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The transcription factor retinoid X receptor-alpha (RXRα) can also form homotetramers. Here the authors show that the anti-cancer agent K-80003 selectively inhibits the nongenomic action of N-terminally-cleaved RXRα in tumour cells by stabilizing its tetramerization but not that of full-length RXRα.

The disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause seizures. Our study aims at revealing therapeutic potential of vitamins B1 and B6 by estimating the short- and long-term effects of their combined administration with the seizure inductor pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to modified Racine’s scale, along with delayed physiological and biochemical consequences the next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than the male rats. The next day after a seizure, sex differences in behavior and brain biochemistry arise. The induced sex differences in anxiety and locomotor activity correspond to the disappearance of sex differences in the brain aspartate and alanine, with appearance of those in glutamate and glutamine. PTZ decreases the brain malate dehydrogenase activity and urea in the males and the phenylalanine in the females. The administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5–2 h) between the administration of the vitamins and PTZ. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. The delayed effects of vitamins and/or PTZ are mostly sex-specific and interacting. Our findings on the sex differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

The results of the GPR observations carried out in three lakes of Karelia: Lake Verkhneye (the White Sea Biological Research Station of the Moscow State University), Nizhneye Nilmozero and Vendyurskoye, were summarized. A screened 300MHz antenna was used for the survey. The GPR potential, including parameters such as propagation distance in water and in soil, was analyzed. Water resistivity measurements were carried out for each lake. Characteristics of the Quaternary profile (being the main factor that influence the propagation depth of electromagnetic waves) were studied. It was demonstrated that high water resistivity and, possibly, the lack of clay in the profile suggest GPR can perform well for the depth range of 10-15 m below the bottom and at water depths up to 12-15 m. The GPR method, which is far more cost efficient compared to seismoacoustics, can be applied to deals with many production as well as scientific problems.

The use of new sources of by-pass protein in the cow diets to optimize milk production and herd reproduction performance indicators in modern economic conditions is relevant. The article presents data on the use of a protein concentrate containing plant and animal components and its effect on the quality of the milk obtained, the state of the rumen bacterial community and reproduction indicators. The use of protein concentrate of both 1.0 kg and 1.5 kg/head/day contributed to improving the quality and increasing the yield of dry matter of cow's milk by 0.17-0.43 %. During the days in milk, with the use of protein concentrate it was observed that increase the content of Selenomonas by 1.7 % and 4.1%, which cleave the urea, indicates a more efficient use of nitrogen in the diet. The inclusion of protein concentrate in the composition of daily diets helps to improve reproduction indicators, reduce the duration of the service period and the number of semen doses spent.

Post-harvest losses of grapes during prolonged storage in refrigerated chambers are mainly associated with dehydration and darkening of stems, wilting of berries and the development of mold. As a result of the physiological processes in the berries, a sufficiently humid environment is created, which contributes to the development of microbiological spoilage. To combat this phenomenon, it is recommended to use natural biodegradable polymers, which prevent the deterioration of quality characteristics by creating a semi-permeable protective barrier. In this regard, the purpose of the study was to determine the optimal dosage of film-forming solutions for treatment of grapes. For this, samples of grapes of the Kishmish Luchistyi variety were prepared with an applied to the surface coating layer of two types: potato starch/gelatin/glycerin/ natamycin and chitosan/sodium alginate/glycerin/natamycin at a biopolymer ratio of 50/50%, with the addition of 1.3% glycerin and 0.3% natamycin. Based on the identified dependence of the weight loss and the value of the resistance of berries to the pressure force on the storage time and the amount of film-forming coating, the optimal amount of film-forming coating required to treat 1000 grams of berries is substantiated – 50 ml.

Breastfeeding in patients with chronic myeloid leukaemia (CML) who take tyrosine kinase inhibitors (TKIs) is not recommended but interruption of TKI treatment may cause the loss of remission. We observed the kinetics of the leukaemic clone in 3 women with CML in accordance with treatment interruptions for pregnancy and breastfeeding. The concentrations of nilotinib and imatinib in maternal milk were measured when the breastfeeding period was over. Nilotinib transfer into human breast milk was demonstrated for the first time and had a maximum concentration (Cmax) 129 ng/ml after 4 hours of the drug intake at a dose of 400 mg. The Cmax of imatinib in maternal milk ranged from 420 to 1411 ng/ml after 4-8 hours of the drug intake at a dose of 400-600 mg. Breastfeeding without TKI treatment may be safe with molecular monitoring, but preferably in those patients with CML who have durable deep molecular response.

Aim of investigation. To investigate options of improvement of anal sphincter function of defunctioning loop by BFT and tibial nerve stimulation.Material and methods. Overall 23 patients with preventive stoma were included in original investigation. Diagnostic profilometry and sphincterometry were carried out. Treatment included BFT and tibial nerve stimulation for 10 days. Results. After treatment profilometry revealed statistically significant increase of mean resting pressure, while sphincterometry — at conation as well.Conclusions. Muscular structures of the defunctioning anal sphincter respond to BFT and tibial nerve stimulation, increasing both tension and force of voluntary contractions.

