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Background and Aim: Recently, viral diseases of honey bees (Apis mellifera) have presented an increasing threat to beekeeping. This study aimed to examine the presence of honey bee viruses in Apis and non-Apis bee species, the mite Varroa destructor, and pollinated plants in Armenia. Materials and Methods: Sampling was performed in Tavush Province, in the northeast of the Republic of Armenia, from August to November 2019. Overall, 200 A. mellifera bees, 50 V. destructor mites, and 20 wasps were collected (corresponding to three bees, five mites, and 2–11 wasps in each investigated sample) and homogenized for RNA isolation and detection of viruses. Ten pollinated plants were taken from each plant, and 2 g of each sample was used for homogenization. In each investigated case Apis mellifera, Varroa destructor, Vespula germanica and plants received percentages of the virus presence. Results: Six important honey bee viruses (acute bee paralysis virus [ABPV], deformed wing virus [DWV], A. mellifera norovirus [ANV], Lake Sinai virus-2 [LSV-2], Big Sioux River virus [BSRV], and A. mellifera filamentous virus [AmFV]) were detected in samples by polymerase chain reaction. Our results showed that DWV, ANV, and ABPV were the most common viruses in honey bees. All viruses were detected in wasps, but LSV-2 and ANV were present in almost all samples. Conclusion: Our results showed that almost all viruses were present in V. destructor. Although ANV is very common in honey bees, it did not appear in any mite samples. Our study indicates that viruses typically associated with honey bees were also actively infecting wasps. Our data suggest that the survival of viruses in plants can be an important source of seasonal transmission of viruses to bees. In addition, pollinated plants can potentially serve as reservoirs for honey bee viruses.

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Abstract Failure to direct axon regeneration to appropriate targets is a major barrier to restoring function after nerve injury. Development of strategies that can direct targeted regeneration of neurons such as retinal ganglion cells (RGCs) are needed to delay or reverse blindness in diseases like glaucoma. Here, we demonstrate that a new class of asymmetric, charge balanced (ACB) waveforms are effective at directing RGC axon growth, in vitro, without compromising cell viability. Unlike previously proposed direct current (DC) stimulation approaches, charge neutrality of ACB waveforms ensures the safety of stimulation while asymmetry ensures its efficacy. Furthermore, we demonstrate the relative influence of pulse amplitude and pulse width on the overall effectiveness of stimulation. This work can serve as a practical guideline for the potential deployment of electrical stimulation as a treatment strategy for nerve injury.

Abstract Oxylipins are derived from enzymatic and non-enzymatic oxidation of n-3 and n-6 long-chain polyunsaturated fatty acids. They are known to be involved in inflammatory processes. The aim of this study was to describe the breast milk oxylipin profile following a docosahexaenoic acid (DHA) supplementation of mothers of preterm infants. We examined the oxylipins profile in breast milk collected at day 14 post-delivery, of 40 mothers who delivered before 29 weeks of gestation and who were supplemented with either DHA-rich algae oil (S-DHA) or a placebo (PL). These mothers were selected from the MOBYDIck cohort (NCT02371460 registered on 25/05/2015 in ClinicalTrials.gov) according to the supplementation received (S-DHA vs. PL) and the DHA content quartiles as measured in breast milk (Low vs. High) to generate four study groups. Milk oxylipins, as ng/mL of milk, were analyzed by LC-MS/MS. Ten oxylipins derived from DHA were higher in the S-DHA-High group than the other three groups (P

This work aimed to manufacture a highly sensitive hydrogen gas sensor based on Fe2O3:ZnO thin film. The Fe2O3:ZnO based sputtering target was synthesized by a solid-state synthesis method. Gas-sensitive thin films were deposited onto the alumina substrate by the high-frequency (RF) magnetron sputtering method. The thickness of the sensing film was measured and the morphology of the sensing layers was studied. The Fe2O3:ZnO sensor showed the highest hydrogen gas response at 100 ᵒC and the operating temperature of 150 ᵒC was selected as the optimum working temperature. The sensor showed sensitivity even to extremely low concentrations of hydrogen (100 ppm), where the response was 4.6. The sensing parameters of the fabricated sensor confirm that the Fe2O3:ZnO material may become an excellent nanostructure for the detection of low concentrations of hydrogen.

