Emerging Patterns of ERW Injuries in Laos

The year 2016 marks the beginning of a new era for international development, with the adoption of seventeen Sustainable Development Goals (SDG) that will drive global development efforts until 2030. In post-conflict countries, humanitarian mine action will be an important enabler in achieving a number of SDGs, including goal 3: “ensure healthy lives and promote well-being for all at all ages.” Of particular relevance is target 3.9 of the SDGs, which specifies the need to reduce the number of deaths and illnesses from soil pollution and contamination. At present this relates primarily to indoor and outdoor air pollution. However, since explosive remnants of war (ERW) contamination can be directly attributed to a significant number of deaths and injuries in post-conflict countries, the inclusion of ERW is relevant. Demonstrating mine action’s contribution to target 3.9 requires accurate, reliable, and readily available ERW injury data, which will also allow for the appropriate allocation of resources to both ERW injury prevention and adequate access to emergency medical and rehabilitation services. As progress on goal 3 will be reported on through the health sector, SDGs provide an opportunity for mine action injury databases to link with national health information systems based on standardized, minimum reporting requirements for injuries using international standards, statistical principles, and global measurement methods

Microbiology: Mind the gaps in cellular evolution

Eukaryotic cells, with complex features such as membrane-bound nuclei, evolved from prokaryotic cells that lack these components. A newly identified prokaryotic group reveals intermediate steps in eukaryotic-cell evolution

Mechanisms that shape microbial pangenomes

Analyses of multiple whole-genome sequences from the same species have revealed that differences in gene content can be substantial, particularly in prokaryotes. Such variation has led to the recognition of pangenomes, the complete set of genes present in a species – consisting of core genes present in all individuals, and accessory genes whose presence is variable. Questions now arise about how pangenomes originate and evolve. We describe how gene content variation can arise as a result of the combination of several processes including random drift, selection, gain-loss balance, and the influence of ecological and epistatic interactions. We believe that identifying the contributions of these processes to pangenomes will need novel theoretical approaches and empirical data

Horizontal gene transfer as a source of conflict and cooperation in prokaryotes

Horizontal gene transfer (HGT) is one of the most important processes in prokaryote evolution. The sharing of DNA can spread neutral or beneficial genes, as well as genetic parasites across populations and communities, creating a large proportion of the variability acted on by natural selection. Here, we highlight the role of HGT in enhancing the opportunities for conflict and cooperation within and between prokaryote genomes. We discuss how horizontally acquired genes can cooperate or conflict both with each other and with a recipient genome, resulting in signature patterns of gene co-occurrence, avoidance, and dependence. We then describe how interactions involving horizontally transferred genes may influence cooperation and conflict at higher levels (populations, communities, and symbioses). Finally, we consider the benefits and drawbacks of HGT for prokaryotes and its fundamental role in understanding conflict and cooperation from the gene-gene to the microbiome level

Considering Intra-individual Genetic Heterogeneity to Understand Biodiversity

In this chapter, I am concerned with the concept of Intra-individual Genetic Hetereogeneity (IGH) and its potential influence on biodiversity estimates. Definitions of biological individuality are often indirectly dependent on genetic sampling -and vice versa. Genetic sampling typically focuses on a particular locus or set of loci, found in the the mitochondrial, chloroplast or nuclear genome. If ecological function or evolutionary individuality can be defined on the level of multiple divergent genomes, as I shall argue is the case in IGH, our current genetic sampling strategies and analytic approaches may miss out on relevant biodiversity. Now that more and more examples of IGH are available, it is becoming possible to investigate the positive and negative effects of IGH on the functioning and evolution of multicellular individuals more systematically. I consider some examples and argue that studying diversity through the lens of IGH facilitates thinking not in terms of units, but in terms of interactions between biological entities. This, in turn, enables a fresh take on the ecological and evolutionary significance of biological diversity

Contemporary update of cancer control after radical prostatectomy in the UK

Despite a significant increase of the number of radical prostatectomies (RPs) to treat organ-confined prostate cancer, there is very limited documentation of its oncological outcome in the UK. Pathological stage distribution and changes of outcome have not been audited on a consistent basis. We present the results of a multicentre review of postoperative predictive variables and prostatic-specific antigen (PSA) recurrence after RP for clinically organ-confined disease. In all, 854 patient's notes were audited for staging parameters and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment as well as patients with incomplete data and follow-up were excluded. Median follow-up was 52 months for the remaining 705 patients. The median PSA was 10 ng ml−1. A large migration towards lower PSA and stage was seen. This translated into improved PSA survival rates. Overall Kaplan–Meier PSA recurrence-free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA recurrence-free survival probability for PSA ranges 20 ng ml−1 was 0.82, 0.73, 0.59 and 0.20, respectively (log rank, P<0.0001). PSA recurrence-free survival probabilities for pathological Gleason grade 2–4, 5 and 6, 7 and 8–10 at 5 years were 0.84, 0.66, 0.55 and 0.21, respectively (log rank, P<0.0001). Similarly, 5-year PSA recurrence-free survival probabilities for pathological stages T2a, T2b, T3a, T3b and T4 were 0.82, 0.78, 0.48, 0.23 and 0.12, respectively (log rank, P=0.0012). Oncological outcome after RP has improved over time in the UK. PSA recurrence-free survival estimates are less optimistic compared to quoted survival figures in the literature. Survival figures based on pathological stage and Gleason grade may serve to counsel patients postoperatively and to stratify patients better for adjuvant treatment

