bluuebunny/crossref_metadata_2025 huggingface dataset:
Are hemodynamics responsible for inflammatory changes in venous vessel walls? A quantitative study of wall-enhancing intracranial arteriovenous malformation draining veins
Authors: Stahl Janneck , McGuire Laura Stone , Rizko Mark , Saalfeld Sylvia , Berg Philipp , Alaraj Ali
Published: April 2024

OBJECTIVE

Signal enhancement of vascular walls on vessel wall MRI might be a biomarker for inflammation. It has been theorized that contrast enhancement on vessel wall imaging (VWI) in draining veins of intracranial arteriovenous malformations (AVMs) may be associated with disease progression and development of venous stenosis. The aim of this study was to investigate the relationship between vessel wall enhancement and hemodynamic stressors along AVM draining veins.

METHODS

Eight AVM patients with 15 draining veins visualized on VWI were included. Based on MR venography data, patient-specific 3D surface models of the venous anatomy distal to the nidus were segmented. The enhanced vascular wall regions were manually extracted and mapped onto the venous surface models after registration of image data. Using image-based blood flow simulations applying patient-specific boundary conditions based on phase-contrast quantitative MR angiography, hemodynamics were investigated in the enhanced vasculature. For the shear-related parameters, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated. Velocity, oscillatory velocity index (OVI), and vorticity were extracted for the intraluminal flow-related hemodynamics.

RESULTS

Visual observations demonstrated overlap of enhancement with local lower shear stresses resulting from decreased velocities. Thus, higher RRT values were measured in the enhanced areas. Furthermore, nonenhancing draining veins showed on average slightly higher flow velocities and TAWSS. Significant decreases of 55% (p = 0.03) for TAWSS and of 24% (p = 0.03) for vorticity were identified in enhanced areas compared with near distal and proximal domains. Velocity magnitude in the enhanced region showed a nonsignificant decrease of 14% (p = 0.06). Furthermore, increases were present in the OSI (32%, p = 0.3), RRT (25%, p = 0.15), and OVI (26%, p = 0.3) in enhanced vessel sections, although the differences were not significant.

CONCLUSIONS

This novel multimodal investigation of hemodynamics in AVM draining veins allows for precise prediction of occurring shear- and flow-related phenomena in enhanced vessel walls. These findings may suggest low shear to be a local predisposing factor for venous stenosis in AVMs.
Indirect revascularization for pediatric moyamoya disease
Authors: Ogawa Shotaro , Ogiwara Hideki
Published: April 2024

OBJECTIVE

Indirect revascularization is a common and effective treatment for pediatric moyamoya disease. However, in several cases postoperative angiogenesis is not sufficient. It is not fully understood which factors are involved in the development of postoperative collateral circulation. In this study, the authors aimed to elucidate the factors related to postoperative angiogenesis in indirect revascularization.

METHODS

Among the patients who underwent indirect revascularization for moyamoya disease from January 2015 to December 2022, those whose angiogenesis was evaluated using angiography were included. Age, onset symptoms, comorbidities, preoperative imaging findings, surgical details, perioperative complications, postoperative imaging findings, and modified Rankin Scale (mRS) score at the last outpatient visit were retrospectively examined.

RESULTS

Ninety cases (53 patients; 37 bilateral, 16 unilateral) were included. Sixty-eight cases (75.6%) were symptomatic. The mean age at surgery was 7.9 years, and the mean postoperative follow-up duration was 48.5 months. Frontotemporal encephalo-duro-arterio-synangiosis (EDAS) was performed in all cases, and simultaneous frontal encephalo-galeo-synangiosis (EGS) was performed in 34 cases. Postoperative angiography revealed insufficient angiogenesis in 14 of 90 cases (15.6%) after frontotemporal EDAS and in 8 of 34 cases (23.5%) after frontal EGS. A high degree of ivy sign depicted on preoperative MRI was found to be significantly correlated with good angiogenesis after both surgical procedures (p = 0.00030 for EDAS and p = 0.0039 for frontal EGS). In addition, an advanced preoperative Suzuki stage was significantly correlated with good postoperative angiogenesis after EDAS (p = 0.00040). Good angiogenesis was significantly correlated with postoperative improvement of the ivy sign in both procedures (p = 0.0005 in EDAS and p = 0.030 in frontal EGS) as well as correlated with a better mRS score at long-term follow-up after EDAS (p = 0.018).

CONCLUSIONS

Preoperative ivy sign and Suzuki classification are related to the degree of angiogenesis achieved after indirect revascularization for pediatric moyamoya disease.
Responsive neurostimulation of thalamic nuclei for regional and multifocal drug-resistant epilepsy in children and young adults
Authors: Mohanty Deepankar , Houck Kimberly M. , Trandafir Cristina , Haneef Zulfi , Karakas Cemal , Lee Steven , Curry Daniel J. , Riviello James J. , Ali Irfan
Published: April 2024

OBJECTIVE

Responsive neurostimulation (RNS) is a US FDA-approved form of neuromodulation to treat patients with focal-onset drug-resistant epilepsy (DRE) who are ineligible for or whose condition is refractory to resection. However, the FDA approval only extends to use in patients with one or two epileptogenic foci. Recent literature has shown possible efficacy of thalamic RNS in patients with Lennox-Gastaut syndrome and multifocal epilepsy. The authors hypothesized that RNS of thalamic nuclei may be effective in seizure reduction for patients with multifocal or regionalized-onset DRE.

