Pharmacological applications of nitric oxide-releasing biomaterials in human skin.

Nitric oxide (NO) is an important endogenous molecule that plays several roles in biological systems. NO is synthesized in human skin by three isoforms of nitric oxide synthase (NOS) and, depending on the produced NO concentration, it can actuate in wound healing, dermal vasodilation, or skin defense against different pathogens, for example. Besides being endogenously produced, NO-based pharmacological formulations have been developed for dermatological applications targeting diverse pathologies such as bacterial infection, wound healing, leishmaniasis, and even esthetic issues such as acne and skin aging.

Insights into complex I assembly: Function of NDUFAF1 and a link with cardiolipin remodeling.

Respiratory complex I is a ~1-MDa proton pump in mitochondria. Its structure has been revealed in great detail, but the structural basis of its assembly, in humans involving at least 15 assembly factors, is essentially unknown. We determined cryo-electron microscopy structures of assembly intermediates associated with assembly factor NDUFAF1 in a yeast model system.

Depletion of Tip60/Kat5 affects the hepatic antioxidant system in mice.

Tat-interactive protein 60 kDa (TIP60, also known as lysine acetyltransferase 5 [KAT5]) is a member of the MYST protein family with histone acetyltransferase activity. Recent studies have reported that TIP60 has multiple functions in many signal transduction mechanisms, especially p53-mediated apoptosis. Although the activation of apoptosis signaling pathways requires the presence of cellular reactive oxygen species (ROS) at a certain level, an imbalance between the production and consumption of ROS in cells results in oxidative stress (OS).

Dynamics of base pairs with low stability in RNA by solid-state nuclear magnetic resonance exchange spectroscopy.

Base pairs are fundamental building blocks of RNA. The base pairs of low stability are often critical in RNA functions. Here, we develop a solid-state NMR-based water-RNA exchange spectroscopy (WaterREXSY) to characterize RNA in solid.

Colloidal delivery of vitamin E into solid lipid nanoparticles as a potential complement for the adverse effects of anemia treatment.

Vitamin E (VitE) is one of the most important antioxidants and plays a key role in decreasing the inflammatory effects of oxidative stress caused by recurrent doses of iron administration in anemia treatment. However, VitE is poorly soluble in aqueous environments. Here, VitE encapsulation into solid lipid nanoparticles (SLN) composed of myristil myristate to improve its bioavailability was proposed.

Correction: Franz et al. Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P Release. . 2021, , 104.

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Electroneutral Polymer Nanodiscs Enable Interference-Free Probing of Membrane Proteins in a Lipid-Bilayer Environment.

Membrane proteins can be examined in near-native lipid-bilayer environments with the advent of polymer-encapsulated nanodiscs. These nanodiscs self-assemble directly from cellular membranes, allowing in vitro probing of membrane proteins with techniques that have previously been restricted to soluble or detergent-solubilized proteins. Often, however, the high charge densities of existing polymers obstruct bioanalytical and preparative techniques.

Visualizing translation dynamics at atomic detail inside a bacterial cell.

Translation is the fundamental process of protein synthesis and is catalysed by the ribosome in all living cells. Here we use advances in cryo-electron tomography and sub-tomogram analysis to visualize the structural dynamics of translation inside the bacterium Mycoplasma pneumoniae. To interpret the functional states in detail, we first obtain a high-resolution in-cell average map of all translating ribosomes and build an atomic model for the M.

The fibrotic niche impairs satellite cell function and muscle regeneration in mouse models of Marfan syndrome.

Aim: It has been suggested that the proliferation and early differentiation of myoblasts are impaired in Marfan syndrome (MFS) mice during muscle regeneration. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we investigated muscle regeneration in MFS mouse models by analyzing the influence of the fibrotic niche on satellite cell function.

Binding of Natural Inhibitors to Respiratory Complex I.

NADH:ubiquinone oxidoreductase (respiratory complex I) is a redox-driven proton pump with a central role in mitochondrial oxidative phosphorylation. The ubiquinone reduction site of complex I is located in the matrix arm of this large protein complex and connected to the membrane via a tunnel. A variety of chemically diverse compounds are known to inhibit ubiquinone reduction by complex I.

The Inflammasome Activity of NLRP3 Is Independent of NEK7 in HEK293 Cells Co-Expressing ASC.

