Fluorescent and bioluminescent bovine H5N1 influenza viruses for evaluation of antiviral interventions.

In early 2024, a clade 2.3.4.

Headless hemagglutinin-containing influenza viral particles direct immune responses toward more conserved epitopes.

Seasonal influenza vaccines provide mostly strain-specific protection due to the elicitation of antibody responses focused on evolutionarily plastic antigenic sites in the hemagglutinin head domain. To direct the humoral response toward more conserved epitopes, we generated an influenza virus particle where the full-length hemagglutinin protein was replaced with a membrane-anchored, "headless" variant while retaining the normal complement of other viral structural proteins such as the neuraminidase as well as viral RNAs. We found that a single administration of a headless virus particle-based vaccine elicited high titers of antibodies that recognized more conserved epitopes on the major viral glycoproteins.

Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.

Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be updated and readministered annually. To increase the breadth of influenza vaccine-mediated protection, we developed an antigenically complex mixture of recombinant HAs designed to redirect immune responses to more conserved domains of the protein.

Segmented, Negative-Sense RNA Viruses of Humans: Genetic Systems and Experimental Uses of Reporter Strains.

Negative-stranded RNA viruses are a large group of viruses that encode their genomes in RNA across multiple segments in an orientation antisense to messenger RNA. Their members infect broad ranges of hosts, and there are a number of notable human pathogens. Here, we examine the development of reverse genetic systems as applied to these virus families, emphasizing conserved approaches illustrated by some of the prominent members that cause significant human disease.

Type I IFN Receptor Signaling on B Cells Promotes Antibody Responses to Polysaccharide Antigens.

We previously reported monophosphoryl lipid A (MPL) and synthetic cord factor trehalose-6,6'-dicorynomycolate (TDCM) significantly increase Ab responses to T cell-independent type 2 Ags (TI-2 Ags) in a manner dependent on B cell-intrinsic TLR4 expression, as well as MyD88 and TRIF proteins. Given the capacity of MPL to drive type I IFN production, we aimed to investigate the extent to which type I IFN receptor (IFNAR) signaling was required for TI-2 responses and adjuvant effects. Using Ifnar1-/- mice and IFNAR1 Ab blockade, we found that IFNAR signaling is required for optimal early B cell activation, expansion, and Ab responses to nonadjuvanted TI-2 Ags, including the pneumococcal vaccine.

The PD-1 Regulatory Axis Inhibits T Cell-Independent B Cell Memory Generation and Reactivation.

The inability of T cell-independent type 2 (TI-2) Ags to induce recall responses is a poorly understood facet of humoral immunity, yet critically important for improving vaccines. Using normal and VB1-8 transgenic mice, we demonstrate that B cell-intrinsic PD-1 expression negatively regulates TI-2 memory B cell (B) generation and reactivation in part through interacting with PDL1 and PDL2 on non-Ag-specific cells. We also identified a significant role for PDL2 expression on B in inhibiting reactivation and Ab production, thereby revealing a novel self-regulatory mechanism exists for TI-2 B This regulation impacts responses to clinically relevant vaccines, because PD-1 deficiency was associated with significantly increased Ab boosting to the pneumococcal vaccine after both vaccination and infection.

Mouse vocal emission and acoustic complexity do not scale linearly with the size of a social group.

Adult mice emit ultrasonic vocalizations (USVs), sounds above the range of human hearing, during social encounters. While mice alter their vocal emissions between isolated and social contexts, technological impediments have hampered our ability to assess how individual mice vocalize in group social settings. We overcame this challenge by implementing an 8-channel microphone array system, allowing us to determine which mouse emitted individual vocalizations across multiple social contexts.

B Cell Subsets Differentially Contribute to the T Cell-Independent Memory Pool.

The roles distinct B cell subsets play in clonal expansion, isotype switching, and memory B cell differentiation in response to T cell-independent type 2 Ags (TI-2 Ags) has been understudied. Using sorted B cells from VB1-8 knock-in mice, we evaluated B-1b, marginal zone, and follicular B cell responses to the TI-2 Ag, NP-Ficoll. All subsets extensively divided in response to NP-Ficoll.

