Organizational Mechanisms for Implementing Russia's Arctic Strategy in the 21st Century

The Arctic in the 21st century remains a popular topic in the natural-scientific, economic, socio-humanitarian, and political spheres. The relevance of studying the Arctic is determined by the fact that in recent decades, deep and irreversible transformations have taken place in this region, and a full under-standing of the causes and consequences of which for the economy and environmental management has not yet developed. As a result of climate change and globalization, there is a growing interest in the Arctic macro-region on the part of many foreign countries that developed strategies and programs for the development of national Arctic zones at the beginning of the XXI century. Against the background of global competition for resources and transport communications, it seems relevant to analyze the features of the development of Russia's state policy for managing the Arctic zone of the Russian Federation in the XXI century. The article analyzes the mechanisms of implementation of Russian state policy in the Arctic based on the strategic planning system and reveals the bottlenecks in the system of state management of the Arctic region. It is concluded that the core of Russia's policy in the Arctic is innovative modernization that can ensure sustainable socio-economic development, infrastructure development, rational use of natural resources, protection of local ecosystems and development of indigenous communities

The Effects of Text Message Reminder on Blood Donor Show Rate

Introduction: Declining blood collection endangers the blood supply at a time when the health care system is requiring an increasingly greater amount of blood products. Blood donation centers are challenged to recruit and develop first-time donors into reliable repeat donors, thereby ensuring a sufficient blood supply. Communication strategies such as e-mail reminders have been shown to be an effective communications tool to promote blood collection. Alternatively, Text Messaging has been shown effective in primary care and preventative medicine. Text messaging improved patient compliance with a schedule of vaccine dosing, as well as improving patient attendance at outpatient clinics. Additionally, text messaging reminders have been shown to be as effective as phone reminders in increasing patient attendance at outpatient appointments. Finally, text messaging has been shown to be useful for managing self-care such as smoking cessation, monitoring asthmatic symptoms, and diabetes control. We investigated whether offering the use a text message reminder to donors would increase attendance at donation events, demonstrating that text messaging can be an effective tool in maintaining a pool of blood donors.https://scholarworks.uvm.edu/comphp_gallery/1008/thumbnail.jp

6-gene promoter methylation assay is potentially applicable for prostate cancer clinical staging based on urine collection following prostatic massage

The detection of prostate cancer (PCa) biomarkers in bodily fluids, a process known as liquid biopsy, is a promising approach and particularly beneficial when performed in urine samples due to their maximal non‑invasiveness requirement of collection. A number of gene panels proposed for this purpose have allowed discrimination between disease‑free prostate and PCa; however, they bear no significant prognostic value. With the purpose to develop a gene panel for PCa diagnosis and prognosis, the methylation status of 17 cancer-associated genes were analyzed in urine cell‑free DNA obtained from 31 patients with PCa and 33 control individuals using methylation‑specific polymerase chain reaction (MSP). Among these, 13 genes indicated the increase in methylation frequency in patients with PCa compared with controls. No prior association has been reported between adenomatosis polyposis coli 2 (APC2), homeobox A9, Wnt family member 7A (WNT7A) and N‑Myc downstream‑regulated gene 4 protein genes with PCa. The 6‑gene panel consisting of APC2, cadherin 1, forkhead box P1, leucine rich repeat containing 3B, WNT7A and zinc family protein of the cerebellum 4 was subsequently developed providing PCa detection with 78% sensitivity and 100% specificity. The number of genes methylated (NGM) value introduced for this panel was indicated to rise monotonically from 0.27 in control individuals to 4.6 and 4.25 in patients with highly developed and metastatic T2/T3 stage cancer, respectively. Therefore, the approach of defining the NGM value may not only allow for the detection of PCa, but also provide a rough evaluation of tumor malignancy and metastatic potential by non‑invasive MSP analysis of urine samples