Objective: Non-alcoholic fatty liver disease (NAFLD) affects 1 in 3 adults and contributes to advanced liver injury and cardiometabolic disease. While recent evidence points to involvement of the brain in NAFLD, the downstream neural circuits and neuronal molecular mechanisms involved in this response, remain unclear. Here, we investigated the role of a unique forebrain-hypothalamic circuit in NAFLD. Methods: Chemogenetic activation and inhibition of circumventricular subfornical organ (SFO) neurons that project to the paraventricular nucleus of the hypothalamus (PVN; SFO→PVN) in mice were used to study the role of SFO→PVN signaling in NAFLD. Novel scanning electron microscopy techniques, histological approaches, molecular biology techniques, and viral methodologies were further used to delineate the role of endoplasmic reticulum (ER) stress within this circuit in driving NAFLD. Results: In lean animals, acute chemogenetic activation of SFO→PVN neurons was sufficient to cause hepatic steatosis in a liver sympathetic nerve dependent manner. Conversely, inhibition of this forebrain-hypothalamic circuit rescued obesity-associated NAFLD. Furthermore, dietary NAFLD is associated with marked ER ultrastructural alterations and ER stress in the PVN, which was blunted following reductions in excitatory signaling from the SFO. Finally, selective inhibition of PVN ER stress reduced hepatic steatosis during obesity. Conclusions: Collectively, these findings characterize a previously unrecognized forebrain-hypothalamic-ER stress circuit that is involved in hepatic steatosis, which may point to future therapeutic strategies for NAFLD.

Abstract Background NADPH oxidase (Nox) plays a crucial role in reactive oxygen spices (ROS) production and mediates different diseases’ development. Under aerobic conditions, the NADPH-containing protein component of the (NCP)-Fe (III) complex produces O2 − continuously and intensively. However, after the removal of Fe (III), the isolated NCP shows only antioxidant properties at the expense of NADPH composite. Based on the fact that the mentioned fruit juices are widely used in everyday life and also in biomedicine, it was aimed to use a universal method: 1. to obtain superoxide generating complex from available and relatively cheap raw materials without using any toxic substances; 2. to isolate, purify and study the components of prooxidant nature: the isoforms of O2 −—producing NCP-Fe (III) complexes obtained from Armenian fruits (raspberries, apricot, grapes), as well, grape seeds. Results Using a licensed method, for the first time isoforms of the superoxide (O2 −) producing a thermostable complex of the NCP component with Fe (III), (NCP-Fe (III)), were isolated and purified from Armenian fruits—raspberries, apricots, grapes, and grapes seeds. The process of isolation and purification of isoforms of these complexes included the following stages of processing: 1. alkaline hydrolysis at pH9,5; 2. their sedimentation at pH4.8; 3. Dissolving of the sediments in water at pH9.5, followed by ion-exchange chromatography on cellulose DE-52, and gel filtration on Sephadex G-100. Further, the heat treatment of the mentioned complexes was carried out. In a lyophilized state, under the anaerobic conditions, the isoforms of the given complexes, hybrid associates (hNCP-Nox), and NCP were stored practically without losing their activity in a mass of 1–1.5 g. Conclusions Isoforms of O2 − -producing complexes are new liquid-phase, thermo-stable prooxidant components found in raspberries, apricots, grapes, and grapes seeds.

