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Abstract DNA polymerase ε (Polε) performs bulk synthesis of DNA on the leading strand during genome replication. Polε binds two substrates, a template:primer and dNTP, and catalyzes a covalent attachment of dNMP to the 3' end of the primer. Previous studies have shown that Polε easily inserts and extends ribonucleotides, which may promote mutagenesis and genome instability. In this work, we analyzed the mechanisms of discrimination against RNA-containing primers by human Polε (hPolε), performing binding and kinetic studies at near-physiological salt concentration. Pre-steady-state kinetic studies revealed that hPolεCD extends RNA primers with approximately 3300-fold lower efficiency in comparison to DNA, and addition of one dNMP to the 3′ end of an RNA primer increases activity 36-fold. Likewise, addition of one rNMP to the 3′ end of a DNA primer reduces activity 38-fold. The binding studies conducted in the presence of 0.15 M NaCl revealed that human hPolεCD has low affinity to DNA (K D of 1.5 µM). Strikingly, a change of salt concentration from 0.1 M to 0.15 M reduces the stability of the hPolεCD/DNA complex by 25-fold. Upon template:primer binding, the incoming dNTP and magnesium ions make hPolε discriminative against RNA and chimeric RNA–DNA primers. In summary, our studies revealed that hPolε discrimination against RNA-containing primers is based on the following factors: incoming dNTP, magnesium ions, a steric gate for the primer 2′OH, and the rigid template:primer binding pocket near the catalytic site. In addition, we showed the importance of conducting functional studies at near-physiological salt concentration.

Vladimir N Nikolenko,1,2 Ekaterina M Shelomentseva,2 Maria M Tsvetkova,2 Elina I Abdeeva,1 Dmitriy B Giller,1 Juliya V Babayeva,1 Evgeny E Achkasov,1 Liliya V Gavryushova,3 Mikhail Y Sinelnikov1,4 1First Moscow State Medical University Named After I.M. Sechenov (Sechenov University), Moscow, 119991, Russia; 2Lomonosov Moscow State University, Moscow, 119991, Russia; 3Saratov State Medical University, Saratov, Russian Federation; 4Research Institute of Human Morphology, Moscow, 119901, Russian FederationCorrespondence: Mikhail Y Sinelnikov, Sechenov University, Trubetskaya 8, Moscow, 119991, Russian Federation, Tel/Fax +7 89199688587, Email sinelnikov_m_e@staff.sechenov.ruAbstract: The human body is constantly under the influence of numerous pathological factors: both external and internal. These factors can be potentially harmful and are perceived as such with a specialized nervous system subunit: the nociceptive system. The functional unit of the nociceptive system is the nociceptor. Recent studies have shown that nociceptors play a crucial role in maintaining of defensive homeostasis (responsive, immune, behavioral). Nociceptors respond to potentially harmful stimuli within viscera, bones, muscles, skin and specialized sensory organs. They function as complex predictors of harm through formation of pain stimulus. Their function and structures vary within different tissues. This variability reflects the anatomical and pathological peculiarities of varying tissues. Nociceptors play a significant role in adaptive, protective and behavioral reactions. Their functional capabilities and vast spread throughout the body make them the main units of the body’s defense system, allowing us to interact with the inner and outer environments.Keywords: nociceptors, defensive homeostasis, tissue specific variability, pain perception

This study investigates the water quality and soil characteristics associated with qanat systems in the Cebrail district of the Karabakh region, Azerbaijan. Qanat systems, traditional underground channels designed for water transport, play a crucial role in providing reliable water sources for drinking and irrigation. Water and soil samples were collected from seven qanat systems and analyzed for various physicochemical properties. Water quality parameters included pH, electrical conductivity, hardness, mineralization, and concentrations of calcium, magnesium, sodium, and other ions. Soil analyses focused on pH, electrical conductivity, organic matter content, salinization degree, and the presence of key ions like sulfate and nitrate. The results indicated that qanat water is generally of high quality, with pH levels suitable for both drinking and irrigation. However, some qanat systems exhibited high electrical conductivity and mineralization levels, suggesting potential salinity issues for sensitive crops. Soil samples showed favorable conditions for agriculture, with good pH levels, low salinity, and high organic matter content. The analysis revealed a significant interaction between water quality and soil characteristics, emphasizing the importance of integrated management practices. In the context of climate change, the sustainability of qanat systems is critical. Recommendations include regular monitoring of water and soil quality, soil amendments to mitigate salinity, efficient irrigation techniques, and the use of climate-resilient infrastructure. This study underscores the importance of qanat systems in arid and semi-arid regions and provides practical recommendations for sustainable land and water resource management, enhancing the socio-economic well-being of local communities. [ABSTRACT FROM AUTHOR]

Copyright of Gazi Medical Journal is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Recently, many problems, such as the energy crisis and environmental pollution, have made the use of alternative energy in the production of electrical and thermal energy relevant. Because alternative energy sources are environmentally friendly, accessible and inexhaustible. In the most advanced and developed countries, heat pump systems are used for heating, ventilation and cooling of buildings. The article examines the efficiency of operating modes of collector-type geothermal heat pumps in the Karabakh economic zone. The heat supply scheme and all characteristic parameters associated with this scheme were calculated using the GeoTSol modeling program. The GeoTSol simulation program is one of the modern simulation programs for planning and designing heat pump systems. As an example, a private residential building located in the city of Khojavend was studied. A monovalent collector-type heat pump system provides hot water supply and heating for a private home. For comparison, a diagram of 4 types of collector-type heat pump systems is proposed. Seasonal performance coefficients, energy consumption, losses, solar energy share, efficiency, etc. were calculated by computer simulation of the entire heat pump system for each cycle and compared with each other. A circuit operating in the most efficient mode has been determined. [ABSTRACT FROM AUTHOR]

This study aims to assess the extent of hydrocarbon and heavy metal contamination in soils from specific areas on Azerbaijan's Absheron Peninsula, including Absheron, Suraxanı, and Baku, and to evaluate the impact of this contamination on soil properties. Soil samples were analyzed for Total Petroleum Hydrocarbons (TPH) and heavy metals, including aluminum, arsenic, cadmium, lead, and iron, alongside assessments of soil physical, chemical and biological properties. The results revealed significant contamination across all studied areas, particularly in Suraxanı, where TPH levels reached 190 ± 20 mg/kg, exceeding the environmental standard of 100 mg/kg. Similarly, Suraxanı soils exhibited alarmingly high concentrations of heavy metals, with aluminum at 30,128 ± 1,500 mg/kg, arsenic at 50.94 ± 2.5 mg/kg, and cadmium at 0.153 ± 0.01 mg/kg, all surpassing acceptable limits. These contaminants severely degraded soil health, evidenced by increased bulk density (1.7 g/cm³ in Suraxanı) and reduced soil porosity. Microbial activity, a key indicator of soil fertility, was also markedly lower in contaminated regions, with the total bacterial count in Suraxanı being less than half that of the uncontaminated area. The findings underscore the urgent need for comprehensive soil management practices and stricter environmental regulations to mitigate contamination's adverse effects and protect both ecosystems and public health in Azerbaijan's petroleum contaminated areas. [ABSTRACT FROM AUTHOR]

Computer networks are by far the most popular way of transmitting information between users, despite the distance and technical and software differences. There are a large number of topologies of such networks, but the standard is client-server architecture with one server and many client machines, which will be considered and analysed in this paper. The purpose of this study is to analyse and evaluate the efficiency and speed of such a network by mathematical calculations considering such network parameters as the number of channels, the number of network nodes, the allocated space for pending requests, the frequency of requests, the average time allocated for processing one network request. The investigation and analysis of this topic will be based on analytical models created using the mathematical theory of queues applied to the principle of operation of the client-server architecture of a computer network containing only one server node. In the course of the study, the possible maximum speed of information transfer in a client-server architecture computer network with a priority of requests to a single server was mathematically calculated and considered, mathematical models were constructed, the formulas describing the dependencies of variables among themselves and their impact on the result were derived, and graphs based on them were constructed. The efficiency of the network was determined at different loads based on the data obtained. In particular, the calculation was made of the number of request packets in the network for its different loads for different percentages of the operation time of such networks. The work carried out will provide a better understanding of the methods of optimising and improving the performance of computer systems of such architecture, which will be useful in the course of their further design and physical implementation. [ABSTRACT FROM AUTHOR]

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective Primary hypophysitis might be challenging to diagnose, and there is a lack of evidence regarding optimal treatment strategies due to rarity of the disease. We aim to investigate the clinical features and compare the outcomes of different management strategies of primary hypophysitis in a large group of patients recruited on a nationwide basis. Design A retrospective observational study. Methods The demographic, clinical, and radiologic features and follow-up data were collected in study protocol templates and analyzed. Results One hundred and thirteen patients (78.8% female, median age: 36 years) were included. Lymphocytic (46.7%) and granulomatous hypophysitis (35.6%) were the prevailing subtypes out of 45 patients diagnosed after pathologic investigations. Headache (75.8%) was the most common symptom, and central hypogonadism (49.5%) was the most common hormone insufficiency. Of the patients, 52.2% were clinically observed without interventions, 18.6% were started on glucocorticoid therapy, and 29.2% underwent surgery at presentation. Headache, suprasellar extension, and chiasmal compression were more common among glucocorticoid-treated patients than who were observed. Cox regression analysis revealed higher hormonal and radiologic improvement rates in the glucocorticoid-treated group than observation group (hazard ratio, 4.60; 95% CI, 1.62-12.84 and HR, 3.1; 95% CI, 1.40-6.68, respectively). The main indication for surgery was the inability to exclude a pituitary adenoma in the presence of compression symptoms, with a recurrence rate of 9%. Conclusion The rate of spontaneous improvement might justify observation in mild cases. Glucocorticoids proved superior to observation in terms of hormonal and radiologic improvements. Surgery may not be curative and might be considered in indeterminate, treatment-resistant, or severe cases. [ABSTRACT FROM AUTHOR]

