Natural variability in hard bottom communities and possible drivers assessed by a time-series study in the SW Baltic Sea: know the noise to detect the change

In order to detect shifts in community structure and function associated with global change, the natural background fluctuation in these traits must be known. In a 6 yr study we characterized the composition of young benthic communities at 7 sites along the 300 km coast of the Kiel and Lübeck bights in the German Baltic Sea and we quantified their interannual variability of taxonomic and functional composition. Along the salinity gradient from NW to SE, the relative abundance of primary producers decreased while that of heterotrophs increased. Along the same gradient, annual productivity tended to increase. Taxonomic and functional richness were higher in Kiel Bight as compared to Lübeck Bight. With increasing species richness functional group richness showed saturation indicating an increasing functional redundancy in species rich communities. While taxonomic fluctuations between years were substantial, functionality of the communities seem preserved in most cases. Environmental conditions potentially driving these fluctuations are winter temperatures and current regimes. We tentatively define a confidence range of natural variability in taxonomic and functional composition a departure from which might help identifying an ongoing regime shift driven by global change. In addition, we propose to use RELATE, a statistical procedure in the PRIMER (Plymouth Routines in Multivariate Ecological Research) package to distinguish directional shifts in time ("signal") from natural temporal fluctuations ("noise"

Long-term records of hard-bottom communities in the southwestern Baltic Sea reveal the decline of a foundation species

Highlights • Records of hard-bottom communities show regional differences in community dynamics. • Regionally, signs of regime shift were detected. • Shift can be explained by the decline of the foundation species Mytilus sp. • Modelling process revealed three environmental variables explaining the decline. • Regional differences in larval dispersal could explain contrary Mytilus recoveries. Abstract Ecological processes modulate ecosystem functioning and services. Foundation species are those exerting intense control on such processes as both their existence and loss have profound implications on the structure of ecological communities. For the distinction between random fluctuations and directional regime shifts in community composition, long-term records are of strategic need. In this study we present the monitoring of benthic hard-bottom communities over 11 years along seven stations in the SW Baltic Sea. Regional differences were found between the communities of Kiel and Lübeck bights, with the former area displaying signs of regime shift. The decline and near disappearance of the foundational species Mytilus edulis from settlement panels deployed in Kiel Bight correlated with three environmental variables: sea surface temperature, water current speed and chlorophyll a concentration. Thus, low spring temperatures, in some cases reinforced by local maxima of chlorophyll a, correlated with reduced recruitment of Mytilus. Moreover, regional differences of larval dispersal and population connectivity could explain the rapid recovery after disturbance of the mussel populations in Lübeck Bight in contrast to Kiel Bight. Our findings underscore the relevance of long-term monitoring programmes to detect the interactive impacts of global climatic and regional environmental drivers

IgG glycosylation and DNA methylation are interconnected with smoking

Background: Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic. Methods: With the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies. In total, 3000 individuals from 4 cohorts were analyzed. Results: The overlap of the results from the two glycan measurement panels yielded DNA methylation of 7 CpG-sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904 (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921 (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation analyses with respect to smoking revealed that the effect of smoking on IgG glycosylation may be at least partially mediated via DNA methylation levels at these 7 CpG-sites. Conclusion: Our results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures. General significance: An epigenome-wide analysis conducted in four population-based cohorts revealed an association between DNA methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates the effect of smoking on IgG glycosylation

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