Morphological and genetic characteristics of garfish Belone belone (L., 1760) (Belonidae, Teleostei) population from the southern Bulgarian Black Sea coast

This study was conducted to investigate genetic and some morphometric and meristic characteristics of garfish Belone belone from Nesebar in the Bulgarian Black Sea coast. Twelve morphometric characters were measured, and six meristic characters were counted for each individual. Based on both sexes’ morphological and meristic analyses, no statistically significant sexual differences were observed. Additionally, DNA barcoding was done. The fragment of the cytochrome oxidase subunit I (COI) gene of mitochondrial DNA was sequenced to supplement the species identification and population diversity study. Two haplotypes were found out of 39 sequences, indicating a low level of haplotype diversity (0.146±0.072). Nucleotide diversity was also found to be low (0.00023±0.00011). The Nesebar population of B. belone requires conservation efforts, due to the highly decreased mtDNA genetic diversity

Morphological and genetic characteristics of garfish Belone belone (L., 1760) (Belonidae, Teleostei) population from the southern Bulgarian Black Sea coast

This study was conducted to investigate genetic and some morphometric and meristic characteristics of garfish Belone belone from Nesebar in the Bulgarian Black Sea coast. Twelve morphometric characters were measured, and six meristic characters were counted for each individual. Based on both sexes’ morphological and meristic analyses, no statistically significant sexual differences were observed. Additionally, DNA barcoding was done. The fragment of the cytochrome oxidase subunit I (COI) gene of mitochondrial DNA was sequenced to supplement the species identification and population diversity study. Two haplotypes were found out of 39 sequences, indicating a low level of haplotype diversity (0.146±0.072). Nucleotide diversity was also found to be low (0.00023±0.00011). The Nesebar population of B. belone requires conservation efforts, due to the highly decreased mtDNA genetic diversity

Impact of CYP3A7, CYP2D6 and ABCC2/ABCC3 polymorphisms on tacrolimus steady state concentrations in Bulgarian kidney transplant recipients

AbstractPolymorphisms in the genes of drug-metabolizing enzymes have the potential to contribute to inter-individual differences in drug pharmacokinetics and toxicity. A custom next-generation sequencing (NGS) panel was used in 71 kidney transplanted patients to study the polymorphisms of 11 genes relevant to the metabolism of immunosuppressive drugs. Cyclosporine A and tacrolimus concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. More than 1000 polymorphisms were found in the studied 11 genes, and 45% of them were different non-synonymous variants. Eleven missense mutations were observed in the CYP3A7 gene, resulting in increased metabolism of tacrolimus at day 21 post-transplantation (6.7 µg/L vs. 10.3 µg/L; p = 0.048). Two alleles encoding a cytochrome P450 2D6 enzyme with impaired function—CYP2D6*4 (non-functional) and CYP2D6*10 (decreased function), were found in the studied group and both of them were associated with higher levels of tacrolimus at day 14 (10.1 µg/L; p = 0.021 and 9.7 µg/L; p = 0.036, vs. 7.7 µg/L respectively). Altered function of ABC transporters C3 and C2 was also associated with increased TAC concentration. ABCC3 significantly influenced TAC metabolism by itself, but polymorphisms affecting both ABCC3 and ABCC2 resulted in higher changes: 13.6 µg/L vs. 7.9 µg/L, day 14 (p = 0.003) and 20 µg/L versus 9.3 µg/L, day 21 (p = 0.019). All associations were also checked for variants affecting the activity of CYP3A4 and CYP3A5. Despite its small size, the study points out that the pharmacogenetics of calcineurin inhibitors may also be influenced by other genes besides CYP3A4 and CYP3A5

DataSheet_1_Primary immunodeficiencies in Bulgaria - achievements and challenges of the PID National Expert Center.pdf

Tremendous progress has been made in the recognition of primary immune deficiencies (PIDs) in Bulgaria since in 2005 we have joined the J Project Central-Eastern European collaborative program. Ten years later an Expert Centre (ExpC) for Rare Diseases - Primary Immune Deficiencies at the University Hospital “Alexandrovska”- Sofia was established. In May 2017 The National Register of Patients with Rare Diseases also became operational as a database containing clinical and genetic information for Bulgarian patients with PID. The transfer of data and information on Bulgarian PID patients to the European Primary Immunodeficiency Database, managed by the European Society for Primary Immunodeficiency (ESID) has started in 2020. The total number of registered patients now is 191 (100 men and 91 women), with more than half of them being children (106; 55.5%). Regular updating of the information in the register showed that 5.2% of patients are deceased and the majority (94.8%) is a subject to continuous monitoring as it has been reported for other European countries as well. With the establishment of the ExpC, the dynamics in the diagnosis and registration of patients with PID significantly intensified. For a period of 5 years (2016-2021) 101 patients were evaluated and registered in comparison with previous period - before ExpC establishment when only 89 patients were diagnosed. The most common pathology was humoral immune deficiency (85 patients; 44.5%). Ninety-six (50.3%) of the patients underwent genetic testing, and 66. 7% had genetically confirmed diagnosis. Three of the variants have not been reported in population databases. Following genetic investigation confirmation of the initial phenotypic diagnosis was achieved in 82.8% of cases and change in the diagnosis - in 17%. Sixty-two patients were on regular replacement or specific therapy, and the rest received symptomatic and supportive treatment. In summary, we present the first epidemiological report of PIDs in Bulgaria, based on the National PID register. Data on the clinical, phenotypic and genetic characteristics of PID patients provided important information about the nature of primary immunodeficiency diseases in our country.</p

