Gene expression correlates of social evolution in coral reef butterflyfishes

Animals display remarkable variation in social behaviour. However, outside of rodents, little is known about the neural mechanisms of social variation, and whether they are shared across species and sexes, limiting our understand- ing of how sociality evolves. Using coral reef butterflyfishes, we examined gene expression correlates of social variation (i.e. pair bonding versus solitary living) within and between species and sexes. In several brain regions, we quantified gene expression of receptors important for social variation in mammals: oxytocin (OTR), arginine vasopressin (V1aR), dopamine (D1R, D2R) and mu-opioid (MOR). We found that social variation across individuals of the oval butterflyfish, Chaetodon lunulatus, is linked to differences in OTR, V1aR, D1R, D2R and MOR gene expression within several forebrain regions in a sexually dimorphic manner. However, this contrasted with social variation among six species representing a single evolutionary transition from pair- bonded to solitary living. Here, OTR expression within the supracommissural part of the ventral telencephalon was higher in pair-bonded than solitary species, specifically in males. These results contribute to the emerging idea that nonapeptide, dopamine and opioid signalling is a central theme to the evolution of sociality across individuals, although the precise mechanism may be flexible across sexes and species

Assessing mangrove restoration practices using species‐interaction networks

Mangroves are uniquely important ecosystems, for preserving biodiversity, sustaining livelihoods and mitigating against climate change. However they are degraded globally and are therefore a priority for ecosystem restoration. To date, the assessment of mangrove restoration outcomes is generally poor, and the limited studies that do exist are focussed largely on forest area. Thus, more holistic ways of assessing the outcomes of mangrove restoration projects on biodiversity and associated ecological processes are urgently needed. Ecological networks are a useful tool for simultaneously examining both. Here, we assessed the utility of using species-interaction networks for evaluating mangrove restoration outcomes for the first time. We compared the structure and complexity of mangrove ecological networks in replicated ‘Monoculture Reforestation’, ‘Mixed Species Regeneration’ and ‘Reference Forest’ plots in two study areas in Sulawesi, Indonesia, an estuarine and a coastal fringe mangrove system. We also combined and evaluated sampling methods, utilising traditional plant-animal sampling while also integrating video recording data in a novel way. We found significant differences in the structure and complexity of mangrove networks between restored and natural plots, with contrasting effects between the two sites. Our results show differences in the complex ways in which taxa interact in mangrove restoration projects, which would be overlooked if common biodiversity metrics such as species-richness were used alone, with consequences for the restoration of ecosystem functioning. We also highlight the utility of video recording data collection for constructing species interaction networks, overcoming the detrimental impacts of observer presence for some key species

Point of (no) return? Vegetation structure and diversity of restored mangroves in Sulawesi, Indonesia, 14–16 years on

Mangrove forests, benefitting millions of people, experience significant degradation. Global recognition of the urgency of halting and reversing this trend have initiated numerous restoration activities. Restoration success is typically evaluated by estimating mangrove survival and area restored, while diversity and structure of vegetation, as proxies for functional forests, are rarely considered. Here we assess mangrove species richness along sea-landward transects and evaluate restoration outcomes by comparing number of mangrove species, relative species abundance, biomass, diameter, and canopy cover in “Monoculture Reforestation”, “Mixed Species Regeneration” and adjacent “Reference” forest stands, 14 (Tiwoho site) and 16 years (Likupang site) after restoration activities took place. In the “Monoculture Reforestation” plots, mangrove diversity and structure still closely reflected the original restoration actions, with only one and two “new” species having established among the originally densely planted “foundation” species. In contrast, the “Mixed Species Regeneration” plots were more similar to the “Reference” plots in terms of tree diameter and canopy coverage, but species number, abundance and biomass were still lower. The trajectory of the “Mixed Species Regeneration” plots suggests their similarity with the “Reference” stands will increase over time, whereas such “smooth” transition is unlikely to happen in the planted “Monoculture Reforestation” stands, in the foreseeable future. Implementing frequent small-scale disturbances in restored forest management would increase stand structure and diversity, accelerating the establishment of a more natural, and likely more functional and resilient forest

