Репозиторий Университета

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 The Authors Genome-wide screening approaches identified the cell adhesion molecule Cadherin-13 (CDH13) as a risk factor for neurodevelopmental disorders, nevertheless the contribution of CDH13 to the disease mechanism remains obscure. CDH13 is involved in neurite outgrowth and axon guidance during early brain development and we previously provided evidence that constitutive CDH13 deficiency influences the formation of the raphe serotonin (5-HT) system by modifying neuron-radial glia interaction. Here, we dissect the specific impact of CDH13 on 5-HT system development and function using a 5-HT neuron-specific Cdh13 knockout mouse model (conditional Cdh13 knockout, Cdh13 cKO). Our results show that exclusive inactivation of CDH13 in 5-HT neurons selectively increases 5-HT neuron density in the embryonic dorsal raphe, with persistence into adulthood, and serotonergic innervation of the developing prefrontal cortex. At the behavioral level, adult Cdh13 cKO mice display delayed acquisition of several learning tasks and a subtle impulsive-like phenotype, with decreased latency in a sociability paradigm alongside with deficits in visuospatial memory. Anxiety-related traits were not observed in Cdh13 cKO mice. Our findings further support the critical role of CDH13 in the development of dorsal raphe 5-HT circuitries, a mechanism that may underlie specific clinical features observed in neurodevelopmental disorders.

© 2020 Elsevier Ltd Manganese (Mn) is the twelfth most abundant element on the earth and an essential metal to human health. Mn is present at low concentrations in a variety of dietary sources, which provides adequate Mn content to sustain support various physiological processes in the human body. However, with the rise of Mn utility in a variety of industries, there is an increased risk of overexposure to this transition metal, which can have neurotoxic consequences. This risk includes occupational exposure of Mn to workers as well as overall increased Mn pollution affecting the general public. Here, we review exposure due to air pollution and inhalation in industrial settings; we also delve into the toxic effects of manganese on the brain such as oxidative stress, inflammatory response and transporter dysregulation. Additionally, we summarize current understandings underlying the mechanisms of Mn toxicity.

© 2020 Elsevier Ltd Manganese (Mn) is the twelfth most abundant element on the earth and an essential metal to human health. Mn is present at low concentrations in a variety of dietary sources, which provides adequate Mn content to sustain support various physiological processes in the human body. However, with the rise of Mn utility in a variety of industries, there is an increased risk of overexposure to this transition metal, which can have neurotoxic consequences. This risk includes occupational exposure of Mn to workers as well as overall increased Mn pollution affecting the general public. Here, we review exposure due to air pollution and inhalation in industrial settings; we also delve into the toxic effects of manganese on the brain such as oxidative stress, inflammatory response and transporter dysregulation. Additionally, we summarize current understandings underlying the mechanisms of Mn toxicity.

© 2020 Elsevier Ltd Manganese (Mn) is the twelfth most abundant element on the earth and an essential metal to human health. Mn is present at low concentrations in a variety of dietary sources, which provides adequate Mn content to sustain support various physiological processes in the human body. However, with the rise of Mn utility in a variety of industries, there is an increased risk of overexposure to this transition metal, which can have neurotoxic consequences. This risk includes occupational exposure of Mn to workers as well as overall increased Mn pollution affecting the general public. Here, we review exposure due to air pollution and inhalation in industrial settings; we also delve into the toxic effects of manganese on the brain such as oxidative stress, inflammatory response and transporter dysregulation. Additionally, we summarize current understandings underlying the mechanisms of Mn toxicity.

