Metagenomic analysis of the biodiversity and seasonal variation in the meromictic Antarctic lake, Ace Lake

Ace lake is a stratified lake in the Vestfold Hills, Antarctica. The presence of a thick ice-cover for ~11 months of the year and a strong salinity gradient are responsible for its permanent stratification. Taxonomy analyses showed depth-based segregation of its microbial community, including viruses. Functional potential analyses of the lake taxa highlighted their roles in nutrient cycling. In this thesis, the seasonal changes in Ace Lake microbial community were studied using a time-series of metagenomes utilizing the Cavlab metagenome analysis pipeline. Statistical analyses of taxa abundance and environmental factors revealed the effects of the polar light cycle, with 24 hours of daylight in summer and no sunlight in winter, on the phototrophs identified in the lake, indicating the importance of light-based primary production in summer to prevail through the dark winter. Analysis of viral data generated from the metagenomes showed the presence of viruses, including a ‘huge phage’, throughout the lake, with a diverse population existing in the oxic zone. Analysis of virus-host associations of phototrophic bacteria revealed that the availability of light, rather than viral predation, was probably responsible for seasonal variations in host abundances. Genomic variation in Synechococcus and Chlorobium populations, analysed using metagenome-assembled genomes (MAGs) from Ace Lake, revealed phylotypes that highlighted their adaptation to the lake environment. Synechococcus phylotypes were linked to complex interaction with viruses, whereas some Chlorobium phylotypes were inferred to interact with Synechococcus. Some Chlorobium phylotypes were also inferred to have improved photosynthetic capacity, which might contribute to the very high abundance of this species in Ace Lake. Comparative genomic analysis of Chlorobium was performed using MAGs from Ace Lake, Ellis Fjord, and Taynaya Bay and the genome of a non-Antarctic Chlorobium phaeovibrioides. A single Chlorobium species, distinct from the non-Antarctic species, was prevalent in the oxycline of all three stratified systems, highlighting its endemicity to the Vestfold Hills. Potential Chlorobium viruses, representing generalist viruses, were identified in aquatic systems from the Vestfold Hills and the Rauer Islands, indicating a widespread geographic distribution. Seasonal variation in the Chlorobium population appeared to be caused by reliance on sunlight rather than the impact of viral predation, and was inferred to benefit the host by restricting the ability of specialist viruses to establish effective lifecycles. The findings in this thesis highlight the seasonal influence on Ace Lake biodiversity, the adaptations and potential interactions of the two key species Synechococcus and Chlorobium, and the endemicity of Ace Lake Chlorobium to the Vestfold Hills

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Genomic variation and biogeography of Antarctic haloarchaea.

BackgroundThe genomes of halophilic archaea (haloarchaea) often comprise multiple replicons. Genomic variation in haloarchaea has been linked to viral infection pressure and, in the case of Antarctic communities, can be caused by intergenera gene exchange. To expand understanding of genome variation and biogeography of Antarctic haloarchaea, here we assessed genomic variation between two strains of Halorubrum lacusprofundi that were isolated from Antarctic hypersaline lakes from different regions (Vestfold Hills and Rauer Islands). To assess variation in haloarchaeal populations, including the presence of genomic islands, metagenomes from six hypersaline Antarctic lakes were characterised.ResultsThe sequence of the largest replicon of each Hrr. lacusprofundi strain (primary replicon) was highly conserved, while each of the strains' two smaller replicons (secondary replicons) were highly variable. Intergenera gene exchange was identified, including the sharing of a type I-B CRISPR system. Evaluation of infectivity of an Antarctic halovirus provided experimental evidence for the differential susceptibility of the strains, bolstering inferences that strain variation is important for modulating interactions with viruses. A relationship was found between genomic structuring and the location of variation within replicons and genomic islands, demonstrating that the way in which haloarchaea accommodate genomic variability relates to replicon structuring. Metagenome read and contig mapping and clustering and scaling analyses demonstrated biogeographical patterning of variation consistent with environment and distance effects. The metagenome data also demonstrated that specific haloarchaeal species dominated the hypersaline systems indicating they are endemic to Antarctica.ConclusionThe study describes how genomic variation manifests in Antarctic-lake haloarchaeal communities and provides the basis for future assessments of Antarctic regional and global biogeography of haloarchaea

Additional file 2: of Genomic variation and biogeography of Antarctic haloarchaea

