High-content screening (HCS) provides an excellent tool to understand the mechanism of action of drugs on disease-relevant model systems. Careful selection of fluorescent labels (FLs) is crucial for successful HCS assay development. HCS assays typically comprise (a) FLs containing biological information of interest, and (b) additional structural FLs enabling instance segmentation for downstream analysis. However, the limited number of available fluorescence microscopy imaging channels restricts the degree to which these FLs can be experimentally multiplexed. In this article, we present a segmentation workflow that overcomes the dependency on structural FLs for image segmentation, typically freeing two fluorescence microscopy channels for biologically relevant FLs. It consists in extracting structural information encoded within readouts that are primarily biological, by fine-tuning pre-trained state-of-the-art generalist cell segmentation models for different combinations of individual FLs, and aggregating the respective segmentation results together. Using annotated datasets that we provide, we confirm our methodology offers improvements in performance and robustness across several segmentation aggregation strategies and image acquisition methods, over different cell lines and various FLs. It thus enables the biological information content of HCS assays to be maximized without compromising the robustness and accuracy of computational single-cell profiling.

Holotomographic microscopy (HTM) measures the refractive index (RI) tomograms of living cells and tissues in three dimensions. The ability to observe biological processes at high spatial and temporal resolution opens uncharted territories for cell biologists, however, current HTM devices have a limited throughput. We show here the first automated multi-well plate-compatible HTM device, the CX-A. Thanks to state-of-the-art environment control and a new type of autofocus, the CX-A can record multiple conditions in parallel over large fields of view, while its software EVE supports automated single-cell segmentation and quantification. This opens the door to new applications for HTM, from drug screening to systems biology.

Tramadol is used worldwide and is listed in many medical guidelines to treat both acute and chronic pains. There is a growing evidence of abuse of tramadol in some African and West Asian countries. Tramadol has some side effects. The present study designed to follow up the treatment of the cellular responses which might be induced in the kidney of tramadol mice. Treated mice received daily injection of tramadol dose (125 μg/100 g b.wt) for 20 and 40 days. Other mice received tramadol for 40 days and then were divided into three groups: the first received distilled water, the second received Lagenaria siceraria, and the third received melatonin daily for 40 days. Both the daily injection of tramadol for 20 and 40 days resulted in radical, extensive, and severe alterations in the normal histological architecture of the kidney. Treatment with Lagenaria siceraria or melatonin after tramadol administration for a long-term, markedly changed the collagen content and other chemical components, that may reach nearly normal levels. Such findings propose that although tramadol has many cytological and histopathological side effects on the kidneys of male mice, the treatments via Lagenaria siceraria and melatonin have effective therapeutic impacts on the tramadol side effects.

Apicomplexans, including species of Eimeria, pose a real threat to the health and wellbeing of animals and humans. Eimeria parasites do not infect humans but cause an important economic impact on livestock, in particular on the poultry industry. Despite its high prevalence and financial costs, little is known about the cell biology of these ‘cosmopolitan’ parasites found all over the world. In this review, we discuss different aspects of the life cycle and stages of Eimeria species, focusing on cellular structures and organelles typical of the coccidian family as well as genus-specific features, complementing some ‘unknowns’ with what is described in the closely related coccidian Toxoplasma gondii.

In the late stage of the mitotic cycle of eukaryotic cells, cytokinesis ensues during which a parent cell replicates its nucleus with the necessary genetical substances (i.e., DNAs and chromosomes) and splits into two similar offspring cells. This mitotic process involves complex chemical, biophysical andmechanical processes whose details are just beginning to be unfolded experimentally. In this paper, we propose a full 3-D hydrodynamical model using a phase field approach to study the cellular morphological change during cytokinesis. In this model, the force along the contracting ring induced by remodeling of actin-myosin filament on cell cortex layer at the division plane of the parent cell during cytokinesis, is approximated using a proxy force anchored on the newly formed nuclei. The symmetric or asymmetric cell division is simulated numerically with the model. Our numerical results show that the location of the division plane and the contracting force along the cytokinetic ring on the division plane are essential for the cell division. In addition, our numerical study also shows that, during cytokinesis, surface tension of the cell membrane also contributes to this process by retaining the morphological integrity of the offspring cells. This model and the accompanying numerical simulation tool provide a solid framework to build upon with more sophisticated whole cell models to probe the cell mitotic process.

