Molecular Genetic Characterization Research Articles

The molecular-genetic characteristics of uropathogenic Escherichia coli isolated from pregnant women with asymptomatic bacteriuria

Introduction. Uropathogenic Escherichia coli (UPEC) are the dominant bacterial pathogens of urinary tract infections (UTIs). UPEC belong to different phylogenetic groups and have many virulence factors, the study of which, in conjuction with the assessment of their relationship with clinical forms of UTI, is necessary for a better understanding of the pathogenesis of UTI and the development of new diagnostic algorithms. Aim: determination of the molecular genetic characteristics of uropathogenic Escherichia coli isolated from pregnant women with asymptomatic bacteriuria. Materials and methods. Clinical isolates of uropathogenic E. coli (n = 70) from pregnant women with asymptomatic bacteriuria were included in the study. The PCR method was used to determine the belonging to phylogenetic groups and detect 15 virulence markers — genes associated with adhesion (fimH, papC, sfa, afa, focG); toxin synthesis (cnf 1, hlyA, sat, vat, usp); siderophores (fyuA, iroN, iuc); capsular antigen (kpsMII). To assess the statistical significance of differences, Fisher's exact test was used. Differences were considered statistically significant at a confidence interval of 95% (p 0.05). Results. Most of the UPEC isolates belonged to phylogroup B2 (51,4%) and were characterized by the detection of all UPEC-associated virulence factors included in this study; genes associated with adhesion (sfa, focG), invasins (ibeA), synthesis of toxins (hlyA, cnf1, vat, usp) and capsule (kpsMII), siderophores (fyuA, iroN, hlyA) were detected significantly more frequently (p 0.05). Two or more virulence determinants were detected in 93% of isolates. Conclusion. The identification of key determinants of virulence and/or a combination of virulence genes can be a prognostic marker for predicting the course of UTI, especially in pregnant women, and will expand diagnostic capabilities taking into account the virulent properties of the uropathogen.

Molecular genetic characteristics of Streptococcus pneumoniae serogroups 15 and 11 representatives circulating in Russia and their relationship with global genetic lineages

Aim of the study. Genetic analysis of Streptococcus pneumoniae serogroups 15 and 11 circulating in Russia according to the following parameters: serotype affiliation; clonal complex (CC); presence of resistance and virulence determinants; relatedness to genetic lineages circulating in the world, and justification of inclusion of the actual serotypes of serogroups 15 and 11 in the future conjugate vaccine composition. Materials and methods. The study included whole genome data of S. pneumoniae serogroups 11 and 15. Results. Genomes of serogroup 15 strains from Russia are represented mainly by serotypes 15B and 15C, the majority of which belong to CC-1025 and CC-1262. CC-1025 is characterized by a more frequent association with invasive diseases. Representatives of CC-1025 and CC-1262 contain virulence determinants unique to these genetic lineages within the studied population of serogroup 15: oligopeptide transporters, fructose-specific PTS system, unique hydrolase variants, additional iron ion transporters, the gene of zinc metalloprotease ZmpC (activating human MMP9). The genomes of serogroup 11 are represented mainly by serotype 11A, the majority belong to CC-62 and CC-1012. The virulence determinants unique to CC-62 (within the studied serogroup 11) include bacteriocins, components of oligopeptide transport, flavin reductase-like protein (adhesin, also protects bacteria from oxidative stress), fucose processing operon, PsaA (adhesin, also a component of the ATP-binding cassette transporter that imports manganese ions). Conclusion. In the Russian Federation, serogroups 15 and 11 are the most common non-vaccine serogroups. No antimicrobial resistance determinants have been identified in the genomes of representatives of these serogroups. For each of the genetic lineages prevalent in Russia and associated with serogroups 15 and 11, unique virulence determinants within the studied serogroup have been identified, which may contribute to the success of these lineages. It is advisable to include serotypes 15B and 11A in vaccines promising for the Russian Federation.

