Sod farms drive habitat selection of a migratory grassland shorebird during a critical stopover period.

Migratory shorebirds are one of the fastest declining groups of North American avifauna. Yet, relatively little is known about how these species select habitat during migration. We explored the habitat selection of Buff-breasted Sandpipers (Calidris subruficollis) during spring and fall migration through the Texas Coastal Plain, a major stopover region for this species.

High dispersal ability versus migratory traditions: Fine-scale population structure and post-glacial colonisation in bar-tailed godwits.

In migratory animals, high mobility may reduce population structure through increased dispersal and enable adaptive responses to environmental change, whereas rigid migratory routines predict low dispersal, increased structure, and limited flexibility to respond to change. We explore the global population structure and phylogeographic history of the bar-tailed godwit, Limosa lapponica, a migratory shorebird known for making the longest non-stop flights of any landbird. Using nextRAD sequencing of 14,318 single-nucleotide polymorphisms and scenario-testing in an Approximate Bayesian Computation framework, we infer that bar-tailed godwits existed in two main lineages at the last glacial maximum, when much of their present-day breeding range persisted in a vast, unglaciated Siberian-Beringian refugium, followed by admixture of these lineages in the eastern Palearctic.

Site fidelity of migratory shorebirds facing habitat deterioration: insights from satellite tracking and mark-resighting.

Background: Site fidelity, the tendency to return to a previously visited site, is commonly observed in migratory birds. This behaviour would be advantageous if birds returning to the same site, benefit from their previous knowledge about local resources. However, when habitat quality declines at a site over time, birds with lower site fidelity might benefit from a tendency to move to sites with better habitats.

Understanding structure activity relationships of Good HEPES lipids for lipid nanoparticle mRNA vaccine applications.

Lipid nanoparticles (LNPs) have shown great promise as delivery vehicles to transport messenger ribonucleic acid (mRNA) into cells and act as vaccines for infectious diseases including COVID-19 and influenza. The ionizable lipid incorporated within the LNP is known to be one of the main driving factors for potency and tolerability. Herein, we describe a novel family of ionizable lipids synthesized with a piperazine core derived from the HEPES Good buffer.

Beta-containing bivalent SARS-CoV-2 protein vaccine elicits durable broad neutralization in macaques and protection in hamsters.

Background: Since the beginning of the COVID-19 pandemic, several variants of concern (VOC) have emerged for which there is evidence of an increase in transmissibility, more severe disease, and/or reduced vaccine effectiveness. Effective COVID-19 vaccine strategies are required to achieve broad protective immunity against current and future VOC.

Methods: We conducted immunogenicity and challenge studies in macaques and hamsters using a bivalent recombinant vaccine formulation containing the SARS-CoV-2 prefusion-stabilized Spike trimers of the ancestral D614 and the variant Beta strains with AS03 adjuvant (CoV2 preS dTM-AS03) in a primary immunization setting.

Beta variant COVID-19 protein booster vaccine elicits durable cross-neutralization against SARS-CoV-2 variants in non-human primates.

The rapid spread of the SARS-CoV-2 Omicron subvariants, despite the implementation of booster vaccination, has raised questions about the durability of protection conferred by current vaccines. Vaccine boosters that can induce broader and more durable immune responses against SARS-CoV-2 are urgently needed. We recently reported that our Beta-containing protein-based SARS-CoV-2 spike booster vaccine candidates with AS03 adjuvant (CoV2 preS dTM-AS03) elicited robust cross-neutralizing antibody responses at early timepoints against SARS-CoV-2 variants of concern in macaques primed with mRNA or protein-based subunit vaccine candidates.

Transplanted organoids empower human preclinical assessment of drug candidate for the clinic.

Pharmacodynamic (PD) studies are an essential component of preclinical drug discovery. Current approaches for PD studies, including the analysis of novel kidney disease targeting therapeutic agents, are limited to animal models with unclear translatability to the human condition. To address this challenge, we developed a novel approach for PD studies using transplanted, perfused human kidney organoids.

Protein-based SARS-CoV-2 spike vaccine booster increases cross-neutralization against SARS-CoV-2 variants of concern in non-human primates.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that partly evade neutralizing antibodies raises concerns of reduced vaccine effectiveness and increased infection. We previously demonstrated that the SARS-CoV-2 spike protein vaccine adjuvanted with AS03 (CoV2 preS dTM-AS03) elicits robust neutralizing antibody responses in naïve subjects. Here we show that, in macaques primed with mRNA or protein-based subunit vaccine candidates, one booster dose of CoV2 preS dTM-AS03 (monovalent D614 or B.

Pan-SARS neutralizing responses after third boost vaccination in non-human primate immunogenicity model.

The emergence of SARS-CoV-2 variants, especially Beta and Delta, has raised concerns about the reduced protection from previous infection or vaccination based on the original Wuhan-Hu-1 (D614) virus. To identify promising regimens for inducing neutralizing titers towards new variants, we evaluated monovalent and bivalent mRNA vaccines either as primary vaccination or as a booster in nonhuman primates (NHPs). Two mRNA vaccines, D614-based MRT5500 and Beta-based MRT5500β, tested in sequential regimens or as a bivalent combination in naïve NHPs produced modest neutralizing titers to heterologous variants.

Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza.

Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines.

Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates.

Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro.

Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models.

Emergency use authorization of COVID vaccines has brought hope to mitigate pandemic of coronavirus disease 2019 (COVID-19). However, there remains a need for additional effective vaccines to meet the global demand and address the potential new viral variants. mRNA technologies offer an expeditious path alternative to traditional vaccine approaches.

Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates.

Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody F receptors mediating effector functions .

Potatoes as a Crop for Space Life Support: Effect of CO, Irradiance, and Photoperiod on Leaf Photosynthesis and Stomatal Conductance.

Potatoes ( L.) have been suggested as a candidate crop for future space missions, based on their high yields of nutritious tubers and high harvest index. Three cultivars of potato, cvs.

Discovery of a Potent and Selective TRPC5 Inhibitor, Efficacious in a Focal Segmental Glomerulosclerosis Model.

The nonselective Ca-permeable transient receptor potential (TRP) channels play important roles in diverse cellular processes, including actin remodeling and cell migration. TRP channel subfamily C, member 5 (TRPC5) helps regulate a tight balance of cytoskeletal dynamics in podocytes and is suggested to be involved in the pathogenesis of proteinuric kidney diseases, such as focal segmental glomerulosclerosis (FSGS). As such, protection of podocytes by inhibition of TRPC5 mediated Ca signaling may provide a novel therapeutic approach for the treatment of proteinuric kidney diseases.

Publisher Correction: Fuelling conditions at staging sites can mitigate Arctic warming effects in a migratory bird.

In the original HTML version of this Article, the order of authors within the author list was incorrect. The consortium VRS Castricum was incorrectly listed after Theunis Piersma and should have been listed after Cornelis J. Camphuysen.

Fuelling conditions at staging sites can mitigate Arctic warming effects in a migratory bird.

Under climate warming, migratory birds should align reproduction dates with advancing plant and arthropod phenology. To arrive on the breeding grounds earlier, migrants may speed up spring migration by curtailing the time spent en route, possibly at the cost of decreased survival rates. Based on a decades-long series of observations along an entire flyway, we show that when refuelling time is limited, variation in food abundance in the spring staging area affects fitness.

Incorporation of RG1 epitope concatemers into a self-adjuvanting Flagellin-L2 vaccine broaden durable protection against cutaneous challenge with diverse human papillomavirus genotypes.

Aim: To achieve durable and broad protection against human papillomaviruses by vaccination with multimers of minor capsid antigen L2 using self-adjuvanting fusions with the toll-like receptor-5 (TLR5) ligand bacterial flagellin (Fla) instead of co-formulation with alum.

Methods: Fla fusions with L2 protective epitopes comprising residues 11-200, 11-88 and/or 17-38 of a single or multiple HPV types were produced in E. coli and their capacity to activate TLR5 signaling was assessed.

Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199).

Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma. In CLL, duvelisib monotherapy is associated with high iwCLL (International Workshop on Chronic Lymphocytic Leukemia) and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial.

Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells.

Recent clinical trials using immunotherapy have demonstrated its potential to control cancer by disinhibiting the immune system. Immune checkpoint blocking (ICB) antibodies against cytotoxic-T-lymphocyte-associated protein 4 or programmed cell death protein 1/programmed death-ligand 1 have displayed durable clinical responses in various cancers. Although these new immunotherapies have had a notable effect on cancer treatment, multiple mechanisms of immune resistance exist in tumours.

Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate.

Optimization of isoquinolinone PI3K inhibitors led to the discovery of a potent inhibitor of PI3K-γ (26 or IPI-549) with >100-fold selectivity over other lipid and protein kinases. IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-γ mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors.

When Siberia came to the Netherlands: the response of continental black-tailed godwits to a rare spring weather event.

1. Extreme weather events have the potential to alter both short- and long-term population dynamics as well as community- and ecosystem-level function. Such events are rare and stochastic, making it difficult to fully document how organisms respond to them and predict the repercussions of similar events in the future.

Low doses of flagellin-L2 multimer vaccines protect against challenge with diverse papillomavirus genotypes.

Genetically modified bacterial flagellin (Fla), a Toll-like receptor-5 (TLR5) ligand, was evaluated as a fusion partner for human papillomavirus (HPV) L2-based immunogens in two animal challenge models; either cutaneous inoculation of rabbits with HPV 'quasivirions' containing cottontail rabbit papillomavirus (CRPV) genomes that induce warts, or intra-vaginal inoculation of mice with HPV 'pseudovirions' encapsidating a luciferase reporter plasmid and measurement of bioluminescence to determine infectivity. An Escherichia coli production system was developed for flagellin-L2 (Fla-L2) fusions containing either monomeric HPV-16 L2 a.a.