METHODS

The authors performed a retrospective chart review of all patients who had an RNS device managed at Texas Children’s Hospital between July 2016 and September 2023, with at least one active electrode in the thalamic nuclei and ≥ 12 months of postimplantation follow-up. Information conveyed by the patient or their caregiver provided data on the change in the clinical seizure frequency, quality of life (QOL), and seizure severity between the preimplantation baseline visit and the last office visit (LOV).

RESULTS

Thirteen patients (ages 8–24 years) were identified with active RNS leads in thalamic nuclei (11 centromedian and 2 anterior nucleus). At LOV, 46% of patients reported 50%–100% clinical seizure reduction (classified as responders), 15% reported 25%–49% reduction, and 38% reported < 25% reduction or no change. Additionally, 42% of patients reported subjective improvement in QOL and 58% reported improved seizure severity. Patients with focal cortical dysplasia (FCD) responded strongly: 3 of 5 (60%) reported ≥ 80% reduction in seizure burden and improvement in seizure severity and QOL. Patients with multifocal epilepsy and bilateral thalamocortical leads also did well, with all 3 reporting ≥ 50% reduction in seizures.

CONCLUSIONS

RNS of thalamic nuclei shows promising results in reducing seizure burden for patients with multifocal or regional-onset DRE, particularly in a bilateral thalamocortical configuration or when addressing an underlying FCD.
Risk factors for vascular injuries in anterior lumbar interbody fusion: a single-institution retrospective study
Authors: Yunga Tigre Joseph , Berry Katherine , Kloehn Andrew J. , Lu Victor M. , Maddy Krisna , Puerto Aiko , Abdullah Naaman , Burks S. Shelby , Levi Allan D.
Published: April 2024

OBJECTIVE

Vascular injuries in anterior lumbar interbody fusion (ALIF) occur due to the vascular manipulation needed to achieve optimal disc space exposure. In this study, the authors aimed to evaluate intraoperative vascular injuries in patients undergoing single- and multilevel ALIF at a large tertiary academic center.

METHODS

Prospectively collected data specifically addressing postoperative complications in patients who underwent ALIF by neurosurgery spine faculty working with a specialized vascular surgeon were retrospectively reviewed. Demographic characteristics and intraoperative data were collected. Patients were split into vascular injury and non–vascular injury groups. Outcome comparisons were conducted using the chi-square exact and Wilcoxon rank-sum tests for categorical and continuous data, respectively. Logistic regression was used to investigate associations with vascular injury, with univariate analysis first conducted to identify candidate associations. Based on these results, variables demonstrating a between-groups test statistic of p < 0.10 were included in the multivariate analysis to determine the independent predictors of vascular injuries.

RESULTS

In total, 323 patients who underwent ALIF procedures were identified: 51% were male (n = 166) and 49% were female (n = 157). The mean age was 57.1 years, with 56% (n = 182) having undergone prior lumbar surgery. Vascular injuries were encountered intraoperatively in 7.1% (n = 23) of patients, and the majority (91% [n = 21]) involved the left common iliac vein. Patients with vascular injuries were statistically older (mean 63.6 vs 56.6 years), had greater incidence rates of coronary artery disease, opioid use, multilevel ALIF surgery involving the L2–3 level, and surgery involving multiple disc spaces, had more multilevel anterior instrumentation, and experienced greater blood loss during surgery and longer length of stay (all p < 0.05). Overall, there was 1 death (0.3%) secondary to aortic artery injury. Multivariate analysis identified opioid use, multilevel ALIF involving L2–3, and multiple interbodies as statistically independent predictors of vascular injury (all p < 0.05).

CONCLUSIONS

Identifying patient risk factors can reduce the risk of vascular injuries in ALIF. Opioid use, multilevel ALIF involving L2–3, and multiple interbodies were independent predictors of vascular injuries in ALIF.
Biomarkers related to hypertrophy of the ligamentum flavum: a systematic review of the literature
Authors: Mualem William , Liu Jiaqi , Balu Alan , Chesney Kelsi , Nair M. Nathan
Published: April 2024

OBJECTIVE

Spinal stenosis is one of the most common spinal disorders in the elderly. Hypertrophy of the ligamentum flavum (HLF) can contribute to spinal stenosis. The current literature suggests that various biomarkers may play important roles in the pathogenesis of HLF. However, the connection between these biomarkers and the development of HLF is still not well understood. This systematic review aims to explore the current literature on biomarkers related to the development of HLF.

METHODS

A literature search was conducted using PubMed, Embase, Web of Science, and Cochrane Library. The search strategy looked for the titles, abstracts, and keywords of studies that contained a combination of the following phrases: "ligamentum flavum OR yellow ligament," "biomarkers," and "hypertrophy." Recorded data included study design, demographic characteristics (number of patients of each gender and mean age), study period, country where the study was conducted, biomarkers, and diagnostic modalities used. Risk of bias was assessed using the Newcastle-Ottawa Scale for case-control studies.

RESULTS

The authors identified 39 studies. After screening, 26 full-text original articles assessing one or more biomarkers related to HLF were included. The included studies were conducted over a 22-year period. The most popular biomarkers studied, in order of frequency reported, were collagen types I and III (n = 10), transforming growth factor β (TGF-β) (n = 8), and interleukin (IL)–6 (n = 6). The authors found that mechanical stretching forces, tissue inhibitor of metalloproteinases 2 (TIMP-2) induction, and TGF-β were associated with increased amounts of collagen I and III. IL-6 expression was increased by microRNA-21, as well as by leptin, through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway.