Molecular Identification and Genetic Characterization of Trypanosoma Evansi from Cattle in Makkah, Saudi Arabia

Molecular Identification and Genetic Characterization of Trypanosoma Evansi from Cattle in Makkah, Saudi Arabia

Activity of East Siberian Trichoderma Isolates against Plant-pathogenic Microorganisms

The genus Trichoderma comprised important antagonists of pathogenic fungi and can be used in agriculture to combat various plant diseases. In the course of the present work, two micromycete strains were isolated from wood cuts in Eastern Siberia, which were identified by morphological and molecular genetic characteristics as Trichoderma atroviride and Trichoderma harzianum. These Trichoderma strains efficiently inhibited the development of the pathogenic fungi studied (by up to 80%). The data presented in the paper indicate that Trichoderma atroviride and Trichoderma harzianum may be promising for further study of the means of biocontrol of plant diseases.

Auditory Phenotype of a Novel Missense Variant in the CEACAM16 Gene in a Large Russian Family With Autosomal Dominant Nonsyndromic Hearing Loss.

Autosomal dominant hearing loss is represented by a large number of genetically determined forms. Over 50 genes associated with dominant nonsyndromic hearing impairments were described. Pathogenic variants in the CEACAM16 gene lead to the development of DFNA4B hearing loss. Currently, 8 pathogenic variants in this gene have been described. The objective of this study was to study the audiological and molecular genetic characteristics of a large family with CEACAM16-associated autosomal dominant nonsyndromic hearing loss. A detailed anamnesis was collected, and a comprehensive audiological examination was performed for 21 family members. Genetic testing was performed, including whole-genome sequencing for the proband's son and Sanger sequence analysis for the proband and for all available family members. In a large Russian family, including 5 generations, an autosomal dominant type of slowly progressing nonsyndromic late-onset hearing loss was observed. Eleven family members suffer from hearing impairment, which starts with tinnitus and threshold increase at high frequencies, since the age of 5-20 years. Hearing loss slowly progresses with age in each person and is similar to age-related hearing loss. We have detected the novel likely pathogenic variant с.419С>T (p.(Thr140Ile)) in exon 3 of the CEACAM16 gene, which segregates with late-onset nonsyndromic hearing loss in this family. The clinical data obtained in the examined family correspond with the phenotype in previously described cases. In general, the study widened the mutation spectrum of the gene, allowing to carry out medical genetic counseling and to answer the questions about the hearing impairment prognosis for future generations.

The prevalence, antimicrobial resistance and molecular genetic characteristics of fosfomycin-resistant Klebsiella pneumoniae isolated from raw milk

This investigation aims to explore the molecular epidemiological characteristics of the fosfomycin resistance gene, fosA5, in unpasteurized raw milk. A total of 385 unpasteurized raw milk samples were collected from dairy farms in Jiangsu province, China. From these samples, 102 strains of Klebsiella pneumoniae were isolated, with 9 of them testing positive for the presence of the fosA5 gene. Antimicrobial susceptibility testing revealed that K. pneumoniae carrying fosA5 exhibited high-level resistance to fosfomycin but also to other tested antibiotics, indicating multidrug resistance. The S1-PFGE and conjugation results indicated that the fosA5 gene was located on the chromosome. Furthermore, the analysis of PFGE patterns, MLST, and WGS elucidated the genetic diversity among K. pneumoniae strains harboring the fosA5 gene, indicating both clonal and horizontal transmission. This study highlights the prevalence and characteristics of the fosA5 fosfomycin resistance gene in large-scale dairy farms in Jiangsu province. Given its potential public health risks, these findings warrant significant attention.

Acral Fibrochondromyxoid Tumor: A Clinicopathologic and Molecular Genetic Study of 37 Cases

Acral fibrochondromyxoid tumor (AFCMT) is a recently described likely benign mesenchymal neoplasm arising in the distal extremities with distinctive histologic features and a recurrent THBS1::ADGRF5 fusion. We studied an additional 37 cases of AFCMT and expanded on the so-far reported clinicopathologic and molecular findings. Tumors occurred in 21 females and 16 males, ranging in age from 17 to 78 years (median age: 47), and solely involved the hands (24/37, 65%) or feet (13/37, 35%). Histologic examination revealed well-delineated uni- or multinodular tumors with prominent vasculature-rich septa and bland, chondrocyte-like tumor cells set within abundant chondromyxoid stroma. Immunohistochemical studies showed that tumor cells were positive for CD34 (25/27; 93%) and ERG (27/27; 100%), whereas negative for S100 protein (0/31). Molecular analysis revealed evidence of a THBS1::ADGRF5 fusion in 17 of 19 (89%) successfully tested tumors. Clinical follow-up was available in 8 cases (median: 97 months), with multiple local recurrences in 1 case at 276, 312, and 360 months. We conclude that AFCMT is a distinct entity with reproducible morphologic, immunohistochemical, and molecular genetic features that should be differentiated from other similar appearing acral mesenchymal neoplasms.

