A single mutation in bovine influenza H5N1 hemagglutinin switches specificity to human receptors.

In 2024, several human infections with highly pathogenic clade 2.3.4.

A blueprint for broadly effective bacteriophage-antibiotic cocktails against bacterial infections.

Bacteriophage (phage) therapy is a promising therapeutic modality for multidrug-resistant bacterial infections, but its application is mainly limited to personalized therapy due to the narrow host range of individual phages. While phage cocktails targeting all possible bacterial receptors could theoretically confer broad coverage, the extensive diversity of bacteria and the complexity of phage-phage interactions render this approach challenging. Here, using screening protocols for identifying "complementarity groups" of phages using non-redundant receptors, we generate effective, broad-range phage cocktails that prevent the emergence of bacterial resistance.

The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is interest in using bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics in vivo remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of i.

Polymicrobial methicillin-resistant bloodstream infections.

Methicillin-resistant (MRSA) bloodstream infection (BSI) is a serious public health concern. At times, MRSA is isolated from the blood along with other pathogens, the significance and consequences of which are not well described. This study aims to outline the clinical characteristics and outcomes of those with polymicrobial MRSA BSI compared with those with monomicrobial MRSA BSI.

Optically multiplexed neutron time-of-flight technique for inertial confinement fusion.

Neutron time-of-flight (nTOF) detectors are crucial in diagnosing the performance of inertial confinement fusion (ICF) experiments, which implode targets of deuterium-tritium fuel to achieve thermonuclear conditions. These detectors utilize the fusion neutron energy spectrum to extract key measurements, including the hotspot ion temperature and fuel areal density. Previous work [Danly et al.

Chemoenzymatic Synthesis of Sulfated -Glycans Recognized by Siglecs and Other Glycan-Binding Proteins.

Sulfated -glycans are present in many glycoproteins, which are implicated in playing important roles in biological recognition processes. Here, we report the systematic chemoenzymatic synthesis of a library of sulfated and sialylated biantennary -glycans and assess their binding to Siglecs and glycan-specific antibodies that recognize them as glycan ligands. The combined use of three human sulfotransferases, GlcNAc-6--sulfotransferase (CHST2), Gal-3--sulfotransferase (Gal3ST1), and keratan sulfate Gal-6--sulfotransferase (CHST1), resulted in asymmetric and symmetric branch-selective sulfation of the GlcNAc and/or Gal moieties of -glycans.

Bovine H5N1 influenza virus binds poorly to human-type sialic acid receptors.

Clade 2.3.4.

Retraction: Synthesis of Yttrium Superhydride Superconductor with a Transition Temperature up to 262 K by Catalytic Hydrogenation at High Pressures [Phys. Rev. Lett. 126, 117003 (2021)].

Retraction of DOI: 10.1103/PhysRevLett.126.

Epistasis mediates the evolution of the receptor binding mode in recent human H3N2 hemagglutinin.

The receptor-binding site of influenza A virus hemagglutinin partially overlaps with major antigenic sites and constantly evolves. In this study, we observe that mutations G186D and D190N in the hemagglutinin receptor-binding site have coevolved in two recent human H3N2 clades. X-ray crystallography results show that these mutations coordinately drive the evolution of the hemagglutinin receptor binding mode.

Acceptability and Feasibility of Survivorship Group Medical Visits for Breast Cancer Survivors in a Safety Net Hospital.

Providing cost-effective, comprehensive survivorship care remains a significant challenge. Breast cancer survivors (BCS) who have limited income and are from marginalized racial and ethnic groups experience a worse quality of life and report higher distress. Thus, innovative care models are required to address the needs of BCS in low resource settings.

Arginine-Functional Methacrylic Block Copolymer Nanoparticles: Synthesis, Characterization, and Adsorption onto a Model Planar Substrate.

Recently, we reported the synthesis of a hydrophilic aldehyde-functional methacrylic polymer (, , , 12032-12037). Herein we demonstrate that such polymers can be reacted with arginine in aqueous solution to produce arginine-functional methacrylic polymers without recourse to protecting group chemistry. Careful control of the solution pH is essential to ensure regioselective imine bond formation; subsequent reductive amination leads to a hydrolytically stable amide linkage.

High-magnification Faraday rotation imaging and analysis of X-pinch implosion dynamics.

