Requirement for a Uroplakin 3a-like protein in the development of zebrafish pronephric tubule epithelial cell function, morphogenesis, and polarity

Uroplakin (UP)3a is critical for urinary tract development and function; however, its role in these processes is unknown. We examined the function of the UP3a-like protein Upk3l, which was expressed at the apical surfaces of the epithelial cells that line the pronephric tubules (PTs) of the zebrafish pronephros. Embryos treated with upk3l-targeted morpholinos showed decreased pronephros function, which was attributed to defects in PT epithelial cell morphogenesis and polarization including: loss of an apical brush border and associated phospho-ERM proteins, apical redistribution of the basolateral Na+/K+-ATPase, and altered or diminished expression of the apical polarity complex proteins Prkcz (atypical protein kinase C zeta) and Pard3 (Par3). Upk3l missing its C-terminal cytoplasmic domain or containing mutations in conserved tyrosine or proline residues did not rescue, or only partially rescued the effects of Upk3l depletion. Our studies indicate that Upk3l promotes epithelial polarization and morphogenesis, likely by forming or stimulating interactions with cytoplasmic signaling or polarity proteins, and that defects in this process may underlie the pathology observed in UP3a knockout mice or patients with renal abnormalities that result from altered UP3a expression. © 2012 Mitra et al

A nitroxide-containing cathode material for organic radical batteries studied with pulsed EPR spectroscopy

An electron spin echo in a nitroxide-containing polymer cathode film for organic radical batteries is observed for various states of charge at cryogenic temperatures. The EPR-detected state of charge (ESOC), as inferred from the number of paramagnetic centers in the film, is compared to the results of Coulomb counting based on galvanostatic charging. Spin concentration, longitudinal relaxation times T(1 )and phase memory times T-m strongly correlate with the ESOC. In the discharged film, the spin concentration reaches 5 +/- 3x10(20) cm(-3), causing a phase memory time T-m << 100 ns (shorter than the resonator ring-down time) that hinders the detection of the spin echo. In the charged film, the decreased spin concentration results in a longer T-m between 100 ns and 300 ns that enables spin-echo detection, yet limits the length of the microwave pulse sequence. The short, broad-band pulses cause instantaneous diffusion in the unoxidized domains across the oxidized film, affecting the relative peak intensities in the pulsed EPR spectrum. By simulating the spectral distortion caused by instantaneous diffusion, we obtain information on the local spin concentration, which complements the information on the 'bulk' spin concentration determined by electrochemistry and continuous-wave EPR spectroscopy

Proposals for the Organization of International Logistics Activities of Agricultural and Agro-Processing Enterprises During the War Period

The agricultural sector is the driver and “point of growth” of the national economy of Ukraine. Agriculture accounts for an average of 16% of gross value added in some regions and play a key role in ensuring food security. However, the current conditions of martial law in Ukraine have led to problems in the organization of logistics activities of enterprises of the agro-industrial complex as a result of non-fulfilment of the terms of contracts; emergence of risks of disruption of the sowing campaign; decrease in final harvest indicators and the level of food security; decrease in the volume of export deliveries of agricultural products; disruption of food supply chains; lack of adequate financing and logistics infrastructure facilities; insufficiently effective use of marketing management tools and a network approach in the process of distributing agricultural products to the final consumer; increase in transaction costs, etc. The article provides a statistical analysis of the main indicators of the development of foreign economic activity of enterprises of the agro-industrial complex of Ukraine in the pre-war period. Barriers that inhibit the effective organization of international logistics activities of agrarian enterprises in wartime have been identified. Priority directions for eliminating existing barriers that prevent the organization of foreign economic logistics activities are proposed, the essence of which is to activate network interaction and partnership relations based on the creation of agro-cluster structures; unification of small farms for the proper execution of contracts, as well as joint activity in the agrarian sphere of two or more companies and different groups of stakeholders to achieve a common goal and a synergistic effect.Аграрний сектор є драйвером і «точкою зростання» національної економіки України. Сільське господарство формує у деяких регіонах у середньому 16% валової доданої вартості та відіграє ключову роль у забезпеченні продовольчої безпеки. Однак сучасні умови воєнного стану в Україні призвели до проблем організації логістичної діяльності підприємств агропромислового комплексу унаслідок невиконання умов контрактів; появі ризиків зриву посівної кампанії; зменшення фінальних показників врожаю та рівня продовольчої безпеки; зниження обсягів експортних поставок сільськогосподарської продукції; порушення ланцюгів постачання продовольства; відсутності належного фінансування та об’єктів логістичної інфраструктури; недостатньо ефективного використання інструментарію маркетингового менеджменту і мережевого підходу в процесі розподілу аграрної продукції до кінцевого споживача; збільшення трансакційних витрат тощо. У статті виконано статистичний аналіз основних показників розвитку зовнішньоекономічної діяльності підприємств агропромислового комплексу України у довоєнний період. Виявлено бар’єри, які гальмують ефективну організацію міжнародної логістичної діяльності аграрних підприємств у воєнний час. Запропоновано пріоритетні напрями усунення існуючих бар’єрів, що перешкоджають організації зовнішньоекономічної логістичної діяльності, суть яких полягає в активізації мережевої взаємодії та партнерських взаємовідносин на основі створення агрокластерних структур; об’єднання дрібним фермерських господарств для належного виконання контрактів, а також спільної діяльності в аграрній сфері двох або більше компаній і різних груп стейкхолдерів для досягнення загальної мети і синергетичного ефекту