The Role of Epithelial-to-Mesenchymal Transition Transcription Factors (EMT-TFs) in Acute Myeloid Leukemia Progression.

Acute myeloid leukemia (AML) is a diverse malignancy originating from myeloid progenitor cells, with significant genetic and clinical variability. Modern classification systems like those from the World Health Organization (WHO) and European LeukemiaNet use immunophenotyping, molecular genetics, and clinical features to categorize AML subtypes. This classification highlights crucial genetic markers such as FLT3, NPM1 mutations, and MLL-AF9 fusion, which are essential for prognosis and directing targeted therapies. The MLL-AF9 fusion protein is often linked with therapy-resistant AML, highlighting the risk of relapse due to standard chemotherapeutic regimes. In this sense, factors like the ZEB, SNAI, and TWIST gene families, known for their roles in epithelial-mesenchymal transition (EMT) and cancer metastasis, also regulate hematopoiesis and may serve as effective therapeutic targets in AML. These genes contribute to cell proliferation, differentiation, and extramedullary hematopoiesis, suggesting new possibilities for treatment. Advancing our understanding of the molecular mechanisms that promote AML, especially how the bone marrow microenvironment affects invasion and drug resistance, is crucial. This comprehensive insight into the molecular and environmental interactions in AML emphasizes the need for ongoing research and more effective treatments.

Clinical, pathological and genetic characteristics of 17 unrelated children with Alagille Syndrome

BackgroundAlagille syndrome (ALGS) is a multisystem genetic disorder frequently characterized by hepatic manifestations. This study analyzed the clinical, pathological, and molecular genetic features of ALGS to improve the efficiency of clinical diagnosis.MethodsWe retrospectively analyzed the clinical manifestations, pathological examination findings, and genetic testing results of 17 children diagnosed with ALGS based on the revised criteria and hospitalized at our center from January 2012 to January 2022.ResultsThe clinical manifestations are as follows: Cholestasis (16/17, 94%), characteristic facies (15/17, 88%), heart disease (12/16, 75%), butterfly vertebrae (12/17, 71%) and posterior embryotoxon (7/12, 58%). Among the 15 patients who underwent liver pathology examination, 13 (87%) were found to have varying degrees of bile duct paucity. Genetic testing was performed on 15 children, and pathogenic variants of the jagged canonical Notch ligand 1 (JAG1) gene were identified in 13 individuals, including 4 novel variants. No pathogenic variant in the notch homolog 2 (NOTCH2) gene were identified, and 2 children exhibited none of the aforementioned gene pathogenic variants. The median follow-up duration was 7 years. Of the remaining 15 patients (excluding 2 lost to follow-up), 11 remained stable, 4 deteriorated, and no patient died during the follow-up period.ConclusionsAmong children diagnosed with ALGS, cholestasis stands as the most common feature. To minimize the risk of misdiagnosis, genetic testing should be performed on children exhibiting cholestasis, followed by the application of the revised diagnostic criteria for ALGS. While pharmacological therapy has shown effectiveness for ALGS patients, liver transplantation may be considered in instances of severe pruritus.

First Report on the Molecular Detection and Genetic Characterization of Toxoplasma gondii From Donkeys in Kenya.

The present study was conducted to determine the presence of Toxoplasma gondii in donkeys by molecular tests and genetic diversity analysis of the obtained DNA samples from central Kenya. A total of 363 blood samples were collected from donkeys in Meru and Kirinyaga Counties, and 96 samples that were previously seropositive for T. gondii using indirect ELISA were subjected to nested PCR based on the amplification of the internal transcribed spacer 1 (ITS-1) gene followed by DNA sequencing and phylogenetic analysis. Genotyping was performed on 15 selected positive samples using multilocus nested polymerase chain reaction restriction fragment length polymorphism (Mn-PCR-RFLP) with eight genetic markers ('SAG 2, 5'SAG 2, Alt. SAG 2, SAG 3, GRA 6, C29-2, BTUB and L358). Toxoplasma gondii DNA was detected in 36.5% (35/96) of the blood samples. The sequences obtained exhibited 98.2-99.5% homology with those deposited in GenBank. Phylogenetic analysis demonstrated that the obtained sequences are conserved and clustered with those of infecting animals from other regions of the world. Eighteen distinct T. gondii haplotypes were identified to be circulating in donkeys from central Kenya. The T. gondii DNA samples exhibited high haplotype diversity (Hd: 0.915) and limited genetic diversity (π = 0.01027). PCR-RFLP of T. gondii DNA-positive samples revealed three different genetic combinations that consisted of alleles I, II and III, indicating the dissemination of atypical genotypes. This study demonstrated that T. gondii is widespread in donkeys from Kenya and could be a possible source of infection in humans. These findings are important for designing control strategies for this parasite to improve the livestock sector, which is one of the main sources of livelihood for farmers in Kenya.