© 2020 Background: Miramistin is a widely used antiseptic, disinfectant and preservative, and one of the most popular antimicrobial agents on pharmaceutical market of the Russian Federation (http://www.dsm.ru/en/news/385/). However, there is a lack of reported systematic data on antibacterial efficacy of this agent obtained in accordance with the international standards. Aim: This paper represents a systematic study of antibacterial properties of miramistin. Another objective of this work is to evaluate and compare the exploratory performance of in vitro and in vivo protocols of antiseptics’ efficacy testing using miramistin as the reference antiseptic. Methods: Antibacterial activity of 0.1% and 0.2% aqueous solutions of miramistin against two museum strains of S. aureus (ATCC 209p) and E. coli (CDC F-50) was studied. Three standard in vitro laboratory tests (microdilution test, suspension test, and metal surface test), and one in vivo test (on rat's skin) were used. The study was conducted in accordance with the international regulatory documents. Results: Miramistin showed high bactericidal activity against the studied bacterial pathogens in the standard in vitro tests. Thus, in the microdilution test it showed expressed activity against S. aureus (MIC 8 μg/ml, MBC 16 μg/ml) and E. coli (MIC 32 μg/ml, MBC 128 μg/ml). In the suspension test, miramistin decreased the amount of colony forming units by at least 6 log10 units for S. aureus, and by at least 4.5 log10 units for E. coli. Transition to the metal surface test led to significant decrease of antibacterial activity by 1–3 log10 units as compared to the suspension test. Further dramatic reduction of antiseptic activity (by 3–4 log10 units) was observed in in vivo rat skin test. Addition of a protein contaminant (bovine serum albumin) led to a general decrease in the effectiveness of miramistin against the test pathogens (typically, by 1–2 log10 units). An interesting effect of exposure time-dependent reversal of miramistin's specificity to the studied Gram-positive S. aureus and the Gram-negative E. coli organisms was observed in the metal surface test. Conclusions: The results of this work provide systematic data on antibacterial efficacy of miramistin. They also underscore the need in relevant in vivo models for evaluation of antiseptics' efficacy. While the existing in vitro methods can be successfully applied at the discovery stages, it is necessary to use more realistic in vivo models at more advanced development stages. The observed selectivity reversal effect should be taken into account when carrying out the antiseptics’ efficacy testing and surface disinfection procedures.

© 2020 Background: Miramistin is a widely used antiseptic, disinfectant and preservative, and one of the most popular antimicrobial agents on pharmaceutical market of the Russian Federation (http://www.dsm.ru/en/news/385/). However, there is a lack of reported systematic data on antibacterial efficacy of this agent obtained in accordance with the international standards. Aim: This paper represents a systematic study of antibacterial properties of miramistin. Another objective of this work is to evaluate and compare the exploratory performance of in vitro and in vivo protocols of antiseptics’ efficacy testing using miramistin as the reference antiseptic. Methods: Antibacterial activity of 0.1% and 0.2% aqueous solutions of miramistin against two museum strains of S. aureus (ATCC 209p) and E. coli (CDC F-50) was studied. Three standard in vitro laboratory tests (microdilution test, suspension test, and metal surface test), and one in vivo test (on rat's skin) were used. The study was conducted in accordance with the international regulatory documents. Results: Miramistin showed high bactericidal activity against the studied bacterial pathogens in the standard in vitro tests. Thus, in the microdilution test it showed expressed activity against S. aureus (MIC 8 μg/ml, MBC 16 μg/ml) and E. coli (MIC 32 μg/ml, MBC 128 μg/ml). In the suspension test, miramistin decreased the amount of colony forming units by at least 6 log10 units for S. aureus, and by at least 4.5 log10 units for E. coli. Transition to the metal surface test led to significant decrease of antibacterial activity by 1–3 log10 units as compared to the suspension test. Further dramatic reduction of antiseptic activity (by 3–4 log10 units) was observed in in vivo rat skin test. Addition of a protein contaminant (bovine serum albumin) led to a general decrease in the effectiveness of miramistin against the test pathogens (typically, by 1–2 log10 units). An interesting effect of exposure time-dependent reversal of miramistin's specificity to the studied Gram-positive S. aureus and the Gram-negative E. coli organisms was observed in the metal surface test. Conclusions: The results of this work provide systematic data on antibacterial efficacy of miramistin. They also underscore the need in relevant in vivo models for evaluation of antiseptics' efficacy. While the existing in vitro methods can be successfully applied at the discovery stages, it is necessary to use more realistic in vivo models at more advanced development stages. The observed selectivity reversal effect should be taken into account when carrying out the antiseptics’ efficacy testing and surface disinfection procedures.

© 2020 Background: Miramistin is a widely used antiseptic, disinfectant and preservative, and one of the most popular antimicrobial agents on pharmaceutical market of the Russian Federation (http://www.dsm.ru/en/news/385/). However, there is a lack of reported systematic data on antibacterial efficacy of this agent obtained in accordance with the international standards. Aim: This paper represents a systematic study of antibacterial properties of miramistin. Another objective of this work is to evaluate and compare the exploratory performance of in vitro and in vivo protocols of antiseptics’ efficacy testing using miramistin as the reference antiseptic. Methods: Antibacterial activity of 0.1% and 0.2% aqueous solutions of miramistin against two museum strains of S. aureus (ATCC 209p) and E. coli (CDC F-50) was studied. Three standard in vitro laboratory tests (microdilution test, suspension test, and metal surface test), and one in vivo test (on rat's skin) were used. The study was conducted in accordance with the international regulatory documents. Results: Miramistin showed high bactericidal activity against the studied bacterial pathogens in the standard in vitro tests. Thus, in the microdilution test it showed expressed activity against S. aureus (MIC 8 μg/ml, MBC 16 μg/ml) and E. coli (MIC 32 μg/ml, MBC 128 μg/ml). In the suspension test, miramistin decreased the amount of colony forming units by at least 6 log10 units for S. aureus, and by at least 4.5 log10 units for E. coli. Transition to the metal surface test led to significant decrease of antibacterial activity by 1–3 log10 units as compared to the suspension test. Further dramatic reduction of antiseptic activity (by 3–4 log10 units) was observed in in vivo rat skin test. Addition of a protein contaminant (bovine serum albumin) led to a general decrease in the effectiveness of miramistin against the test pathogens (typically, by 1–2 log10 units). An interesting effect of exposure time-dependent reversal of miramistin's specificity to the studied Gram-positive S. aureus and the Gram-negative E. coli organisms was observed in the metal surface test. Conclusions: The results of this work provide systematic data on antibacterial efficacy of miramistin. They also underscore the need in relevant in vivo models for evaluation of antiseptics' efficacy. While the existing in vitro methods can be successfully applied at the discovery stages, it is necessary to use more realistic in vivo models at more advanced development stages. The observed selectivity reversal effect should be taken into account when carrying out the antiseptics’ efficacy testing and surface disinfection procedures.

© 2020 Elsevier B.V. The chemical and biochemical analysis of bodily fluids after death is an important thanatochemical approach to assess the cause and time since death. Vitreous humor (VH) has been used as a biofluid for forensic purposes since the 1960s. Due to its established relevance in toxicology, a literature review highlighting the use of VH with an emphasis on endogenous compounds has not yet been undertaken. VH is a chemically complex aqueous solution of carbohydrates, proteins, electrolytes and other small molecules present in living organisms; this biofluid is useful tool for its isolated environment, preserved from bacterial contamination, decomposition, autolysis, and metabolic reactions. The post-mortem analysis of VH provides an important tool for the estimation of the post-mortem interval (PMI), which can be helpful in determining the cause of death. Consequently, the present review evaluates the recent chemical and biochemical advances with particular importance on the endogenous compounds present at the time of death and their modification over time, which are valuable for the PMI prediction and to identify the cause of death.

© 2020 Elsevier B.V. The chemical and biochemical analysis of bodily fluids after death is an important thanatochemical approach to assess the cause and time since death. Vitreous humor (VH) has been used as a biofluid for forensic purposes since the 1960s. Due to its established relevance in toxicology, a literature review highlighting the use of VH with an emphasis on endogenous compounds has not yet been undertaken. VH is a chemically complex aqueous solution of carbohydrates, proteins, electrolytes and other small molecules present in living organisms; this biofluid is useful tool for its isolated environment, preserved from bacterial contamination, decomposition, autolysis, and metabolic reactions. The post-mortem analysis of VH provides an important tool for the estimation of the post-mortem interval (PMI), which can be helpful in determining the cause of death. Consequently, the present review evaluates the recent chemical and biochemical advances with particular importance on the endogenous compounds present at the time of death and their modification over time, which are valuable for the PMI prediction and to identify the cause of death.

© 2019 Elsevier B.V. The present study presents an attempt to modify the surface properties of macroporous resins (MRs) in order to improve anthocyanin adsorption and desorption from Pyrus communis var Starkrimson fruit peel extract. A number of MRs were tested to optimise the ultrasonic-assisted adsorption (UAA) conditions; including ultrasonic power (100–400 W), resin-to-extract ratio (1–3 g/50 mL) and temperature (20–40 °C). Similarly, varying ultrasonic-assisted desorption (UAD) conditions were optimised; including ultrasonic power (200–600 W), resin-to-solvent ratio (1–4 g/50 mL), ethanol concentration (60–90% v/v) and temperature (20–40 °C). The Amberlyst 15 (H) cationic resin was found to be superior to the other tested resins. The maximum adsorption capacity (659 µg/g) of cyanidin 3-galactoside (Cy 3-gal) was achieved under the optimised UAA conditions (400 W, 20 °C and 1 g/50 mL), while 616 µg/g of Cy 3-gal was recovered under the optimised UAD conditions (582 W, 1 g/50 mL, 60% and 20 °C). Moreover, titratable-acid and total-sugar contents were found to be significantly lower under UAA than under conventional-assisted adsorption (CAA). ANOVA revealed that process factors had significant effects on the Cy 3-gal purification, as depicted by their linear, quadratic and interactive effects. While anthocyanin adsorption was found to be significantly improved at lower ultrasonic power, higher power promoted the desorption process. Adsorption under optimized UAA conditions followed pseudo second-order kinetics and multilayer adsorption (Freundlich isotherm) onto the Amberlyst 15 (H) resin surface was observed. The particle-size distribution curve and scanning electron microscopic images also revealed higher resin-surface roughness, peeling and the appearance of pores on the surface under ultrasonication. This is the first study to use ultrasonication to modify a cationic exchange resin for the improvement of Cy 3-gal purification from a fruit extract. This study can recommend the use of ultrasonication as a low-cost green technique that can improve macroporous resin characteristics for better purification of compounds from an extract.

