Fitness effects of CTX-M-15-encoding IncF plasmids on their native Escherichia coli ST131 H30Rx hosts

Objectives: The objective of this study was to investigate effects of large CTX-M-15-encoding IncF plasmids on the fitness of their native E. coli ST131 H30Rx hosts in order to understand possible plasmid-host coevolution. Methods: We selected five E. coli ST131 H30Rx strains of diverse origin, each carrying a multireplicon IncF plasmid encoding the gene blaCTX-M-15. The plasmid was eliminated from each isolate by displacement using an incompatible plasmid vector pMDP5_cureEC958. Whole-genome sequencing (WGS) was performed to obtain complete chromosome and plasmid sequences of wild-type isolates and to detect chromosomal mutations in plasmid-free strains. Competition assays were conducted to determine the relative fitness of plasmid-free clones compared to the corresponding wild-type isolates. Results: We were able to successfully eliminate the IncF plasmids from all of the wild-type strains using the curing vector pMDP5_cureEC958. The chromosomes of plasmid-free clones contained zero to six point mutations. Plasmid-free strains of three isolates showed no significant difference in relative fitness compared to the corresponding plasmid-free strains. In the two remaining isolates, the plasmids produced a small but significant fitness cost. Conclusion: We conclude that IncF plasmids produce moderate fitness effects in their E. coli ST131 H30Rx hosts. This fitness compatibility is likely to promote the maintenance of antibiotic resistance in this worrisome E. coli lineage.

Fruit carbonate in Lithospermeae: 14C, stable isotope composition and potential as a paleoenvrionmental proxy

<p>The tribe Lithospermeae (fam. Boraginaceae) represents one of very few taxa vascular plants that accumulate appreciable amounts of calcium carbonate in their tissues. The CaCO<sub>3</sub> is localized in the pericarp sclerenchyma, which makes their small fruits (nutlets) mechanically durable and provides their good preservation in sediments and cultural layers. Fossil Lithospermeae fruits appear as whitish, slightly elongated entities, 3-5 mm in length.  At archaeological sites, the nutlets can be of diverse origin: in most contexts they represent carpological evidence for weed flora of the past, however, some findings suggest that they were used for decorative purposes (beads etc.).  </p><p>Here we overview the potential use of fruit carbonate of Lithospermeae in paleoecological research.   </p><p><sup>14</sup>C-dating: Fruit carbonate of the taxon can be successfully dated with radiocarbon.  </p><p>The <sup>14</sup>C concentration in the CaCO<sub>3</sub> fraction of modern nutlets is well-correlated to the recent atmospheric <sup>14</sup>C levels. Radiocarbon ages of old nutlets are in good correspondence with the age ranges of archaeological contexts. Obviously, fruit carbonate can represent a geochemically closed system for millennia in sediment environments.               </p><p>δ<sup>18</sup>O values: Our data based on an array of herbarium exemplars of Lithospermeae, suggest that the δ<sup>18</sup>O of fruit carbonate is distinctively sensitive to the amount of atmospheric precipitation during the warm season. The degree of correlation between δ<sup>18</sup>O and local air temperatures is lower.</p><p>We further performed an experiment on gromwell (Buglossoides arvensis (L.) I.M.Johnst), irrigated by water with different oxygen isotope signatures. The δ<sup>18</sup>O values of fruit CaCO<sub>3 </sub>showed correlation to the δ<sup>18</sup>O of irrigation water. The oxygen isotope fractionation in fruit carbonate turned out to be surprisingly low with 1000lnα = 4.72±3.49, which is relatively close to foraminiferal CaCO<sub>3</sub>.</p><p> δ<sup>13</sup>C values: In contrast to the oxygen isotope signature, we did not find a strong correlation of the δ<sup>13</sup>C values of fruit carbonate to precipitation and temperature.  However, the photosynthetic origin of carbon in fruit CaCO<sub>3</sub> admits a possibility of some links of δ<sup>13</sup>C to ambient factors.  </p><p>   </p>