Organ-specific LPS-induced inflammatory gene expression in adult Zebrafish

Systemic inflammation is known to be a key component of infection and non-infection diseases progression and may lead to multiorgan failure, persistent inflammation, immunosuppression, catabolism syndrome or even indolent death. This importance dictates the need for relevant in vivo models of inflammation to investigate the pathogenesis of numerous diseases and to perform drug screening. Danio rerio (zebrafish) became one of the most important models to explore biological processes in vivo. The aim of the study was to generate a lipopolysaccharide (LPS) model of systemic inflammation in vivo using zebrafish and to identify organspecific proinflammatory genes activity after intraperitoneal LPS infusion. We performed organ specific analysis of main proinflammatory genes expression in zebrafish after LPS stimulation. Comparing 18s, eef1a1l1, gapdh, and actb as potential housekeeping genes, we came to conclusion that eef1a1l1 with 99% effectiveness is the most promising for further normalization in this model. The genes activity was the most pronounced in the heart where the expression of IL6, CXCL8a, and CXCL18β was increased up to 100-fold. Moreover, the kidneys were the most involved in the inflammatory process since the highest number of analysed genes were up-regulated there: expression levels of CXCL18β, CXCL8a, IL1β, IL6, Mpeg1.2, and TNFa were significantly increased. This was probably related to the kidney activity as an immune and hematopoietic organ. The lowest reactivity was detected in the muscles. Immune reactions could be dose-dependent, for instance the infusion of 20 µg LPS led to decrease of expression of IFNy, Mpeg 1.2, and Mpeg 1.1 in the liver and to increase of Mpeg 1.2 expression in the kidney comparing with 10 µg dosage. Thus, due to the high degree of the similarity and other unique properties, Danio rerio has the advantage of being relevant model of inflammation. Our model demonstrated that the investigation of isolated zebrafish organs could be useful and informative for the investigation of inflammatory processes

Regulation of BMAL1 Protein Stability and Circadian Function by GSK3β-Mediated Phosphorylation

Circadian rhythms govern a large array of physiological and metabolic functions. To achieve plasticity in circadian regulation, proteins constituting the molecular clock machinery undergo various post-translational modifications (PTMs), which influence their activity and intracellular localization. The core clock protein BMAL1 undergoes several PTMs. Here we report that the Akt-GSK3beta signaling pathway regulates BMAL1 protein stability and activity.GSK3beta phosphorylates BMAL1 specifically on Ser 17 and Thr 21 and primes it for ubiquitylation. In the absence of GSK3beta-mediated phosphorylation, BMAL1 becomes stabilized and BMAL1 dependent circadian gene expression is dampened. Dopamine D2 receptor mediated signaling, known to control the Akt-GSK3beta pathway, influences BMAL1 stability and in vivo circadian gene expression in striatal neurons.These findings uncover a previously unknown mechanism of circadian clock control. The GSK3beta kinase phosphorylates BMAL1, an event that controls the stability of the protein and the amplitude of circadian oscillation. BMAL1 phosphorylation appears to be an important regulatory step in maintaining the robustness of the circadian clock

Potassium channel gene mutations rarely cause atrial fibrillation

BACKGROUND: Mutations in several potassium channel subunits have been associated with rare forms of atrial fibrillation. In order to explore the role of potassium channels in inherited typical forms of the arrhythmia, we have screened a cohort of patients from a referral clinic for mutations in the channel subunit genes implicated in the arrhythmia. We sought to determine if mutations in KCNJ2 and KCNE1-5 are a common cause of atrial fibrillation. METHODS: Serial patients with lone atrial fibrillation or atrial fibrillation with hypertension were enrolled between June 1, 2001 and January 6, 2005. Each patient underwent a standardized interview and physical examination. An electrocardiogram, echocardiogram and blood sample for genetic analysis were also obtained. Patients with a family history of AF were screened for mutations in KCNJ2 and KCNE1-5 using automated sequencing. RESULTS: 96 patients with familial atrial fibrillation were enrolled. Eighty-three patients had lone atrial fibrillation and 13 had atrial fibrillation and hypertension. Patients had a mean age of 56 years at enrollment and 46 years at onset of atrial fibrillation. Eighty-one percent of patients had paroxysmal atrial fibrillation at enrollment. Unlike patients with an activating mutation in KCNQ1, the patients had a normal QT(c )interval with a mean of 412 ± 42 ms. Echocardiography revealed a normal mean ejection fraction of 62.0 ± 7.2 % and mean left atrial dimension of 39.9 ± 7.0 mm. A number of common polymorphisms in KCNJ2 and KCNE1-5 were identified, but no mutations were detected. CONCLUSION: Mutations in KCNJ2 and KCNE1-5 rarely cause typical atrial fibrillation in a referral clinic population

Загальноосвітнє та професійно-технічне навчання як засоби виправлення і ресоціалізації засуджених до позбавлення волі

