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Recombinantly produced collagens present a sustainable, ethical, and safe substitute for collagens derived from natural sources. However, controlling the folding of the recombinant collagens, crucial for replicating the mechanical properties of natural materials, remains a formidable task. Collagen-like proteins from willow sawfly are relatively small and contain no hydroxyprolines, presenting an attractive alternative to the large and post-translationally modified mammalian collagens. Utilizing CD spectroscopy and analytical ultracentrifugation, we demonstrate that recombinant willow sawfly collagen assembles into collagen triple helices in a concentration-dependent manner. Interestingly, we observed that the lower concentration threshold for the folding can be overcome by freezing or adding crowding agents. Microscopy data show that both freezing and the addition of crowding agents induce phase separation. We propose that the increase in local protein concentration during phase separation drives the nucleation-step of collagen folding. Finally, we show that freezing also induces the folding of recombinant human collagen fragments and accelerates the folding of natural bovine collagen, indicating the potential to apply phase separation as a universal mechanism to control the folding of recombinant collagens. We anticipate that the results provide a method to induce the nucleation of collagen folding without any requirements for genetic engineering or crosslinking., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Recombinant adeno-associated viruses (rAAVs) play a pivotal role in the treatment of genetic diseases. However, current production and purification processes yield AAV-based preparations that often contain unwanted empty, partially filled or damaged viral particles and impurities, including residual host cell DNA and proteins, plasmid DNA, and viral aggregates. To precisely understand the composition of AAV preparations, we systematically compared four different single-stranded AAV (ssAAV) and self-complementary (scAAV) fractions extracted from the CsCl ultracentrifugation gradient using established methods (transduction efficiency, analytical ultracentrifugation (AUC), quantitative and digital droplet PCR (qPCR and ddPCR), transmission electron microscopy (TEM) and enzyme-linked immunosorbent assay (ELISA)) alongside newer techniques (multiplex ddPCR, multi-angle light-scattering coupled to size-exclusion chromatography (SEC-MALS), multi-angle dynamic light scattering (MADLS), and high-throughput sequencing (HTS)). Suboptimal particle separation within the fractions resulted in unexpectedly similar infectivity levels. No single technique could simultaneously provide comprehensive insights in the presence of both bioactive particles and contaminants. Notably, multiplex ddPCR revealed distinct vector genome fragmentation patterns, differing between ssAAV and scAAV. This highlights the urgent need for innovative analytical and production approaches to optimize AAV vector production and enhance therapeutic outcomes.

Birds are long-known as important disseminators of ixodid ticks, in which context mostly their latitudinal, south-to-north migration is considered. However, several bird species that occur in the eastern part of the northern Palaearctic are known to migrate westward. In this study, a female tick collected from the sedge warbler, Acrocephalus schoenobaenus , in Lithuania was identified morphologically and analyzed with molecular-phylogenetic methods. In addition, literature data were reviewed on ixodid tick species known to be associated with birds that have recorded east-to-west migratory route in the Palaearctic. The tick collected from A. schoenobaenus was morphologically identified as Ixodes apronophorus . Two mitochondrial genetic markers for this specimen showed 100% identity with a conspecific tick reported previously in Western Siberia, Russia. Based on literature data, as many as 82 bird species from 11 orders were found to have records of ringing in the easternmost part of the northern Palaearctic and recaptures in Europe. Of these bird species, 31 ixodid tick species were reported in the Euro-Siberian region. Nearly all passeriform bird species with east-to-west migration were reported to carry ticks, whereas no reports of tick infestation were documented from the majority of wetland-associated bird species, mostly from the orders Anseriformes and Charadriiformes. The first European sequences of bona fide I. apronophorus revealed genetic connectedness with conspecific ticks reported from Siberia. Since the principal hosts of this tick species are rodents which do not migrate large distances, the most likely explanation for genetic similarity in this direction is dispersal of this tick species via migratory birds. Given the high number of tick species that are known to associate with bird species migrating in westward direction, this appears to be an important means of the gene flow between geographically distant tick populations in the northern Palaearctic., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: It is currently unknown whether high-resolution 3D-mapping and micro-electrodes add meaningful benefits in catheter ablation of Wolff-Parkinson-White (WPW) syndrome and challenging, e.g. para -Hisian accessory pathways (APs)., Objectives: To compare the mapping resolution, acute success and complication rates in patients with WPW syndrome undergoing a first-time catheter ablation using only a contact force-sensing ablation catheter for mapping or a multi-electrode high-resolution mapping catheter., Methods: Fifty consecutive 3D-mapping procedures for WPW syndrome using a 3.5-mm ablation catheter (n = 27) or a multi-electrode high-resolution catheter (n = 23) were retrospectively analyzed regarding mapping resolution defined as first 5/10 msec isochronal activation area, number of RF applications to achieve AP block, occurence of AP automaticity during RF delivery, and acute success and complication rates., Results: Catheter ablation was successful in 48/50 patients with a median of 1 (IQR 1-2) RF applications. Compared to ablation catheter mapping, high-resolution mapping showed a significantly smaller isochronal activation area in the first 5/10 msec (1.25 ± 0.29 vs 0.15 ± 0.03 cm 2 ; P  < 0.001 and 3.41 ± 0.58 vs 0.55 ± 0.12 cm 2 ; P  < 0.0001) and significantly higher incidence of AP automaticity during RF delivery (0 vs 22 %; P  < 0.05). In para -Hisian APs, micro-electrodes recorded distinct His electrograms and AP potentials without fusion and without AP bumping permitting safe and effective para -Hisian AP ablation., Conclusions: High-resolution mapping increases the mapping accuracy of the AP and its insertion site leading to a significantly higher incidence of AP automaticity during RF delivery. Micro-electrodes provide clinically relevant advantages in para -hisian AP mapping improving efficacy and safety of para -Hisian AP ablation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Hard ticks (Acari: Ixodidae) are the economically and ecologically most important blood-sucking arthropod vectors that can transmit disease agents under temperate climate. In this group, the highest number of species (currently nearing 270) belongs to the genus Ixodes . For this review, more than 400 papers related to this genus in the context of Russia were checked for data on the host records, locations of collection, as well as ecology of assigned tick species. This monograph compensates for the lack of a similarly comprehensive English-language overview of Ixodes species in the region of Russia for nearly half century, and also makes a large set of data easily available for international readers, which is especially important if the original source is difficult to access from outside this country. In addition, the data from a significant number of papers on this topic available only in the Russian language are made accessible through this work., Competing Interests: The authors have declared that no competing interests exist., (Denis Fedorov, Sándor Hornok.)

The presented paper discusses the production of radioactive ion beams of francium, radium, and actinium from thick uranium carbide (UC x ) targets at ISOLDE, CERN. This study focuses on the release curves and extractable yields of francium, radium and actinium isotopes. The ion source temperature was varied in order to study the relative contributions of surface and laser ionization to the production of the actinium ion beams. The experimental results are presented in the form of release parameters. Representative extractable yields per μ C are presented for 222 - 231 Ac, several Ra and Fr isotopes in the mass ranges 214 ≤ A ≤ 233 and 205 ≤ A ≤ 231 respectively. The release efficiency for several isotopes of each of the studied elements was calculated by comparing their yields to the estimated in-target production rates modeled by CERN-FLUKA. The maximal extraction efficiency of actinium was calculated to be 2.1(6)% for a combination of surface ionization using a Ta ion source and resonant laser ionization using the two-step 438.58 nm, and 424.69 nm scheme., (© 2024. The Author(s).)

