Antigenic Structural Similarity as a Predictor for Antibody Cross-Reactivity

Antibodies are an essential component of the adaptive immune system that function to neutralize foreign invaders, such as bacterial and parasitic pathogens. However, B-cell epitopes remain difficult to predict due to their general indistinguishability from other protein regions. Epitope prediction tools in the past have largely relied on amino acid sequence similarity; however, implementing three-dimensional protein structure analyses into the epitope prediction algorithms has been shown to increase detection accuracy. Furthermore, structural comparisons between antigenic proteins for their potential to bind cross-reactive antibodies have not been explored extensively in the literature. Recent studies have pointed to the utility of looking at shared epitope structures in predicting antibody cross- reactivity, which may shed light on cross-immunity between infectious pathogens and autoimmune diseases induced after infection. Thus, herein, the potential impact of including structural similarity comparisons in detecting shared epitopes is discussed. With the large amount of structural information being determined by three-dimensional computational protein modelling methods, the ability to perform these analyses is becoming more feasible.Antibiotic Research UK (PHZJ/687

Development of a Compact Eleven Feed Cryostat for the Patriot 12-m Antenna System

The Eleven antenna has constant beam width, constant phase center location, and low spillover over a decade bandwidth. Therefore, it can feed a reflector for high aperture efficiency (also called feed efficiency). It is equally important that the feed efficiency and its subefficiencies not be degraded significantly by installing the feed in a cryostat. The MIT Haystack Observatory, with guidance from Onsala Space Observatory and Chalmers University, has been working to integrate the Eleven antenna into a compact cryostat suitable for the Patriot 12-m antenna. Since the analysis of the feed efficiencies in this presentation is purely computational, we first demonstrate the validity of the computed results by comparing them to measurements. Subsequently, we analyze the dependence of the cryostat size on the feed efficiencies, and, lastly, the Patriot 12-m subreflector is incorporated into the computational model to assess the overall broadband efficiency of the antenna system

The Wettzell System Monitoring Concept and First Realizations

Automated monitoring of operational system parameters for the geodetic space techniques is becoming more important in order to improve the geodetic data and to ensure the safety and stability of automatic and remote-controlled observations. Therefore, the Wettzell group has developed the system monitoring software, SysMon, which is based on a reliable, remotely-controllable hardware/software realization. A multi-layered data logging system based on a fanless, robust industrial PC with an internal database system is used to collect data from several external, serial, bus, or PCI-based sensors. The internal communication is realized with Remote Procedure Calls (RPC) and uses generative programming with the interface software generator idl2rpc.pl developed at Wettzell. Each data monitoring stream can be configured individually via configuration files to define the logging rates or analog-digital-conversion parameters. First realizations are currently installed at the new laser ranging system at Wettzell to address safety issues and at the VLBI station O Higgins as a meteorological data logger. The system monitoring concept should be realized for the Wettzell radio telescope in the near future

Searching for New Z-DNA/Z-RNA Binding Proteins Based on Structural Similarity to Experimentally Validated Zα Domain.

Z-DNA and Z-RNA are functionally important left-handed structures of nucleic acids, which play a significant role in several molecular and biological processes including DNA replication, gene expression regulation and viral nucleic acid sensing. Most proteins that have been proven to interact with Z-DNA/Z-RNA contain the so-called Zα domain, which is structurally well conserved. To date, only eight proteins with Zα domain have been described within a few organisms (including human, mouse, Danio rerio, Trypanosoma brucei and some viruses). Therefore, this paper aimed to search for new Z-DNA/Z-RNA binding proteins in the complete PDB structures database and from the AlphaFold2 protein models. A structure-based similarity search found 14 proteins with highly similar Zα domain structure in experimentally-defined proteins and 185 proteins with a putative Zα domain using the AlphaFold2 models. Structure-based alignment and molecular docking confirmed high functional conservation of amino acids involved in Z-DNA/Z-RNA, suggesting that Z-DNA/Z-RNA recognition may play an important role in a variety of cellular processes

The effect of fraud assessment documentation structure on auditors’ ability to identify control weaknesses: The moderating role of reviewer experience

Paper presented at the 2006 American Accounting Association Annual Meeting, Washington, D.C.The current regulatory environment, brought on by recent high-profile audit failures, expands the auditor’s role in detecting fraud. For example, auditors must now provide an opinion on clients’ internal controls, addressing their effectiveness at preventing or detecting fraud. While the structure of workpaper documentation has been shown to affect audit workpaper preparers’ assessments of overall fraud risk, prior research has not addressed the role their reviewers’ experience plays in mitigating documentation structure effects. Our study matches audit workpaper preparers with reviewers to investigate whether reviewer task-specific experience moderates the effect of fraud assessment documentation structure on the audit review team’s ability to identify the presence of significant control weaknesses. Consistent with expectations, we find that preparers who are required to document components of their fraud assessments provided more favorable (and lower quality) assessments of significant control weaknesses than those using either a supporting or balanced documentation structure. More importantly, results indicate that reviewer task-specific experience moderated the effect of documentation structure on reviewers’ identification of control weaknesses such that experienced reviewers compensated more for the effect of component documentation than reviewers with less experience. Our results suggest that experienced reviewers are better able to overcome challenges presented by documentation structure and more effectively assess the impact of control weaknesses than their less experienced counterparts. These results provide support for new regulations emphasizing the role of experience during the control assessment process

