Correction: Podlutskii et al. Arabidopsis thaliana Accessions from the Chernobyl Exclusion Zone Show Decreased Sensitivity to Additional Acute Irradiation. Plants 2022, 11, 3142.

In the original publication [...].

Genetic and Epigenetic Aspects of Type 1 Diabetes Mellitus: Modern View on the Problem.

Omics technologies accumulated an enormous amount of data that advanced knowledge about the molecular pathogenesis of type 1 diabetes mellitus and identified a number of fundamental problems focused on the transition to personalized diabetology in the future. Among them, the most significant are the following: (1) clinical and genetic heterogeneity of type 1 diabetes mellitus; (2) the prognostic significance of DNA markers beyond the HLA genes; (3) assessment of the contribution of a large number of DNA markers to the polygenic risk of disease progress; (4) the existence of ethnic population differences in the distribution of frequencies of risk alleles and genotypes; (5) the infancy of epigenetic research into type 1 diabetes mellitus. Disclosure of these issues is one of the priorities of fundamental diabetology and practical healthcare. The purpose of this review is the systemization of the results of modern molecular genetic, transcriptomic, and epigenetic investigations of type 1 diabetes mellitus in general, as well as its individual forms. The paper summarizes data on the role of risk HLA haplotypes and a number of other candidate genes and loci, identified through genome-wide association studies, in the development of this disease and in alterations in T cell signaling. In addition, this review assesses the contribution of differential DNA methylation and the role of microRNAs in the formation of the molecular pathogenesis of type 1 diabetes mellitus, as well as discusses the most currently central trends in the context of early diagnosis of type 1 diabetes mellitus.

Comparative Analysis of the Effect of Gamma-, Electron, and Proton Irradiation on Transcriptomic Profile of Hordeum vulgare L. Seedlings: In Search for Molecular Contributors to Abiotic Stress Resilience.

The development of adaptation strategies for crops under ever-changing climate conditions is a critically important food security issue. Studies of barley responses to ionising radiation showed that this evolutionarily ancient stress factor can be successfully used to identify molecular pathways involved in adaptation to a range of abiotic stressors. In order to identify potential molecular contributors to abiotic stress resilience, we examined the transcriptomic profiles of barley seedlings after exposure to γ-rays, electrons, and protons. A total of 553 unique differentially expressed genes with increased expression and 124 with decreased expression were detected. Among all types of radiation, the highest number of differentially expressed genes was observed in electron-irradiated samples (428 upregulated and 56 downregulated genes). Significant upregulation after exposure to the three types of radiation was shown by a set of ROS-responsive genes, genes involved in DNA repair, cell wall metabolism, auxin biosynthesis and signalling, as well as photosynthesis-related genes. Most of these genes are known to be involved in plant ROS-mediated responses to other abiotic stressors, especially with genotoxic components, such as heavy metals and drought. Ultimately, the modulation of molecular pathways of plant responses to ionising radiation may be a prospective tool for stress tolerance programmes.

Radiation Hormesis in Barley Manifests as Changes in Growth Dynamics Coordinated with the Expression of PM19L-like, CML31-like, and AOS2-like.

The stimulation of growth and development of crops using ionising radiation (radiation hormesis) has been reported by many research groups. However, specific genes contributing to the radiation stimulation of plant growth are largely unknown. In this work, we studied the impact of the low-dose γ-irradiation of barley seeds on the growth dynamics and gene expression of eight barley cultivars in a greenhouse experiment. Our findings confirmed that candidate genes of the radiation growth stimulation, previously established in barley seedlings (PM19L-like, CML31-like, and AOS2-like), are significant in radiation hormesis throughout ontogeny. In γ-stimulated cultivars, the expression of these genes was aligned with the growth dynamics, yield parameters, and physiological conditions of plants. We identified contrasting cultivars for future gene editing and found that the γ-stimulated cultivar possessed some specific abiotic stress-responsive elements in the promotors of candidate genes, possibly revealing a new level of radiation hormesis effect execution. These results can be used in creating new productive barley cultivars, ecological toxicology of radionuclides, and eustress biology studies.

Comparative analysis of epigenetic variability in two pine species exposed to chronic radiation in the Chernobyl and Fukushima affected zones.

