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Mark JA Schoonderwoerd,1,* Sarah K Hakuno,1,* Martijn Sassen,1 Eleonore B Kuhlemaijer,1 Madelon Paauwe,1 Marije Slingerland,2 Marieke F Fransen,3 Lukas JAC Hawinkels1 1Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, the Netherlands; 2Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands; 3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands*These authors contributed equally to this workCorrespondence: Lukas JAC Hawinkels Tel +31 71 526 6736Email L.J.A.C.Hawinkels@lumc.nlBackground: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer and is known to have low immunogenicity and an immunosuppressive microenvironment. It is also characterized by high accumulation of dense stroma, composed of mostly cancer-associated fibroblasts (CAFs). Multiple subsets of CAFs are described, with one of them expressing the transforming growth factor (TGF)-β co-receptor endoglin. In previous work, we and others have shown that endoglin-expressing CAFs stimulate tumor progression and metastasis. Therefore, in this study, we set out to investigate the role of endoglin-expressing CAFs in pancreatic cancer progression.Methods: First, we investigated the expression of endoglin on CAFs in both human tissues as well as a mouse model for PDAC. Since CAF-specific endoglin expression was high, we targeted endoglin by using the endoglin neutralizing antibody TRC105 in the murine KPC model for PDAC.Results: Although some signs of immune activation were observed, TRC105 did not affect tumor growth. Since 90% of the CD8+ T-cells expressed the immune checkpoint PD-1, we investigated the combination with a PD1 checkpoint inhibitor, which did not enhance therapeutic responses. Finally, genetic deletion of endoglin from collagen 1a1 expressing cells also did not affect the growth of the mouse KPC tumors.Conclusion: Our results show that although endoglin is highly expressed on PDAC-CAFs and signaling is efficiently inhibited by TRC105, this does not result in decreased tumor growth in the KPC model for pancreatic cancer.Keywords: endoglin, PDAC, cancer-associated fibroblasts, TRC105, stroma, KPC

Transforming existing cocoa landscapes through agroforestry practices can support national and sub-national forest restoration targets now and under future climate change and provide multiple benefits through improved ecosystem service provisioning and biodiversity conservation.

Interventions and policies in the cocoa, tea and coffee sectors have failed to ensure that all smallholder commodity farmers earn more than the $1.90 World Bank poverty line or a living income, and they have not halted deforestation. Commodity farming is strongly associated with deforestation, in spite of interventions. For more than 50% of the cocoa and tea farmers in our datasets, household income would need to double in order for them to earn a living income. For those farmers, farming will never be a primary pathway out of poverty.

Key words: tropical forest, conservation management, local livelihoods, forest cover change, disturbance, fuelwood, forest structure, species richness, biomass, Mount Elgon A growing world population has important consequences for forests. In this study I investigate how conflicting goals by different actors under different historical contexts impacted the protected area of Mt Elgon, Uganda, and I consider what this means for conservation. Mt Elgon is an important water catchment area for Uganda and Kenya with important biodiversity values. The forest on Mt Elgon is also a source of agricultural land, timber, fuel wood and other forest resources for local communities. In this study I explore the factors that influenced local people’s motivations for forest clearing, the impacts of local forest use, including as a source of fuelwood, on Mt Elgon, Uganda. I also evaluate the use of radar satellite data to estimate above ground biomass on Mt Elgon. Finally I discuss the implications for the design of interventions that seek to reconcile the needs of local people and forest conservation. A major wave of deforestation on Mt Elgon, Uganda took place in the 1970s and 1980s and by 2009, 25% of the forest on Mt Elgon was lost. However, locally, there were areas of recovery. This study demonstrated that agricultural expansion on Mt Elgon cannot simply be linked to individual drivers such as population or high crop prices, and these were not always associated with increased deforestation. By analysing local variations, I found that it is the context (institutional, social, political) under which drivers such as population, wealth or commodity prices operate, rather than the drivers per se, that influences outcomes for forest cover. I found that local forest uses strongly influenced forest structure, even where people had a collaborative management agreement with the park authorities. The type of resources collected varied with the land use systems around the park: small stem-harvesting affected regeneration in areas where people grew crops that require supports such as bananas and climbing beans, and seedlings were almost absent where in-forest cattle grazing was important. Studying the characteristics and impacts of fuelwood harvesting revealed high levels of fuelwood collection and depletion of dead wood on the edge of the park. Human impacts affected highly preferred and used tree species. Allowing the collection of fuelwood or other non-timber products creates opportunities for more destructive activities such as timber harvesting or charcoal making. On the other hand it helps to improve relations between local people and park staff, which this study showed helps limit agricultural encroachment. I also found indications that trees on people’s own land can provide alternative sources of fuel. Mt Elgon has a history of conservation and development projects in an attempt to better reconcile local livelihood improvement and forest conservation. The most recent include pilot REDD+ schemes both inside and outside the protected area. Such schemes need consistent biomass estimations. I used a cost-effective field method for direct basal area estimation that yielded consistent estimates of above ground biomass (AGB), which reached above 800Mg/ ha on Mt Elgon’s northern slopes. Radar (ALOS PALSAR) data produced realistic classifications of the different vegetation types. However, using radar backscatter values in combination with field estimated AGB data to produce a biomass map had limited success. This was likely linked to the sampling strategy and topography. Our study showed that simple theoretical models based on single drivers of deforestation cannot explain local variation, nor can simple models that lead to “simplified institutional prescriptions” lead to sustainable solutions, as they do not reflect complex local social and ecological realities. This has important implications for the design of more locally adapted and ecologically and socially sustainable management arrangements on Mt Elgon and elsewhere. These are necessary because current practices appear to lead to forest degradation and resource depletion. Building trust between stakeholders and developing alternative resources are vital to support more sustainable forest management. Both international conservation actors, as well as forest management authorities need to recognise that incentives that influence people’s motivation for action vary locally and can therefore not be designed globally.