NATURE OF LEGAL BEHAVIOR: THE CONCEPTS OF DEFINITION AND THEIR EVOLUTION

Purpose: The purpose of the study is determining nature of legal behavior: the concepts of definition and their evolution Methodology: This is intellectual research and we used here historical methods for analyzing. Result: The genesis of the concept of legal behavior implies a link between research and the praxeological dimension of the legal system in which the legal personality is a central element. Applications: This research can be used for universities, teachers, and students. Novelty/Originality: In this research, the model of nature of legal behavior: the concepts of definition and their evolution are presented in a comprehensive and complete manner

Haplotype analysis of APOE intragenic SNPs

BACKGROUND: APOE epsilon4 allele is most common genetic risk factor for Alzheimer\u27s disease (AD) and cognitive decline. However, it remains poorly understood why only some carriers of APOE epsilon4 develop AD and how ethnic variabilities in APOE locus contribute to AD risk. Here, to address the role of APOE haplotypes, we reassessed the diversity of APOE locus in major ethnic groups and in Alzheimer\u27s Disease Neuroimaging Initiative (ADNI) dataset on patients with AD, and subjects with mild cognitive impairment (MCI), and control non-demented individuals. RESULTS: We performed APOE gene haplotype analysis for a short block of five SNPs across the gene using the ADNI whole genome sequencing dataset. The compilation of ADNI data with 1000 Genomes identified the APOE epsilon4 linked haplotypes, which appeared to be distant for the Asian, African and European populations. The common European epsilon4-bearing haplotype is associated with AD but not with MCI, and the Africans lack this haplotype. Haplotypic inference revealed alleles that may confer protection against AD. By assessing the DNA methylation profile of the APOE haplotypes, we found that the AD-associated haplotype features elevated APOE CpG content, implying that this locus can also be regulated by genetic-epigenetic interactions. CONCLUSIONS: We showed that SNP frequency profiles within APOE locus are highly skewed to population-specific haplotypes, suggesting that the ancestral background within different sites at APOE gene may shape the disease phenotype. We propose that our results can be utilized for more specific risk assessment based on population descent of the individuals and on higher specificity of five site haplotypes associated with AD

Identical Functional Organization of Nonpolytene and Polytene Chromosomes in Drosophila melanogaster

Salivary gland polytene chromosomes demonstrate banding pattern, genetic meaning of which is an enigma for decades. Till now it is not known how to mark the band/interband borders on physical map of DNA and structures of polytene chromosomes are not characterized in molecular and genetic terms. It is not known either similar banding pattern exists in chromosomes of regular diploid mitotically dividing nonpolytene cells. Using the newly developed approach permitting to identify the interband material and localization data of interband-specific proteins from modENCODE and other genome-wide projects, we identify physical limits of bands and interbands in small cytological region 9F13-10B3 of the X chromosome in D. melanogaster, as well as characterize their general molecular features. Our results suggests that the polytene and interphase cell line chromosomes have practically the same patterns of bands and interbands reflecting, probably, the basic principle of interphase chromosome organization. Two types of bands have been described in chromosomes, early and late-replicating, which differ in many aspects of their protein and genetic content. As appeared, origin recognition complexes are located almost totally in the interbands of chromosomes

Paucity and preferential suppression of transgenes in late replication domains of the D. melanogaster genome

<p>Abstract</p> <p>Background</p> <p>Eukaryotic genomes are organized in extended domains with distinct features intimately linking genome structure, replication pattern and chromatin state. Recently we identified a set of long late replicating euchromatic regions that are underreplicated in salivary gland polytene chromosomes of <it>D. melanogaster</it>.</p> <p>Results</p> <p>Here we demonstrate that these underreplicated regions (URs) have a low density of <it>P</it>-<it>element </it>and <it>piggyBac </it>insertions compared to the genome average or neighboring regions. In contrast, <it>Minos</it>-based transposons show no paucity in URs but have a strong bias to testis-specific genes. We estimated the suppression level in 2,852 stocks carrying a single <it>P</it>-<it>element </it>by analysis of eye color determined by the mini-<it>white </it>marker gene and demonstrate that the proportion of suppressed transgenes in URs is more than three times higher than in the flanking regions or the genomic average. The suppressed transgenes reside in intergenic, genic or promoter regions of the annotated genes. We speculate that the low insertion frequency of <it>P-elemen</it>ts and <it>piggyBac</it>s in URs partially results from suppression of transgenes that potentially could prevent identification of transgenes due to complete suppression of the marker gene. In a similar manner, the proportion of suppressed transgenes is higher in loci replicating late or very late in Kc cells and these loci have a lower density of <it>P-elements </it>and <it>piggyBac </it>insertions. In transgenes with two marker genes suppression of mini-<it>white </it>gene in eye coincides with suppression of <it>yellow </it>gene in bristles.</p> <p>Conclusions</p> <p>Our results suggest that the late replication domains have a high inactivation potential apparently linked to the silenced or closed chromatin state in these regions, and that such inactivation potential is largely maintained in different tissues.</p

Characteristics of eating behavior and the level of hormones regulating the appetite in patients with type 2 diabetes mellitus and body mass index more than 35 kg /m2