Comparative analysis of epigenetic variability in two pine species affected as a result of the Chernobyl and Fukushima accidents is presented. The absorbed dose rate within the affected Chernobyl sites varies over a wider range (1.5-24.6 µGy/h) than within the Fukushima sites (3.5-6.5 µGy/h). It was shown that chronic irradiation can change the level of whole genome methylation in pine populations, but in different ways. The genomes of Japanese red pines are hypomethylated, and the degree of methylation and hydroxymethylation decreases with an increase in the level of radiation exposure. In contrast, the percentages of genome methylation and hydroxymethylation in Scots pine populations exceed the reference levels. The observed discrepancy in the patterns of genome-wide DNA methylation can be attributed partly to the design of the study (differences in the climate, radiation dose, age and species of the pines) which could affect the results. In the frame of IRAP analysis, a larger number of different bands was observed in the Chernobyl populations compared to the Japanese populations. Both the Japanese and Chernobyl populations are characterized by significant genetic variability. However, the main part of this variability is observed within populations. The dendrograms, based on presence/absence of IRAP fragments and Nei's genetic distances, revealed subdivisions of the Chernobyl and Japanese populations according to the level of radioactive contamination. Analysis of the results presented will improve our understanding of the mechanisms underlying the responses of pine trees to chronic radiation exposure.

Silent intrathyroid parathyroid carcinoma.

Summary: A 59-year-old male presented with an accidental thyroid mass in 2022. Ultrasound and CT scan showed a nodule 5.2 × 4.9 × 2.8 cm (EU-TIRADS 4) in the right lobe of the thyroid gland. Taking into account the results of the fine needle aspiration biopsy (Bethesda V), intrathyroid localization, and absence of clinical symptoms, a malignant tumor of the thyroid gland was suspected. The patient underwent total thyroidectomy using fluorescence angiography with indocyanine green, and two pairs of intact parathyroid glands were visualized in typical localization. Unexpected histological and immunohistochemistry examinations revealed parathyroid carcinoma. Due to the asymptomatic course of the disease and atypical localization of parathyroid tumor, primary hyperparathyroidism was not suspected before the surgery. The diagnosis of asymptomatic intrathyroid parathyroid cancer is a serious diagnostic challenge for a wide range of specialists. Learning points: Parathyroid cancer is a rare disease that may be asymptomatic. Intrathyroidal localization of parathyroid carcinoma is casuistic and challenging for diagnosis, and the treatment strategy is not well defined. Preoperative parathyroid hormone and serum calcium testing are recommended for patients with solid thyroid nodules (Bethesda IV-V).

Growth, antioxidant system, and phytohormonal status of barley cultivars contrasting in cadmium tolerance.

Cadmium leads to disturbance of plant growth, and the manifestation of toxicity can vary greatly in different genotypes within one species. In this work we studied the effect of Cd on growth, antioxidant enzyme activity, and phytohormonal status of four barley cultivars (cvs. Simfoniya, Mestnyj, Ca 220702, Malva). According to the earlier study on seedlings, these cultivars were contrast in tolerance to Cd: Simfoniya and Mestnyj are Cd-tolerant and Ca 220702 and Malva are Cd-sensitive. The results presented showed that barley plants accumulated more Cd in straw than in grain. Tolerant cultivars accumulated significantly less Cd in grain than sensitive ones. The leaf area appeared to be a growth parameter susceptible to Cd treatment. The significant differences in leaf area values depended on Cd contamination and were not associated with cultivars' tolerance. Tolerance of cultivars was contingent on the activity of the antioxidant defense system. Indeed, activity of enzymes decreased in sensitive cultivars Ca 220702 and Malva under Cd stress. In contrast, in tolerant cultivars, increased activity of guaiacol peroxidase was revealed. The concentrations of abscisic acid and salicylic acid mostly increased as a result of Cd treatment, while the concentrations of auxins and trans-zeatin either decreased or did not change. The results obtained indicate that antioxidant enzymes and phytohormones play an important role in the response of barley plants to elevated concentrations of cadmium; however, these parameters are not able to explain the differentiation of barley cultivars in terms of tolerance to cadmium at the seedling stage. Therefore, barley intraspecific polymorphism for cadmium resistance is determined by the interplay of antioxidant enzymes, phytohormones, and other factors that require further elucidation.

