Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

Computerized general practice based networks yield comparable performance with sentinel data in monitoring epidemiological time-course of influenza-like illness and acute respiratory illness

<p>Abstract</p> <p>Background</p> <p>Computerized morbidity registration networks might serve as early warning systems in a time where natural epidemics such as the H₁N₁flu can easily spread from one region to another.</p> <p>Methods</p> <p>In this contribution we examine whether general practice based broad-spectrum computerized morbidity registration networks have the potential to act as a valid surveillance instrument of frequently occurring diseases. We compare general practice based computerized data assessing the frequency of influenza-like illness (ILI) and acute respiratory infections (ARI) with data from a well established case-specific sentinel network, the European Influenza Surveillance Scheme (EISS). The overall frequency and trends of weekly ILI and ARI data are compared using both networks.</p> <p>Results</p> <p>Detection of influenza-like illness and acute respiratory illness occurs equally fast in EISS and the computerized network. The overall frequency data for ARI are the same for both networks, the overall trends are similar, but the increases and decreases in frequency do not occur in exactly the same weeks. For ILI, the overall rate was slightly higher for the computerized network population, especially before the increase of ILI, the overall trend was almost identical and the increases and decreases occur in the same weeks for both networks.</p> <p>Conclusions</p> <p>Computerized morbidity registration networks are a valid tool for monitoring frequent occurring respiratory diseases and the detection of sudden outbreaks.</p

Detection of Biochemical Pathways by Probabilistic Matching of Phyletic Vectors

A phyletic vector, also known as a phyletic (or phylogenetic) pattern, is a binary representation of the presences and absences of orthologous genes in different genomes. Joint occurrence of two or more genes in many genomes results in closely similar binary vectors representing these genes, and this similarity between gene vectors may be used as a measure of functional association between genes. Better understanding of quantitative properties of gene co-occurrences is needed for systematic studies of gene function and evolution. We used the probabilistic iterative algorithm Psi-square to find groups of similar phyletic vectors. An extended Psi-square algorithm, in which pseudocounts are implemented, shows better sensitivity in identifying proteins with known functional links than our earlier hierarchical clustering approach. At the same time, the specificity of inferring functional associations between genes in prokaryotic genomes is strongly dependent on the pathway: phyletic vectors of the genes involved in energy metabolism and in de novo biosynthesis of the essential precursors tend to be lumped together, whereas cellular modules involved in secretion, motility, assembly of cell surfaces, biosynthesis of some coenzymes, and utilization of secondary carbon sources tend to be identified with much greater specificity. It appears that the network of gene coinheritance in prokaryotes contains a giant connected component that encompasses most biosynthetic subsystems, along with a series of more independent modules involved in cell interaction with the environment

Emergence and Modular Evolution of a Novel Motility Machinery in Bacteria

Bacteria glide across solid surfaces by mechanisms that have remained largely mysterious despite decades of research. In the deltaproteobacterium Myxococcus xanthus, this locomotion allows the formation stress-resistant fruiting bodies where sporulation takes place. However, despite the large number of genes identified as important for gliding, no specific machinery has been identified so far, hampering in-depth investigations. Based on the premise that components of the gliding machinery must have co-evolved and encode both envelope-spanning proteins and a molecular motor, we re-annotated known gliding motility genes and examined their taxonomic distribution, genomic localization, and phylogeny. We successfully delineated three functionally related genetic clusters, which we proved experimentally carry genes encoding the basal gliding machinery in M. xanthus, using genetic and localization techniques. For the first time, this study identifies structural gliding motility genes in the Myxobacteria and opens new perspectives to study the motility mechanism. Furthermore, phylogenomics provide insight into how this machinery emerged from an ancestral conserved core of genes of unknown function that evolved to gliding by the recruitment of functional modules in Myxococcales. Surprisingly, this motility machinery appears to be highly related to a sporulation system, underscoring unsuspected common mechanisms in these apparently distinct morphogenic phenomena

Divergence of selenocysteine tRNA recognition by archaeal and eukaryotic O-phosphoseryl-tRNASec kinase

