Publisher Correction: Cortical-like mini-columns of neuronal cells on zinc oxide nanowire surfaces.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Computational Drug Repositioning for Chagas Disease Using Protein-Ligand Interaction Profiling.

Chagas disease, caused by (), affects nearly eight million people worldwide. There are currently only limited treatment options, which cause several side effects and have drug resistance. Thus, there is a great need for a novel, improved Chagas treatment.

Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells.

Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis are still unknown.

Modular gateway-ness connectivity and structural core organization in maritime network science.

Around 80% of global trade by volume is transported by sea, and thus the maritime transportation system is fundamental to the world economy. To better exploit new international shipping routes, we need to understand the current ones and their complex systems association with international trade. We investigate the structure of the global liner shipping network (GLSN), finding it is an economic small-world network with a trade-off between high transportation efficiency and low wiring cost.

Structure-based drug repositioning explains ibrutinib as VEGFR2 inhibitor.

Many drugs are promiscuous and bind to multiple targets. On the one hand, these targets may be linked to unwanted side effects, but on the other, they may achieve a combined desired effect (polypharmacology) or represent multiple diseases (drug repositioning). With the growth of 3D structures of drug-target complexes, it is today possible to study drug promiscuity at the structural level and to screen vast amounts of drug-target interactions to predict side effects, polypharmacological potential, and repositioning opportunities.

Drug repositioning or target repositioning: A structural perspective of drug-target-indication relationship for available repurposed drugs.

Drug repositioning aims to find new indications for existing drugs in order to reduce drug development cost and time. Currently,there are numerous stories of successful drug repositioning that have been reported and many repurposed drugs are already available on the market. Although drug repositioning is often a product of serendipity, repositioning opportunities can be uncovered systematically.

Prominins control ciliary length throughout the animal kingdom: New lessons from human prominin-1 and zebrafish prominin-3.

Prominins (proms) are transmembrane glycoproteins conserved throughout the animal kingdom. They are associated with plasma membrane protrusions, such as primary cilia, as well as extracellular vesicles derived thereof. Primary cilia host numerous signaling pathways affected in diseases known as ciliopathies.

Structure-based drug repositioning: Potential and limits.

Drug repositioning, the assignment of new therapeutic purposes to known drugs, is an established strategy with many repurposed drugs on the market and many more at experimental stage. We review three use cases, a herpes drug with benefits in cancer, a cancer drug with potential in autoimmune disease, and a selective and an unspecific drug binding the same target (GPCR). We explore these use cases from a structural point of view focusing on a deep understanding of the underlying drug-target interactions.

Modification of titanium implants using biofunctional nanodiamonds for enhanced antimicrobial properties.

The present study describes a novel antimicrobial surface using anodic oxidation of titanium and biofunctional detonation nanodiamonds (ND). ND have been loaded with antibiotics (amoxicillin or ampicillin) using poly(diallyldimethylammonium chloride) (PDDA). Successful conjugation with PDDA was determined by dynamic light scattering, which showed increase in the hydrodynamic diameter of ND agglomerates and shift of zeta potential towards positive values.

StructureDistiller: Structural relevance scoring identifies the most informative entries of a contact map.

Protein folding and structure prediction are two sides of the same coin. Contact maps and the related techniques of constraint-based structure reconstruction can be considered as unifying aspects of both processes. We present the Structural Relevance (SR) score which quantifies the information content of individual contacts and residues in the context of the whole native structure.

Characterization of Tissue Transglutaminase as a Potential Biomarker for Tissue Response toward Biomaterials.

Tissue transglutaminase (TGase 2) is proposed to be important for biomaterial-tissue interactions due to its presence and versatile functions in the extracellular environment. TGase 2 catalyzes the cross-linking of proteins through its Ca-dependent acyltransferase activity. Moreover, it enhances the interactions between fibronectin and integrins, which in turn mediates the adhesion, migration, and motility of the cells.