Case report: Sagliker syndrome in the patient with recurrent tertiary hyperparathyroidism due to intrathyroidal parathyroid carcinoma.

Sagliker syndrome (SS) is an extremely rare disorder that manifests in patients with advanced chronic kidney disease (CKD) undergoing programmed hemodialysis as a renal replacement therapy. Treatment of secondary hyperparathyroidism (SHPT) in these patients is still challenging. The main clinical manifestations of SS include craniofacial and fingertip deformities, dental anomalies, gingival hyperplasia, short stature, hearing loss, neurological and psychiatric impairment. The etiology and pathogenesis of SS in patients with SHPT require further clarification. However, mutations in the GNAS1, FGF23, and FGFR3 genes were described in some patients, suggesting a possible role of genetic predisposition to the syndrome. The preferred therapeutic approach for SS is surgery, but the volume of the operation is debated. The main surgical strategies include total, subtotal parathyroidectomy, or total parathyroidectomy with autotransplantation of the parathyroid gland (PG). Unfortunately, parathyroidectomy does not contribute to the regression of significant skeletal deformities. We present a unique clinical case of a patient with classical features of SS, recurrent tertiary hyperparathyroidism (THPT) after total parathyroidectomy due to intrathyroidal parathyroid carcinoma (PC).

Arabidopsis thaliana Accessions from the Chernobyl Exclusion Zone Show Decreased Sensitivity to Additional Acute Irradiation.

Chronic ionising radiation exposure is a main consequence of radioactive pollution of the environment. The development of functional genomics approaches coupled with morphological and physiological studies allows new insights into plant adaptation to life under chronic irradiation. Using morphological, reproductive, physiological, and transcriptomic experiments, we evaluated the way in which Arabidopsis thaliana natural accessions from the Chernobyl exclusion zone recover from chronic low-dose and acute high-dose γ-irradiation of seeds. Plants from radioactively contaminated areas were characterized by lower germination efficiency, suppressed growth, decreased chlorophyll fluorescence, and phytohormonal changes. The transcriptomes of plants chronically exposed to low-dose radiation indicated the repression of mobile genetic elements and deregulation of genes related to abiotic stress tolerance. Furthermore, these chronically irradiated natural accessions showed higher tolerance to acute 150 Gy γ-irradiation of seeds, according to transcriptome and phytohormonal profiles. Overall, the lower sensitivity of the accessions from radioactively contaminated areas to acute high-dose irradiation may come at the cost of their growth performance under normal conditions.

STRUCTURAL AND FUCNTIONAL PARAMETERS OF THE CARDIOVASCULAR SYSTEM DURING ATRIAL FIBRILLATION IN PATIENTS AFTER STROKE.

OBJECTIVE: The aim: To evaluate the structural and functional parameters of the cardiovascular system during atrial fibrillation (AF) in patients after a stroke. PATIENTS AND METHODS: Materials and methods: In the main group, we selected 28 patients with non-valvular AF who had previously suffered an ischemic stroke (IS). The comparison group (30 people) included patients with AF without a stroke, comparable in age and gender. RESULTS: Results: As a result of the study, we discovered an increase in the risk of stroke with an increase in the thickness of the intima-media complex>0.9mm. The thickness of the interventricular septum was 1.19 (1.1; 1.25) in the group of patients with IS, and in the group of patients without IS - 1.09 (1.0; 1.19) cm (p = 0.019), the thickness of the LV posterior wall is greater in the main group 1.14 (1.05; 1.24) and 1.09 (1.01; 1.18) cm in the comparison group (p = 0.038). The myocardial mass index is 123.3 in the main group and 107.4 g/m2 in the comparison group (p = 0.41), which indicates left ventricle (LV) hypertrophy in the main group. CONCLUSION: Conclusions: thus, during AF in stroke patients, changes in the following structural and functional parameters of the cardiovascular system were discovered: an increase in the thickness of the interventricular septum, thickness of the posterior wall of the LV, and in the thickness of the intima-media complex.

Characterization of a New Positive Allosteric Modulator of AMPA Receptors - PAM-43: Specific Binding of the Ligand and its Ability to Potentiate AMPAR Currents.