The pathogenic Theileria species Theileria parva and T. annulata infect bovine leukocytes and erythrocytes causing acute, often fatal lymphoproliferative diseases in cattle. The parasites are of interest not only because of their economic importance as pathogens, but also because of their unique ability to transform the leukocytes they infect. The latter property allows parasitized leukocytes to be cultured as continuously growing cell lines in vitro, thus providing an amenable in vitro system to study the parasite/host cell relationship and parasite-specific cellular immune responses. This paper summarizes important advances in knowledge of the immunobiology of these parasites over the last 40 years, focusing particularly on areas of relevance to vaccination.

The invasive blood stage of malaria parasites, merozoites, are complex entities specialized for the capture and entry of red blood cells. Their potential for vaccination and other anti-malaria strategies have attracted much research attention over the last 40 years, and there is now a considerable body of data relating to their biology. In this article some of the major advances over this period and remaining challenges are reviewed.

The development of dynamic substrates that can modulate the behavior of adherent cells is important for fundamental studies in cell biology, applications in biomaterials, and engineering microsystems that combine cellular and material components. This review outlines several strategies based on physical transduction schemes (including electrical, photochemical, thermal, and mechanical forces) for designing interfaces that are active and can signal changes in the behavior of attached cells.

Viruses replicate inside host cells, where they use host biochemical and structural components to facilitate the production of new virus particles. As a consequence of co-evolution with their hosts, viruses have acquired host genes and genetic mutations that confer dominance over normal cell function. Research on virus–cell interactions has focused on the identification of mechanisms of virus dominance in order to develop therapeutic strategies for preventing productive infection. Although such research remains an essential part of molecular virology, viruses are also important genetic tools that can be used to analyse cell function. Because virus genomes contain genetic information, some of which was derived from host cells, it is possible that the analyses of virus–host interactions might lead to the identification of functionally dominant virus genes and novel eukaryotic counterparts. In this article, we have described how transforming and non-transforming viruses can control cell motility (cell migration or membrane projection), and explained how the analysis of virus cytopathic effects (CPEs) led to the identification of a novel family of cellular genes that regulate diverse aspects of cell motility.

The basic properties of living systems are remarkably consistent and involve energy interactions between intracellular and extracellular environments. These interactions predispose living systems to deposit minerals from many solutions. The evolution of biomineralisation was not a single cellular invention but rather the association and perfection of a few of these fundamental properties of cell biology. The components of biomineralisation systems involve some mechanism for modifying the activity of at least one ion, an interface for initiating and possibly controlling crystal growth, a diffusion limited size and a mechanism for manipulating the growth of the crystal lattice. The evolution of these components of biomineralisation in the context of geological time inevitably concentrates on the Precambrian–Cambrian boundary. Over a time scale of less than 50 × 106 years there was a proliferation of metazoan phyla, the mineralisation in a large number of taxa and the exploitation of a diverse set of processes involving agglutinated sediments, silica, phosphates and carbonates. A large number of theories have been proposed to explain why biomineralisation occurred at this particular time. Such theories should recognise the importance of the incorporation of the citric acid cycle into the cellular metabolism of many organisms and its exploitation in an aerobic environment, the development of multicellularity which enormously increased the opportunities for modifying ion activities in diffusion-limited sites, and the exploitation of browsing and carnivorous feeding habits. These influences had major effects on ecosystems and population structures and put considerable selective pressure on the advantages that could be gained from a skeleton.