Application of alternative de novo motif recognition models for analysis of structural heterogeneity of transcription factor binding sites: a case study of FOXA2 binding sites.

The most popular model for the search of ChIP-seq data for transcription factor binding sites (TFBS) is the positional weight matrix (PWM). However, this model does not take into account dependencies between nucleotide occurrences in different site positions. Currently, two recently proposed models, BaMM and InMoDe, can do as much. However, application of these models was usually limited only to comparing their recognition accuracies with that of PWMs, while none of the analyses of the co-prediction and relative positioning of hits of different models in peaks has yet been performed. To close this gap, we propose the pipeline called MultiDeNA. This pipeline includes stages of model training, assessing their recognition accuracy, scanning ChIP-seq peaks and their classification based on scan results. We applied our pipeline to 22 ChIP-seq datasets of TF FOXA2 and considered PWM, dinucleotide PWM (diPWM), BaMM and InMoDe models. The combination of these four models allowed a significant increase in the fraction of recognized peaks compared to that for the sole PWM model: the increase was 26.3 %. The BaMM model provided the main contribution to the recognition of sites. Although the major fraction of predicted peaks contained TFBS of different models with coincided positions, the medians of the fraction of peaks containing the predictions of sole models were 1.08, 0.49, 4.15 and 1.73 % for PWM, diPWM, BaMM and InMoDe, respectively. Thus, FOXA2 BSs were not fully described by only a sole model, which indicates theirs heterogeneity. We assume that the BaMM model is the most successful in describing the structure of the FOXA2 BS in ChIP-seq datasets under study.

[Preventative repair of postoperative ventral hernia considering the markers of connective tissue dysplasia]. / Opredelenie pokazaniia k preventivnomu éndoprotezirovaniiu na osnovanii markerov displazii soedinitel'noi tkani u bol'nykh s posleoperatsionnymi ventral'nymi gryzhami.

OBJECTIVE: To define the indication for preventive mesh implantation in patients scheduled for laparotomy. MATERIAL AND METHODS: There were 108 patients divided into the control (52 patients without anterior abdominal wall hernia) and the main (56 patients with ventral hernia) groups. RESULTS: Predominance of collagen type III over type I was observed in patients older 60 years in the main group. The maximum ratio of collagen types I and III was 1.4 in the main group. The minimum number of inter-fiber spaces (n=5) was noted in patients aged 30-40 years. The maximum density of connective tissue was 250 pixels per inch. CONCLUSION: Analysis of connective tissue structures revealed some important age-related features and markers of connective tissue dysplasia in the main group. An indication for preventive mesh implantation in patients scheduled for laparotomy was determined.

[Computer methods of analysis of chromosome contacts in the cell nucleus based on sequencing technology data]. / Komp'iuternye metody analiza khromosomnykh kontaktov v iadre kletki po dannym tekhnologii sekvenirovaniia.

The study spatial chromosome structure and chromosome folding in the interphase cell nucleus is an important challenge of world science. Detection of eukaryotic genome regions that physically interact with each other could be done by modern sequencing technologies. A basic method of chromosome folding by total sequencing of contacting DNA fragments is HI-C. Long-range chromosomal interactions play an important role in gene transcription and regulation. The study of chromosome interactions, 3D (three-dimensional) genome structure and its effect on gene transcription allows revealing fundamental biological processes from a viewpoint of structural regulation and are important for cancer research. The technique of chromatin immunoprecipitation and subsequent sequencing (ChIP-seq) make possible to determine binding sites of transcription factors that regulate expression of eukaryotic genes; genome transcription factors binding maps have been. The ChIA-PET technology allows exploring not only target protein binding sites, but also pairs of such sites on proximally located and interacting with each other chromosomes co-located in three-dimensional space of the cell nucleus. Here we discuss the principles of the construction of genomic maps and matrices of chromosome contacts according to ChIA-PET and Hi-C data that capture the chromosome conformation and overview existing software for 3D genome analysis including in house programs of gene location analysis in topological domains.

[Collagen types ratio in prediction of postoperative ventral hernias]. / Sootnoshenie tipov kollagena v prognozirovanii posleoperatsionnykh ventral'nykh gryzh.

AIM: To analyze collagen types ratio in skin and aponeurosis in order to predict postoperative ventral hernias. MATERIAL AND METHODS: The trial included 141 patients for the period 2012-2015. Group I (n=65) of patients without ventral hernias was divided into subgroup AI (primary operation, n=41) and BI (re-operation, n=24). Group II consisted of 76 patients with ventral hernias. We performed histological examination of skin and aponeurosis to define the collagen structure of connective tissue. RESULTS: There were significant differences between collagen type I/III ratio in skin (2.81±0.52 in group I vs. 1.13±0.48 in group II) and aponeurosis (2.69±0.41 vs. 1.09±0.21, respectively, p≤0.05). We revealed strong direct correlation (r=+0.92) between aponeurosis and skin specimens in one group. Collagen type I level was 73.81±2.74% in subgroup AI and 72.03±2.47% in subgroup BI. Collagen type I was predominant (p≤0.05). CONCLUSION: In patients with ventral hernias collagen type I/III ratio in skin is 2.54 times lower than in patients without hernias. Significant correlation of collagen types in skin and aponeurosis (r= +0.92) allows to predict the risk of postoperative ventral hernias on basis of skin fragment.

[The influence of 'potassium orotate' on neocollagenogenesis in implantation of polypropylene endoprosthesis and polypropylene combined with polylactic acid endoprosthesis]. / Vliyanie orotata kaliya na neokollagenogenez pri implantatsii polipropilenovogo endoproteza i endoproteza iz polipropilena s polimolochnoi kislotoi v eksperimente.