BACKGROUND: Currently, the most dynamic areas in the glutamate receptor system neurobiology are the identification and development of positive allosteric modulators (PAMs) of glutamate ionotropic receptors. PAM-based drugs are of great interest as promising candidates for the treatment of neurological diseases, such as epilepsy, Alzheimer's disease, schizophrenia, etc. Understanding the molecular mechanisms underlying the biological action of natural and synthetic PAMs is a key point for modifying the original chemical compounds as well as for new drug design. OBJECTIVE: We are trying to elaborate a system of molecular functional screening of ionotropic glutamate receptor probable PAMs. METHODS: The system will be based on the radioligand - receptor method of analysis and will allow rapid quantification of new AMPAR probable PAMs molecular activity. We plan to use a tritiumlabeled analogue of recently elaborated ionotropic GluR probable PAM ([3H]PAM-43) as the main radioligand. RESULTS: Here, we characterized the specific binding of the ligand and its ability to potentiate ionotropic GluR currents. The existence of at least two different sites of [3H]PAM-43 specific binding has been shown. One of the above sites is glutamate-dependent and is characterized by higher affinity. "Patchclamp" technique showed the ability of PAM-43 to potentiate ionotropic GluR currents in rat cerebellar Purkinje neurons in a concentration-dependent manner. CONCLUSION: The possibility of using PAM-43 as a model compound to study different allosteric effects of potential regulatory drugs (AMPAR allosteric regulators) was shown. [3H]PAM-43 based screening system will allow rapid selection of new AMPAR probable PAM structures and quantification of their molecular activity.

Seed Gamma Irradiation of Arabidopsis thaliana ABA-Mutant Lines Alters Germination and Does Not Inhibit the Photosynthetic Efficiency of Juvenile Plants.

Plant growth response to γ-irradiation includes stimulating or inhibitory effects depending on plant species, dose applied, stage of ontogeny and other factors. Previous studies showed that responses to irradiation could depend on ABA accumulation and signaling. To elucidate the role of ABA in growth and photosynthetic responses to irradiation, lines Col-8, abi3-8 and aba3 -1 of Arabidopsis thaliana were used. Seeds were γ-irradiated using 60Co in the dose range 50-150 Gy. It was revealed that the dose of 150 Gy affected germination parameters of aba3 -1 and Col-8 lines, while abi3-8 line was the most resistant to the studied doses and even showed faster germination at early hours after γ-irradiation at 50 Gy. These results suggest that susceptibility to ABA is probably more important for growth response to γ-irradiation than ABA synthesis. The photosynthetic functioning of 16-day-old plants mainly was not disturbed by γ-irradiation of seeds, and no indication of photosystem II photoinhibition was noticed, revealing the robustness of the photosynthetic system of A. thaliana. Glutathione peroxidase activity and ABA concentrations in plant tissues were not affected in the studied dose range. These results contribute to the understanding of germination and photosynthesis fine-tuning and of mechanisms of plant tolerance to ionizing radiation.

Effect of in vivo and in vitro exposure to electrostatic field on some hematological parameters in rats.

The aim of this study was to investigate the effect of the external electrostatic field (ESF) on some hematological parameters in rats. Both in vivo and in vitro experiments were carried out. In in vivo investigations, rats were exposed to ESF (200 kV/m) during short (1 h) and long periods (6 days, 6 h daily). For in vitro study, the blood of intact rats was exposed to ESF for 1 h. Blood hematology was measured using validated ABX Micros ESV 60 Veterinary Hematology Analyzer. DNA damage in blood leucocytes was detected by means of comet assay. ESF effect on blood cell count was mainly manifested in white blood cells (WBC) and platelets. Damage of WBC was shown both in vitro and in vivo despite alterations in the count. This means the observed increase in WBC count in some cases might be a result of WBC compensatory mobilization from the bone marrow. Red blood cell (RBC) count and related parameters were slightly affected by ESF. Nevertheless, alterations in the shape and size of RBC were manifested. All ESF effects were extinguished in 14 days after the end of exposure. Bioelectromagnetics. 37:513-526, 2016. © 2016 Wiley Periodicals, Inc.