Genetic diversity and morphological characterisation of three turbot (Scophthalmus maximus L., 1758) populations along the Bulgarian Black Sea coast

Turbot (Scophthalmus maximus L., 1758) is a valuable commercial fish species classified as endangered. The conservation and sustainability of the turbot populations require knowledge of the population’s genetic structure and constant monitoring of its biodiversity. The present study was performed to evaluate the population structure of turbot along the Bulgarian Black Sea coast using seven pairs of microsatellites, two mitochondrial DNA (COIII and CR) and 23 morphological (15 morphometric and 8 meristic) markers. A total of 72 specimens at three locations were genotyped and 59 alleles were identified. The observed number of alleles of microsatellites was more than the effective number of alleles. The overall mean values of observed (Ho) and expected heterogeneity (He) were 0.638 and 0.685. A high rate of migration between turbot populations (overall mean of Nm = 17.484), with the maximum value (19.498) between Shabla and Nesebar locations, was observed. This result corresponded to the low level of genetic differentiation amongst these populations (overall mean Fst = 0.014), but there was no correlation between genetic and geographical distance. A high level of genetic diversity in the populations was also observed. The average Garza-Williamson M index value for all populations was low (0.359), suggesting a reduction in genetic variation due to a founder effect or a genetic bottleneck. Concerning mitochondrial DNA, a total number of 17 haplotypes for COIII and 41 haplotypes for CR were identified. The mitochondrial DNA control region showed patterns with high haplotype diversity and very low nucleotide diversity, indicating a significant number of closely-related haplotypes and suggesting that this population may have undergone a recent expansion. Tajima’s D test and Fu’s FS test suggested recent population growth. Pairwise Fst values were very low. The admixture and lack of genetic structuring found pointed to the populations analysed probably belonging to the same genetic unit. Therefore, a proper understanding and a sound knowledge of the level and distribution of genetic diversity in turbot is an important prerequisite for successful sustainable development and conservation strategies to preserve their evolutionary potential

On Two Cases with Autosomal Dominant Hyper IgE Syndrome: Importance of Immunological Parameters for Clinical Course and Follow-Up

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare disease described in 1966. It is characterized by severe dermatitis, a peculiar face, frequent infections, extremely high levels of serum IgE and eosinophilia, all resulting from a defect in the STAT3 gene. A variety of mutations in the SH2 and DNA-binding domain have been described, and several studies have searched for associations between the severity of the clinical symptoms, laboratory findings, and the type of genetic alteration. We present two children with AD-HIES–a girl with the most common STAT3 mutation (R382W) and a boy with a rare variant (G617E) in the same gene, previously reported in only one other patient. Herein, we discuss the clinical and immunological findings in our patients, focusing on their importance on disease course and management

Effects of anthropogenic and environmental stressors on the current status of red mullet (Mullus barbatus L., 1758) populations inhabiting the Bulgarian Black Sea waters

The red mullet (Mullus barbatus Linnaeus, 1758) is a keynote species for the Bulgarian Black Sea ecosystem and fisheries; nevertheless, existing knowledge on population status is very scarce. The present study was intended to assess the health status and adaptive potential of M. barbatus populations inhabiting the Bulgarian waters of the Black Sea. Our findings revealed that populations of M. barbatus are exposed to a variety of anthropogenic and environmental stressors. The species’ status was assessed using representative genetic, morphological, biochemical and chemical biomarkers from specimens obtained in the research area’s northern and southern regions. Based on mtDNA markers, genetic analysis revealed low haplotype and nucleotide diversity, typically observed in overexploited or “threatened” populations. Examining the morphology of the specimens revealed no discernible pattern of differentiation. Except for aluminium and chrome, metal and PAH concentrations in fish were below the regulatory thresholds. The specimens from the southern region ingested more microplastics than those from the northern region. The majority of specimens collected from the southern region also exhibited elevated levels of oxidative stress and decreased antioxidant defence, which can be interpreted as an early indication that they had reached the limits of their adaptive potential. Further research on the composite effects of the stressogenic environment on the Black Sea biota are critically needed, as well as the introduction of new indicators and thresholds at molecular and cellular levels for adequate monitoring of both the ecological state of the marine environment and its biota

Effects of anthropogenic and environmental stressors on the current status of red mullet (Mullus barbatus L., 1758) populations inhabiting the Bulgarian Black Sea waters

The red mullet (Mullus barbatus Linnaeus, 1758) is a keynote species for the Bulgarian Black Sea ecosystem and fisheries; nevertheless, existing knowledge on population status is very scarce. The present study was intended to assess the health status and adaptive potential of M. barbatus populations inhabiting the Bulgarian waters of the Black Sea. Our findings revealed that populations of M. barbatus are exposed to a variety of anthropogenic and environmental stressors. The species’ status was assessed using representative genetic, morphological, biochemical and chemical biomarkers from specimens obtained in the research area’s northern and southern regions. Based on mtDNA markers, genetic analysis revealed low haplotype and nucleotide diversity, typically observed in overexploited or “threatened” populations. Examining the morphology of the specimens revealed no discernible pattern of differentiation. Except for aluminium and chrome, metal and PAH concentrations in fish were below the regulatory thresholds. The specimens from the southern region ingested more microplastics than those from the northern region. The majority of specimens collected from the southern region also exhibited elevated levels of oxidative stress and decreased antioxidant defence, which can be interpreted as an early indication that they had reached the limits of their adaptive potential. Further research on the composite effects of the stressogenic environment on the Black Sea biota are critically needed, as well as the introduction of new indicators and thresholds at molecular and cellular levels for adequate monitoring of both the ecological state of the marine environment and its biota