© 2019 Elsevier B.V. The present study presents an attempt to modify the surface properties of macroporous resins (MRs) in order to improve anthocyanin adsorption and desorption from Pyrus communis var Starkrimson fruit peel extract. A number of MRs were tested to optimise the ultrasonic-assisted adsorption (UAA) conditions; including ultrasonic power (100–400 W), resin-to-extract ratio (1–3 g/50 mL) and temperature (20–40 °C). Similarly, varying ultrasonic-assisted desorption (UAD) conditions were optimised; including ultrasonic power (200–600 W), resin-to-solvent ratio (1–4 g/50 mL), ethanol concentration (60–90% v/v) and temperature (20–40 °C). The Amberlyst 15 (H) cationic resin was found to be superior to the other tested resins. The maximum adsorption capacity (659 µg/g) of cyanidin 3-galactoside (Cy 3-gal) was achieved under the optimised UAA conditions (400 W, 20 °C and 1 g/50 mL), while 616 µg/g of Cy 3-gal was recovered under the optimised UAD conditions (582 W, 1 g/50 mL, 60% and 20 °C). Moreover, titratable-acid and total-sugar contents were found to be significantly lower under UAA than under conventional-assisted adsorption (CAA). ANOVA revealed that process factors had significant effects on the Cy 3-gal purification, as depicted by their linear, quadratic and interactive effects. While anthocyanin adsorption was found to be significantly improved at lower ultrasonic power, higher power promoted the desorption process. Adsorption under optimized UAA conditions followed pseudo second-order kinetics and multilayer adsorption (Freundlich isotherm) onto the Amberlyst 15 (H) resin surface was observed. The particle-size distribution curve and scanning electron microscopic images also revealed higher resin-surface roughness, peeling and the appearance of pores on the surface under ultrasonication. This is the first study to use ultrasonication to modify a cationic exchange resin for the improvement of Cy 3-gal purification from a fruit extract. This study can recommend the use of ultrasonication as a low-cost green technique that can improve macroporous resin characteristics for better purification of compounds from an extract.

© 2020 Elsevier B.V. Herein four modified polymers were prepared from readily available addition poly(5-vinyl-2-norbornene) (PVNB) and their gas-transport properties were studied in detail. Hydrogenation, epoxidation, cyclopropanation and thiol-en reactions were chosen for the modifications of PVNB. Hydrogenation of PVNB was performed using p-toluenesulfonyl hydrazide. Epoxidation of PVNB was realized employing m-chloroperoxybenzoic acid. Cyclopropanation of PVNB was carried out using diazomethane in the presence of a Pd-catalyst. For thiol-en reaction, thioacetic acid was applied as the source of a thiol and AIBN as an initiator. All listed modifications were performed in high yields (≥80%) without the destruction of polymer main chains. The degree of functionalizations was up to 99%. The influence of these modifications on the properties of the resulting polymers was evaluated. Cyclopropanation and hydrogenation of PVNB led to an enhancement of gas permeability with minimal decrease in selectivity, while epoxidation or thioacetylation gave a substantial increase in CO2/N2 selectivity with decrease in permeability. The modified polymers with polar side-groups exhibited attractive selectivities for CO2/N2, CO2/CH4 and H2/N2 gas separations.

© 2019 Elsevier B.V. The α-Fe core/PrDy-FeCo-B(48 at.%)α-Fe(52 at.%) shell and GdPrDy(FeCo)B microwires were grown by pendant drop melt (PDM) extraction technique. Single core–shell microwires of ~80–100 μm diameter and 2–20 mm length manifest rectangular hysteresis loops corresponding to ~100 Oe switching magnetic fields. Bistability of the microwires relates to single domain state of the α-Fe inner core revealed by scanning electron microscopy (SEM). Rare-earth amorphous PrDy-FeCo-B shell of the microwire scanned by magnetic force microscope (MFM) possesses magnetization reversal nuclei corresponding to the α-Fe inclusions. Interwire magnetic dipole interaction and scattering of microwire size change shape of the magnetic hysteresis loop and increase coercive field up to 983 Oe, in chaotic ensembles of the core–shell microwires. The GdPrDy(FeCo)B microwires of the same sizes with no Fe core possess “butterfly” type of the hysteresis loop of high coercivity ~20 kOe.