Multisite Randomized Trial of a Single-Session Versus Multisession Literacy-Sensitive Self-Care Intervention for Patients With Heart Failure

Self-care training can reduce hospitalization for heart failure (HF), and more intensive intervention may benefit more vulnerable patients, including those with low literacy

Connexin channels and phospholipids: association and modulation

<p>Abstract</p> <p>Background</p> <p>For membrane proteins, lipids provide a structural framework and means to modulate function. Paired connexin hemichannels form the intercellular channels that compose gap junction plaques while unpaired hemichannels have regulated functions in non-junctional plasma membrane. The importance of interactions between connexin channels and phospholipids is poorly understood.</p> <p>Results</p> <p>Endogenous phospholipids most tightly associated with purified connexin26 or connexin32 hemichannels or with junctional plaques in cell membranes, those likely to have structural and/or modulatory effects, were identified by tandem electrospray ionization-mass spectrometry using class-specific interpretative methods. Phospholipids were characterized by headgroup class, charge, glycerol-alkyl chain linkage and by acyl chain length and saturation. The results indicate that specific endogenous phospholipids are uniquely associated with either connexin26 or connexin32 channels, and some phospholipids are associated with both. Functional effects of the major phospholipid classes on connexin channel activity were assessed by molecular permeability of hemichannels reconstituted into liposomes. Changes to phospholipid composition(s) of the liposome membrane altered the activity of connexin channels in a manner reflecting changes to the surface charge/potential of the membrane and, secondarily, to cholesterol content. Together, the data show that connexin26 and connexin32 channels have a preference for tight association with unique anionic phospholipids, and that these, independent of headgroup, have a positive effect on the activity of both connexin26 and connexin32 channels. Additionally, the data suggest that the likely in vivo phospholipid modulators of connexin channel structure-function that are connexin isoform-specific are found in the cytoplasmic leaflet. A modulatory role for phospholipids that promote negative curvature is also inferred.</p> <p>Conclusion</p> <p>This study is the first to identify (endogenous) phospholipids that tightly associate with connexin channels. The finding that specific phospholipids are associated with different connexin isoforms suggests connexin-specific regulatory and/or structural interactions with lipid membranes. The results are interpreted in light of connexin channel function and cell biology, as informed by current knowledge of lipid-protein interactions and membrane biophysics. The intimate involvement of distinct phospholipids with different connexins contributes to channel structure and/or function, as well as plaque integrity, and to modulation of connexin channels by lipophilic agents.</p

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

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

Figure 5. A in Small islands and large biogeographic barriers have driven contrasting speciation patterns in Indo-Pacific sunbirds (Aves: Nectariniidae)

Figure 5. A, map of the Indo-Pacific with the range of the olive-backed sunbird shaded, as currently recognized by BirdLife International. Sampling sites of the birds included in our 697 bp partial ND2 analysis are marked with different triangles, according to the species they were assigned to by ABGD. Currently recognized subspecies are labelled (Gill et al., 2022). B, mean genetic distance (uncorrected p-distance) between each of the species recognized by ABGD, based on a 697 bp partial ND2 alignment. C, simplified version of a combined maximum likelihood (ML) and Bayesian phylogenetic tree of 697 bp of olive-backed sunbird ND2. In this figure the outgroup is omitted and each of the ABGD species is collapsed into a single branch. Nodes are labelled with Bayesian probability/ ML bootstraps.Published as part of Marcaigh, Fionn Ó, Kelly, David J., O'Connell, Darren P., Analuddin, Kangkuso, Karya, Adi, Mccloughan, Jennifer, Tolan, Ellen, Lawless, Naomi, Marples, Nicola M., O, Darren P. & Connell, 2022, Small islands and large biogeographic barriers have driven contrasting speciation patterns in Indo-Pacific sunbirds (Aves: Nectariniidae), pp. 1-21 in Zoological Journal of the Linnean Society CLXVI (CLXVI) on page 12, DOI: 10.1093/zoolinnean/zlac081, http://zenodo.org/record/757383