Vitamin A in the cerebrospinal fluid of patients with and without idiopathic intracranial hypertension

Journal ArticleWe quantified vitamin A in the cerebrospinal fluid of patients with idiopathic intracranial hypertension, elevated intracranial pressure of other causes and normal intracranial pressure. Vitamin A could be detected by high-pressure liquid chromatography in most of the specimens. There was a significantly higher level of vitamin A in the cerebrospinal fluid of some patients with idiopathic intracranial hypertension. Vitamin A toxicity may play a role in the pathogenesis of idiopathic intracranial hypertension

Європейський досвід у сфері взаємодії держави та інститутів громадянського суспільства

У статті розглянуто питання взаємодії держави та громадянського суспільства в контексті досвіду європейських країн, визначено форми такої взаємодії, можливість застосування європейського досвіду в Україні. Вказано на те що розбудова демократичної, правової, соціальної держави є ключовим та важливим пріоритетом, а реалізація надважливого стратегічного курсу на інтеграцію з Європейським Союзом – є кінцевою метою цього процесу, цьому сприяє також забезпечення всебічного входження України у європейський політичний, економічний і правовий простір. Розкрито взаємодію інститутів громадянського суспільства і держави яка має формуватися на європейських загальноприйнятих засадах, таких як взаємна співпраця, партнерство. Показано що держава формуючи інституційно-правове середовище всебічно сприяє взаємодії та розвитку громадянського суспільства. Зазначено що сучасною тенденцією у відносинах державних органів та інститутів громадянського суспільства є трансформація системи грантів у систему контрактів, яка посилює скорочення фінансової залежності громадянського суспільства від державної влади. Констатовано що загалом, у країнах ЄС поступово відмовляються від формату засідань консультативно-дорадчих органів на користь онлайн-консультацій з громадськістю

Deletion of the glucocorticoid receptor chaperone FKBP51 prevents glucocorticoid-induced skin atrophy

FKBP51 (FK506-binding protein 51) is a known co-chaperone and regulator of the glucocorticoid receptor (GR), which usually attenuates its activity. FKBP51 is one of the major GR target genes in skin, but its role in clinical effects of glucocorticoids is not known. Here, we used FKBP51 knockout (KO) mice to determine FKBP51's role in the major adverse effect of topical glucocorticoids, skin atrophy. Unexpectedly, we found that all skin compartments (epidermis, dermis, dermal adipose and CD34+ stem cells) in FKBP51 KO animals were much more resistant to glucocorticoid-induced hypoplasia. Furthermore, despite the absence of inhibitory FKBP51, the basal level of expression and glucocorticoid activation of GR target genes were not increased in FKBP51 KO skin or CRISPR/Cas9-edited FKBP51 KO HaCaT human keratinocytes. FKBP51 is known to negatively regulate Akt and mTOR. We found a significant increase in AktSer473 and mTORSer2448 phosphorylation and downstream pro-growth signaling in FKBP51-deficient keratinocytes in vivo and in vitro. As Akt/mTOR-GR crosstalk is usually negative in skin, our results suggest that Akt/mTOR activation could be responsible for the lack of increased GR function and resistance of FKBP51 KO mice to the steroid-induced skin atrophy

Androgen receptor targets NFKB and TSPI to suppress prostate tumor growth in vivo

