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  • American Association for the Advancement of Science (AAAS)  (2)
  • 1
    In: Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 10, No. 423 ( 2018-01-10)
    Abstract: Crohn’s disease (CD), a form of inflammatory bowel disease, has a higher prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi Jewish patients with CD, followed by array-based genotyping and association analysis in 2066 CD cases and 3633 healthy controls. We detected association signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 × 10 −10 ) or protection from CD (N551K variant, tagging R1398H-associated haplotype, P = 3.3 × 10 −8 ). These variants affected CD age of onset, disease location, LRRK2 activity, and autophagy. Bayesian network analysis of CD patient intestinal tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended LRRK2 locus in 24,570 CD cases, patients with Parkinson’s disease (PD), and healthy controls revealed extensive pleiotropy, with shared genetic effects between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2 N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation that is the major genetic cause of familial and sporadic PD. Like the G2019S mutation, the N2081D variant was associated with increased kinase activity, whereas neither N551K nor R1398H variants on the protective haplotype altered kinase activity. We also confirmed that R1398H, but not N551K, increased guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides refined insight into disease mechanisms and may have major implications for the treatment of these two seemingly unrelated diseases.
    Type of Medium: Online Resource
    ISSN: 1946-6234 , 1946-6242
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
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  • 2
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 379, No. 6630 ( 2023-01-27)
    Abstract: Most analyses of land-use and land-cover change in the Amazon forest have focused on the causes and effects of deforestation. However, anthropogenic disturbances cause degradation of the remaining Amazon forest and threaten their future. Among such disturbances, the most important are edge effects (due to deforestation and the resulting habitat fragmentation), timber extraction, fire, and extreme droughts that have been intensified by human-induced climate change. We synthesize knowledge on these disturbances that lead to Amazon forest degradation, including their causes and impacts, possible future extents, and some of the interventions required to curb them. ADVANCES Analysis of existing data on the extent of fire, edge effects, and timber extraction between 2001 and 2018 reveals that 0.36 ×10 6 km 2 (5.5%) of the Amazon forest is under some form of degradation, which corresponds to 112% of the total area deforested in that period. Adding data on extreme droughts increases the estimate of total degraded area to 2.5 ×10 6 km 2 , or 38% of the remaining Amazonian forests. Estimated carbon loss from these forest disturbances ranges from 0.05 to 0.20 Pg C year −1 and is comparable to carbon loss from deforestation (0.06 to 0.21 Pg C year −1 ). Disturbances can bring about as much biodiversity loss as deforestation itself, and forests degraded by fire and timber extraction can have a 2 to 34% reduction in dry-season evapotranspiration. The underlying drivers of disturbances (e.g., agricultural expansion or demand for timber) generate material benefits for a restricted group of regional and global actors, whereas the burdens permeate across a broad range of scales and social groups ranging from nearby forest dwellers to urban residents of Andean countries. First-order 2050 projections indicate that the four main disturbances will remain a major threat and source of carbon fluxes to the atmosphere, independent of deforestation trajectories. OUTLOOK Whereas some disturbances such as edge effects can be tackled by curbing deforestation, others, like constraining the increase in extreme droughts, require additional measures, including global efforts to reduce greenhouse gas emissions. Curbing degradation will also require engaging with the diverse set of actors that promote it, operationalizing effective monitoring of different disturbances, and refining policy frameworks such as REDD+. These will all be supported by rapid and multidisciplinary advances in our socioenvironmental understanding of tropical forest degradation, providing a robust platform on which to co-construct appropriate policies and programs to curb it. An overview of tropical forest degradation processes in the Amazon. Underlying drivers (a few of which are shown in gray at the bottom) stimulate disturbances (timber extraction, fire, edge effects, and extreme drought) that cause forest degradation. A satellite illustrates the attempts to estimate degradation’s spatial extent and associated carbon losses. Impacts (in red and insets) are either local—causing biodiversity losses or affecting forest-dweller livelihoods—or remote, for example, with smoke affecting people’s health in cities or causing the melting of Andean glaciers owing to black carbon deposition. Credit: Alex Argozino/Studio Argozino
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    RVK:
    RVK:
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2023
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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