Background:  Bioprosthetic stentless aortic valves may degenerate over time and will require replacement. This study aimed to evaluate early- and mid-term outcomes after isolated surgical redo aortic valve replacement (redo-SAVR) and transcatheter valve-in-valve implantation (TAVI-VIV) for degenerated stentless Freestyle bioprostheses., Methods:  We reviewed records of 56 patients at a single center. Overall, 37 patients (66.1%) received TAVI-VIV and 19 (33.9%) received redo-SAVR., Results:  Thirty-day survival was similar in both groups (100%). One-year survival was comparable between groups (97.3% in TAVI-VIV and 100% in redo-SAVR, p  = 1.0). The difference in mid-term survival after adjusting for age and EuroScore II was not significant ( p  = 0.41). The incidence of pacemaker implantation after TAVI-VIV was higher than after redo-SAVR (19.4% vs. 0%, p  = 0.08)., Conclusion:  The 30-day and 1-year survival rates after both procedures were outstanding, irrespective of baseline characteristics. Isolated redo-SAVR should be favored in young patients, as the pacemaker implantation rate is lower. TAVI-VIV for degenerated Freestyle prosthesis can be a method of choice in elderly patients and those with high operative risk., Competing Interests: None declared., (Thieme. All rights reserved.)

Condensates are molecular assemblies that are formed through liquid-liquid phase separation and play important roles in many biological processes. The rational design of condensate formation and their properties is central to applications, such as biosynthetic materials, synthetic biology, and for understanding cell biology. Protein engineering is used to make a triblock structure with varying terminal blocks of folded proteins on both sides of an intrinsically disordered mid-region. Dissociation constants are determined in the range of micromolar to millimolar for a set of proteins suitable for use as terminal blocks. Varying the weak dimerization of terminal blocks leads to an adjustable tendency for condensate formation while keeping the intrinsically disordered region constant. The dissociation constants of the terminal domains correlate directly with the tendency to undergo liquid-liquid phase separation. Differences in physical properties, such as diffusion rate are not directly correlated with the strength of dimerization but can be understood from the properties and interplay of the constituent blocks. The work demonstrates the importance of weak interactions in condensate formation and shows a principle for protein design that will help in fabricating functional condensates in a predictable and rational way., (© 2023 The Authors. Small published by Wiley‐VCH GmbH.)

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Swetnam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Recent advancements in next-generation sequencing (NGS) technology have ushered in significant improvements in sequencing speed and data throughput, thereby enabling the simultaneous analysis of a greater number of samples within a single sequencing run. This technology has proven particularly valuable in the context of microbial community profiling, offering a powerful tool for characterizing the microbial composition at the species level within a given sample. This profiling process typically involves the sequencing of 16S ribosomal RNA (rRNA) gene fragments. By scaling up the analysis to accommodate a substantial number of samples, sometimes as many as 2,000, it becomes possible to achieve cost-efficiency and minimize the introduction of potential batch effects. Our study was designed with the primary objective of devising an approach capable of facilitating the comprehensive analysis of 1,711 samples sourced from diverse origins, including oropharyngeal swabs, mouth cavity swabs, dental swabs, and human fecal samples. This analysis was based on data obtained from 16S rRNA metagenomic sequencing conducted on the Illumina MiSeq and HiSeq sequencing platforms., Results: We have designed a custom set of 10-base pair indices specifically tailored for the preparation of libraries from amplicons derived from the V3-V4 region of the 16S rRNA gene. These indices are instrumental in the analysis of the microbial composition in clinical samples through sequencing on the Illumina MiSeq and HiSeq platforms. The utilization of our custom index set enables the consolidation of a significant number of libraries, enabling the efficient sequencing of these libraries in a single run., Conclusions: The unique array of 10-base pair indices that we have developed, in conjunction with our sequencing methodology, will prove highly valuable to laboratories engaged in sequencing on Illumina platforms or utilizing Illumina-compatible kits., (© 2024. The Author(s).)

The changes in mean-squared charge radii of neutron-deficient gold nuclei have been determined using the in-source, resonance-ionization laser spectroscopy technique, at the ISOLDE facility (CERN). From these new data, nuclear deformations are inferred, revealing a competition between deformed and spherical configurations. The isotopes ^{180,181,182}Au are observed to possess well-deformed ground states and, when moving to lighter masses, a sudden transition to near-spherical shapes is seen in the extremely neutron-deficient nuclides, ^{176,177,179}Au. A case of shape coexistence and shape staggering is identified in ^{178}Au which has a ground and isomeric state with different deformations. These new data reveal a pattern in ground-state deformation unique to the gold isotopes, whereby, when moving from the heavy to light masses, a plateau of well-deformed isotopes exists around the neutron midshell, flanked by near-spherical shapes in the heavier and lighter isotopes-a trend hitherto unseen elsewhere in the nuclear chart. The experimental charge radii are compared to those from Hartree-Fock-Bogoliubov calculations using the D1M Gogny interaction and configuration mixing between states of different deformation. The calculations are constrained by the known spins, parities, and magnetic moments of the ground states in gold nuclei and show a good agreement with the experimental results.

Melittin, a peptide from bee venom, was found to be able to interact with many proteins, including calmodulin target proteins and ion-transporting P-type ATPases. It is assumed that melittin mimics a protein module involved in protein-protein interactions within cells. Previously, a Na^(+)/K^(+)-ATPase containing the α1 isoform of the catalytic subunit was found to co-precipitate with a protein with a molecular weight of about 70 κDa that interacts with antibodies against melittin by cross immunoprecipitation. In the presence of a specific Na^(+)/K^(+)-ATPase inhibitor (ouabain), the amount of protein with a molecular weight of 70 κDa interacting with Na^(+)/K^(+)-ATPase increases. In order to identify melittin-like protein from murine kidney homogenate, a fraction of melittin-like proteins with a molecular weight of approximately 70 κDa was obtained using affinity chromatography with immobilized antibodies specific to melittin. By mass spectrometry analysis, the obtained protein fraction was found to contain three molecular chaperones of Hsp70 superfamily: mitochondrial mtHsp70 (mortalin), Hsp73, Grp78 (BiP) of endoplasmic reticulum. These data suggest that chaperones from the HSP-70 superfamily contain a melittin-like module.

