«Unity in diversity» as a Socio-Political Technology: Perspectives and Limitations Applicable in the Context of the Ukrainian

В статье рассматривается возможность применения схемы «единство в многообразии» к решению проблемы раскола в украинском обществе. Для этого была проанализирована актуализация данной схемы в социологическом и политическом дискурсе. В качестве главной линии раскола рассматриваются языковая проблема и ее причины в контексте государственной политики и национальной идеи, анализируется степень сконструированности данной проблемы. Относительно «единства в многообразии» делается вывод о том, что данная схема применима к обществам с одной доминирующей культурой и для украинского общества схема нуждается в адаптации и конкретизации, а также должна сопровождаться реальным законодательным закреплением автономии регионов. Для дальнейших исследований представляется актуальным поиск конкретных вариантов данной схемы применительно к специфическим реалиям украинского общества. У статті розглянуто можливість застосування схеми «єдність у розмаїтті» для розв’язання проблеми розколу в українському суспільстві. Для цього проаналізовано актуалізацію цієї схеми в соціологічному та політичному дискурсі. У якості головної лінії розколу розглянуто мовну проблему та її причини в контексті державної політики й національної ідеї, проаналізовано ступінь сконструйованості. Щодо «єдності в розмаїтті» зроблено висновок, що ця схема може бути впроваджена в суспільства з однією домінуючою культурою та для українського суспільства повинна бути адаптована й конкретизована, а також має супроводжуватися реальним законодавчим закріпленням автономії регіонів. Для подальших досліджень убачаємо актуальним пошук конкретних варіантів цієї схеми, придатних до специфічних реалій українського суспільства. The topic of the article is the inter-regional break-up in Ukrainian community which can primarily be seen at cultural and socio-political levels. According to the author, one of its main causes is the limitation of rights of Russian-speaking people of Eastern Ukraine as well as the repression and pushing Russian language out of educational and public spheres. There has been revealed the imbalance between the real correlation of Russian and Ukrainian languages in the society and the adopted policy of introduction Ukrainian culture into life, as well as the ignoring the protests of Russian-speaking population against this policy, which brings the author to the conclusion that this break-up is not artificial but a natural one. As a possible solution of the problem there has been considered the "unity in diversity" scheme actualized in scientific and political discourse, which presumes that variety of cultures can be the foundation of unity of the country. The author has analyzed some scientific and journalistic articles which study the conception of unity in diversity. As a result, it has been revealed that this scheme is abstract and does not contain any mechanisms of its implementation. It has also been noticed that this scheme implies having cultural diversity around one main culture, which is not suitable for Ukrainian community that does not have this basic culture. Thus the author concludes that this scheme can be put into practice until after considerable improvement and specification which appears to be an urgent task for further research on this topic

A rational approach for generating cardiac troponin I selective Spiegelmers

We report the first protein selective Spiegelmers of diagnostic relevance by rational identification of a target epitope and reverse screening of Spiegelmer candidates following the selection procedure. Application of the presented approach resulted in isolation of cardiac troponin I selective Spiegelmers with low nanomolar dissociation constant and functionality in serum

Cardiac troponin I but not cardiac troponin T adheres to polysulfone dialyser membranes in an in vitro haemodialysis model: explanation for lower serum cTnI concentrations following dialysis.

BACKGROUND: Elevated serum cardiac troponin T (cTnT) and I (cTnI) can occur in patients with chronic kidney disease. Differences in cTn concentrations between cTnT and cTnI have been reported but the mechanism of such discrepancy has not been investigated. This study investigates the clearance of cTn with the aid of an in vitro model of haemodialysis (HD). METHODS: Serum was obtained before and after a single session of dialysis from 53 patients receiving HD and assayed for cTnT and cTnI. An in vitro model of the dialysis process was used to investigate the mechanism of clearance of cTn during HD. RESULTS: Serum cTnI was significantly lower (p=0.043) following a session of HD whereas cTnT concentrations were similar to those obtained before HD. Using an in vitro model of dialysis, it was demonstrated that cTnI is not dialysed from the vascular compartment but adheres to the dialyser membrane. CONCLUSIONS: The adherence of cTnI to the dialyser membrane is responsible for the observed decrease in serum cTnI following a session of dialysis. The adherence of cTnT or T-I-C complex to the dialyser membrane could not be demonstrated and supports the observation that pre-HD and post-HD serum concentrations of cTnT are similar

Myosin-V Opposes Microtubule-Based Cargo Transport and Drives Directional Motility on Cortical Actin

SummaryIntracellular transport is driven by motor proteins that either use microtubules or actin filaments as their tracks [1], but the interplay between these transport pathways is poorly understood [2–4]. Whereas many microtubule-based motors are known to drive long-range transport, several actin-based motors have been proposed to function predominantly in cargo tethering [4–6]. How these opposing activities are integrated on cargoes that contain both types of motors is unknown. Here we use inducible intracellular transport assays to show that acute recruitment of myosin-V to kinesin-propelled cargo reduces their motility near the cell periphery and enhances their localization at the actin-rich cell cortex. Myosin-V arrests rapid microtubule-based transport without the need for regulated auto- or other inhibition of kinesin motors. In addition, myosin-V, despite being an ineffective long-range transporter, can drive slow, medium-range (1–5 μm), point-to-point transport in cortical cell regions. Altogether, these data support a model in which myosin-V establishes local cortical delivery of kinesin-bound cargos through a combination of tethering and active transport

Characterization of the Antibiotic Compound No. 70 Produced by Streptomyces sp. IMV-70

We describe the actinomycete strain IMV-70 isolated from the soils of Kazakhstan, which produces potent antibiotics with high levels of antibacterial activity. After the research of its morphological, chemotaxonomic, and cultural characteristics, the strain with potential to be developed further as a novel class of antibiotics with chemotherapeutics potential was identified as Streptomyces sp. IMV-70. In the process of fermentation, the strain Streptomyces spp. IMV-70 produces the antibiotic no. 70, which was isolated from the culture broth by extraction with organic solvents. Antibiotic compound no. 70 was purified and separated into individual components by HPLC, TLC, and column chromatography methods. The main component of the compound is the antibiotic 70-A, which was found to be identical to the peptolide etamycin A. Two other antibiotics 70-B and 70-C have never been described and therefore are new antibiotics. The physical-chemical and biological characteristics of these preparations were described and further researched. Determination of the optimal growth conditions to cultivate actinomycete-producer strain IMV-70 and development of methods to isolate, purify, and accumulate preparations of the new antibiotic no. 70 enable us to research further the potential of this new class of antibiotics

CT-IGFBP-4 as a novel prognostic biomarker in acute heart failure

Aims Insulin-like growth factor binding protein-4 (IGFBP-4) fragments have been shown to predict the risk of major adverse cardiovascular events, including segment-elevation myocardial infarction, in patients with acute coronary syndrome. We evaluated the prognostic value of the carboxy-terminal fragment of IGFBP-4 (CT-IGFBP-4) for all-cause mortality in emergency room patients with acute heart failure (AHF). Methods and results CT-IGFBP-4, N-terminal pro brain natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) were measured at admission from the lithium-heparin plasma of 156 patients with AHF. All-cause mortality was recorded for 1 year. Receiver operator characteristic (ROC) curves, Kaplan-Meier, and Cox proportional hazard ratio analyses were performed to evaluate the prognostic value of the various clinical variables, CT-IGFBP-4, NT-proBNP, CRP, and their combinations. During 1 year of follow-up, 52 (33.3%) patients died. CT-IGFBP-4 only weakly correlated with NT-proBNP (Pearson correlation coefficient r = 0.16, P = 0.044) and did not correlate with CRP (r = 0.08, P = 0.35), emphasizing the different nature of these biomarkers. The receiver operator characteristic area under the curve (ROC AUC) of CT-IGFBP-4 for the prediction of all-cause mortality (0.727) was significantly higher than that of NT-proBNP (0.680, P = 0.045) and CRP (0.669, P = 0.016). The combination of CT-IGFBP-4, NT-proBNP, and CRP predicted mortality significantly better (ROC AUC = 0.788) than any of the biomarkers alone (P <0.01 for all). The addition of CT-IGFBP-4 to a clinical prediction model that included age, gender, systolic blood pressure, creatinine, and sodium levels, as well as the history of previous heart failure, coronary artery disease, and hypertension significantly improved the mortality risk prediction (ROC AUC 0.774 vs. 0.699, P = 0.025). Cox hazard analysis indicated that elevated CT-IGFBP-4 was independently associated with 1 year mortality (hazard ratio 3.26, P = 0.0008) after adjustment for age, gender, history of previous heart failure, coronary artery disease, hypertension, chronic kidney failure, history of diabetes, heart rate, haemoglobin, plasma sodium, NT-proBNP, CRP, cystatin C, and elevated cardiac troponin I or T. Patients with increased levels of either two or three of the biomarkers CT-IGFBP-4, NT-proBNP, and CRP had significantly higher mortality risk (adjusted hazard ratio 10.04, P <0.0001) than patients with increased levels of one or none of the biomarkers. Conclusions CT-IGFBP-4 was independently associated with all-cause mortality in patients with AHF. Compared with single biomarkers, the combination of CT-IGFBP-4, NT-proBNP, and CRP improved the prediction of all-cause mortality in patients with AHF.Peer reviewe