The cytosolic immune receptor NLRP3 (nucleotide-binding domain, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3) oligomerizes into the core of a supramolecular complex termed inflammasome in response to microbes and danger signals. It is thought that NLRP3 has to bind NEK7 (NIMA (never in mitosis gene a)-related kinase 7) to form a functional inflammasome core that induces the polymerization of the adaptor protein ASC (Apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)), which is a hallmark for NLRP3 activity. We reconstituted the NLRP3 inflammasome activity in modified HEK293 (human embryonic kidney 293) cells and showed that the ASC speck polymerization is independent of NEK7 in the context of this cell system.

Field and magic angle spinning frequency dependence of proton resonances in rotating solids.

Proton detection in solid state NMR is continuously developing and allows one to gain new insights in structural biology. Overall, this progress is a result of the synergy between hardware development, new NMR methodology and new isotope labeling strategies, to name a few factors. Even though current developments are rapid, it is worthwhile to summarize what can currently be achieved employing proton detection in biological solids.

Non-ergodicity of a globular protein extending beyond its functional timescale.

Internal motions of folded proteins have been assumed to be ergodic, , that the dynamics of a single protein molecule averaged over a very long time resembles that of an ensemble. Here, by performing single-molecule fluorescence resonance energy transfer (smFRET) experiments and molecular dynamics (MD) simulations of a multi-domain globular protein, cytoplasmic protein-tyrosine phosphatase (SHP2), we demonstrate that the functional inter-domain motion is observationally non-ergodic over the time spans 10 to 10 s and 10 to 10 s. The difference between observational non-ergodicity and simple non-convergence is discussed.

Ectosomes and exosomes modulate neuronal spontaneous activity.

Extracellular vesicles (EVs) are important mediators in intercellular communication. However, understanding the biological origin and functional effects of EVs subtypes has been challenging due to the moderate differences in their physical properties and absence of reliable markers. Here, we characterize the proteomes of ectosomes and exosomes using an improved differential ultracentrifugation protocol and quantitative proteomics.

Identification of a Thyroid Hormone Binding Site in Hsp90 with Implications for Its Interaction with Thyroid Hormone Receptor Beta.

While many proteins are known clients of heat shock protein 90 (Hsp90), it is unclear whether the transcription factor, thyroid hormone receptor beta (TRb), interacts with Hsp90 to control hormonal perception and signaling. Higher Hsp90 expression in mouse fibroblasts was elicited by the addition of triiodothyronine (T3). T3 bound to Hsp90 and enhanced adenosine triphosphate (ATP) binding of Hsp90 due to a specific binding site for T3, as identified by molecular docking experiments.

Nanostructured Lipid Carriers Loaded with Dexamethasone Prevent Inflammatory Responses in Primary Non-Parenchymal Liver Cells.

Liver inflammation represents a major clinical problem in a wide range of pathologies. Among the strategies to prevent liver failure, dexamethasone (DXM) has been widely used to suppress inflammatory responses. The use of nanocarriers for encapsulation and sustained release of glucocorticoids to liver cells could provide a solution to prevent severe side effects associated with systemic delivery as the conventional treatment regime.

An In Vivo Model for Elucidating the Role of an Erythroid-Specific Isoform of Nuclear Export Protein Exportin 7 (Xpo7) in Murine Erythropoiesis.

Erythroid nuclear condensation is a complex process in which compaction to one-tenth its original size occurs in an active nucleus simultaneously undergoing transcription and cell division. We previously found that the nuclear exportin Exportin7 (Xpo7), which is erythroid- specific and highly induced during terminal erythropoiesis, facilitates nuclear condensation. We also identified a previously unannotated, erythroid-specific isoform of Xpo7 (Xpo7B) containing a novel first exon Xpo7-1b expressed only in late Ter119 erythroblasts.

Stereodynamics of adiabatic and non-adiabatic energy transfer in a molecule surface encounter.

Molecular energy transfer and reactions at solid surfaces depend on the molecular orientation relative to the surface. While such steric effects have been largely understood in electronically adiabatic processes, the orientation-dependent energy transfer in NO scattering from Au(111) was complicated by electron-mediated nonadiabatic effects, thus lacking a clear interpretation and posing a great challenge for theories. Herein, we investigate the stereodynamics of adiabatic and nonadiabatic energy transfer molecular dynamics simulations of NO( = 3) scattering from Au(111) using realistic initial orientation distributions based on accurate neural network fitted adiabatic potential energy surface and electronic friction tensor.