Prevalence of Different Types of Integrative Conjugative Element SXT/R391 Encoding Multiple Antibiotic Resistance Among Clinical Strains of Cholera Agent

The aim of the work was to study the prevalence of different types of SXT element with different composition of antibiotic resistance genes among clinical strains of the El Tor cholera pathogen isolated in Russia, Ukraine and cholera-endemic countries in Asia and Africa.Materials and methods. The subject of the study was 27 strains and nucleotide sequences of 77 strains of Vibrio cholerae El Tor available from the NCBI GenBank. The structure of the SXT element and its type were determined using the Mauve and BLAST v.2.9.0 programs. Phylogenetic relations of strains with different types of SXT were identified using Snippy v.4.6.0 and MrBayes v.3.2.7 software. Assessment of strain sensitivity to antibiotics was carried out in accordance with Methodological Regulations 4.2.2495-09.Results and discussion. Two types of SXT element (ICEVchInd5 and ICEVchBan9) have been identified among the studied strains from Russia and Ukraine, which have different composition of antibiotic resistance genes: floR, strAB, sul2, dfrA1 and floR, tetAR, strAB, sul2, dfrA1, respectively. At the same time, the studied strains from Asia and Africa contain five types of SXT: ICEVchInd5, ICEVchBan9, ICEVchBan5, SXTTET, ICEVchInd5ΔVRIII, which differ in size and/or composition of resistance genes. Of these, the last three have not been found in Russia and Ukraine. Due to the high level of genomic diversity of SXT in the population of V. cholerae in endemic regions, there is a risk of importation of cholera pathogen strains with altered resistance to antibiotics into Russia. Phylogenetic relations of 76 strains with different SXT types and different alleles of the ctxB gene encoding the B subunit of cholera toxin have been assessed based on SNP analysis. A close phylogenetic relation between strains with the same type of SXT isolated in Russia and Asian countries has been demonstrated, which confirms the importation of the causative agent of cholera with multiple resistance to antibiotics from this region and the need for constant monitoring of the sensitivity of V. cholerae to antimicrobial drugs

EFFECT OF THE PROPHAGE CTXΦ DELETION UPON PHENOTYPIC PROPERTIES IN STRAINS OF VIBRIO CHOLERAE BIOVAR EL TOR, ASSOCIATED WITH VIRULENCE AND PERSISTENCE

Objective of the study is to evaluate the influence of CTXφ prophage deletion, which carries ctxAB genes, on phenotypical properties associated with pathogenicity or biofilm formation in non-toxigenic mutants. Materials and methods. Utilized have been the clinical strains of Vibrio cholerae biovar El Tor and their spontaneous non-toxigenic mutants that lost CTXφ prophage. Applied have been microbiological and biochemical methods, inoculation of model animals with cells of the strains under study. Results and conclusions. The results of comparative analysis of phenotypic properties in isogenic toxigenic and non-toxigenic strains of Vibrio cholerae biovar El Tor, which lost CTXφ prophage encoding the cholera toxin, are represented. It is established that the deletion of CTXφ prophage leads to the simultaneous change of several phenotypic properties associated with virulence (colonizing ability, production of soluble hemagglutinin/protease and heat labile hemolysin/cytolysin) and biofilm formation (motility, exopolysaccharide biosynthesis) in spontaneous non-toxigenic mutants. It is suggested that the reason for these phenotypic changes in the mutants might be the changes in activity of the related to each other regulatory genes controlling virulence and biofilm formation process in cholera agent

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

SIT for African malaria vectors: Epilogue

As a result of increased support and the diligent application of new and conventional anti-malaria tools, significant reductions in malaria transmission are being accomplished. Historical and current evolutionary responses of vectors and parasites to malaria interventions demonstrate that it is unwise to assume that a limited suite of tools will remain effective indefinitely, thus efforts to develop new interventions should continue. This collection of manuscripts surveys the prospects and technical challenges for applying a novel tool, the sterile insect technique (SIT), against mosquitoes that transmit malaria. The method has been very successful against many agricultural pest insects in area-wide programs, but demonstrations against malaria vectors have not been sufficient to determine its potential relative to current alternatives, much of which will hinge ultimately upon cost. These manuscripts provide an overview of current efforts to develop SIT and identify key research issues that remain

Tenascin-C as a cardiovascular marker

Novel biological markers, such as fibrosis marker galectin-3, peptide hormone adrenomedullin, soluble ST2, chemokine CX3CL1, surrogate marker of vasopressin, and others, are every year one step closer to being introduced into health practice. Over the past decades, significant progress has been made in the study of cardiovascular biomarkers. A key moment was the introduction of deter mining the concentration of natriuretic peptides used as markers for the diagnostic and prognostic evaluation of patients with heart failure. Currently, in order to search for novel markers for early diagnosis and risk stratification, studies have been conducted on the analysis of promising inflammatory marker tenascin-C (TNC) in cardiovascular patients. Data have been obtained that allow us to consider TNC as a tool for risk stratification and assessment of cardiovascular disease prognosis. The combination of TNC with other biological markers, in particular brain natriuretic peptide, may improve prognostic power. Nevertheless, serial testing to assess the prognosis and effectiveness of ongoing treatment, including in the conditions of a multimarker model, requires further research

