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Prime-2-CoV_Beta is a novel Orf virus (ORFV)-based COVID-19 vaccine candidate expressing both the nucleocapsid and spike proteins of SARS-CoV-2 with the receptor-binding domain (RBD) of the Beta strain. This candidate was shown to be safe and immunogenic in a first-in-human Phase I clinical trial. With the shift in the immune landscape toward the Omicron variant and the widespread vaccine- and/or infection-derived immunity, further pre-clinical research was needed to characterize Prime-2-CoV. Here, we quantified the humoral and cellular response to Prime-2-CoV_Beta in pre-immunized mice and compared the protective efficacy of mono- and bivalent variant-based Prime-2-CoV vaccine candidates in hamsters. Prime-2-CoV_Beta induced robust humoral and cellular immune responses in naïve animals but did not further boost antibody titers in the tested setting when given as repeat booster at short interval. We furthermore showed that Prime-2-CoV_Beta-based mono- and bivalent immunization strategies produced comparable immunogenicity and protection from infection. Our results highlight the potential of the Orf virus as a vaccine platform against SARS-CoV-2 and potentially other infectious viruses.

Introduction: Hydropower plants are frequently equipped with physical and behavioral fish protection barriers to prevent downstream moving fish from harmful turbine passage and to guide them to alternative bypasses. As not only diadromous but also potamodromous fish species migrate and inevitably have to pass hydropower plants, knowledge on corridor usage for a wide range of species is important to identify potential deficits and to improve bypass efficiency.Methods: In this study, the corridor usage of downstream moving fish (6,646 individuals from 42 species) was investigated at four small-scale hydropower plants with different concepts to prevent turbine entrainment and to bypass fish.Results: Despite existing bypasses and fine screens with 15 mm and 20 mm bar spacing to prevent turbine entrainment, a large proportion of fish (35%–88%) still passed the turbines. The mainly poor efficiency of the investigated bypasses was probably due to low discharge and unfavorable bypass location or detectability. The various bypass types were used by a different range of fish species and sizes due to species-specific behavior and differing fish communities between sites. The effectiveness of the investigated downstream corridors was positively correlated with the share of discharge.Discussion: To reduce the negative ecological impacts of hydropower plants on downstream moving fish, well-performing bypasses are required that consider not only current requirements regarding design, dimensioning and location, but also the site-specific fish community. Thus, bypasses should function for the widest possible range of species, which can be achieved through less selective bypass types such as full-depth bypasses, or a combination of different bypass systems. Moreover, less harmful turbine technologies and more effective fish protection systems need to be implemented, since fine screens with 15 mm and 20 mm bar spacing cannot prevent small-bodied fish species and juvenile fish

Knowledge on the extent and mechanisms of fish damage caused by hydropower facilities is important for the conservation of fish populations. Herein, we assessed the effects of hydropower turbine passage on internal fish injuries using X-ray technology. A total of 902 specimens from seven native European fish species were screened for 36 types of internal injuries and 86 external injuries evaluated with a previously published protocol. The applied systematic visual evaluation of X-ray images successfully detected skeletal injuries, swim bladder anomalies, emphysema, free intraperitoneal gas and hemorrhages. Injuries related to handling and to impacts of different parts of the hydropower structure could be clearly distinguished applying multivariate statistics and the data often explained delayed mortality within 96 h after turbine passage. The internal injuries could clearly be assigned to specific physical impacts resulting from turbine passage such as swim bladder rupture due to abrupt pressure change or fractures of skeletal parts due to blade-strike, fluid shear or severe turbulence. Generally, internal injuries were rarely depicted by external evaluation. For example, 29% of individuals with vertebral fractures did not present externally visible signs of severe injury. A combination of the external and internal injury evaluation allows quantifying and comparing fish injuries across sites, and can help to identify the technologies and operational procedures which minimize harm to fish in the context of assessing hydropower-related fish injuries as well as in assessing fish welfare.

