Molecular Insights in Psychiatry

6 days 23 hours ago
This Special Issue included articles discussing several important psychiatric phenomena whose elucidation can be provided by cellular and subcellular molecular mechanisms [...].
Giovanna Traina

Computational Investigation of the Ordered Water System Around Microtubules: Implications for Protein Interactions

1 week ago
The existence of an exclusion zone in which particles of a colloidal suspension in water are repelled from hydrophilic surfaces has been experimentally demonstrated in numerous studies, especially in the case of Nafion surfaces. Various explanations have been proposed for the origin of this phenomenon, which is not completely understood yet. In particular, the existence of a fourth phase of water has been proposed by G. Pollack and if this theory is proven correct, its implications on our...
Francesco Chierici

Decoding the Bell-Shaped Calcium Spikes in Phosphorylation Cycles of Flagella

1 month 1 week ago
We investigate the messenger role of calcium ions implicated in the regulation of wave-like bending dynamics of flagella. The emphasis is on microtubules of flagellar axoneme serving as nonlinear transmission lines for bell-shaped spikes of calcium ions. The calcium sensitive proteins, such as calmodulin, exhibit activation dependence on the spike train frequency and amplitude. Here, we analyze a Ca^(2+) decoding module IDA-I1 whose activity is controlled by Ca^(2+) activated kinase. We find...
Miljko Satarić

A Review of the Recent Developments of Molecular Hybrids Targeting Tubulin Polymerization

1 month 1 week ago
Microtubules are cylindrical protein polymers formed from αβ-tubulin heterodimers in the cytoplasm of eukaryotic cells. Microtubule disturbance may cause cell cycle arrest in the G2/M phase, and anomalous mitotic spindles will form. Microtubules are an important target for cancer drug action because of their critical role in mitosis. Several microtubule-targeting agents with vast therapeutic advantages have been developed, but they often lead to multidrug resistance and adverse side effects....
Oluwakemi Ebenezer

Modulation of ERCC1-XPF Heterodimerization Inhibition <em>via</em> Structural Modification of Small Molecule Inhibitor Side-Chains

1 month 2 weeks ago
Inhibition of DNA repair enzymes is an attractive target for increasing the efficacy of DNA damaging chemotherapies. The ERCC1-XPF heterodimer is a key endonuclease in numerous single and double strand break repair processes, and inhibition of the heterodimerization has previously been shown to sensitize cancer cells to DNA damage. In this work, the previously reported ERCC1-XPF inhibitor 4 was used as the starting point for an in silico study of further modifications of the piperazine...
Claudia Weilbeer

Alteration of lipid bilayer mechanics by volatile anesthetics: Insights from μs-long molecular dynamics simulations

2 months 1 week ago
Very few drugs in clinical practice feature the chemical diversity, narrow therapeutic window, unique route of administration, and reversible cognitive effects of volatile anesthetics. The correlation between their hydrophobicity and their potency and the increasing amount of evidence suggesting that anesthetics exert their action on transmembrane proteins, justifies the investigation of their effects on phospholipid bilayers at the molecular level, given the strong functional and structural...
Eric A Zizzi

Melatonin mediates the reversibility of brain hyperphosphorylated tau protein induced by synthetic torpor in rats

3 months 2 weeks ago
CONCLUSIONS: Our results could pave the way for an effective new strategy to contrast tauopathies, with next-step studies aimed to pharmacologically interacting with this process at physiological temperature. References: (1) Luppi et al. Front Neuroanat 2019, 13:57; (2) Stieler et al. PLoS One 2011, 6: e14530. ³ Craddock, et al. Sci Reports 2017, 7:1.
Marco Luppi

Search for magnetic monopoles produced via the Schwinger mechanism

3 months 2 weeks ago
Electrically charged particles can be created by the decay of strong enough electric fields, a phenomenon known as the Schwinger mechanism¹. By electromagnetic duality, a sufficiently strong magnetic field would similarly produce magnetic monopoles, if they exist². Magnetic monopoles are hypothetical fundamental particles that are predicted by several theories beyond the standard model^(3-7) but have never been experimentally detected. Searching for the existence of magnetic monopoles via the...
B Acharya

The Effect of the Protein Synthesis Entropy Reduction on the Cell Size Regulation and Division Size of Unicellular Organisms

