Recent publications
Obligatory parthenogenesis in vertebrates is restricted to squamate reptiles and evolved through hybridisation. Parthenogens can hybridise with sexual species, resulting in individuals with increased ploidy levels. We describe two successive hybridisations of the parthenogenetic butterfly lizards (genus Leiolepis) in Vietnam with a parental sexual species. Contrary to previous proposals, we document that parthenogenetic L. guentherpetersi has mitochondrial DNA and two haploid sets from L. guttata and one from L. reevesii, suggesting that it is the result of a backcross of a parthenogenetic L. guttata × L. reevesii hybrid with a L. guttata male increasing ploidy from 2n to 3n. Within the range of L. guentherpetersi, we found an adult tetraploid male with three L. guttata and one L. reevesii haploid genomes. It probably originated from fertilisation of an unreduced triploid L. guentherpetersi egg by a L. guttata sperm. Although its external morphology resembles that of the maternal species, it possessed exceptionally large erythrocytes and was likely sterile. As increased ploidy level above triploidy or tetraploidy appears to be harmful for amniotes, all-female asexual lineages should evolve a strategy to prevent incorporation of other haploid genomes from a sexual species by avoiding fertilisation by sexual males.
The human genome contains millions of candidate cis-regulatory elements (cCREs) with cell-type-specific activities that shape both health and many disease states¹. However, we lack a functional understanding of the sequence features that control the activity and cell-type-specific features of these cCREs. Here we used lentivirus-based massively parallel reporter assays (lentiMPRAs) to test the regulatory activity of more than 680,000 sequences, representing an extensive set of annotated cCREs among three cell types (HepG2, K562 and WTC11), and found that 41.7% of these sequences were active. By testing sequences in both orientations, we find promoters to have strand-orientation biases and their 200-nucleotide cores to function as non-cell-type-specific ‘on switches’ that provide similar expression levels to their associated gene. By contrast, enhancers have weaker orientation biases, but increased tissue-specific characteristics. Utilizing our lentiMPRA data, we develop sequence-based models to predict cCRE function and variant effects with high accuracy, delineate regulatory motifs and model their combinatorial effects. Testing a lentiMPRA library encompassing 60,000 cCREs in all three cell types further identified factors that determine cell-type specificity. Collectively, our work provides an extensive catalogue of functional CREs in three widely used cell lines and showcases how large-scale functional measurements can be used to dissect regulatory grammar.
Background
The ε4 allele of the apolipoprotein E (APOE4+) genotype and aging synergistically contribute to the risk of Alzheimer's disease (AD), but the mechanisms underlying their influence are not completely understood. The methylation of ELOVL2 DNA accounts for 70% of the variance in the aging epigenetic clock. The ELOVL2 gene is essential for synthesizing long polyunsaturated fatty acids, crucial for cell membrane integrity, inflammation modulation, and energy maintenance. This study investigated the impact of APOE genotype and ELOVL2 methylation on EEG alpha rhythm and functional MRI (fMRI) resting‐state functional connectivity (rsFC) of brain networks in non‐demented adults during aging.
Method
We examined EEG alpha sub‐bands power and individual alpha peak frequency (IAPF) and the fMRI rsFC in 151 non‐demented volunteers, age range 20‐84 years, stratified by APOE genotype. APOE ε3/ε3 subgroup (APOE4‐) included 104 subjects, APOE ε4/ε3 (APOE4+) subgroup – 47 subjects. ELOVL2 cg16867657 methylation was examined in the blood in subgroup of 56 individuals (35 APOE4‐ and 21 APOE4+). The individuals underwent fMRI tsFC of the brain using the CONN Matlab/SPM‐based toolbox (Whitfield‐Gabrieli and Nieto‐Castanon, 2012). Informed written consent was obtained from all participants. All subjects underwent a neurological examination and cognitive screening.
Result
The presence of the APOE4+ genotype was associated with more pronounced alpha rhythm slowing and more pronounced decrease of fMRI rsFC during aging. Age‐related increase of ELOVL2 methylation was observed. The partial correlation analysis, with age as a covariate, revealed a significant correlation between ELOVL2 methylation and IAPF.
