Aquatic toxicity and mode of action of CdS and ZnS nanoparticles in four microalgae species
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01.07.2020 |
Pikula K.
Mintcheva N.
Kulinich S.A.
Zakharenko A.
Markina Z.
Chaika V.
Orlova T.
Mezhuev Y.
Kokkinakis E.
Tsatsakis A.
Golokhvast K.
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Environmental Research |
10.1016/j.envres.2020.109513 |
0 |
Ссылка
© 2020 Elsevier Inc. This study reports the differences in toxic action between cadmium sulfide (CdS) and zinc sulfide (ZnS) nanoparticles (NPs) prepared by recently developed xanthate-mediated method. The aquatic toxicity of the synthesized NPs on four marine microalgae species was explored. Growth rate, esterase activity, membrane potential, and morphological changes of microalgae cells were evaluated using flow cytometry and optical microscopy. CdS and ZnS NPs demonstrated similar level of general toxicity and growth-rate inhibition to all used microalgae species, except the red algae P. purpureum. More specifically, CdS NPs caused higher inhibition of growth rate for C. muelleri and P. purpureum, while ZnS NPs were more toxic for A. ussuriensis and H. akashiwo species. Our findings suggest that the sensitivity of different microalgae species to CdS and ZnS NPs depends on the chemical composition of NPs and their ability to interact with the components of microalgal cell-wall. The red microalga was highly resistant to ZnS NPs most likely due to the presence of phycoerythrin proteins in the outer membrane bound Zn2+ cations defending their cells from further toxic influence. The treatment with CdS NPs caused morphological changes and biochemical disorder in all tested microalgae species. The toxicity of CdS NPs is based on their higher photoactivity under visible light irradiation and lower dissociation in water, which allows them to generate more reactive oxygen species and create a higher risk of oxidative stress to aquatic organisms. The results of this study contribute to our understanding of the parameters affecting the aquatic toxicity of semiconductor NPs and provide a basis for further investigations.
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Correlation of synovial caspase-3 concentration and the photodynamic effectiveness in osteoarthritis treatment
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01.06.2020 |
Zharova T.
Kogan E.
Makarov V.
Smorchkov M.
Lychagin A.
Ivannikov S.
Zharkov N.
Loschenov V.
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Photodiagnosis and Photodynamic Therapy |
10.1016/j.pdpdt.2020.101669 |
0 |
Ссылка
© 2020 Elsevier B.V. Background: The present study focuses on investigation of Intra-articular PDT mechanisms for OA treatment. Also, a search for determination of the most effective dose of chlorin e6 (Ce6) for anti-inflammatory PDT of OA was carried out. Methods: The study was carried out on laboratory animals (11 Chinchilla rabbits, 1 year, 2.5 kg) with a gonarthritis model of post-traumatic OA. According to the instructions for using Photoditazin (Ce6 based PS) for PDT of human oncological and non-oncological diseases, the recommended dose is 0.7–1.2 mg/kg. For studies on rabbits, taking into account the conversion coefficient (3.2), the PS doses of 2.4, 3.2 and 6.4 mg/kg were selected. Fluorescence spectra were measured intra-articular before and after PDT using spectrometer with fiber-optic probe. The intrajoint PDT was carried out using a laser (662 ± 10 nm) and a fiber-optic catheter with a cylindrical diffuser inside a sapphire needle for a uniform distribution of the laser radiation. The immunohistochemical study was carried out by staining the samples with caspase-3. Results: Histological and immunohistochemical analysis showed that the best PS dose for intravenous administration for PDT of rabbit gonarthritis is 3.2 mg/kg. The PS concentration directly in the synovial tissue was 0.5 mg/kg, and this was enough to achieve the most positive results to reduce the caspase-3 level. Conclusion: The caspase-3 level correlates well with other signs of inflammation in the synovial membrane (edema, etc.). Therefore, to assess the PDT effectiveness in the treatment of gonarthritis accompanied by synovitis, it is sufficient to analyze only for caspase-3. The efficacy of PDT with Ce6 showed that 3.2 mg/kg PS dose (1 mg/kg for a human) is the most effective.
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Correlation of synovial caspase-3 concentration and the photodynamic effectiveness in osteoarthritis treatment
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01.06.2020 |
Zharova T.
Kogan E.
Makarov V.
