Single immunization with an influenza hemagglutinin nanoparticle-based vaccine elicits durable protective immunity.

Vaccination is the most effective strategy to combat influenza. Ideally, potent and persistent vaccine effects would be induced with a single vaccine dose. Here, we designed a virus-like particle (VLP)-based vaccine presenting multiple copies of the influenza hemagglutinin (HA) from A/Puerto Rico/8/1934 (PR8HA-VLP) and examined its immunogenicity and protective efficacy in ferrets.

Intraobserver and Interobserver Reliability of the Snyder and Expanded SLAP Classification System: A Video Study.

Background: Superior labral anterior and posterior (SLAP) tears are a common finding in overhead athletes. The original classification system produced by Snyder in 1990 contained 4 types of SLAP tears and was later expanded to 10 types. The classification has been challenging because of inconsistencies between surgeons making diagnoses and treatments based on the diagnosis.

Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses.

Background: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 "variants of concern" have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity.

Geometrical variations of two manganese(II) complexes with closely related quinoline-based tripodal ligands.

Structural analyses of the compounds di-μ-acetato-κ :'-bis-{[2-meth-oxy-,-bis-(quinolin-2-ylmeth-yl)ethanamine-κ ,','',]manganese(II)} bis-(tetra-phen-yl-borate) di-chloro-methane 1.45-solvate, [Mn(CO)(CHNO)](CHB)·1.45CHCl or [Mn(DQMEA)(μ-OAc)Mn(DQMEA)](BPh)·1.

Potent neutralization of SARS-CoV-2 including variants of concern by vaccines presenting the receptor-binding domain multivalently from nanoscaffolds.

The persistence of the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought to the forefront the need for safe and effective vaccination strategies. In particular, the emergence of several variants with greater infectivity and resistance to current vaccines has motivated the development of a vaccine that elicits a broadly neutralizing immune response against all variants. In this study, we used a nanoparticle-based vaccine platform for the multivalent display of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein, the primary target of neutralizing antibodies.

Multivalent nanoparticle-based vaccines protect hamsters against SARS-CoV-2 after a single immunization.

The COVID-19 pandemic continues to wreak havoc as worldwide SARS-CoV-2 infection, hospitalization, and death rates climb unabated. Effective vaccines remain the most promising approach to counter SARS-CoV-2. Yet, while promising results are emerging from COVID-19 vaccine trials, the need for multiple doses and the challenges associated with the widespread distribution and administration of vaccines remain concerns.

The Design of Vaccines Based on the Shielding of Antigenic Site Ø of a Respiratory Syncytial Virus Fusion Protein Immunogen.

Respiratory syncytial virus (RSV), for which there is currently no licensed vaccine, displays a fusion (F) protein that is considered a vaccine target. This protein has an antigenic site called site Ø, which has been shown to elicit potent, neutralizing antibodies and has therefore been considered important in the formulation of RSV vaccines. However, this site is also the least conserved region on the F protein across RSV subtypes.

One-pot synthesis of heterodimeric agonists that activate the canonical Wnt signaling pathway.

Fragment antigen-binding domains (Fabs) from anti-Frizzled and anti-LRP6 monoclonal antibodies were conjugated using SpyTag-SpyCatcher chemistry via a one-pot reaction. The resulting synthetic heterodimeric agonist outperformed the natural ligand, Wnt-3a, in activating canonical Wnt signaling in mammalian cells. This approach should be broadly applicable to activate receptor-mediated cellular signaling.

Designing Multivalent Ligands to Control Biological Interactions: From Vaccines and Cellular Effectors to Targeted Drug Delivery.

Multivalent interactions in which multiple ligands on one object bind to multiple receptors on another are commonly found in natural biological systems. In addition, these interactions can lead to increased strength and selectivity when compared to the corresponding monovalent interaction. These attributes have also guided the design of synthetic multivalent ligands to control biological interactions.

Natural Stimuli Calibration with Fining Direction Regularization in an Integrated Hydrologic Model.