A Multi-dimensional Integrative Scoring Framework for Predicting Functional Regions in the Human Genome

Attempts to identify and prioritize functional DNA elements in coding and noncoding regions, particularly through use of in silico functional annotation data, continue to increase in popularity. However, specific functional roles may vary widely from one variant to another, making it challenging to summarize different aspects of variant function. Here we propose Multi-dimensional Annotation Class Integrative Estimation (MACIE), an unsupervised multivariate mixed model framework capable of integrating annotations of diverse origin to assess multi-dimensional functional roles for both coding and noncoding variants. Unlike existing one-dimensional scoring methods, MACIE views variant functionality as a composite attribute encompassing multiple different characteristics, and estimates the joint posterior functional probability vector of each genomic position, a quantity that offers richer and more interpretable information in the presence of multiple aspects of functionality. Applied to a variety of independent coding and non-coding datasets, MACIE demonstrates powerful and robust performance in discriminating between functional and non-functional variants. We also show an application of MACIE to fine-mapping using lipids GWAS summary statistics data from the European Network for Genetic and Genomic Epidemiology Consortium.

Isolation and Characterization of Enterococcus faecalis-Infecting Bacteriophages From Different Cheese Types

Enterococci are a diverse group of Gram-positive, lactic acid bacteria (LAB). They are found in many environments, including fermented foods, in which they could constitute a health threat since they produce biogenic amines, which consumption can lead to intoxication. Moreover, enterococci has also emerged as an important hospital-acquired pathogens via its acquisition of antimicrobial resistance. Bacteriophages possess features that make them optimal biotechnological weapons for controlling bacterial growth in disease and food spoilage contexts. However, no silver bullet bacteriophage exists that can eliminate all the undesirable bacteria in a complex environment. Rather, a combination of phages with different host ranges would be required which implies the need for large collections of diverse phages. This work reports the isolation of several Enterococcus faecalis-infecting bacteriophages from different types of cheese, along with the range of E. faecalis strains of diverse origin (from dairy to clinical environments) they are able to infect. The isolated phages showed a large diversity regarding the number and origin of strains they infect. Some of these phages were subjected to morphological and genomic characterization which confirmed their diversity and showed they belong to different families and genera. The present findings increase the potential arsenal for the bacteriophage-based biocontrol of harmful E. faecalis populations.

Funerary Practices as a Testimony of Ideology in Western Linearbandkeramik Culture

The Linearbandkeramik (LBK) is behind the spread of the Neolithic way of life in a large part of Western Europe. This period is often regarded as the beginning of social inequalities whose ideological frameworks deserve to be highlighted. According to social anthropologists, funerary practices are relevant for this debate as they reflect the symbolic thought in relation to death. In addition, as they are perpetuated by the living, funerary practices are pertinent in addressing the ideological values, symbolic systems, and thoughts that support social organisation. Whilst examining how grave goods are allocated amongst the LBK population, we have identified a small group of dominant men characterised by a specific burial kit (adzes, arrows, lighter set, and red deer antlers), a richer protein intake in diet, and their local origin. Comparing them to other social categories characterised by minor marking of identity in grave goods, poorer protein intake in diet, and of diverse origin, we aim to explore the ideological frameworks and values sustaining the social LBK system. LBK dominant ideology appears to revolve around hunting and exploits in warfare, manhood, and virility, in short around violent behaviours perhaps linked to a territorial competition.

Therapeutic Approaches to Employ Monoclonal Antibody for Cancer Treatment

With the evolution of the tissue system and division of function among differentiated cells/tissues, the property of controlled cell growth also evolved in animals. It is when this very control is lost that cancers develop. The immune system's ability to distinguish between self and non-self is central to impeding cancer progression. However, cancer cells in time can develop multiple ways of escaping immune control. Even today, cancer remains a disease of baffling complexity on account of its diverse origin and pathogenesis. Classical methods like surgery, radiation, and chemotherapy have failed to make the cut as idyllic therapy, especially considering the encumbering side-effects and high failure rate. Alternative therapeutic strategies that exploit the immune system itself have proved promising. One of these is monoclonal antibody therapy. In this chapter, the relationship between the immune system and cancer and various forms of immunotherapy are discussed in detail.

