Surface-enhanced infrared spectroscopic study of extracellular vesicles using plasmonic gold nanoparticles.

Extracellular vesicles (EVs), sub-micrometer lipid-bound particles released by most cells, are considered a novel area in both biology and medicine. Among characterization methods, infrared (IR) spectroscopy, especially attenuated total reflection (ATR), is a rapidly emerging label-free tool for molecular characterization of EVs. The relatively low number of vesicles in biological fluids (∼10 particle/mL), however, and the complex content of the EVs' milieu (protein aggregates, lipoproteins, buffer molecules) might result in poor signal-to-noise ratio in the IR analysis of EVs.

PED in 2024: improving the community deposition of structural ensembles for intrinsically disordered proteins.

The Protein Ensemble Database (PED) (URL: https://proteinensemble.org) is the primary resource for depositing structural ensembles of intrinsically disordered proteins. This updated version of PED reflects advancements in the field, denoting a continual expansion with a total of 461 entries and 538 ensembles, including those generated without explicit experimental data through novel machine learning (ML) techniques.

Interactions of the Anti-SARS-CoV-2 Agents Molnupiravir and Nirmatrelvir/Paxlovid with Human Drug Transporters.

Orally administered small molecules may have important therapeutic potential in treating COVID-19 disease. The recently developed antiviral agents, Molnupiravir and Nirmatrelvir, have been reported to be efficient treatments, with only moderate side effects, especially when applied in the early phases of this disease. However, drug-drug and drug-transporter interactions have already been noted by the drug development companies and in the application notes.

The evolution and polymorphism of mono-amino acid repeats in androgen receptor and their regulatory role in health and disease.

Androgen receptor (AR) is a key member of nuclear hormone receptors with the longest intrinsically disordered N-terminal domain (NTD) in its protein family. There are four mono-amino acid repeats (polyQ1, polyQ2, polyG, and polyP) located within its NTD, of which two are polymorphic (polyQ1 and polyG). The length of both polymorphic repeats shows clinically important correlations with disease, especially with cancer and neurodegenerative diseases, as shorter and longer alleles exhibit significant differences in expression, activity and solubility.

A Novel Tandem-Tag Purification Strategy for Challenging Disordered Proteins.

Intrinsically disordered proteins (IDPs) lack well-defined 3D structures and can only be described as ensembles of different conformations. This high degree of flexibility allows them to interact promiscuously and makes them capable of fulfilling unique and versatile regulatory roles in cellular processes. These functional benefits make IDPs widespread in nature, existing in every living organism from bacteria and fungi to plants and animals.

The Importance of Mg -Free State in Nucleotide Exchange of Oncogenic K-Ras Mutants.

For efficient targeting of oncogenic K-Ras interaction sites, a mechanistic picture of the Ras-cycle is necessary. Herein, we used NMR relaxation techniques and molecular dynamics simulations to decipher the role of slow dynamics in wild-type and three oncogenic P-loop mutants of K-Ras. Our measurements reveal a dominant two-state conformational exchange on the ms timescale in both GDP- and GTP-bound K-Ras.

Storage conditions determine the characteristics of red blood cell derived extracellular vesicles.

Extracellular vesicles (EVs) are released during the storage of red blood cell (RBC) concentrates and might play adverse or beneficial roles throughout the utilization of blood products (transfusion). Knowledge of EV release associated factors and mechanism amends blood product management. In the present work the impact of storage time and medium (blood preserving additive vs isotonic phosphate buffer) on the composition, size, and concentration of EVs was studied using attenuated total reflection infrared (ATR-IR) spectroscopy, microfluidic resistive pulse sensing (MRPS) and freeze-fraction combined transmission electron micrography (FF-TEM).

Intense video gaming is not essentially problematic.

Video games are more popular than ever and the general public, including parents, educators, and the media, tends to consider intense video gaming fundamentally problematic. To test this hypothesis, participants were recruited via gaming-related websites resulting in a sample of N = 5,222 online video gamers (mean age: 22.2 years, SD = 6.

Cross-species inhibition of dUTPase via the Staphylococcal Stl protein perturbs dNTP pool and colony formation in Mycobacterium.

Proteins responsible for the integrity of the genome are often used targets in drug therapies against various diseases. The inhibitors of these proteins are also important to study the pathways in genome integrity maintenance. A prominent example is Ugi, a well known cross-species inhibitor protein of the enzyme uracil-DNA glycosylase, responsible for uracil excision from DNA.