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1. Several decades of frustrated attempts to prevent fires in the Brazilian Savanna (Cerrado) have led to deleterious ecological and management consequences. In 2014, the first Integrated Fire Management (IFM) programme was launched in three protected areas (PAs). 2. The IFM programme considers local practices, ecological information, management options and aims to create landscape mosaics of different fire histories to conserve biodiversity, reduce the prevalence of late-dry season (LDS) wildfires, protect fire-sensitive vegetation and reduce conflicts between PA managers and local communities. 3. The first 3 years of imposed fire management regimes led to 40%-57% reduction in LDS fires, improved dialogue between researchers, managers and local communities, generating fire management learning communities. 4. Synthesis and applications. This Integrated Fire Management programme represents a major advance in Cerrado management and conservation, by actively managing fires and decreasing the proportion of areas burnt by late-dry season wildfires. It can contribute to PAs' management in the Cerrado and other South American fire-prone ecosystems. Long-term monitoring and research are essential to understand the ecological implications and to improve fire management practices.

Anthropogenic fire has long shaped landscapes and livelihoods in South American savanna environments. With the growing recognition of the failures of fire suppression policies and the relevance of local peoples' practices, the Brazilian and Venezuelan governments have begun to shift to fire management policies in savanna ecosystems. Using case studies from protected areas in Cerrado and Gran Sabana, and results from two multi-stakeholder meetings held in Parupa (Venezuela) and Brasilia (Brazil), we identify advances, resistances and challenges to inter-cultural fire management in both countries. We show that the two regions host pioneer experiences in collaborative research based on improved dialogue and knowledge exchanges between scientists, institutions, Indigenous and local communities as well as fire management implementation including \"controlled\" and \"prescribed\" burnings. However, in some places, narrow understanding of the complexity and historical dynamics of local fire practices and the strong resistance to recognise the value of traditional fire knowledge might restrain effective participation of local communities. We argue that more collaborative research is necessary to support community owned solutions for intercultural and participative fire management in changing environmental and socio-cultural contexts.

Wildfires continue to cause damage to property, livelihoods and environments around the world. Acknowledging that dealing with wildfires has to go beyond fire-fighting, governments in countries with fire-prone ecosystems have begun to recognize the multiple perspectives of landscape burning and the need to engage with local communities and their practices. In this perspective, we outline the experiences of Brazil and Venezuela, two countries where fire management has been highly contested, but where there have been recent advances in fire management approaches. Success of these new initiatives have been measured by the reduction in wildfire extent through prescribed burning, and the opening of a dialogue on fire management between government agencies and local communities. Yet, it is clear that further developments in community participation need to take place in order to avoid the appropriation of local knowledge systems by institutions, and to better reflect more equitable fire governance.

Native vegetation across the Brazilian Cerrado is highly heterogeneous and biodiverse and provides important ecosystem services, including carbon and water balance regulation, however, land-use changes have been extensive. Conservation and restoration of native vegetation is essential and could be facilitated by detailed landcover maps. Here, across a large case study region in Goiás State, Brazil (1.1 Mha), we produced physiognomy level maps of native vegetation (n = 8) and other landcover types (n = 5). Seven different classification schemes using different combinations of input satellite imagery were used, with a Random Forest classifier and 2-stage approach implemented within Google Earth Engine. Overall classification accuracies ranged from 88.6–92.6% for native and non-native vegetation at the formation level (stage-1), and 70.7–77.9% for native vegetation at the physiognomy level (stage-2), across the seven different classifications schemes. The differences in classification accuracy resulting from varying the input imagery combination and quality control procedures used were small. However, a combination of seasonal Sentinel-1 (C-band synthetic aperture radar) and Sentinel-2 (surface reflectance) imagery resulted in the most accurate classification at a spatial resolution of 20 m. Classification accuracies when using Landsat-8 imagery were marginally lower, but still reasonable. Quality control procedures that account for vegetation burning when selecting vegetation reference data may also improve classification accuracy for some native vegetation types. Detailed landcover maps, produced using freely available satellite imagery and upscalable techniques, will be important tools for understanding vegetation functioning at the landscape scale and for implementing restoration projects.