Selenocysteine (Sec) biosynthesis in archaea and eukaryotes requires three steps: serylation of tRNASec by seryl-tRNA synthetase (SerRS), phosphorylation of Ser-tRNASec by O-phosphoseryl-tRNASec kinase (PSTK), and conversion of O-phosphoseryl-tRNASec (Sep-tRNASec) by Sep-tRNA:Sec-tRNA synthase (SepSecS) to Sec-tRNASec. Although SerRS recognizes both tRNASec and tRNASer species, PSTK must discriminate Ser-tRNASec from Ser-tRNASer. Based on a comparison of the sequences and secondary structures of archaeal tRNASec and tRNASer, we introduced mutations into Methanococcus maripaludis tRNASec to investigate how Methanocaldococcus jannaschii PSTK distinguishes tRNASec from tRNASer. Unlike eukaryotic PSTK, the archaeal enzyme was found to recognize the acceptor stem rather than the length and secondary structure of the D-stem. While the D-arm and T-loop provide minor identity elements, the acceptor stem base pairs G2-C71 and C3-G70 in tRNASec were crucial for discrimination from tRNASer. Furthermore, the A5-U68 base pair in tRNASer has some antideterminant properties for PSTK. Transplantation of these identity elements into the tRNASerUGA scaffold resulted in phosphorylation of the chimeric Ser-tRNA. The chimera was able to stimulate the ATPase activity of PSTK albeit at a lower level than tRNASec, whereas tRNASer did not. Additionally, the seryl moiety of Ser-tRNASec is not required for enzyme recognition, as PSTK efficiently phosphorylated Thr-tRNASec

A New Highly Conserved Antibiotic Sensing/Resistance Pathway in Firmicutes Involves an ABC Transporter Interplaying with a Signal Transduction System

Signal transduction systems and ABC transporters often contribute jointly to adaptive bacterial responses to environmental changes. In Bacillus subtilis, three such pairs are involved in responses to antibiotics: BceRSAB, YvcPQRS and YxdJKLM. They are characterized by a histidine kinase belonging to the intramembrane sensing kinase family and by a translocator possessing an unusually large extracytoplasmic loop. It was established here using a phylogenomic approach that systems of this kind are specific but widespread in Firmicutes, where they originated. The present phylogenetic analyses brought to light a highly dynamic evolutionary history involving numerous horizontal gene transfers, duplications and lost events, leading to a great variety of Bce-like repertories in members of this bacterial phylum. Based on these phylogenetic analyses, it was proposed to subdivide the Bce-like modules into six well-defined subfamilies. Functional studies were performed on members of subfamily IV comprising BceRSAB from B. subtilis, the expression of which was found to require the signal transduction system as well as the ABC transporter itself. The present results suggest, for the members of this subfamily, the occurrence of interactions between one component of each partner, the kinase and the corresponding translocator. At functional and/or structural levels, bacitracin dependent expression of bceAB and bacitracin resistance processes require the presence of the BceB translocator loop. Some other members of subfamily IV were also found to participate in bacitracin resistance processes. Taken together our study suggests that this regulatory mechanism might constitute an important common antibiotic resistance mechanism in Firmicutes. [Supplemental material is available online at http://www.genome.org.

Assessment of ecosystem services of an urbanized tropical estuary with a focus on habitats and scenarios

Tropical estuaries are one of the most valuable ecosystems on the planet because of the number of ecosystem services they provide. The increasing anthropogenic pressure to which these estuaries are subject has caused a reduction in their natural capital stock. Therefore, the application of a pragmatic and rational ecosystem-based management approach to sustainably manage the multiple ecosystem services provided by this ecosystem is necessary. The aim of our study is to present an approach that combines prospective scenarios with habitat-based perspective to assess the supply capacity of ecosystem services, plus determine the impact of protected areas in an urbanized tropical estuary. The current situation and two scenarios were generated to evaluate the capacity of habitats to supply ecosystem services. This type of assessment will allow the decision makers to visualize the effect of their choices or the occurrence of events which might produce significant changes in the estuary. Thus, over time, measures can be taken to sustain the supply of ecosystem services. We determined that the establishment of protected areas have a positive impact; however, the effect is not the same for all of them. Consequently, indicating that actions such as community participation, research, education, management planning and infrastructure development must accompany the development of a protected area