CONCLUSIONS

Biomarkers such as TGF-β, IL-6, and collagen I and III have been consistently correlated with the development of HLF. However, the pathogenesis of HLF remains unclear due to the heterogeneity of the studies, patient populations, and research at the molecular level. Further studies are necessary to better characterize the pathogenesis of HLF and provide a more comprehensive understanding of how these biomarkers may aid in the diagnosis and treatment of HLF.
Evidence of the Genetic Mating System in Viviparity White-Edged Rockfish, Sebastes taczanowskii Steindachner, 1880
Authors: Batishcheva N. M. , Yagodina V. D. , Brykov V. A.
Published: April 2024

Internal fertilization and viviparity are characteristic of some species of the genus Sebastes. Polyandry has also been reported for some species of this genus. We used five microsatellite markers and three main statistical approaches to estimate the level of polyandry in a wild population of white-edged rockfish (Sebastes taczanowskii). In some clutches, we detected multiple paternity. This study is the first record of multiple paternity in white-edged rockfish from the Far East. Polyandry is probably quite a widespread strategy in this species inhabiting the Far Eastern seas, and also an important factor in the regulation of genetic diversity and productivity.
The Role of rs2238296 of the Mitochondrial DNA Polymerase Gamma Gene in Combination with Polymorphic Variants of Antioxidant Defense Genes in the Development of Postinfarction Left Ventricular Aneurysm
Authors: Kuzheleva E. A. , Garganeeva A. A. , Tukish O. V. , Nesova A. K. , Golubenko M. V. , Andreev S. L. , Shipulin V. M.
Published: April 2024

Studied the relationship of the polymorphic variant of the mitochondrial DNA polymerase gamma gene (POLG rs2238296) in combination with single-nucleotide polymorphic variants of the genes of the antioxidant system of the body (mitochondrial transcription factor A (TFAM rs1937), superoxide dismutase (SOD2 rs4880), glutathione peroxidase (GPX1 rs1050450), catalase (CAT rs1001179), paraoxonase 1 (PON1 rs854560) and NADP-H oxidase (CYBA rs4673)) with features of postinfarction remodeling of the left ventricle (LV). One hundred and fifty-three patients with coronary heart disease (137 men and 16 women) aged 56 (50; 60.5) years were examined. Genotyping was carried out using a polymerase chain reaction followed by analysis of the polymorphism of the lengths of restriction fragments. No significant difference was found in the SOD2, GPX1, CAT, PON1, TFAM genes in the studied groups. Significant differences were found with respect to the POLG and CYBA genes: the CC rs2238296 genotype of the POLG gene was found in every third patient with LV aneurysm (30.3%), where as in the group without aneurysm – only in every eighth case (12.3%, p = 0.006). The CC rs4673 genotype of the CYBA gene was found in every second patient with an aneurysm (51.8%) and in 32% without LV aneurysm (p = 0.01). Patients with a combination of CC (POLG) and CC (CYBA) genotypes were represented exclusively by younger men, who were characterized by a less burdened comorbid background, in comparison with patients with a different genotype of these genes. At the same time, the LV ejection fraction in such patients was significantly lower (40 (27; 52) and 50 (40; 61), p = = 0.006), and the development of LV aneurysm was recorded in 73% of cases.
Chloroplast DNA Markers on the Phylogeography Study of Roburoid Oaks (Quercus L. sect. Quercus, Fagaceae) in the Crimean-Caucasian Region
Authors: Semerikova S. A.
Published: April 2024

The variability of five fragments of chloroplast DNA (ASq, CDq, TFq, trnH-psbA and trnK-matK) with a total length of more than 10,000 bp in three species of roburoid oaks of the Crimean-Caucasian region (Q. robur, Q. petraea, Q. pubescens) was studied. A total of 11 haplotypes were found in 290 individuals from 20 populations, 10 of which differed from the haplotypes of the main range. The obtained results show a pronounced structure of the geographical distribution of haplotypes of roburoid oaks in the Crimea and the Caucasus, and the chloroplast haplotypes of the region belong to several divergent phylogenetic lines. A comparison with data from other studies was carried out, with an assessment of the degree of effectiveness of the use of various chloroplast fragments and markers. The isolated phylogenetic position of the haplotypes of the Crimean-Caucasian populations and deep differences from the haplotypes of the main area allows us to conclude that robouroid oaks have historically been isolated for a long time in the Caucasus and Crimea. At the same time, the presence of common haplotypes indicates closer historical ties between the Crimean-Caucasian populations with Asia Minor and the Balkans. All haplotypes are identified by three fragments (ASq, CDq and TFq), with a sufficient level of variability and suitable for solving problems of oak phylogeography in the Crimean-Caucasian region. The trnH-psbA and trnK-matK markers had a low level of variability and did not reveal additional haplotypes. Optimized genotyping options have been proposed, including both step by step sequencing, and a combination of analysis of chloroplast DNA microsatellite loci (cpSSR), restriction analysis (PCR-RFLP), and sequencing. To assess the variability of markers in a larger taxonomic range, representatives of other sections of the genus Quercus were included in the analysis. It was shown that the oak-specific primers proposed for ASq, CDq, and TFq fragments are suitable for species of other sections.
Polymorphism and Differentiation of the Evoron Vole Three Populations according to the mtDNA Control Region Variability
Authors: Sheremetyeva I. N. , Kartavtseva I. V. , Frisman L. V.
Published: April 2024

