Challenges and priorities for river cetacean conservation

River cetaceans are particularly vulnerable to anthropogenic impacts due to their constrained ranges in freshwater systems of China, South Asia, and South America. We undertook an exhaustive review of 280 peer-reviewed papers and grey literature reports (1998-2020) to examine the current status of knowledge regarding these cetaceans and their conservation. We aimed to better understand the scale of threats they face, and to identify and propose priority future efforts to better conserve these species. We found that the species have been studied with varying frequency and that most of the research on threats has focused on habitat degradation and fragmentation (43%, mainly driven by dams and extractive activities such as sand mining and deforestation), and fishery interactions (39%, in the form of bycatch and direct take). These threats occur across all species, but more information is needed, primarily on quantifying the population impacts as a basis for designing mitigation measures. Other threats identified include pollution, vessel collisions, traditional use, and poorly managed tourism. Emerging methods such as environmental DNA and unmanned aerial vehicles are described for studying these species. Promising conservation interventions include cetacean-specific protected areas, natural ex situ protection, community-led conservation, and education programmes. However, transnational political will is required for a step change towards broad-scale protection in freshwater environments. In addition, we propose increasing capacity building, developing management plans, working closely with fishing communities, enhancing public awareness, expanding regional collaborations, and diversifying funding

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons. A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons. A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

A cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.peer-reviewe

Analysis of brain atrophy and local gene expression in genetic frontotemporal dementia

Abstract Frontotemporal dementia is a heterogeneous neurodegenerative disorder characterized by neuronal loss in the frontal and temporal lobes. Despite progress in understanding which genes are associated with the aetiology of frontotemporal dementia, the biological basis of how mutations in these genes lead to cell loss in specific cortical regions remains unclear. In this work, we combined gene expression data for 16 772 genes from the Allen Institute for Brain Science atlas with brain maps of grey matter atrophy in symptomatic C9orf72, GRN and MAPT mutation carriers obtained from the Genetic Frontotemporal dementia Initiative study. No significant association was seen between C9orf72, GRN and MAPT expression and the atrophy patterns in the respective genetic groups. After adjusting for spatial autocorrelation, between 1000 and 5000 genes showed a negative or positive association with the atrophy pattern within each individual genetic group, with the most significantly associated genes being TREM2, SSBP3 and GPR158 (negative association in C9Orf72, GRN and MAPT respectively) and RELN, MXRA8 and LPA (positive association in C9Orf72, GRN and MAPT respectively). An overrepresentation analysis identified a negative association with genes involved in mitochondrial function, and a positive association with genes involved in vascular and glial cell function in each of the genetic groups. A set of 423 and 700 genes showed significant positive and negative association, respectively, with atrophy patterns in all three maps. The gene set with increased expression in spared cortical regions was enriched for neuronal and microglial genes, while the gene set with increased expression in atrophied regions was enriched for astrocyte and endothelial cell genes. Our analysis suggests that these cell types may play a more active role in the onset of neurodegeneration in frontotemporal dementia than previously assumed, and in the case of the positively associated cell marker genes, potentially through emergence of neurotoxic astrocytes and alteration in the blood–brain barrier, respectively

Fisheries in a border area of the Moxos Lowlands (Bolivia) after invasion of Arapaima gigas

Abstract Fish in the upper Madeira River basin (Bolivian Amazon) are an important source of livelihoods and protein for both rural and urban human populations. We characterised fisheries in the area of the port city of Riberalta, which possesses some of the most important fisheries landing sites bordering the Moxos lowlands, and evaluated the contribution of an invasive species (Arapaima gigas) to the landings. We compared the regional economic contribution of urban‐based and rural indigenous fisheries. Both fisheries contribute significantly to local food security and livelihoods and take advantage in a different but complementary way of the abundance of the invasive species, avoiding conflicts by partitioning the fish catch and supplying different urban markets. Both fisher groups are involved in a debt peonage system making them dependent on middlemen. A. gigas represented 57.6% of the overall economic value of fish in the region. The socioeconomic impact of the invasive species might increase considerably if it would invade and colonise the available habitats in the nuclear area of the Moxos lowlands

Visions for nature and nature’s contributions to people for the 21st century : Report from an IPBES visioning workshop held on 4-8 September 2017 in Auckland, New Zealand

Existing scenarios of biodiversity and ecosystem services (BES) have important limitations and gaps that constrain their usefulness for the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES). Specifically, they fail to incorporate policy objectives related to nature conservation and social-ecological feedbacks, they do not address the linkages between biodiversity and ecosystem services, and they are typically relevant at only a particular spatial scale. In addition, nature and its benefits are treated as the consequence of human decisions, but are not at the centre of the analysis. To address these issues, the IPBES Scenarios and Models Expert Group initiated the development of a set of Multiscale Scenarios for Nature Futures based on positive visions for human relationships with nature.The first step of this process was a visioning workshop with stakeholders and experts on 4-8 September 2017 in Auckland, New Zealand. A total of 73 participants from inter-governmental organisations, national government organisations, non-governmental organisations, academia and the private sector, from 31 countries, and with a range of sectoral expertise on biodiversity topics, from urban development to agriculture to fisheries, worked together in a visioning exercise. This report documents the results from this visioning workshop to inform further stakeholder consultation and the development of the associated multiscale scenarios by modelers and experts. This creative visioning exercise was carried out in four steps based on a suite of participatory methods that were used to develop visions of alternative futures. First the participants identified important themes to develop the visions. Next, thematic groups identified the main trends for BES in each theme and a set of “Seeds” of emerging initiatives leading to positive futures for our relationship with nature. Implications of what would happen across a range of sectors were identified for each seed. Then a pathway analysis of how the current regime in each theme may be transformed into the future desirable regime was carriedout. Narratives were then built for the visions emerging from each group. Finally, commonalities of visions across the groups were identified, and the regional relevance of each vision for different parts of the world was assessed

Visions for nature and nature’s contributions to people for the 21st century : Report from an IPBES visioning workshop held on 4-8 September 2017 in Auckland, New Zealand

Existing scenarios of biodiversity and ecosystem services (BES) have important limitations and gaps that constrain their usefulness for the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES). Specifically, they fail to incorporate policy objectives related to nature conservation and social-ecological feedbacks, they do not address the linkages between biodiversity and ecosystem services, and they are typically relevant at only a particular spatial scale. In addition, nature and its benefits are treated as the consequence of human decisions, but are not at the centre of the analysis. To address these issues, the IPBES Scenarios and Models Expert Group initiated the development of a set of Multiscale Scenarios for Nature Futures based on positive visions for human relationships with nature.The first step of this process was a visioning workshop with stakeholders and experts on 4-8 September 2017 in Auckland, New Zealand. A total of 73 participants from inter-governmental organisations, national government organisations, non-governmental organisations, academia and the private sector, from 31 countries, and with a range of sectoral expertise on biodiversity topics, from urban development to agriculture to fisheries, worked together in a visioning exercise. This report documents the results from this visioning workshop to inform further stakeholder consultation and the development of the associated multiscale scenarios by modelers and experts. This creative visioning exercise was carried out in four steps based on a suite of participatory methods that were used to develop visions of alternative futures. First the participants identified important themes to develop the visions. Next, thematic groups identified the main trends for BES in each theme and a set of “Seeds” of emerging initiatives leading to positive futures for our relationship with nature. Implications of what would happen across a range of sectors were identified for each seed. Then a pathway analysis of how the current regime in each theme may be transformed into the future desirable regime was carriedout. Narratives were then built for the visions emerging from each group. Finally, commonalities of visions across the groups were identified, and the regional relevance of each vision for different parts of the world was assessed