Кондратов, Д. Ю. Загальноосвітнє та професійно-технічне навчання як засоби виправлення і ресоціалізації засуджених до позбавлення волі / Дмитро Юрійович Кондратов, Костянтин Євгенович Шевелев // Вісник Кримінологічної асоціації України. – 2022. – № 2 (27). – С. 110-119.У статті досліджено загальноосвітню та професійно-технічну підготовку як засоби виправлення та ресоціалізації засуджених до позбавлення волі. Наведено окремі положення кримінально-виконавчого законодавства зарубіжних країн щодо порядку та організації навчання засуджених до позбавлення волі з метою виявлення позитивного досвіду та впровадження його в чинне законодавство України. Зазначається, що в цілому пріоритетним напрямом організації професійного навчання засуджених в установах виконання покарань України залишається подальший розвиток мережі професійно-технічних навчальних закладів. Автори стверджують, що модернізація освіти залишається важливою складовою сучасної політики України.The article examines general education and vocational training as means of correction and resocialization of persons sentenced to imprisonment. Some provisions of the penitentiary legislation of foreign countries regarding the order and organization of providing education to those sentenced to deprivation of liberty with the aim of identifying positive experience and introducing it into the current legislation of Ukraine are given. It is noted that, in general, the further development of the network of vocational educational institutions remains a priority in relation to the organization of vocational training of convicts in the penal institutions of Ukraine. The authors state that the modernization of education remains an important component of the modern policy of Ukraine.В статье рассматривается общее образование и профессиональное обучение как средство исправления и ресоциализации осужденных к лишению свободы. Приведены некоторые положения пенитенциарного законодательства зарубежных стран относительно порядка и организации обеспечения воспитания осужденных к лишению свободы с целью выявления положительного опыта и внедрения его в действующее законодательство Украины. Отмечается, что в целом дальнейшее развитие сети профессионально-технических учебных заведений остается приоритетным направлением организации профессионального обучения осужденных в пенитенциарных учреждениях Украины. Авторы констатируют, что модернизация образования остается важной составляющей современной политики Украины

A Large Scale shRNA Barcode Screen Identifies the Circadian Clock Component ARNTL as Putative Regulator of the p53 Tumor Suppressor Pathway

BACKGROUND: The p53 tumor suppressor gene is mutated in about half of human cancers, but the p53 pathway is thought to be functionally inactivated in the vast majority of cancer. Understanding how tumor cells can become insensitive to p53 activation is therefore of major importance. Using an RNAi-based genetic screen, we have identified three novel genes that regulate p53 function. RESULTS: We have screened the NKI shRNA library targeting 8,000 human genes to identify modulators of p53 function. Using the shRNA barcode technique we were able to quickly identify active shRNA vectors from a complex mixture. Validation of the screening results indicates that the shRNA barcode technique can reliable identify active shRNA vectors from a complex pool. Using this approach we have identified three genes, ARNTL, RBCK1 and TNIP1, previously unknown to regulate p53 function. Importantly, ARNTL (BMAL1) is an established component of the circadian regulatory network. The latter finding adds to recent observations that link circadian rhythm to the cell cycle and cancer. We show that cells having suppressed ARNTL are unable to arrest upon p53 activation associated with an inability to activate the p53 target gene p21(CIP1). CONCLUSIONS: We identified three new regulators of the p53 pathway through a functional genetic screen. The identification of the circadian core component ARNTL strengthens the link between circadian rhythm and cancer

Deficient of a Clock Gene, Brain and Muscle Arnt-Like Protein-1 (BMAL1), Induces Dyslipidemia and Ectopic Fat Formation

A link between circadian rhythm and metabolism has long been discussed. Circadian rhythm is controlled by positive and negative transcriptional and translational feedback loops composed of several clock genes. Among clock genes, the brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) play important roles in the regulation of the positive rhythmic transcription. In addition to control of circadian rhythm, we have previously shown that BMAL1 regulates adipogenesis. In metabolic syndrome patients, the function of BMAL1 is dysregulated in visceral adipose tissue. In addition, analysis of SNPs has revealed that BMAL1 is associated with susceptibility to hypertension and type II diabetes. Furthermore, the significant roles of BMAL1 in pancreatic β cells proliferation and maturation were recently reported. These results suggest that BMAL1 regulates energy homeostasis. Therefore, in this study, we examined whether loss of BMAL1 function is capable of inducing metabolic syndrome. Deficient of the Bmal1 gene in mice resulted in elevation of the respiratory quotient value, indicating that BMAL1 is involved in the utilization of fat as an energy source. Indeed, lack of Bmal1 reduced the capacity of fat storage in adipose tissue, resulting in an increase in the levels of circulating fatty acids, including triglycerides, free fatty acids, and cholesterol. Elevation of the circulating fatty acids level induced the formation of ectopic fat in the liver and skeletal muscle in Bmal1 -/- mice. Interestingly, ectopic fat formation was not observed in tissue-specific (liver or skeletal muscle) Bmal1 -/- mice even under high fat diet feeding condition. Therefore, we were led to conclude that BMAL1 is a crucial factor in the regulation of energy homeostasis, and disorders of the functions of BMAL1 lead to the development of metabolic syndrome