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Abstract Background The goal of this study was to assess the effect of melatonin on blood redox systems in mice simultaneously exposed to ethanol and low-dose lipopolysaccharide (LPS). Methods Oxidative stress parameters were assessed in eight groups: untreated control, melatonin (10 mg kg−1, 10 days), LPS (injected once intraperitoneally at a dose of 150 μg per mouse), LPS with previous melatonin treatment, acute ethanol-induced stress (AES, 0.75 g kg−1 per day, 10 days), AES with previous melatonin treatment, LPS- and AES-induced toxicity, and melatonin treatment. Results Both ethanol and LPS induced oxidative stress. The combination of these two factors was even more toxic to the organism. Melatonin stabilized erythrocyte membranes and decreased the high level of free radical oxidation at the initial and final stages. Furthermore, melatonin limited protein damage through maintenance in the functional ability of the blood redox system to counteract pathological conditions. Conclusions Melatonin limited the negative effects associated with alcohol consumption and low-intensity inflammation.

AbstractBoth human and animal studies indicate that the dentate gyrus (DG) of the hippocampus is highly exploited by drug and alcohol abuse. Yet, it is poorly understood how DG dysfunction affects addiction-related behaviors. Here, we used an animal model of alcohol use disorder (AUD) in automated IntelliCages and performed local genetic manipulation to investigate how synaptic transmission in the dorsal DG (dDG) affects alcohol-related behaviors. We show that a cue light induces potentiation-like plasticity of dDG synapses in alcohol-naive mice. This process is impaired in mice trained to drink alcohol. Acamprosate (ACA), a drug that reduces alcohol relapse, rescues the impairment of dDG synaptic transmission in alcohol mice. A molecular manipulation that reduces dDG synaptic AMPAR and NMDAR levels increases impulsive alcohol seeking during cue relapse (CR) in alcohol mice but does not affect alcohol reward, motivation or craving. These findings suggest that hindered dDG synaptic transmission specifically underlies impulsive alcohol seeking induced by alcohol cues, a core symptom of AUD.

The paper presents research on the electromagnetic hazards related to the flow of electric currents throughout the bodies of employees using portable radios. The values often exceed established limits, which may lead to potential dysfunctions of the body and affect the safety of performed professional duties. The measurements of the electric field (E-field) distribution of a typical commercial portable radio, the limb contact current calculations, and the computer simulations determining a specific absorption rate (SAR) were supplemented with pilot neurophysiological tests. The assessment indicated a large spatial variability of the E-field strength around the devices. The head of the operator and the hand holding the radio were often in the electromagnetic field (EMF), which exceeded the established limits. The calculated SAR values ranged within the permitted limits. The conducted neurophysiological tests showed no effects of EMF exposure in comparison to the control group. The assessment of exposure to the EMF using a portable radio is initially performed by analyzing external measures: both computer simulations and measurements of workers’ limb currents. The SAR values exclude thermal effects; however, they do not eliminate potential neuromuscular effects. More neurophysiological tests are needed to obtain a broader picture of possible health effects.

Xanthone derivatives constitute an interesting and widely studied group of compounds, both in terms of the activity of naturally occurring plant ingredients and as a scaffold with high biological activity potential for medicinal chemists. This group of compounds has already been the subject of reviews. However, our purpose was to prepare a publication for medicinal chemists to have a clear overview of anticancer activity, particularly in central nervous system cancer glioblastoma, and to be able to compare their new achievements to the anticancer activity that has already been found in this group. An integral part of the work is a tabular summary of the literature results of antineoplastic activity (e.g., IC50 values) for xanthone derivatives in various types of in vitro viability assays.

AbstractWith the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites.

Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts.

Despite scientific and clinical advances, stroke is still considered one of the main causes of disability, including gait disorders. The search for more effective methods of gait re-education in post-stroke patients is one of the most important issues in contemporary neurorehabilitation. In this paper, we propose a transformation of the feature space and definition of class labels in the post-stroke gait problem to more efficiently study related phenomena and assess gait faster. Clustering is used to define two class labels (improvement and recurrence) in the data labeling process. The proposed approach was tested on a real-world dataset consisting of 50 patients (male and female, aged 49–82 years) after ischemic stroke who participated in a gait rehabilitation program. Gait in the study was described using speed, cadence, and stride length and their normalized values. Ten treatment sessions (10 therapy days) were conducted over two weeks (10 working days). The same specialist took measurements, and hence inter-rater reliability can be neglected. Machine learning methods, support vector machine and quadratic discriminant analysis were used to classify post-stroke gait for three cases with different class labels. The proposed novel approach, characterized by its speed of execution and accuracy of classification, may be helpful for screening, better targeting, and rehabilitation monitoring. The proposed approach minimizes clinical testing and supports the work of physicians, physiotherapists, and diagnosticians.