Ultrashort-range, high-frequency communication by female mice shapes social interactions.

Animals engage in complex social encounters that influence social groups and resource allocation. During these encounters, acoustic signals, used at both short and long ranges, play pivotal roles in regulating the behavior of conspecifics. Mice, for instance, emit ultrasonic vocalizations, signals above the range of human hearing, during close-range social interactions.

Sex differences in vocal communication of freely interacting adult mice depend upon behavioral context.

Ultrasonic vocalizations (USVs) are believed to play a critical role in mouse communication. Although mice produce USVs in multiple contexts, signals emitted in reproductive contexts are typically attributed solely to the male mouse. Only recently has evidence emerged showing that female mice are also vocally active during mixed-sex interactions.

An Expert Map of Gambling Risk Perception.

The purpose of the current study was to investigate the moderating or mediating role played by risk perception in decision-making, gambling behaviour, and disordered gambling aetiology. Eleven gambling expert clinicians and researchers completed a semi-structured interview derived from mental models and grounded theory methodologies. Expert interview data was used to construct a comprehensive expert mental model 'map' detailing risk-perception related factors contributing to harmful or safe gambling.

Gambler Risk Perception: A Mental Model and Grounded Theory Analysis.

Few studies have investigated how gamblers perceive risk or the role of risk perception in disordered gambling. The purpose of the current study therefore was to obtain data on lay gamblers' beliefs on these variables and their effects on decision-making, behaviour, and disordered gambling aetiology. Fifteen regular lay gamblers (non-problem/low risk, moderate risk and problem gamblers) completed a semi-structured interview following mental models and grounded theory methodologies.

Risk perception in gambling: a systematic review.

Perception of the consequences of risk affects motivation and behaviour. In gambling, distorted expectations and preferences towards outcomes are associated with significant social and clinical harms. A systematic review was conducted to examine the relationship between gambling risk perception and behaviour.

Optimization of a LSO-Based Detector Module for Time-of-Flight PET.

We have explored methods for optimizing the timing resolution of an LSO-based detector module for a single-ring, "demonstration" time-of-flight PET camera. By maximizing the area that couples the scintillator to the PMT and minimizing the average path length that the scintillation photons travel, a single detector timing resolution of 218 ps fwhm is measured, which is considerably better than the ~385 ps fwhm obtained by commercial LSO or LYSO TOF detector modules. We explored different surface treatments (saw-cut, mechanically polished, and chemically etched) and reflector materials (Teflon tape, ESR, Lumirror, Melinex, white epoxy, and white paint), and found that for our geometry, a chemically etched surface had 5% better timing resolution than the saw-cut or mechanically polished surfaces, and while there was little dependence on the timing resolution between the various reflectors, white paint and white epoxy were a few percent better.

Performance of coimmobilized yeast and amyloglucosidase in a fluidized bed reactor for fuel ethanol production.

The performance of coimmobilized Saccharomyces cerevisiae and amyloglucosidase (AG) was evaluated in a fluidized-bed reactor. Soluble starch and yeast extracts were used as feed stocks. Conversion of soluble starch streams to ethanol has potential practical applications in corn dry and wet milling and in developmental lignocellulosic processes.

Nosocomial meningitis due to Citrobacter diversus in neonates: new aspects of the epidemiology.

Two term neonates born within four days of each other at a small hospital developed sepsis and meningitis caused by a unique strain of Citrobacter diversus not previously reported to cause meningitis. Eleven (27.5%) of 40 other infants admitted to the nursery during the epidemic period developed rectal or umbilical colonization by C.

Identification of gonococcal cultures by means of their cytoplasmic antigens and an anti-cytoplasm antiserum.

Soluble antigens were released by sonication from the cells of 60 primary cultures of Neiserria gonorrhoeae, 7 other species of neisseriae and 26 "mixed" cultures containing colonies of N. gonorrhoeae and other bacteria. Rabbits were injected with the soluble antigens of four strains of gonococci (clonal types 1 and 2), four other species of neisseriae and ten bacterial genera other than Neisseria.