3 months 4 weeks ago
The underlying mechanism determining the size of a particular cell is one of the fundamental unknowns in cell biology. Here, using a new approach that could be used for most of unicellular species, we show that the protein synthesis and cell size are interconnected biophysically and that protein synthesis may be the chief mechanism in establishing size limitations of unicellular organisms. This result is obtained based on the free energy balance equation of protein synthesis and the second law...
Mohammad Razavi

Thermal hysteresis in microtubule assembly/disassembly dynamics: The aging-induced degradation of tubulin dimers

4 months ago
The assembly/disassembly of biological macromolecules plays an important role in their biological functionalities. Although the dynamics of tubulin polymers and their super-assembly into microtubule structures is critical for many cellular processes, details of their cyclical polymerization/depolymerization are not fully understood. Here, we use a specially designed light scattering technique to continuously examine the effects of temperature cycling on the process of microtubule...
R Wu

A Nanometric Probe of the Local Proton Concentration in Microtubule-Based Biophysical Systems

4 months 3 weeks ago
We show a double-functional fluorescence sensing paradigm that can retrieve nanometric pH information on biological structures. We use this method to measure the extent of protonic condensation around microtubules, which are protein polymers that play many roles crucial to cell function. While microtubules are believed to have a profound impact on the local cytoplasmic pH, this has been hard to show experimentally due to the limitations of conventional sensing techniques. We show that subtle...
Aarat P Kalra

Novel colchicine derivative CR42-24 demonstrates potent anti-tumor activity in urothelial carcinoma

5 months 3 weeks ago
Bladder cancers, and specifically urothelial carcinoma, have few effective treatment options, and tumors typically develop resistance against standard of care chemotherapies leading to significant mortality. The development of alternative therapies with increased selectivity and improved tolerability would significantly impact this patient population. Here, we investigate a novel colchicine derivative, CR42-24, with increased selectivity for the βIII tubulin subtype as a treatment for urothelial...
Clayton J Bell

Disassembly of microtubules by intense terahertz pulses

6 months 3 weeks ago
The biological effects of terahertz (THz) radiation have been observed across multiple levels of biological organization, however the sub-cellular mechanisms underlying the phenotypic changes remain to be elucidated. Filamentous protein complexes such as microtubules are essential cytoskeletal structures that regulate diverse biological functions, and these may be an important target for THz interactions underlying THz-induced effects observed at the cellular or tissue level. Here, we show...
Cameron M Hough

Computational determination of toxicity risks associated with a selection of approved drugs having demonstrated activity against COVID-19

6 months 4 weeks ago
CONCLUSION: In summary, this manuscript aims to provide a potentially useful source of essential knowledge on toxicity assessment of 90 compounds for healthcare practitioners and researchers to find off-label alternatives for the treatment for COVID-19. The majority of the molecules discussed in this manuscript have already moved into clinical trials and thus their known pharmacological and human safety profiles are expected to facilitate a fast track preclinical and clinical assessment for...
Maral Aminpour

Computational Study of Potential Galectin-3 Inhibitors in the Treatment of COVID-19

7 months 3 weeks ago
Galectin-3 is a carbohydrate-binding protein and the most studied member of the galectin family. It regulates several functions throughout the body, among which are inflammation and post-injury remodelling. Recent studies have highlighted the similarity between Galectin-3's carbohydrate recognition domain and the so-called "galectin fold" present on the N-terminal domain of the S1 sub-unit of the SARS-CoV-2 spike protein. Sialic acids binding to the N-terminal domain of the Spike protein are...
Maral Aminpour

<em>In silico</em> identification of RBD subdomain of spike protein from Pro<sup>322</sup>-Thr<sup>581</sup> for applications in vaccine development against SARS-CoV2

1 year ago
The three-dimensional hybrid structures of coronavirus spike proteins including the C-terminal sequence and receptor binding motif (RBM) was remodeled and energy minimized. Further, protein-protein docking show that Receptor Binding Domain (RBD) of SARS-CoV 2 Lys^(457)-Pro^(490) bind on the surface of ACE2 receptor near N-terminal helices to form host-pathogen attachment. In this binding interface, SARS-CoV 2 shows a tight network of hydrogen bonds than other spike proteins from BtRsRaTG13-CoV,...
Nataraj S Pagadala