Oxford nanopore sequencing enables rapid discovery of single-domain antibodies from phage display libraries.

Antibody (Ab) repertoire sequencing using high-throughput massively parallel technologies has contributed substantially to the understanding of Ab responses following infection, vaccination and autoimmunity. Because individual B-cell receptors are recombined and diversified somatically, genomic comparisons are limited, and distinguishing rare variants from sequencing errors is a major challenge. Oxford Nanopore Technologies' MinION is a highly portable and cost-effective third-generation sequencing instrument, but has not been used for Ab repertoire sequencing due to its high error rate (approximately 1/10 bases). Here, we applied nanopore sequencing to single-domain Ab (sdAb) repertoires and phage-displayed sdAb libraries. We show that despite low overall data fidelity, sdAb sequences could be reconstructed above a frequency threshold (∼100 copies); however, distinguishing clonal sdAb variants was not always possible. The data quality was sufficient to enable rapid identification of antigen-specific sdAb sequences enriched during panning of phage display libraries, obviating the need for screening single clones

Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline

Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington’s disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington’s disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival) in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition

Learning from lockdown

No abstract available

Learning from lockdown

No abstract available

Pathogenic Adaptation of Intracellular Bacteria by Rewiring a Cis-Regulatory Input Function

The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones

Industrial work placement in higher education: a study of civil engineering student engagement

For civil engineering undergraduates, the opportunity to spend a period of time in formal industrial work placement provides an invaluable learning experience. This paper reviews student engagement with short-term industrial placement and provides analysis of questionnaires (n=174) returned by undergraduates studying civil engineering at four Higher Education Institutes (HEI’s) in the West of Scotland. The data captures industrial placement statistics, employability skill-sets and presents brief testimonies from students. Whilst the journey to becoming a professional civil engineer is undoubtedly enhanced by short-term placement clear opportunities exist for HEI’s to affect and change existing pedagogical discourse. Commentary is likely to resonate beyond civil engineering and serve as a timely reminder of the need to re-invigorate academia / industry curriculum partnerships

Structural relaxation in a system of dumbbell molecules

The interaction-site-density-fluctuation correlators, the dipole-relaxation functions, and the mean-squared displacements of a system of symmetric dumbbells of fused hard spheres are calculated for two representative elongations of the molecules within the mode-coupling theory for the evolution of glassy dynamics. For large elongations, universal relaxation laws for states near the glass transition are valid for parameters and time intervals similar to the ones found for the hard-sphere system. Rotation-translation coupling leads to an enlarged crossover interval for the mean-squared displacement of the constituent atoms between the end of the von Schweidler regime and the beginning of the diffusion process. For small elongations, the superposition principle for the reorientational $\alpha$-process is violated for parameters and time intervals of interest for data analysis, and there is a strong breaking of the coupling of the $\alpha$-relaxation scale for the diffusion process with that for representative density fluctuations and for dipole reorientations.Comment: 15 pages, 14 figures, Phys. Rev. E in pres

What might the Covid pandemic mean for the SERA Poverty and Education Network?

No abstract available