Abstract
Expression Atlas is EMBL-EBI’s resource for gene and protein expression. It sources and compiles data on the abundance and localisation of RNA and proteins in various biological systems and ...contexts and provides open access to this data for the research community. With the increased availability of single cell RNA-Seq datasets in the public archives, we have now extended Expression Atlas with a new added-value service to display gene expression in single cells. Single Cell Expression Atlas was launched in 2018 and currently includes 123 single cell RNA-Seq studies from 12 species. The website can be searched by genes within or across species to reveal experiments, tissues and cell types where this gene is expressed or under which conditions it is a marker gene. Within each study, cells can be visualized using a pre-calculated t-SNE plot and can be coloured by different features or by cell clusters based on gene expression. Within each experiment, there are links to downloadable files, such as RNA quantification matrices, clustering results, reports on protocols and associated metadata, such as assigned cell types.
How small, fast-growing bacteria ensure tight cell-size distributions remains elusive. High-throughput measurement techniques have propelled efforts to build modeling tools that help to shed light on ...the relationships between cell size, growth and cycle progression. Most proposed models describe cell division as a discrete map between size at birth and size at division with stochastic fluctuations assumed. However, such models underestimate the role of cell size transient dynamics by excluding them.
We propose an efficient approach for estimation of cell size transient dynamics. Our technique approximates the transient size distribution and statistical moment dynamics of exponential growing cells following an adder strategy with arbitrary precision.
We approximate, up to arbitrary precision, the distribution of division times and size across time for the adder strategy in rod-shaped bacteria cells. Our approach is able to compute statistical moments like mean size and its variance from such distributions efficiently, showing close match with numerical simulations. Additionally, we observed that these distributions have periodic properties. Our approach further might shed light on the mechanisms behind gene product homeostasis.
Molecular dynamics simulation using enhanced sampling methods is one of the powerful computational tools used to explore protein conformations and free energy landscapes. Enhanced sampling methods ...often employ either an increase in temperature or a flattening of the potential energy surface to rapidly sample phase space, and a corresponding reweighting algorithm is used to recover the Boltzmann statistics. However, potential energies of complex biomolecules usually involve large fluctuations on a magnitude of hundreds of kcal/mol despite minimal structural changes during simulation. This leads to noisy reweighting statistics and complicates the obtainment of accurate final results. To overcome this common issue in enhanced conformational sampling, we propose a scaled molecular dynamics method, which modifies the biomolecular potential energy surface and employs a reweighting scheme based on configurational populations. Statistical mechanical theory is applied to derive the reweighting formula, and the canonical ensemble of simulated structures is recovered accordingly. Test simulations on alanine dipeptide and the fast folding polypeptide Chignolin exhibit sufficiently enhanced conformational sampling and accurate recovery of free energy surfaces and thermodynamic properties. The results are comparable to long conventional molecular dynamics simulations and exhibit better recovery of canonical statistics over methods which employ a potential energy term in reweighting.
Essential cellular functions as diverse as genome maintenance and tissue morphogenesis rely on the dynamic organization of filamentous assemblies. For example, the precise structural organization of ...DNA filaments has profound consequences on all DNA-mediated processes including gene expression, whereas control over the precise spatial arrangement of cytoskeletal protein filaments is key for mechanical force generation driving animal tissue morphogenesis. Polarized fluorescence is currently used to extract structural organization of fluorescently labeled biological filaments by determining the orientation of fluorescent labels, however with a strong drawback: polarized fluorescence imaging is indeed spatially limited by optical diffraction, and is thus unable to discriminate between the intrinsic orientational mobility of the fluorophore labels and the real structural disorder of the labeled biomolecules. Here, we demonstrate that quantitative single-molecule polarized detection in biological filament assemblies allows not only to correct for the rotational flexibility of the label but also to image orientational order of filaments at the nanoscale using superresolution capabilities. The method is based on polarized direct stochastic optical reconstruction microscopy, using dedicated optical scheme and image analysis to determine both molecular localization and orientation with high precision. We apply this method to double-stranded DNA in vitro and microtubules and actin stress fibers in whole cells.
