Characterization of Pulmonary Pathology in the Golden Syrian Hamster Model of COVID-19 Using Micro-Computed Tomography.

The Golden Syrian hamster is a well-characterized rodent model for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-associated pneumonia. We sought to characterize the pulmonary disease course during SARS-CoV-2 infection (strain USA-WA1/2020) in the hamster model using micro-computed tomography (micro-CT) and compare radiologic observations with histopathologic findings. We observed a range of radiologic abnormalities, including ground glass opacities (GGOs), consolidations, air bronchograms, and pneumomediastinum.

A cynomolgus monkey urinary tract infection model confirms efficacy of new FimH vaccine candidates.

The increase in urinary tract infections (UTI) caused by antibiotic-resistant requires the development of new therapeutic agents and prophylactic vaccines. To evaluate the efficacy of new lead candidates, we implemented a cynomolgus macaque UTI challenge model that mimics human uncomplicated cystitis in response to transurethral challenge with a multidrug-resistant (MDR) serotype O25b ST131 isolate. fimbrial adhesin FimH and O-antigens are separately under clinical evaluation by others as vaccine candidates to prevent UTI and invasive urosepsis disease, respectively.

Preclinical Evidence for the Protective Capacity of Antibodies Induced by Lyme Vaccine Candidate VLA15 in People.

Background: Vaccine candidate VLA15 is designed to protect against the dominant genospecies-causing Lyme disease in North America and Europe. Active immunization with VLA15 has protected in the mouse model of tick challenge. VLA15 is currently under evaluation in clinical studies for the prevention of Lyme borreliosis.

Evidence of Reduced Virulence and Increased Colonization Among Pneumococcal Isolates of Serotype 3 Clade II Lineage in Mice.

Recent phylogenetic profiling of pneumococcal serotype 3 (Pn3) isolates revealed a dynamic interplay among major lineages with the emergence and global spread of a variant termed clade II. The cause of Pn3 clade II dissemination along with epidemiological and clinical ramifications are currently unknown. Here, we sought to explore biological characteristics of dominant Pn3 clades in a mouse model of pneumococcal invasive disease and carriage.

Comparison of pneumococcal immunogenicity elicited by the PCV13 and PCV15 vaccines in adults 18 through 49 years of age.

Aim: Pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) effectively target the capsular polysaccharides of the most common disease-causing Streptococcus pneumoniae serotypes. In this short communication, we analyzed healthy participants who received PCV13 and PCV15 vaccines as part of a recently concluded exploratory clinical trial and report antibody responses to the 13 shared serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) as well as functional OPA responses to serotype 3.

Methods: Sera from 87 adult participants (18 through 49 years of age) randomized to receive either PCV13 or PCV15 were collected (n = 46 or n = 41, respectively), from 17 study centers in the US.

Animal models for studying COVID-19, prevention, and therapy: Pathology and disease phenotypes.

Translational models have played an important role in the rapid development of safe and effective vaccines and therapeutic agents for the ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Animal models recapitulating the clinical and underlying pathological manifestations of COVID-19 have been vital for identification and rational design of safe and effective vaccines and therapies. This manuscript provides an overview of commonly used COVID-19 animal models and the pathologic features of SARS-CoV-2 infection in these models in relation to their clinical presentation in humans.

Preclinical Immunogenicity and Efficacy of Optimized O25b O-Antigen Glycoconjugates To Prevent MDR ST131 E. coli Infections.

Multivalent O-antigen polysaccharide glycoconjugate vaccines are under development to prevent invasive infections caused by pathogenic . Sequence type 131 (ST131) Escherichia coli of serotype O25b has emerged as the predominant lineage causing invasive multidrug-resistant extraintestinal pathogenic E. coli (ExPEC) infections.

Modeling SARS-CoV-2: Comparative Pathology in Rhesus Macaque and Golden Syrian Hamster Models.