The interaction between surface water and groundwater during flood events is a complex process that has traditionally been described using simplified analytical solutions, or abstracted numerical models. To make the problem tractable, it is common to idealize the flood event, simplify river channel geometry, and ignore bank soil heterogeneity, often resulting in a model that only loosely represents the site, thus limiting its applicability to any specific river cross-section. In this study, we calibrate a site-specific fully-integrated surface and subsurface HydroGeoSphere model using flood events for a cross-section along the South River near Waynesboro, VA.

Crystal structure of a mononuclear copper(II) complex with 2-methoxy-,-bis-(quinolin-2-yl-meth-yl)-ethyl-amine (DQMEA).

Structural characterization of the compound [Cu(CHN)(CHNO)](ClO)] or [Cu(CHN)(DQMEA)](ClO)] [DQMEA = 2-methoxy-,-bis-(quinolin-2-ylmeth-yl)ethyl-amine] {systematic name: (aceto-nitrile)[2-methoxy-,-bis(quinolin-2-ylmeth-yl)ethyl-amine]-copper(II) diperchlorate} by single-crystal X-ray diffraction reveals a complex cation with a tetra-dentate coordination of the DQMEA ligand along with monodentate coordination of a CHCN ligand to a single Cu center, with two perchlorate anions providing charge balance. The Cu center has a distorted square-pyramidal geometry in which the nitro-gen atoms of the DQMEA and CHCN ligands occupy the equatorial positions, while the oxygen atom of the DQMEA ligand resides in the axial position with an elongated Cu-O bond. The quinoline ring systems are nearly co-planar in the structure, while the linear CHCN ligand is tilted significantly below this plane, and the central nitro-gen of DQMEA is above it.

Crystal structure of a seven-coordinate manganese(II) complex with tris-(pyridin-2-ylmeth-yl)amine (TMPA).

Structural analysis of (acetato-κ,')(methanol-κ)[tris-(pyridin-2-ylmeth-yl)amine-κ,','',''']manganese(II) tetraphenyl-borate, [Mn(CHO)(CHN)(CHOH)](CHB) or [Mn(TMPA)(Ac)(CHOH)]BPh [TMPA = tris-(pyridin-2-ylmeth-yl)amine, Ac = acetate, BPh = tetra-phenyl-borate] by single-crystal X-ray diffraction reveals a complex cation with tetra-dentate coordination of the tripodal TMPA ligand, bidentate coordination of the Ac ligand and monodentate coordination of the methanol ligand to a single Mn center, balanced in charge by the presence of a tetra-phenyl-borate anion. The Mn complex has a distorted penta-gonal-bipyramidal geometry, in which the central amine nitro-gen and two pyridyl N atoms of the TMPA ligand, and two oxygen atoms of the acetate ligand occupy positions in the penta-gonal plane, while the third pyridyl nitro-gen of TMPA and the oxygen from the methanol ligand occupy the axial positions. Within the complex, the acetate O atoms participate in weak C-H⋯O hydrogen-bonding inter-actions with neighboring pyridyl moieties.

Quantitative real-time PCR-based assessment of tile drainage management influences on bacterial pathogens in tile drainage and groundwater.

This study compared the impact of controlled tile drainage (CD) and freely draining (FD) systems on the prevalence and quantitative real-time PCR-based enumeration of four major pathogens including Arcobacter butzleri, Campylobacter jejuni, Campylobacter coli, and Helicobacter pylori in tile- and groundwater following a fall liquid swine manure (LSM) application on clay loam field plots. Although the prevalence of all target pathogens were detected in CD and FD systems, the loads of A. butzleri, C.

Bionanotechnology for vaccine design.

There have been significant advances in the design of nanostructured scaffolds for eliciting robust immune responses. One method to produce strong immune responses is to emulate the appearance of a pathogen. Since pathogens such as viruses and bacteria often display multiple copies of ligands on their surfaces, the immune system is particularly sensitive towards multivalent displays of antigens.

Quantitative Campylobacter spp., antibiotic resistance genes, and veterinary antibiotics in surface and ground water following manure application: Influence of tile drainage control.

This work investigated chlortetracycline, tylosin, and tetracycline (plus transformation products), and DNA-based quantitative Campylobacter spp. and Campylobacter tetracycline antibiotic resistant genes (tet(O)) in tile drainage, groundwater, and soil before and following a liquid swine manure (LSM) application on clay loam plots under controlled (CD) and free (FD) tile drainage. Chlortetracycline/tetracycline was strongly bound to manure solids while tylosin dominated in the liquid portion of manure.