OBJECTIVE: To delineate research priorities for improving clinical management of laryngeal dystonia, the NIH convened a multidisciplinary panel of experts for a 1-day workshop to examine the current progress in understanding its etiopathophysiology and clinical care. METHODS: The participants reviewed the current terminology of disorder and discussed advances in understanding its pathophysiology since a similar workshop was held in 2005. Clinical and research gaps were identified, and recommendations for future directions were delineated. RESULTS: The panel unanimously agreed to adopt the term laryngeal dystonia instead of spasmodic dysphonia to reflect the current progress in characterizations of this disorder. Laryngeal dystonia was recognized as a multifactorial, phenotypically heterogeneous form of isolated dystonia. Its etiology remains unknown, whereas the pathophysiology likely involves large-scale functional and structural brain network disorganization. Current challenges include the lack of clinically validated diagnostic markers and outcome measures and the paucity of therapies that address the disorder pathophysiology. CONCLUSION: Research priorities should be guided by challenges in clinical management of laryngeal dystonia. Identification of disorder-specific biomarkers would allow the development of novel diagnostic tools and unified measures of treatment outcome. Elucidation of the critical nodes within neural networks that cause or modulate symptoms would allow the development of targeted therapies that address the underlying pathophysiology. Given the rarity of laryngeal dystonia, future rapid research progress may be facilitated by multicenter, national and international collaborations.

Eastern European post-communist countries inherited pervasive corruption after the breakup of the USSR. Public trust was the crucial factor in tackling corruption and democracy building in these countries. This article takes Armenia as a case to study the antecedents and evolution of trust in Eastern European post-communist countries that went through a government coup in the 21st century. By comparing the corruption situation in Armenia before and after the Velvet Revolution 2018, we scrutinise how trust was and is critical to combating corruption and democracy building. We argue that in transition governments, one can distinguish two sources of creating public trust. The first wave generates when the government is newly established, and people trust the leader and his persona. Arguably, in this stage, the level of trust generated is based on expectations. The second wave of trust comes with the government’s actual performance, measured partly based on corruption perception.

Abstract We performed a mathematical analysis of functional connectivity in electroencephalography (EEG) of patients with obstructive sleep apnea (OSA) (N = 10; age: 52.8 ± 13 years; median age: 49 years; male/female ratio: 7/3), compared with a group of apparently healthy participants (N = 15; age: 51.5 ± 29.5 years; median age: 42 years; male/female ratio: 8/7), based on the calculation of wavelet bicoherence from nighttime polysomnograms. Having observed the previously known phenomenon of interhemispheric synchronization deterioration, we demonstrated a compensatory increase in intrahemispheric connectivity, as well as a slight increase in the connectivity of the central and occipital areas for high-frequency EEG activity. Significant changes in functional connectivity were extremely stable in groups of apparently healthy participants and OSA patients, maintaining the overall pattern when comparing different recording nights and various sleep stages. The maximum variability of the connectivity was observed at fast oscillatory processes during REM sleep. The possibility of observing some changes in functional connectivity of brain activity in OSA patients in a state of passive wakefulness opens up prospects for further research. Developing the methods of hypnogram evaluation that are independent of functional connectivity may be useful for implementing a medical decision support system.

Metric studies of teeth is a rapidly developing direction in odontological research, which is supported by means of corresponding imaging techniques for obtaining detailed digital reconstructions, and by application of image analysis methods. The current article presents methodological extension of teeth 3D models’ orientation tactics, which have been used in measurement techniques in dental, palaeoanthropological and palaeontological studies. Today image analysis has sufficient potential to perform orientation of teeth on the bases of their natural features; at the same time teeth possesses all necessary morphological structures for performing orientation on 3D reconstructions obtained by means of widely used today imaging techniques. Our aim is in providing an approach to orientation of teeth for its further use in morphologically relevant, accurate and applicable for various types of research, measurement techniques. The palaeoanthropological material presented in this paper, on which the proposed technique has been tested, is from territories of European part of Russian Federation and Republic of Armenia; it has been classified as related to the Middle Bronze Age, and is planned to be studied in a wider scope in the future. X-ray micro-focus tomography has been used for obtaining reconstructions of lower molars, which were segmented from semi-mandible 3D models. These teeth were used for setting vertical axis direction by means of surface curvature analysis and calculations based on points’ coordinates, which delineate functionally and morphologically important parts of teeth. This approach to accurate and morphologically relevant orientation of the studied teeth uses more than one structure at a time for choosing correct orientation according to aims of research and features of the studied material. This provides the proposed technique necessary potential to be applied for measurements of teeth and studies of their functional changes.