Conclusion
More pronounced alpha rhythm slowing and fMRI rsFC reduction in APOE4+ carriers during aging can be linked to synaptic dysfunction and deterioration of white matter integrity. Impaired lipid metabolism, driven by age‐dependent ELOVL2 methylation, may accelerate the impact of the APOE4+ genotype on neurophysiological alterations during aging. These changes increase the risk of AD developed.
Funding:
This study was supported by Russian Science Foundation (Project No. 19‐75‐30039 to TA genotyping; Project No. 22‐15‐00448 to NP, RK, VF, EK EEG and fMRI analysis and MP for genotyping) and by Ministry of Science and Higher Education of the Russian Federation (Agreement 075‐10‐2021‐093 project GEN‐RND‐2017).
Objective: We evaluate the immunotherapeutic potential of the yellow fever virus vaccine strain 17D (YFV 17D) for intratumoral therapy of pancreatic cancer in mice. Methods: The cytopathic effect of YFV 17D on mouse syngeneic pancreatic cancers cells were studied both in vitro and in vivo and on human pancreatic cancers cells in vitro. Results: YFV 17D demonstrated a strong cytopathic effect against human cancer cells in vitro. Although YFV 17D did not exhibit a lytic effect against Pan02 mouse cells in vitro, a single intratumoral administration of 17D caused a delay in tumor growth and an increase in median survival by 30%. Multiple injections of 17D did not further improve the effect on tumor growth; however, it notably extended the median survival. Furthermore, preliminary immunization with 17D enhanced its oncotherapeutic effect. Conclusions: Intratumoral administration of yellow fever virus vaccine strain 17D delayed tumor in a murine model of pancreatic cancer. The fact that YFV 17D in vitro affected human cancer cells much more strongly than mouse cancer cells appears promising. Hence, we anticipate that the in vivo efficacy of YFV-17D-based oncolytic therapy will also be higher against human pancreatic carcinomas compared to its effect on the mouse pancreatic tumor.
The size of viral genomes is limited, thus the majority of encoded proteins possess multiple functions. The main function of tobamoviral movement protein (MP) is to perform plasmodesmata gating and mediate intercellular transport of the viral RNA. MP is a remarkable example of a protein that, in addition to the initially discovered and most obvious function, carries out numerous activities that are important both for the manifestation of its key function and for successful and productive infection in general. Briefly, MP binds the viral genome, delivers it to the plasmodesmata (PD) and mediates its intercellular transfer. To implement the transport function, MP interacts with diverse cellular factors. Each of these cellular proteins has its own function, which could be different under normal conditions and upon viral infection. Here, we summarize the data available at present on the plethora of cellular factors that were identified as tobamoviral MP partners and analyze the role of these interactions in infection development.
By addition reaction between [Zn(phen)X2] (phen=1,10-phenanthroline, X=CF3SO3- (Otf), CF3COO- (1)) and lanthanide carboxylates in acetonitrile heterometallic molecular [Zn2Gd2(phen)2(µ-fur)8(OOCCF3)2(H2O)2] (2) and ionic [Zn2Eu2(phen)2(µ-piv)8(H2O)4](Otf)2 (3) (fur = furoate-anion, piv = trimethylacetate-anion) complexes...
The study was conducted to determine the possibility of using phenotypic correlations between traits as an indirect indicator of genetic correlations in domestic reindeer (Rangifer tarandus L.). The assessment of phenotypic parameters of the exterior and live weight of reindeer was carried out at the Yamal Experimental Station, a separate structural subdivision of the Federal State Budgetary Scientific Institution, the Tyumen Scientific Center, Siberian Branch of the Russian Academy of Sciences. The object of the study was a population sample of 94 adult females of the Nenets breed, selected at random, without constitution defects and having a calf. in October 2020. A total of 94 does (adult females) aged 3 to 9 years were examined. The animals were well-fed, had a calf and had no visible constitution defects. The sample showed high positive phenotypic correlations between “height at withers” and “height at elbow” (=0.84), “height at withers” and “chest depth” (=0.71), “live weight” and “chest girth” (=0.63), as well as between “live weight” and “chest depth” (=0.6). Genetic correlations between traits calculated using genotypes of microsatellite markers showed comparable results. For the pair of measurements “height at withers” and “height at elbow”, the genetic correlation was about 0.83, and for the pair “height at withers” and “chest depth” it was about 0.71. The results of comparative analysis between phenotypic and genetic correlation matrices demonstrated a high degree of consistency. It has been shown that phenotypic correlations can potentially be used as an indirect indicator of genetic correlations for reindeer selection for live weight and linear body dimensions.