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

N-gram analysis of 970 microbial organisms reveals presence of biological language models

<p>Abstract</p> <p>Background</p> <p>It has been suggested previously that genome and proteome sequences show characteristics typical of natural-language texts such as "signature-style" word usage indicative of authors or topics, and that the algorithms originally developed for natural language processing may therefore be applied to genome sequences to draw biologically relevant conclusions. Following this approach of 'biological language modeling', statistical n-gram analysis has been applied for comparative analysis of whole proteome sequences of 44 organisms. It has been shown that a few particular amino acid n-grams are found in abundance in one organism but occurring very rarely in other organisms, thereby serving as genome signatures. At that time proteomes of only 44 organisms were available, thereby limiting the generalization of this hypothesis. Today nearly 1,000 genome sequences and corresponding translated sequences are available, making it feasible to test the existence of biological language models over the evolutionary tree.</p> <p>Results</p> <p>We studied whole proteome sequences of 970 microbial organisms using n-gram frequencies and cross-perplexity employing the Biological Language Modeling Toolkit and Patternix Revelio toolkit. Genus-specific signatures were observed even in a simple unigram distribution. By taking statistical n-gram model of one organism as reference and computing cross-perplexity of all other microbial proteomes with it, cross-perplexity was found to be predictive of branch distance of the phylogenetic tree. For example, a 4-gram model from proteome of <it>Shigellae flexneri 2a</it>, which belongs to the <it>Gammaproteobacteria </it>class showed a self-perplexity of 15.34 while the cross-perplexity of other organisms was in the range of 15.59 to 29.5 and was proportional to their branching distance in the evolutionary tree from <it>S. flexneri</it>. The organisms of this genus, which happen to be pathotypes of <it>E.coli</it>, also have the closest perplexity values with <it>E. coli.</it></p> <p>Conclusion</p> <p>Whole proteome sequences of microbial organisms have been shown to contain particular n-gram sequences in abundance in one organism but occurring very rarely in other organisms, thereby serving as proteome signatures. Further it has also been shown that perplexity, a statistical measure of similarity of n-gram composition, can be used to predict evolutionary distance within a genus in the phylogenetic tree.</p

Conflict between Translation Initiation and Elongation in Vertebrate Mitochondrial Genomes

The strand-biased mutation spectrum in vertebrate mitochondrial genomes results in an AC-rich L-strand and a GT-rich H-strand. Because the L-strand is the sense strand of 12 protein-coding genes out of the 13, the third codon position is overall strongly AC-biased. The wobble site of the anticodon of the 22 mitochondrial tRNAs is either U or G to pair with the most abundant synonymous codon, with only one exception. The wobble site of Met-tRNA is C instead of U, forming the Watson-Crick match with AUG instead of AUA, the latter being much more frequent than the former. This has been attributed to a compromise between translation initiation and elongation; i.e., AUG is not only a methionine codon, but also an initiation codon, and an anticodon matching AUG will increase the initiation rate. However, such an anticodon would impose selection against the use of AUA codons because AUA needs to be wobble-translated. According to this translation conflict hypothesis, AUA should be used relatively less frequently compared to UUA in the UUR codon family. A comprehensive analysis of mitochondrial genomes from a variety of vertebrate species revealed a general deficiency of AUA codons relative to UUA codons. In contrast, urochordate mitochondrial genomes with two tRNA(Met) genes with CAU and UAU anticodons exhibit increased AUA codon usage. Furthermore, six bivalve mitochondrial genomes with both of their tRNA-Met genes with a CAU anticodon have reduced AUA usage relative to three other bivalve mitochondrial genomes with one of their two tRNA-Met genes having a CAU anticodon and the other having a UAU anticodon. We conclude that the translation conflict hypothesis is empirically supported, and our results highlight the fine details of selection in shaping molecular evolution

Eukaryotic Evolutionary Transitions Are Associated with Extreme Codon Bias in Functionally-Related Proteins

Codon bias in the genome of an organism influences its phenome by changing the speed and efficiency of mRNA translation and hence protein abundance. We hypothesized that differences in codon bias, either between-species differences in orthologous genes, or within-species differences between genes, may play an evolutionary role. To explore this hypothesis, we compared the genome-wide codon bias in six species that occupy vital positions in the Eukaryotic Tree of Life. We acquired the entire protein coding sequences for these organisms, computed the codon bias for all genes in each organism and explored the output for relationships between codon bias and protein function, both within- and between-lineages. We discovered five notable coordinated patterns, with extreme codon bias most pronounced in traits considered highly characteristic of a given lineage. Firstly, the Homo sapiens genome had stronger codon bias for DNA-binding transcription factors than the Saccharomyces cerevisiae genome, whereas the opposite was true for ribosomal proteins – perhaps underscoring transcriptional regulation in the origin of complexity. Secondly, both mammalian species examined possessed extreme codon bias in genes relating to hair – a tissue unique to mammals. Thirdly, Arabidopsis thaliana showed extreme codon bias in genes implicated in cell wall formation and chloroplast function – which are unique to plants. Fourthly, Gallus gallus possessed strong codon bias in a subset of genes encoding mitochondrial proteins – perhaps reflecting the enhanced bioenergetic efficiency in birds that co-evolved with flight. And lastly, the G. gallus genome had extreme codon bias for the Ciliary Neurotrophic Factor – which may help to explain their spontaneous recovery from deafness. We propose that extreme codon bias in groups of genes that encode functionally related proteins has a pathway-level energetic explanation