Biomolecular Concepts

The current millennium brought up a revolutionary paradigm shift in molecular biology: many operative proteins, rather than being quasi-rigid polypeptide chains folded into unique configurations - as believed throughout most of the past century - are now known to be intrinsically disordered, dynamic, pleomorphic, and multifunctional structures with stochastic behaviors. Yet, part of this knowledge, including suggestions about possible mechanisms and plenty of evidence for the same, became available by the 1950s and 1960s to remain then nearly forgotten for over 40 years...

The study of the GABAA receptor itself and its pharmacology is of paramount importance for shedding light on the role of this receptor in the central nervous system. Caged compounds have emerged as powerful tools to support research in this field, as they allow to control, in space and time, the release of neurotransmitters enabling, for example, to map receptors' distribution and dynamics. Here we focus on γ-aminobutyric acid (GABA)-caged compounds, particularly on a commercial complex called RuBi-GABA, which has high efficiency of uncaging upon irradiation at visible wavelengths...

Following structural determination by recent advances in electron cryomicroscopy, it is now well established that the respiratory Complexes I-IV in oxidative phosphorylation (OXPHOS) are organized into supercomplexes in the respirasome. Nonetheless, the reason for the existence of the OXPHOS supercomplexes and their functional role remains an enigma. Several hypotheses have been proposed for the existence of these supercomplex supercomplexes. A commonly-held view asserts that they enhance catalysis by substrate channeling...

The use of light for therapeutic purposes dates back to ancient Egypt, where the sun itself was an innovative source, probably used for the first time to heal skin diseases. Since then, technical innovation and advancement in medical sciences have produced newer and more sophisticated solutions for light-emitting sources and their applications in medicine. Starting from a brief historical introduction, the concept of innovation in light sources is discussed and analysed, first from a technical point of view and then in the light of their fitness to improve existing therapeutic protocols or propose new ones...

Super-resolution image acquisition has turned photo-activated far-infrared thermal imaging into a promising tool for the characterization of biological tissues. By the sub-diffraction localization of sparse temperature increments primed by the sample absorption of modulated focused laser light, the distribution of (endogenous or exogenous) photo-thermal biomarkers can be reconstructed at tunable ∼10-50 μm resolution. We focus here on the theoretical modeling of laser-primed temperature variations and provide the guidelines to convert super-resolved temperature-based images into quantitative maps of the absolute molar concentration of photo-thermal probes...

Microglial activation in the central nervous system (CNS) has been associated with brain damage and neurodegenerative disorders. Ochratoxin A (OTA) is a mycotoxin that occurs naturally in food and feed and has been associated with neurotoxicity, while corticosteroids are CNS' physiological function modulators. This study examined how OTA affected microglia activation and how corticosteroids influenced microglial neuroinflammation. Murine microglial cells (BV-2) were stimulated by OTA, and the potentiation effects on OTA-induced inflammation were determined by corticosterone pre-treatment...

The exposure of organisms and cells to unfavorable conditions such as increased temperature, antibiotics, reactive oxygen species, and viruses could lead to protein misfolding and cell death. The increased production of proteins such as heat shock proteins (HSPs) and polyamines has been linked to protein misfolding sequestration, thus maintaining, enhancing, and regulating the cellular system. For example, heat shock protein 40 (Hsp40) works hand in hand with Hsp70 and Hsp90 to successfully assist the newly synthesized proteins in folding properly...

Passive transport of molecules through nanopores is characterized by the interaction of molecules with pore internal walls and by a general crowding effect due to the constricted size of the nanopore itself, which limits the presence of molecules in its interior. The molecule-pore interaction is treated within the diffusion approximation by introducing the potential of mean force and the local diffusion coefficient for a correct statistical description. The crowding effect can be handled within the Markov state model approximation...

The potential role of styrene oxide in altering the dopaminergic pathway in the ear is investigated by means of molecular docking and molecular dynamics simulations. We estimate the binding affinity of both styrene oxide and dopamine to the dopaminergic receptor DrD2 by computing the free-energy difference, ∆ G , between the configuration where the ligand is bound to the receptor and the situation in which it is "infinitely" far away from it. The results show that the styrene oxide has a somewhat lower affinity for binding with respect to dopamine, which, however, may not be enough to prevent exogenous high concentration styrene oxide to compete with endogenous dopamine for DrD2 binding...

Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects...

The photodynamic treatment for antimicrobial applications or anticancer therapy relies on reactive oxygen species generated by photosensitizing molecules after absorption of visible or near-infrared light. If the photosensitizing molecule is in close vicinity of the microorganism or the malignant cell, a photocytotoxic action is exerted. Therefore, the effectiveness of photosensitizing compounds strongly depends on their capability to target microbial or cancer-specific proteins. In this study, we report on the preparation and preliminary characterization of human recombinant myoglobin fused to the vasoactive intestinal peptide to target vasoactive intestinal peptide receptor (VPAC) receptors...

Mr 4511 from Methylobacterium radiotolerans is a photoreceptor of the light, oxygen voltage (LOV) family, binding flavin mononucleotide (FMN) as a chromophore. It exhibits the prototypical LOV photocycle, with the reversible formation of an FMN-Cys71 adduct via fast decay of the FMN triplet state. Mr 4511 has high potential as a photosensitiser for singlet oxygen (SO) upon mutation of C71. Mr 4511-C71S shows a triplet lifetime ( τ T ) of several hundreds of microseconds, ensuring efficient energy transfer to dioxygen to form SO...

Calcium signaling controls a large variety of cell functions, including proliferation and apoptosis, and plays a major role in neoplastic transformation. Prostate cancer (PCa) is one of the most common malignancies in men. The transition to castration-resistant prostate cancer (CRPC), a lethal form that is still lacking an effective cure, could be influenced by fine tuning intracellular calcium ([Ca2+ ]i ) homeostasis. This study investigates [Ca2+ ]i dynamics in metastatic PCa cell lines that mimic the progression of PCa to CRPC: (i) well differentiated LNCaP cells that require androgen for survival, and (ii) poorly differentiated, highly aggressive androgen-insensitive prostate cancer (AIPC) PC3 and DU145 cells...

Extracellular vesicles (EVs)-mediated communication relies not only on the delivery of complex molecular cargoes as lipids, proteins, genetic material, and metabolites to their target cells but also on the modification of the cell surface local properties induced by the eventual fusion of EVs' membranes with the cells' plasma membrane. Here we applied scanning calorimetry to study the phase transition of single phospholipid (DMPC) monolamellar vesicles, investigating the thermodynamical effects caused by the fusion of doping amounts of mesenchymal stem cells-derived EVs...

Photodynamic therapy (PDT) is a clinically approved procedure that can exert a curative action against malignant cells. The treatment implies the administration of a photoactive molecular species that, upon absorption of visible or near infrared light, sensitizes the formation of reactive oxygen species. These species are cytotoxic and lead to tumor cell death, damage vasculature, and induce inflammation. Clinical investigations demonstrated that PDT is curative and does not compromise other treatment options...

In the present work, we discuss the way in which the parallel application of the patch-clamp technique and the 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) fluorescence detection for recording luminal proton changes allows the functional characterization of nonelectrogenic potassium/proton vacuolar antiporters of the NHX (Na+ /H+ exchanger) family. Moreover, we review the functional role of the tonoplast-specific phosphoinositide PI(3,5)P2 , able to simultaneously inhibit the activity of NHXs and CLC-a transporters, whose coordinated action can play an important role in the water balance of plant cells...

This study aims to increase Bacillus and Streptomyces antagonistic activity against the root rot and wilt diseases of pulses caused by Macrophomina phaseolina and Fusarium oxysporum f. sp. udum , respectively. To increase antagonistic action, Bacillus subtilis BRBac4, Bacillus siamensis BRBac21, and Streptomyces cavourensis BRAcB10 were subjected to random mutagenesis using varying doses of gamma irradiation (0.5-3.0 kGy). Following the irradiation, 250 bacterial colonies were chosen at random for each antagonistic strain and their effects against pathogens were evaluated in a plate assay...

Hydration of water affects the dynamics and in turn the activity of biomacromolecules. We investigated the dependence of the librational oscillations and the dynamical transition on the hydrating conditions of two globular proteins with different structure and size, namely β-lactoglobulin (βLG) and human serum albumin (HSA), by spin-label electron paramagnetic resonance (EPR) in the temperature range of 120-270 K. The proteins were spin-labeled with 5-maleimide spin-label on free cysteins and prepared in the lyophilized state, at low ( h = 0...

Recently, there has been increased interest in the development of novel antimicrobial compounds for utilization in a variety of sectors, including pharmaceutical, biomedical, textile, and food. The use, overuse, and misuse of synthetic compounds or derivatives have led to an increase of pathogenic microorganisms gaining resistance to the traditional antimicrobial therapies, which has led to an increased need for alternative therapeutic strategies. Seaweed are marine organisms that can be cultivated sustainably, and they are a source of polar molecules, such as pigments and phenolic compounds, which demonstrated antimicrobial potential...

One pillar of the predictive, preventive, and personalized medicine framework strategies is the female health. The evaluation of women's lifestyle and dietary habits in context with genetic and modifiable risk factors may reflect the prevention of cervical cancer before the occurrence of clinical symptoms and prediction of cervical lesion behavior. The main aim of this review is to analyze publications in the field of precision medicine that allow the use of research knowledge of cervical microbiome, epigenetic modifications, and inflammation in potential application in clinical practice...