Molecular pathology associated with altered synaptic transcriptome in the dorsolateral prefrontal cortex of depressed subjects

Disrupted synaptic plasticity is the hallmark of major depressive disorder (MDD), with accompanying changes at the molecular and cellular levels. Often, the maladaptive molecular changes at the synapse are the result of global transcriptional reprogramming dictated by activity-dependent synaptic modulation. Thus far, no study has directly studied the transcriptome-wide expression changes locally at the synapse in MDD brain. Here, we have examined altered synaptic transcriptomics and their functional relevance in MDD with a focus on the dorsolateral prefrontal cortex (dlPFC). RNA was isolated from total fraction and purified synaptosomes of dlPFC from well-matched 15 non-psychiatric controls and 15 MDD subjects. Transcriptomic changes in synaptic and total fractions were detected by next-generation RNA-sequencing (NGS) and analyzed independently. The ratio of synaptic/total fraction was estimated to evaluate a shift in gene expression ratio in MDD subjects. Bioinformatics and network analyses were used to determine the biological relevance of transcriptomic changes in both total and synaptic fractions based on gene–gene network, gene ontology (GO), and pathway prediction algorithms. A total of 14,005 genes were detected in total fraction. A total of 104 genes were differentially regulated (73 upregulated and 31 downregulated) in MDD group based on 1.3-fold change threshold and p < 0.05 criteria. In synaptosomes, out of 13,236 detectable genes, 234 were upregulated and 60 were downregulated (>1.3-fold, p < 0.05). Several of these altered genes were validated independently by a quantitative polymerase chain reaction (qPCR). GO revealed an association with immune system processes and cell death. Moreover, a cluster of genes belonged to the nervous system development, and psychological disorders were discovered using gene–gene network analysis. The ratio of synaptic/total fraction showed a shift in expression of 119 genes in MDD subjects, which were primarily associated with neuroinflammation, interleukin signaling, and cell death. Our results suggest not only large-scale gene expression changes in synaptosomes, but also a shift in the expression of genes from total to synaptic fractions of dlPFC of MDD subjects with their potential role in immunomodulation and cell death. Our findings provide new insights into the understanding of transcriptomic regulation at the synapse and their possible role in MDD pathogenesis.

Analgesia additive interaction between tadalafil and morphine in an experimental animal model

Since both morphine and tadalafil have been proven to exert some of their analgesic activity through modulation of the NO–cGMP pathway, the aim of the current study is to evaluate the pharmacologic interaction between tadalafil and morphine to decrease the dose of morphine and subsequently its side effects. The assessment was carried out through isobolographic analysis relative to ED50s of both morphine and tadalafil obtained by tail-flick test on BALB/c mice. Morphine and tadalafil ED50s calculated from the dose–response curves were 8303 and 2080 μg/kg, respectively. The experimental ED50 values of morphine and tadalafil in their mixture were 4800 and 1210 μg/kg, respectively. Those results showed an additive interaction between morphine and tadalafil presented by a total fraction value for the mixture of 1160 μg/kg. This outcome can be interpreted by the fact that both drugs share common pathways, namely, NO–cGMP and opioid receptors. As a conclusion, the morphine and tadalafil combination showed an additive effect against acute pain, which is mediated through the central nervous system, thus providing a rationale for combining them to decrease morphine dose and thus minimizing its side effects.