Figures S1-S8 and Tables S1-S13: Figure S1. Archaellin protein sequence alignment. Figure S2. arCOG functional classes of genes present on ACAM34 and R1S1 secondary replicons. Figure S3. arCOG functional classes of the genes within HIRs specific to R1S1 and DL1, DL31 and Hht. litchfieldiae tADL. Figure S4. New HIRs present in R1S1 that are shared with Hht. litchfieldiae tADL. Figure S5 Genomic islands on primary replicons of Antarctic haloarchaea. Figure S6. Metagenome coverage and HCA of selected secondary replicons. Figure S7. Contigs assembled from metagenomes mapped to replicons. Figure S8. Clustering and scaling of samples. Table S1. Description of the Rauer Islands and Vestfold Hills hypersaline lakes sampled in this study. Table S2. Antarctic lake metagenomes used in this study. Table S3. Unique transposases of ACAM34 and R1S1. Table S4. Unique protein-coding genes. Table S5. Unique sequence duplications and non-coding RNAs on the R1S1 primary replicon. Table S6. Regions with low sequence similarity between ACAM34 and R1S1 primary replicons. Table S7. New HIRs identified in R1S1. Table S8. HIR conserved between Hrr. lacusprofundi R1S1 and DL1 that encodes a type I-B CRISPR system. Table S9. R1S1 CRISPR spacer matching Hlac-Pro1 in ACAM34. Table S10. Presence of 16S rRNA gene sequences for known Antarctic haloarchaeal species in Antarctic hypersaline lakes. Table S11. Relative abundance of Hrr. lacusprofundi ACAM34, Hht. litchfieldiae tADL, DL31 and DL1 in Antarctic lake metagenomes. Table S12. Relative abundance of lake taxa assessed from read coverage and taxonomic assignment of contigs assembled from metagenome data. Table S13. Genome coverage and percent identity for contigs mapped to replicons of Hrr. lacusprofundi R1S1 and ACAM34, Hht. litchfieldiae tADL, DL31 and DL1. (PDF 7786 kb

Additional file 1: of Genomic variation and biogeography of Antarctic haloarchaea

Supplementary results: Sampling during the 2013–2015 season. (PDF 13433 kb

Influence of the polar light cycle on seasonal dynamics of an Antarctic lake microbial community.

BackgroundCold environments dominate the Earth's biosphere and microbial activity drives ecosystem processes thereby contributing greatly to global biogeochemical cycles. Polar environments differ to all other cold environments by experiencing 24-h sunlight in summer and no sunlight in winter. The Vestfold Hills in East Antarctica contains hundreds of lakes that have evolved from a marine origin only 3000-7000 years ago. Ace Lake is a meromictic (stratified) lake from this region that has been intensively studied since the 1970s. Here, a total of 120 metagenomes representing a seasonal cycle and four summers spanning a 10-year period were analyzed to determine the effects of the polar light cycle on microbial-driven nutrient cycles.ResultsThe lake system is characterized by complex sulfur and hydrogen cycling, especially in the anoxic layers, with multiple mechanisms for the breakdown of biopolymers present throughout the water column. The two most abundant taxa are phototrophs (green sulfur bacteria and cyanobacteria) that are highly influenced by the seasonal availability of sunlight. The extent of the Chlorobium biomass thriving at the interface in summer was captured in underwater video footage. The Chlorobium abundance dropped from up to 83% in summer to 6% in winter and 1% in spring, before rebounding to high levels. Predicted Chlorobium viruses and cyanophage were also abundant, but their levels did not negatively correlate with their hosts.ConclusionOver-wintering expeditions in Antarctica are logistically challenging, meaning insight into winter processes has been inferred from limited data. Here, we found that in contrast to chemolithoautotrophic carbon fixation potential of Southern Ocean Thaumarchaeota, this marine-derived lake evolved a reliance on photosynthesis. While viruses associated with phototrophs also have high seasonal abundance, the negative impact of viral infection on host growth appeared to be limited. The microbial community as a whole appears to have developed a capacity to generate biomass and remineralize nutrients, sufficient to sustain itself between two rounds of sunlight-driven summer-activity. In addition, this unique metagenome dataset provides considerable opportunity for future interrogation of eukaryotes and their viruses, abundant uncharacterized taxa (i.e. dark matter), and for testing hypotheses about endemic species in polar aquatic ecosystems. Video Abstract

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc