Reconstructed Serine 288 in the Left Flipper Region of the Rat P2X7 Receptor Stabilizes Nonsensitized States

© 2017 American Chemical Society. Serine 275, a conserved residue of the left flipper region of ATP-gated P2X3 receptors, plays a key role in both agonist binding and receptor desensitization. It is conserved in most of the P2X receptors except P2X7 and P2X6. By combining experimental patch-clamp and modeling approaches, we explored the role of the corresponding residue in the rat P2X7 receptor (rP2X7) by replacing the phenylalanine at position 288 with serine and characterizing the membrane currents generated by either the wild-type (WT) or the mutated rP2X7 receptor. F288S, an rP2X7 mutation, slowed the deactivation subsequent to 2 and 20 s applications of 1 mM ATP. F288S also prevented sensitization (a progressive current growth) observed with the WT in response to a 20 s application of 1 mM ATP. Increasing the ATP concentration to 5 mM promoted sensitization also in the mutated rP2X7 receptor, accelerating the deactivation rate to typical WT values. YO-PRO1 uptake in cells expressing either the WT or the F288S P2X7 receptor was consistent with recorded membrane current data. Interestingly, in the human P2X7 (hP2X7) receptor, substitution Y288S did not change the deactivation rate, while the Y288F mutant generated a "rat-like" phenotype with a fast deactivation rate. Our combined experimental, kinetic, and molecular modeling data suggest that the rat F288S novel phenotype is due to a slower rate of ATP binding and/or unbinding and stabilization of nonsensitized receptor states

Comparison of open femoral exposure and percutaneous access in endovascular reconstruction of the thoracic aorta: a two-center retrospective study

Aim. To analyze the efficacy and safety of the percutaneous transfemoral puncture technique for TEVAR (thoracis endovascular aortic repair).Material and methods. The retrospective study included 89 patients with aortic pathologies, for whom endovascular repair was performed: 51 patients (57%) with aortic dissection (type I DeBakey — 30 cases (58,8%) and type III — 21 (41,2%)), 38 (43%) patients with aortic aneurism. 82% of patients were male, the median age was 57 years (minimum age 17 years, maximum age 75 years). All patients were divided into two groups: in the first group (48 patients) endovascular aortic repair was performed under endotracheal anesthesia with open femoral exposure of the common femoral artery (CFA), in the second group (41 patients) — by percutaneous puncture method under local anesthesia. Technical and clinical aspects of procedures were analyzed.Results. Technical success of endovascular repair was achieved in 100% cases in both groups. The duration of the operation in the group with percutaneous access was statically significantly shorter (120 (94-150) minutes vs 87(60-120) minutes, p=0,001). Also, the time spent by patients in the intensive care unit and the period of hospitalization (18 (14-22) hours versus 1 (0-3) hours, p=0,001; 5 (4-6) days versus 4 (3-5) days, p=0,03) was shorter. In the open access group 2 (4,2%) patients developed access-related complications - acute thrombosis of the common femoral artery and hematoma of the postoperative wound, which required additional surgical aid - thrombectomy from the CFA, the second patient had evacuation of the hematoma of the postoperative wound. Cite-related complications in the second group were not observed. No major complications including neurological deficits and hospital mortality were observed in both groups.Conclusions. Thoracic endovascular aortic repair (TEVAR) using percutaneous access under local anesthesia in stable patients has proven to be safe and effective. The operation time is significantly reduced and this approach in most cases eliminates the need for the patient to stay in the intensive care unit in the early postoperative period. Possibility of early mobilization of the patient appears with reducing of the duration of hospitalization

Comparative analysis of Illumina and Ion Torrent high-throughput sequencing platforms for identification of plant components in herbal teas

© 2018 Elsevier Ltd The rapid development of high-throughput sequencing (HTS) methods offers new opportunities for food quality control and identification of food components using the DNA barcoding approach (metabarcoding in cases of complex mixes). However, the protocols of DNA barcoding applied to food analysis are not yet fully established; testing and optimization are required to achieve the highest accuracy and cost efficiency. We report here a comparative study of the two most widely used sequencing platforms - Illumina and Ion Torrent - for composition analysis of herbal teas, and show that both technologies yield congruent results, both qualitatively and quantitatively. They have revealed the substitution of fireweed (Epilobium angustifolium L.) by Lythrum sp. in one of the samples. It was confirmed by classic methods of botanical analysis (anatomy and palynology). In most samples, undeclared components have been detected, such as bindweed (Convolvulus) and ragweed (Ambrosia), which are known toxic and allergy-causing plants