Smorchkov M.
Lychagin A.
Ivannikov S.
Zharkov N.
Loschenov V.
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Photodiagnosis and Photodynamic Therapy |
10.1016/j.pdpdt.2020.101669 |
0 |
Ссылка
© 2020 Elsevier B.V. Background: The present study focuses on investigation of Intra-articular PDT mechanisms for OA treatment. Also, a search for determination of the most effective dose of chlorin e6 (Ce6) for anti-inflammatory PDT of OA was carried out. Methods: The study was carried out on laboratory animals (11 Chinchilla rabbits, 1 year, 2.5 kg) with a gonarthritis model of post-traumatic OA. According to the instructions for using Photoditazin (Ce6 based PS) for PDT of human oncological and non-oncological diseases, the recommended dose is 0.7–1.2 mg/kg. For studies on rabbits, taking into account the conversion coefficient (3.2), the PS doses of 2.4, 3.2 and 6.4 mg/kg were selected. Fluorescence spectra were measured intra-articular before and after PDT using spectrometer with fiber-optic probe. The intrajoint PDT was carried out using a laser (662 ± 10 nm) and a fiber-optic catheter with a cylindrical diffuser inside a sapphire needle for a uniform distribution of the laser radiation. The immunohistochemical study was carried out by staining the samples with caspase-3. Results: Histological and immunohistochemical analysis showed that the best PS dose for intravenous administration for PDT of rabbit gonarthritis is 3.2 mg/kg. The PS concentration directly in the synovial tissue was 0.5 mg/kg, and this was enough to achieve the most positive results to reduce the caspase-3 level. Conclusion: The caspase-3 level correlates well with other signs of inflammation in the synovial membrane (edema, etc.). Therefore, to assess the PDT effectiveness in the treatment of gonarthritis accompanied by synovitis, it is sufficient to analyze only for caspase-3. The efficacy of PDT with Ce6 showed that 3.2 mg/kg PS dose (1 mg/kg for a human) is the most effective.
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Quasi-isothermal modulated DSC as a valuable characterisation method for soft tissue biomaterial crosslinking reactions
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01.06.2020 |
Joyce K.
Rahmani S.
Rochev Y.
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Bioactive Materials |
10.1016/j.bioactmat.2020.03.002 |
0 |
Ссылка
© 2020 Glutaraldehyde (Glut) is an extensively used sterilant and fixative for the crosslinking of natural soft tissue biomaterials like bovine pericardium (BP) to provide stability and is required for its application in vivo. There is plenty of debate around the reaction mechanism of Glut with natural biomaterials. Differential scanning calorimetry (DSC) is a commonly used technique that is typically used to measure the thermal profile of polymers. However, a variation known as quasi-isothermal modulated differential scanning calorimetry (QiMDSC) has been utilised for the analysis of polymorphic transformations in both the pharmaceutical and food industries. This communication will address QiMDSC as a method for analysing soft tissue biomaterials and their crosslinking mechanisms and how it can be applied to other biomaterial applications.
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Quasi-isothermal modulated DSC as a valuable characterisation method for soft tissue biomaterial crosslinking reactions
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01.06.2020 |
Joyce K.
Rahmani S.
Rochev Y.
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Bioactive Materials |
10.1016/j.bioactmat.2020.03.002 |
0 |
Ссылка
© 2020 Glutaraldehyde (Glut) is an extensively used sterilant and fixative for the crosslinking of natural soft tissue biomaterials like bovine pericardium (BP) to provide stability and is required for its application in vivo. There is plenty of debate around the reaction mechanism of Glut with natural biomaterials. Differential scanning calorimetry (DSC) is a commonly used technique that is typically used to measure the thermal profile of polymers. However, a variation known as quasi-isothermal modulated differential scanning calorimetry (QiMDSC) has been utilised for the analysis of polymorphic transformations in both the pharmaceutical and food industries. This communication will address QiMDSC as a method for analysing soft tissue biomaterials and their crosslinking mechanisms and how it can be applied to other biomaterial applications.
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Criterion of non monotonic magnetic relaxation in Pt/Co/Ir/Co/Pt synthetic ferrimagnet with perpendicular anisotropy
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01.06.2020 |
Morgunov R.B.
Bezverkhnii A.I.
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Superlattices and Microstructures |
10.1016/j.spmi.2020.106509 |
0 |
Ссылка
© 2020 Elsevier Ltd In Pt/Co/Ir/Co/Pt synthetic ferrimagnet, non-monotonic magnetic relaxation (NMMR) caused by switching of external magnetic dependends on Co layer thicknesse and temperature. In this paper, we have varied thickness of one of the Co layers in the Pt/Co/Ir/Co/Pt synthetic ferrimagnet in the 0.6–1.0 nm range at fixed Co layer thickness of another layer 1.1 nm in the 50–300 K range to find experimental conditions for NMMR. We found interdependence between Co layer thickness tCo and temperature T providing NMMR. Energy balance between magnetic anisotropies and exchange interaction of the two Co layers stipulates linear dependence of nessecary T on tCo. Exsact expression limitating magnetic anisotropies of the thick and thin Co layers and predicting NMMR conditions in tCo - T space is proposed. Altough all mentioned results relates to experiments in permanent magnetic field, the contribution of the NMMR to the magnetic hysteresis loops recorded in sweeping magetic field was experimentally found. Obtained results can be used for wide family of synthetic ferrimagnets with perpendicular anisotropy.
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Spectral analysis combined with nonlinear optical measurement of laser printed biopolymer composites comprising chitosan/SWCNT
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01.06.2020 |
Savelyev M.S.
Gerasimenko A.Y.
Vasilevsky P.N.
Fedorova Y.O.
Groth T.
Ten G.N.
Telyshev D.V.
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Analytical Biochemistry |
10.1016/j.ab.2020.113710 |
0 |
Ссылка
© 2020 Elsevier Inc. Biopolymer composites based on two types of chitosan (chitosan succinate and low-molecular weight chitosan) with single-walled carbon nanotubes (SWCNT) were created by laser printing. SWCNT have good dispersibility in chitosan solutions and therefore, can form relatively homogeneous films that was shown in scanning electron microscopy images. For the studies film composites were formed under the action of laser radiation on aqueous dispersion media. Study of the nonlinear optical process during the interaction of laser radiation with a disperse media has shown that low-molecular chitosan has a large nonlinear absorption coefficient of 17 cm/GW, while the addition of SWCNT lead to a significant increase up to 902 cm/GW. The threshold intensity for these samples was 5.5 MW/cm2 with nanotubes. If intensity exceeds the threshold value, nonlinear effects occur, which, in turn, lead to the transformation of a liquid into a solid phase. Characterization of films by FTIR and Raman spectroscopy indicated arising molecular interactions between chitosan and SWCNT detected as a small frequency shift and a change in the shape of radial breathing mode (RBM). The results indicate the possibility using aqueous dispersion media based on chitosan and SWCNT to create three-dimensional films and scaffolds for tissue engineering by laser printing.
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Effects of plasma concentration of micro-RNA Mir-27b and CYP3A4*22 on equilibrium concentration of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder
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20.05.2020 |
Zastrozhin M.S.
Skryabin V.Y.
Smirnov V.V.
Petukhov A.E.
Pankratenko E.P.
Zastrozhina A.K.
Grishina E.A.
Ryzhikova K.A.
Bure I.V.
Golovinskii P.A.
Koporov S.G.
Bryun E.A.
Sychev D.A.