Background: Among hard ticks (Acari: Ixodidae), the genus Ixodes comprises the highest number of species, which in turn are most numerous in the Afrotropical zoogeographic region. In South Africa extensive morphological studies have been performed on Ixodes species but only few reports included molecular analyses., Methods: In this study, 58 Ixodes spp. ticks, collected from ten mammalian and eight avian host species in South Africa, were molecularly and phylogenetically analyzed. In addition, a newly collected sample of the Palearctic Ixodes trianguliceps was included in the analyses., Results: Among the ticks from South Africa, 11 species were identified morphologically. The majority of ticks from mammals represented the Ixodes pilosus group with two species (n = 20), followed by ticks resembling Ixodes rubicundus (n = 18) and Ixodes alluaudi (n = 3). In addition, single specimens of Ixodes rhabdomysae, Ixodes ugandanus, Ixodes nairobiensis and Ixodes simplex were also found. Considering bird-infesting ticks, Ixodes theilerae (n = 7), Ixodes uriae (n = 4) and ticks most similar to Ixodes daveyi (provisionally named I. cf. daveyi, n = 2) were identified. Molecular analyses confirmed two species in the I. pilosus group and a new species (I. cf. rubicundus) closely related to I. rubicundus sensu stricto. Phylogenetic trees based on concatenated mitochondrial or mitochondrial and nuclear gene sequences indicated that the subgenus Afrixodes forms a monophyletic clade with bird-associated exophilic ticks (subgenus Trichotoixodes). Ixodes trianguliceps clustered separately whereas I. alluaudi with their morphologically assigned subgenus, Exopalpiger., Conclusions: Phylogenetic analyses shed new lights on the relationships of Ixodes subgenera when including multiple sequences from subgenus Afrixodes and African as well as Palearctic species of subgenera Trichotoixodes and Exopalpiger. Subgenera Afrixodes and bird-associated Trichotoixodes share common ancestry, suggesting that the latter might have also originated in Africa. Regarding the subgenus Exopalpiger, I. alluaudi is properly assigned as it clusters among different Australian Ixodes, whereas I. trianguliceps should be excluded., (© 2023. The Author(s).)

The non-competitive NMDA glutamate receptor antagonist memantine has neuroprotective properties and is the first non-cholinergic drug approved for the treatment of Alzheimer's disease. The purpose of this work was to test the hypothesis that injections of memantine to healthy animals can affect the subunit composition of NMDA receptors in the brain, which may explain the effects of its chronic administration. For this, the expression of subunits GluN1, GluN2A, GluN2B, and GluN2C was studied in the hippocampus and prefrontal cortex of rats after single or five subchronic injections of memantine. The results showed that the GluN2C subunit (GRIN2C) plays an important role in the effects of memantine; against the background of memantine treatment, the expression of this subunit markedly decreased in the prefrontal cortex, but not in the hippocampus, which significantly affected the excitation/inhibition balance in cortical structures., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

We show by extensive experimental characterization combined with molecular simulations that pH has a major impact on the assembly mechanism and properties of poly(L-lysine) (PLL) and poly(L-glutamic acid) (PGA) complexes. A combination of dynamic light scattering (DLS) and laser Doppler velocimetry (LDV) is used to assess the complexation, charge state, and other physical characteristics of the complexes, isothermal titration calorimetry (ITC) is used to examine the complexation thermodynamics, and circular dichroism (CD) is used to extract the polypeptides' secondary structure. For enhanced analysis and interpretation of the data, analytical ultracentrifugation (AUC) is used to define the precise molecular weights and solution association of the peptides. Molecular dynamics simulations reveal the associated intra- and intermolecular binding changes in terms of intrinsic vs. extrinsic charge compensation, the role of hydrogen bonding, and secondary structure changes, aiding in the interpretation of the experimental data. We combine the data to reveal the pH dependency of PLL/PGA complexation and the associated molecular level mechanisms. This work shows that not only pH provides a means to control complex formation but also that the associated changes in the secondary structure and binding conformation can be systematically used to control materials assembly. This gives access to rational design of peptide materials via pH control.

Introduction: Prostate cancer (PCa) occupies a leading position in the structure of oncological morbidity and mortality and is an urgent problem of modern oncourology. In recipients after organ transplantation, due to the intake of immunosuppressants, the risk of aggressive forms of cancer increases, which necessitates active treatment. In the world, there is not enough data on the radical treatment of PCa in patients after heart transplantation (HT), especially on surgical treatment. We present the first experience in Russia and Eastern Europe of 3 robot-assisted radical prostatectomy for localized PCa in patients after HT., Materials and Methods: The procedures were performed from February 2021 to November 2021 at the FGBU NMRC named after V.A. Almazov. Preoperative preparation, as well as postoperative management of patients was carried out jointly by urologists and transplant cardiologists., Results: The main demographic, perioperative indicators, as well as oncological and non-oncological outcomes are presented. All patients were discharged from the hospital in a satisfactory condition. During the follow-up period, there were no biochemical recurrences of PCa. Early urinary continence in all three patients was satisfactory., Conclusion: Thus, robot-assisted radical prostatectomy in patients after HT is a technically feasible, effective, and safe treatment for PCa. The comparative studies with prolonged follow-up are needed.

The microbiome plays a key role in the health of the human body. Interest often lies in finding features of the microbiome, alongside other covariates, which are associated with a phenotype of interest. One important property of microbiome data, which is often overlooked, is its compositionality as it can only provide information about the relative abundance of its constituting components. Typically, these proportions vary by several orders of magnitude in datasets of high dimensions. To address these challenges we develop a Bayesian hierarchical linear log-contrast model which is estimated by mean field Monte-Carlo co-ordinate ascent variational inference (CAVI-MC) and easily scales to high dimensional data. We use novel priors which account for the large differences in scale and constrained parameter space associated with the compositional covariates. A reversible jump Monte Carlo Markov chain guided by the data through univariate approximations of the variational posterior probability of inclusion, with proposal parameters informed by approximating variational densities via auxiliary parameters, is used to estimate intractable marginal expectations. We demonstrate that our proposed Bayesian method performs favourably against existing frequentist state of the art compositional data analysis methods. We then apply the CAVI-MC to the analysis of real data exploring the relationship of the gut microbiome to body mass index., (© 2023. The Author(s).)

The limited diversity in targets of available antibiotic therapies has put tremendous pressure on the treatment of bacterial pathogens, where numerous resistance mechanisms that counteract their function are becoming increasingly prevalent. Here, we utilize an unconventional anti-virulence screen of host-guest interacting macrocycles, and identify a water-soluble synthetic macrocycle, Pillar[5]arene, that is non-bactericidal/bacteriostatic and has a mechanism of action that involves binding to both homoserine lactones and lipopolysaccharides, key virulence factors in Gram-negative pathogens. Pillar[5]arene is active against Top Priority carbapenem- and third/fourth-generation cephalosporin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii, suppressing toxins and biofilms and increasing the penetration and efficacy of standard-of-care antibiotics in combined administrations. The binding of homoserine lactones and lipopolysaccharides also sequesters their direct effects as toxins on eukaryotic membranes, neutralizing key tools that promote bacterial colonization and impede immune defenses, both in vitro and in vivo. Pillar[5]arene evades both existing antibiotic resistance mechanisms, as well as the build-up of rapid tolerance/resistance. The versatility of macrocyclic host-guest chemistry provides ample strategies for tailored targeting of virulence in a wide range of Gram-negative infectious diseases., (© 2023. The Author(s).)

