Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within-and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.Asian cultivated rice is grown worldwide and comprises the staple food for half of the global population. It is envisaged that by the year 2035 1 feeding this growing population will necessitate that an additional 112 million metric tons of rice be produced on a smaller area of land, using less water and under more fluctuating climatic conditions, which will require that future rice cultivars be higher yielding and resilient to multiple abiotic and biotic stresses. The foundation of the continued improvement of rice cultivars is the rich genetic diversity within domesticated populations and wild relatives [2][3][4] . For over 2,000 years, two major types of O. sativa-O. sativa Xian group (here referred to as Xian/Indica (XI) and also known as , Hsien or Indica) and O. sativa Geng Group (here referred to as Geng/Japonica (GJ) and also known as , Keng or Japonica)-have historically been recognized [5][6][7] . Varied degrees of post-reproductive barriers exist between XI and GJ rice accessions 8 ; this differentiation between XI and GJ rice types and the presence of different varietal groups are well-documented at isozyme and DNA levels 6,9 . Two other distinct groups have also been recognized using molecular markers 10 ; one of these encompasses the Aus, Boro and Rayada ecotypes from Bangladesh and India (which we term the circum-Aus group (cA)) and the other comprises the famous Basmati and Sadri aromatic varieties (which we term the circum-Basmati group (cB)).Approximately 780,000 rice accessions are available in gene banks worldwide 11 . To enable the more efficient use of these accessions in future rice improvement, the Chinese Academy of Agricultural Sciences, BGI-Shenzhen and International Rice Research Institute sequenced over 3,000 rice genomes (3K-RG) as part of the 3,000 Rice Genomes Project 12. Here we present analyses of genetic variation in the 3K-RG that focus on important aspects of O. sativa diversity, single nucleotide polymorphisms (SNPs) and structural variation (deletions, duplications, inversions and translocations). We also construct a species pangenome consisting of 'core...

In eukaryotic cells, the endoplasmic reticulum is essential for the folding and trafficking of proteins that enter the secretory pathway. Environmental insults or increased protein synthesis often lead to protein misfolding in the organelle, the accumulation of misfolded or unfolded proteins - known as endoplasmic reticulum stress - and the activation of the adaptive unfolded protein response to restore homeostasis. If protein misfolding is not resolved, cells die. Endoplasmic reticulum stress and activation of the unfolded protein response help to determine cell fate and function. Furthermore, endoplasmic reticulum stress contributes to the aetiology of many human diseases.

The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells for the storage and regulated release of calcium and as the entrance to the secretory pathway. Protein misfolding in the ER causes accumulation of misfolded proteins (ER stress) and activation of the unfolded protein response (UPR), which has evolved to maintain a productive ER protein-folding environment. Both ER stress and UPR activation are documented in many different human cancers. In this Review, we summarize the impact of ER stress and UPR activation on every aspect of cancer and discuss outstanding questions for which answers will pave the way for therapeutics.