Polymorphisms of Fatty Acid Elongase 2 Gene Afftects Risk of Pulmonary Tuberculosis in China Han Population

Background: As an infectious disease closely related to Mycobacterium tuberculosis, autoimmunity, inflammation, environment and heredity, the relationship between the single nucleotide polymorphism of elongase 2 gene and the susceptibility to tuberculosis is still unknown. Methods: Between January 2016 and November 2018, a hospital-based case-control study was conducted. This epidemiological survey was conducted in both hospitals every three months. rs3798719, rs1570069, and rs2236212 in ELOVL2 gene were detected by Sanger sequencing. Results: Stratified by gender, the genotypes and allele frequencies of rs3798719, rs1570069 and rs2236212 showed significant differences between the two groups (χ2 = 6.987, P = 0.030), Genetic modeling showed that rs3798719 was statistically different in the overdominance model (χ2 = 4.784, OR = 1.414, 95% CI: 1.036-1.929, P < 0.05). The polymorphism of rs2236212 between male TB patients and healthy controls was statistically different in the dominance model. (χ2 = 4.192, OR = 0.507; 95% CI: 0.262-0.981, P < 0.05). Conclusion: The rs3798719 of ELOVL2 gene may be associated with susceptibility to TB in female population and the rs2236212 of ELOVL2 gene may be associated with TB incidence in male patients.

Recent Advances in Implantation-Based Genetic Modeling of Biliary Carcinogenesis in Mice

Epithelial cells in the biliary system can develop refractory types of cancers, which are often associated with inflammation caused by viruses, parasites, stones, and chemicals. Genomic studies have revealed recurrent genetic changes and deregulated signaling pathways in biliary tract cancer (BTC). The causal roles have been at least partly clarified using various genetically engineered mice. Technical advances in Cre-LoxP technology, together with hydrodynamic tail injection, CRISPR/Cas9 technology, in vivo electroporation, and organoid culture have enabled more precise modeling of BTC. Organoid-based genetic modeling, combined with implantation in mice, has recently drawn attention as a means to accelerate the development of BTC models. Although each model may not perfectly mimic the disease, they can complement one another, or two different approaches can be integrated to establish a novel model. In addition, a comparison of the outcomes among these models with the same genotype provides mechanistic insights into the interplay between genetic alterations and the microenvironment in the pathogenesis of BTCs. Here, we review the current status of genetic models of BTCs in mice to provide information that facilitates the wise selection of models and to inform the future development of ideal disease models.

ANALYSIS OF SCIENTIFIC APPROACHES TO THE ESSENCE OF SOCIAL ACTIVITY OF STUDENT YOUTH

Based on the identification of the main approaches to understanding the content of personality activity in general, the article highlights the main scientific approaches to interpreting of the essence of social activity of the individual: activity, acmeological, systemic, subjective, axiological, genetic modeling. It is determined that the most appropriate is the author’s proposed subject-activity approach to the interpretation of the essence of social activity of student youth. We consider the subjectivity of the individual as an important prerequisite and, at the same time, the result of social activity of students, which is realized through an active and responsible attitude to themselves, to various objects, to another person, to educational and future professional activities. At the heart of the activity of the independent subject of life we see: readiness and ability to realize their interests and the interests of society; constant and strong desire to influence social processes and real participation in public affairs; the desire to strengthen and improve the existing social order, based on the assimilation of social values and the realization of their goals, taking into account the interests of society. According to the subject-activity approach, social activity of the individual is considered by us as a personal formation of prosocial orientation, internally determined by individual needs, values, volitional characteristics and characteristics of person, and outwardly manifested in the transformation of society and personality, that is in social activity.

Methods for studying genetic modifications

Objects and modern methods of genome editing are considered. The immune system of prokaryote and their protective mechanisms that prevent the purposeful editing of the genome for the benefit of the researcher is characterized. This mechanism in prokaryotes are cluster regulatory interspatial short palindrome repetitions. The number of such repetitions varies from object to object, which ultimately makes it impossible to get the perfect standard model. Three types of such systems that have their own mechanism for generating proteins have now been identified. The proteins, which are now most commonly used to edit the genome and identify areas of proto-special adjacent motifs, are described. Detailed characteristics of the organization of the immune system prokaryote and phases of its activity are given. Three types of short-palin re-recurrence systems have now been identified, and the teams are being identified as cluster regulatory interspatial short palindrome repetitions-Cas9. Each system uses its own mechanism to generate proteins that catalyze the fission of nucleic acids. The type II cluster regulatory interspatial short palindrome repetitions system is most commonly used, better adapted to edit the genome because of its simplicity. It has been established that the cluster regulatory interspatial short palindrome repetitions-Cas9 system can be used for point editing of the genome and in eukaryotes. This is done either through non-homological annexation of the end, or by homologically directed reparation. A promising variant of genetic modeling is the use of the enzyme-endonuclease Cpf1, which is the effector protein of the cluster regulatory interspatial short palindrome repetitions-Cas V type systems. Cpf1 is smaller than the enzyme protein Cas9 and for the system to function only require specers of ribonucleic acid, without additional ribonucleic acid. Unlike Cas9, which cuts both chains of deoxyribonucleic acid in the same place, Cpf1 generates an incision, creating ticky ends that can be used to insert interesting sequences by complementing and ligation. It is likely that the system using the enzyme-endonuclease Cpf1 will be more convenient than the system where the protein is used Cas9, as the range of editing of the controlled genome of ribonucleic acid is expanded to make the necessary edits.