Hybridisation and introgression of native and foreign Sorbus tree species in unique environments of protected mountainous areas

Hybridisation and introgression are important processes influencing the genetic diversity and evolution of species. These processes are of particular importance in protected areas, where they can lead to the formation of hybrids between native and foreign species and may ultimately result in the loss of parental species from their natural range. Despite their importance, the contribution of hybridisation and introgression to genetic diversity in Sorbus genus remains not fully recognised. We analysed the genetic and morphological variability of several Sorbus species including native (Sorbus aria), foreign (S. intermedia) and potentially hybrid (S. carpatica) individuals from the Polish Carpathian range. Patterns of variation at 13 nuclear microsatellite loci show hybridisation between the tested species and confirm the existence of the hybrid form Sorbus carpatica. Biometric analysis on leaves, based of ten metric features and three parameters, identified several characters for preliminary taxonomic classification, however none of them could be used as a fully diagnostic marker for faultless annotation of Sorbus intermedia and S. carpatica. The genetic structure analysis indicated complex patterns of population differentiation and its diverse origin. The results allow assessment of genetic variation and identification of parental species participating in hybridisation. This knowledge will advance the management of genetic diversity and development of conservation strategies for efficient maintenance of the unique protected ecosystem.

Exploring the genetic variability and diversity of pearl millet core collection germplasm for grain nutritional traits improvement

Improving essential nutrient content in staple food crops through biofortification breeding can overcome the micronutrient malnutrition problem. Genetic improvement depends on the availability of genetic variability in the primary gene pool. This study was aimed to ascertain the magnitude of variability in a core germplasm collection of diverse origin and predict pearl millet biofortification prospects for essential micronutrients. Germplasm accessions were evaluated in field trials at ICRISAT, India. The accessions differed significantly for all micronutrients with over two-fold variation for Fe (34–90 mg kg−1), Zn (30–74 mg kg−1), and Ca (85–249 mg kg−1). High estimates of heritability (> 0.81) were observed for Fe, Zn, Ca, P, Mo, and Mg. The lower magnitude of genotype (G) × environment (E) interaction observed for most of the traits implies strong genetic control for grain nutrients. The top-10 accessions for each nutrient and 15 accessions, from five countries for multiple nutrients were identified. For Fe and Zn, 39 accessions, including 15 with multiple nutrients, exceeded the Indian cultivars and 17 of them exceeded the biofortification breeding target for Fe (72 mg kg−1). These 39 accessions were grouped into 5 clusters. Most of these nutrients were positively and significantly associated among themselves and with days to 50% flowering and 1000-grain weight (TGW) indicating the possibility of their simultaneous improvement in superior agronomic background. The identified core collection accessions rich in specific and multiple-nutrients would be useful as the key genetic resources for developing biofortified and agronomically superior cultivars.

Characterization of Hormone-Dependent Pathways in Six Human Prostate-Cancer Cell Lines: A Gene-Expression Study

Prostate cancer (PCa), the most incident cancer in men, is tightly regulated by endocrine signals. A number of different PCa cell lines are commonly used for in vitro experiments, but these are of diverse origin, and have very different cell-proliferation rates and hormone-response capacities. By analyzing the gene-expression pattern of main hormone pathways, we systematically compared six PCa cell lines and parental primary cells. We compared these cell lines (i) with each other and (ii) with PCa tissue samples from 11 patients. We found major differences in the gene-expression levels of androgen, insulin, estrogen, and oxysterol signaling between PCa tissue and cell lines, and between different cell lines. Our systematic characterization gives researchers a solid basis to choose the appropriate PCa cell model for the hormone pathway of interest.