Photodynamic inactivation of bacteriophage MS2: the A- protein is the target of virus inactivation

Singlet oxygen mediated oxidation has been shown to be responsible for photodynamic inactivation (PDI) of viruses in solution with photosensitisers such as 5, 10, 15, 20-tetrakis (1-methyl-4-pyridinio) porphyrin tetra p-toluenesulfonate (TMPyP). The capsids of non-enveloped viruses, such as bacteriophage MS2, are possible targets for viral inactivation by singlet oxygen oxidation. Within the capsid (predominantly composed of coat protein), the A-protein acts as the host recognition and attachment protein. The A-protein has two domains; an α-helix domain and a β-sheet domain. The α-helix domain is attached to the viral RNA genome inside the capsid while the β-sheet domain, which is on the surface of the capsid, is believed to be the site for attachment to the host bacteria pilus during infection. In this study, 4 sequence-specific antibodies were raised against 4 sites on the A-protein. Changes induced by the oxidation of singlet oxygen were compared to the rate of PDI of the virus. Using these antibodies, our results suggest that the rate of PDI is relative to loss of antigenicity of two sites on the A-protein. Our data further showed that PDI caused aggregation of MS2 particles and crosslinking of MS2 coat protein. However, these inter- and intra-capsid changes did not correlate to the rate of PDI we observed in MS2. Possible modes of action are discussed as a means to gaining insight to the targets and mechanisms of PDI of viruses

Photodynamic inactivation of non-enveloped RNA viruses

We recently reported the photodynamic inactivation (PDI) of bacteriophage MS2 with a photosensitiser- 5, 10, 15, 20-tetrakis (1-methyl-4-pyridinio) porphyrin- tetra- p-toluene sulfonate (TMPyP) in solution and concluded that the A-protein of the virus is the main target of inactivation. Here, we have extended these studies and carried out PDI of bacteriophage Qβ, bovine enterovirus 2 (BEV-2) and type 1 murine norovirus (MNV-1). The rate of inactivation observed was in the order MS2 > Qβ > MNV-1 > BEV-2. Data suggested that TMPyP-treatment could also target the viral genome as well as result in disintegration/disassembly of viral particles. Although emergence of viral drug resistance is a well-documented phenomenon, it was not possible to generate PDI-resistant MS2. However, emergence of a mutation in the lysis protein was detected after serial exposure to PDI

Transmogrifying Fuzzy Vortices

We show that the construction of vortex solitons of the noncommutative Abelian-Higgs model can be extended to a critically coupled gauged linear sigma model with Fayet-Illiopolous D-terms. Like its commutative counterpart, this fuzzy linear sigma model has a rich spectrum of BPS solutions. We offer an explicit construction of the degree$-k$ static semilocal vortex and study in some detail the infinite coupling limit in which it descends to a degree$-k$ \C\Pk^{N} instanton. This relation between the fuzzy vortex and noncommutative lump is used to suggest an interpretation of the noncommutative sigma model soliton as tilted D-strings stretched between an NS5-brane and a stack of D3-branes in type IIB superstring theory.Comment: 21 pages, 4 figures, LaTeX(JHEP3

Thrombotic microangiopathy following onasemnogene abeparvovec for spinal muscular atrophy: A case series

Spinal muscular atrophy is treated with onasemnogene abeparvovec, which replaces the missing survival motor neuron 1 gene via an adeno-associated virus vector. As of July 1, 2020, we had identified 3 infants who developed thrombotic microangiopathy following onasemnogene abeparvovec. Early recognition and treatment of drug-induced thrombotic microangiopathy may lessen mortality and morbidity

Chaos in an Exact Relativistic 3-body Self-Gravitating System

We consider the problem of three body motion for a relativistic one-dimensional self-gravitating system. After describing the canonical decomposition of the action, we find an exact expression for the 3-body Hamiltonian, implicitly determined in terms of the four coordinate and momentum degrees of freedom in the system. Non-relativistically these degrees of freedom can be rewritten in terms of a single particle moving in a two-dimensional hexagonal well. We find the exact relativistic generalization of this potential, along with its post-Newtonian approximation. We then specialize to the equal mass case and numerically solve the equations of motion that follow from the Hamiltonian. Working in hexagonal-well coordinates, we obtaining orbits in both the hexagonal and 3-body representations of the system, and plot the Poincare sections as a function of the relativistic energy parameter $\eta$. We find two broad categories of periodic and quasi-periodic motions that we refer to as the annulus and pretzel patterns, as well as a set of chaotic motions that appear in the region of phase-space between these two types. Despite the high degree of non-linearity in the relativistic system, we find that the the global structure of its phase space remains qualitatively the same as its non-relativisitic counterpart for all values of $\eta$ that we could study. However the relativistic system has a weaker symmetry and so its Poincare section develops an asymmetric distortion that increases with increasing $\eta$. For the post-Newtonian system we find that it experiences a KAM breakdown for $\eta \simeq 0.26$: above which the near integrable regions degenerate into chaos.Comment: latex, 65 pages, 36 figures, high-resolution figures available upon reques

