Growth and ecophysiology of two Antarctic benthic predators; Isotealia antarctica and Urticinopsis antarctica

There is a dearth of basic life history and physiological data from Southern Ocean species, particularly from benthic vagile predators. This is an important data gap because species inhabiting the Southern Ocean live in a more temperature stable but seasonally varying environment than temperate and tropical counterparts. For many species living below 0 ◦C for a significant proportion of the year, bodily functions are slowed to disproportionately lower rates than would be predicted by temperature alone. Certain life history and physiological processes are often aligned with the short summer season of productivity. However, predators may behave differently because they are decoupled from the phytoplankton bloom and some have been shown to exhibit less seasonal physiological change. To further our understanding of Antarctic predator growth and seasonal ecophysiology, field growth rates were measured for two soft-bodied Antarctic anemone benthic predators, Isotealia antarctica and Urticinopsis antarctica, using in situ sampling of anemones on uniquely marked tiles. Ex situ measurements of oxygen consumption and seven-day faecal output were obtained from recently collected specimens in aquaria and compared between summer and winter. Winter physiological data for Antarctic species are rare, and we tested the hypothesis that generalist feeders or predators continue to feed during the winter. Growth rates differed between species and between years. I. antarctica and U. antarctica both exhibited overall positive field growth rates across a 15 month period between 2020 and 2021; with U. antarctica increasing 199.80% (± SE 25.8) in mass compared to a 16.85% (± SE 8.9) increase in I. antarctica. There was no significant difference in I. antarctica’s growth between 15 and 25 months field deployment. After 25 months, I. antarctica showed an average 7.96% (± SE 8.05) increase in buoyant weight. Ex situ oxygen consumption and faecal egestion did not differ seasonally, which, demonstrates that anemones fed at similar rates during the winter and summer. In contrast to some members of the Antarctica benthos, I. antarctica and U. antarctica actively feed all year round, whereas several other species have been reported to enter a state of torpor in winter

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt

ACTIV-2: A Platform Trial for the Evaluation of Novel Therapeutics for the Treatment of Early COVID-19 in Outpatients

Clinical Trials Registration ClinicalTrials.gov Identifier: NCT04518410

Species abundance distributions: moving beyond single prediction theories to integration within an ecological framework

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75247/1/j.1461-0248.2007.01094.x.pd

Variant-Specific Viral Kinetics in Acute COVID-19

Understanding variant-specific differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics may explain differences in transmission efficiency and provide insights on pathogenesis and prevention. We evaluated SARS-CoV-2 kinetics from nasal swabs across multiple variants (Alpha, Delta, Epsilon, Gamma) in placebo recipients of the ACTIV-2/A5401 trial. Delta variant infection led to the highest maximum viral load and shortest time from symptom onset to viral load peak. There were no significant differences in time to viral clearance across the variants. Viral decline was biphasic with first- and second-phase decays having half-lives of 11 hours and 2.5 days, respectively, with differences among variants, especially in the second phase. These results suggest that while variant-specific differences in viral kinetics exist, post-peak viral load all variants appeared to be efficiently cleared by the host. Clinical Trials Registration. NCT04518410

Statistical Challenges When Analyzing SARS-CoV-2 RNA Measurements Below the Assay Limit of Quantification in COVID-19 Clinical Trials

Most clinical trials evaluating coronavirus disease 2019 (COVID-19) therapeutics include assessments of antiviral activity. In recently completed outpatient trials, changes in nasal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA levels from baseline were commonly assessed using analysis of covariance (ANCOVA) or mixed models for repeated measures (MMRM) with single imputation for results below assay lower limits of quantification (LLoQ). Analyzing changes in viral RNA levels with singly imputed values can lead to biased estimates of treatment effects. In this article, using an illustrative example from the ACTIV-2 trial, we highlight potential pitfalls of imputation when using ANCOVA or MMRM methods, and illustrate how these methods can be used when considering value

Association Between Anterior Nasal and Plasma SARS-CoV-2 RNA Levels and Hospitalization or Death in Nonhospitalized Adults With Mild-to-Moderate COVID-19

BackgroundThere is little information regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA as a predictor for clinical outcomes in outpatients with mild-to-moderate coronavirus disease 2019 (COVID-19).MethodsAnterior nasal (AN) and plasma SARS-CoV-2 RNA data from 2115 nonhospitalized adults who received monoclonal antibodies (mAbs) or placebo in the ACTIV-2/A5401 trial were analyzed for associations with hospitalization or death.ResultsOne hundred two participants were hospitalized or died through 28 days of follow-up. Higher day 0 (pretreatment) AN RNA was associated with increasing risk of hospitalization/death (risk ratio [RR], 1.24 per log10 copies/mL [95% confidence interval {CI}, 1.04-1.49]) among placebo recipients, ranging from 3% to 16% for <2 to ≥6 log10 copies/mL. Although only 1% had quantifiable levels, there was a similar trend across day 0 plasma RNA categories. Higher day 3 AN RNA was associated with subsequent hospitalization/death among placebo recipients (RR, 1.42 per log10 copies/mL [95% CI, 1.00-2.03]), but not mAb recipients (RR, 1.02 per log10 copies/mL [95% CI, 0.68-1.56]). The proportion of treatment effect (reduction in hospitalizations/deaths after day 3 for mAb vs placebo) explained by day 3 AN RNA was 8%.ConclusionsSARS-CoV-2 RNA levels are predictive of hospitalization/death in the natural history setting, but AN RNA levels may not be a reliable surrogate marker of mAb treatment effect in COVID-19 trials. Clinical Trials Registration. NCT04518410