An X-pinch load driven by an intense current pulse (>100 kA in ∼100 ns) can result in the formation of a small radius, runaway compressional micro-pinch. A micro-pinch is characterized by a hot (>1 keV), current-driven (>100 kA), high-density plasma column (near solid density) with a small neck diameter (1-10 µm), a short axial extent (<1 mm), and a short duration (≲1 ns). With material pressures often well into the multi-Mbar regime, a micro-pinch plasma often radiates an intense, sub-ns burst of sub-keV to multi-keV x rays.

Low-Viscosity Route to High-Molecular-Weight Water-Soluble Polymers: Exploiting the Salt Sensitivity of Poly(-acryloylmorpholine).

We report a new one-pot low-viscosity synthetic route to high molecular weight non-ionic water-soluble polymers based on polymerization-induced self-assembly (PISA). The RAFT aqueous dispersion polymerization of -acryloylmorpholine (NAM) is conducted at 30 °C using a suitable redox initiator and a poly(2-hydroxyethyl acrylamide) (PHEAC) precursor in the presence of 0.60 M ammonium sulfate.

The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo.

With the increasing prevalence of antimicrobial-resistant bacterial infections, there is great interest in using lytic bacteriophages (phages) to treat such infections. However, the factors that govern bacteriophage pharmacokinetics remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of intravenously administered bacteriophage in uninfected mice.

Evolution of human H3N2 influenza virus receptor specificity has substantially expanded the receptor-binding domain site.

Hemagglutinins (HAs) from human influenza viruses descend from avian progenitors that bind α2-3-linked sialosides and must adapt to glycans with α2-6-linked sialic acids on human airway cells to transmit within the human population. Since their introduction during the 1968 pandemic, H3N2 viruses have evolved over the past five decades to preferentially recognize human α2-6-sialoside receptors that are elongated through addition of poly-LacNAc. We show that more recent H3N2 viruses now make increasingly complex interactions with elongated receptors while continuously selecting for strains maintaining this phenotype.

Merging trait-based ecology and regime shift theory to anticipate community responses to warming.

Anthropogenic warming is altering species abundance, distribution, physiology, and more. How changes observed at the species level alter emergent community properties is an active and urgent area of research. Trait-based ecology and regime shift theory provide complementary ways to understand climate change impacts on communities, but these two bodies of work are only rarely integrated.

Expression of Concern: Synthesis of Yttrium Superhydride Superconductor with a Transition Temperature up to 262 K by Catalytic Hydrogenation at High Pressures [Phys. Rev. Lett. 126, 117003 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.126.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. In this study, we use dynamic light scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

One Step Encapsulation of Mesenchymal Stromal Cells in PEG Norbornene Microgels for Therapeutic Actions.

Cell therapies require control over the cellular response under standardized conditions to ensure continuous delivery of therapeutic agents. Cell encapsulation in biomaterials can be particularly effective at providing cells with a uniformly supportive and permissive cell microenvironment. In this study, two microfluidic droplet device designs were used to successfully encapsulate equine mesenchymal stromal cells (MSCs) into photopolymerized polyethylene glycol norbornene (PEGNB) microscale (∼100-200 μm) hydrogel particles (microgels) in a single on-chip step.

Rapid assessment of changes in phage bioactivity using dynamic light scattering.

Extensive efforts are underway to develop bacteriophages as therapies against antibiotic-resistant bacteria. However, these efforts are confounded by the instability of phage preparations and a lack of suitable tools to assess active phage concentrations over time. Here, we use Dynamic Light Scattering (DLS) to measure changes in phage physical state in response to environmental factors and time, finding that phages tend to decay and form aggregates and that the degree of aggregation can be used to predict phage bioactivity.

Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.

Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development and have suggested a role for superinfection as a potential enhancer of neutralization breadth. Here we describe the development of a potent bnAb lineage that was elicited by two founder viruses to inform vaccine design.

Personalized aerosolised bacteriophage treatment of a chronic lung infection due to multidrug-resistant Pseudomonas aeruginosa.

Bacteriophage therapy has been suggested as an alternative or complementary strategy for the treatment of multidrug resistant (MDR) bacterial infections. Here, we report the favourable clinical evolution of a 41-year-old male patient with a Kartagener syndrome complicated by a life-threatening chronic MDR Pseudomonas aeruginosa infection, who is treated successfully with iterative aerosolized phage treatments specifically directed against the patient's isolate. We follow the longitudinal evolution of both phage and bacterial loads during and after phage administration in respiratory samples.