Photogrammetry is a non-destructive, three-dimensional modeling technique that has been widely adopted in archaeology. Archaeological monuments are particularly vulnerable to natural and anthropogenic activities, such as destruction, weathering, and erosion. Therefore, precise fixation and documentation of the monument are essential for preserving cultural layers for future generations. Digital technologies, especially photogrammetry, enable us to obtain better results for the photogrammetric survey. In recent years, this method has been employed in the excavation sites of Shengavit settlement and Verin Naver tombs, demonstrating its effectiveness in archaeological research. To obtain a better view of the stratigraphy of the site, the data was merged with archival drawings of previously collected information. This integration of data has allowed for a more comprehensive understanding of the site's history and evolution.

Abstract Background: NADPH oxidase 1 (Nox1), which is highly expressed in the colon, is thought to play a potential role in host defense as a physical and innate immune barrier against commensal or pathogenic microbes in the gastrointestinal epithelium. Diabetes can be caused by several biological factors, including insulin resistance is one of them. Alloxan is widely used to induce insulin-dependent diabetes in experimental animals. Alloxan increases the generation of reactive oxygen species as a result of metabolic reactions in the body, along with a massive increase in cytosolic calcium concentration. Methods Using a universal method, a superoxide radical (О2 −)-thermostable associate between NADPH-containing lipoprotein (NLP) and NADPH oxidase (Nox)- NLP-Nox was isolated and purified from the small intestine (SI) of control (C) and alloxan-induced diabetic (AD) albino rats. Results In comparison to the C indices, in AD in the SI, an increase in the specific content of NLP-Nox associate and a decrease in the stationary concentration of produced О2 − in liquid phase (in solution) and gas phase (during blowing by oxygen of the NLP-Nox solution) were observed. The NLP-Nox of SI associate in C and AD rats produced О2 − by an immediate mechanism, using NLP as a substrate. The phenomenon of the hiding of the optical absorption maxima of the Nox in oxidized states at pH10,5 was observed in the composition of these SI associates of the C and AD rat groups. The characteristic absorption maxima of the «hidden» Nox were observed under these conditions after reduction by potassium dithionite. Conclusion Thus, at AD, the decrease in the stationary concentration of produced О2 − in the solution and gas phase was compensated for by an increase in the specific amount of associate. In addition, the decrease in the stationary concentration of produced О2 − by NLP-Nox associates at AD can be linked to a decrease in the level of NADPH in NLP-Nox composition. This could be used as a new mechanism of AD pathogenesis.

Lipid peroxidation plays an important role in various pathologies and aging, at least partially mediated by ferroptosis. The role of mitochondrial lipid peroxidation during ferroptosis remains poorly understood. We show that supplementation of exogenous iron in the form of ferric ammonium citrate at submillimolar doses induces production of reactive oxygen species (ROS) and lipid peroxidation in mitochondria that precede ferroptosis in H9c2 cardiomyocytes. The mitochondria-targeted antioxidant SkQ1 and the redox mediator methylene blue, which inhibits the production of ROS in complex I of the mitochondrial electron transport chain, prevent both mitochondrial lipid peroxidation and ferroptosis. SkQ1 and methylene blue also prevented accumulation of lipofuscin observed after 24 h incubation of cardiomyocytes with ferric ammonium citrate. Using isolated cardiac mitochondria as an in vitro ferroptosis model, it was shown that rotenone (complex I inhibitor) in the presence of ferrous iron stimulates lipid peroxidation and lipofuscin accumulation. Our data indicate that ROS generated in complex I stimulate mitochondrial lipid peroxidation, lipofuscin accumulation, and ferroptosis induced by exogenous iron.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to the low micrometric size range. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in the secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. In more detail, the dimer formation achieved by molecular self-docking showed two distinct poses, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.