Background: The subgenus Pholeoixodes contains Ixodes species typically associated with birds that nest in cavities or with carnivorous mammals that are burrow-dwelling. Among ticks infesting the latter, Ixodes rugicollis is regarded as the rarest species in the western Palearctic. Despite the unique morphology of this species, its identification (especially of subadult stages) is difficult, and molecular-phylogenetic data to offer other diagnostic methods and a better understanding of its taxonomy are not available., Methods: In this study, a female and a male of I. rugicollis were collected in Romania. The female was compared morphologically to another female of this species collected in France and to the lectotype of Ixodes cornutus (from Tajikistan), which has similar morphology and host association. Following DNA extraction, two mitochondrial (cytochrome c oxidase subunit I: cox1 and the 16S rRNA gene) and two nuclear genetic markers (18S and 28S rRNA genes) of I. rugicollis were amplified and analyzed in a phylogenetic context., Results: Females of I. rugicollis and I. cornutus differed in the shape of their palps, scutum and areae porosae and the size of peritremes, but they were similar in palpal setal length, dental formula and arrangement of anal setae. Measurements of two I. rugicollis females examined were not less different from each other than from I. cornutus. Phylogenetically, I. rugicollis clustered with other members of its subgenus. The topology of all trees showed the position of bat-associated tick species of the subgenus Eschatocephalus among Pholeoixodes species., Conclusions: For the first time to our knowledge, this study provides high-resolution digital pictures of male and female I. rugicollis as well as corresponding molecular data. Morphological comparison of this species with I. cornutus could not resolve uncertainties in the validity of the latter species, which can only be accomplished after collecting new specimens of I. cornutus and consequent molecular comparisons. This study includes the first comprehensive molecular-phylogenetic analysis of western Palearctic Pholeoixodes species based on both nuclear and mitochondrial genetic markers and including I. rugicollis. The results of these confirm the phylogenetic position of subgenus Eschatocephalus within Pholeoixodes, justifying the need to merge them to comply with the taxonomic criterion of monophyly., (© 2023. The Author(s).)

Here, we report the complete mitochondrial genome of sabellid Pseudopotamilla reniformis (Bruguière, 1789) (16,408 bp) and comprised of two ribosomal RNAs, the ubiquitous set of 13 protein-coding sequences, and 22 tRNAs. The order of protein-coding genes is consistent with the proposed conserved pattern, which contradicts recent discovery in other members of the family ( Sabella spallanzanii in Daffe et al., 2021 and Bispira melanostigma in Hornfeck et al., 2022)., Competing Interests: No conflict of interest was reported by the authors., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The relationship between neurological damage and cardiovascular disease is often observed. This type of damage is both a cause and an effect of cardiovascular disease. Mitochondria are the key organelles of the cell and are primarily subject to oxidative stress. Mitochondrial dysfunctions are involved in the etiology of various diseases. A decrease in the efficiency of the heart muscle can lead to impaired blood flow and decreased oxygen supply to the brain. Astaxanthin (AST), a marine-derived xanthophyll carotenoid, has multiple functions and its effects have been shown in both experimental and clinical studies. We investigated the effects of AST on the functional state of brain mitochondria in rats after heart failure. Isoproterenol (ISO) was used to cause heart failure. In the present study, we found that ISO impaired the functional state of rat brain mitochondria (RBM), while the administration of AST resulted in an improvement in mitochondrial efficiency. The respiratory control index (RCI) in RBM decreased with the use of ISO, while AST administration led to an increase in this parameter. Ca 2+ retention capacity (CRC) decreased in RBM isolated from rat brain after ISO injection, and AST enhanced CRC in RBM after heart failure. The study of changes in the content of regulatory proteins such as adenine nucleotide translocase 1 and 2 (ANT1/2), voltage dependent anion channel (VDAC), and cyclophilin D (CyP-D) of mitochondrial permeability transition pore (mPTP) showed that ISO reduced their level, while AST restored the content of these proteins almost to the control value. In general, AST improves the functional state of mitochondria and can be considered as a prophylactic drug in various therapeutic approaches., Competing Interests: The authors declare no conflicts of interest.

Aim: To identify features of the taxonomic composition of the oropharyngeal microbiota of COVID-19 patients with different disease severity., Materials and Methods: The study group included 156 patients hospitalized with confirmed diagnosis of COVID-19 in the clinical medical center of Yevdokimov Moscow State University of Medicine and Dentistry between April and June 2021. There were 77 patients with mild pneumonia according to CT (CT1) and 79 patients with moderate to severe pneumonia (CT2 and CT3). Oropharyngeal swabs were taken when the patient was admitted to the hospital. Total DNA was isolated from the samples, then V3V4 regions of the 16s rRNA gene were amplified, followed by sequencing using Illumina HiSeq 2500 platform. DADA2 algorithm was used to obtain amplicon sequence variants (ASV)., Results: When comparing the microbial composition of the oropharynx of the patients with different forms of pneumonia, we have identified ASVs associated with the development of both mild and severe pneumonia outside hospital treatment. Based on the results obtained, ASVs associated with a lower degree of lung damage belong predominantly to the class of Gram-negative Firmicutes (Negativicutes), to various classes of Proteobacteria, as well as to the order Fusobacteria. In turn, ASVs associated with a greater degree of lung damage belong predominantly to Gram-positive classes of Firmicutes Bacilli and Clostridia. While being hospitalized, patients with severe pneumonia demonstrated negative disease dynamics during treatment significantly more often., Conclusion: We have observed differences in the taxonomic composition of the oropharyngeal microbiota in patients with different forms of pneumonia developed outside hospital treatment against COVID-19. Such differences might be due to the presumed barrier function of the oropharyngeal microbiota, which reduces the risk of virus titer increase.

(Ca 2+ )-dependent pyrroloquinolinequinone (PQQ)-dependent methanol dehydrogenase (MDH) (EC: 1.1.2.7) is one of the key enzymes of primary C1-compound metabolism in methylotrophy. PQQ-MDH is a promising catalyst for electrochemical biosensors and biofuel cells. However, the large-scale use of PQQ-MDH in bioelectrocatalysis is not possible due to the low yield of the native enzyme. Homologously overexpressed MDH was obtained from methylotrophic bacterium Methylorubrum extorquens AM1 by cloning the gene of only one subunit, mxaF . The His-tagged enzyme was easily purified by immobilized metal ion affinity chromatography (36% yield). A multimeric form (α6β6) of recombinant PQQ-MDH possessing enzymatic activity (0.54 U/mg) and high stability was demonstrated for the first time. pH-optimum of the purified protein was about 9-10; the enzyme was activated by ammonium ions. It had the highest affinity toward methanol (K M = 0.36 mM). The recombinant MDH was used for the fabrication of an amperometric biosensor. Its linear range for methanol concentrations was 0.002-0.1 mM, the detection limit was 0.7 µM. The properties of the invented biosensor are competitive to the analogs, meaning that this enzyme is a promising catalyst for industrial methanol biosensors. The developed simplified technology for PQQ-MDH production opens up new opportunities for the development of bioelectrocatalytic systems.

