Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here, we describe an extended conformational selection model that embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein (‘discrete breathers’) can govern conformational transitions and allosteric propagation that accompany binding processes and, as such, might be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment.
Most genome-wide assays provide averages across large numbers of cells, but recent technological advances promise to overcome this limitation. Pioneering single-cell assays are now available for genome, epigenome, transcriptome, proteome, and metabolome profiling. Here, we describe how these different dimensions can be combined into multi-omics assays that provide comprehensive profiles of the same cell.
Is the European Union (EU) regulatory framework for genetically modified organisms (GMOs) adequate for emerging techniques, such as genome editing? This has been discussed extensively for more than 10 years. A recent proposal from The Netherlands offers a way to break the deadlock. Here, we discuss how the proposal would affect examples from public plant research.
Clustered regularly interspaced short palindromic repeats (CRISPR) technology has enabled genetic engineering feats previously considered impracticable, offering great hopes for solutions to problems facing society. We consider it timely to highlight how CRISPR can benefit public health, medicine, and agriculture in sub-Saharan Africa (SSA) and offer recommendations for successful implementation.
Highlights • The current status of the Pichia pastoris genome is shown to lack extensive functional annotation. • GO annotation transfer and literature curation pipelines improve the functional annotation of genomes. • Pipelines and tools that can improve the annotation status of the genomes of Pichia pastoris and many industrial microbes are considered. • Well-annotated genome sequences will facilitate the utilization of these microbes in a broader range of synthetic biology applications.
The current view of the cytoplasm as a ‘bustling and well-organized metropolitan city’ raises the issue of how physicochemical forces control the macromolecular interactions and transport of metabolites and energy in the cell. Motivated by studies on bacterial osmosensors, we argue that charged cytoplasmic macromolecules are stabilized electrostatically by their ionic atmospheres. The high cytoplasmic crowding (25–50% of cell volume) shapes the remaining cell volume (50–75%) into transient networks of electrolyte pathways and pools. The predicted ‘semi-conductivity’ of the electrolyte pathways guides the flow of biochemical ions throughout the cytoplasm. This metabolic and signaling current is powered by variable electrochemical gradients between the pools. The electrochemical gradients are brought about by cellular biochemical reactions and by extracellular stimuli. The cellular metabolism is thus vectorial not only across the membrane but also throughout the cytoplasm.
Highlights • We review recent advances in nucleic acid chemistry and polymerase engineering that have enabled the synthesis, replication, and evolution of a wide range of nucleic acid-like synthetic genetic polymers (XNAs) with improved chemical and biological stability. • We discuss the likely biotechnological impact of the further development of XNA technology for the generation of novel ligands, enzymes, and nanostructures with tailor-made chemistry.
The identification and validation of biomarkers for diagnosing Alzheimer's disease (AD) and other forms of dementia are increasingly important. To date, ELISA measurement of β-amyloid(1–42), total tau and phospho-tau-181 in cerebrospinal fluid (CSF) is the most advanced and accepted method to diagnose probable AD with high specificity and sensitivity. However, it is a great challenge to search for novel biomarkers in CSF and blood by using modern potent methods, such as microarrays and mass spectrometry, and to optimize the handling of samples (e.g. collection, transport, processing, and storage), as well as the interpretation using bioinformatics. It seems likely that only a combined analysis of several biomarkers will define a patient-specific signature to diagnose AD in the future.
Multiplexed point-of-care testing (xPOCT), which is simultaneous on-site detection of different analytes from a single specimen, has recently gained increasing importance for clinical diagnostics, with emerging applications in resource-limited settings (such as in the developing world, in doctors’ offices, or directly at home). Nevertheless, only single-analyte approaches are typically considered as the major paradigm in many reviews of point-of-care testing. Here, we comprehensively review the present diagnostic systems and techniques for xPOCT applications. Different multiplexing technologies (e.g., bead- or array-based systems) are considered along with their detection methods (e.g., electrochemical or optical). We also address the unmet needs and challenges of xPOCT. Finally, we critically summarize the in-field applicability and the future perspectives of the presented approaches.
Combustion of Liquid Fuel Sprays outlines the fundamentals of the combustion of sprays in a unified way which may be applied to any technological application. The book begins with a discussion of the general nature of spray combustion, the sources of liquid fuels used in spray combustion, biomass sources of liquid fuels, and the nature and properties of fuel oils. Subsequent chapters focus on the properties of sprays, the atomization of liquid fuels, and the theoretical modeling of the behavior of a spray flame in a combustion chamber. The nature and control of pollutants from spray combustion, the formation of deposits in oil-fired systems, and the combustion of sprays in furnaces and engines are elucidated as well. The text is intended for students undertaking courses or research in fuel, combustion, and energy studies..