Participants were selected from among patients who were examined for presumed AHC during the outbreak period, were identified within 24 hr of onset of symptoms, and who met the case definition. ...Patients were randomized in adouble-blind setting to one of the two groups: a treatment group receiving HLI (antiviral activity, 2.4 x 10 super(6) IU/ml; Revlon Health Care Corp, Tuckahoe, NY) ophthalmic drops packaged in a sterile solution administered at a dosage of one drop, two times a day (50,000 units per drop) for five days and a placebo group receiving a commercial artificial tear solution. Both eyes were treated in every case, even if only one eye was affected. Unaffected family members accompanying any of the study patients were also invited to participate in the study. Within each household, all members who participated, both affected and unaffected, received the same treatment (HLI or placebo).
The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a ...hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.
Excitation localization involving dynamic nanoscale distortions is a central aspect of photocatalysis
, quantum materials
and molecular optoelectronics
. Experimental characterization of such ...distortions requires techniques sensitive to the formation of point-defect-like local structural rearrangements in real time. Here, we visualize excitation-induced strain fields in a prototypical member of the lead halide perovskites
via femtosecond resolution diffuse X-ray scattering measurements. This enables momentum-resolved phonon spectroscopy of the locally distorted structure and reveals radially expanding nanometre-scale strain fields associated with the formation and relaxation of polarons in photoexcited perovskites. Quantitative estimates of the magnitude and shape of this polaronic distortion are obtained, providing direct insights into the dynamic structural distortions that occur in these materials
. Optical pump-probe reflection spectroscopy corroborates these results and shows how these large polaronic distortions transiently modify the carrier effective mass, providing a unified picture of the coupled structural and electronic dynamics that underlie the optoelectronic functionality of the hybrid perovskites.
Of 445 eyes (305 of which were aphakic) that underwent penetrating keratoplasty, 11 developed endophthalmitis, three immediately after surgery, two after subsequent secondary surgery, and six after ...late ulceration of the transplanted cornea. The diagnosis was based clinically on the loss of the red reflex and vitreous opacification, and was confirmed by culture of vitreous aspirate. All patients who developed endophthalmitis were aphakic and had received corticosteroids at the time of infection; most had undergone previous ocular surgery. These patients differed from those previously described with this condition because neither the donor tissue nor the storage medium was the source of infection. Treatment included intracameral, systemic, and topical administration of antibiotics. When the endophthalmitis originated from a corneal ulcer in a graft, the infected tissue was replaced with a new transplant. Despite treatment, the final visual outcomes were not good. One eye had a final visual acuity of 20/200 and one eye had a final visual acuity of 20/400. Three eyes had light perception and six eyes had no light perception. One eye was eventually enucleated.
The high-mannose patch on the HIV-1 envelope (Env) glycoprotein is the epicenter for binding of the potent broadly neutralizing PGT121 family of antibodies, but strategies for generating such ...antibodies by vaccination have not been defined. We generated structures of inferred antibody intermediates by X-ray crystallography and electron microscopy to elucidate the molecular events that occurred during evolution of this family. Binding analyses revealed that affinity maturation was primarily focused on avoiding, accommodating, or binding the N137 glycan. The overall antibody approach angle to Env was defined very early in the maturation process, yet some variation evolved in the PGT121 family branches that led to differences in glycan specificities in their respective epitopes. Furthermore, we determined a crystal structure of the recombinant BG505 SOSIP.664 HIV-1 trimer with a PGT121 family member at 3.0 Å that, in concert with these antibody intermediate structures, provides insights to advance design of HIV vaccine candidates.
Display omitted
•X-ray and EM structures of inferred precursors of the PGT121 family were generated•The N137 glycan is a major factor in affinity maturation of the PGT121 family•The antibody approach angle differs in the two main branches of the PGT121 lineage•A 3.0 Å crystal structure of an HIV trimer with a PGT121 family member was determined
Strategies for generating broadly neutralizing antibodies (bnAbs) against the high-mannose patch of the HIV envelope have not been defined. Wilson and colleagues find that affinity maturation of the potent PGT121 family of bnAbs is focused on accommodating or avoiding glycans. These findings provide insights to advance structure-based vaccine design.
In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non‐fatal case, the virus continues to circulate in Taiwanese ...poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human‐type receptor specificity could enable transmission in the human population. Despite mutations in the receptor‐binding pocket of the human H6N1 isolate, it has retained avian‐type (NeuAcα2‐3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human‐type (NeuAcα2‐6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human‐type receptor, stabilizing human receptor binding.
Synopsis
To transmit between humans, zoonotic viruses need to acquire human‐type receptor specificity. Analyzing the effects of different amino acid mutations in the receptor binding site revealed that H6 HA only requires a single amino acid mutation to specifically adapt to human‐type receptor binding.
G225D in H6 HA confers human‐type receptor binding.
H6‐G225D lost binding to chicken and gained binding to human airway tissues.
Structural analyses show classic human‐type receptor binding.
H6 G225D still maintains low thermostability and is thus not yet fully adapted to transmit between humans.
To transmit between humans, zoonotic viruses need to acquire human‐type receptor specificity. Analyzing the effects of different amino acid mutations in the receptor binding site revealed that H6 HA only requires a single amino acid mutation to specifically adapt to human‐type receptor binding.
PDF