© 2019 Elsevier Ltd The lens capsule, a thin specialized basement membrane that encloses the crystalline lens, is essential for both the structural and biomechanical integrity of the lens. Knowing the mechanical properties of the lens capsule is important for understanding its physiological functioning, role in accommodation, age-related changes, and for providing a better treatment of a cataract. In this review, we have described the techniques used for the lens capsule biomechanical testing on the macro- and microscale and summarized the current knowledge about its mechanical properties.

© 2019 Elsevier B.V. Background: A large number of systemic diseases can be linked to oral candida pathogenicity. The global trend of invasive candidiasis has increased progressively and is often accentuated by increasing Candida albicans resistance to the most common antifungal medications. Photodynamic therapy (PDT) is a promising therapeutic approach for oral microbial infections. A new formulation of 5-aminolevulinic acid (5%ALA) in a thermosetting gel (t) (5%ALA-PTt) was patented and recently has become available on the market. However, its antimicrobial properties, whether mediated or not by PDT, are not yet known. In this work we characterised them. Methods: We isolated a strain of C. albicans from plaques on the oral mucus membrane of an infected patient. Colonies of this strain were exposed for 1 24 h, to 5%ALA-PTt, 5%ALA-PTt buffered to pH 6.5 (the pH of the oral mucosa) (5%ALA-PTtb) or not exposed (control). The 1 h-exposed samples were also irradiated at a wavelength of 630 nm with 0.14 watts (W) and 0.37 W/cm2 for 7 min at a distance of <1 mm. Results and conclusion: The 5% ALA-PTt preparation was shown to be effective in reducing the growth of biofilm and inoculum of C. albicans. This effect seems to be linked to the intrinsic characteristics of 5%ALA-TPt, such acidic pH and the induction of free radical production. This outcome was significantly enhanced by the effect of PDT at relatively short incubation and irradiation times, which resulted in growth inhibition of both treated biofilm and inoculum by ∼80% and ∼95%, respectively.

© 2019 Elsevier Ltd The lens capsule, a thin specialized basement membrane that encloses the crystalline lens, is essential for both the structural and biomechanical integrity of the lens. Knowing the mechanical properties of the lens capsule is important for understanding its physiological functioning, role in accommodation, age-related changes, and for providing a better treatment of a cataract. In this review, we have described the techniques used for the lens capsule biomechanical testing on the macro- and microscale and summarized the current knowledge about its mechanical properties.

© 2019 Elsevier B.V. Background: A large number of systemic diseases can be linked to oral candida pathogenicity. The global trend of invasive candidiasis has increased progressively and is often accentuated by increasing Candida albicans resistance to the most common antifungal medications. Photodynamic therapy (PDT) is a promising therapeutic approach for oral microbial infections. A new formulation of 5-aminolevulinic acid (5%ALA) in a thermosetting gel (t) (5%ALA-PTt) was patented and recently has become available on the market. However, its antimicrobial properties, whether mediated or not by PDT, are not yet known. In this work we characterised them. Methods: We isolated a strain of C. albicans from plaques on the oral mucus membrane of an infected patient. Colonies of this strain were exposed for 1 24 h, to 5%ALA-PTt, 5%ALA-PTt buffered to pH 6.5 (the pH of the oral mucosa) (5%ALA-PTtb) or not exposed (control). The 1 h-exposed samples were also irradiated at a wavelength of 630 nm with 0.14 watts (W) and 0.37 W/cm2 for 7 min at a distance of <1 mm. Results and conclusion: The 5% ALA-PTt preparation was shown to be effective in reducing the growth of biofilm and inoculum of C. albicans. This effect seems to be linked to the intrinsic characteristics of 5%ALA-TPt, such acidic pH and the induction of free radical production. This outcome was significantly enhanced by the effect of PDT at relatively short incubation and irradiation times, which resulted in growth inhibition of both treated biofilm and inoculum by ∼80% and ∼95%, respectively.

© 2019 Elsevier Ltd The lens capsule, a thin specialized basement membrane that encloses the crystalline lens, is essential for both the structural and biomechanical integrity of the lens. Knowing the mechanical properties of the lens capsule is important for understanding its physiological functioning, role in accommodation, age-related changes, and for providing a better treatment of a cataract. In this review, we have described the techniques used for the lens capsule biomechanical testing on the macro- and microscale and summarized the current knowledge about its mechanical properties.