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Gene |
10.1016/j.gene.2020.144513 |
0 |
Ссылка
© 2020 Elsevier B.V. Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene. Objective: The objective of our study was to investigate the effect of 99366316G>A polymorphism of the CYP3A4 gene on the concentration/dose indicator of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder, using findings on enzymatic activity of CYP3A (as evaluated by the 6-beta-hydroxy-cortisol/cortisol ratio measurement) and on CYP3A4 expression level obtained by measuring the miR-27b plasma concentration levels in patients with anxiety disorders comorbid with alcoholism. Material and methods: Our study enrolled 105 patients with anxiety disorders comorbid with alcohol use disorder (age - 37.8±14.6 years). Therapy included alprazolam in an average daily dose of 5.6±2.4 mg per day. Treatment efficacy was evaluated using the psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6- beta-hydroxy-cortisol/cortisol). Therapeutic drug monitoring (TDM) has been performed using HPLC-MS/MS. Results: Our study revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 3.0 [2.0; 5.0] and (GA) 4.0 [4.0; 5.0], p = 0.007; at the same time, the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 3.8] and (GA) 3.0 [1.5; 4.0], p = 0.650. We revealed a statistical significance for concentration/dose indicator of alprazolam in patients with different genotypes: (GG) 1.583 [0.941; 2.301] and (GA) 2.888 [2.305; 4.394], p = 0.001). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the miR-27b plasma levels in patients with different genotypes: (GG) 25.6 [20.4; 28.8], (GA) 25.7 [19.7; 33.1], p = 0.423. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam efficacy profile evaluated by changes in HAMA scale scores and the miR-27b plasma concentration: rs = 0.20, p = 0.042. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.15, p = 0.127. In addition, we revealed the relationship between the CYP3A enzymatic activity (as evaluated by 6-beta-hydroxycortisol/ cortisol ratio measurement) and the miR-27b plasma concentration: rs = −0.27, p = 0.006. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam concentration and the miR-27b plasma concentration: rs = 0.28, p = 0.003. Conclusion: The effect of genetic polymorphism of the CYP3A4 gene on the efficacy and safety profiles of alprazolam was demonstrated in a group of 105 patients with anxiety disorders comorbid with alcohol use disorder. At the same time, miR-27b remains a promising biomarker for assessing the level of CYP3A4 expression, because it correlates with the encoded isoenzyme's activity.
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тезис
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Effects of plasma concentration of micro-RNA Mir-27b and CYP3A4*22 on equilibrium concentration of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder
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20.05.2020 |
Zastrozhin M.S.
Skryabin V.Y.
Smirnov V.V.
Petukhov A.E.
Pankratenko E.P.
Zastrozhina A.K.
Grishina E.A.
Ryzhikova K.A.
Bure I.V.
Golovinskii P.A.
Koporov S.G.
Bryun E.A.
Sychev D.A.
|
Gene |
10.1016/j.gene.2020.144513 |
0 |
Ссылка
© 2020 Elsevier B.V. Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene. Objective: The objective of our study was to investigate the effect of 99366316G>A polymorphism of the CYP3A4 gene on the concentration/dose indicator of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder, using findings on enzymatic activity of CYP3A (as evaluated by the 6-beta-hydroxy-cortisol/cortisol ratio measurement) and on CYP3A4 expression level obtained by measuring the miR-27b plasma concentration levels in patients with anxiety disorders comorbid with alcoholism. Material and methods: Our study enrolled 105 patients with anxiety disorders comorbid with alcohol use disorder (age - 37.8±14.6 years). Therapy included alprazolam in an average daily dose of 5.6±2.4 mg per day. Treatment efficacy was evaluated using the psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6- beta-hydroxy-cortisol/cortisol). Therapeutic drug monitoring (TDM) has been performed using HPLC-MS/MS. Results: Our study revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 3.0 [2.0; 5.0] and (GA) 4.0 [4.0; 5.0], p = 0.007; at the same time, the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 3.8] and (GA) 3.0 [1.5; 4.0], p = 0.650. We revealed a statistical significance for concentration/dose indicator of alprazolam in patients with different genotypes: (GG) 1.583 [0.941; 2.301] and (GA) 2.888 [2.305; 4.394], p = 0.001). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the miR-27b plasma levels in patients with different genotypes: (GG) 25.6 [20.4; 28.8], (GA) 25.7 [19.7; 33.1], p = 0.423. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam efficacy profile evaluated by changes in HAMA scale scores and the miR-27b plasma concentration: rs = 0.20, p = 0.042. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.15, p = 0.127. In addition, we revealed the relationship between the CYP3A enzymatic activity (as evaluated by 6-beta-hydroxycortisol/ cortisol ratio measurement) and the miR-27b plasma concentration: rs = −0.27, p = 0.006. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam concentration and the miR-27b plasma concentration: rs = 0.28, p = 0.003. Conclusion: The effect of genetic polymorphism of the CYP3A4 gene on the efficacy and safety profiles of alprazolam was demonstrated in a group of 105 patients with anxiety disorders comorbid with alcohol use disorder. At the same time, miR-27b remains a promising biomarker for assessing the level of CYP3A4 expression, because it correlates with the encoded isoenzyme's activity.
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Rhythm and blues: Influence of CLOCK T3111C on peripheral electrophysiological indicators of negative affective processing
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15.05.2020 |
Armbruster D.