As a result of the control region mtl DNA analysis for the Evoron vole, a high haplotype (97%) and nucleotide (1.53%) diversity was found. The data obtained indicate a low level of genetic differentiation populations. At the same time, populations geographically located closer are subdivided more strongly than remote ones. In general, there is agreement between the data on the variability of the mitochondrial DNA control region and chromosome races. However, if the data of chromosomal analysis indicate the preservation of the karyotype more ancient variants in the Evoron-Chukchagir lowland (“evoron” chromosomal race), then the data of molecular genetic analysis testify in favor of the preservation of the most ancient mt haplotype (106-19) in the upper Bureya depression population (“argi” chromosomal race).
Study of Population Genetic Structure of Atlantic Chub Mackerel Scomber colias Gmelin, 1789 (Scombridae) in the Central-East Atlantic
Authors: Stroganov A. N. , Nikitenko A. I. , Rakitskaya T. A. , Belyaev V. A.
Published: April 2024

A study of genetic diversity in groups of Atlantic Сhub mackerel from the waters of the Central-East Atlantic was carried out on the basis of seven microsatellite loci. All loci were polymorphic, the estimates of expected heterozygosity varied from 0.021 to 0.914. For all studied samples of Atlantic Сhub mackerel, a heterozygosity deficiency was identified, associated with the presence of null alleles in four of the seven studied microsatellite loci. A low but significant value of genetic differentiation was obtained, calculated for all loci (θ = 0.0052), which, presumably, may also be associated with the violation of panmixia due to the formation of individual subpopulations as a result of the uneven impact of fishing in different localities.
The Effect of the aPKC Gene Encoding Atypical Protein Kinase C on the Lifespan of Drosophila melanogaster Depends on the Expression Level of Protein Kinase GSK3
Authors: Trostnikov M. V. , Veselkina E. R. , Andreev Y. A. , Khryachkova A. Y. , Roshina N. V. , Pasyukova E. G.
Published: April 2024

Drosophila melanogaster shaggy and aPKC genes encode highly conserved GSK3 (Glycogen Syntase Kinase 3) and aPKC (Protein Kinase C) proteinkinases that play key roles in many cellular processes. We previously demonstrated that changes in shaggy expression in neurons affect lifespan. In this article we show that changing the expression of the aPKC gene in neurons also affects lifespan. Changing the expression of the two protein kinases in all male or female neurons and in male motoneurons led to changes in lifespan, indicating that aPKC has no effect on GSK3 and GSK3 has a possible inhibitory effect on aPKC. At the same time, changes in the expression of two protein kinases in female motoneurons led to changes in lifespan, indicating the existence of a still unclear mechanism of interaction between these proteins. The elucidation of the mechanisms of interaction between aPKC, GSK3 and their other partners will deepen and expand our understanding of the causes of longevity and the ways to extend life.
The CRP Gene’s Role in the Relations between Childhood Adversity and History of Suicide Attempts in Schizophrenia
Authors: Alfimova M. V. , Lezheiko T. V. , Gabaeva M. V. , Plakunova V. V. , Mikhailova V. A. , Kaleda V. G. , Golimbet V. E.
Published: April 2024

Research suggests that, in contrast to circulating C-reactive protein (CRP), genetic variants conferring higher CRP levels have protective effects against schizophrenia and moderate influences of season of birth on the development of the disease. This study aimed to explore whether the CRP gene also moderates the relations between childhood adversity and clinical characteristics of schizophrenia. The relations between childhood adversity, genotypes at rs2794521within the CRP locus, syndromes measured as five factors and two negative subfactors of the Positive and Negative Syndrome Scale, and history of suicide attempts were analyzed in 921 schizophrenia patients using analyses of covariances, Pearson’s chi-squared test, and logistic regression. A significant effect of genotype on suicide attempts in patients exposed to childhood adversity was found. The result suggests a moderating role of genetic determinants of inflammation in translating early life psychological stress effects into risk of suicide attempts in schizophrenia.
Polygenic Analysis of Cytokine and Inflammatory Genes Polymorphisms in Chronic Obstructive Pulmonary Disease
Authors: Korytina G. F. , Aznabaeva Y. G. , Kochetova O. V. , Nasibullin T. R. , Akhmadishina L. Z. , Khusnutdinova N. N. , Zagidullin N. Sh. , Victorova T. V.
Published: April 2024

Chronic obstructive pulmonary disease (COPD) is a complex lung disease characterized by progressive airflow limitation and abnormal inflammatory response of the lungs to inhaled noxious particles or gases. COPD pathogenesis was linked to oxidative stress and systemic inflammation. We aimed to assess the association of cytokines and inflammatory genes polymorphisms and their combinations with COPD. SNPs of inflammatory genes FASLG (rs763110), IL19 (rs2243193), IL20 (rs2981573), IL24 (rs291107), PPBP (rs352010), IL4 (rs2243250), IL4 (rs2070874), С5 (rs17611), FAS (rs1800682), IL4RA (rs1805010), TGFb1 (rs1800469) was genotyped by the real-time polymerase chain reaction (PCR) among 601 COPD patients and 617 controls. Significant associations with COPD in the study group under additive genetic model were identified for IL19 (rs2243193) (P = 0.00001, OR = 0.73), IL4 (rs2243250) (P = 0.024, OR = 1.27), IL4 (rs2070874) (P = 0.00001, OR = 0.62), and for PPBP (rs352010) under the recessive model (P = 0.00001, OR = 2.34). Using the APSampler algorithm, we obtained gene-gene combinations that remained significantly associated with COPD; A allele of IL19 (rs2243193) and C allele of PPBP (rs352010) were the core element of the majority of protective patterns associated with COPD. The highest risk of COPD was conferred by combination of alleles: G of IL12A (rs2243115) with A of IL13 (rs20541) and C of IL4 (rs2070874) (OR = 2.72). The receiver operating characteristic (ROC) analysis resulted in an area under the curve (AUC) of 0.895 (95%CI 0.874–0.916) for model including SNPs: A allele of IL19 (rs2243193) and AA genotype of IL20 (rs2981573) combination, IL19 (rs2243193), IL12A (rs2243115), PPBP (rs352010), IL4 (rs2070874) together with age and smoking pack years, indicating a high ability of the model to correctly classify individuals with and without COPD.
Genetic Differentiation of the Fourhorn Sculpin Myoxocephalus quadricornis (Linnaeus, 1758) and Its Position in the Tribe Myoxocephalini Taranetz (Cottidae: Myoxocephalinae)
Authors: Moreva I. N. , Radchenko O. A. , Petrovskaya A. V.
Published: April 2024

