Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins

The global Alzheimer's Association round robin study on plasma amyloid β methods

Introduction: Blood-based assays to measure brain amyloid beta (Aβ) deposition are an attractive alternative to the cerebrospinal fluid (CSF)-based assays currently used in clinical settings. In this study, we examined different blood-based assays to measure Aβ and how they compare among centers and assays. Methods: Aliquots from 81 plasma samples were distributed to 10 participating centers. Seven immunological assays and four mass-spectrometric methods were used to measure plasma Aβ concentrations. Results: Correlations were weak for Aβ42 while Aβ40 correlations were stronger. The ratio Aβ42/Aβ40 did not improve the correlations and showed weak correlations. Discussion: The poor correlations for Aβ42 in plasma might have several potential explanations, such as the high levels of plasma proteins (compared to CSF), sensitivity to pre-analytical sample handling and specificity, and cross-reactivity of different antibodies. Different methods might also measure different pools of plasma Aβ42. We, however, hypothesize that greater correlations might be seen in future studies because many of the methods have been refined during completion of this study

Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic.

Biomarker discovery and development for clinical research, diagnostics and therapy monitoring in clinical trials have advanced rapidly in key areas of medicine - most notably, oncology and cardiovascular diseases - allowing rapid early detection and supporting the evolution of biomarker-guided, precision-medicine-based targeted therapies. In Alzheimer disease (AD), breakthroughs in biomarker identification and validation include cerebrospinal fluid and PET markers of amyloid-β and tau proteins, which are highly accurate in detecting the presence of AD-associated pathophysiological and neuropathological changes. However, the high cost, insufficient accessibility and/or invasiveness of these assays limit their use as viable first-line tools for detecting patterns of pathophysiology. Therefore, a multistage, tiered approach is needed, prioritizing development of an initial screen to exclude from these tests the high numbers of people with cognitive deficits who do not demonstrate evidence of underlying AD pathophysiology. This Review summarizes the efforts of an international working group that aimed to survey the current landscape of blood-based AD biomarkers and outlines operational steps for an effective academic-industry co-development pathway from identification and assay development to validation for clinical use.I recieved an honorarium from Roche Diagnostics for my participation in the advisory panel meeting leading to this pape

Adaptation of Higher Medical Education to the Conditions of Digitalization of Healthcare

The aim of the work is to study the features of digitalization in medicine, healthcare, professional education, and to determine the directions of their further adaptation to the requirements of the time on the example of the medical university. The provision is based on the use of methods such as content analysis of modern publications on the problem, their logical analysis, generalization and systemization of published information, as well as the presentation of the experience of digitalization in the higher medical education.The article shows the relevance of digitalization for health care, with which it is possible to optimize the tasks of managing the quality and accessibility of medical care. They require a quick quantitative assessment using modern information technology, mathematical methods, software, big data analysis, and other technology tools. Content in digitalization in healthcare also includes the creation of innovative services and platforms that enable remote communication with patients, doctors, medical and pharmaceutical services, and the use of monitoring of medical and preventive processes in medical organizations.The digitalization of higher education is one of the areas of innovative policy of universities, implemented in accordance with the requirements and conditions of the external environment and own funds. Training of professionals with the right knowledge and digital technology requires appropriate educational information resources for educational and scientific processes in universities. To do this, the electronic information education environment (EIEE) is formed as a set of information, telecommunications and technology tools. The experience of creating EIEE at Kursk State Medical University over the past decades is presented. Various forms and methods of learning and knowledge control are being computerized. The university has subdivision management systems (dean’s offices, departments, library, staff, admissions committees, educational and methodological management and others). Many continuing medical education programs at the Faculty of Postgraduate Education are being implemented remotely. Methods and forms of practice-oriented and project-based training using information technology are being developed