Coronavirus disease 2019 (COVID-19) in humans has a wide range of presentations, ranging from asymptomatic or mild symptoms to severe illness. Suitable animal models mimicking varying degrees of clinical disease manifestations could expedite development of therapeutics and vaccines for COVID-19. Here we demonstrate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulted in subclinical disease in rhesus macaques with mild pneumonia and clinical disease in Syrian hamsters with severe pneumonia.

The effect of SARS-CoV-2 D614G mutation on BNT162b2 vaccine-elicited neutralization.

Initial COVID-19 vaccine candidates were based on the original sequence of SARS-CoV-2. However, the virus has since accumulated mutations, among which the spike D614G is dominant in circulating virus, raising questions about potential virus escape from vaccine-elicited immunity. Here, we report that the D614G mutation modestly reduced (1.

BNT162b vaccines protect rhesus macaques from SARS-CoV-2.

A safe and effective vaccine against COVID-19 is urgently needed in quantities that are sufficient to immunize large populations. Here we report the preclinical development of two vaccine candidates (BNT162b1 and BNT162b2) that contain nucleoside-modified messenger RNA that encodes immunogens derived from the spike glycoprotein (S) of SARS-CoV-2, formulated in lipid nanoparticles. BNT162b1 encodes a soluble, secreted trimerized receptor-binding domain (known as the RBD-foldon).

Evidence for an unknown agent antigenically related to the hepatitis E virus in dairy cows in the United States.

Genotypes 3 and 4 hepatitis E virus (HEV) strains within the species Orthohepevirus A in the family Hepeviridae are zoonotic. Recently, a genotype 4 HEV was reportedly detected in fecal samples of cows, although independent confirmation is lacking. In this study, we first tested serum samples from 983 cows in different regions in the United States for the presence of immunoglobulin G (IgG) anti-HEV and found that 20.

Structural determinants of TAR RNA-DNA annealing in the absence and presence of HIV-1 nucleocapsid protein.

Annealing of the TAR RNA hairpin to the cTAR DNA hairpin is required for the minus-strand transfer step of HIV-1 reverse transcription. HIV-1 nucleocapsid protein (NC) plays a crucial role by facilitating annealing of the complementary hairpins. To gain insight into the mechanism of NC-mediated TAR RNA-DNA annealing, we used structural probes (nucleases and potassium permanganate), gel retardation assays, fluorescence anisotropy and cTAR mutants under conditions allowing strand transfer.

Structural and dynamic characterization of the upper part of the HIV-1 cTAR DNA hairpin.

First strand transfer is essential for HIV-1 reverse transcription. During this step, the TAR RNA hairpin anneals to the cTAR DNA hairpin; this annealing reaction is promoted by the nucleocapsid protein and involves an initial loop-loop interaction between the apical loops of TAR and cTAR. Using NMR and probing methods, we investigated the structural and dynamic properties of the top half of the cTAR DNA (mini-cTAR).

Structural requirements for nucleocapsid protein-mediated dimerization of avian leukosis virus RNA.

The avian leukosis virus (ALV) belongs to the alpha group of retroviruses that are widespread in nature. The 5'-untranslated region of ALV genome contains the L3 element that is important for virus infectivity and the formation of an unstable RNA dimer in vitro. The L3 sequence is predicted to fold into a long stem-loop structure with two internal loops and an apical one.

Analysis of hepatitis C virus RNA dimerization and core-RNA interactions.

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3'-untranslated region (3'-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C.

Teaching pigeons to commit base-rate neglect.

Whereas humans display base-rate neglect in a behavioral analogue of the base-rate problem, pigeons have been shown to behave optimally in a comparable task, appropriately weighting base-rate and case-cue information. Previous studies have shown that prior experience may interfere with optimal decisions for human subjects, a result consistent with the position that poor and illogical decisions often follow from the misapplication of learned rules. The present study shows that pigeons will also display base-rate neglect if given extensive pretraining with informative case cues.