BackgroundPatients experiencing cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) often die or suffer from severe neurological impairment. Post resuscitation syndrome is characterized by a systemic inflammatory response. Toll-like receptor 4 (TLR4) is a major mediator of inflammation and TLR4 has been implicated in the pathogenesis of post-resuscitation encephalopathy. The aim of this study was to evaluate whether TLR4 deficiency or inhibition can modulate survival and neurofunctional outcome after CA/CPR.MethodsFollowing intubation and central venous cannulation, CA was induced in wild type (C57Bl/6J, n = 38), TLR4 deficient (TLR4-/-, n = 37) and TLR4 antibody treated mice (5mg/kg MTS510, n = 15) by high potassium. After 10min, CPR was performed using a modified sewing machine until return of spontaneous circulation (ROSC). Cytokines and cerebral TNFalpha levels were measured 8h after CA/CPR. Survival, early neurological recovery, locomotion, spatial learning and memory were assessed over a period of 28 days.ResultsFollowing CA/CPR, all mice exhibited ROSC and 31.5% of wild type mice survived until day 28. Compared to wild type mice, neither TLR4-/- nor MTS510 treated wild type mice had statistically significant altered survival following CA/CPR (51.3 and 26.7%, P = 0.104 and P = 0.423 vs. WT, respectively). Antibody-treated but not TLR4-/- mice had higher IL-1β and IL-6 levels and TLR4-/- mice had higher IL-10 and cerebral TNFalpha levels. No differences existed between mice of all groups in early neurological recovery, locomotion, spatial learning ability or remembrance.ConclusionTherapeutic strategies targeting TLR4 may not be suitable for the reduction of mortality or neurofunctional impairment after CA/CPR.

Abstract The theoretical concept of the ecosystem approach (EA) aims at assessing ecosystem function based on integrative assessments of multiple levels of biological organization. Since the United Nations Convention on Biological Diversity in 1992, the EA has been increasingly integrated into environmental policy and legislation, but to date, its practical implementation remains vague with a lack of universal guidelines and concrete recommendations for its use across ecosystem boundaries. On the basis of a review of scientific literature, worldwide environmental legislation and existing monitoring approaches, we identified the most important factors which hamper the feasibility of the EA. We propose a generally applicable methodology for implementing the EA in ecological and environmental monitoring across different ecosystems and habitat types. Successful application of the EA largely depends on adequately standardized and synchronized sampling designs for all abiotic and biotic components, appropriate depth of taxonomic identification, and sufficient spatial and temporal replication. The proposed step‐by‐step guidelines for using the EA are valid across ecosystem types, geographic regions, and for a variety of data types, making them promising tools for ecological monitoring.

The purpose of the present study was to determine if trihydroxymethamphetamine (THMA), a metabolite of methylenedioxymethamphetamine (MDMA, “ecstasy”), or its thioether conjugate, 6-(N-acetylcystein-S-yl)-2,4,5-trihydroxymethamphetamine (6-NAC-THMA), play a role in the lasting effects of MDMA on brain serotonin (5-HT) neurons. To this end, novel high-yield syntheses of THMA and 6-NAC-THMA were developed. Lasting effects of both compounds on brain serotonin (5-HT) neuronal markers were then examined. A single intraventricular injection of THMA produced a significant lasting depletion of regional rat brain 5-HT and 5-hydroxyindoleacetic acid (5-HIAA), consistent with previous reports that THMA harbors 5-HT neurotoxic potential. The lasting effect of THMA on brain 5-HT markers was blocked by the 5-HT uptake inhibitor fluoxetine, indicating that persistent effects of THMA on 5-HT markers, like those of MDMA, are dependent on intact 5-HT transporter function. Efforts to identify THMA in the brains of animals treated with a high, neurotoxic dose (80 mg/kg) of MDMA were unsuccessful. Inability to identify THMA in the brains of these animals was not related to the unstable nature of the THMA molecule because exogenous THMA administered intracerebroventricularly could be readily detected in the rat brain for several hours. The thioether conjugate of THMA, 6-NAC-THMA, led to no detectable lasting alterations of cortical 5-HT or 5-HIAA levels, indicating that it lacks significant 5-HT neurotoxic activity. The present results cast doubt on the role of either THMA or 6-NAC-THMA in the lasting serotonergic effects of MDMA. The possibility remains that different conjugated forms of THMA or oxidized cyclic forms (e.g., the indole of THMA) play a role in MDMA-induced 5-HT neurotoxicity in vivo. [ABSTRACT FROM AUTHOR]