Triphenilphosphonium Analogs of Chloramphenicol as Dual-Acting Antimicrobial and Antiproliferating Agents

Activitat antibiòtica; Ribosoma bacterià; Simulacions de dinàmica molecularActividad antibiótica; Ribosoma bacteriano; Simulaciones de dinámica molecularAntibiotic activity; Bacterial ribosome; Molecular dynamics simulationsIn the current work, in continuation of our recent research, we synthesized and studied new chimeric compounds, including the ribosome-targeting antibiotic chloramphenicol (CHL) and the membrane-penetrating cation triphenylphosphonium (TPP), which are linked by alkyl groups of different lengths. Using various biochemical assays, we showed that these CAM-Cn-TPP compounds bind to the bacterial ribosome, inhibit protein synthesis in vitro and in vivo in a way similar to that of the parent CHL, and significantly reduce membrane potential. Similar to CAM-C4-TPP, the mode of action of CAM-C10-TPP and CAM-C14-TPP in bacterial ribosomes differs from that of CHL. By simulating the dynamics of CAM-Cn-TPP complexes with bacterial ribosomes, we proposed a possible explanation for the specificity of the action of these analogs in the translation process. CAM-C10-TPP and CAM-C14-TPP more strongly inhibit the growth of the Gram-positive bacteria, as compared to CHL, and suppress some CHL-resistant bacterial strains. Thus, we have shown that TPP derivatives of CHL are dual-acting compounds targeting both the ribosomes and cellular membranes of bacteria. The TPP fragment of CAM-Cn-TPP compounds has an inhibitory effect on bacteria. Moreover, since the mitochondria of eukaryotic cells possess qualities similar to those of their prokaryotic ancestors, we demonstrate the possibility of targeting chemoresistant cancer cells with these compounds.This research was funded by RFBR [grants 20-04-00873 to N.V.S. (synthesis of analogs, binding assays, in vitro translation), 20-015-00537 to P.A.N. (potential measurement, screening of TolC-containing transporters), and 20-54-76002 to I.A.O. (toeprinting and in vitro translation)], President grant MD 2626.2021.1.4 to I.A.O. (bacteria inhibition assays), grants from the Instituto de Salud Carlos III: PI17/02087 to A.L. (cancer cell proliferation assays) by the Ministry of Science and Higher Education of the Russian Federation [grant FENU-2020-0019 to G.I.M. (molecular dynamics simulations)] and by the Government of the Russian Federation [No. AAAA-A17-117120570004-6 to A.A.B.]