Cellular NAD(P)H-dependent oxidoreductase activity with artificial dyes (NAD(P)H-OR) is an indicator of viability, as the cellular redox state is important for biosynthesis and antioxidant defense. However, high NAD(P)H due to impaired mitochondrial oxidation, known as reductive stress, should increase NAD(P)H-OR yet perturb viability. To better understand this complex behavior, we assayed NAD(P)H-OR with resazurin (Alamar Blue) in glioblastoma cell lines U87 and T98G, treated with inhibitors of central metabolism, oxythiamin, and phosphonate analogs of 2-oxo acids. Targeting the thiamin diphosphate (ThDP)-dependent enzymes, the inhibitors are known to decrease the NAD(P)H production in the pentose phosphate shuttle and/or upon mitochondrial oxidation of 2-oxo acids. Nevertheless, the inhibitors elevated NAD(P)H-OR with resazurin in a time- and concentration-dependent manner, suggesting impaired NAD(P)H oxidation rather than increased viability. In particular, inhibition of the ThDP-dependent enzymes affects metabolism of malate, which mediates mitochondrial oxidation of cytosolic NAD(P)H. We showed that oxythiamin not only inhibited mitochondrial 2-oxo acid dehydrogenases, but also induced cell-specific changes in glutamate and malate dehydrogenases and/or malic enzyme. As a result, inhibition of the 2-oxo acid dehydrogenases compromises mitochondrial metabolism, with the dysregulated electron fluxes leading to increases in cellular NAD(P)H-OR. Perturbed mitochondrial oxidation of NAD(P)H may thus complicate the NAD(P)H-based viability assay.

We'd like to present a specific grid infrastructure and web application development and deployment. The purpose of infrastructure and web application is to solve particular geophysical problems that require heavy computational resources. Here we cover technology overview and connector framework internals. The connector framework links problem-specific routines with middleware in a manner that developer of application doesn't have to be aware of any particular grid software. That is, the web application built with this framework acts as an interface between the user 's web browser and Grid's (often very) own middleware. Our distributed computing system is built around Gridway metascheduler. The metascheduler is connected to TORQUE resource managers of virtual compute nodes that are being run atop of compute cluster utilizing the virtualization technology. Such approach offers several notable features that are unavailable to bare-metal compute clusters. The first application we've integrated with our framework is seismic anisotropic parameters determination by inversion of SKS and converted phases. We've used probabilistic approach to inverse problem solution based on a posteriory probability distribution function (APDF) formalism. To get the exact solution of the problem we have to compute the values of multidimensional function. Within our implementation we used brute-force APDF calculation on rectangular grid across parameter space. The result of computation is stored in relational DBMS and then represented in familiar human-readable form. Application provides several instruments to allow analysis of function's shape by computational results: maximum value distribution, 2D cross-sections of APDF, 2D marginals and a few other tools. During the tests we've run the application against both synthetic and observed data.

Children with acute pulmonary bleeding (8 cases) due to different pathology of trancheobronchial tree were followed-up at the period from 2008 to 2014. Diagnostic angiography and X-ray endovascular occlusion of bronchial arteries were performed in the case of insufficiency of conservative and endoscopic methods of hemostasis. Microembolic spheres were used for embolization of distal vessels. The embolization coils and micro-coils were applied for occlusion of great vessels. Children (5 cases) were discharged from the hospital after embolization at the terms of 6-12 months. They hadn’t any ischemic complications associated with bronchial artery occlusion. The sequelae of main disease caused deaths of 3 other kids. The X-ray occlusion is a low-invasive and highly effective method of arrest of all types of bleeding from pool of bronchial arteries. The method could be applied even in extremely severe condition of the patients.

The literature on hidradenitis suppurativa in sexual and gender minorities remains sparse. This review article aims to discuss critical factors for providers to consider in lesbian, gay, bisexual, transgender, queer, intersex, and asexual patients with hidradenitis suppurativa, including associated comorbidities, gender-affirming hormonal therapy, squamous cell carcinoma, infections in HIV-positive patients, and creating a welcoming clinic for sexual and gender minority patients. [ABSTRACT FROM AUTHOR]

This article is devoted to the transformations of the subject of legal science in the conditions of postmodern. The latter is characterized as a current period when the concepts of the foundations of the world order are radically changed. The transition to a non-classical rationality with it’s basic principles of variability, decentration, contextuality is the expression of it in the socio-humanitarian field. The last of those principles is explored more thoroughly. The recognition of contextuality of the law accents its social conditionality, what renders impossible the isolated studying of a legal reality. The article considers the different types of contexts, to which it is accepted to address within the continental and Anglo-American traditions of legal researches, their importance for the law studying are shown. The special attention is paid to social challenges which legal regulation and legal science face in the conditions of postmodern, such as «death of a legal entity» (the radical change of position and the self-consciousness of person in the postmodern epoch), mediatization of law and influence of mass culture on it.