Phenotypic and molecular characterizations of 46,XY disorders of sex development due to variants of NR5A1 gene

The clinical and molecular genetic characteristics of 46,XY disorders of sex development caused by NR5A1 gene variants in 15 cases were analyzed to improve the understanding of this disease. The clinical data of children with NR5A1 gene variants diagnosed at the Children's Hospital Affiliated to Zhengzhou University from March 2016 to December 2021 were retrospectively analyzed. Whole exome sequencing was performed to confirm the candidate sites, and Sanger sequencing was performed for validation. The patients were treated and followed up according to their disease characteristics. At the initial diagnosis, 5 of the 15 cases were raised as females and 10 as males. The gonadal tissue was testis without residual Müllerian or ooticular structure, and all had various degrees of genital abnormalities. The average EMS masculinity score was 4.8 (1 ~ 9), including micropenis (100.0%), hypospadias (86.7%), unfused scrotum (46.7%), and abnormal testicular position (60.0%), in which the hypospadias was Ⅱ°~ Ⅳ°. There was no skin pigmentation in 5 patients with growth retardation. Chromosomal karyotypes were 46,XY, adrenocorticotropin and cortisol levels were normal, electrolyte levels were normal, HCG stimulation test in 5 cases had normal response, 9 cases had low response. Anti-Müllerian hormone and statin B had decreased abnormally with age. A total of 14 NR5A1 variants were detected in the 15 children, most of which occurred in exon 4, of which 9 variant loci were not included in the HGMD database as of December 2022. The clinical phenotype of 46,XY abnormal sexual development caused by NR5A1 gene variants is extensive, with the external genitals showing varying degrees of insufficient masculinization. Adrenal involvement is rare.

TBK1 p.Y153Qfs*9 variant may be associated with young-onset, rapidly progressive amyotrophic lateral sclerosis through a haploinsufficiency mechanism.

TBK1 variants have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia spectrum disorder. The current study elucidated the clinical and molecular genetic features of a novel TBK1 variant identified in a patient with young-onset, rapidly progressive ALS. The coding regions of TBK1, SOD1, TARDBP, and FUS were genetically analyzed using Sanger sequencing. Repeat-primed PCR was used to survey the GGGGCC repeat in C9ORF72. The study participant underwent a comprehensive clinical evaluation. The functional effects of the TBK1 variant were analyzed through in vitro transfection studies. We identified a novel frameshift truncating TBK1 variant, c.456_457delGT (p.Y153Qfs*9), in a man with ALS. The disease initially manifested as right hand weakness at the age of 39 years but progressed rapidly, with the revised ALS Functional Rating Scale score declining at an average monthly rate of 1.92 points in the first year after diagnosis. The patient had no cognitive dysfunction. However, Technetium-99m single photon emission tomography indicated hypoperfusion in his bilateral superior and middle frontal cortices. In vitro studies revealed that the p.Y153Qfs*9 variant resulted in a truncated TBK1 protein product, reduced TBK1 protein expression, loss of kinase function, reduced interaction with optineurin, and impaired dimerization. The heterozygous TBK1 p.Y153Qfs*9 variant may be associated with young-onset, rapidly progressive ALS through a haploinsufficiency mechanism.