Searching for a BNP standard: Glycosylated proBNP as a common calibrator enables improved comparability of commercial BNP immunoassays

AbstractBackgroundCirculating B-type natriuretic peptide (BNP) is widely accepted as a diagnostic and risk assessment biomarker of cardiac function. Studies suggest that there are significant differences in measured concentrations among different commercial BNP immunoassays. The purpose of our study was to compare BNP-related proteins to determine a form that could be used as a common calibrator to improve the comparability of commercial BNP immunoassay results.MethodsBNP was measured in 40 EDTA-plasma samples from acute and chronic heart failure patients using five commercial BNP assays: Alere Triage, Siemens Centaur XP, Abbott I-STAT, Beckman Access2 and ET Healthcare Pylon. In parallel with internal calibrators from each manufacturer, six preparations containing BNP 1–32 motif a) synthetic BNP, b) recombinant BNP (E. coli), c) recombinant nonglycosylated proBNP (E. coli), d) recombinant His-tagged (N-terminal) nonglycosylated proBNP (E. coli), e) recombinant glycosylated proBNP (HEK cells), and f) recombinant glycosylated proBNP (CHO cells) were also used as external calibrators for each assay.ResultsUsing the internal standards provided by manufacturers and for five of six external calibrators, up to 3.6-fold differences (mean 1.9-fold) were observed between BNP immunoassays (mean between-assay CV 24.5–47.2%). A marked reduction of the between-assay variability was achieved, when glycosylated proBNP expressed in HEK cells was used as the common calibrator for all assays (mean between-assay CV 14.8%).ConclusionsOur data suggest that recombinant glycosylated proBNP could serve as a common calibrator for BNP immunoassays to reduce between-assay variability and achieve better comparability of BNP concentrations of commercial BNP immunoassays

Taxanes convert regions of perturbed microtubule growth into rescue sites

Microtubules are polymers of tubulin dimers, and conformational transitions in the microtubule lattice drive microtubule dynamic instability and affect various aspects of microtubule function. The exact nature of these transitions and their modulation by anti -cancer drugs such as Taxol and epothilone, which can stabilize microtubules but also perturb their growth, are poorly understood. Here, we directly visualize the action of fluorescent Taxol and epothilone derivatives and show that microtubules can transition to a state that triggers cooperative drug binding to form regions with altered lattice conformation. Such regions emerge at growing microtubule ends that are in a pre-catastrophe state and inhibit microtubule growth and shortening. Electron microscopy and in vitro dynamics data indicate that taxane accumulation zones represent incomplete tubes that can persist, incorporate tubulin dimers and repeatedly induce microtubule rescues. Thus, taxanes modulate the material properties of microtubules by converting destabilized growing microtubule ends into regions resistant to depolymerization

Concerted action of kinesins kif5b and kif13b promotes efficient secretory vesicle transport to microtubule plus ends

Intracellular transport relies on multiple kinesins, but it is poorly understood which kinesins are present on particular cargos, what their contributions are and whether they act simultaneously on the same cargo. Here, we show that Rab6-positive secretory vesicles are transported from the Golgi apparatus to the cell periphery by kinesin-1 KIF5B and kinesin-3 KIF13B, which determine the location of secretion events. KIF5B plays a dominant role, whereas KIF13B helps Rab6 vesicles to reach freshly polymerized microtubule ends, to which KIF5B binds poorly, likely because its cofactors, MAP7-family proteins, are slow in populating these ends. Sub-pixel localization demonstrated that during microtubule plus-end directed transport, both kinesins localize to the vesicle front and can be engaged on the same vesicle. When vesicles reverse direction, KIF13B relocates to the middle of the vesicle, while KIF5B shifts to the back, suggesting that KIF5B but not KIF13B undergoes a tug-of-war with a minus-end directed motor.info:eu-repo/semantics/publishe

Probing aggrephagy using chemically-induced protein aggregates

Selective types of autophagy mediate the clearance of specific cellular components and are essential to maintain cellular homeostasis. However, tools to directly induce and monitor such pathways are limited. Here we introduce the PIM (particles induced by multimerization) assay as a tool for the study of aggrephagy, the autophagic clearance of aggregates. The assay uses an inducible multimerization module to assemble protein clusters, which upon induction recruit ubiquitin, p62, and LC3 before being delivered to lysosomes. Moreover, use of a dual fluorescent tag allows for the direct observation of cluster delivery to the lysosome. Using flow cytometry and fluorescence microscopy, we show that delivery to the lysosome is partially dependent on p62 and ATG7. This assay will help in elucidating the spatiotemporal dynamics and control mechanisms underlying aggregate clearance by the autophagy-lysosomal system