Refinement of cryo-EM 3D maps with a self-supervised denoising model: crefDenoiser.

Cryogenic electron microscopy (cryo-EM) is a pivotal technique for imaging macromolecular structures. However, despite extensive processing of large image sets collected in cryo-EM experiments to amplify the signal-to-noise ratio, the reconstructed 3D protein-density maps are often limited in quality due to residual noise, which in turn affects the accuracy of the macromolecular representation. Here, crefDenoiser is introduced, a denoising neural network model designed to enhance the signal in 3D cryo-EM maps produced with standard processing pipelines.

Iron-carbohydrate complexes treating iron anaemia: Understanding the nano-structure and interactions with proteins through orthogonal characterisation.

Intravenous (IV) iron-carbohydrate complexes are widely used nanoparticles (NPs) to treat iron deficiency anaemia, often associated with medical conditions such as chronic kidney disease, heart failure and various inflammatory conditions. Even though a plethora of physicochemical characterisation data and clinical studies are available for these products, evidence-based correlation between physicochemical properties of iron-carbohydrate complexes and clinical outcome has not fully been elucidated yet. Studies on other metal oxide NPs suggest that early interactions between NPs and blood upon IV injection are key to understanding how differences in physicochemical characteristics of iron-carbohydrate complexes cause variance in clinical outcomes.

Artemisia Species with High Biological Values as a Potential Source of Medicinal and Cosmetic Raw Materials.

species play a vital role in traditional and contemporary medicine. Among them, , , , , and are the most popular. The chemical composition and bioactivity of these species have been extensively studied.

Conformational Effects on the Passive Membrane Permeability of Synthetic Macrocycles.

Macrocyclic compounds (MCs) can have complex conformational properties that affect pharmacologically important behaviors such as membrane permeability. We measured the passive permeability of 3600 diverse nonpeptidic MCs and used machine learning to analyze the results. Incorporating selected properties based on the three-dimensional (3D) conformation gave models that predicted permeability with = 0.

Posttranscriptional Regulation of the Human LDL Receptor by the U2-Spliceosome.

Background: The LDLR (low-density lipoprotein receptor) in the liver is the major determinant of LDL-cholesterol levels in human plasma. The discovery of genes that regulate the activity of LDLR helps to identify pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease.

Methods: We performed a genome-wide RNA interference screen for genes limiting the uptake of fluorescent LDL into Huh-7 hepatocarcinoma cells.

Defining and navigating macrocycle chemical space.

Macrocyclic compounds (MCs) are of growing interest for inhibition of challenging drug targets. We consider afresh what structural and physicochemical features could be relevant to the bioactivity of this compound class. Using these features, we performed Principal Component Analysis to map oral and non-oral macrocycle drugs and clinical candidates, and also commercially available synthetic MCs, in structure-property space.

(Tarragon): A Review of Its Traditional Uses, Phytochemistry and Pharmacology.

L. (tarragon), Asteraceae, is a species that has long been used in traditional Asian medicine, mainly in Iran, Pakistan, Azerbaijan and India. It is known as a spice species in Asia, Europe and the Americas.

L. (Southern Wormwood)-History, Current Knowledge on the Chemistry, Biological Activity, Traditional Use and Possible New Pharmaceutical and Cosmetological Applications.

L. (southern wormwood) is a plant species with an important position in the history of European and Asian medicine. It is a species famous as a medicinal plant in Central Asia, Asia Minor, and in South-East and Central Europe.

Artemisia annua - Importance in Traditional Medicine and Current State of Knowledge on the Chemistry, Biological Activity and Possible Applications.

(annual mugwort) is a species that has long been used in traditional Asian medicine, mainly Chinese and Hindu. The species is widespread and known as a medicinal plant not only in Asia but also in Europe, in both Americas, and Australia. The species has become a subject of particular interest due to the 2015 Nobel Prize awarded for detecting the sesquiterpene lactone artemisinin in it and proving its antimalarial activities.

Significance of L. (Common Mugwort) in the History of Medicine and Its Possible Contemporary Applications Substantiated by Phytochemical and Pharmacological Studies.

L. (common mugwort) is a species with great importance in the history of medicine and was called the "mother of herbs" in the Middle Ages. It is a common herbaceous plant that exhibits high morphological and phytochemical variability depending on the location where it occurs.

L.-Importance in the History of Medicine, the Latest Advances in Phytochemistry and Therapeutical, Cosmetological and Culinary Uses.

-wormwood (Asteraceae)-is a very important species in the history of medicine, formerly described in medieval Europe as "". It is a species known as a medicinal plant in Europe and also in West Asia and North America. The raw material obtained from this species is and The main substances responsible for the biological activity of the herb are: the essential oil, bitter sesquiterpenoid lactones, flavonoids, other bitterness-imparting compounds, azulenes, phenolic acids, tannins and lignans.