A DREAM complex gene expression program involving E2F4, E2F6, SIN3A and NFYB in human breast cancer and in murine breast cancers arising from genetic modeling of transformation induced by viral infection.

We recently reported that nearly half of the most differentially expressed genes in the the breast tumors of mice resulting from genetic modeling of integration events or oncogene expression occurring during viral infection by viruses including the murine mammary tumor virus, SV40 and polyomavirus are also significantly differentially expressed in human breast cancer, the majority of which are of unknown etiology (1, 2). Here we present evidence of the existence of a gene expression program operating through the DREAM complex, E2F transcription factors E2F4 and E2F6, as well as NFYB and SIN3A, both in the tumors of mice resulting from genetic modeling of viral infection and in the primary tumors of human patients with breast cancer through blind analysis of published whole transcriptome data (3-5). The similarity between human breast cancer and cancers induced by genetic engineering of integration events and oncogene expression in mice is not limited to differential expression of single genes in isolation, nor multiple numbers of single genes; a centrally regulated, major transcriptional network is perturbed in a mirrored fashion in human breast cancer and virally-induced breast cancers in mice.

A shared transcriptional landscape between human breast cancers and breast cancers induced by genetic modeling of viral infection in mice.

We recently demonstrated, through analysis of published transcriptome data from human and murine breast cancer that eight genes whose expression was most different in tumors that arise in the mouse breast following transgenic expression of the SV40 large T-antigen or modeling of integration following infection with multiple mammary tumor viruses, including CD36, ASPM, PDGFD and CEP55 were also among the genes most differentially expressed in the primary tumors of humans with breast cancer (1). We report here that these transcriptional similarities are a much larger phenomena, with 45-54% of the top one hundred most differentially expressed genes in murine breast cancer resulting from genetic modeling of viral infection with the murine mammary tumor virus MMTV or transgenic expression of SV40 large T also among the most differentially expressed genes in human breast cancer. Despite inherent differences in transcription due to species divergence, blind whole transcriptome (2-4) analyses reveals striking transcriptional similarity in the landscape of human breast cancer and murine breast cancers resulting from genetic modeling of viral infection, providing further evidence to support the hypothesis that one or more viral agents with transformation capacity may contribute to the development of human breast cancer.

Transcriptional similarities between human breast cancers and breast cancers resulting from genetic modeling of viral infection in mice.

Breast cancer affects women in the United States and worldwide at relatively high frequency (1). Mutations in BRCA1 have been identified as a cause of breast cancer in a minority of patients with the familiar or inherited form of breast cancer (2, 3), but it remains unknown what factor or factors trigger development of breast cancer in the vast majority of women. It has been suggested that infection with a spectrum of viruses, including DNA tumor viruses like human papillomavirus and SV40, and retroviruses like the mouse mammary tumor virus (MMTV) can be associated with human breast cancer (4-6) but experimental evidence to support the claim that viral infections cause human breast cancer is lacking. We evaluated the hypothesis that primary tumors from humans with breast cancers will share transcriptional similarity at the systems level with experimental breast cancers induced by genetic modeling of viral infection or transgenic expression of a viral oncoprotein by mining published microarray data (7-9). We identified, in a blind fashion, eight independent genes with crucial functions in cancer cell survival among the most differentially expressed genes transcriptome-wide, including genes not previously implicated in human breast cancer, both when comparing normal breast tissue and primary tumors from women with breast cancer, and when comparing breast tissue to breast tumors from 5 independent strains of mice genetically engineered to model viral induction of transformation in the mammalian breast, including MMTV-PyMT, MMTV-Wnt11 and the large T-antigen of SV40. These marked transcriptional changes between breast and tumor were not only shared by humans with breast cancer and breast cancer resulting from genetic modeling of viral integration or oncogene expression events in mice, but also by mice genetically engineered to model familial breast cancer, lacking BRCA1 and one copy of the tumor suppressor p53. These data demonstrate that key changes in the human breast cancer tumor transcriptome are also found in mice that develop breast cancer as a direct result of viral infection, and are one piece of experimental evidence, obtained through unbiased methods, to support the assertion that viral infection can contribute to breast cancer in humans.