Brocke B.
Kirschbaum C.
Witt S.H.
Lesch K.P.
Strobel A.
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Physiology and Behavior |
10.1016/j.physbeh.2020.112831 |
0 |
Ссылка
© 2020 Elsevier Inc. Dysfunction in the circadian system has been linked to emotion regulation and mood disorders with genetic variation in clock genes as likely contributors. Here, we focused on endophenotypes of affective processing and investigated in two independent samples of healthy individuals (n1=99, n2=108) whether genotypes of a functional single nucleotide polymorphism (SNP) in the gene encoding CLOCK (CLOCK T3111C, rs1801260) differed in physiological responses to emotional stimuli. Both samples underwent an emotional startle paradigm with startle responses being measured via EMG. In the second sample, skin conductance responses as well as corrugator and zygomaticus activity were also assessed. In both samples, CLOCK T3111C was associated with overall startle responses to loud noise bursts with T/T homozygotes showing consistently more marked responses. However, in the all-female second sample, the effects of CLOCK on skin conductance responses to the same loud noise bursts depended on hormone status: similar to the startle results, in free-cycling women T/T homozygotes showed more pronounced skin conductance response (SCR) compared to C allele carriers. The opposite was true for women using combined oral contraceptives (COC). A further CLOCK × hormone status interaction effect was found for corrugator activity. In free-cycling women, T/T homozygotes presented with less corrugator activity to affective pictures compared to C allele carriers, while the opposite pattern emerged for COC users. The findings emphasize the potential role of CLOCK for affect and mood.
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тезис
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Rhythm and blues: Influence of CLOCK T3111C on peripheral electrophysiological indicators of negative affective processing
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15.05.2020 |
Armbruster D.
Brocke B.
Kirschbaum C.
Witt S.H.
Lesch K.P.
Strobel A.
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Physiology and Behavior |
10.1016/j.physbeh.2020.112831 |
0 |
Ссылка
© 2020 Elsevier Inc. Dysfunction in the circadian system has been linked to emotion regulation and mood disorders with genetic variation in clock genes as likely contributors. Here, we focused on endophenotypes of affective processing and investigated in two independent samples of healthy individuals (n1=99, n2=108) whether genotypes of a functional single nucleotide polymorphism (SNP) in the gene encoding CLOCK (CLOCK T3111C, rs1801260) differed in physiological responses to emotional stimuli. Both samples underwent an emotional startle paradigm with startle responses being measured via EMG. In the second sample, skin conductance responses as well as corrugator and zygomaticus activity were also assessed. In both samples, CLOCK T3111C was associated with overall startle responses to loud noise bursts with T/T homozygotes showing consistently more marked responses. However, in the all-female second sample, the effects of CLOCK on skin conductance responses to the same loud noise bursts depended on hormone status: similar to the startle results, in free-cycling women T/T homozygotes showed more pronounced skin conductance response (SCR) compared to C allele carriers. The opposite was true for women using combined oral contraceptives (COC). A further CLOCK × hormone status interaction effect was found for corrugator activity. In free-cycling women, T/T homozygotes presented with less corrugator activity to affective pictures compared to C allele carriers, while the opposite pattern emerged for COC users. The findings emphasize the potential role of CLOCK for affect and mood.
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Serotonin (5-HT) neuron-specific inactivation of Cadherin-13 impacts 5-HT system formation and cognitive function
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15.05.2020 |
Forero A.
Ku H.P.
Malpartida A.B.
Wäldchen S.
Alhama-Riba J.
Kulka C.
Aboagye B.
Norton W.H.J.
Young A.M.J.
Ding Y.Q.
Blum R.
Sauer M.
Rivero O.
Lesch K.P.
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Neuropharmacology |
10.1016/j.neuropharm.2020.108018 |
0 |
Ссылка
© 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.
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тезис
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Serotonin (5-HT) neuron-specific inactivation of Cadherin-13 impacts 5-HT system formation and cognitive function
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15.05.2020 |
Forero A.
Ku H.P.
Malpartida A.B.
Wäldchen S.
Alhama-Riba J.
Kulka C.
Aboagye B.
Norton W.H.J.
Young A.M.J.
Ding Y.Q.
Blum R.
Sauer M.
Rivero O.
Lesch K.P.