The relevance of the study is caused by the necessity to form a plan for the development of secondary vocational education that provides training of the most popular and promising specialties and working professions in accordance with international standards and advanced technologies on the basis of the leading professional educational organizations. The goal of this article is to identify the main motives and meanings of applicants' choices of popular and prospective specialties of secondary vocational education and working professions during the psychological, pedagogical and sociological research to paint a sociological portrait of students of vocational education and specialties from the TOP-50 list. The goals of the research are to carry out a comparative analysis of: 1) professional self-determination, 2) value orientations, 3) attitudes toward the teaching and upbringing, 4) life plans of applicants and students. The leading method in investigating this problem is the method of questioning. In our study we surveyed the applicants and students of specialties from the TOP-50 list. Results of the research: In order to study certain aspects of the sociological portrait of students through the method of questioning of students from the TOP-50 specialties we compiled a sociological questionnaire that included four blocks. The questionnaire for students included 28 questions and the questionnaire for applicants included 33 open and closed questions with the use of different scales with the possibility of selecting several of the listed options and the fields for answers. The results of the questioning of applicants and students are presented; the similarities and differences of the key motives, life plans, values of applicants and students who have chosen perspective professions of secondary vocational education are identified and summarized.

Abstract Background Metabolic dependencies of chronic lymphocytic leukaemia (CLL) cells may represent new personalized treatment approaches in patients harbouring unfavourable features. Methods Here, we used untargeted metabolomics and lipidomics analyses to isolate metabolomic features associated with aggressive CLL and poor survival outcomes. We initially focused on profiles associated with overexpression of the adverse metabolic marker glycosyltransferase (UGT2B17) associated with poor survival and drug resistance. Results Leukaemic B‐cell metabolomes indicated a significant perturbation in lipids, predominantly bio‐active sphingolipids. Expression of numerous enzyme‐encoding genes of sphingolipid biosynthesis pathways was significantly associated with shorter patient survival. Targeted metabolomics further exposed higher circulating levels of glucosylceramides (C16:0 GluCer) in CLL patients relative to healthy donors and an aggressive cancer biology. In multivariate analyses, C16:0 GluCer and sphinganine were independent prognostic markers and were inversely linked to treatment‐free survival. These two sphingolipid species function as antagonistic mediators, with sphinganine being pro‐apoptotic and GluCer being pro‐proliferative, tested in leukemic B‐CLL cell models. Blocking GluCer synthesis using ceramide glucosyltransferase inhibitors induced cell death and reduced the proliferative phenotype, which further sensitized a leukaemic B‐cell model to the anti‐leukaemics fludarabine and ibrutinib in vitro. Conclusions Specific sphingolipids may serve as prognostic markers in CLL, and inhibiting enzymatic pathways involved in their biosynthesis has potential as a therapaeutic approach.

Postictal apnea is thought to be a major cause of sudden unexpected death in epilepsy (SUDEP). However, the mechanisms underlying postictal apnea are unknown. To understand causes of postictal apnea, we used a multimodal approach to study brain mechanisms of breathing control in 20 patients (ranging from pediatric to adult) undergoing intracranial electroencephalography for intractable epilepsy. Our results indicate that amygdala seizures can cause postictal apnea. Moreover, we identified a distinct region within the amygdala where electrical stimulation was sufficient to reproduce prolonged breathing loss persisting well beyond the end of stimulation. The persistent apnea was resistant to rising CO2 levels, and air hunger failed to occur, suggesting impaired CO2 chemosensitivity. Using es-fMRI, a potentially novel approach combining electrical stimulation with functional MRI, we found that amygdala stimulation altered blood oxygen level–dependent (BOLD) activity in the pons/medulla and ventral insula. Together, these findings suggest that seizure activity in a focal subregion of the amygdala is sufficient to suppress breathing and air hunger for prolonged periods of time in the postictal period, likely via brainstem and insula sites involved in chemosensation and interoception. They further provide insights into SUDEP, may help identify those at greatest risk, and may lead to treatments to prevent SUDEP.