A molecular genetic and karyological study of the fourhorn sculpin Myoxocephalus quadricornis (Linnaeus, 1758) was carried out. The karyotype was studied for the first time and the results of Ag-staining of the chromosomes of specimens of the species from the East Siberian Sea are presented. The karyotype of M. quadricornis is stable, contains 32 (10 metacentrics, 2 submetacentrics, 20 subtelocentrics) chromosomes, the number of chromosome arms is 44. Nucleolar organizers were found in the telomeric regions of the short arms of two homologous medium-sized subtelocentrics. Variability in the number of nucleolarforming chromosomes and stained blocks of nucleolar organizers was found. Common features in the chromosome sets of M. quadricornis and Megalocottus platycephalus indicate their greater similarity compared to species of the genus Myoxocephalus. The results of the karyological analysis are consistent with the molecular genetic data about the sister relationships between M. quadricornis and Megalocottus platycephalus. A complex of karyological and molecular-genetic features has been identified that allow one to reliably distinguish M. quadricornis from species of the tribe Myoxocephalini and indicate the need for its removal from the genus Myoxocephalus.
Association of Allelic Variants A and B of the Beta-Lactoglobulin Gene with Dairy Productivity of Cattle
Authors: Parygina E. V. , Kozhevnikova I. S.
Published: April 2024

The effectiveness of cattle selection for quantitative and qualitative traits that are of economic importance in dairy cattle breeding largely depends on the identification of the genes that control these traits, as well as their allelic polymorphism. One such gene is the gene LGB encoding the protein beta-lactoglobulin. The review provides brief information about the structure and biological role of this protein, gene polymorphism. An analysis of the literature data of various studies was carried out, which made it possible to identify and evaluate the effect of the two most common alleles of the gene LGB (A and B) on the efficiency indicators of dairy production.
Associations of Polymorphic Loci of Matrix Metalloproteinase Genes with the Development of Breast Cancer in Women Central Chernozem Region of Russia
Authors: Pavlova N. V. , Ponomarenko I. V. , Orlova V. S. , Batlutskaya I. V. , Efremova O. A. , Churnosov M. I.
Published: April 2024

The association of polymorphic variants of matrix metalloproteinase (MMP) genes with breast cancer (BC) in women of the Central Chernozem region of Russia, taking into account the presence/absence of a burdened family history, was studied. The study included 358 patients with breast cancer (68 patients had a burdened family history) and 746 women of the control group. Genotyping of 10 polymorphic loci of MMP genes (rs1799750 MMP1; rs243865 MMP2; rs679620 MMP3; rs1940475 MMP8; rs17576, rs17577, rs3918242, rs2250889, rs3787268, rs3918249 MMP9) was performed. To study the associations of polymorphic variants of MMP genes with breast cancer in two subgroups, taking into account the presence/absence of a burdened family history (the control group for these two subgroups was the same), the method of logistic regression analysis was used. It was revealed that a low risk of developing the disease among women with a burdened family history is associated with polymorphisms rs243865 MMP2 (OR = 0.53–0.54, pperm ≤ 0.03) and rs2250889 MMP9 (OR = 0.36–0.37, pperm ≤ 0.04). In women without burdened heredity, an increased risk of developing breast cancer is associated with rs3787268 MMP9 (OR = 2.16, pperm = 0.03) and haplotypes of polymorphic loci of the MMP9 gene (pperm ≤ 0.05): CA rs3918249–rs17576 (OR = 2.15), CCA rs3918242–rs3918249–rs17576 (OR = 1.69), CCAG rs3918242–rs3918249–rs17576–rs3787268 (OR = 1.69), CAGCG rs3918249–rs17576–rs3787268–rs2250889–rs17577 (OR = 3.06). Three haplotypes are associated with a low risk of breast cancer in women without burdened heredity: GG rs17576–rs3787268 (OR = 0.60), GGC rs17576–rs3787268–rs2250889 (OR = 0.63), and CGG rs3918249–rs17576–rs3787268 (OR = 0.62).
Characterization of Novel F5 Intronic Variant Associated with Aberrant Splicing and Severe Factor V Deficiency
Authors: Pshenichnikova O. S. , Yakovleva E. V. , Zozulya N. I. , Poznyakova Yu. M. , Demidova E. Yu. , Surin V. L.
Published: April 2024