Background: PET with radiolabeled amino acids is used in the preoperative evaluation of patients with glial neoplasms. This study aimed to assess the role of [11C]methionine (MET) PET in assessing molecular features, tumor extent, and prognosis in newly diagnosed lower-grade gliomas (LGGs) surgically treated., Methods: One hundred and fifty-three patients with a new diagnosis of grade 2/3 glioma who underwent surgery at our Institution and were imaged preoperatively using [11C]MET PET/CT were retrospectively included. [11C]MET PET images were qualitatively and semi-quantitatively analyzed using tumor-to-background ratio (TBR). Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method and Cox proportional-hazards regression was used to test the association of clinicopathological and imaging data to PFS., Results: Overall, 111 lesions (73%) were positive, while thirty-two (21%) and ten (6%) were isometabolic and hypometabolic at [11C]MET PET, respectively. [11C]MET uptake was more common in oligodendrogliomas than IDH-mutant astrocytomas (87% vs 50% of cases, respectively). Among [11C]MET-positive gliomas, grade 3 oligodendrogliomas had the highest median TBRmax (3.22). In 25% of patients, PET helped to better delineate tumor margins compared to MRI only. In IDH-mutant astrocytomas, higher TBRmax values at [11C]MET PET were independent predictors of shorter PFS., Conclusions: This work highlights the role of preoperative [11C]MET PET in estimating the type of suspected LGGs, assessing tumor extent, and predicting biological behavior and prognosis of histologically confirmed LGGs. Our findings support the implementation of [11C]MET PET in routine clinical practice to better manage these neoplasms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

The SARS-CoV-2 pandemic is a big challenge for humanity. The COVID-19 severity differs significantly from patient to patient, and it is important to study the factors protecting from severe forms of the disease. Respiratory microbiota may influence the patient's susceptibility to infection and disease severity due to its ability to modulate the immune system response of the host organism. This data article describes the microbiome dataset from the upper respiratory tract of SARS-CoV-2 positive patients from Russia. This dataset reports the microbial community profile of 335 human nasopharyngeal swabs collected between 2020-05 and 2021-03 during the first and the second epidemic waves. Samples were collected from both inpatients and outpatients in 4 cities of the Russian Federation (Moscow, Kazan, Irkutsk, Nizhny Novgorod) and sequenced using the 16S rRNA gene amplicon sequencing of V3-V4 region. Data contains information about the patient such as age, sex, hospitalization status, percent of damaged lung tissue, oxygen saturation (SpO2), respiratory rate, need for supplemental oxygen, chest computer tomography severity score, SARS-CoV-2 lineage, and also information about smoking and comorbidities. The amplicon sequencing data were deposited at NCBI SRA as BioProject PRJNA751478., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

Objective: To present a patient with brainstem abscess treated by microsurgical resection., Case Presentation: A 53-years-old female patient admitted to the neurosurgical department in a severe condition with symptoms of intracranial hypertension, hyperthermia, general infectious signs and laboratory manifestations of infectious process. Contrast-enhanced MRI revealed a large brainstem lesion (abscess). Retrosigmoid craniotomy with total microsurgical resection of the abscess was performed. External ventricular drainage was incerted on the second postoperative day due to progressive hydrocephalus with clinical deterioration, it was removed in 8 days. Slow positive dynamics was observed in postoperative period. The patient was discharged in 2 weeks after surgery., Conclusion: There are no established algorithm for the treatment of brainstem abscesses. Therapeutic approach is advisable for small abscesses. There are 2 neurosurgical options for this lesion: stereotactic drainage and microsurgical resection with or without external ventricular drainage. Treatment strategy depends on location and size of abscess, as well as clinical state of the patient.

The changes in the mean-square charge radius (relative to ^{209}Bi), magnetic dipole, and electric quadrupole moments of ^{187,188,189,191}Bi were measured using the in-source resonance-ionization spectroscopy technique at ISOLDE (CERN). A large staggering in radii was found in ^{187,188,189}Bi^{g}, manifested by a sharp radius increase for the ground state of ^{188}Bi relative to the neighboring ^{187,189}Bi^{g}. A large isomer shift was also observed for ^{188}Bi^{m}. Both effects happen at the same neutron number, N=105, where the shape staggering and a similar isomer shift were observed in the mercury isotopes. Experimental results are reproduced by mean-field calculations where the ground or isomeric states were identified by the blocked quasiparticle configuration compatible with the observed spin, parity, and magnetic moment.

High-salt consumption contributes to the development of hypertension and is considered an independent risk factor for vascular remodelling, cardiac hypertrophy and stroke incidence. Alterations in NO production, inflammation and endothelial cell stiffening are considered now as plausible mediators of cardiovascular dysfunction. We studied early responses of endothelial cells (HUVEC) caused by a moderate increase in extracellular sodium concentration. Exposure of HUVEC to elevated sodium within the physiological range up to 24 h is accompanied by changes in monovalent cations fluxes and Na,K-ATPase activation, and, in turn, results in a significant decrease in the content of PTGS2 , IL6 and IL1LR1 mRNAs. The expression of NOS3 and FOS genes, as well as the abundance of cytosolic and nuclear NFAT5 protein, remained unchanged. We assessed the mechanical properties of endothelial cells by estimating Young's modulus and equivalent elastic constant using atomic force and interference microscopy, respectively. These parameters were unaffected by elevated-salt exposure for 24 h. The data obtained suggest that even small and short-term elevations of extracellular sodium concentration affect the expression of genes involved in the control of endothelial function through the Na + i /K + i -dependent mechanism(s)., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Chemicals reactivating epigenetically silenced genes target diverse classes of enzymes, including DNMTs, HDACs, HMTs and BET protein family members. They can strongly influence the expression of genes and endogenous retroviral elements with concomitant dsRNA synthesis and massive transcription of LTRs. Chemicals reactivating gene expression may cause both beneficial effects in cancer cells and may be hazardous by promoting carcinogenesis. Among chemicals used in medicine and commerce, only a small fraction has been studied with respect to their influence on epigenetic silencing. Screening of chemicals reactivating silent genes requires adequate systems mimicking whole-genome processes. We used a HeLa TSA-inducible cell population (HeLa TI cells) obtained by retroviral infection of a GFP-containing vector followed by several rounds of cell sorting for screening purposes. Previously, the details of GFP epigenetic silencing in HeLa TI cells were thoroughly described. Herein, we show that the epigenetically repressed gene GFP is reactivated by 15 agents, including HDAC inhibitors-vorinostat, sodium butyrate, valproic acid, depsipeptide, pomiferin, and entinostat; DNMT inhibitors-decitabine, 5-azacytidine, RG108; HMT inhibitors-UNC0638, BIX01294, DZNep; a chromatin remodeler-curaxin CBL0137; and BET inhibitors-JQ-1 and JQ-35. We demonstrate that combinations of epigenetic modulators caused a significant increase in cell number with reactivated GFP compared to the individual effects of each agent. HeLa TI cells are competent to metabolize xenobiotics and possess constitutively expressed and inducible cytochrome P450 mono-oxygenases involved in xenobiotic biotransformation. Thus, HeLa TI cells may be used as an adequate test system for the extensive screening of chemicals, including those that must be metabolically activated. Studying the additional metabolic activation of xenobiotics, we surprisingly found that the rat liver S9 fraction, which has been widely used for xenobiotic activation in genotoxicity tests, reactivated epigenetically silenced genes. Applying the HeLa TI system, we show that N-nitrosodiphenylamine and N-nitrosodimethylamine reactivate epigenetically silenced genes, probably by affecting DNA methylation., Competing Interests: The authors have declared that no competing interests exist.