Background. The role of the hormones in eating behavior in the regulation of appetite has been well studied, but their relationship with various types of eating behavior has not been established. Aims. To study the frequency of different types of eating behavior, hunger/satiety feeling estimated by the visual analog scale and levels of leptin and gastrointestinal tract hormones that are involved in appetite regulation, fat and carbohydrate metabolism (ghrelin and glucagon-like peptide 1) in patients with diabetes mellitus type 2 and obesity. Materials and methods. The study included 35 people with obesity (BMI&gt;35 kg/m2) and diabetes mellitus type 2 (T2DM) who received the stable sugar-lowering therapy, the median body mass index (BMI) was 40,1 [36,5; 49,6] kg/m2, the median age was 58 [52,5; 64] years. Blood tests for insulin, leptin, ghrelin, glucagon-like peptide-1, C-peptide, glucose, glycated hemoglobin and lipids profile were done in all cases, also HOMA-IR and HOMA-&beta; were calculated. All patients completed questionnaires determining eating behavior type and hunger/satiety feeling severity. Results. In patients with T2DM and obesity a high frequency of combination of different types of eating behavior were found, it was 54,3%. Among the isolated types, restrictive eating behavior was more common &ndash; in 40%. In patients with different types of eating behavior the tendency to difference in the level of hormones regulating appetite was found, but it was not significant. High frequency of an appropriate reduction of postprandial ghrelin level was found in patients with restrictive type of eating behavior. Correlation between the level of hormones regulating appetite and hunger/satiety feeling was weak, it might reflect the resistance to these hormones in patients with severe obesity and T2DM. At the same time the relationship between the ghrelin level and the &beta;-cells functional state parameters was significant. Conclusions. The severity of leptin and ghrelin resistance correlated with each other in T2DM and obesity patients; the severity of ghrelin resistance was associated with the beta cells functional state; according to our data postprandial ghrelin level may have opposite changes in patients with T2DM and obesity and its adequate reduction is more common for patients with restrictive type of eating behavior

Effect Trichoderma spp on wheat (Triticum aestivum)

The objective this study were to determine effect of Trichoderma spp and Humic acid 60% on three Varieties of wheat (Triticum aestivum). The study included two factors،first factor was immersion of seeds in Humic acid 60% solution Humic acid 60% + Trichoderma spp150Mg/l ،Humic acid 60% + Trichoderma spp 250Mg/l،symbols T1 ،T2، T3،T4 respectively. The second factor is three varieties of wheat (Iba99 ،Adina ،Dijlla) and the plant variety is represented by V1 ،V2،V3 respectively. Treatments were Design (RCBD) with three replicates Statistics were evaluated followed by Duncan multiple range test to compare means at P<(0.05). Data presented the use of Humic acid 60% + Trichoderma spp250 Mg/l led to a significant increase in the studied traits as well as the interaction between variables where treatment V2T4 were highest significant increase in plant height، root length and spike length ، which reached 95.07 cm plant height ،14.93 cm length Root ،spike length is 11.50 cm ،while treatment V1T4 were the highest significant increase in leaf reach ،reaching 26.80 cm

Cerium Oxide Nanoparticles Protect Cortical Astrocytes from Oxygen–Glucose Deprivation through Activation of the Ca²⁺ Signaling System

Most of the works aimed at studying the cytoprotective properties of nanocerium are usually focused on the mechanisms of regulation of the redox status in cells while the complex effects of nanocerium on calcium homeostasis, the expression of pro-apoptotic and protective proteins are generally overlooked. There is a problem of a strong dependence of the effects of cerium oxide nanoparticles on their size, method of preparation and origin, which significantly limits their use in medicine. In this study, using the methods of molecular biology, immunocytochemistry, fluorescence microscopy and inhibitory analysis, the cytoprotective effect of cerium oxide nanoparticles obtained by laser ablation on cultured astrocytes of the cerebral cortex under oxygen–glucose deprivation (OGD) and reoxygenation (ischemia-like conditions) are shown. The concentration effects of cerium oxide nanoparticles on ROS production by astrocytes in an acute experiment and the effects of cell pre-incubation with nanocerium on ROS production under OGD conditions were studied. The dose dependence for nanocerium protection of cortical astrocytes from a global increase in calcium ions during oxygen–glucose deprivation and cell death were demonstrated. The concentration range of cerium oxide nanoparticles at which they have a pro-oxidant effect on cells has been identified. The effect of nanocerium concentrations on astrocyte preconditioning, accompanied by increased expression of protective proteins and limited ROS production induced by oxygen–glucose deprivation, has been investigated. In particular, a correlation was found between an increase in the concentration of cytosolic calcium under the action of nanocerium and the suppression of cell death. As a result, the positive and negative effects of nanocerium under oxygen–glucose deprivation and reoxygenation in astrocytes were revealed at the molecular level. Nanocerium was found to act as a “double-edged sword” and to have a strictly defined concentration therapeutic “window”

A Study of Safety and Efficacy of Nivolumab and Bendamustine (NB) in Patients With Relapsed/Refractory Hodgkin Lymphoma After Nivolumab Monotherapy Failure

Abstract. This single-center prospective clinical trial evaluated the combination of nivolumab plus bendamustine (NB) as a salvage regimen in classical Hodgkin lymphoma patients after failure of nivolumab monotherapy. A total of 30 patients received nivolumab (3 mg/kg) on D1,14 and bendamustine (90 mg/m2) on D1, 2 of a 28-day cycle for up to 3 cycles. The ORR was 87% with 57% CR, 30% PR. With median follow-up of 25 months, the estimated 2-year OS was 96,7% (95% CI, 90.2%–100%), PFS was 23,3% (95% CI, 8.2%–38.4%) median PFS was 10.2 months (95% CI, 7.7–14.2 months) with median DOR 6.6 months (95% CI 3.9–11.6 months). Ten patients (33.3%) experienced grade 3 to 4 AE during therapy. Infections were most common AEs of the combined therapy. NB was a highly efficient salvage regimen in relapsed/refractory cHL with a manageable toxicity profile and modest potential for achievement of long-term remission. Registered at www.clinicaltrials.gov (#NCT0334365)