The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Fluctuating optimum and temporally variable selection on breeding date in birds and mammals

International audienceTemporal variation in natural selection is predicted to strongly impact the evolution and demography of natural populations, with consequences for the rate of adaptation, evolution of plasticity, and extinction risk. Most of the theory underlying these predictions assumes a moving optimum phenotype, with predictions expressed in terms of the temporal variance and autocorrelation of this optimum. However, empirical studies seldom estimate patterns of fluctuations of an optimum phenotype, precluding further progress in connecting theory with observations. To bridge this gap, we assess the evidence for temporal variation in selection on breeding date by modeling a fitness function with a fluctuating optimum, across 39 populations of 21 wild animals, one of the largest compilations of long-term datasets with individual measurements of trait and fitness components. We find compelling evidence for fluctuations in the fitness function, causing temporal variation in the magnitude, but not the direction of selection. However, fluctuations of the optimum phenotype need not directly translate into variation in selection gradients, because their impact can be buffered by partial tracking of the optimum by the mean phenotype. Analyzing individuals that reproduce in consecutive years, we find that plastic changes track movements of the optimum phenotype across years, especially in bird species, reducing temporal variation in directional selection. This suggests that phenological plasticity has evolved to cope with fluctuations in the optimum, despite their currently modest contribution to variation in selection

Global human footprint on the linkage between biodiversity and ecosystem functioning in reef fishes

Copyright: © 2011 Mora et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Difficulties in scaling up theoretical and experimental results have raised controversy over the consequences of biodiversity loss for the functioning of natural ecosystems. Using a global survey of reef fish assemblages, we show that in contrast to previous theoretical and experimental studies, ecosystem functioning (as measured by standing biomass) scales in a non-saturating manner with biodiversity (as measured by species and functional richness) in this ecosystem. Our field study also shows a significant and negative interaction between human population density and biodiversity on ecosystem functioning (i.e., for the same human density there were larger reductions in standing biomass at more diverse reefs). Human effects were found to be related to fishing, coastal development, and land use stressors, and currently affect over 75% of the world's coral reefs. Our results indicate that the consequences of biodiversity loss in coral reefs have been considerably underestimated based on existing knowledge and that reef fish assemblages, particularly the most diverse, are greatly vulnerable to the expansion and intensity of anthropogenic stressors in coastal areas

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

Type I interferon responses are impaired in latently HIV infected cells

Abstract Background The latent HIV-1 reservoir represents the primary barrier to the eradication of HIV-1 infection. The design of novel reservoir-clearance strategies, however, is impeded in part by the inability to distinguish latently HIV-infected cells from uninfected cells. Significant impairment of the type I interferon (IFN-I) response is observed during productive HIV-1 infection. Although this remains poorly described in the context of latent HIV-1 infection, presence of potential defects may serve as a novel therapeutic target. Therefore, IFN-I pathways were characterized using two latently HIV-1-infected cell lines, U1 and OM10.1, in comparison to their respective uninfected parental U937 and HL60 cell lines. Findings Constitutive expression and induction of important mediators of IFN-I signaling including IFNα/β cytokines, IFNAR1, MHC-I, ISG15, and PKR were evaluated following exogenous IFNα or poly(I:C) treatment. Differences in basal expression of IFNAR1, MHC-I, and PKR were observed between the latently HIV-1 infected and uninfected cell lines. In parallel, significant impairments in the induction of MHC-I, ISG15 and PKR, as well as secretion of IFNα/β cytokines were observed in response to appropriate exogenous stimulation within the two latently HIV-infected U1 and OM10.1 cells, relative to their HIV-uninfected parental cells. Conclusions In comparison to the HIV-uninfected U937 and HL60 cell lines, widespread defects in IFN-I responsiveness were observed within the latently HIV-infected U1 and OM10.1 cells. These impairments represent novel therapeutic targets, which may be amenable to strategies currently employed in cancer therapy

Dectin-1/TLR2 and NOD2 Agonists Render Dendritic Cells Susceptible to Infection by X4-Using HIV-1 and Promote <i>cis</i>-Infection of CD4⁺ T Cells