The β - -particle-emitting erbium-169 is a potential radionuclide toward therapy of metastasized cancer diseases. It can be produced in nuclear research reactors, irradiating isotopically-enriched 168 Er 2 O 3 . This path, however, is not suitable for receptor-targeted radionuclide therapy, where high specific molar activities are required. In this study, an electromagnetic isotope separation technique was applied after neutron irradiation to boost the specific activity by separating 169 Er from 168 Er targets. The separation efficiency increased up to 0.5% using resonant laser ionization. A subsequent chemical purification process was developed as well as activity standardization of the radionuclidically pure 169 Er. The quality of the 169 Er product permitted radiolabeling and pre-clinical studies. A preliminary in vitro experiment was accomplished, using a 169 Er-PSMA-617, to show the potential of 169 Er to reduce tumor cell viability., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Talip, Borgna, Müller, Ulrich, Duchemin, Ramos, Stora, Köster, Nedjadi, Gadelshin, Fedosseev, Juget, Bailat, Fankhauser, Wilkins, Lambert, Marsh, Fedorov, Chevallay, Fernier, Schibli and van der Meulen.)

Liquid-liquid phase separation of biomacromolecules is crucial in various inter- and extracellular biological functions. This includes formation of condensates to control, e.g., biochemical reactions and structural assembly. The same phenomenon is also found to be critically important in protein-based high-performance biological materials. Here, we use a well-characterized model triblock protein system to demonstrate the molecular level formation mechanism and structure of its condensate. Large-scale molecular modeling supported by analytical ultracentrifuge characterization combined with our earlier high magnification precision cryo-SEM microscopy imaging leads to deducing that the condensate has a bicontinuous network structure. The bicontinuous network rises from the proteins having a combination of sites with stronger mutual attraction and multiple weakly attractive regions connected by flexible, multiconfigurational linker regions. These attractive sites and regions behave as stickers of varying adhesion strength. For the examined model triblock protein construct, the β-sheet-rich end units are the stronger stickers, while additional weaker stickers, contributing to the condensation affinity, rise from spring-like connections in the flexible middle region of the protein. The combination of stronger and weaker sticker-like connections and the flexible regions between the stickers result in a versatile, liquid-like, self-healing structure. This structure also explains the high flexibility, easy deformability, and diffusion of the proteins, decreasing only 10-100 times in the bicontinuous network formed in the condensate phase in comparison to dilute protein solution. The here demonstrated structure and condensation mechanism of a model triblock protein construct via a combination of the stronger binding regions and the weaker, flexible sacrificial-bond-like network as well as its generalizability via polymer sticker models provide means to not only understand intracellular organization, regulation, and cellular function but also to identify direct control factors for and to enable engineering improved protein and polymer constructs to enhance control of advanced fiber materials, smart liquid biointerfaces, or self-healing matrices for pharmaceutics or bioengineering materials.

The mean-square charge radii of ^{207,208}Hg (Z=80, N=127, 128) have been studied for the first time and those of ^{202,203,206}Hg (N=122, 123, 126) remeasured by the application of in-source resonance-ionization laser spectroscopy at ISOLDE (CERN). The characteristic kink in the charge radii at the N=126 neutron shell closure has been revealed, providing the first information on its behavior below the Z=82 proton shell closure. A theoretical analysis has been performed within relativistic Hartree-Bogoliubov and nonrelativistic Hartree-Fock-Bogoliubov approaches, considering both the new mercury results and existing lead data. Contrary to previous interpretations, it is demonstrated that both the kink at N=126 and the odd-even staggering (OES) in its vicinity can be described predominately at the mean-field level and that pairing does not need to play a crucial role in their origin. A new OES mechanism is suggested, related to the staggering in the occupation of the different neutron orbitals in odd- and even-A nuclei, facilitated by particle-vibration coupling for odd-A nuclei.

Cellulose binding modules (CBMs) are found widely in different proteins that act on cellulose. Because they allow a very easy way of binding recombinant proteins to cellulose, they have become widespread in many biotechnological applications involving cellulose. One commonly used variant is the CBM CipA from Clostridium thermocellum. Here we studied the oligomerization behavior of CBM CipA , as such solution association may have an impact on its use. As the principal approach, we used sedimentation velocity and sedimentation equilibrium analytical ultracentrifugation. To enhance our understanding of the possible interactions, we used molecular dynamics simulations. By analysis of the sedimentation velocity data by a discrete model genetic algorithm and by building a binding isotherm based on weight average sedimentation coefficient and by global fitting of sedimentation equilibrium data we found that the CBM CipA shows a weak dimerization interaction with a dissociation constant K D of 90 ± 30 μM. As the K D of CBM CipA binding to cellulose is below 1 μM, we conclude that the dimerization is unlikely to affect cellulose binding. However, at high concentrations used in some applications of the CBM CipA , its dimerization is likely to have a marked effect on its solution behavior., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Anti-PD-1 immunotherapy has a large impact on cancer treatment but the rate of positive treatment outcomes is 40-45% and depends on many factors. One of the factors affecting the outcome of immunotherapy is the gut microbiota composition. This effect has been demonstrated both in model objects and in clinical patients groups. However, in order to identify clear causal relationships between microbiota and anti-PD1 immunotherapy response, it is necessary to expand the number of patients and experimental samples. This work presents an analysis of metagenomic data obtained using whole-genome sequencing of stool samples from melanoma patients (n=45) with different responses to anti-PD1 therapy. The analysis of the differential representation of microbial species has shown a difference in the composition of the microbiota between the experimental groups. Results of this study indicate existence of a strong link between the composition of the gut microbiota and the outcome of anti-PD1 therapy. Expansion of similar research may help develop additional predictive tools for the outcome of anti-PD1 cancer immunotherapy, as well as increase its effectiveness.

Comparative genomics studies may be used to acquire new knowledge regarding genome architecture, which defines the rules for combining sets of genes in the genome of living organisms. Hundreds of thousands of prokaryotic genomes have been sequenced and assembled. However, computational tools capable of simultaneously comparing large numbers of genomes are lacking. We developed the Genome Complexity Browser, a tool that allows the visualization of gene contexts, in a graph-based format, and the quantification of variability for different segments of a genome. The graph-based visualization allows the inspection of changes in gene contents and neighborhoods across hundreds of genomes, simultaneously, which may facilitate the identification of conserved and variable segments of operons or the estimation of the overall variability associated with a particular genome locus. We introduced a measure called complexity, to quantify genome variability. Intraspecies and interspecies comparisons revealed that regions with high complexity values tended to be located in areas that are conserved across different strains and species., Competing Interests: The authors have declared that no competing interests exist.