TFE3-rearranged perivascular epithelioid cell tumors: a clinicopathological analysis of eight cases

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Methods: Eight cases of PEComa with TFE3 rearrangement diagnosed in the First Affiliated Hospital of Air Force Medical University from January 2014 to July 2022 were collected. Three were consultation cases and 5 were collected from our hospital; 7 cases were resection specimens and 1 case was a needle biopsy specimen. Routine histolopathological analysis, immunohistochemical staining, fluorescence in situ hybridization (FISH) and the next-generation sequencing were performed. Clinical data were collected and the prognosis was assessed. Results: The 8 patients consisted of 5 females and 3 males with a median age of 45 years (ranged from 25 to 65 years). The tumor location included 1 uterus, 1 liver, 1 urachus, 2 kidneys, 1 abdominal cavity, 1 colon, and 1 retroperitoneum (3 subsequent recurrences in the abdominal cavity, pelvis and ovary, and abdominal cavity, respectively). Morphologically, the tumor cells were uniform and epithelioid with translucent or eosinophilic cytoplasm. They were arranged in nests or sheets, most of which were separated by thin-walled blood vessels. There were no papillary structures, and no overt smooth muscle or fat components. Atypical features were seen in 3 cases, with bizarre nuclei and tumor giant cells. Large areas of necrosis were visible, and mitosis was common (up to 28/50 HPF). Melanin deposition was present in 3 cases. Immunohistochemical staining showed diffuse and strong positivity for TFE3 in 8/8 cases and for HMB45 in 6/8 cases; focal positivity for Cathepsin K and Melan-A in 6/8 cases and for SMA in 2/8 of cases. All cases were negative for CKpan, PAX8 and Desmin. TFE3 gene break-apart was detected by FISH in all 8 cases, 4 of which underwent next-generation sequencing, and it revealed that 2 cases presented with SFPQ::TFE3 fusion, 1 case with ASPSCR1::TFE3 fusion, and 1 case with no chimeric fusion. Seven cases were followed up for 4-94 months. All cases were alive; 4 cases were disease-free, 2 cases showed recurrence, and 1 case had metastasis at initial diagnosis. Conclusions: TFE3-rearranged PEComa has unique histomorphological, immunohistochemical and molecular characteristics. The biological behavior is aggressive, which could lead to recurrence and metastasis, and warrants close clinical follow-up.

Molecular genetic characterization of hepatitis B virus in blood donors from South Vietnam

The problem of transfusion safety preventing parenteral viral hepatitis transmission remains relevant. Viral hepatitis B (HB) is the most common viral infection transmitted through transfusion procedures. One of the natural phases of a chronic viral hepatitis B (CHB) course is occult hepatitis B infection (OBI) characterized by undetectable HBsAg level (regardless of other serological marker levels) along with detected hepatic HBV DNA as well as blood viral load ranging from extremely low to undetectable. In Vietnam, prevention of transfusion-based HBV transmission is focused on donor screening; it is still based solely on HBsAg serology. As such, OBI remains a potential threat to blood transfusion safety. Assessing hepatitis B virus (HBV) DNA is a reliable preventive measure against HBV transmission from HBsAg– donors, especially in highly endemic regions. The aim of our work was HBV identification and molecular genetic characterization in blood donors from South Vietnam. The study material was presented by 500 donor serum samples. Subjects were examined for HBV markers with qualitative detection of HBsAg, HBs IgG, and HBcore IgG. Amplification and subsequent HBV sequencing were performed using nested PCR with overlapping primer pairs jointly flanking the complete HBV genome (S, P, C, X genes). Full-size HBV genome nucleotide sequences were obtained for 58 samples. Among blood donors, taking into account HBsAg+ and HBsAg– samples, HBV DNA was detected in 11.6%, including 8.6% OBI. HBV phylogenetic analysis showed genotypes B and C. Vaccine escape mutations and mutations that contribute to disease progression were identified. Current screening in Vietnam is insufficient for eliminating the risk of transfusion-transmitted HBV infection. The major risk factor is OBI. PCR testing for HBV should be considered for blood donor screening.

