Science for a wilder Anthropocene: synthesis and future directions for trophic rewilding research

Trophic rewilding is an ecological restoration strategy that uses species introductions to restore top-down trophic interactions and associated trophic cascades to promote self-regulating biodiverse ecosystems. Given the importance of large animals in trophic cascades and their widespread losses and resulting trophic downgrading, it often focuses on restoring functional megafaunas. Trophic rewilding is increasingly being implemented for conservation, but remains controversial. Here, we provide a synthesis of its current scientific basis, highlighting trophic cascades as the key conceptual framework, discussing the main lessons learned from ongoing rewilding projects, systematically reviewing the current literature, and highlighting unintentional rewilding and spontaneous wildlife comebacks as underused sources of information. Together, these lines of evidence show that trophic cascades may be restored via species reintroductions and ecological replacements. It is clear, however, that megafauna effects may be affected by poorly understood trophic complexity effects and interactions with landscape settings, human activities, and other factors. Unfortunately, empirical research on trophic rewilding is still rare, fragmented, and geographically biased, with the literature dominated by essays and opinion pieces. We highlight the need for applied programs to include hypothesis testing and science-based monitoring, and outline priorities for future research, notably assessing the role of trophic complexity, interplay with landscape settings, land use, and climate change, as well as developing the global scope for rewilding and tools to optimize benefits and reduce human–wildlife conflicts. Finally, we recommend developing a decision framework for species selection, building on functional and phylogenetic information and with attention to the potential contribution from synthetic biology

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8þ) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3 0 region of BRCA2 (c.7914þ) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR ¼ 1.78; 95% confidence interval (CI), 1.25–2.52; P ¼ 0.001], as well as elevated risk of Gleason 8þ prostate cancer (HR ¼ 3.11; 95% CI, 1.63–5.95; P ¼ 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR ¼ 2.83; 95% CI, 1.71–4.68; P ¼ 0.00004) and elevated risk of Gleason 8þ prostate cancer (HR ¼ 4.95; 95% CI, 2.12–11.54; P ¼ 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer