Semi-empirical proof of long bond states as intermediates in mass spectrometry fragmentation of aldohexofuranose derivatives

Following the observation that the m/z 101 peak is usually the base peak in the electron ionization mass spectra of di-O-isopropylidenated aldohexofuranose derivatives, quantum chemical calculations were carried out in order to provide a judicious explanation for the preference of these derivatives towards the cleavage of the exocyclic dioxolane moiety. It was also established that geminal electron donor functional groups play an important part in the stabilization of the radical cation generated during the loss of one electron from these compounds (the ionization process). In this paper, by using the PM7 semi-empirical method we show that the radical character is preferentially located between the C4-C5 carbon atoms from the di-O-isopropylidenated derivatives, which is why the C4-C5 bond becomes elongated, thus justifying the cleavage that produces the high intensity peak at m/z 101

TLC-Densitometric investigation of bioactive components from Mediterranean algae

Several photosynthetic pigments from two algae, namely Padina pavonica and Codium fragile, were extracted in different solvents and subsequently analyzed through TLC. The optimization of the separation parameters led to the choosing of the optimum eluent (hexane/acetone mixture) for polar silica gel plates. The isolated compounds were evaluated through densitometric measurements and by the acquisition of their UV-Vis spectra. While xanthophylls, chlorophyll a and pheophytin a were the most typical pigments of Padina pavonica, chlorophyll a and b, xanthophyll and β-carotene were the most characteristic pigments for Codium fragile

Mathematical Modeling of Brain Activity under Specific Auditory Stimulation

Understanding the connection between different stimuli and the brain response represents a complex research area. However, the use of mathematical models for this purpose is relatively unexplored. The present study investigates the effects of three different auditory stimuli on cerebral biopotentials by means of mathematical functions. The effects of acoustic stimuli (S1, S2, and S3) on cerebral activity were evaluated by electroencephalographic (EEG) recording on 21 subjects for 20 minutes of stimulation, with a 5-minute period of silence before and after stimulation. For the construction of the mathematical models used for the study of the EEG rhythms, we used the Box-Jenkins methodology. Characteristic mathematical models were obtained for the main frequency bands and were expressed by 2 constant functions, 8 first-degree functions, a second-degree function, a fourth-degree function, 6 recursive functions, and 4 periodic functions. The values obtained for the variance estimator are low, demonstrating that the obtained models are correct. The resulting mathematical models allow us to objectively compare the EEG response to the three stimuli, both between the stimuli itself and between each stimulus and the period before stimulation

Determination of sulfation pattern in brain glycosaminoglycans by chip-based electrospray ionization ion trap mass spectrometry

Chondroitin sulfate (CS) and dermatan sulfate (DS) glycosaminoglycans display variability of sulfation in their constituent disaccharide repeats during chain elongation. Since a large proportion of the extracellular matrix of the central nervous system (CNS) is composed of proteoglycans, CS/DS disaccharide degree and profile of sulfation play important roles in the functional diversity of neurons, brain development, and some of its pathological states. To investigate the sulfation pattern of CS/DS structures expressed in CNS, we introduced here a novel method based on an advanced system encompassing fully automated chip nanoelectrospray ionization (nanoESI) in the negative ion mode and high capacity ion trap multistage mass spectrometry (MS2 MS3) by collision-induced dissociation (CID). This method, introduced here for the first time in glycomics of brain glycosaminoglycans, was particularly applied to structural investigation of disaccharides obtained by β-elimination and digestion with chondroitin B and AC I lyase of hybrid CS/DS chains from wild-type mouse brain. Screening in the chip-MS mode of DS disaccharide fraction resulting after depolymerization with chondroitin B lyase revealed molecular ions assigned to monosulfated disaccharide species having a composition of 4,5-Δ-[IdoA-GalNAc]. By optimized CID MS2 MS3, fragment ions supporting the localization of sulfate ester group at C4 within GalNAc were produced. Chip ESI MS profiling of CS disaccharide fraction obtained by depolymerization of the same CS/DS chain using chondroitin AC I lyase indicated the occurrence of mono- and bisulfated 4,5-Δ-[GlcA-GalNAc]. The site of oversulfation was determined by MS2 MS3, which provided sequence patterns consistent with a rare GlcA-3-sulfate GalNAc-6-sulfate structural motif

Determination of ganglioside composition and structure in human brain hemangioma by chip-based nanoelectrospray ionization tandem mass spectrometry

We report here on a preliminary investigation of ganglioside composition and structure in human hemangioma, a benign tumor in the frontal cortex (HFC) in comparison to normal frontal cortex (NFC) tissue using for the first time advanced mass spectrometric methods based on fully automated chip-nanoelectrospray (nanoESI) high-capacity ion trap (HCT) and collision-induced dissociation (CID). The high ionization efficiency, sensitivity and reproducibility provided by the chip-nanoESI approach allowed for a reliable MS-based ganglioside comparative assay. Unlike NFC, ganglioside mixture extracted from HFC was found dominated by species of short glycan chains exhibiting lower overall sialic acid content. In HFC, only GT1 (d18:1/20:0), and GT3 (d18:1/25:1) polysialylated species were detected. Interestingly, none of these trisialylated forms was detected in NFC, suggesting that such components might selectively be associated with HFC. Unlike the case of previously investigated high malignancy gliosarcoma, in HFC one modified O-Ac-GD2 and one modified O-Ac-GM4 gangliosides were observed. This aspect suggests that these O-acetylated structures could be associated with cerebral tumors having reduced malignancy grade. Fragmentation analysis by CID in MS2 mode using as precursors the ions corresponding to GT1 (d18:1/20:0) and GD1 (d18:1/20:0) provided data corroborating for the first time the presence of the common GT1a and GT1b isomers and the incidence of unusual GT1c and GT1d glycoforms in brain hemangioma tumor

Computed Mass-Fragmentation Energy Profiles of Some Acetalized Monosaccharides for Identification in Mass Spectrometry

Our study found that quantum calculations can differentiate fragmentation energies into isomeric structures with asymmetric carbon atoms, such as those of acetalized monosaccharides. It was justified by the good results that have been published in recent years on the discrimination of structural isomers and diastereomers by correlating the calculated mass energy fragmentation profiles with their mass spectra. Based on the quantitative structure–fragmentation relationship (QSFR), this technique compares the intensities of primary ions from the experimental spectrum using the mass energy profiles calculated for the candidate structures. Maximum fit is obtained for the true structure. For a preliminary assessment of the accuracy of the identification of some di-O-isopropylidene monosaccharide diastereomers, we used fragmentation enthalpies (ΔfH) and Gibbs energies (ΔfG) as the energetic descriptors of fragmentation. Four quantum chemical methods were used: RM1, PM7, DFT ΔfH and DFT ΔfG. The mass energy database shows that the differences between the profiles of the isomeric candidate structures could be large enough to be distinguished from each other. This database allows the optimization of energy descriptors and quantum computing methods that can ensure the correct identification of these isomers

Rhoa/ROCK, mTOR and Secretome-Based Treatments for Ischemic Stroke: New Perspectives

Ischemic stroke triggers a complex cascade of cellular and molecular events leading to neuronal damage and tissue injury. This review explores the potential therapeutic avenues targeting cellular signaling pathways implicated in stroke pathophysiology. Specifically, it focuses on the articles that highlight the roles of RhoA/ROCK and mTOR signaling pathways in ischemic brain injury and their therapeutic implications. The RhoA/ROCK pathway modulates various cellular processes, including cytoskeletal dynamics and inflammation, while mTOR signaling regulates cell growth, proliferation, and autophagy. Preclinical studies have demonstrated the neuroprotective effects of targeting these pathways in stroke models, offering insights into potential treatment strategies. However, challenges such as off-target effects and the need for tissue-specific targeting remain. Furthermore, emerging evidence suggests the therapeutic potential of MSC secretome in stroke treatment, highlighting the importance of exploring alternative approaches. Future research directions include elucidating the precise mechanisms of action, optimizing treatment protocols, and translating preclinical findings into clinical practice for improved stroke outcomes

Neuropunk Revolution. Hacking Cognitive Systems towards Cyborgs 3.0

This work is dedicated to the review and perspective of the new direction that we call "Neuropunk revolution" resembling the cultural phenomenon of cyberpunk. This new phenomenon has its foundations in advances in neuromorphic technologies including memristive and bio-plausible simulations, BCI, and neurointerfaces as well as unconventional approaches to AI and computing in general. We present the review of the current state-of-the-art and our vision of near future development of scientific approaches and future technologies. We call the "Neuropunk revolution" the set of trends that in our view provide the necessary background for the new generation of approaches technologies to integrate the cybernetic objects with biological tissues in close loop system as well as robotic systems inspired by the biological processes again integrated with biological objects. We see bio-plausible simulations implemented by digital computers or spiking networks memristive hardware as promising bridge or middleware between digital and (neuro)biological domains