Nucleoli and Promyelocytic Leukemia Protein (PML) bodies are phase separated nuclear protein quality control compartments for misfolded proteins.

We uncovered a role for nucleoli and PML-bodies as phase-separated protein quality control organelles that compartmentalize protein quality control factors and misfolded proteins for their efficient clearance. Failure to dispose misfolded proteins converts nucleoli and PML-bodies into a solid state that immobilizes ubiquitin, limiting its recycling for genome integrity maintenance.

Machine learning of human plasma lipidomes for obesity estimation in a large population cohort.

Obesity is associated with changes in the plasma lipids. Although simple lipid quantification is routinely used, plasma lipids are rarely investigated at the level of individual molecules. We aimed at predicting different measures of obesity based on the plasma lipidome in a large population cohort using advanced machine learning modeling.

Nucleolus: A Liquid Droplet Compartment for Misbehaving Proteins.

A new study reports an unexpected function of the nucleolus as a protein quality control compartment for misfolded and aggregation-prone proteins. These findings have important implications for protein misfolding diseases.

Liquid-Liquid Phase Separation in Disease.

We have made rapid progress in recent years in identifying the genetic causes of many human diseases. However, despite this recent progress, our mechanistic understanding of these diseases is often incomplete. This is a problem because it limits our ability to develop effective disease treatments.

Systems Network Genomic Analysis Reveals Cardioprotective Effect of MURC/Cavin-4 Deletion Against Ischemia/Reperfusion Injury.

Background Ischemia/reperfusion (I/R) injury is a critical issue in the development of treatment strategies for ischemic heart disease. MURC (muscle-restricted coiled-coil protein)/Cavin-4 (caveolae-associated protein 4), which is a component of caveolae, is involved in the pathophysiology of dilated cardiomyopathy and cardiac hypertrophy. However, the role of MURC in cardiac I/R injury remains unknown.

Defective ribosomal products challenge nuclear function by impairing nuclear condensate dynamics and immobilizing ubiquitin.

Nuclear protein aggregation has been linked to genome instability and disease. The main source of aggregation-prone proteins in cells is defective ribosomal products (DRiPs), which are generated by translating ribosomes in the cytoplasm. Here, we report that DRiPs rapidly diffuse into the nucleus and accumulate in nucleoli and PML bodies, two membraneless organelles formed by liquid-liquid phase separation.

ALS and FTD: Where RNA metabolism meets protein quality control.

Recent genetic and biochemical evidence has improved our understanding of the pathomechanisms that lead to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurodegenerative diseases with overlapping symptoms and causes. Impaired RNA metabolism, enhanced aggregation of protein-RNA complexes, aberrant formation of ribonucleoprotein (RNP) granules and dysfunctional protein clearance via autophagy are emerging as crucial events in ALS/FTD pathogenesis. Importantly, these processes interact at the molecular level, converging on a common pathogenic cascade.

Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery.

Cancer cells can switch between signaling pathways to regulate growth under different conditions. In the tumor microenvironment, this likely helps them evade therapies that target specific pathways. We must identify all possible states and utilize them in drug screening programs.

Highly Conductive, Stretchable, and Cell-Adhesive Hydrogel by Nanoclay Doping.

Electrically conductive materials that mimic physical and biological properties of tissues are urgently required for seamless brain-machine interfaces. Here, a multinetwork hydrogel combining electrical conductivity of 26 S m , stretchability of 800%, and tissue-like elastic modulus of 15 kPa with mimicry of the extracellular matrix is reported. Engineering this unique set of properties is enabled by a novel in-scaffold polymerization approach.

Cortical-like mini-columns of neuronal cells on zinc oxide nanowire surfaces.

A long-standing goal of neuroscience is a theory that explains the formation of the minicolumns in the cerebral cortex. Minicolumns are the elementary computational units of the mature neocortex. Here, we use zinc oxide nanowires with controlled topography as substrates for neural-cell growth.