The effect of differential rotation on Jupiter's low-degree even gravity moments

The close-by orbits of the ongoing Juno mission allow measuring with unprecedented accuracy Jupiter's low-degree even gravity moments J(2), J(4), J(6), and J(8). These can be used to better determine Jupiter's internal density profile and constrain its core mass. Yet the largest unknown on these gravity moments comes from the effect of differential rotation, which gives a degree of freedom unaccounted for by internal structure models. Here considering a wide range of possible internal flow structures and dynamical considerations, we provide upper bounds to the effect of dynamics (differential rotation) on the low-degree gravity moments. In light of the recent Juno gravity measurements and their small uncertainties, this allows differentiating between the various models suggested for Jupiter's internal structure.Israeli Ministry of Science; Minerva foundation; Federal German Ministry of Education and Research; Helen Kimmel Center for Planetary Science at the Weizmann Institute of Science; CNES; BSF; NSF; Juno project6 month embargo; Published Online: 19 June 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A Remnant Planetary Core In The Hot-Neptune desert

The interiors of giant planets remain poorly understood. Even for the planets in the Solar System, difficulties in observation lead to large uncertainties in the properties of planetary cores. Exoplanets that have undergone rare evolutionary processes provide a route to understanding planetary interiors. Planets found in and near the typically barren hot-Neptune ‘desert’1,2 (a region in mass–radius space that contains few planets) have proved to be particularly valuable in this regard. These planets include HD149026b3, which is thought to have an unusually massive core, and recent discoveries such as LTT9779b4 and NGTS-4b5, on which photoevaporation has removed a substantial part of their outer atmospheres. Here we report observations of the planet TOI-849b, which has a radius smaller than Neptune’s but an anomalously large mass of 39.1+2.7−2.6 Earth masses and a density of 5.2+0.7−0.8 grams per cubic centimetre, similar to Earth’s. Interior-structure models suggest that any gaseous envelope of pure hydrogen and helium consists of no more than 3.9+0.8−0.9 per cent of the total planetary mass. The planet could have been a gas giant before undergoing extreme mass loss via thermal self-disruption or giant planet collisions, or it could have avoided substantial gas accretion, perhaps through gap opening or late formation6. Although photoevaporation rates cannot account for the mass loss required to reduce a Jupiter-like gas giant, they can remove a small (a few Earth masses) hydrogen and helium envelope on timescales of several billion years, implying that any remaining atmosphere on TOI-849b is likely to be enriched by water or other volatiles from the planetary interior. We conclude that TOI-849b is the remnant core of a giant planet

Connecting Planetary Composition with Formation

The rapid advances in observations of the different populations of exoplanets, the characterization of their host stars and the links to the properties of their planetary systems, the detailed studies of protoplanetary disks, and the experimental study of the interiors and composition of the massive planets in our solar system provide a firm basis for the next big question in planet formation theory. How do the elemental and chemical compositions of planets connect with their formation? The answer to this requires that the various pieces of planet formation theory be linked together in an end-to-end picture that is capable of addressing these large data sets. In this review, we discuss the critical elements of such a picture and how they affect the chemical and elemental make up of forming planets. Important issues here include the initial state of forming and evolving disks, chemical and dust processes within them, the migration of planets and the importance of planet traps, the nature of angular momentum transport processes involving turbulence and/or MHD disk winds, planet formation theory, and advanced treatments of disk astrochemistry. All of these issues affect, and are affected by the chemistry of disks which is driven by X-ray ionization of the host stars. We discuss how these processes lead to a coherent end-to-end model and how this may address the basic question.Comment: Invited review, accepted for publication in the 'Handbook of Exoplanets', eds. H.J. Deeg and J.A. Belmonte, Springer (2018). 46 pages, 10 figure

Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?

One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131Irelated risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiationrelated risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer

Beyond the Hypercube:Evolutionary Accessibility of Fitness Landscapes with Realistic Mutational Networks

Evolutionary pathways describe trajectories of biological evolution in the space of different variants of organisms (genotypes). The probability of existence and the number of evolutionary pathways that lead from a given genotype to a better-adapted genotype are important measures of accessibility of local fitness optima and the reproducibility of evolution. Both quantities have been studied in simple mathematical models where genotypes are represented as binary sequences of two types of basic units, and the network of permitted mutations between the genotypes is a hypercube graph. However, it is unclear how these results translate to the biologically relevant case in which genotypes are represented by sequences of more than two units, for example four nucleotides (DNA) or 20 amino acids (proteins), and the mutational graph is not the hypercube. Here we investigate accessibility of the best-adapted genotype in the general case of K > 2 units. Using computer generated and experimental fitness landscapes we show that accessibility of the global fitness maximum increases with K and can be much higher than for binary sequences. The increase in accessibility comes from the increase in the number of indirect trajectories exploited by evolution for higher K. As one of the consequences, the fraction of genotypes that are accessible increases by three orders of magnitude when the number of units K increases from 2 to 16 for landscapes of size N ∼ 106 genotypes. This suggests that evolution can follow many different trajectories on such landscapes and the reconstruction of evolutionary pathways from experimental data might be an extremely difficult task