Copyright of Przegląd Elektrotechniczny is the property of Przeglad Elektrotechniczny and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Turkish Music (TM) / Türk Müziği is the property of Young Wise Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This research was caused by an accidental discovery of a photo reproduction of one unknown in Russia masterpiece of British stained glass art of the Victorian age found on open spaces of the Internet: a full-height portrait of John Colet, a famous member of clergy of the pre-reform period, Erasmus' and Thomas More's friend and mentor. Exquisite lines of the picture give evidence of masters' using the latest technique of glass processing of the time--so called Tiffany technique. The stained glass is a panel in the opening of a Romanesque window, in the centre of which the John Colet's side-drawn figure is depicted. The figure is encircled in intricate architectural framing: low white-stone gold plated carved columns to the right and to the left are joined overhead with a semi-circular arch with high canopy. Looking back at experiences of interpreting stained-glass artworks of Anglican Emmanuel College Chapel of Cambridge University, we clearly realized how perception of the visual had been changed. This stage of research clearly demonstrated how much the image's content depends on the beholder and that the image has designing nature. "Panoramic" perception of the stained glass composition led to emerging a new image--an ideas man of Broad Church the composition's author F. Horn adhered to.

Abstract Recombinant protein approaches offer major promise for safe and effective vaccine prevention of SARS-CoV-2 infection. We developed a recombinant spike protein vaccine (called NARUVAX-C19) and characterized its ability when formulated with a nanoemulsion adjuvant to induce anti-spike antibody and T-cell responses and provide protection including against viral transmission in rodent. In mice, NARUVAX-C19 vaccine administered intramuscularly twice at 21-day interval elicited balanced Th1/Th2 humoral and T-cell responses with high titers of neutralizing antibodies against wild-type (D614G) and delta (B.1.617.2) variants. In Syrian hamsters, NARUVAX-C19 provided complete protection against wild-type (D614G) infection and prevented its transmission to naïve animals (n = 2/group) placed in the same cage as challenged animals (n = 6/group). The results contrasted with only weak protection seen with a monomeric spike receptor-binding domain (RBD) vaccine even when formulated with the same adjuvant. These encouraging results warrant the ongoing development of this COVID-19 vaccine candidate.

There is no apical morphological data being available for mandibular first or second premolars in the Turkish population. The aims of the study were (I) to assess apical morphological data of mandibular first and second premolars in a Turkish population at a young-adult age range (II) to analyze potential correlations between the size and position of the apical foramina (AF). Extracted sound teeth were collected from an adult volunteer population as willing to donate. Morphological data were obtained from specimens using a stereomicroscope. The number, size, shape, and position of AF and frequency of accessory foramina were quantified. Mann-Whitney U and Spearman's rank correlation tests were performed (α=0.05). A total of 237 teeth were investigated. The majority of the specimens had one major AF. The frequency of major AF was between 1–3 for both groups. The median AF size in mandibular first and second premolars were 55,180 µm2 and 67,483 µm2, respectively. The majority of foramina shape was irregular for the mandibular first premolars whereas, was oval for the second premolars. The median location of AF with respect to the anatomic apex was 664 µm in mandibular first premolars and 677 µm in mandibular second premolars. The size and location of AF mostly overlap between the mandibular first and second premolars. The shape of the AF might be the only relevant variation concerning the apical morphology between the mandibular first and second premolars in young adults. The interaction between the size and location of AF in mandibular premolars of young adults seems not significant

The effect of doping with holmium (Ho) and erbium (Er) rare-earth elements (REE) on the main parameters and characteristics of photocells based on p-GaSe/n-InSe heterostructures has been experimentally studied. Photo-electromotive force measurements were performed for undoped and rare-earth doped samples and obtained results comparatively analyzed. The light characteristic of the samples shows that significant improvement are observed in the rare-earth doped crystals. The possibility of targeted control, as well as increasing their reproducibility and stability by changing the content of the introduced impurity (NREE), is shown. The optimal situation is provided by alloying Er with NREE≈10−1 at.%. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age–sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of S ubdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy. [ABSTRACT FROM AUTHOR]

Background: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. Methods: International, prospective, non‐interventional registry of the management of H. pylori infection by European gastroenterologists (Hp‐EuReg). Treatment‐näive patients registered from 2013 to 2023 at e‐CRF AEG‐REDCap were analyzed. The effectiveness was assessed by modified intention‐to‐treat analysis. Results: Overall, 53,636 treatment‐naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non‐investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non‐investigated dyspepsia (87%). Bismuth‐metronidazole‐tetracycline and clarithromycin‐amoxicillin‐bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin‐amoxicillin‐tinidazole/metronidazole reached 90% cure rates except in patients with non‐investigated dyspepsia; whereas sequential clarithromycin‐amoxicillin‐tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). Conclusion: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non‐bismuth quadruple therapies achieved optimal results in almost all indications. Trial Registration: ClinicalTrials.gov identifier: NCT02328131. [ABSTRACT FROM AUTHOR]

Copyright of Ege Üniversitesi Ziraat Fakültesi Dergisi is the property of Ege Universitesi, Ziraat Fakultesi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)