Introduction
Back pain (BP) is a complex heritable trait with an estimated heritability of 40% to 60%. Less than half of this can be explained by known genetic variants identified in genome-wide association studies.
Objectives
We applied a powerful multi-trait and gene-based approach to association analysis of BP to identify novel genes associated with BP.
Methods
Using phenotypes and imputed genotypes from the UK Biobank 500k dataset, we generated a multi-trait phenotype by combining 3 BP-related phenotypes: chronic BP, dorsalgia, and intervertebral disk disorders. We performed gene-based association analysis for 3 BP-related phenotypes and multi-trait phenotype. Conditional analysis was applied to account for the effects of genetic variants outside the gene. Finally, we replicated significantly associated genes using the FinnGen database.
Results
We identified 32 genes associated with BP and replicated 16 of them. Thirteen genes were detected using the multi-trait phenotype. Seven of the detected genes, MIPOL1, PTPRC, RHOA, MAML3, JADE2, MLLT10, and RERG, were not previously reported. Several new genes are known to be associated with traits genetically correlated with BP or to be involved in pathways associated with BP.
Conclusion
Using new powerful methods of association analysis, we identified 7 novel genes associated with BP. Our results provide new insights into the genetics of back pain.
Background/Objectives: The aim was to study the possibilities of biomedical application of gadolinium oxide nanoparticles (Gd2O3 NPs) synthesized under industrial conditions, and evaluate their physicochemical properties, redox activity, biological activity, and safety using different human cell lines. Methods: The powder of Gd2O3 NPs was obtained by a process of thermal decomposition of gadolinium carbonate precipitated from nitrate solution, and was studied using transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectroscopy, mass spectrometry, and scanning electron microscopy (SEM) with energy dispersive X-ray analyzer (EDX). The redox activity of different concentrations of Gd2O3 NPs was studied by the optical spectroscopy (OS) method in the photochemical degradation process of methylene blue dye upon irradiation with an optical source. Biological activity was studied on different human cell lines (keratinocytes, fibroblasts, mesenchymal stem cells (MSCs)) with evaluation of the effect of a wide range of Gd2O3 NP concentrations on metabolic and proliferative cellular activity (MTT test, direct cell counting, dead cell assessment, and visual assessment of cytoarchitectonics). The test of migration activity assessment on a model wound was performed on MSC culture. Results: According to TEM data, the size of the NPs was in the range of 2–43 nm, with an average of 20 nm. XRD analysis revealed that the f Gd2O3 nanoparticles had a cubic structure (C-form) of Gd2O3 (Ia3)¯ with lattice parameter a = 10.79(9) Å. Raman spectroscopy showed that the f Gd2O3 nanoparticles had a high degree of crystallinity. By investigating the photooxidative degradation of methylene blue dye in the presence of f Gd2O3 NPs under red light irradiation, it was found that f Gd2O3 nanoparticles showed weak antioxidant activity, which depended on the particle content in the solution. At a concentration of 10−3 M, the highest antioxidant activity of f Gd2O3 nanoparticles was observed when the reaction rate constant of dye photodegradation decreased by 5.5% to 9.4 × 10−3 min−1. When the concentration of f Gd2O3 NPs in solution was increased to 10−2 M upon irradiation with a red light source, their antioxidant activity changed to pro-oxidant activity, accompanied by a 15% increase in the reaction rate of methylene blue degradation. Studies on cell lines showed a high level of safety and regenerative potential of Gd2O3 NPs, which stimulated fibroblast metabolism at a concentration of 10−3 M (27% enhancement), stimulated keratinocyte metabolism at concentrations of 10−3 M–10−5 M, and enhanced keratinocyte proliferation by an average of 35% at concentrations of 10−4 M. Furthermore, it accelerated the migration of MSCs, enhancing their proliferation, and promoting the healing of the model wound. Conclusions: The results of the study demonstrated the safety and regenerative potential of redox-active Gd2O3 NPs towards different cell lines. This may be the basis for further research to develop nanomaterials based on Gd2O3 NPs for skin wound healing and in regenerative medicine generally.