Aquarium Nitrification Revisited: Thaumarchaeota Are the Dominant Ammonia Oxidizers in Freshwater Aquarium Biofilters

Ammonia-oxidizing archaea (AOA) outnumber ammonia-oxidizing bacteria (AOB) in many terrestrial and aquatic environments. Although nitrification is the primary function of aquarium biofilters, very few studies have investigated the microorganisms responsible for this process in aquaria. This study used quantitative real-time PCR (qPCR) to quantify the ammonia monooxygenase (amoA) and 16S rRNA genes of Bacteria and Thaumarchaeota in freshwater aquarium biofilters, in addition to assessing the diversity of AOA amoA genes by denaturing gradient gel electrophoresis (DGGE) and clone libraries. AOA were numerically dominant in 23 of 27 freshwater biofilters, and in 12 of these biofilters AOA contributed all detectable amoA genes. Eight saltwater aquaria and two commercial aquarium nitrifier supplements were included for comparison. Both thaumarchaeal and bacterial amoA genes were detected in all saltwater samples, with AOA genes outnumbering AOB genes in five of eight biofilters. Bacterial amoA genes were abundant in both supplements, but thaumarchaeal amoA and 16S rRNA genes could not be detected. For freshwater aquaria, the proportion of amoA genes from AOA relative to AOB was inversely correlated with ammonium concentration. DGGE of AOA amoA genes revealed variable diversity across samples, with nonmetric multidimensional scaling (NMDS) indicating separation of freshwater and saltwater fingerprints. Composite clone libraries of AOA amoA genes revealed distinct freshwater and saltwater clusters, as well as mixed clusters containing both freshwater and saltwater amoA gene sequences. These results reveal insight into commonplace residential biofilters and suggest that aquarium biofilters may represent valuable biofilm microcosms for future studies of AOA ecology

Emergency vaccination of rabies under limited resources – combating or containing?

BACKGROUND: Rabies is the most important viral zoonosis from a global perspective. Worldwide efforts to combat the disease by oral vaccination of reservoirs have managed to eradicate wildlife rabies in large areas of central Europe and North-America. Thus, repeated vaccination has been discontinued recently on a geographical scale. However, as rabies has not yet been eradicated globally, a serious risk of re-introduction remains. What is the best spatial design for an emergency vaccination program – particularly if resources are limited? Either, we treat a circular area around the detected case and run the risk of infected hosts leaving the limited control area, because a sufficient immunisation level has not yet been built up. Or, initially concentrate the SAME resources in order to establish a protective ring which is more distant from the infected local area, and which then holds out against the challenge of the approaching epidemic. METHODS: We developed a simulation model to contrast the two strategies for emergency vaccination. The spatial-explicit model is based on fox group home-ranges, which facilitates the simulation of rabies spread to larger areas relevant to management. We used individual-based fox groups to follow up the effects of vaccination in a detailed manner. Thus, regionally – bait distribution orientates itself to standard schemes of oral immunisation programs and locally – baits are assigned to individual foxes. RESULTS: Surprisingly, putting the controlled area ring-like around the outbreak does not outperform the circular area of the same size centred on the outbreak. Only during the very first baitings, does the ring area result in fewer breakouts. But then as rabies is eliminated within the circle area, the respective ring area fails, due to the non-controlled inner part. We attempt to take advantage of the initially fewer breakouts beyond the ring when applying a mixed strategy. Therefore, after a certain number of baitings, the area under control was increased for both strategies towards the same larger circular area. The circle-circle strategy still outperforms the ring-circle strategy and analysis of the spatial-temporal disease spread reveals why: improving control efficacy by means of a mixed strategy is impossible in the field, due to the build-up time of population immunity. CONCLUSION: For practical emergency management of a new outbreak of rabies, the ring-like application of oral vaccination is not a favourable strategy at all. Even if initial resources are substantially low and there is a serious risk of rabies cases outside the limited control area, our results suggest circular application instead of ring vaccination