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Neuropharmacology |
10.1016/j.neuropharm.2020.108018 |
0 |
Ссылка
© 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.
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тезис
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Serotonin (5-HT) neuron-specific inactivation of Cadherin-13 impacts 5-HT system formation and cognitive function
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15.05.2020 |
Forero A.
Ku H.P.
Malpartida A.B.
Wäldchen S.
Alhama-Riba J.
Kulka C.
Aboagye B.
Norton W.H.J.
Young A.M.J.
Ding Y.Q.
Blum R.
Sauer M.
Rivero O.
Lesch K.P.
|
Neuropharmacology |
10.1016/j.neuropharm.2020.108018 |
0 |
Ссылка
© 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.
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Mitochondrial permeability transition pore is involved in oxidative burst and NETosis of human neutrophils
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01.05.2020 |
Vorobjeva N.
Galkin I.
Pletjushkina O.
Golyshev S.
Zinovkin R.
Prikhodko A.
Pinegin V.
Kondratenko I.
Pinegin B.
Chernyak B.
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Biochimica et Biophysica Acta - Molecular Basis of Disease |
10.1016/j.bbadis.2020.165664 |
0 |
Ссылка
© 2020 Elsevier B.V. Neutrophils release neutrophil extracellular traps (NETs) in response to numerous pathogenic microbes as the last suicidal resource (NETosis) in the fight against infection. Apart from the host defense function, NETs play an essential role in the pathogenesis of various autoimmune and inflammatory diseases. Therefore, understanding the molecular mechanisms of NETosis is important for regulating aberrant NET release. The initiation of NETosis after the recognition of pathogens by specific receptors is mediated by an increase in intracellular Ca2+ concentration, therefore, the use of Ca2+ ionophore A23187 can be considered a semi-physiological model of NETosis. Induction of NETosis by various stimuli depends on reactive oxygen species (ROS) produced by NADPH oxidase, however, NETosis induced by Ca2+ ionophores was suggested to be mediated by ROS produced in mitochondria (mtROS). Using the mitochondria-targeted antioxidant SkQ1 and specific inhibitors of NADPH oxidase, we showed that both sources of ROS, mitochondria and NADPH oxidase, are involved in NETosis induced by A23187 in human neutrophils. In support of the critical role of mtROS, SkQ1-sensitive NETosis was demonstrated to be induced by A23187 in neutrophils from patients with chronic granulomatous disease (CGD). We assume that Ca2+-triggered mtROS production contributes to NETosis either directly (CGD neutrophils) or by stimulating NADPH oxidase. The opening of the mitochondrial permeability transition pore (mPTP) in neutrophils treated by A23187 was revealed using the electron transmission microscopy as a swelling of the mitochondrial matrix. Using specific inhibitors, we demonstrated that the mPTP is involved in mtROS production, NETosis, and the oxidative burst induced by A23187.
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тезис
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Laser-triggered drug release from polymeric 3-D micro-structured films via optical fibers
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01.05.2020 |
Kurochkin M.
Sindeeva O.
Brodovskaya E.
Gai M.
Frueh J.
Su L.
Sapelkin A.
Tuchin V.
Sukhorukov G.
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Materials Science and Engineering C |
10.1016/j.msec.2020.110664 |
0 |
Ссылка
© 2020 Elsevier B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.
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Laser-triggered drug release from polymeric 3-D micro-structured films via optical fibers
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01.05.2020 |
Kurochkin M.
Sindeeva O.
Brodovskaya E.
Gai M.
Frueh J.
Su L.
Sapelkin A.
Tuchin V.
Sukhorukov G.
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Materials Science and Engineering C |
10.1016/j.msec.2020.110664 |
0 |
Ссылка
© 2020 Elsevier B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.
Читать
тезис
|
Laser-triggered drug release from polymeric 3-D micro-structured films via optical fibers
|
01.05.2020 |
Kurochkin M.
Sindeeva O.
Brodovskaya E.
Gai M.
Frueh J.
Su L.
Sapelkin A.
Tuchin V.