One of the most important properties influencing the chemical behavior of an element is the electron affinity (EA). Among the remaining elements with unknown EA is astatine, where one of its isotopes, 211 At, is remarkably well suited for targeted radionuclide therapy of cancer. With the At - anion being involved in many aspects of current astatine labeling protocols, the knowledge of the electron affinity of this element is of prime importance. Here we report the measured value of the EA of astatine to be 2.41578(7) eV. This result is compared to state-of-the-art relativistic quantum mechanical calculations that incorporate both the Breit and the quantum electrodynamics (QED) corrections and the electron-electron correlation effects on the highest level that can be currently achieved for many-electron systems. The developed technique of laser-photodetachment spectroscopy of radioisotopes opens the path for future EA measurements of other radioelements such as polonium, and eventually super-heavy elements.

The effects of dynamic and static load on the intracellular concentrations of sodium [Formula: see text] and potassium (K + i ) in m. soleus and m. biceps, respectively, were studied in mice. Both dynamic (swimming for 60 min) and static (hanging on the grid for 40 min) load led to a 2-fold increase in [Formula: see text] level, a decrease in K + i concentration by 25-35%, and 3-4-fold increase in the [Formula: see text] ratio. These effects of dynamic and static loads on the studied parameters remained unchanged in mice subjected to regular physical exercise (swimming or hanging on the grid for 1 h a day over 4 weeks). Our results suggest that dissipation of sodium and potassium transmembrane gradients during physical exercise can be considered as a factor of regulation of functional activity of skeletal muscles, which includes changes in transcription and translation of myokines observed previously.

Long-term study on the identification of Na,K-ATPase endogenous inhibitors in mammalian tissues has resulted in the discovery of ouabain, marinobufagenin (MBG), and other cardiotonic steroids (CTS) in the blood plasma. Production of ouabain and MBG is increased in essential hypertension and other diseases associated with hypervolemia. Here, we compared the effects of ouabain and MBG on the Na,K-ATPase activity (measured as the transport of Na+, K+, and Rb + ions) and proliferation and death of human renal epithelial cells (HRECs) and human umbilical vein endothelial cells (HUVEC) expressing α1-Na,K-ATPase. Ouabain concentration that provided the half-maximal inhibition of the Rb + influx (IC 50 ) into HRECs and HUVECs was 0.07 μM. In both types of cells, the IC 50 values for MBG were 10 times higher than for ouabain. Incubation of HREC and HUVEC with 0.001-0.01 μM ouabain for 30 h resulted in 40% increase in the [3H]thymidine incorporation into DNA; further elevation of ouabain concentration to 0.1 μM completely suppressed DNA synthesis. MBG at the concentration of 0.1 μM activated DNA synthesis by 25% in HRECs, but not in HUVECs; 1 μM MBG completely inhibited DNA synthesis in HRECs and by 50% in HUVECs. In contrast to HRECs, incubation of HUVECs in the serum-free medium induced apoptosis, which was almost completely suppressed by ouabain and MBG at the concentrations of 0.1 and 3 μM, respectively. Based on these data, we can conclude that (i) the effect of MBG at the concentrations detected in the blood plasma (<0.01 μM) on HRECs and HUVECs was not due to the changes in the [Na+] i /[K+] i ratio; (ii) the effect of physiological concentrations of ouabain on these cells might be mediated by the activation of Na,K-ATPase, leading to cell proliferation.

Numerous studies confirm the high degree of involvement of the intestinal microbiota in most processes in the human body. There is evidence for the effect of intestinal microbiota on the success of chemo and immunotherapy of oncological diseases. It is assumed that the intestinal microbiota exhibits an indirect effect on the antitumor therapy through such mechanisms as general immunomodulation, an increase in cells that specifically respond to antigens of both microbial and tumor origin, metabolism, degradation (utilization) of drug compounds. The intestinal microbiota is currently considered as an additional, but important target for studying the effective use of antitumor therapy and reducing its toxicity, as well as a predictor of the success of immunotherapy. In this review, we highlight the results of studies published to date that confirm the relationship between gut microbiome and antitumor efficacy of immune checkpoint inhibitors. Despite the promising and theoretically substantiated conclusions, there are still some discrepancies among the existing data that will have to be addressed in order to facilitate the further development of this direction.

Absorption of hydrogen by palladium causes PdH to become superconducting below [Formula: see text]. Due to the presence of one octapore and two tetrapores per each Pd atom, it is believed that [Formula: see text] of PdH[Formula: see text] should increase further. Here, using ab initio calculation we show that (i) H placed in tetrapores of PdH[Formula: see text] induces a wide optical gap in the phonon density of states, which significantly reduces the electron-phonon coupling, and that (ii) the energetically preferable octapores filled by H enable the 9 K superconductivity only. This scenario may close a long-standing problem of the high-[Formula: see text] palladium hydrides. Moreover, simulating the pore population by H and D, within ab initio molecular dynamics, we are able to explain the inverse isotope effect in the framework of the Bardeen-Cooper-Schrieffer theory.

Background/aims: Prolonged hyperosmotic shrinkage evokes expression of osmoprotective genes via nuclear factor NFAT5-mediated pathway and activates Na + influx via hypertonicity-induced cation channels (HICC). In human umbilical vein endothelial cells (HUVEC) elevation of intracellular sodium concentration ([Na + ] i ) triggers transcription of dozens of early response genes (ERG). This study examined the role of monovalent cations in the expression of Na + i -sensitive ERGs in iso- and hyperosmotically shrunken HUVEC., Methods: Cell volume was measured by 3D reconstruction of cell shape and as 14 C-urea available space. Intracellular Na + and K + content was measured by flame atomic absorption spectrometry. ERG transcription was estimated by RT-PCR., Results: Elevation of medium osmolality by 150 mM mannitol or cell transfer from hypo- to isosmotic medium decreased cell volume by 40-50%. Hyperosmotic medium increased [Na + ] i by 2-fold whereas isosmotic shrinkage had no impact on this parameter. Hyperosmotic but not isosmotic shrinkage increased up-to 5-fold the content of EGR1, FOS, ATF3, ZFP36 and JUN mRNAs. Expression of these ERGs triggered by hyperosmotic shrinkage and Na + ,K + -ATPase inhibition by 0.1 µM ouabain exhibited positive correlation (R 2 =0.9383, p=0.0005). Isosmotic substitution of NaCl by N-methyl-D-glucamine abolished an increment of [Na + ] i and ERG expression triggered by mannitol addition., Conclusion: Augmented expression of ERGs in hyperosmotically shrunken HUVEC is mediated by elevation of [Na + ] i ., Competing Interests: The authors declare no competing financial interests., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