<div><p>HIV-1 pathogenesis is intimately linked with microbial infections and innate immunity during all stages of the disease. While the impact of microbial-derived products in transmission of R5-using virus to CD4⁺ T cells by dendritic cells (DCs) has been addressed before, very limited data are available on the effect of such compounds on DC-mediated dissemination of X4-tropic variant. Here, we provide evidence that treatment of DCs with dectin-1/TLR2 and NOD2 ligands increases <i>cis</i>-infection of autologous CD4⁺ T cells by X4-using virus. This phenomenon is most likely associated with an enhanced permissiveness of DCs to productive infection with X4 virus, which is linked to increased surface expression of CXCR4 and the acquisition of a maturation profile by DCs. The ensuing DC maturation enhances susceptibility of CD4⁺ T cells to productive infection with HIV-1. This study highlights the crucial role of DCs at different stages of HIV-1 infection and particularly in spreading of viral strains displaying a X4 phenotype.</p></div

Treatment of DCs with PAMPs promotes <i>cis</i>-infection of CD4⁺ T cells with X4 virus.

<p>iDCs were left untreated or treated with the indicated PAMPs for 24 hours. Cells were next either left untreated (A) or treated with EFV (B) to block productive infection of DCs prior to loading with NL4-3 for 4 hours at 37°C. Cells were extensively washed and incubated for 16 hours before addition of autologous resting CD4⁺ T cells. Cell-free supernatants were collected at 3, 6 and 9 days following initiation of the co-culture. Data shown represent the mean ± SEM of quadruplicate samples from one representative donor out of four at 6 days following initiation of the co-culture. (*: p<0.05; **: p<0.01). The small insert shows kinetics of virus production for this donor (only iDCs either left untreated or treated with zymosan or flagellin are illustrated).</p

PAMPs enhance CXCR4 expression on DCs and susceptibility to productive infection with X4 virus.

<p>(A) iDCs were left untreated or treated for 24 hours with the listed PAMPs. Next, DCs were washed and pretreated, or not, with EFV for 15 minutes, and then exposed to NL4-3 for another 24 hours. Cell-free supernatants were harvested at 3, 6, 9, 12 and 15 days post-infection (dpi). Data depicted in the upper left panel represent the means ± SEM of quadruplicate samples from one representative donor out of four at 6 days post-infection. The small insert shows kinetics of virus production for this donor (only iDCs either left untreated or treated with zymosan, LPS, or flagellin are illustrated). Each point depicted in the right panel represents the mean of quadruplicate samples for each of the four donors tested. The horizontal line represents median results of all four distinct donors. (B) iDCs were left untreated or treated for 72 hours with the indicated PAMPs. Cell surface expression of CXCR4 was analyzed by flow cytometry. Expression of CXCR4 is depicted as the percentage of positive cells multiplied by the mean fluorescence intensity for the treated condition, over that of untreated cells. Each point represents a different donor while the horizontal bar represents the mean of all donors. One representative CXCR4 staining is depicted in the left panel. (C) iDCs were left untreated or treated with the indicated PAMPs for 72 hours to allow CXCR4 surface expression. Cells were next either left untreated (left panel) or treated with EFV (right panel) prior to loading with NL4-3 for 4 hours at 37°C. Cells were extensively washed and incubated for 16 hours before addition of resting CD4⁺ T cells. Supernatants were collected at 3, 6 and 9 days following initiation of the co-culture. Data represents the mean ± SEM of quadruplicates from one representative donor out of four at 6 days following initiation of the co-culture. The small insert on the left panel represents the kinetics of virus infection for this donor. (D) iDCs were either left untreated or treated with the indicated PAMPs for 72 hours. Cells were either left untreated or treated with EFV (small insert) and next incubated with NL4-3 for 72 hours. Total RNA was extracted and the relative amount of spliced <i>tat</i> mRNA was evaluated by semi-quantitative RT-PCR. After normalization on 18S ribosomal RNA subunit, the amount of spliced <i>tat</i> mRNA in PAMP-treated DCs was expressed as folds of that of untreated cells. Each point represents a different donor and the horizontal bar represents the median of all donors. Asterisks denote statistically significant data (*: p<0.05; **: p<0.01).</p