produce estimates for key climate indicators related to forcing of the climate system: emissions of greenhouse gases and short-lived climate forcers, greenhouse gas concentrations, radiative forcing, the Earth's energy imbalance, surface temperature changes, warming attributed to human activities, the remaining carbon budget, and estimates of global temperature extremes. The purpose of this effort, grounded in an open-data, open-science approach, is to make annually updated reliable global climate indicators available in the public domain (https://doi.org/10.5281/zenodo.11388387, Smith et al., 2024a). As they are traceable to IPCC report methods, they can be trusted by all parties involved in UNFCCC negotiations and help convey wider understanding of the latest knowledge of the climate system and its direction of travel. The indicators show that, for the 2014–2023 decade average, observed warming was 1.19 [1.06 to 1.30] °C, of which 1.19 [1.0 to 1.4] °C was human-induced. For the single-year average, human-induced warming reached 1.31 [1.1 to 1.7] °C in 2023 relative to 1850–1900. The best estimate is below the 2023-observed warming record of 1.43 [1.32 to 1.53] °C, indicating a substantial contribution of internal variability in the 2023 record. Human-induced warming has been increasing at a rate that is unprecedented in the instrumental record, reaching 0.26 [0.2–0.4] °C per decade over 2014–2023. This high rate of warming is caused by a combination of net greenhouse gas emissions being at a persistent high of 53±5.4 Gt CO2e yr−1 over the last decade, as well as reductions in the strength of aerosol cooling. Despite this, there is evidence that the rate of increase in CO2 emissions over the last decade has slowed compared to the 2000s, and depending on societal choices, a continued series of these annual updates over the critical 2020s decade could track a change of direction for some of the indicators presented here.HORIZON EUROPE Framework ProgrammeH2020 European Research CouncilResearch Councils UKEngineering and Physical Sciences Research CouncilPeer Reviewe

Mainstreaming climate change education in UK higher education institutions

Key messages: • Mainstreaming Climate Change Education (CCE) across all learning and operational activities enables Higher Education Institutions (HEIs) to better serve their core purpose of preparing learners for their roles in work and wider society, now and in the future. • Student and employer demand for climate change education is growing, not just in specialist subjects but across all degree pathways. • The attitudes, mindsets, values and behaviours that graduates need to engage with climate change include the ability to deal with complexity, work collaboratively across sectors and disciplines and address challenging ethical questions. • The complexity of the climate crisis means all disciplines have a role to play in delivering education for the net-zero transition. Embedding interdisciplinarity is crucial to ensuring that our response to climate change makes use of all of the expertise HEIs have to offer and promotes knowledge exchange and integration for students and staff. • Student-centered CCE, including peer-to-peer learning, is a powerful tool for facilitating an inclusive and empowering learning experience, and developing graduates as change agents for the climate and ecological crisis. • HEIs should develop learning outcomes for CCE that include understanding the scale, urgency, causes, consequences and solutions of climate change; how social norms and practices are driving the climate crisis; and the ability to identify routes to direct involvement in solutions via every discipline. • Pedagogical approaches to teaching CCE should enable learners to engage with, and respond to, climate change as a “real-world” problem, such as through experiential learning. • Further recommendations for the HEI sector include developing a strategy for aligning CCE teaching provision with governance structures; partnering with industry, government and third sector organisations to enable context-specific CCE; and working with trade unions and accreditation bodies to enable curriculum reform

Mainstreaming Climate Change Education in UK Higher Education Institutions

Key messages• Mainstreaming Climate Change Education (CCE) across all learning and operational activities enables Higher Education Institutions (HEIs) to better serve their core purpose of preparing learners for their roles in work and wider society, now and in the future.• Student and employer demand for climate change education is growing, not just in specialist subjects but across all degree pathways.• The attitudes, mindsets, values and behaviours that graduates need to engage with climate change include the ability to deal with complexity, work collaboratively across sectors and disciplines and address challenging ethical questions.• The complexity of the climate crisis means all disciplines have a role to play in delivering education for the net-zero transition. Embedding interdisciplinarity is crucial to ensuring that our response to climate change makes use of all of the expertise HEIs have to offer and promotes knowledge exchange and integration for students and staff.• Student-centered CCE, including peer-to-peer learning, is a powerful tool for facilitating an inclusive and empowering learning experience, and developing graduates as change agents for the climate and ecological crisis.• HEIs should develop learning outcomes for CCE that include understanding the scale, urgency, causes, consequences and solutions of climate change; how social norms and practices are driving the climate crisis; and the ability to identify routes to direct involvement in solutions via every discipline.• Pedagogical approaches to teaching CCE should enable learners to engage with, and respond to, climate change as a “real-world” problem, such as through experiential learning.• Further recommendations for the HEI sector include developing a strategy for aligning CCE teaching provision with governance structures; partnering with industry, government and third sector organisations to enable context-specific CCE; and working with trade unions and accreditation bodies to enable curriculum reform

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p