The androgen role in the maintenance of prostate epithelium is subject to conflicting opinions. While androgen ablation drives the regression of normal and cancerous prostate, testosterone may cause both proliferation and apoptosis. Several investigators note decreased proliferation and stronger response to chemotherapy of the prostate cancer cells stably expressing androgen receptor (AR), however no mechanistic explanation was offered. In this paper we demonstrate in vivo anti-tumor effect of the AR on prostate cancer growth and identify its molecular mediators. We analyzed the effect of AR on the tumorigenicity of prostate cancer cells. Unexpectedly, the AR-expressing cells formed tumors in male mice at a much lower rate than the AR-negative controls. Moreover, the AR-expressing tumors showed decreased vascularity and massive apoptosis. AR expression lowered the angiogenic potential of cancer cells, by increasing secretion of an anti-angiogenic protein, thrombospondin-1. AR activation caused a decrease in RelA, a subunit of the pro-survival transcription factor NF kappa B, reduced its nuclear localization and transcriptional activity. This, in turn, diminished the expression of its anti-apoptotic targets, Bcl-2 and IL-6. Increased apoptosis within AR-expressing tumors was likely due to the NF kappa B suppression, since it was restricted to the cells lacking nuclear (active) NF kappa B. Thus we for the first time identified combined decrease of NF kappa B and increased TSP1 as molecular events underlying the AR anti-tumor activity in vivo. Our data indicate that intermittent androgen ablation is preferable to continuous withdrawal, a standard treatment for early-stage prostate cancer. (C) 2007 Wiley-Liss, Inc.The androgen role in the maintenance of prostate epithelium is subject to conflicting opinions. While androgen ablation drives the regression of normal and cancerous prostate, testosterone may cause both proliferation and apoptosis. Several investigators note decreased proliferation and stronger response to chemotherapy of the prostate cancer cells stably expressing androgen receptor (AR), however no mechanistic explanation was offered. In this paper we demonstrate in vivo anti-tumor effect of the AR on prostate cancer growth and identify its molecular mediators. We analyzed the effect of AR on the tumorigenicity of prostate cancer cells. Unexpectedly, the AR-expressing cells formed tumors in male mice at a much lower rate than the AR-negative controls. Moreover, the AR-expressing tumors showed decreased vascularity and massive apoptosis. AR expression lowered the angiogenic potential of cancer cells, by increasing secretion of an anti-angiogenic protein, thrombospondin-1. AR activation caused a decrease in RelA, a subunit of the pro-survival transcription factor NF kappa B, reduced its nuclear localization and transcriptional activity. This, in turn, diminished the expression of its anti-apoptotic targets, Bcl-2 and IL-6. Increased apoptosis within AR-expressing tumors was likely due to the NF kappa B suppression, since it was restricted to the cells lacking nuclear (active) NF kappa B. Thus we for the first time identified combined decrease of NF kappa B and increased TSP1 as molecular events underlying the AR anti-tumor activity in vivo. Our data indicate that intermittent androgen ablation is preferable to continuous withdrawal, a standard treatment for early-stage prostate cancer. (C) 2007 Wiley-Liss, Inc

Androgen Receptor Drives Cellular Senescence

The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ΔN isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor

Evaluation and selection of servicing youngling bulls for immunity to diseases

Available from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

Composite Scheduling Strategies in Distributed Computing with Non-dedicated Resources

AbstractThis work presents dispatching strategies based on methods of job-flow and application-level scheduling in virtual organizations of distributed computational environments with non-dedicated resources. Job-flow management is implemented with the set of specific rules for resource usage. Applications are considered as parallel jobs. Strategies are based on economic scheduling models and diverse administration policies inside resource domains (clusters, computational nodes equipped with multicore processors etc.). Methods of priority economic scheduling of global job flows and local-level applications in distributed computations are studied. Job management structures and economic mechanisms for load balancing in distributed environments are considered

Scheduling Optimization in Grid with VO Stakeholders’ Preferences

The problem of intelligent Grid computing and job-flow scheduling with regard to preferences given by various groups of virtual organization (VO) stakeholders (such as users, resource owners and administrators) is studied. A specific flexible resources share algorithm is proposed for job-flow scheduling which enables to achive a balance between the VO stakeholders’ conflicting preferences and policies. This approach provides greater VO scheduling fairness, improves the overall quality of service and resource load efficiency. Two different metrics are introduced to find a scheduling solution balanced between VO stakeholders. Experimental results prove that the cyclic scheduling scheme allows establishing efficient cooperation between different VO stakeholders even if their goals and preferences are contradictory