The Continuous Sampling Plan for Two Production Lines: The CSP-2L

This paper presents the CSP-2L continuous sampling plan, which is designed for product inspectionon two independent production lines at the same time. The purpose of the CSP-2L is to improve the CSP-1-2Lin order to reduce the number of defective products that have passed without being inspected during thetemporary inspection stop, so the quality of the products is better. Therefore, if the manufacturer who uses theCSP-2L plan to inspect the production lines then resulting in higher quality of the products than the CSP-1-2L.This presentation includes the product inspection procedures and the formulas for performance measures suchas average total fraction inspected (ATFI), average total outgoing quality (ATOQ), and average total outgoingquality limit (ATOQL) which are carried out using a Markov chain. The formulas for performance measures ofthe CSP-2L have been tested to be accurate. When defined, the probability of a unit produced by the processbeing nonconforming of line 1 and line 2 are equal (p1 = p2 = p = 0.005, 0.015 and 0.035), the clearance numberof line 1 and line 2 are equal (i1 = i2 = 10, 20, 30, 40 and 50), the sampling fraction of line 1 and line 2 are equal(f1 = f2 =12and13) and the number of units to be found when inspection of line 1 and line 2 are in the phaseof sampling inspection at the same time (m = i1 and 2i1). Moreover, the ATOQ values from the CSP-2L and theCSP-1-2L plans were compared. The results showed that, the formulas for performance measures are accurateand in the case of p, the levels are low and moderate, the ATOQ of the CSP-2L are less than those of theCSP-1-2L in all cases. But in the case of p is at a high level, the ATOQ of the CSP-2L is less than those of theCSP-1-2L for some cases of i.

Bi-stability of SUDR+K model of epidemics and test kits applied to COVID-19

Motivated by the many diverse responses of different countries to the COVID-19 emergency, here we develop a toy model of the dependence of the epidemics spreading on the availability of tests for disease. Our model, that we call SUDR+K, grounds on the usual SIR model, with the difference of splitting the total fraction of infected individuals in two components: patients that are still undetected and patients that have been already detected through tests. Moreover, we assume that available tests increase at a constant rate from the beginning of epidemics but are consumed to detect infected individuals. Strikingly, we find a bi-stable behavior between a phase with a giant fraction of infected and a phase with a very small fraction. We show that the separation between these two regimes is governed by a match between the rate of testing and a rate of infection spread at given time. We also show that the existence of two phases does not depend on the mathematical choice of the form of the term describing the rate at which undetected individuals are tested and detected. Presented research implies that a vigorous early testing activity, before the epidemics enters its giant phase, can potentially keep epidemics under control, and that even a very small change of the testing rate around the bi-stable point can determine a fluctuation of the size of the whole epidemics of various orders of magnitude. For the real application of realistic model to ongoing epidemics, we would gladly collaborate with field epidemiologists in order to develop quantitative models of testing process.

Fatty acid composition in trochophores of mussel Mytilus galloprovincialis grown under contamination with polychlorinated biphenyls

Status of Mytilus galloprovincialis populations in the natural habitat is known to directly depend on development of Black Sea mussel at all its stages, including initial stages of larval ontogenesis, which are very sensitive to environmental pollution. Organic pollutants adversely affect mussel larvae by inhibiting their growth and development. Patterns of mussel reproduction are well studied, which makes it possible to obtain larvae from artificially fertilized eggs of this mollusc species in controlled laboratory conditions. In this work, the fatty acid composition of M. galloprovincialis larvae at the trochophore stage on the 3rd day in the control experiment and under artificial contamination with polychlorinated biphenyls (PCBs) in different concentrations is studied for the first time. The fatty acid composition of total lipids in the biomass of larvae obtained on the 3rd day of the experiment was studied by means of gas chromatography – mass spectrometry. Totally, 14 fatty acids were identified in the samples; 59 % of them were saturated fatty acids, 24 % were monounsaturated fatty acids, and 17 % were polyunsaturated fatty acids. Statistical analysis was performed using Statistical Toolbox of MATLAB software (version 8.2). The totals of monounsaturated and polyunsaturated fatty acids significantly differed in lipids of M. galloprovincialis trochophores in the experiment with different PCB concentrations. The totals of saturated fatty acids did not significantly differ. The major saturated fatty acids in all mussel trochophores studied were palmitic (C16:0) and stearic (C18:0) acids. Their concentration did not significantly change under the exposure to PCBs. The main monounsaturated fatty acids were oleic (C18:1ω9), palmitoleic (C16:1ω7), and vaccenic (C18:1ω7) acids. The fraction of monounsaturated fatty acids was twice as low when exposed to the PCB concentrations 0.1 and 1.0 μg·L−1. However, when the PCB concentration was 10 μg·L−1, the total of these acids did not differ from the control. Among polyunsaturated fatty acids having biological essentiality, it was possible to identify arachidonic (C20:4ω6), eicosapentaenoic (C20:5ω3), and docosahexaenoic (C22:6ω3) acids. The total fraction of omega-3 and omega-6 acids in mussel larvae in the control did not exceed 12.8 %. With an increase of the PCB concentration in the growth medium 0.1 to 1.0 μg·L−1, the fraction of polyunsaturated fatty acids increased 2.5-fold. At the PCB concentration 10 μg·L−1 and in the sample with pure acetone added, the total fraction of polyunsaturated fatty acids was comparable with that in the control. The results of the study indicate that fatty acid response is the highest when the medium is exposed to the PCB concentrations ranging 0.1 to 1.0 μg·L−1. At the PCB concentrations equal to 10 μg·L−1 or higher, biochemical processes in larvae seem to slow down. The results of this study will contribute to a better understanding of biochemical rearrangements that allow molluscs at larval developmental stages to adapt to environmental pollution with organic xenobiotics.