Sukhorukov G.
|
Materials Science and Engineering C |
10.1016/j.msec.2020.110664 |
0 |
Ссылка
© 2020 Elsevier B.V. Photosensitive polymeric three-dimensional microstructured film (PTMF) is a new type of patterned polymeric films functionalized with an array of sealed hollow 3D containers. The microstructured system with enclosed chemicals provides a tool for the even distribution of biologically active substances on a given surface that can be deposited on medical implants or used as a cells substrate. In this work, we proposed a way for photothermally activating and releasing encapsulated substances at picogram amounts from the PTMF surface in different environments using laser radiation delivered with a multimode optical fiber. The photosensitive PTMFs were prepared by the layer-by-layer (LbL) assembly from alternatively charged polyelectrolytes followed by covering with a layer of hydrophobic polylactic acid (PLA) and a layer of gold nanoparticles (AuNPs). Moreover, the typical photothermal cargo release amounts were determined on the surface of the PTMF for a range of laser powers delivered to films placed in the air, deionized (DI) water, and 1% agarose gel. The agarose gel was used as a soft tissue model for developing a technique for the laser activation of PTMFs deep in tissues using optical waveguides. The number of PTMF chambers activated by a near-infrared (NIR) laser beam was evaluated as the function of optical parameters.
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Lipid dynamics in nanoparticles formed by maleic acid-containing copolymers: EPR spectroscopy and molecular dynamics simulations
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01.05.2020 |
Colbasevici A.
Voskoboynikova N.
Orekhov P.
Bozdaganyan M.
Karlova M.
Sokolova O.
Klare J.
Mulkidjanian A.
Shaitan K.
Steinhoff H.
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Biochimica et Biophysica Acta - Biomembranes |
10.1016/j.bbamem.2020.183207 |
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Ссылка
© 2020 Elsevier B.V. Amphiphilic maleic acid-containing copolymers account for a recent methodical breakthrough in the study of membrane proteins. Their application enables a detergent-free extraction of membrane proteins from lipid bilayers, yielding stable water-soluble, discoidal lipid bilayer particles with incorporated proteins, which are wrapped with copolymers. Although many studies confirm the potential of this approach for membrane protein research, the interactions between the maleic acid-containing copolymers and extracted lipids, as well as possible effects of the copolymers on lipid-embedded proteins deserve further scrutinization. Here, we combine electron paramagnetic resonance spectroscopy and coarse-grain molecular dynamics simulations to compare the distribution and dynamics of lipids in lipid particles of phospholipid bilayers encased either by an aliphatic diisobutylene/maleic acid copolymer (DIBMALPs) or by an aromatic styrene/maleic acid copolymer (SMALPs). Nitroxides located at the 5th, 12th or 16th carbon atom positions in phosphatidylcholine-based spin labels experience restrictions of their reorientational motion depending on the type of encasing copolymer. The dynamics of the lipids was less constrained in DIBMALPs than in SMALPs with the affinity of spin labeled lipids to the polymeric rim being more pronounced in SMALPs.
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Dental anomalies in people living in radionuclide-contaminated regions
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01.05.2020 |
Sevbitov A.
Kuznetsova M.
Dorofeev A.
Borisov V.
Mironov S.
Yusupova L.
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Journal of Environmental Radioactivity |
10.1016/j.jenvrad.2020.106190 |
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Ссылка
© 2020 Elsevier Ltd The 1986 accident at the Chernobyl Nuclear Power Plant led to large-scale changes in the environmental situation. The purpose of our study was to conduct a comparative analysis of the morphological states of the dentition of individuals living in regions exposed to radiation to determine the groups at risk for the main classes of dental anomalies. We believe our results will support the development of a differentiated system for dental rehabilitation and follow-up of individuals exposed to radiation. The prevalence rate of dental anomalies was studied in 1,889 patients of both sexes divided by age in accordance with dentition formation stages and by regions of residence in accordance with the 137Cs soil-contamination level. A statistically significant decrease was observed in the number of patients with normal dentition for their age among those who had been exposed to prenatal radiation. A sharp increase in combined dental anomalies was revealed in patients who lived in regions with a137Cs soil-contamination level ranging from 555 to 1665 GBq/km2; concomitantly, multidirectional fluctuations were observed in the numbers of tooth and occlusion anomalies. Among the examined population, the most severe pathology of the oral organs was found in prenatally irradiated patients (born between April 26, 1986, and April 30, 1987). The prevalence of dental anomalies is interrelated not only with the level of radioactive contamination in the soil of the dwelling area, but also with the age of the surveyed individuals at the moment of the accident.
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