Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1

To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols

Downscaling of Long-Term Global Scenarios to Regions with a Forest Sector Model

Research Highlights: Long-term global scenarios give insights on how social and economic developments and international agreements may impact land use, trade, product markets, and carbon balances. They form a valuable basis for forming national forest policies. Many aspects related to long-term management of forests and consequences for biodiversity and ecosystem services can only be addressed at regional and landscape levels. In order to be attended to in the policy process, there is a need for a method that downscales national scenarios to these finer levels. Background and Objectives: Regional framework conditions depend on management activities in the country as a whole. The aim of this study is to evaluate the use of a forest sector model (FSM) as a method for downscaling national scenarios results to regional level. The national FSM takes the global scenario data (e.g., harvest level and market prices over time) and solves the national problem. The result for the region of interest is taken as framework conditions for the regional study. Materials and Methods: Two different specifications are tested. One lets product volumes and prices represent endogenous variables in the FSM model. The other takes volumes and prices from the global scenario as exogenous parameters. The first specification attains a maximum net social payoff whereas the second specification means that net present value is maximized under a harvest constraint. Results: The maximum net social payoff specification conforms better to economic factors than the maximum net present value specification but could give national harvest volume trajectories that deviates from what is derived from the global model. This means that regional harvest activity can deviate considerably from the national average, attesting to the benefit of the use of the FSM-based metho

Downscaling of Long-Term Global Scenarios to Regions with a Forest Sector Model

Research Highlights: Long-term global scenarios give insights on how social and economic developments and international agreements may impact land use, trade, product markets, and carbon balances. They form a valuable basis for forming national forest policies. Many aspects related to long-term management of forests and consequences for biodiversity and ecosystem services can only be addressed at regional and landscape levels. In order to be attended to in the policy process, there is a need for a method that downscales national scenarios to these finer levels. Background and Objectives: Regional framework conditions depend on management activities in the country as a whole. The aim of this study is to evaluate the use of a forest sector model (FSM) as a method for downscaling national scenarios results to regional level. The national FSM takes the global scenario data (e.g., harvest level and market prices over time) and solves the national problem. The result for the region of interest is taken as framework conditions for the regional study. Materials and Methods: Two different specifications are tested. One lets product volumes and prices represent endogenous variables in the FSM model. The other takes volumes and prices from the global scenario as exogenous parameters. The first specification attains a maximum net social payoff whereas the second specification means that net present value is maximized under a harvest constraint. Results: The maximum net social payoff specification conforms better to economic factors than the maximum net present value specification but could give national harvest volume trajectories that deviates from what is derived from the global model. This means that regional harvest activity can deviate considerably from the national average, attesting to the benefit of the use of the FSM-based metho

Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates

Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoproteins (Envs) have proven difficult to elicit by immunization. Therefore, to identify effective Env neutralization targets, efforts are underway to define the specificities of bNAbs in chronically infected individuals. For a prophylactic vaccine, it is equally important to define the immunogenic properties of the heavily glycosylated Env in healthy primates devoid of confounding HIV-induced pathogenic factors. We used rhesus macaques to investigate the magnitude and kinetics of B cell responses stimulated by Env trimers in adjuvant. Robust Env-specific memory B cell responses and high titers of circulating antibodies developed after trimer inoculation. Subsequent immunizations resulted in significant expansion of Env-specific IgG-producing plasma cell populations and circulating Abs that displayed increasing avidity and neutralization capacity. The neutralizing activity elicited with the regimen used was, in most aspects, superior to that elicited by a regimen based on monomeric Env immunization in humans. Despite the potency and breadth of the trimer-elicited response, protection against heterologous rectal simian-HIV (SHIV) challenge was modest, illustrating the challenge of eliciting sufficient titers of cross-reactive protective NAbs in mucosal sites. These data provide important information for the design and evaluation of vaccines aimed at stimulating protective HIV-1 immune responses in humans

