Microbial evolution-An under-appreciated driver of soil carbon cycling.

Although substantial advances in predicting the ecological impacts of global change have been made, predictions of the evolutionary impacts have lagged behind. In soil ecosystems, microbes act as the primary energetic drivers of carbon cycling; however, microbes are also capable of evolving on timescales comparable to rates of global change. Given the importance of soil ecosystems in global carbon cycling, we assess the potential impact of microbial evolution on carbon-climate feedbacks in this system. We begin by reviewing the current state of knowledge concerning microbial evolution in response to global change and its specific effect on soil carbon dynamics. Through this integration, we synthesize a roadmap detailing how to integrate microbial evolution into ecosystem biogeochemical models. Specifically, we highlight the importance of microscale mechanistic soil carbon models, including choosing an appropriate evolutionary model (e.g., adaptive dynamics, quantitative genetics), validating model predictions with 'omics' and experimental data, scaling microbial adaptations to ecosystem level processes, and validating with ecosystem-scale measurements. The proposed steps will require significant investment of scientific resources and might require 10-20 years to be fully implemented. However, through the application of multi-scale integrated approaches, we will advance the integration of microbial evolution into predictive understanding of ecosystems, providing clarity on its role and impact within the broader context of environmental change.

MAR4 Streptomyces: A Unique Resource for Natural Product Discovery.

Marine-derived Streptomyces have long been recognized as a source of novel, pharmaceutically relevant natural products. Among these bacteria, the MAR4 clade within the genus Streptomyces has been identified as metabolically rich, yielding over 93 different compounds to date. MAR4 strains are particularly noteworthy for the production of halogenated hybrid isoprenoid natural products, a relatively rare class of bacterial metabolites that possess a wide range of biological activities. MAR4 genomes are enriched in vanadium haloperoxidase and prenyltransferase genes, thus accounting for the production of these compounds. Functional characterization of the enzymes encoded in MAR4 genomes has advanced our understanding of halogenated, hybrid isoprenoid biosynthesis. Despite the exceptional biosynthetic capabilities of MAR4 bacteria, the large body of research they have stimulated has yet to be compiled. Here we review 35 years of natural product research on MAR4 strains and update the molecular diversity of this unique group of bacteria.

Substrate complexity buffers negative interactions in a synthetic community of leaf litter degraders.

Leaf litter microbes collectively degrade plant polysaccharides, influencing land-atmosphere carbon exchange. An open question is how substrate complexity-defined as the structure of the saccharide and the amount of external processing by extracellular enzymes-influences species interactions. We tested the hypothesis that monosaccharides (i.e. xylose) promote negative interactions through resource competition, and polysaccharides (i.e. xylan) promote neutral or positive interactions through resource partitioning or synergism among extracellular enzymes. We assembled a three-species community of leaf litter-degrading bacteria isolated from a grassland site in Southern California. In the polysaccharide xylan, pairs of species stably coexisted and grew equally in coculture and in monoculture. Conversely, in the monosaccharide xylose, competitive exclusion and negative interactions prevailed. These pairwise dynamics remained consistent in a three-species community: all three species coexisted in xylan, while only two species coexisted in xylose, with one species capable of using peptone. A mathematical model showed that in xylose these dynamics could be explained by resource competition. Instead, the model could not predict the coexistence patterns in xylan, suggesting other interactions exist during biopolymer degradation. Overall, our study shows that substrate complexity influences species interactions and patterns of coexistence in a synthetic microbial community of leaf litter degraders.

Prevalence and progression of LV dysfunction and dyssynchrony in patients with new-onset LBBB post TAVR.

BACKGROUND: The impact of new-onset left bundle branch block (N-LBBB) developing after Transcatheter Aortic Valve Replacement (TAVR) on cardiac function and mechanical dyssynchrony is not well defined. METHODS: We retrospectively screened all patients who underwent TAVR in our centre between Oct 2018 and Sept 2021 (n = 409). We identified 38 patients with N-LBBB post-operatively (of which 28 were persistent and 10 were transient), and 17 patients with chronic pre-existent LBBB (C-LBBB). We excluded patients requiring pacing post TAVR. For all groups, we retrospectively analysed stored echocardiograms at 3 time points: before TAVR (T0), early after TAVR (T1, 1.2 ± 1.1 days), and late follow-up (T2, 1.5 ± 0.8 years), comparing LV mass and volumes, indices of LV function (LV ejection fraction, LVEF; global longitudinal strain, GLS), and mechanical dyssynchrony indices (systolic stretch index, severity of septal flash). RESULTS: At baseline (T0), C-LBBB had worse cardiac function, and larger LV volumes and LV mass, compared with patients with N-LBBB. At T1, N-LBBB resulted in mild dyssynchrony and decreased LVEF and GLS. Dyssynchrony progressed at T2 in persistent N-LBBB but not C-LBBB. In both groups however, LVEF remained stable at T2, although individual response was variable. Patients with better LVEF at baseline demonstrated a higher proportion of developing LBBB-induced LV dysfunction at T2. Lack of improvement of LVEF immediately after TAVR predicted deteriorating LVEF at T2. In transient LBBB, cardiac function and most dyssynchrony indices returned to baseline. CONCLUSIONS: N-LBBB after TAVR results in an immediate reduction of cardiac function, in spite of only mild dyssynchrony. When LBBB persists, patients with better cardiac function before TAVR are more likely to have LBBB-induced LV dysfunction after TAVR.

