Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation of p38 mitogen-activated protein kinase (MAPK) is implicated in ALS.

Twisted-plywood-like tissue formation . Does curvature do the twist?

Little is known about the contribution of 3D surface geometry to the development of multilayered tissues containing fibrous extracellular matrix components, such as those found in bone. In this study, we elucidate the role of curvature in the formation of chiral, twisted-plywood-like structures. Tissues consisting of murine preosteoblast cells (MC3T3-E1) were grown on 3D scaffolds with constant-mean curvature and negative Gaussian curvature for up to 32 days.

On shape forming by contractile filaments in the surface of growing tissues.

Growing tissues are highly dynamic, and flow on sufficiently long timescales due to cell proliferation, migration, and tissue remodeling. As a consequence, growing tissues can often be approximated as viscous fluids. This means that the shape of microtissues growing in vitro is governed by their surface stress state, as in fluid droplets.

Site-specific inhibition of the thalamic reticular nucleus induces distinct modulations in sleep architecture.

The thalamic reticular nucleus (TRN) is crucial for the modulation of sleep-related oscillations. The caudal and rostral subpopulations of the TRN exert diverse activities, which arise from their interconnectivity with all thalamic nuclei, as well as other brain regions. Despite the recent characterization of the functional and genetic heterogeneity of the TRN, the implications of this heterogeneity for sleep regulation have not been assessed.

Curvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales.

Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface curvature in biology is supported by numerous experimental and theoretical investigations in recent years. In this review, first, a brief introduction to the key ideas of surface curvature in the context of biological systems is given and the challenges that arise when measuring surface curvature are discussed.

Wall Shear Stress Analysis and Optimization in Tissue Engineering TPMS Scaffolds.

When designing scaffolds for bone tissue engineering (BTE), the wall shear stress (WSS), due to the fluid flow inside the scaffold, is an important factor to consider as it influences the cellular process involved in new tissue formation. The present work analyzed the average WSS in Schwartz diamond (SD) and gyroid (SG) scaffolds with different surface topologies and mesh elements using computational fluid dynamics (CFD) analysis. It was found that scaffold meshes with a smooth surface topology with tetrahedral elements had WSS levels 35% higher than the equivalent scaffold with a non-smooth surface topology with hexahedral elements.

Challenges in computational fluid dynamics applications for bone tissue engineering.

Bone injuries or defects that require invasive surgical treatment are a serious clinical issue, particularly when it comes to treatment success and effectiveness. Accordingly, bone tissue engineering (BTE) has been researching the use of computational fluid dynamics (CFD) analysis tools to assist in designing optimal scaffolds that better promote bone growth and repair. This paper aims to offer a comprehensive review of recent studies that use CFD analysis in BTE.

Rubbing Powders: Direct Spectroscopic Observation of Triboinduced Oxygen Radical Formation in MgO Nanocube Ensembles.

Powder compaction-induced surface chemistry in metal oxide nanocrystal ensembles is important for very diverse fields such as triboelectrics, tribocatalysts, surface abrasion, and cold sintering of ceramics. Using a range of spectroscopic techniques, we show that MgO nanocube powder compaction with uniaxial pressures that can be achieved by gentle manual rubbing or pressing ( ≥ 5 MPa) excites energetic electron-hole pairs and generates oxygen radicals at interfacial defect structures. While the identification of paramagnetic O radicals and their adsorption complexes with O point to the emergence of hole centers, triboemitted electrons become scavenged by molecular oxygen to convert into adsorbed superoxide anions O as measured by electron paramagnetic resonance (EPR).

Advanced materials design based on waste wood and bark.

Trees belong to the largest living organisms on Earth and plants in general are one of our main renewable resources. Wood as a material has been used since the beginning of humankind. Today, forestry still provides raw materials for a variety of applications, for example in the building industry, in paper manufacturing and for various wood products.

Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome.

Kabuki syndrome (KS) is a rare cause of intellectual disability primarily caused by loss-of-function mutations in lysine-specific methyltransferase 2D (), which normally adds methyl marks to lysine 4 on histone 3. Previous studies have shown that a mouse model of KS ( ) demonstrates disruption of adult neurogenesis and hippocampal memory. Proof-of-principle studies have shown postnatal rescue of neurological dysfunction following treatments that promote chromatin opening; however, these strategies are non-specific and do not directly address the primary defect of histone methylation.

Surface tension determines tissue shape and growth kinetics.

The collective self-organization of cells into three-dimensional structures can give rise to emergent physical properties such as fluid behavior. Here, we demonstrate that tissues growing on curved surfaces develop shapes with outer boundaries of constant mean curvature, similar to the energy minimizing forms of liquids wetting a surface. The amount of tissue formed depends on the shape of the substrate, with more tissue being deposited on highly concave surfaces, indicating a mechano-biological feedback mechanism.

Protecting Offspring Against Fire: Lessons From Seed Pods.