Clinical features and prognosis of patients with myeloid neoplasms harboring t(7;11)(p15;p15) translocation: a single-center retrospective study

BackgroundFor myeloid neoplasms with t(7;11)(p15;p15) translocation, the prognosis is quite dismal. Because these tumors are rare, most occurrences are reported as single cases. Clinical results and optimal treatment approaches remain elusive. This study endeavors to elucidate the clinical implications and prognosis of this cytogenetic aberration.MethodsThis study retrospectively analyzed 23 cases of myeloid neoplasm with t(7;11)(p15;p15). Clinicopathological characteristics, genetic alterations, and outcomes were evaluated, and the Kaplan-Meier method was employed to construct survival curves.ResultsOf these, nine cases were newly diagnosed acute myeloid leukemia (ND AML), seven presented with relapsed refractory AML (R/R AML), four had myelodysplastic syndrome (MDS), two had secondary AML, and one exhibited a mixed germinoma associated with MDS. Patients with t(7;11)(p15;p15) in AML were primarily younger females who preferred subtype M2. Interestingly, these patients had decreased hemoglobin and red blood cell counts, along with markedly elevated levels of lactic dehydrogenase and interleukin-6, and exhibited the expression of CD117. R/R AML patients exhibited a higher likelihood of additional chromosome abnormalities (ACAs) besides t(7;11). WT1 and FLT3-ITD were the most commonly found mutated genes, and 10 of those instances showed evidence of the NUP98::HOXA9 fusion gene. The composite complete remission rate was 66.7% (12/18), while the cumulative graft survival rate was 100% (4/4). However, the survival outcomes were dismal. Interestingly, the median overall survival for R/R AML patients was 4.0 months (95% CI: 1.7–6.4). Additionally, the type of AML diagnosis or the presence of ACAs or molecular prognostic stratification did not significantly influence clinical outcomes (p = 0.066, p = 0.585, p = 0.570, respectively).ConclusionMyeloid leukemia with t(7;11) exhibits unique clinical features, cytogenetic properties, and molecular genetic characteristics. These survival outcomes were dismal. R/R AML patients have a limited lifespan. For myeloid patients with t(7;11), targeted therapy or transplantation may be an effective course of treatment.

Anamnestic, clinical, laboratory and molecular genetic characteristics of patients with neonatal diabetes mellitus

BACKGROUND: Currently, there is an increase in the incidence of diabetes mellitus throughout the world, including the steadily increasing number of rare, genetically determined forms of diabetes. Of particular interest are monogenic forms, including neonatal diabetes mellitus, which is a rare heterogeneous disease that manifests, as a rule, in the first 6 months of a child’s life, characterized by a severe labile course and a high risk of complications. Neonatal diabetes mellitus is a rare heterogeneous disease that usually manifests itself in the first 6 months of a child’s life, characterized by a severe, labile course and a high risk of complications. Currently, more than 25 genes are known, mutations in which cause both permanent and transient neonatal diabetes mellitus, as well as syndromic variants of this disease, which are of particular interest due to their severity and polymorphic clinical picture. In this regard, timely verification of the diagnosis is of particular importance. AIM: The aim of this study is to increase the efficiency of diagnosis of neonatal diabetes mellitus based on the analysis of anamnestic, clinical, laboratory and molecular genetic characteristics of patients. MATERIALS AND METHODS: 14 patients with transient and permanent neonatal diabetes mellitus were examined. RESULTS: 11 (78.6%) patients had isolated neonatal diabetes, in three of them the disease was verified in the structure of hereditary syndromes (Wolcott–Rallison syndrome, IPEX syndrome and Donohue syndrome). According to molecular genetic analysis, 14 variants were found in the genes ABCC8, KCNJ11, GCK, GATA6, WFS1, CACNA1D, EIF2AK3, FOXP3, PAX4, INSR, IGF1R, three of which were not previously described in the literature. CONCLUSIONS: The clinical heterogeneity identified in patients is determined primarily by the diversity of verified variants in causative genes. New variants in the CACNA1D and IGF1R genes that may be associated with the development of NDM, remain poorly understood and require further research.

Morphological and Molecular Characterization of Three Myxosporean Species of the Genera Myxobolus, Henneguya, and Myxidium (Cnidaria: Myxozoa) Infecting Freshwater Fish, Isolated for the First Time in Japan.