AIM: To study neocollagenogenesis after implantation of polypropylene endoprosthesis and polypropylene combined with polylactic acid endoprosthesis on background of «potassium orotate¼ administration. MATERIAL AND METHODS: We used two different types of endoprosthesis in the experiment. The first type was made of just polypropylene, the second type was made of polypropylene combined with polylactic acid. Histological examination was performed using polarizing microscopy. Collagen types I and III ratio in connective tissue around the prosthesis was analyzed according to the color that was individual for each type. RESULTS: The results were significantly better in case of collagenogenesis stimulation with Potassium orotate within 30 days and later for one type of endoprosthesis. Also we revealed that collagenogenesis and paraprosthesis capsule formation were more active in case of combined endoprosthesis. We revealed stimulating action of «Potassium Orotate¼ for collegenogenesis process, this fact was proved by increased collagen I/III ratio. CONCLUSION: Optimization of collagenogenesis was based on persistent 1,37-fold increase of collagen I/III ratio in case of combined endoprosthesis after 90 days. It was manifested by accelerated formation of connective tissue capsule and facilitated early isolation of the implant from surrounding tissues.

THE INFLUENCE OF VITAMIN C ON THE DYNAMIC OF RELATION OF COLLAGEN I AND III TYPES IN THE PERIPROSTHESIS AREA.

The aim of the study was to learn the degree of biocompatibility of synthetic herniological prostheses «Progrip¼, with collagen-stimulating effect of ascorbic acid on the growth of connective tissue in the experiment. We examined characteristics of collagenogenesis in the anterior abdominal wall depending on the effect of vitamin C using the method of polarization microscopy. We suggest a new way to stimulate reparation process by ascorbic acid which would help to optimize forming functionally matured structures of connective tissue of the anterior abdominal wall surrounding endoprosthesis. Due to the results of our investigation it has been clear that modification effect of vitamin C is positive for synthesis of collagen in the periprosthetic capsule for any type of endoprosthesis. It has been proves by statistically reliable increase in ratio of collagen types I and III when vitamin C is used in the diet of experimental animals.

[Dynamics of cytokine profile in patients with postoperative hernias the abdominal wall in prosthesis with polytetrafluoroethylene and polyvinylidene fluoride application].

The results of experimental and clinical studies for the comparative evaluation of implants used in herniology of polytetrafluoroethylene (PTFE) and polyvinylidene fluoride (PVDF) are presented. Experimental investigations conducted on 200 mice, which in the anterior abdominal wall mesh prosthesis implanted. All animals, regardless of the type of implanted prosthesis, deduced from the experiment at 10, 30 th and 60 th day. Histological investigation of the submissions received. The clinical part is based on an analysis of surgical treatment results of postoperative abdominal wall hernia (POGBS) in 121 patients during the period from 2003 to 2011 patients were divided into 2 groups. The control group included 73 patients who were operated during the period 2005-2007, used PTFE graft "Ecoflon", in the main - 48 patients who from 2008 to 2011 the prosthesis was implanted PVDF - "Uniflex" firm "Linteks". In each group, selected patients whom have examined the profile of cytokines. The results of the studies found that both the material cause marked inflammatory reaction with a characteristic stepwise increased levels of proinflammatory and antiinflammatory cytokines, the dynamics of cytokines indicative of a less pronounced local inflammatory reaction to the prosthesis from the PVDF. In the application of the implant "Uniflex" a lower incidence of exudative complications in comparison with that when using the prosthesis "Ecoflon" it is preferable in clinical use.

[Comparative morphology of tissues when using polypropylene and polytetrafluoretilen prostheses].

The synthetic mesh is widely used for treatment of hernias. We conducted a comparative study of the morphological pattern of inflammation, the cellular composition of tissues and dynamics of scar formation in mice when using implants "Esfil" and "Unifleks" under influence of single and double injection of cultured fibroblast and without such injection to the region of stents location. A more pronounced inflammatory reaction during the study period of investigation was observed in the case of "Esfil". In the late period of the study, a higher percentage of fibroblasts was observed in the case of the prosthesis "Unifleks" compared to the prosthesis "Esfil". Injection of cultured fibroblasts modifies the curve of the dynamics of the inflammatory process by making it smoother in the case of both prostheses. So, more preferred is the use of prostheses "Unifleks".

[Local immunity and methods for its assessment upon exposure to ambient air-polluting biologicals].

The investigators studied the impact of biological air contamination by the dusts resulting from protein feedstuff manufacture and grain on local immunity of the mucosae in children and adults living in the areas that were differently distant from industrial objects, the sources of contamination, as well as in workers of the shops contaminated by dust containing various amounts of protein. The studies showed that the workers of a biochemical plant exhibited a considerable change in the majority of immunological parameters (lysozyme activity, heterophile antibody titers, salivary and skin bactericidity, salivary total and R-protein, and immunoglobulins A, M, G, and E). There was a significant decrease in salivary IgA activity. The immunological parameters of children and adults were further compared with their morbidity as the most important health index. It was found that with the production rates being steadily raised, the average annual morbidity increment was 1.3; children less than 14 years of age in whom the incidence of bronchial asthma and bronchitis with asthmatic components increased 5-fold were most susceptible.

Charge qubit entanglement via conditional single-electron transfer in an array of quantum dots.

We propose a novel scheme to generate entanglement among quantum-dot-based charge qubits via sequential electron transfer in an auxiliary quantum dot structure whose transport properties are conditioned by qubit states. The transfer protocol requires the utilization of resonant optical pulses combined with an appropriate voltage gate pattern. As an example illustrating the application of this scheme, we examine the nine-qubit Shor code state preparation together with the error syndrome measurement.