Effect of the total fraction of Bacillus subtilis GM5 lipopeptides on the growth parameters and formation of the bacterial microbiota of broiler chickens

Intestinal microbes play a key role in the energy metabolism of broiler chickens, participate in the development of the gastrointestinal tract, including the regulation of intestinal epithelial proliferation, vitamin synthesis and ion absorption, fermentation of carbohydrates and proteins, biotransformation of bile acids, protection from pathogens and modulation of the immune system. Metagenomic analysis of the gastrointestinal microbiota allows to find approaches to improve the growth and productivity of chickens by introducing a diet based on beneficial bacterial strains or their secondary metabolites. In this paper, we studied the effect of the total fraction of Bacillus subtilis GM5 lipopeptides on the growth parameters and formation of bacterial communities in the caecum of cross Cobb 500 broiler chickens. It was found that the addition of bacillary lipopeptides to the feed resulted in an increase in chicken weight by 12.7% and a decrease in feed conversion by 6.36% compared to the control (P < 0.05). It was also shown that the introduction of a feed additive in the form of a lipopeptide fraction modulates the structure of the bacterial microbiota of the caecum of chickens. Thus, the proportion of classes Bacteroidia, Negativicutes, Betaproteobacteria, Epsilonproteobacteria, Deltaproteobacteria, Synergistia in the caecal microbiota of chickens of the experimental group increases, and the proportion of Clostridia, Methanobacteria decreases in comparison with the control.

Фазовые превращения в оксидах железа под действием микроволнового излучения

It is shown that microwave radiation induces structure changes and, consequently, magnetic phase transitions in iron oxide alpha-Fe2O3. We subjected finely dispersed partially amorphized particles of iron oxide Fe2O3 to 10-minute-long microwave field treatment in a humid air environment. This resulted in a reduction of the hematite crystalline phase by 40%. At the same time the total fraction of crystalline components increased due to the creation of a new ferromagnetic modification which is maghemite alpha-Fe2O3. The original antiferromagnetic samples and the finial ferrimagnetic batches were powders composed of spherical particles with similar values of the area of a coherent X-ray scattering area (40-60 nm).

Do zealots increase or decrease the polarization of social networks?

Zealots are the vertices in a social network who do not change their opinions under social pressure and are crucial to the study of opinion dynamics on complex networks. In this article, we study the effect of zealots on the polarization dynamics of a deterministic majority rule model using the configuration model as a substrate. To this end, we propose a novel quantifier, called ‘correlated polarization’, for measuring the amount of polarization in the network when vertices can exist in two opposite states. The quantifier takes into account not only the fraction of vertices with each opinion but also how they are connected to each other. We then show that the presence of zealots does not have a fixed effect on the polarization, and can change it in positive, negative or neutral way depending upon their topological characteristics like degree, their total fraction in the network, density and degree heterogeneity of the network and the type of initial conditions of the dynamics. Our results particularly highlight the importance of the role played by the initial conditions in drifting the polarization towards lower or higher values as the total number of zealots is increased.