Specific interactions between HIV-1 nucleocapsid protein and the TAR element.

During retroviral reverse transcription, the minus-strand strong-stop DNA (ss-cDNA) is transferred to the 3' end of the genomic RNA and this requires the repeat (R) sequences present at both ends of the genome. In vitro, the human immunodeficiency virus type 1 (HIV-1) R sequence can promote DNA strand transfer when present in ectopic internal positions. Using HIV-1 model systems, the R sequences and nucleocapsid protein (NC) were found to be key determinants of ss-cDNA transfer.

In vitro characterization of a base pairing interaction between the primer binding site and the minimal packaging signal of avian leukosis virus genomic RNA.

The 5' leader region of avian sarcoma-leukosis viruses (ASLVs) folds into a series of RNA secondary structures which are involved in key steps in the viral replication cycle such as reverse transcription, dimerization and packaging of genomic RNA. The O3 stem and three stem-loops (O3SLa, O3SLb and O3SLc) form the minimal packaging signal that is located downstream of the primer binding site (PBS). The U5-PBS region contributes to packaging via a mechanism that remains unknown.

Phylogenetic relationships of Staphylococcus aureus from bovine mastitis based on coagulase gene polymorphism.

Coagulase gene restriction fragment length polymorphism (RFLP) patterns were analyzed to determine the phylogenetic relationship among isolates of Staphylococcus aureus from the Czech Republic (n = 27), France (n = 48), Korea (n = 115) and the United States (n = 278). A total of 468 isolates of S. aureus were subtyped into 41 coagulase genotypes.

Efficient synthesis of DNA dumbbells using template-induced chemical ligation in double-stranded polynucleotides closed by minihairpin fragments.

The chemical ligation of 17 50-54-membered nicked DNA dumbbells with different closing fragments, nick positions, and nucleotides facing the nick were investigated. T4, T5, GTA4C, GCGA2GC, and GCGA3GC sequences were chosen as the closing fragments. The nicks were placed in the center of the duplex stem or were adjacent to the closing fragments.

Design and synthesis of double-stranded oligonucleotides containing reactive acylphosphate internucleotide groups.

DNA duplex and dumbbells containing chemically active acylphosphate internucleotide groups were synthesized. To obtain these compounds the chemical ligation method was used. The acylphosphate group was inserted into a DNA duplex and dumbbells as a result of template-directed condensation of 5'-phosphate and especially introduced 3'-carboxy groups of oligonucleotides.

Modified substrates as probes for studying uracil-DNA glycosylase.

In order to study the mechanism of action of uracil-DNA glycosylase (UDG) from human placenta, single-stranded (ss) and double-stranded (ds) oligodeoxyribonucleotides (oligos), containing deoxyuridine (dU) and a wide variety of their analogs were used. It was shown that UDG has a twofold preference for ss oligos over ds oligos and a twofold preference for intermolecular duplexes over similar hairpin-like duplexes. The replacement of dU with 1-(beta-D-2'-deoxy-threo-pentofuranosil)uracil (xU) or 1-(beta-D-3'-deoxy-threo-pentofuranosil)uracil (tU), which results in a change in sugar hydroxyl configuration, has no influence on UDG binding to such substrates, but inhibits uracil removal.

A 268 bp upstream sequence mediates the circadian clock-regulated transcription of the wheat Cab-1 gene in transgenic plants.

We previously reported that the expression of the wheat Cab-1 gene is regulated by an endogenous circadian rhythm and by the photoreceptor phytochrome both in wheat and in transgenic tobacco plants. To define regulatory elements necessary for the circadian rhythm-regulated Cab-1 gene expression, we now analysed the fluctuation of steady-state mRNA levels in a series of 5' deletion mutants in transgenic tobacco plants. We found that the expression of a deletion mutant containing 211 bp upstream sequence still exhibited circadian rhythm.