Spins at work: probing charging and discharging of organic radical batteries by electron paramagnetic resonance spectroscopy

Organic radical batteries (ORBs) are a promising class of electrochemical power sources employing organic radicals as redox-active groups. This article reports on the development of a versatile on-substrate electrode setup for spectroelectrochemical Electron Paramagnetic Resonance (EPR) measurements on redox conductive polymers for ORBs. Quantitative in operando EPR experiments performed on electrochemical cells with a di-TEMPO Ni-Salen polymer as active electrode material demonstrate a strong decrease in the number of paramagnetic centers upon oxidizing the film. The distinct EPR signatures of the TEMPO-containing polymer and its fragments in different molecular environments are used to study its degradation upon repeated cycling. A comparison between the number of EPR-active sites and the number of electrochemically active charges, as measured by cyclic voltammetry, provides information on the nature of the degradation process. Low-temperature ex situ pulse EPR measurements on the oxidized polymer film reveal the spectrum of dilute nitroxide species, which may be associated with electrochemically inactive islands. These experiments pave the way for advanced EPR techniques for accurately determining distances between adjacent paramagnetic centers and thus for identifying performance-limiting loss mechanisms, which can eventually help develop strategies for making ORBs powerful contenders on the path towards sustainable electrochemical power sources

О ПРОМЫШЛЕННОЙ БЕЗОПАСНОСТИ В МОСТОСТРОЕНИИ

Industrial safety system evolved on the railways for decades. In new economic conditions, many of its basic principles remain, but also those factors have arisen that require scientific analysis, experimental verification, modern technical and technological means. At the example of construction and maintenance of bridgeworks, the authors examine and evaluate the situation with safety, injury rate, fire hazard in railway transport.Система промышленной безопасности складывалась на железных дорогах десятилетиями. В новых экономических условиях многие ее базовые принципы сохранились, но появились и те факторы, которые требуют научного анализа, экспериментальной проверки, современных технико-технологических средств. На примере строительства и обслуживания мостовых сооружений авторы исследуют и оценивают ситуацию с безопасностью труда, травматизмом, пожароопасностью на объектах железнодорожного транспорта

Methods for Mesh Implantation Efficacy Assessment in Rectocele

Aim. A methodological review on mesh implantation efficacy assessment in surgery for rectocele.Key points. Specialised quiz surveys are among the most appropriate methods to assess surgical intervention efficacy. The questionnaires that enable pre- and postsurgery rectocele grading include PFDI-20 (Pelvic Floor Distress Inventory), the colonic evacuation disorder scale and Cleveland Constipation Scoring System. These surveys determine the surgical intervention efficacy dynamically in conjunction with instrumental surgery assessment techniques.Conclusion. Clinical practice at the Ryzhikh National Medical Research Centre for Coloproctology combines the originally developed colonic evacuation disorder scale (2003) and PFDI-20. The combined scales allow for a comprehensive symptom assessment in patients with rectocele and other descending perineum syndrome manifestations prior to surgery, as well as symptom dynamics evaluation postoperatively, which, in link with defecography, enables a complete appraisal of the surgical effect

Vaginal dysbiosis as a factor contributing to the development of recurrent lower urinary tract infections

Introduction. It is known that women are significantly more likely to suffer from lower urinary tract infections (LUTIs) than men. Nowadays, there is growing evidence to demonstrate the impact of vaginal microbiota on the development of recurrent LUTIs.Objectives. To demonstrate the impact of vaginal microbiota disorders on the development of recurrent lower urinary tract infections.Materials &amp; methods. Seventy-five women with recurrent LUTIs 19 – 76 years old were enrolled in this study. The examination was performed according to the algorithm developed in the Department of Urology and Surgical Andrology, Russian Medical Academy of Continuous Professional Education. Real-time PCR of vaginal epithelial cell scrapings (Femoflor 16) was performed to comprehensively evaluate the vaginal microbiota.Results. Vaginal dysbiosis was detected in 47/75 (62.7%) women with recurrent UTIs: moderate vaginal dysbiosis was detected in 25/75 (33.3%) women and severe dysbiosis — in 22/75 (29.3%) women. A moderate correlation between the presence/absence of vaginal dysbiosis and the number of LUTI recurrences over 6 months was found (r = 0.310; p = 0.007). Vaginal dysbiosis was significantly more common among peri- and postmenopausal women with recurrent LUTIs than reproductive women (OR = 4.85; 95% CI = 1.45 – 16.17).Conclusion. Vaginal dysbiosis contributes to the development of recurrent LUTIs with more relapses. Vaginal microbiota disorders and, consequently, recurrent LUTIs are more common in peri- and postmenopausal women than reproductive women