EFFECT OF CARBON TETRACHLORIDE ON THE LIPID COMPOSITION OF RAT’S BLOOD AND ITS CORRECTION BY NATURAL HERBAL POLYPHENOLS

The possibility of blood lipid metabolism recovery in rats after intoxication with carbon tetrachloride using Kalifen® extract from viburnum and the comparison preparation Legalon® has been shown. The experiments were conducted on male white rats of the Wistar line in standard vivarium conditions. Animals were divided into 5 groups: 1st group - control; 2nd group - introduction of carbon tetrachloride for 4 days; 3rd - introduction of carbon tetrachloride for 4 days followed by cancellation within 7 days; 4th group - introduction of carbon tetrachloride for 4 days followed by introduction of Kalifen® for 7 days; 5th - introduction of carbon tetrachloride for 4 days followed by introduction of Legalon® for 7 days. It has been found that intoxication with carbon tetrachloride was accompanied by the development of severe hypercholesterolemia, as well as the increase in the content of the total fraction of lipoproteins of very low density with reducing the concentration of high density lipoproteins in the serum. There were a decrease in the main structural phospholipids and metabolically active fractions, an increase in the number of triacylglycerols, free fatty acids, and lysophospholipids. During the cancellation of carbon tetrachloride within 7 days lipid metabolism indicators did not recover, indicating that free-radical reactions occur even in the absence of the toxicant. The introduction of Kalifen® and Legalon® in animals under the conditions of the withdrawal of the toxicant contributed to the recovery of the studied parameters to control values, but the most pronounced effect has been manifested using Kalifen®.

ВЗАЄМОЗВ’ЯЗОК СКЛАДУ АМНІОТИЧНОЇ РІДИНИ ТА «ЗРІЛОСТІ» СУРФАКТАНТНОЇ СИСТЕМИ ЛЕГЕНЬ У НОВОНАРОДЖЕНИХ КЛІНІЧНО ЗДОРОВИХ ТЕЛЯТ

Наведено дані про амінокислотний склад і взаємо-зв’язок амніотичної рідини та «зрілості» сурфакта-нтної системи легень у новонароджених клінічноздорових телят. Встановлено, що «зрілість» сурфа-ктантної системи легень була виявлена у 40,0 % те-лят від корів-первісток. Вона була менша у 1,80–1,70рази (р<0,01) у телят, отриманих від корів другого-третього отелення. Сумарна фракція фосфоліпідівамніотичної рідини була в 1,38 разу більшою, ніж утварин, народжених у стані гіпоксії (р<0,01). Зага-льний вміст амінокислот у навколоплідній рідині клі-нічно здорових новонароджених телят становив330,39±7,52 нмоль/0,1 мл. Вміст вільних амінокислотзнаходиться на рівіні 222,97±3,82 нмоль/0,1 мл. Із нихна частку незамінних амінокислот припадало38,40±1,32 нмоль/0,1 мл, а замінних – 184,57±3,44нмоль/0,1 мл. Data are provided in article about aminokislotny structure and interrelation of amniotic liquid and "maturity" of surfaktantny system of lungs at newborn clinically healthy calfs. It is established that "maturity" of surfaktantny system of lungs was installed at 40,0% of calfs of firstcalf heifers. It was 1,80-1,70 times less (р<0,01) at calfs received from cows of the second - the third time. The total fraction phospholipid was 1,38 times higher than amniotic liquid, than at animals given rise in a condition of a hypoxia (р<0,01). The general content of amino acids in amniotic liquid of clinically healthy newborn calfs makes 330,39±7,52 nmol / 0,1 ml. The content of free amino acids was at the level 222,97±3,82 nmol / 0,1 of ml. From them, it was the share of part of irreplaceable amino acids 38,40±1,32 nmol / 0,1 to ml, and replaceable – 184,57±3,44 nmol / 0,1 to ml.