1. Understanding how management activities impact plant population dynamics is necessary to conserve at-risk species, control invasive species and sustainably harvest non-timber forest products (NTFP). For NTFP, knowledge about how the sustainability of harvest varies by plant life-form and part harvested is limited and needed to inform management of the thousands of species providing income to millions of people world-wide. 2. Matrix population models are commonly used to generate management recommendations. We reviewed studies of 46 NTFP species that used matrix models and synthesize the current knowledge on harvest effects. For 19 species with harvested and control populations, we assessed the impacts of harvest on projected population growth rates (λ) using meta-analysis and analysed trends in population responses to harvest across species, life-forms and plant part harvested using elasticity and life table response experiment (LTRE) analyses, and the combination of both, to assess vulnerability to harvest. 3. NTFP harvest significantly reduced λ across species. On the scale of individual studies, however, λ provided little information about harvest sustainability unless replication was sufficiently high. Most studies had low levels of replication over space or time and did not include contrasting levels of harvest. 4. Whole-plant harvest of herbs and bark harvest from trees were not sustainable largely because of decreases in survival. Palm leaf or fruit harvest and rattan stem harvest were potentially sustainable. Combined elasticity—LTRE analysis was especially valuable in assessing the sustainability of harvest when differences in λ between harvested and control populations were small, for studies with limited replicates, and where harvest effects varied regionally. 5. Synthesis and applications. The use of matrix models to assess the impacts of NTFP harvest is still rare in regions where trade of wild plants is heaviest and for several commonly harvested life-forms. Given the high variance in estimates for most NTFP species, λ does not provide a precise assessment of harvest impacts. We recommend that managers consider the combined elasticity—LTRE analysis in addition to λ in making management decisions for NTFP. NTFP research that accounts for environmental drivers of population dynamics in addition to harvest should be prioritized.

Stimulator of interferon genes (STING) is a central component of the cytosolic nucleic acids sensing pathway and as such master regulator of the type I interferon response. Due to its critical role in physiology and its’ involvement in a variety of diseases, STING has been a focus for drug discovery. Targeted protein degradation (TPD) has emerged as a promising pharmacology for targeting previously considered undruggable proteins by hijacking the cellular ubiquitin proteasome system (UPS) with small molecules. Here, we identify AK59 as a STING degrader leveraging HERC4, a HECT-domain E3 ligase. Additionally, our data reveals that AK59 is effective on the common pathological STING mutations, suggesting a potential clinical application of this mechanism. Thus, these findings introduce HERC4 to the fields of TPD and of compound-induced degradation of STING, suggesting potential therapeutic applications. In this paper, Mutlu et al. identifies a STING degrader, AK59, which inhibits downstream cGAS/STING activity through STING degradation employing a HECT-domain E3 ligase HERC4 and proteasomal ubiquitination pathway.

PARKIN, an E3 ligase mutated in familial Parkinson’s disease, promotes mitophagy by ubiquitinating mitochondrial proteins for efficient engagement of the autophagy machinery. Specifically, PARKIN-synthesized ubiquitin chains represent targets for the PINK1 kinase generating phosphoS65-ubiquitin (pUb), which constitutes the mitophagy signal. Physiological regulation of PARKIN abundance, however, and the impact on pUb accumulation are poorly understood. Using cells designed to discover physiological regulators of PARKIN abundance, we performed a pooled genome-wide CRISPR/Cas9 knockout screen. Testing identified genes individually resulted in a list of 53 positive and negative regulators. A transcriptional repressor network including THAP11 was identified and negatively regulates endogenous PARKIN abundance. RNAseq analysis revealed the PARKIN-encoding locus as a prime THAP11 target, and THAP11 CRISPR knockout in multiple cell types enhanced pUb accumulation. Thus, our work demonstrates the critical role of PARKIN abundance, identifies regulating genes, and reveals a link between transcriptional repression and mitophagy, which is also apparent in human induced pluripotent stem cell-derived neurons, a disease-relevant cell type.

Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model.

Hermann Kantorowicz crossed the Atlantic twice: to take up a visiting professorship at Columbia Law School in the summer of 1927, and to find refuge at New York's University in Exile in 1933/1934. Between his first and second stay, the German-Jewish émigré changed his mind about America and its law fundamentally. While he had—patronizingly—praised his US colleagues for “catch[ing] up… intellectually” in 1927, he accused them of “destroy[ing] the Law itself” in 1934. Reconstructing Kantorowicz's change of heart, my article uncovers just how open the transatlantic 1930s still were in jurisprudential matters. As leader of the so-called “free law” movement, Kantorowicz had sparked a turn to “life” in German legal science in the years before World War I. Throughout the 1920s, he had then watched contentedly, as American “realist” scholars drew on free law ideas for their own critical projects. By 1934, however, Kantorowicz could not help but notice parallels between New Deal and Nazi law. To his mind, both Roosevelt's and Hitler's jurists had started turning his moderate free law ideas into a radical—and dangerous—legal nihilism: in designating law as life's only source, they shunned scientific legal methods. In light of these concerns, my article excavates life-law's delicate suspension between peril and potential. My sources reveal a striking, triangular relationship between German free law, American legal realism, and Nazi life-jurisprudence.