Клиническое наблюдение пациента с синхронными опухолями левой почки и правого мочеточника. Описание клинического случая

The paper describes a rare case of synchronous bilateral tumor involvement of the urinary tract.Приводится описание редкого наблюдения больного с синхронным двусторонним опухолевым поражением мочевыделительной системы

A role for diatom-like silicon transporters in calcifying coccolithophores

Biomineralization by marine phytoplankton, such as the silicifying diatoms and calcifying coccolithophores, plays an important role in carbon and nutrient cycling in the oceans. Silicification and calcification are distinct cellular processes with no known common mechanisms. It is thought that coccolithophores are able to outcompete diatoms in Si-depleted waters, which can contribute to the formation of coccolithophore blooms. Here we show that an expanded family of diatom-like silicon transporters (SITs) are present in both silicifying and calcifying haptophyte phytoplankton, including some globally important coccolithophores. Si is required for calcification in these coccolithophores, indicating that Si uptake contributes to the very different forms of biomineralization in diatoms and coccolithophores. Significantly, SITs and the requirement for Si are absent from highly abundant bloom-forming coccolithophores, such as Emiliania huxleyi. These very different requirements for Si in coccolithophores are likely to have major influence on their competitive interactions with diatoms and other siliceous phytoplankton

ВЛИЯНИЕ ПОВТОРНОЙ ТРАНСУРЕТРАЛЬНОЙ РЕЗЕКЦИИ НА РЕЗУЛЬТАТЫ ЛЕЧЕНИЯ БОЛЬНЫХ НЕМЫШЕЧНО-ИНВАЗИВНЫМ РАКОМ МОЧЕВОГО ПУЗЫРЯ

The results of treatment were analyzed in 308 in patients with non-muscle-invasive (NMI) bladder cancer (BC). The incidence of recurrences was studied in patients with NMI BC who had undergone primary and second look (SL) transurethral resection (TUR). SL TUR is used to identify residual Т1G2−G3 tumors and to specify the stage of the disease, owing to which treatment policy for BC is changed. The authors revealed significant differences between the groups in the rate of early and recurrent NMI BC and its occurrence time during 5 years. The findings show the benefit of relapse-free survival after SL TUR in the T1G2-G3 BC group (p = 0.018). The authors also discuss whether it is reasonable to use SL TUR that allows this procedure to be recommended for patients with G2-G3 NMI BC in routine clinical practice.Проанализированы результаты лечения 308 пациентов с немышечно-инвазивным (НМИ) раком мочевого пузыря (РМП). Изучена частота встречаемости рецидивов у пациентов с НМИ РМП с однократной и повторной (second look – SL) трансуретральной резекцией (ТУР). Посредством SL ТУР выявляются резидуальные опухоли Т1G2−G3, уточняется стадия заболевания, благодаря чему изменяется тактика лечения РМП. Нами выявлены достоверные различия между группами в частоте и сроках возникновения ранних и рецидивов в течение 5 лет. Полученные результаты отражают преимущество безрецидивной выживаемости после выполнения SL ТУР в группах больных РМП T1G2–3 (р = 0,018). Также обсуждается целесообразность применения SL ТУР, позволяющая рекомендовать эту методику пациентам с НМИ РМП G2−3 для рутинной клинической практики

Insights into the Binding of Phenyltiocarbamide (PTC) Agonist to Its Target Human TAS2R38 Bitter Receptor

Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models

НЕЙРОЭНДОКРИННЫЙ РАК ПРЕДСТАТЕЛЬНОЙ ЖЕЛЕЗЫ (ОПИСАНИЕ КЛИНИЧЕСКОГО СЛУЧАЯ)

Neuroendocrine carcinoma of the prostate belongs to the so-called small-cell neuroendocrine carcinomas and amounts to 1–2 % of all prostate malignancies. With allowance made for the low incidence of this pathology, the paper describes a case of high-grade neuroendocrine (small-cell) prostate cancer with an aggressive course.Нейроэндокринный рак предстательной железы (РПЖ) относится к так называемым мелкоклеточным нейроэндокринным формам рака и составляет 1–2 % всех злокачественных опухолей предстательной железы. С учетом низкой встречаемости этой патологии приводится описание низкодифференцированного нейроэндокринного (мелкоклеточного) РПЖ с крайне агрессивным течением