The majority of myxosporean species (Cnidaria: Myxozoa) of the genera Myxobolus (35 species), Henneguya (8 species), and Myxidium (9 species) from freshwater or brackish fish in Japan were recorded more than 30 years ago (accumulatively 81.1% [43/53]). The re-discovery and molecular-genetic characterization of these species is a current research priority. During our myxosporean survey in Japanese freshwater fish, we detected three species that had never been recorded in Japan, but in the Russian Far East (Sakhalin Island, and Maritime Province): Myxobolus tribolodonus sp. n., forming cysts in the gills of Tribolodon sachalinensis (syn. M. marinus sensu Aseeva, 2000; M. marinus sensu Sokolov et Frolova, 2015, recorded from the gills of Pseudaspius (syn. Tribolodon) spp.); Henneguya pungitii Achmerov, 1953, forming cysts in the subcutis of external skin and buccal submucosa of Pungitius sinensis; and Myxidium salvelini Konovalov et Shulman, 1966, in the urinary bladder of Oncorhynchus masou ishikawae. These new isolates were characterized by integrated taxonomic approaches, i.e., myxospore morphology and molecular-genetic characterization of the small subunit ribosomal RNA gene (SSU rDNA). These new isolates were phylogenetically differentiated from any species whose SSU rDNA sequences were deposited in the DNA databases, and concurrently compared with recorded species based on classical morphological criteria. All three species were differentiated from myxosporeans previously recorded in Japan, indicating new distribution records out of the Russian Far East. For reliable species identification, accumulation of at least SSU rDNA sequences of known species worldwide is critically important.

Molecular genetics and research progress of uterine leiomyosarcoma.

Uterine leiomyosarcoma (uLMS) is a type of malignant soft-tissue tumor, which is developed from myometrium in the female reproductive system. This disease is difficult to be distinguished from benign uterine leiomyoma in the early stages, but it progresses aggressively and relentlessly. Hence, uLMS has a dismal prognosis and high rates of both misdiagnosis and missed diagnosis. Unfortunately, current studies of uLMS pathogenesis and disease biology are inadequate. uLMS disease models are also very limited, hindering the development of effective therapeutics. In this review, we focus on the pathological molecular biology of uLMS, and systematically review the molecular genetic features, epigenetic variants, experimental models, and clinical research progress of uLMS. We further discuss the development direction and potential needs of uLMS in the fields of tumor evolution, tumor microenvironment, and tumor therapy, with the aim of providing a better understanding of the pathobiological mechanism of uLMS and providing a reference for the development of potential diagnostic and therapeutic strategies.

Phylogenetic analysis and molecular genetic characteristics of West Nile virus lineage 2 isolates circulating in the Russian Federation.

Since its initial detection in Africa, the West Nile virus has disseminated widely across all continents, becoming endemic in numerous countries, including the Russian Federation. A substantial expansion of the West Nile virus range was observed in the European part of the Russian territory in 1999. In light of this epidemiological trend, research endeavours focusing on monitoring West Nile virus circulation activity in endemic regions of the country have gained paramount significance. A substantial dataset has been accrued from 2007 onwards regarding genomic variability and dissemination dynamics across the country throughout the entire monitoring period for the West Nile fever pathogen. The objective of this study was to characterise West Nile virus isolates that have been circulating in the Russian Federation and identify their molecular and genetic characteristics. A phylogenetic analysis of 55 complete genome sequences revealed that the West Nile virus population within the Russian Federation is genetically heterogeneous and is represented by four major clades. One of these clades is currently exhibiting extensive spread into new regions of the country.

Hyper IgE Syndromes.

The Hyper IgE Syndromes are rare primary immunodeficiencies characterized by eczema, recurrent skin and respiratory infections and elevated serum IgE levels. Nowadays a geneticmolecular characterization is possible and allows the distinction in various monogenic pathologies, which share some clinical characteristics but also important differences. In addition to long-known STAT3 and DOCK8 gene mutations, in fact, also ZNF341, CARD11, ERBB2IP, IL6R and IL6ST genes mutations can cause the disease. The main clinical manifestations are represented by newborn rash, eczema similar to atopic dermatitis, bacterial and viral skin infections, cold abscesses, respiratory infections with possible pulmonary complications, allergies, gastrointestinal manifestations, malignancies and connective tissue abnormalities. Diagnosis is still a challenge because, especially in the early stages of life, it is difficult to distinguish from other pathologies characterized by eczema and high IgE, such as atopic dermatitis. Several scores and diagnostic pathways have been developed, but it is essential to seek a genetic diagnosis. Treatment is based on prevention and early treatment of infections, meticulous skincare, intravenous immunoglobulins and HSCT, which, in some HIES subtypes, can modify the prognosis. Prognosis is related to the affected gene, but also to early diagnosis, timely treatment of infections and early HSCT.