Altering the spectrum of immunoglobulin V gene somatic hypermutation by modifying the active site of AID

High-affinity antibodies are generated by somatic hypermutation with nucleotide substitutions introduced into the IgV in a semirandom fashion, but with intrinsic mutational hotspots strategically located to optimize antibody affinity maturation. The process is dependent on activation-induced deaminase (AID), an enzyme that can deaminate deoxycytidine in DNA in vitro, where its activity is sensitive to the identity of the 5′-flanking nucleotide. As a critical test of whether such DNA deamination activity underpins antibody diversification and to gain insight into the extent to which the antibody mutation spectrum is dependent on the intrinsic substrate specificity of AID, we investigated whether it is possible to change the IgV mutation spectrum by altering AID’s active site such that it prefers a pyrimidine (rather than a purine) flanking the targeted deoxycytidine. Consistent with the DNA deamination mechanism, B cells expressing the modified AID proteins yield altered IgV mutation spectra (exhibiting a purine→pyrimidine shift in flanking nucleotide preference) and altered hotspots. However, AID-catalyzed deamination of IgV targets in vitro does not yield the same degree of hotspot dominance to that observed in vivo, indicating the importance of features beyond AID’s active site and DNA local sequence environment in determining in vivo hotspot dominance

Ludwig Koch and the Music of Nature

Ludwig Koch was a pioneer of outside broadcast, natural history recording in the first half of the 20th century. This programme explores his methods, techniques and personality through archive recordings and interviews, and includes attempts t recreating his experiments using modern equipment

Design of a compact all-permanent magnet ECR ion source injector for ReA at the MSU NSCL

The design of a compact all-permanent magnet electron cyclotron resonance (ECR) ion source injector for the ReAccelerator Facility (ReA) at the Michigan State University (MSU) National Superconducting Cyclotron Laboratory (NSCL) is currently being carried out. The ECR ion source injector will complement the electron beam ion trap (EBIT) charge breeder as an off-line stable ion beam injector for the ReA linac. The objective of the ECR ion source injector is to provide continuous-wave beams of heavy ions from hydrogen to masses up to 136Xe within the ReA charge-to-mass ratio (Q/A) operational range from 0.2 to 0.5. The ECR ion source will be mounted on a high-voltage platform that can be adjusted to obtain the required 12 keV/u injection energy into a room temperature radio-frequency quadrupole (RFQ) for further acceleration. The beam line consists of a 30 kV tetrode extraction system, mass analyzing section, and optical matching section for injection into the existing ReA low energy beam transport (LEBT) line. The design of the ECR ion source and the associated beam line are discussed

A framework for the development of a global standardised marine taxon reference image database (SMarTaR-ID) to support image-based analyses

Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure maps to the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem

Combing Chromosomal DNA Mediated by the SMC Complex: Structure and Mechanisms

Genome maintenance requires various nucleoid‐associated factors in prokaryotes. Among them, the SMC (Structural Maintenance of Chromosomes) protein has been thought to play a static role in the organization and segregation of the chromosome during cell division. However, recent studies have shown that the bacterial SMC is required to align left and right arms of the emerging chromosome and that the protein dynamically travels from origin to Ter region. A rod form of the SMC complex mediates DNA bridging and has been recognized as a machinery responsible for DNA loop extrusion, like eukaryotic condensin or cohesin complexes, which act as chromosome organizers. Attention is now turning to how the prototype of the complex is loaded on the entry site and translocated on chromosomal DNA, explaining its overall conformational changes at atomic levels. Here, we review and highlight recent findings concerning the prokaryotic SMC complex and discuss possible mechanisms from the viewpoint of protein architecture

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Pattern recognition for bivariate process mean shifts using feature-based artificial neural network

In multivariate quality control, the artificial neural networks (ANN)-based pattern recognition schemes generally performed better for monitoring bivariate process mean shifts and provided more efficient information for diagnosing the source variable(s) compared to the traditional multivariate statistical process control charting. However, these schemes revealed disadvantages in term of reference bivariate patterns in identifying the joint effect and excess false alarms in identifying stable process condition. In this study, feature-based ANN scheme was investigated for recognizing bivariate correlated patterns. Feature-based input representation was utilized into an ANN training and testing towards strengthening discrimination capability between bivariate normal and bivariate mean shift patterns. Besides indicating an effective diagnosis capability in dealing with low correlation bivariate patterns, the proposed scheme promotes a smaller network size and better monitoring capability as compared to the raw data-based ANN scheme