Increasing global wood demand will risk forest sustainability

The European Union aims to be climate neutral by 2050, driving ambitious mitigation efforts. Our study investigates how climate and bioeconomy policies impact biodiversity in Sweden. Using GLOBIOM Model, we project the wood demand under three policy scenarios: Current policy, Bioenergy and Bioeconomy. Focal biodiversity indicators are mean deadwood volume, area of old forest, area of old forest rich in broadleaves and mean age of standing trees. Forest dynamics are simulated using Heureka-Planwise. We identify management strategies balancing economic objectives with biodiversity, employing both intensive and extensive approaches. Mean deadwood volume increased substantially in set-asides in all policy scenarios, while in production landscape, nearly tripling under Current Policy scenario and doubled under Bioenergy and Bioeconomy scenarios. The area of old forest on production land declined drastically, reaching 0.1 million ha in Bioeconomy scenario by 2100. Optimization favored intensive management strategies, particularly Bioenergy extraction in Bioenergy and Bioeconomy scenarios. Under Current policy, both intensive and extensive management strategies were equally dominant. Management strategies like Continuous cover forestry and Unmanaged were the least implemented. Wood demand consistently increased across scenarios, stabilizing under the Current policy scenario after 2040. In the Bioeconomy scenario the demand continued to increase, surpassing supply potential by 2070

Tracking climate mitigation efforts in 30 major emitters: Economy-wide projections and progress on key sectoral policies

Reducing global greenhouse gas (GHG) emissions to zero is a crucial step to minimise the worst effects of climate change. The growing political consensus on the dangers of climate change and the increasing number of climate policies implemented is a sign for cautious optimism. Countries increasingly recognise the need to achieve net zero emissions globally by mid-century but still need to implement near-term policy actions and measures to ensure this long-term ambition trigger the transformation necessary to meet the collective goals of the Paris Agreement. This report documents near-term climate policies and measures adopted in the 30 major economies and assesses resulting future GHG emissions trajectories up to 2030. The countries analysed jointly account for 80% of total GHG emissions in 2019. Emissions trends remain far from the goals of the Paris Agreement in the period post-2020. Global emissions should fall 7.6% each year up until 2030 to get on track to meet the goals of the Paris Agreement (UNEP, 2019). Our projections show that emissions reductions under current policies remain woefully insufficient. Emissions in the 30 economies as a group are projected to increase on average by approximately 0.4% per year between 2021 and 2030

Land-based climate change mitigation potentials within the agenda for sustainable development

Even though enormous expectations for greenhouse gas mitigation in the land use sector exist at the same time worries about potential implications for sustainable development have been raised as many Sustainable Development Goals (SDGs) are closely tied to developments in the sector. Here we assess the implications of achieving selected key SDG indicators for Zero Hunger, Clean Water and Sanitation, Responsible Consumption and Production, and Life on Land on the land-based climate change mitigation potential. We find that protecting highly biodiverse ecosystems has profound impacts on biomass potentials (−30% at >12 US dollar per gigajoule) while other SDGs mainly affect greenhouse gas abatement potentials. Achieving SDGs delivers synergies with greenhouse gas abatement and may even in the absence of additional mitigation policies allow to realize up to 25% of the expected greenhouse gas abatement from land use required to stay on track with the 1.5 °C target until 2050. Future land use mitigation policies should consider and take advantage of these synergies across SDGs

Global forest carbon leakage and substitution effect potentials: The case of the Swedish forest sector

The forest sector's climate change mitigation depends on forest carbon sequestration, storing carbon in wood products, and avoidance of fossil greenhouse gas emissions by replacing more emission intensive products or energy sources, i.e., the substitution effect. In addition, market responses to changes in wood supply following altered forest management by one region induce climate relevant changes in form of compensatory roundwood harvest outside the region, and thus forest carbon leakage. This study presents a global climate change mitigation assessment of the forest sector, accounting for market-effects leakage. We use a global forest sector model, wood flow analysis and life cycle inventory data to assess the impact of forest management changes on climate change mitigation, with a focus on Sweden. Results suggest decreased wood harvesting causes global net climate change mitigation until 2070, despite forest carbon leakage, forgone wood product carbon storage and forgone substitution effect potentials. Increasing domestic wood removals induces global additional emissions until 2100. Additional domestic wood product consumption is climate beneficial which however depends on substitution effects actually materializing. Roundwood harvest leakage ranges from 40 % to 60 % and forest carbon leakage from 50 % to 80 %. Leakage effects occur mainly in North America and Asia, with a gradual shift towards Latin America over time. To further the climate benefit, drivers of growing demand should be addressed and measures be implemented which promote more efficient and sustainable use of wood as a resource. Only concerted global forest policy cooperation would avoid leakage and with that result in improved global climate change mitigation