Wildfires are a natural component in many terrestrial ecosystems and often play a crucial role in maintaining biodiversity, particularly in the fire-prone regions of Australia. A prime example of plants that are able to persist in these regions is the genus . Most species that occur in fire-prone regions produce woody seed pods (follicles), which open during or soon after fire to release seeds into the post-fire environment.

Organic Molecule-Driven Polymeric Actuators.

Inspired by the motions of plant tissues in response to external stimuli, significant attention has been devoted to the development of actuating polymeric materials. In particular, polymeric actuators driven by organic molecules have been designed due to their combined superiorities of tunable functional monomers, designable chemical structures, and variable structural anisotropy. Here, the recent progress is summarized in terms of material synthesis, structure design, polymer-solvent interaction, and actuating performance.

Tensile forces drive a reversible fibroblast-to-myofibroblast transition during tissue growth in engineered clefts.

Myofibroblasts orchestrate wound healing processes, and if they remain activated, they drive disease progression such as fibrosis and cancer. Besides growth factor signaling, the local extracellular matrix (ECM) and its mechanical properties are central regulators of these processes. It remains unknown whether transforming growth factor-β (TGF-β) and tensile forces work synergistically in up-regulating the transition of fibroblasts into myofibroblasts and whether myofibroblasts undergo apoptosis or become deactivated by other means once tissue homeostasis is reached.

Comparative in situ analysis reveals the dynamic nature of sclerenchyma cell walls of the fern Asplenium rutifolium.

Background And Aims: A key structural adaptation of vascular plants was the evolution of specialized vascular and mechanical tissues, innovations likely to have generated novel cell wall architectures. While collenchyma is a strengthening tissue typically found in growing organs of angiosperms, a similar tissue occurs in the petiole of the fern Asplenium rutifolium.

Methods: The in situ cell wall (ultra)structure and composition of this tissue was investigated and characterized mechanically as well as structurally through nano-indentation and wide-angle X-ray diffraction, respectively.

Scaffold curvature-mediated novel biomineralization process originates a continuous soft tissue-to-bone interface.

Unlabelled: A myriad of shapes are found in biological tissues, often naturally evolved to fulfill a particular function. In the field of tissue engineering, substrate geometry influences cell behavior and tissue formation in vitro, yet little is known how this translates to an in vivo scenario. Here we investigate scaffold curvature-induced tissue growth, without additional growth factors or cells, in an ovine animal model.

Curvature-controlled defect dynamics in active systems.

We have studied the collective motion of polar active particles confined to ellipsoidal surfaces. The geometric constraints lead to the formation of vortices that encircle surface points of constant curvature (umbilics). We have found that collective motion patterns are particularly rich on ellipsoids with four umbilics where vortices tend to be located near pairs of umbilical points to minimize their interaction energy.

Materials Nanoarchitecturing via Cation-Mediated Protein Assembly: Making Limpet Teeth without Mineral.

Teeth are designed to deliver high forces while withstanding the generated stresses. Aside from isolated mineral-free exception (e.g.

Flexible and Actuating Nanoporous Poly(Ionic Liquid)-Paper-Based Hybrid Membranes.

Porous and flexible actuating materials are important for the development of smart systems. We report here a facile method to prepare scalable, flexible actuating porous membranes based on a poly(ionic liquid)-modified tissue paper. The targeted membrane property profile was based on synergy of the gradient porous structure of a poly(ionic liquid) network and flexibility of a tissue paper.

The Role of Titanium Surface Nanostructuring on Preosteoblast Morphology, Adhesion, and Migration.

Surface structuring of titanium-based implants is known to modulate the behavior of adherent cells, but the influence of different nanotopographies is poorly understood. The aim is to investigate preosteoblast proliferation, adhesion, morphology, and migration on surfaces with similar surface chemistry but distinct nanotopographical features. Sonochemical treatment and anodic oxidation are employed to fabricate disordered, mesoporous titania (TMS) and ordered titania nanotubular (TNT) topographies on titanium, respectively.

Protein misfolding in neurodegenerative diseases: implications and strategies.

A hallmark of neurodegenerative proteinopathies is the formation of misfolded protein aggregates that cause cellular toxicity and contribute to cellular proteostatic collapse. Therapeutic options are currently being explored that target different steps in the production and processing of proteins implicated in neurodegenerative disease, including synthesis, chaperone-assisted folding and trafficking, and degradation via the proteasome and autophagy pathways. Other therapies, like mTOR inhibitors and activators of the heat shock response, can rebalance the entire proteostatic network.

Cytoplasmic Relocalization of TAR DNA-Binding Protein 43 Is Not Sufficient to Reproduce Cellular Pathologies Associated with ALS .

Mutations in the gene , which encodes TAR DNA-binding protein 43 (TDP-43), are a rare cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While the majority of mutations are found in the C-terminal glycine-rich domain, an alanine to valine amino acid change at position 90 (A90V) in the bipartite nuclear localization signal (NLS) of TDP-43 has been described. This sequence variant has previously been shown to cause cytoplasmic mislocalization of TDP-43 and decrease protein solubility, leading to the formation of insoluble aggregates.

Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation.

Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials.