Horizontal gene transfer of zinc and non-zinc forms of bacterial ribosomal protein S4

<p>Abstract</p> <p>Background</p> <p>The universal ribosomal protein S4 is essential for the initiation of small subunit ribosomal assembly and translational accuracy. Being part of the information processing machinery of the cell, the gene for S4 is generally thought of as being inherited vertically and has been used in concatenated gene phylogenies. Here we report the evolution of ribosomal protein S4 in relation to a broad sharing of zinc/non-zinc forms of the gene and study the scope of horizontal gene transfer (HGT) of S4 during bacterial evolution.</p> <p>Results</p> <p>In this study we present the complex evolutionary history of ribosomal protein S4 using 660 bacterial genomes from 16 major bacterial phyla. According to conserved characteristics in the sequences, S4 can be classified into C+ (zinc-binding) and C- (zinc-free) variants, with 26 genomes (mainly from the class <it>Clostridia</it>) containing genes for both. A maximum likelihood phylogenetic tree of the S4 sequences was incongruent with the standard bacterial phylogeny, indicating a departure from strict vertical inheritance. Further analysis using the genome content near the S4 genes, which are usually located in a conserved gene cluster, showed not only that HGT of the C- gene had occurred at various stages of bacterial evolution, but also that both the C- and C+ genes were present before the individual phyla diverged. To explain the latter, we theorize that a gene pool existed early in bacterial evolution from which bacteria could sample S4 gene variants, according to environmental conditions. The distribution of the C+/- variants for seven other zinc-binding ribosomal proteins in these 660 bacterial genomes is consistent with that seen for S4 and may shed light on the evolutionary pressures involved.</p> <p>Conclusion</p> <p>The complex history presented for "core" protein S4 suggests the existence of a gene pool before the emergence of bacterial lineages and reflects the pervasive nature of HGT in subsequent bacterial evolution. This has implications for both theoretical models of evolution and practical applications of phylogenetic reconstruction as well as the control of zinc economy in bacterial cells.</p

Heterogeneities in infection outcomes across species: sex and tissue differences in virus susceptibility

This is the final version. Available on open access from the PCI organisation via the DOI in this recordData availability: All data and scripts are available at http://doi.org/10.6084/m9.figshare.21437223Species vary in their susceptibility to pathogens, and this can alter the ability of a pathogen to infect a novel host. However, many factors can generate heterogeneity in infection outcomes, obscuring our ability to understand pathogen emergence. Such heterogeneities can alter the consistency of responses across individuals and host species. For example, sexual dimorphism in susceptibility means males are often intrinsically more susceptible than females (although this can vary by host and pathogen). Further, we know little about whether the tissues infected by a pathogen in one host are the same in another species, and how this relates to the harm a pathogen does to its host. Here, we first take a comparative approach to examine sex differences in susceptibility across 31 species of Drosophilidae infected with Drosophila C Virus (DCV). We found a strong positive inter-specific correlation in viral load between males and females, with a close to 1:1 relationship, suggesting that susceptibility to DCV across species is not sex specific. Next, we made comparisons of the tissue tropism of DCV across seven species of fly. We found differences in viral load between the tissues of the seven host species, but no evidence of tissues showing different patterns of susceptibility in different host species. We conclude that, in this system, patterns of viral infectivity across host species are robust between males and females, and susceptibility in a given host is general across tissue types.Wellcome TrustRoyal Societ

Vertex functions for d-wave mesons in the light-front approach

While the light-front quark model (LFQM) is employed to calculate hadronic transition matrix elements, the vertex functions must be pre-determined. In this work we derive the vertex functions for all d-wave states in this model. Especially, since both of $^3D_1$ and $^3S_1$ are $1^{--}$ mesons, the Lorentz structures of their vertex functions are the same. Thus when one needs to study the processes where $^3D_1$ is involved, all the corresponding formulas for $^3S_1$ states can be directly applied, only the coefficient of the vertex function should be replaced by that for $^3D_1$. The results would be useful for studying the newly observed resonances which are supposed to be d-wave mesons and furthermore the possible 2S-1D mixing in $\psi'$ with the LFQM.Comment: 12 pages, 2 figures, some typos corrected and more discussions added. Accepted by EPJ

Between virus correlations in the outcome of infection across host species: Evidence of virus by host species interactions

This is the final version. Available from Wiley via the DOI in this record. Virus host shifts are a major source of outbreaks and emerging infectious diseases, and predicting the outcome of novel host and virus interactions remains a key challenge for virus research. The evolutionary relationships between host species can explain variation in transmission rates, virulence, and virus community composition between hosts, but it is unclear if correlations exist between related viruses in infection traits across novel hosts. Here, we measure correlations in viral load of four Cripavirus isolates across experimental infections of 45 Drosophilidae host species. We find positive correlations between every pair of viruses tested, suggesting that some host clades show broad susceptibility and could act as reservoirs and donors for certain types of viruses. Additionally, we find evidence of virus by host species interactions, highlighting the importance of both host and virus traits in determining the outcome of virus host shifts. Of the four viruses tested here, those that were more closely related tended to be more strongly correlated, providing tentative evidence that virus evolutionary relatedness may be a useful proxy for determining the likelihood of novel virus emergence, which warrants further research.Wellcome TrustRoyal SocietyNatural Environment Research Counci

Glue ear, hearing loss and IQ:an association moderated by the child's home environment

BACKGROUND: Glue ear or otitis media with effusion (OME) is common in children and may be associated with hearing loss (HL). For most children it has no long lasting effects on cognitive development but it is unclear whether there are subgroups at higher risk of sequelae. OBJECTIVES: To examine the association between a score comprising the number of times a child had OME and HL (OME/HL score) in the first four/five years of life and IQ at age 4 and 8. To examine whether any association between OME/HL and IQ is moderated by socioeconomic, child or family factors. METHODS: Prospective, longitudinal cohort study: the Avon Longitudinal Study of Parents and Children (ALSPAC). 1155 children tested using tympanometry on up to nine occasions and hearing for speech (word recognition) on up to three occasions between age 8 months and 5 years. An OME/HL score was created and associations with IQ at ages 4 and 8 were examined. Potential moderators included a measure of the child's cognitive stimulation at home (HOME score). RESULTS: For the whole sample at age 4 the group with the highest 10% OME/HL scores had performance IQ 5 points lower [95% CI -9, -1] and verbal IQ 6 points lower [95% CI -10, -3] than the unaffected group. By age 8 the evidence for group differences was weak. There were significant interactions between OME/HL and the HOME score: those with high OME/HL scores and low 18 month HOME scores had lower IQ at age 4 and 8 than those with high OME/HL scores and high HOME scores. Adjusted mean differences ranged from 5 to 8 IQ points at age 4 and 8. CONCLUSIONS: The cognitive development of children from homes with lower levels of cognitive stimulation is susceptible to the effects of glue ear and hearing loss

A study on the safety and efficacy of reveglucosidase alfa in patients with late-onset Pompe disease.

BackgroundLate-onset Pompe disease is a rare genetic neuromuscular disorder caused by lysosomal acid alpha-glucosidase (GAA) deficiency that ultimately results in mobility loss and respiratory failure. Current enzyme replacement therapy with recombinant human (rh)GAA has demonstrated efficacy in subjects with late-onset Pompe disease. However, long-term effects of rhGAA on pulmonary function have not been observed, likely related to inefficient delivery of rhGAA to skeletal muscle lysosomes and associated deficits in the central nervous system. To address this limitation, reveglucosidase alfa, a novel insulin-like growth factor 2 (IGF2)-tagged GAA analogue with improved lysosomal uptake, was developed. This study evaluated the pharmacokinetics, safety, and exploratory efficacy of reveglucosidase alfa in 22 subjects with late-onset Pompe disease who were previously untreated with rhGAA.ResultsReveglucosidase alfa plasma concentrations increased linearly with dose, and the elimination half-life was &lt;1.2 h. Eighteen of 22 subjects completed 72 weeks of treatment. The most common adverse events were hypoglycemia (63%), dizziness, fall, headache, and nausea (55% for each). Serious adverse events included hypersensitivity (n = 1), symptomatic hypoglycemia (n = 2), presyncope (n = 1), and acute cardiac failure (n = 1). In the dose-escalation study, all treated subjects tested positive for anti-reveglucosidase alfa, anti-rhGAA, anti-IGF1, and anti-IGF2 antibodies at least once. Subjects receiving 20 mg/kg of reveglucosidase alfa demonstrated increases in predicted maximum inspiratory pressure (13.9%), predicted maximum expiratory pressure (8.0%), forced vital capacity (-0.4%), maximum voluntary ventilation (7.4 L/min), and mean absolute walking distance (22.3 m on the 6-min walk test) at 72 weeks.ConclusionsAdditional studies are needed to further assess the safety and efficacy of this approach. Improvements in respiratory muscle strength, lung function, and walking endurance in subjects with LOPD may make up for the risk of hypersensitivity reactions and hypoglycemia. Reveglucosidase alfa may provide a new treatment option for patients with late-onset Pompe disease.Trial registrationISRCTN01435772 and ISRCTN01230801 , registered 27 October 2011

A Convex Geodesic Selective Model for Image Segmentation

Selective segmentation is an important application of image processing. In contrast to global segmentation in which all objectsare segmented, selective segmentation is used to isolate specific objects in an image and is of particular interest in medicalimaging—permitting segmentation and review of a single organ. An important consideration is to minimise the amount of userinput to obtain the segmentation; this differs from interactive segmentation in which more user input is allowed than selectivesegmentation. To achieve selection, we propose a selective segmentation model which uses the edge-weighted geodesicdistance from a marker set as a penalty term. It is demonstrated that this edge-weighted geodesic penalty term improveson previous selective penalty terms. A convex formulation of the model is also presented, allowing arbitrary initialisation.It is shown that the proposed model is less parameter dependent and requires less user input than previous models. Furthermodifications are made to the edge-weighted geodesic distance term to ensure segmentation robustness to noise and blur. Wecan show that the overall Euler–Lagrange equation admits a unique viscosity solution. Numerical results show that the resultis robust to user input and permits selective segmentations that are not possible with other models