ABSTRACT
Recent advances in single-cell technologies have enabled high-throughput molecular profiling of cells across modalities and locations. Single-cell transcriptomics data can now be complemented by chromatin accessibility, surface protein expression, adaptive immune receptor repertoire profiling and spatial information. The increasing availability of single-cell data across modalities has motivated the development of novel computational methods to help analysts derive biological insights. As the field grows, it becomes increasingly difficult to navigate the vast landscape of tools and analysis steps. Here, we summarize independent benchmarking studies of unimodal and multimodal single-cell analysis across modalities to suggest comprehensive best-practice workflows for the most common analysis steps. Where independent benchmarks are not available, we review and contrast popular methods. Our article serves as an entry point for novices in the field of single-cell (multi-)omic analysis and guides advanced users to the most recent best practices.
Subject(s)
Gene Expression Profiling , Proteomics , Gene Expression Profiling/methods , Single-Cell Analysis/methodsABSTRACT
During transmission of malaria-causing parasites from mosquitoes to mammals, Plasmodium sporozoites migrate rapidly in the skin to search for a blood vessel. The high migratory speed and narrow passages taken by the parasites suggest considerable strain on the sporozoites to maintain their shape. Here, we show that the membrane-associated protein, concavin, is important for the maintenance of the Plasmodium sporozoite shape inside salivary glands of mosquitoes and during migration in the skin. Concavin-GFP localizes at the cytoplasmic periphery and concavin(-) sporozoites progressively round up upon entry of salivary glands. Rounded concavin(-) sporozoites fail to pass through the narrow salivary ducts and are rarely ejected by mosquitoes, while normally shaped concavin(-) sporozoites are transmitted. Strikingly, motile concavin(-) sporozoites disintegrate while migrating through the skin leading to parasite arrest or death and decreased transmission efficiency. Collectively, we suggest that concavin contributes to cell shape maintenance by riveting the plasma membrane to the subtending inner membrane complex. Interfering with cell shape maintenance pathways might hence provide a new strategy to prevent a malaria infection.
Subject(s)
Anopheles , Malaria , Parasites , Plasmodium , Animals , Anopheles/parasitology , Mammals , Sporozoites/metabolismABSTRACT
People in countries of the global south are affected by a unique spectrum of diseases, while costs for health care are a huge burden in the context of poverty. Furthermore, non-communicable diseases increasingly play a role in these countries. The management of translational research, potential clinical applications and marketing of new drugs in Germany is thus getting more and more important for global health. Regarding this, universities have a particular responsibility for two reasons. First, through basic research, they contribute significantly to the development of new medicines. Second, the university is a public institution and has thus the responsibility to return the gained knowledge to the public. Marketing of publicly funded innovations should provide benefits to patients in wealthy and poor countries alike. As a first step towards this goal, we demand the introduction of a globally responsible licensing policy at German universities. Different mechanisms which have been described in the German speaking areas such as "Equitable Licensing" provide a basis for the realization of this ambitious aim and have been introduced successfully at the universities of Muenster, Tuebingen and Freiburg.
Subject(s)
Global Health , Universities , Delivery of Health Care , Germany , HumansABSTRACT
Bead-rod-spring models are the foundation of the kinetic theory of polymer solutions. We derive the diffusion equation for the probability density function of the configuration of a general bead-rod-spring model in short-correlated Gaussian random flows. Under isotropic conditions, we solve this equation analytically for the elastic rhombus model introduced by Curtiss, Bird, and Hassager [Adv. Chem. Phys. 35, 31 (1976)].