Loss of TSC complex enhances gluconeogenesis via upregulation of locus miRNAs.

Loss of the tumor suppressor tuberous sclerosis complex 1 () in the liver promotes gluconeogenesis and glucose intolerance. We asked whether this could be attributed to aberrant expression of small RNAs. We performed small-RNA sequencing on liver of -knockout mice, and found that miRNAs of the delta-like homolog 1 ()-deiodinase iodothyronine type III () locus are up-regulated in an mTORC1-dependent manner.

Bidirectional Propagation of Signals and Nutrients in Fungal Networks via Specialized Hyphae.

Intercellular distribution of nutrients and coordination of responses to internal and external cues via endogenous signaling molecules are hallmarks of multicellular organisms. Vegetative mycelia of multicellular fungi are syncytial networks of interconnected hyphae resulting from hyphal tip growth, branching, and fusion. Such mycelia can reach considerable dimensions and, thus, different parts can be exposed to quite different environmental conditions.

Single-cell mRNA profiling reveals the hierarchical response of miRNA targets to miRNA induction.

miRNAs are small RNAs that regulate gene expression post-transcriptionally. By repressing the translation and promoting the degradation of target mRNAs, miRNAs may reduce the cell-to-cell variability in protein expression, induce correlations between target expression levels, and provide a layer through which targets can influence each other's expression as "competing RNAs" (ceRNAs). However, experimental evidence for these behaviors is limited.

High-Resolution Cryoelectron Microscopy Structure of the Cyclic Nucleotide-Modulated Potassium Channel MloK1 in a Lipid Bilayer.

Eukaryotic cyclic nucleotide-modulated channels perform their diverse physiological roles by opening and closing their pores to ions in response to cyclic nucleotide binding. We here present a structural model for the cyclic nucleotide-modulated potassium channel homolog from Mesorhizobium loti, MloK1, determined from 2D crystals in the presence of lipids. Even though crystals diffract electrons to only ∼10 Å, using cryoelectron microscopy (cryo-EM) and recently developed computational methods, we have determined a 3D map of full-length MloK1 in the presence of cyclic AMP (cAMP) at ∼4.

VEGF-A Regulates Cellular Localization of SR-BI as Well as Transendothelial Transport of HDL but Not LDL.

Objective: Low- and high-density lipoproteins (LDL and HDL) must pass the endothelial layer to exert pro- and antiatherogenic activities, respectively, within the vascular wall. However, the rate-limiting factors that mediate transendothelial transport of lipoproteins are yet little known. Therefore, we performed a high-throughput screen with kinase drug inhibitors to identify modulators of transendothelial LDL and HDL transport.

Benchmark of Schemes for Multiscale Molecular Dynamics Simulations.

In multiscale molecular dynamics simulations the accuracy of detailed models is combined with the efficiency of a reduced representation. For several applications - namely those of sampling enhancement - it is desirable to combine fine-grained (FG) and coarse-grained (CG) approaches into a single hybrid approach with an adjustable mixing parameter. We present a benchmark of three algorithms that use a mixing of the two representation layers using a Lagrangian formalism.

Quantifying the strength of miRNA-target interactions.

We quantify the strength of miRNA-target interactions with MIRZA, a recently introduced biophysical model. We show that computationally predicted energies of interaction correlate strongly with the energies of interaction estimated from biochemical measurements of Michaelis-Menten constants. We further show that the accuracy of the MIRZA model can be improved taking into account recently emerged experimental data types.

Efficient Algorithms for Langevin and DPD Dynamics.

In this article, we present several algorithms for stochastic dynamics, including Langevin dynamics and different variants of Dissipative Particle Dynamics (DPD), applicable to systems with or without constraints. The algorithms are based on the impulsive application of friction and noise, thus avoiding the computational complexity of algorithms that apply continuous friction and noise. Simulation results on thermostat strength and diffusion properties for ideal gas, coarse-grained (MARTINI) water, and constrained atomic (SPC/E) water systems are discussed.

Hybrid simulations: combining atomistic and coarse-grained force fields using virtual sites.

Hybrid simulations, in which part of the system is represented at atomic resolution and the remaining part at a reduced, coarse-grained, level offer a powerful way to combine the accuracy associated with the atomistic force fields to the sampling speed obtained with coarse-grained (CG) potentials. In this work we introduce a straightforward scheme to perform hybrid simulations, making use of virtual sites to couple the two levels of resolution. With the help of these virtual sites interactions between molecules at different levels of resolution, i.