High-Rate Solid-Liquid Separation Coupled With Nitrogen and Phosphorous Treatment of Swine Manure: Effect on Ammonia Emission

A new treatment system was developed to meet multiple environmental performance standards including to substantially reduce ammonia emissions. It was tested full-scale for 2-years in a 5,145-head finishing swine farm with two anaerobic lagoons. The system combined high-rate solid-liquid separation with nitrogen and phosphorus removal processes. Both vertical radial plum mapping (VRPM) and floating static chamber techniques were used to measure NH3 emission fluxes from anaerobic storage lagoons and the total farm-level NH3 emission rates. The VRPM used an open-path tunable diode laser absorption spectroscopy (TDL) and the flux chamber used a photoacoustic gas analyzer to accurately measure NH3 concentration. After the treatment system started, one of the two lagoons became inactive without receiving anymore flushed manure. The ammonia emission flux from the other lagoon with the treated effluent decreased from 43.9 to 6.8 kg-N ha−1 d−1 1.5 years after implementation of the new treatment system. The NH3 emission flux from the inactive lagoon also decreased similarly because the already stored old manure of the lagoon prior to inactivation was diluted with rainfalls and lost some NH3 via volatilization. The total farm-level NH3 emission rates decreased from 1.72 g s−1 to below detection level of the VRPM technique. Using the minimum detection level of the TDL with R2 > 90% (i.e., 8.1 8.1 μL L−1-m), the total farm-level NH3 emission rates in the second year were less than 0.04–0.15 g s−1. These results suggested that the impact of the new treatment system on NH3 emission reduction was equivalent to closing conventional swine lagoons while actively growing 5,145 pigs with minimal ammonia emissions from the farm

Shedding Light on Fish Otolith Biomineralization Using a Bioenergetic Approach

Otoliths are biocalcified bodies connected to the sensory system in the inner ears of fish. Their layered, biorhythm-following formation provides individual records of the age, the individual history and the natural environment of extinct and living fish species. Such data are critical for ecosystem and fisheries monitoring. They however often lack validation and the poor understanding of biomineralization mechanisms has led to striking examples of misinterpretations and subsequent erroneous conclusions in fish ecology and fisheries management. Here we develop and validate a numerical model of otolith biomineralization. Based on a general bioenergetic theory, it disentangles the complex interplay between metabolic and temperature effects on biomineralization. This model resolves controversial issues and explains poorly understood observations of otolith formation. It represents a unique simulation tool to improve otolith interpretation and applications, and, beyond, to address the effects of both climate change and ocean acidification on other biomineralizing organisms such as corals and bivalves

Nuclei, Superheavy Nuclei and Hypermatter in a chiral SU(3)-Modell

A model based on chiral SU(3)-symmetry in nonlinear realisation is used for the investigation of nuclei, superheavy nuclei, hypernuclei and multistrange nuclear objects (so called MEMOs). The model works very well in the case of nuclei and hypernuclei with one Lambda-particle and rules out MEMOs. Basic observables which are known for nuclei and hypernuclei are reproduced satisfactorily. The model predicts Z=120 and N=172, 184 and 198 as the next shell closures in the region of superheavy nuclei. The calculations have been performed in self-consistent relativistic mean field approximation assuming spherical symmetry. The parameters were adapted to known nuclei.Comment: 19 pages, 11 figure

Barium yttrium fluoride based upconversion nanoparticles as dual mode image contrast agents

Dual labeled contrast agents could provide better complementary information for bioimaging than available solely from a single modality. In this paper we investigate the suitability of Yb3+ and Er3+-doped BaYF5 upconversion nanoparticles (UCNPs) as both optical and X-ray micro computed tomography (μCT) contrast agents. Stable, aqueous UCNP dispersions were synthesised using a hydrothermal method with the addition of polyethyleneimine (PEI). UCNPs were single crystal and had a truncated cuboidal morphology, with average particle size of 47 ± 9 nm from transmission electron microscopy which was further used to characterize the structure and composition in detail. A zeta potential value of +51 mV was measured for the aqueous nanoparticle dispersions which is beneficial for cell permeability. The outer hydrated PEI layer is also advantageous for the attachment of proteins for targeted delivery in biological systems. The prepared UCNPs were proven to be non-toxic to endothelial cells up to a concentration of 3.5 mg/mL, when assessed using an MTT assay. The particles showed intense green upconversion photoluminescence when excited at a wavelength of 976 nm using a diode laser. Quantitative X-ray μCT contrast imaging confirmed the potential of these UCNPs as X-ray contrast agents and confirming their dual modality for bioimaging