Congenital factor V deficiency is a rare autosomal recessive bleeding disorder, caused by defects in F5 gene and associated with bleeding manifestations of variable severity. In this study we report molecular and functional characterization of a novel F5 variant which causes aberrant splicing and significantly reduces protein expression in a patient with severe FV deficiency. We performed F5 mutation screening and functional study in a proband (FV:C 0.4%) with a history of gastrointestinal bleeding, post-traumatic bleeding, hematomas, ecchymoses, and discomfort in ankle joints since infancy. Sequencing revealed a novel homozygous F5 gene variant NC_000001.10:169519985GC (or NM_000130.5:c.1297 –8CG). Bioinformatics sequence analysis predicted that this variant would lead to the acceptor site loss of the intron 8/exon 9 junction. However mRN-A analysis identified, that it also activated the aberrant splice site located 7 nucleotides upstream of the normal one and was associated with the production of an anomalous F5 transcript with retention of seven nucleotides of intron 8 resulting in a premature stop codon. We revealed no traces of normal transcript in the patient. Our findings confirm that not only changes in canonical splicing dinucleotides could significantly disrupt the splicing sites and impair pre-mRNA processing.
Biased Expression of Parental Alleles in the Human Placenta
Authors: Sazhenova E. A. , Vasilev S. A. , Lebedev I. N.
Published: April 2024

The biased expression of parental alleles plays a fundamental role in the formation of the placenta as a multifunctional organ necessary for the development and survival of the fetus. First of all, this is expressed in the phenomenon of imprinting, when only the maternal or paternal allele is expressed in placental cells. The placenta uses an extended range of imprinting mechanisms compared to the embryo – histone modifications that suppress or, conversely, activate the expression of nearby genes, regulatory sequences and genes derived from retroviruses or retrotransposons, microRNAs that function as antisense RNAs and participate in transcriptional and post-transcriptional regulation of gene expression. In addition, incomplete suppression of the activity of one of the parental alleles is detected in the placenta, leading to a biased imprinted expression of some genes. This review shows the role of biased expression of parental alleles in the development of placental structures of an embryo, discusses the mechanisms of epigenetic control of parental alleles, mainly expressed in the placenta.
A New 5'-UTR LcyE allele Correlates with Increased Expression of the Lycopine-ε-Cyclase Gene Determining the Flow of the β-ε Branch of the Carotenoid Biosynthesis Pathway in Maize
Authors: Arkhestova D. H. , Efremov G. I. , Appaev S. P. , Kochieva E. Z. , Shchennikova A. V.
Published: April 2024

The color of Zea mays L. kernel is determined by the content and composition of carotenoids, including provitamin A, which is a product of the β-β (β-carotene, β-cryptoxanthin) and β-ε (α-carotene) branches of carotenogenesis. The ratio of the fluxes of the branches depends on the activity of the lycopene-ε-cyclase LcyE, which determines the β-ɛ branch. In this work, we analyzed allelic variants of the LcyE gene, which are potentially effective for increasing the biosynthesis of β-carotene, in 20 maize inbred lines of domestic selection, which differ in grain color. The 5'-UTR region of the LcyE gene were amplified and sequenced. Fragment analysis showed the presence of allele “2” in four lines and a new allele “5” in 16 lines. The polymorphism of the new allele “5” was characterized – four mononucleotide polymorphisms and two deletions. The comparison of cis-regulatory elements in the analyzed region of the 5'-UTR of alleles “2” and “5” revealed a difference in binding sites with transcription factors. Expression of the LcyE gene was determined in the leaves of two lines with the allele “2” and three lines with the allele “5”. A direct relationship was shown between the presence of the allele “5” and a decrease in gene expression: the level of gene transcription in the case of the allele “2” was 10–15 times higher than in the case of the allele “5”. It has been suggested that the presence of allele “5” of the LcyE gene in the maize genome correlates with a decrease or suppression of the LcyE expression and, with stable activity of other carotenogenesis enzymes, with grain color. The use of allele “5” donors in combination with the known dark yellow or orange color of the grain can be used in the breeding of maize with increased synthesis of provitamin A in the grain.
Application of DNA Barcoding to the Study of Green Lizards (Sauria: Lacertidae: Lacerta)
Authors: Doronina M. A. , Doronin I. V. , Lukonina S. A. , Mazanaeva L. F. , Lotiev K. Yu. , Ananjeva N. B.
Published: April 2024

DNA barcoding remains a recognized and widely used method for taxon identification in biodiversity inventory and monitoring. In this publication, we present information about the results of using this method in the study of green lizards of the genus Lacerta. A total of 67 sequences of the COI gene fragment of three species (L. agilis, L. media, L. strigata) were analyzed. For the first time, all subspecies of L. agilis known in the Caucasus were studied using DNA barcoding, and a phylogeographic hypothesis for L. strigata in the Caucasian part of the range was proposed. Genetic identification has been successful at the species level. In the composition of L. agilis within the Caucasus, we can diagnose only the subspecies L. a. boemica and L. a. exigua, while L. a. brevicaudata, L. a. grusinica and L. a. mzymtensis are identical from L. a. exigua, while L. a. ioriensis from L. a. boemica.
Epigenetics of Cardiomyopathy: Histone Modifications and DNA Methylation
Authors: Kucher A. N. , Nazarenko M. S.
Published: April 2024

