Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DR hi CD11c hi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DR lo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.

The release of the 1000th complete microbial genome will occur in the next two to three years. In anticipation of this milestone, the Fellowship for Interpretation of Genomes (FIG) launched the Project to Annotate 1000 Genomes. The project is built around the principle that the key to improved accuracy in high-throughput annotation technology is to have experts annotate single subsystems over the complete collection of genomes, rather than having an annotation expert attempt to annotate all of the genes in a single genome. Using the subsystems approach, all of the genes implementing the subsystem are analyzed by an expert in that subsystem. An annotation environment was created where populated subsystems are curated and projected to new genomes. A portable notion of a populated subsystem was defined, and tools developed for exchanging and curating these objects. Tools were also developed to resolve conflicts between populated subsystems. The SEED is the first annotation environment that supports this model of annotation. Here, we describe the subsystem approach, and offer the first release of our growing library of populated subsystems. The initial release of data includes 180 177 distinct proteins with 2133 distinct functional roles. This data comes from 173 subsystems and 383 different organisms.

New insights into other importantPublisher: NPG; Journal: Nature: Nature; Article Type: Biology letter DOI: 10.1038/nature06269Page 2 of 33 symbiotic functions including H 2 metabolism, CO 2 -reductive acetogenesis and N 2 fixation are also provided by this first system-wide gene analysis of a microbial community specialized towards plant lignocellulose degradation. Our results underscore how complex even a 1-μl environment can be.All known termite species form obligate, nutritional mutualisms with diverse gut microbial species found nowhere else in nature 3 . Despite nearly a century of study, however, science still has only a meagre understanding of the exact roles of the host and symbiotic microbiota in the complex processes of lignocellulose degradation and conversion. Especially conspicuous is our poor understanding of the hindgut communities of wood-feeding 'higher'termites, the most species-rich and abundant of all termite lineages 4 . Higher termites do not contain hindgut flagellate protozoa, which have long been known to be sources of cellulases and hemicellulases in the 'lower' termites. The host tissue of all wood-feeding termites is known to be the source of one cellulase, a single-domain glycohydrolase family 9 enzyme that is secreted and active in the anterior compartments of the gut tract 5 . Only in recent years has research provided support for a role of termite gut bacteria in the production of relevant hydrolytic enzymes. That evidence includes the observed tight attachment of bacteria to wood particles, the antibacterial sensitivity of particle-bound cellulase activity 2 , and the discovery of a gene encoding a novel endoxylanase (glycohydrolase family 11) from bacterial DNA harvested from the gut tract of a Nasutitermes species 6 . Here, in an effort to learn about gene-centred details relevant to the diverse roles of bacterial symbionts in these successful wood-degrading insects,we initiated a metagenomic analysis of a wood-feeding 'higher' termite hindgut community, performed a proteomic analysis with clarified gut fluid from the same sample, and examined a set of candidate enzymes identified during the course of the study for demonstrable cellulase activity.A nest of an arboreal species closely related to Nasutitermes ephratae and N. corniger ( Supplementary Fig. 1) was collected near Guápiles, Costa Rica. From worker specimens, luminal contents were sampled specifically from the largest hindgut compartment, the microbedense, microlitre-sized region alternatively known as the paunch or the third proctodeal segment (P3; Fig. 1a). In the interest of interpretive clarity, we specifically excluded sampling from and analysis of the microbiota attached to the P3 epithelium and the other distinct microbial communities associated with the other hindgut compartments.Publisher: NPG; Journal: Nature: Nature; Article Type: Biology letter DOI: 10.1038/nature06269Page 3 of 33Total community DNA from pooled P3 luminal contents was purified, cloned and sequenced. About 71 million base pairs of Sang...

Roots and leaves of healthy plants host taxonomically structured bacterial assemblies, and members of these communities contribute to plant growth and health. We established Arabidopsis leaf- and root-derived microbiota culture collections representing the majority of bacterial species that are reproducibly detectable by culture-independent community sequencing. We found an extensive taxonomic overlap between the leaf and root microbiota. Genome drafts of 400 isolates revealed a large overlap of genome-encoded functional capabilities between leaf- and root-derived bacteria with few significant differences at the level of individual functional categories. Using defined bacterial communities and a gnotobiotic Arabidopsis plant system we show that the isolates form assemblies resembling natural microbiota on their cognate host organs, but are also capable of ectopic leaf or root colonization. While this raises the possibility of reciprocal relocation between root and leaf microbiota members, genome information and recolonization experiments also provide evidence for microbiota specialization to their respective niche.