Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Spectral hole burning and Raman heterodyne signals associated with an avoided crossing in the NV centre in diamond

The nitrogen-vacancy centre in diamond exhibits an avoided crossing of ground state electron spin levels in a magnetic field of approximately 1028 G applied along the 〈1 1 1〉 direction. In this paper, the magnetic field dependence of Raman heterodyn

A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates

As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge

Successful long-term outcome after renal transplantation in a patient with atypical haemolytic uremic syndrome with combined membrane cofactor protein CD46 and complement factor I mutations

BACKGROUND: Atypical haemolytic uremic syndrome (aHUS) is often associated with a high risk of disease recurrence and subsequent graft loss after isolated renal transplantation. Evidence-based recommendations for a mutation-based management after renal transplantation in aHUS caused by a combined mutation with complement factor I (CFI) and membrane cofactor protein CD46 (MCP) are limited. CASE-DIAGNOSIS/TREATMENT: We describe a 9-year-old boy with a first manifestation of aHUS at the age of 9 months carrying combined heterozygous mutations in the CFI and MCP genes. At the age of 5 years, he underwent isolated cadaveric renal transplantation. Fresh frozen plasma was administered during and after transplantation, tapered and finally stopped after 3 years. CONCLUSIONS: During the 5-year follow-up after transplantation there have been no signs of aHUS recurrence and graft function has remained good. The combination of heterozygous MCP and CFI mutations with aHUS might have a positive impact on the post-transplant course, possibly predicting a lower risk of aHUS recurrence after an isolated cadaveric renal transplantation

Chirality-Driven Folding of Short β-Lactam Pseudopeptides

Novel enantiopure pseudopeptide models containing a central -(β-lactam)-(Aa)- scaffold characterized by the combined presence of an α-alkyl-α-amino-β-lactam (i+1) residue and a α-substituted (i + 2) amino acid have been readily synthesized from α-alkyl serines. The conformational analysis of such β-lactam pseudopeptides conducted in CDCl3 and DMSO-d6 solutions using 1D- and 2D-NMR techniques revealed an equilibrium between β-II turn and γ-turn conformers, which was ultimately modulated by the relative configuration of the -(β-lactam)-(Aa)- residues. Long-range chiral effects on the α-lactam pseudopeptide conformers were also found when two (i) and (i + 3) chiral residues were attached to the termini of a central -(β-lactam)-(Aib)- segment. In such mimetics, heterochiral (i) and (i + 3) residues reinforced a β-II turn conformer, whereas homochiral corner residues stabilized an overlapped β-II/ β-I double turn motif. No β-hairpin nucleation was observed in any instance. In good agreement with the conformers found in solution, β-turned and open structures were also characterized by X-ray crystallography. Relative stabilities of the different conformers were estimated computationally at a B3LYP/6-31++G** calculation level, and finally, a conformation equilibrium model based on steric inter-residual interactions around the -(β-lactam)-(i + 2)- segment was proposed to account for the observed chiral effects