SARS-CoV-2 3D database: Understanding the Coronavirus Proteome and Evaluating Possible Drug Targets.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly growing infectious disease, widely spread with high mortality rates. Since the release of the SARS-CoV-2 genome sequence in March 2020, there has been an international focus on developing target-based drug discovery, which also requires knowledge of the 3D structure of the proteome. Where there are no experimentally solved structures, our group has created 3D models with coverage of 97.5% and characterised them using state-of-the-art computational approaches. Models of protomers and oligomers, together with predictions of substrate and allosteric binding sites, protein- ligand docking, SARS-CoV-2 protein interactions with human proteins, impacts of mutations, and mapped solved experimental structures are freely available for download. These are imple- mented in SARS CoV-2 3D, a comprehensive and user-friendly database, available at https://sars3d.com/. This provides essential information for drug discovery, both to evaluate targets and design new potential therapeutics.This work is supported and funded by King Abdullah scholarship (Saudi Arabia research coun- cil), and American Leprosy Missions grants (G88726), SET is funded by the Cystic Fibrosis Trust (RG 70975) and Fondation Botnar (RG91317). A.R.J is funded by the Biotechnology and Biological Sciences Research Council (BBSRC) DTP studentship (BB/M011194/1). B.B. is funded by the Cystic Fibrosis Trust and L.C. on a studentship from Ipsen. T.L.B. is funded by a the Wellcome Trust Investigator Award, PHZJ/489 RG83114 (2016-2021

Unheeded SARS-CoV-2 proteins? A deep look into negative-sense RNA.

SARS-CoV-2 is a novel positive-sense single-stranded RNA virus from the Coronaviridae family (genus Betacoronavirus), which has been established as causing the COVID-19 pandemic. The genome of SARS-CoV-2 is one of the largest among known RNA viruses, comprising of at least 26 known protein-coding loci. Studies thus far have outlined the coding capacity of the positive-sense strand of the SARS-CoV-2 genome, which can be used directly for protein translation. However, it has been recently shown that transcribed negative-sense viral RNA intermediates that arise during viral genome replication from positive-sense viruses can also code for proteins. No studies have yet explored the potential for negative-sense SARS-CoV-2 RNA intermediates to contain protein-coding loci. Thus, using sequence and structure-based bioinformatics methodologies, we have investigated the presence and validity of putative negative-sense ORFs (nsORFs) in the SARS-CoV-2 genome. Nine nsORFs were discovered to contain strong eukaryotic translation initiation signals and high codon adaptability scores, and several of the nsORFs were predicted to interact with RNA-binding proteins. Evolutionary conservation analyses indicated that some of the nsORFs are deeply conserved among related coronaviruses. Three-dimensional protein modeling revealed the presence of higher order folding among all putative SARS-CoV-2 nsORFs, and subsequent structural mimicry analyses suggest similarity of the nsORFs to DNA/RNA-binding proteins and proteins involved in immune signaling pathways. Altogether, these results suggest the potential existence of still undescribed SARS-CoV-2 proteins, which may play an important role in the viral lifecycle and COVID-19 pathogenesis

Effect of Age and Vaccination on Extent and Spread of Chlamydia pneumoniae Infection in C57BL/6 Mice

BACKGROUND: Chlamydia pneumoniae is an obligate intracellular respiratory pathogen for humans. Infection by C. pneumoniae may be linked etiologically to extra-respiratory diseases of aging, especially atherosclerosis. We have previously shown that age promotes C. pneumoniae respiratory infection and extra-respiratory spread in BALB/c mice. FINDINGS: Aged C57BL/6 mice had a greater propensity to develop chronic and/or progressive respiratory infections following experimental intranasal infection by Chlamydia pneumoniae when compared to young counterparts. A heptavalent CTL epitope minigene (CpnCTL7) vaccine conferred equal protection in the lungs of both aged and young mice. This vaccine was partially effective in protecting against C. pneumoniae spread to the cardiovascular system of young mice, but failed to provide cardiovascular protection in aged animals. CONCLUSIONS: Our findings suggest that vaccine strategies that target the generation of a C. pneumoniae-specific CTL response can protect the respiratory system of both young and aged animals, but may not be adequate to prevent dissemination of C. pneumoniae to the cardiovascular system or control replication in those tissues in aged animals