Cardiomyopathy is clinically and genetically heterogeneous group of pathologies of myocardium that are being actively studied by researchers. It is now generally accepted that, along with genetic factors, epigenetic mechanisms can be significant in both risk for cardiomyopathy and different clinical manifestations of the disease. This article provides an overview of scientific publications devoted to the study of histone modifications and chromatin remodeling, as well as DNA methylation changes in different types of cardiomyopathy. Most of the reports focused on epigenome profiling of myocardium of patients with dilated cardiomyopathy. The development of cardiomyopathy (dilated, hypertrophic, ischemic, arrhythmogenic, and restrictive) is associated with epigenetic changes of myocardium and this leads to gene expression alteration and metabolic pathways imbalance with pathogenetic significance for heart diseases. The genes of cardiomyopathies (LMNA, TNNI3, ANKRD1, SLC25A4, EYA4, GATAD1, PRDM16, and DMD) are also involved in epigenetic changes of myocardium. Epigenetic modifications, and enzymes that regulate epigenetic processes, are promising for the identification of new molecular markers and metabolic pathways significant for cardiomyopathies, as well as for the development of diagnostic panels and new drugs. At the same time, the high clinical and etiological heterogeneity of cardiomyopathies, a large number of diverse and interrelated epigenetic processes that occur both under physiological conditions and during the pathogenesis of the disease indicate the need to expand epigenetic studies in various forms of cardiomyopathies, including epigenome, transcriptome, and epitranscriptome levels using omics analysis of single cells of myocardium in humans and model animals, as well as in cell lines in disease modeling.
Comparative Analysis of the HAP2/GCS1, GEX2 Genes Expression in Maize Lines of Saratov Selection
Authors: Moiseeva E. M. , Gusev Yu. S. , Gutorova O. V. , Chumakov M. I.
Published: April 2024

The haploinduction phenomenon have a scientific and practical aspects for development the effective haploid-inducing maize line and diploid homozygous lines creation. The article discusses the relationship between the maize haploid–induction and the violation of the gamete interactions, in particular for GEX2-HAP2/GCS1-mediated adhesion and fusion of gamete membranes in Zarodishevii Marker Saratovskii Purpurnii (ZMSP) maize lines. Using real-time RT-PCR method, it was found that the GEX2, HAP2/GCS1 genes are expressed in sperm and ovules, but the maize haploid-inducing ability does not correlate with their expression. It was shown that the ZMSP haploid-inducing line have 27 SNP, one 9-bp insertion, 2-bp SNP and the corresponding 10 amino acid substitutions with two insertions in the GEX2 protein in comparing with reference B73 line. It was found that HAP2/GCS1, as a conservative protein for membrane fusion has only one amino acid substitution in ZMSP in comparing with B73 maize and Brown Marker maize lines.
Genetic Differentiation and Relationships Cottus kolymensis Sideleva et Goto, 2012 (Cottidae)
Authors: Radchenko O. A. , Moreva I. N. , Petrovskaya A. V.
Published: April 2024

For the first time, a karyological and molecular genetic (COI, cytochrome b, 16S rRNA genes) study of the freshwater fish species Cottus kolymensis, recently described from the Dukcha and Kolyma rivers in northeast Asia, was carried out. A complex of karyological and molecular-genetic marker traits has been determined to identify the species. Genetic differences between the populations of C. kolymensis inhabiting the water bodies of the river basins of Kolyma and the northern part of the Sea of Okhotsk were found. On their basis the species is divided into groups in accordance with the habitat. The existence of a separate group “Cottus poecilopus” within the genus Cottus, which includes taxa of the species rank, including C. kolymensis, has been confirmed.
Genetic Susceptibility to Ketosis in Cattle: Current State of Research
Authors: Sokolova O. V. , Bytov M. V. , Belousov A. I. , Bezborodova N. A. , Zubareva V. D. , Martynov N. A. , Zaitseva O. S. , Shkuratova I. A.
Published: April 2024

High-yield productivity in dairy cows is due to intense functioning of all organs and organism systems, that predisposes animals to various forms of disorders of metabolic processes. Progress of energy disbalance in high-yield dairy cows during lactation contributes to the development of systemic metabolic disorders, negatively affecting milk production and reproductive potential of animals. Interest in breeding ketosis resistant cattle is global and finding of mutations, gene variants and molecular and genetic processes contributing to one or another phenotype are considered as key steps in understanding a degree of susceptibility to ketosis. These steps will also give an insight in etiology of ketosis and provide basis for designing novel effective breeding programs. In this paper we present an overview of studies based on genetic and molecular research methods in finding genetic markers of cattle ketosis development. We discuss comprehensive SNPs localization of GWAS meta-analysis data, protein-protein interactions of associated with SNPs candidate genes via STRING, as well as SNPs annotation of associated biological processes. We provide candidate gene expression profiles for associated with ketosis tissues based on human data with GTEx tool.
The ATOX1 Gene Role in Copper Metabolism and in the Copper-Induced Diseases Pathogenesis
Authors: Zhalsanova I. Zh. , Fonova E. A. , Zhigalina D. I. , Skryabin N. A.
Published: April 2024

The ATOX1 (Antioxidant Protein 1) is a human copper metal chaperone that plays an important role in cellular copper homeostasis. The protein is responsible for cytosolic copper absorption from CTR1 (copper transporter 1) and transport to the copper pumps in the Trans Golgi network to the ATP7A and ATP7B proteins. This review collected data on the antioxidant role of ATOX1, the gene role in the angiogenesis regulation and cancer cell proliferation, and the role in the copper-induced diseases pathogenesis – Wilson’s disease and Menkes disease.
Genetically Isolated Population of Saccharomyces bayanus in New Zealand and Australia
Authors: Borovkova A. N. , Naumov G. I. , Shnyreva A. V. , Naumova E. S.
Published: April 2024