Single-molecule localization microscopy provides insights into the nanometer-scale spatial organization of proteins in cells, however it does not provide information on their conformation and ...orientation, which are key functional signatures. Detecting single molecules' orientation in addition to their localization in cells is still a challenging task, in particular in dense cell samples. Here, we present a polarization-splitting scheme which combines Stochastic Optical Reconstruction Microscopy (STORM) with single molecule 2D orientation and wobbling measurements, without requiring a strong deformation of the imaged point spread function. This method called 4polar-STORM allows, thanks to a control of its detection numerical aperture, to determine both single molecules' localization and orientation in 2D and to infer their 3D orientation. 4polar-STORM is compatible with relatively high densities of diffraction-limited spots in an image, and is thus ideally placed for the investigation of dense protein assemblies in cells. We demonstrate the potential of this method in dense actin filament organizations driving cell adhesion and motility.
Polycaprolactone (PCL) has been extensively applied on tissue engineering because of its low‐melting temperature, good processability, biodegradability, biocompatibility, mechanical resistance, and ...relatively low cost. The advance of additive manufacturing (AM) technologies in the past decade have boosted the fabrication of customized PCL products, with shorter processing time and absence of material waste. In this context, this review focuses on the use of AM techniques to produce PCL scaffolds for various tissue engineering applications, including bone, muscle, cartilage, skin, and cardiovascular tissue regeneration. The search for optimized geometry, porosity, interconnectivity, controlled degradation rate, and tailored mechanical properties are explored as a tool for enhancing PCL biocompatibility and bioactivity. In addition, rheological and thermal behavior is discussed in terms of filament and scaffold production. Finally, a roadmap for future research is outlined, including the combination of PCL struts with cell‐laden hydrogels and 4D printing.
Land cover-land use (LCLU) classification tasks can take advantage of the fusion of radar and optical remote sensing data, leading generally to increase mapping accuracy. Here we propose a ...methodological approach to fuse information from the new European Space Agency Sentinel-1 and Sentinel-2 imagery for accurate land cover mapping of a portion of the Lower Magdalena region, Colombia. Data pre-processing was carried out using the European Space Agency's Sentinel Application Platform and the SEN2COR toolboxes. LCLU classification was performed following an object-based and spectral classification approach, exploiting also vegetation indices. A comparison of classification performance using three commonly used classification algorithms was performed. The radar and visible-near infrared integrated dataset classified with a Support Vector Machine algorithm produce the most accurate LCLU map, showing an overall classification accuracy of 88.75%, and a Kappa coefficient of 0.86. The proposed mapping approach has the main advantages of combining the all-weather capability of the radar sensor, spectrally rich information in the visible-near infrared spectrum, with the short revisit period of both satellites. The mapping results represent an important step toward future tasks of aboveground biomass and carbon estimation in the region.
Derived from the extensive work in the area of small molecule zinc(II) ion sensors, chelating fragment libraries of quinoline- and benzimidazole-sulfonamides have been prepared and screened against ...several different zinc(II)-dependent matrix metalloproteinases (MMPs). The fragments show impressive inhibition of these metalloenzymes and preferences for different MMPs based on the nature of the chelating group. The findings show that focused chelator libraries are a powerful strategy for the discovery of lead fragments for metalloprotein inhibition.
Lignin is a polymer of phenylpropanoid compounds formed through a complex biosynthesis route, represented by a metabolic grid for which most of the genes involved have been sequenced in several ...plants, mainly in the model-plants Arabidopsis thaliana and Populus. Plants are exposed to different stresses, which may change lignin content and composition. In many cases, particularly for plant-microbe interactions, this has been suggested as defence responses of plants to the stress. Thus, understanding how a stressor modulates expression of the genes related with lignin biosynthesis may allow us to develop study-models to increase our knowledge on the metabolic control of lignin deposition in the cell wall. This review focuses on recent literature reporting on the main types of abiotic and biotic stresses that alter the biosynthesis of lignin in plants.
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