| 1. |
- Cuni-Sanchez, Aida, et al.
(författare)
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High aboveground carbon stock of African tropical montane forests
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
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Tidskriftsartikel (refereegranskat)abstract
- Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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| 2. |
- Abdelrazak Morsy, Mohammad Hamdy, et al.
(författare)
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SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma
- 2024
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 143:19, s. 1953-1964
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Tidskriftsartikel (refereegranskat)abstract
- Sterile alpha motif and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara -C) resistance in several hematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara -C ef fi cacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMGbox containing protein 11 (SOX11) as a novel direct binding partner and fi rst known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Coimmunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identi fi ed SAMHD1 as the top SOX11 interaction partner, which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar af fi nity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara -C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identi fi ed SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its fi rst known endogenous inhibitor with potentially important implications for clinical therapy strati fi cation.
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| 3. |
- Illini, Oliver, et al.
(författare)
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Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis
- 2024
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade >= 3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naive patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.
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| 4. |
- Pendrill, Florence, 1983, et al.
(författare)
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Disentangling the numbers behind agriculture-driven tropical deforestation
- 2022
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 377:6611, s. eabm9267-
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Forskningsöversikt (refereegranskat)abstract
- Tropical deforestation continues at alarming rates with profound impacts on ecosystems, climate, and livelihoods, prompting renewed commitments to halt its continuation. Although it is well established that agriculture is a dominant driver of deforestation, rates and mechanisms remain disputed and often lack a clear evidence base. We synthesize the best available pantropical evidence to provide clarity on how agriculture drives deforestation. Although most (90 to 99%) deforestation across the tropics 2011 to 2015 was driven by agriculture, only 45 to 65% of deforested land became productive agriculture within a few years. Therefore, ending deforestation likely requires combining measures to create deforestation-free supply chains with landscape governance interventions. We highlight key remaining evidence gaps including deforestation trends, commodity-specific land-use dynamics, and data from tropical dry forests and forests across Africa.
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| 5. |
- van Dijke, Anne J. Hoek, et al.
(författare)
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Shifts in regional water availability due to global tree restoration
- 2022
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Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 15:5, s. 363-368
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Tidskriftsartikel (refereegranskat)abstract
- Tree restoration is an effective way to store atmospheric carbon and mitigate climate change. However, large-scale tree-cover expansion has long been known to increase evaporation, leading to reduced local water availability and streamflow. More recent studies suggest that increased precipitation, through enhanced atmospheric moisture recycling, can offset this effect. Here we calculate how 900 million hectares of global tree restoration would impact evaporation and precipitation using an ensemble of data-driven Budyko models and the UTrack moisture recycling dataset. We show that the combined effects of directly enhanced evaporation and indirectly enhanced precipitation create complex patterns of shifting water availability. Large-scale tree-cover expansion can increase water availability by up to 6% in some regions, while decreasing it by up to 38% in others. There is a divergent impact on large river basins: some rivers could lose 6% of their streamflow due to enhanced evaporation, while for other rivers, the greater evaporation is counterbalanced by more moisture recycling. Several so-called hot spots for forest restoration could lose water, including regions that are already facing water scarcity today. Tree restoration significantly shifts terrestrial water fluxes, and we emphasize that future tree-restoration strategies should consider these hydrological effects.
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| 6. |
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| 7. |
- Araza, Arnan, et al.
(författare)
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Past decade above-ground biomass change comparisons from four multi-temporal global maps
- 2023
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Ingår i: International Journal of Applied Earth Observation and Geoinformation. - 1569-8432. ; 118
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Tidskriftsartikel (refereegranskat)abstract
- Above-ground biomass (AGB) is considered an essential climate variable that underpins our knowledge and information about the role of forests in mitigating climate change. The availability of satellite-based AGB and AGB change (ΔAGB) products has increased in recent years. Here we assessed the past decade net ΔAGB derived from four recent global multi-date AGB maps: ESA-CCI maps, WRI-Flux model, JPL time series, and SMOS-LVOD time series. Our assessments explore and use different reference data sources with biomass re-measurements within the past decade. The reference data comprise National Forest Inventory (NFI) plot data, local ΔAGB maps from airborne LiDAR, and selected Forest Resource Assessment country data from countries with well-developed monitoring capacities. Map to reference data comparisons were performed at levels ranging from 100 m to 25 km spatial scale. The comparisons revealed that LiDAR data compared most reasonably with the maps, while the comparisons using NFI only showed some agreements at aggregation levels <10 km. Regardless of the aggregation level, AGB losses and gains according to the map comparisons were consistently smaller than the reference data. Map-map comparisons at 25 km highlighted that the maps consistently captured AGB losses in known deforestation hotspots. The comparisons also identified several carbon sink regions consistently detected by all maps. However, disagreement between maps is still large in key forest regions such as the Amazon basin. The overall ΔAGB map cross-correlation between maps varied in the range 0.11–0.29 (r). Reported ΔAGB magnitudes were largest in the high-resolution datasets including the CCI map differencing (stock change) and Flux model (gain-loss) methods, while they were smallest according to the coarser-resolution LVOD and JPL time series products, especially for AGB gains. Our results suggest that ΔAGB assessed from current maps can be biased and any use of the estimates should take that into account. Currently, ΔAGB reference data are sparse especially in the tropics but that deficit can be alleviated by upcoming LiDAR data networks in the context of Supersites and GEO-Trees.
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| 8. |
- Barucca, G., et al.
(författare)
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The potential of Λ and Ξ- studies with PANDA at FAIR
- 2021
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Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
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Tidskriftsartikel (refereegranskat)abstract
- The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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| 9. |
- Battaglia, Manuela, et al.
(författare)
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Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:1, s. 5-12
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Tidskriftsartikel (refereegranskat)abstract
- The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.
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| 10. |
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