To date, natural species are widely used as pharmaceutical agents for many human diseases. One of these is the seeds of Nigella sativa and its constituent thymoquinone (TQ). Being a biologically active compound, TQ has a variety of therapeutic properties, including antioxidant, anti-inflammatory, antitumor and a number of others. TQ is an absorber of free and superoxide radicals, therefore it is a promising natural radioprotector against the immunosuppressive and oxidative effects of ionizing radiation. The review presents data on the radioprotective properties of TQ and some mechanisms of its activity. In addition, TQ exhibits antitumor activity by inhibiting cell proliferation, migration and invasion. Despite the fact that TQ induces apoptosis by regulating the expression of pro-apoptotic and anti-apoptotic genes in many types of cancer, the mechanism of action of TQ in oncological diseases has not yet been fully studied. Thus, this review highlights the mechanisms of action of TQ as a promising radioprotector and as a future candidate for antitumor therapy.
The theory of the evolutionary role of hereditary tumors, or carcino-evo-devo theory, may be considered as the next step after A.N. Severtsov theory of phylembryogenesis, the theory of evo-devo, and Susumu Ohno theory of evolution by gene duplication. The carcino-evo-devo theory pretends to be a unifying biological theory, because it unifies within an integrated consideration three main types of biological development – individual, evolutionary and neoplastic development. The carcino-evo-devo theory explains a series of unexplained biological phenomena. In the first place, it explains the mechanisms of progressive evolution and biological complexity increase using the concept of relatively unstable transitory forms and autonomous uncontrolled processes. The theory of the evolutionary role of hereditary tumors has formulated several non-trivial predictions in various fields of biology, which have been confirmed in the lab of the author and in other laboratories. The consequences of the carcino-evo-devo theory have implications in medicine and biotechnology. The first part of the article describes the basic principles from which the main hypothesis followed, the progressive developments of the concept, and the first experimental data in support of non-trivial predictions obtained in the laboratory of the author in the period before 2014, when our monograph “Evolution by Tumor Neofunctionalization” (Kozlov, 2014) has been published.
The article discusses the issues of conservation, distribution and acclimatization of sika deer on the territory of the Russian Federation, the Central Federal District and of the National Park “State Complex “Zavidovo”. A detailed analysis of the condition of the first range of sika deer in the Primorsky Krai, as well as the history of settlement and dynamics of its population in the Russian Federation. For the regions of the Central Federal District, the results of the cadastral assessment of sika deer resources were calculated, including the average long-term week, the average long-term illumination of the population (animals) per 1000 hectares of characteristic lands and the average long-term cost of resources (million rubles). As an effective model for the acclimatization of sika deer, an experience of its economic use was carried out in the National Park “State сomplex “Zavidovo” (Tver region).
To ensure the success of genetic rescue, we must minimise the potential negative effects of outbreeding depression that may arise from selecting source populations. The difficulty in assessing the likelihood of outbreeding depression has hindered its consideration in endangered species conservation. However, genomic research offers feasible indications. Here, we conduct conservation genomic analyses on the East Asian (EA) population and the relict Western/Central Asian (WCA) population of the critically endangered Siberian crane (Leucogeranus leucogeranus). We aim to assess genetic rescue's potential advantages and disadvantages between the two populations. Our analysis shows genomic evidence of limited genetic differentiation between them. The persistent decline in population size due to historical climatic oscillations leads to a decrease in genetic diversity and an increase in inbreeding. The WCA population has excessive deleterious homozygous mutations than the EA population, suggesting suffering from inbreeding depression resulting from less effective purifying selection. Forward simulations support the increase in genetic load due to elevated levels of inbreeding compromises fitness during population collapse. We strongly recommend an urgent genetic rescue for the WCA population through population supplementation from the EA population. However, the continuous monitoring of fitness outcomes is required through captive breeding. This work provides useful insights into the genetic management of a critically endangered species and emphasises the importance of evaluating the likelihood of outbreeding depression through genomic approaches.
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