The genetic relatedness of yeasts in the Saccharomyces bayanus complex has been studied using the methods of molecular and classical genetics. A divergent population of S. bayanus has been found in New Zealand and Australia. The S. bayanus complex includes four genetic populations: S. bayanus var. bayanus, S. bayanus var. uvarum, S. eubayanus and New Zealand population. The strains of the New Zealand population differ significantly in the nucleotide sequences of nuclear (FSY1, HIS3, MET2) and mitochondrial (FUN14, COX2) genes and form semi-sterile hybrids with other populations: viability of ascospores is 6.2–23.3%. There is no complete interspecific postzygotic isolation between S. bayanus var. bayanus, S. bayanus var. uvarum, S. eubayanus, and New Zealand populations: all hybrids showed regular meiotic segregation of control auxotrophic markers. According to the results obtained, four genetic populations belong to the same biological species with genomic divergence at the level of taxonomic varieties.
Monitoring the Genetic Structure of the Sable Population (Martes zibellina Linnaeus, 1758) Middle Amur Region
Authors: Frisman L. V. , Brykova A. L.
Published: April 2024

Based on the analysis of microsatellite loci Ma3 and Mer041, the genetic structure of the sable population of the Middle Amur Region was monitored. Materials of hunting fees of winter seasons from 2011 to 2021 were studied. Three geographic subpopulations of sable from the Bureya Highlands and one from the eastern slopes of the Sikhote-Alin Ridge are considered. It was shown that the group of specific alleles characterizing the differences between the sable populations of the Bureya Highlands and the Sikhote-Alin is represented by four alleles. The monitoring of two microsatellite loci in the subpopulations of the Bureinsky Highlands showed a higher allelic diversity in the northern autochthonous compared to the more southern ones that arose on the basis of the settlement of the northern in the first half of the 20th century. The relative homogeneity of the population structure of the sable of the Bureinsky Highlands is shown, which does not lead to a statistically significant level of differentiation of subpopulations either in space or in time. A different character of the dynamics of allelic diversity was found in the subpopulations of the left bank (Bureya Highland) and right bank (Sikhote-Alin Ridge) of the Amur River. It has been hypothesized that temporal heterogeneity in the Sikhote-Alin subpopulation may indicate the existence on the eastern slopes of the Sikhote-Alin of a spatially heterogeneous population structure formed from descendants and possible hybrids of autochthonous and introduced forms. The influence of the anthropogenic factor on the dynamics of the genetic structure is considered.
Association of VNTR Polymorphism of the AS3MT Gene with the Risk of Schizophrenia
Authors: Korovaitseva G. I. , Lezheiko T. V. , Oleichik I. V. , Golimbet V. E.
Published: April 2024

The AS3MT gene encodes arsenic(III) methyltransferase. VNTR polymorphism of the AS3MT gene is characteristic only for the human genome. It is associated with the expression of a human-specific AS3MTd2d3 protein isoform, which is a potential risk factor for the development of schizophrenia. In this study, we for the first time have analyzed the distribution of frequencies of alleles and genotypes of VNTR polymorphism in a large sample of ethnic Russians. The association of VNTR with the risk of schizophrenia has been studied. The study included 1002 patients with schizophrenia and schizophrenia spectrum disorders and 1510 people of the control group. Women with the V3/V3 genotype have an increased risk of schizophrenia (OR = 1.4, 95% CI: 1.11–1.77).
Regulatory Potential of Non-Coding RNAs Colocalized with Cardiomyopathy-Related Genes
Authors: Kucher A. N. , Nazarenko M. S.
Published: April 2024

Non-coding RNAs (ncRNAs) play an important role in the regulation of the activity of genes essential for the development and function of the cardiovascular system. Intragenic ncRNAs have been shown to be coordinately regulated and/or expressed with their host genes, including ncRNAs resided within cardiomyopathy (CMP)-related genes. This review summarizes the results of CMP-related intragenic ncRNA studies in the function of the healthy heart and in the development of different forms of CMPs. CMP-related intragenic ncRNAs such as miRNAs (miR-1, miR-133a, miR-208a, miR-208b, miR-324, miR-490, miR-499a) and long ncRNAs (MHRT, TTN-AS1 and KCNQ1OT1) are actively involved in research. It has been established that the level of these of ncRNAs in myocardium is characterized by developmental-stage-specific dynamics, gender-specific and chamber-specific patterns. These ncRNAs exhibit differential expression in myocardium/serum of humans and model animals under the influence of exogenous and endogenous factors. The expression levels of these ncRNAs in the myocardium/serum is associated with clinical features during the development and progression of CMPs. The change in the level of ncRNAs preceding clinical manifestation of CMPs have been reported. The possibility to arrest the development of CMPs and even the restoration of the normal phenotype by controlling the levels of these regulatory molecules indicate their involvement in the pathogenesis of the disease. miRNAs and long ncRNAs, whose genes resided within CMP-related genes, are involved in various metabolic processes that are important for the heart function, including their involvement in epigenetic processes.
Study of the Genotoxicity of Beta-Propiolactone Using E. coli lux Biosensors and Nematode Caenorhabditis elegans
Authors: Machigov E. A. , Abilev S. K. , Igonina E. V. , Marsova M. V.
Published: April 2024

For the first time, lux biosensors of E. coli and the nematode Caenorhabditis elegans were used to study the genotoxicity of beta-propiolactone (BPL) used in the production of inactivated viral vaccines as an inactivator. It has been shown that the DNA-damaging activity of BPL is due not only to its ability to bind to bacterial DNA, but also to the ability to generate in the cell such reactive oxygen species as superoxide anion and peroxide, which have genotoxic activity. It was found that BPL in a dose-dependent manner, starting from a concentration of 0.001 mol/L, reduces the survival of bacteria. However, the intensity of expression of the antioxidant defense gene of superoxide dismutase soxS and the DNA repair gene colD increased. BPL induced DNA breaks in nematode cells detected by electrophoresis. The antioxidant acetylcysteine (ACC) reduced the genotoxic effects of BPL on both bacteria and nematode.