Small molecule in situ resin capture provides a compound first approach to natural product discovery.

Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we introduce Small Molecule In situ Resin Capture (SMIRC), a culture-independent method to obtain natural products directly from the environments in which they are produced. We use SMIRC to capture numerous compounds including two new carbon skeletons that were characterized using NMR and contain structural features that are, to the best of our knowledge, unprecedented among natural products. Applications across diverse marine habitats reveal biome-specific metabolomic signatures and levels of chemical diversity in concordance with sequence-based predictions. Expanded deployments, in situ cultivation, and metagenomics facilitate compound discovery, enhance yields, and link compounds to candidate producing organisms, although microbial community complexity creates challenges for the later. This compound-first approach to natural product discovery provides access to poorly explored chemical space and has implications for drug discovery and the detection of chemically mediated biotic interactions.

Very early invasive strategy in higher risk non-ST-elevation acute coronary syndrome: the RAPID NSTEMI trial.

OBJECTIVE: To investigate whether a very early invasive strategy (IS)±revascularisation improves clinical outcomes compared with standard care IS in higher risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Multicentre, randomised, controlled, pragmatic strategy trial of higher risk patients with NSTE-ACS, defined by Global Registry of Acute Coronary Events 2.0 score of ≥118, or ≥90 with at least one additional high-risk feature. Participants were randomly assigned to very early IS±revascularisation (<90 min from randomisation) or standard care IS±revascularisation (<72 hours). The primary outcome was a composite of all-cause mortality, new myocardial infarction or hospitalisation for heart failure at 12 months. RESULTS: The trial was discontinued early by the funder due to slow recruitment during the COVID-19 pandemic. 425 patients were randomised, of whom 413 underwent an IS: 204 to very early IS (median time from randomisation: 1.5 hours (IQR: 0.9-2.0)) and 209 to standard care IS (median: 44.0 hours (IQR: 22.9-72.6)). At 12 months, there was no significant difference in the primary outcome between the early IS (5.9%) and standard IS (6.7%) groups (OR 0.93, 95% CI 0.42 to 2.09; p=0.86). The incidence of stroke and major bleeding was similar. The length of hospital stay was reduced with a very early IS (3.9 days (SD 6.5) vs 6.3 days (SD 7.6), p<0.01). CONCLUSIONS: A strategy of very early IS did not improve clinical outcomes compared with a standard care IS in higher risk patients with NSTE-ACS. However, the primary outcome rate was low and the trial was underpowered to detect such a difference. TRIAL REGISTRATION NUMBER: NCT03707314.

Complex percutaneous coronary intervention in patients unable to undergo coronary artery bypass grafting during the COVID-19 pandemic: insights from the UK-ReVasc Registry.

OBJECTIVES: Cardiac surgery for coronary artery disease was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with disease ordinarily treated with coronary artery bypass grafting (CABG) instead underwent percutaneous coronary intervention (PCI). We sought to describe 12-month outcomes following PCI in patients who would typically have undergone CABG. METHODS: Between March 1 and July 31, 2020, patients who received revascularization with PCI when CABG would have been the primary choice of revascularization were enrolled in the prospective, multicenter UK-ReVasc Registry. We evaluated the following major adverse cardiovascular events at 12 months: all-cause mortality, myocardial infarction, repeat revascularization, stroke, major bleeding, and stent thrombosis. RESULTS: A total of 215 patients were enrolled across 45 PCI centers in the United Kingdom. Twelve-month follow up data were obtained for 97% of the cases. There were 9 deaths (4.3%), 5 myocardial infarctions (2.4%), 12 repeat revascularizations (5.7%), 1 stroke (0.5%), 3 major bleeds (1.4%), and no cases of stent thrombosis. No difference in the primary endpoint was observed between patients who received complete vs incomplete revascularization (residual SYNTAX score £ 8 vs > 8) (P = .22). CONCLUSIONS: In patients with patterns of coronary disease in whom CABG would have been the primary therapeutic choice outside of the pandemic, PCI was associated with acceptable outcomes at 12 months of follow-up. Contemporary randomized trials that compare PCI to CABG in such patient cohorts may be warranted.