The last decade has seen active development of minimally invasive (endovenous) methods of surgical removal of lower limb varicose veins (LLVV); however, the problem of increasing efficacy of these methods and improving long-term results still remains of current importance. The authors of this work propose a method of ultrasound ablation of subcutaneous veins of lower extremities. Our experimental study was aimed at determining the pattern of venous wall damage after ultrasound exposure. Samples of segments of the trunk of the great saphenous vein (GSV) were divided into 5 groups: group 1 - the control group, group 2 - treatment with a sclerosant in the amount of 0.3 ml for 30 s, group 3 - treatment with ultrasound at a frequency of 26 kHz and amplitude 40 μm and 0.3-ml sclerosant for 30 s, group 4 - exposure to ultrasound at a frequency of 26 kHz and amplitude 40 μm and 0.3-ml sclerosant for 60 s, group 5 samples were exposed to ultrasound at 26 kHz and amplitude of 40 μm for 60 s. The results of analysing the histological sections of the samples of the 2nd and 3rd groups demonstrated that the degree of alteration in the GSV wall on combined exposure to ultrasound and a sclerosant was 4.5-fold higher as compared with treatment with a sclerosant solution alone. During ultrasound exposure, the maximum temperature of the venous wall of group 5 samples was by 20 °C higher than in samples of group 4. Analysing the histological sections demonstrated a similar pattern of structural alterations of the samples of group 4 and 5, thus suggesting a possibility of controlling the temperature of the venous wall during ultrasound ablation without changing quality of structural lesions. The obtained findings showed a possibility of initiating irreversible dystrophic alterations in the venous wall on exposure to ultrasound by means of combining the mechanisms of chemical, mechanical, and thermal ablation.

RNA is an attractive biopolymer for engineering self-assembling materials suitable for biomedical applications. Previously, programmable hexameric RNA rings were developed for the controlled delivery of up to six different functionalities. To increase the potential for functionalization with little impact on nanoparticle topology, we introduce gaps into the double-stranded regions of the RNA rings. Molecular dynamic simulations are used to assess the dynamic behavior and the changes in the flexibility of novel designs. The changes suggested by simulations, however, cannot be clearly confirmed by the conventional techniques such as nondenaturing polyacrylamide gel electrophoresis (native-PAGE) and dynamic light scattering (DLS). Also, an in vitro analysis in primary cultures of human peripheral blood mononuclear cells does not reveal any discrepancy in the immunological recognition of new assemblies. To address these deficiencies, we introduce a computer-assisted quantification strategy. This strategy is based on an algorithmic atomic force microscopy (AFM)-resolved deformation analysis of the RNA nanoparticles studied on a mica/air interface. We validate this computational method by manual image analysis and fitting it to the simulation-predicted results. The presented nanoparticle modification strategy and subsequent AFM-based analysis are anticipated to provide a broad spectrum approach for the future development of nucleic acid-based nanotechnology.

The neutron-rich isotopes ^{58-63}Cr were produced for the first time at the ISOLDE facility and their masses were measured with the ISOLTRAP spectrometer. The new values are up to 300 times more precise than those in the literature and indicate significantly different nuclear structure from the new mass-surface trend. A gradual onset of deformation is found in this proton and neutron midshell region, which is a gateway to the second island of inversion around N=40. In addition to comparisons with density-functional theory and large-scale shell-model calculations, we present predictions from the valence-space formulation of the ab initio in-medium similarity renormalization group, the first such results for open-shell chromium isotopes.

We investigate the emergence of halos and Efimov states in nuclei by use of a newly designed model that combines self-consistent mean-field and three-body descriptions. Recent interest in neutron heavy calcium isotopes makes ^{72}Ca (^{70}Ca+n+n) an ideal realistic candidate on the neutron dripline, and we use it as a representative example that illustrates our broadly applicable conclusions. By smooth variation of the interactions we simulate the crossover from well-bound systems to structures beyond the threshold of binding, and find that halo configurations emerge from the mean-field structure for three-body binding energy less than ∼100  keV. Strong evidence is provided that Efimov states cannot exist in nuclei. The structure that bears the most resemblance to an Efimov state is a giant halo extending beyond the neutron-core scattering length. We show that the observable large-distance decay properties of the wave function can differ substantially from the bulk part at short distances, and that this evolution can be traced with our combination of few- and many-body formalisms. This connection is vital for interpretation of measurements such as those where an initial state is populated in a reaction or by a beta decay.

Liver resection remains the method of choice for treatment of colorectal liver metastases with good long-term results. Regional lymph nodes involvement is significant negative prognostic factor. Moreover, it has been considered as a contraindication for liver resection for a long time. The role of lymphadenectomy remains controversial. Current state of this problem is reviewed in the article. Liver regional lymph nodes involvement takes place in 10-20% of cases. PET/CT is the most sensitive method of preoperative diagnosis. Involvement of liver regional lymph nodes is currently not absolute contraindication for liver resection. Routine lymphadenectomy does not make sense, and, perhaps, is justified only within scientific trials for more accurate disease staging. Indications for lymphadenectomy are suspicious changes of lymph nodes revealed by preoperative visualization methods or by intraoperative exploration. Modern chemotherapy regimens allow to reconsider the prognostic importance of liver regional lymph node metastases and to extend indications for liver resections.

The paper describes a case of chromophobe renal cell carcinoma growing into the muscular layer of the descending colon and with metastases in 4 lymph nodes of paranephral tissue in a 66-year-old woman. The tumor had a zonal structure with an alternation of epithelioid and sarcomatoid structural sites and with the signs of grades I, II and III according to the grading system by Paner and et al. (2010). The sarcomatoid renal component occupied about 70.0% of the tumor. There was a pronounced immunohistochemical reaction with VEGF-A (5 scores), a high Ki-67 proliferation index (70%), and a large number of tumor cells with nuclear p53 expression (85%) in the areas with minimal differentiation and sarcomatoid elements (Grade III). These signs can serve as criteria for the aggressive behavior of the tumor. A large volume of the sarcomatoid carcinoma component and a strong reaction with VEGF-A are indications for targeted therapy with anti-VEGF drugs.

The paper describes a case of solitary epithelioid hemangioendothelioma concurrent with nodular parenchymal AL amyloidosis of the lung and Rosai-Dorfman disease in a 70-year-old woman. The core of the tumor was represented by bone tissue with dendriform ossification, as well as by amyloid that showed green apple birefringence at polarized light microscopy. The peripheral portions of the tumor and the myxohyaline stroma exhibited slit-like structures, epithelioid and fusiform cells with small cytoplasmic vacuoles. These cells expressed CD31, CD34, factor VIII, and cytokeratins 7 and 18. The Ki-67 proliferation index was 10%. S100- and CD68-positive histiocytes with the phenomenon of emperipolesis were revealed in the tumor and in the lymph nodes of the mediastinum and lung hilum. There was a positive reaction to immunoglobulin lambda light chains in the lymphocytic infiltration around amyloid clumps. The frequency of epithelioid hemangioendothelioma was less than 1 case per million people annually. We found only one case of its concurrence with pulmonary amyloidosis in the English-language literature. No relationship could be revealed between this tumor and Rosai-Dorfman disease.