Using SWAT, Bacteroidales microbial source tracking markers, and fecal indicator bacteria to predict waterborne pathogen occurrence in an agricultural watershed.

Developing the capability to predict pathogens in surface water is important for reducing the risk that such organisms pose to human health. In this study, three primary data source scenarios (measured stream flow and water quality, modelled stream flow and water quality, and host-associated Bacteroidales) are investigated within a Classification and Regression Tree Analysis (CART) framework for classifying pathogen (Escherichia coli 0157:H7, Salmonella, Campylobacter, Cryptosporidium, and Giardia) presence and absence (P/A) for a 178 km(2) agricultural watershed. To provide modelled data, a Soil Water Assessment Tool (SWAT) model was developed to predict stream flow, total suspended solids (TSS), total N and total P, and fecal indicator bacteria loads; however, the model was only successful for flow and total N and total P simulations, and did not accurately simulate TSS and indicator bacteria transport.

Tile Drainage Management Influences on Surface-Water and Groundwater Quality following Liquid Manure Application.

This study investigated the potential for controlled tile drainage (CD) to reduce bacteria and nutrient loading to surface water and groundwater from fall-season liquid manure application (LMA) on four macroporous clay loam plots, of which two had CD and two had free-draining (FD) tiles. Rhodamine WT (RWT) was mixed into the manure and monitored in the tile water and groundwater following LMA. Tile water and groundwater quality were influenced by drainage management.

Immobilization of the aminopeptidase from Aeromonas proteolytica on Mg2+/Al3+ layered double hydroxide particles.

A novel biomaterial formed by the immobilization of the Aminopeptidase from Aeromonas proteolytica (AAP) on synthetic Mg2+ and Al3+ ion-containing layered double hydroxide (LDH) particles was prepared. Immobilization of AAP on the LDH particles in a buffered, aqueous mixture is rapid such that the maximum loading capacity, 1×10(-9) moles of AAP/mg LDH, is achieved in a few minutes. X-ray powder diffraction of LDH samples before and after treatment with AAP indicates that the enzyme does not intercalate between the layers of LDH, but instead binds to the surface.

Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.

Broadly neutralizing antibodies (bNAbs), which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, we have examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and have selected donors for monoclonal antibody (mAb) generation. We then used a high-throughput neutralization screen of antibody-containing culture supernatants from about 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent mAbs that target a broadly neutralizing epitope.

Tibial tuberosity fractures in adolescents.

Background: Tibial tuberosity fractures in adolescents are uncommon. We retrospectively reviewed all tibial tuberosity fractures in adolescents (10-19) who presented to our level 1 pediatric trauma center over a 7-year period to review fracture morphology, mechanism of injury, fracture management including return to play, as well as complications. Additionally, we present a review of the literature and treatment algorithm.

Subtrochanteric fracture in a patient with trabecular metal osteonecrosis intervention implant.

We present an unreported case of a sixty-four year old woman who suffered a subtrochanteric fracture of the femur four weeks after implantation of a trabecular metal osteonecrosis intervention implant for osteonecrosis of the femoral head. Traditional treatments for femoral head avascular necrosis include observation, core decompression, bone grafting, vascularized fibular grafting, osteotomy, hemiarthroplasty and total hip arthroplasty. With the recent development of trabecular metal, a new implant system has been developed using the properties of trabecular metal for treatment of osteonecrosis.

Rare case of upper arm compartment syndrome following biceps tendon rupture.

We present a case of upper arm compartment syndrome following a biceps tendon rupture in a 77-year old man on warfarin sodium. Compartment syndrome is common in the forearm and leg, but rare in the upper arm with only a handful of cases reported in the literature. Our patient's anticoagulated state predisposed him to the development of compartment syndrome.

Bilateral symptomatic snapping biceps femoris tendon due to fibular exostosis.

We present an unusual case of an athletic 17-year-old male cyclist with bilateral chronic dislocating biceps femoris tendons. On flexion of the knee, the biceps tendon subluxed over a large exostosis, creating a snapping sound. Snapping of tendons is common around the hip, ankles, shoulder, and elbow, but rare at the knee.