A multidisciplinary approach to the implementation of non-pharmacological strategies to manage infant pain

Hills E., Rosenberg J., Banfield N., Harding C. A multidisciplinary approach to the implementation of non-pharmacological strategies to manage infant pain. Infant 2020; 16(2): 78-81. 1. Newborn infants are capable of experiencing pain. 2. Infants requiring specialist hospital care are likely to experience painful medical procedures. 3. Unmanaged pain has a long-lasting impact on an infant’s behaviour and physiological status

mADP-RTs: versatile virulence factors from bacterial pathogens of plants and mammals

Mono ADP-ribosyltransferases (mADP-RTs) are a family of enzymes that cleave NAD+ and covalently attach the ADP-ribosyl moiety to target proteins. mADP-RTs are well established as important virulence factors of bacteria that infect mammals. Cholera toxin, pertussis toxin, and diphtheria toxin are three of the best-known examples of mADP-RTs. They modify host target proteins in order to promote infection and/or killing of the host cell. Despite low sequence similarity at the primary amino acid level, mADP-RTs share a conserved core catalytic fold and structural biology has made important contributions to elucidating how mADP-RTs modify mammalian host targets. Recently, mADP-RTs were shown to be present in plant pathogenic bacteria, suggesting that mADP-RTs are also important virulence factors of plant pathogens. Crystal structures of plant pathogenic bacterial mADP-RTs are also now available. Here we review the structure/function of mADP-RTs from pathogens of mammals and plants, highlighting both commonalities and differences

Radio galaxies and their magnetic fields out to z <= 3

We present polarisation properties at $1.4\,$GHz of two separate extragalactic source populations: passive quiescent galaxies and luminous quasar-like galaxies. We use data from the {\it Wide-Field Infrared Survey Explorer} data to determine the host galaxy population of the polarised extragalactic radio sources. The quiescent galaxies have higher percentage polarisation, smaller radio linear size, and $1.4\,$GHz luminosity of $6\times10^{21}<L_{\rm 1.4}<7\times10^{25}\,$W Hz$^{-1}$, while the quasar-like galaxies have smaller percentage polarisation, larger radio linear size at radio wavelengths, and a $1.4\,$GHz luminosity of $9\times10^{23}<L_{\rm 1.4}<7\times10^{28}\,$W Hz$^{-1}$, suggesting that the environment of the quasar-like galaxies is responsible for the lower percentage polarisation. Our results confirm previous studies that found an inverse correlation between percentage polarisation and total flux density at $1.4\,$GHz. We suggest that the population change between the polarised extragalactic radio sources is the origin of this inverse correlation and suggest a cosmic evolution of the space density of quiescent galaxies. Finally, we find that the extragalactic contributions to the rotation measures (RMs) of the nearby passive galaxies and the distant quasar-like galaxies are different. After accounting for the RM contributions by cosmological large-scale structure and intervening Mg\,{II} absorbers we show that the distribution of intrinsic RMs of the distant quasar-like sources is at most four times as wide as the RM distribution of the nearby quiescent galaxies, if the distribution of intrinsic RMs of the WISE-Star sources itself is at least several rad m$^{-2}$ wide.Comment: 12 pages, 8 figures, accepted for publication into MNRA

Structural and biochemical studies of an NB-ARC domain from a plant NLR immune receptor.

Plant NLRs are modular immune receptors that trigger rapid cell death in response to attempted infection by pathogens. A highly conserved nucleotide-binding domain shared with APAF-1, various R-proteins and CED-4 (NB-ARC domain) is proposed to act as a molecular switch, cycling between ADP (repressed) and ATP (active) bound forms. Studies of plant NLR NB-ARC domains have revealed functional similarities to mammalian homologues, and provided insight into potential mechanisms of regulation. However, further advances have been limited by difficulties in obtaining sufficient yields of protein suitable for structural and biochemical techniques. From protein expression screens in Escherichia coli and Sf9 insect cells, we defined suitable conditions to produce the NB-ARC domain from the tomato NLR NRC1. Biophysical analyses of this domain showed it is a folded, soluble protein. Structural studies revealed the NRC1 NB-ARC domain had co-purified with ADP, and confirmed predicted structural similarities between plant NLR NB-ARC domains and their mammalian homologues

Unusual Metabolism and Hypervariation in the Genome of a Gracilibacterium (BD1-5) from an Oil-Degrading Community.

The candidate phyla radiation (CPR) comprises a large monophyletic group of bacterial lineages known almost exclusively based on genomes obtained using cultivation-independent methods. Within the CPR, Gracilibacteria (BD1-5) are particularly poorly understood due to undersampling and the inherent fragmented nature of available genomes. Here, we report the first closed, curated genome of a gracilibacterium from an enrichment experiment inoculated from the Gulf of Mexico and designed to investigate hydrocarbon degradation. The gracilibacterium rose in abundance after the community switched to dominance by Colwellia Notably, we predict that this gracilibacterium completely lacks glycolysis, the pentose phosphate and Entner-Doudoroff pathways. It appears to acquire pyruvate, acetyl coenzyme A (acetyl-CoA), and oxaloacetate via degradation of externally derived citrate, malate, and amino acids and may use compound interconversion and oxidoreductases to generate and recycle reductive power. The initial genome assembly was fragmented in an unusual gene that is hypervariable within a repeat region. Such extreme local variation is rare but characteristic of genes that confer traits under pressure to diversify within a population. Notably, the four major repeated 9-mer nucleotide sequences all generate a proline-threonine-aspartic acid (PTD) repeat. The genome of an abundant Colwellia psychrerythraea population has a large extracellular protein that also contains the repeated PTD motif. Although we do not know the host for the BD1-5 cell, the high relative abundance of the C. psychrerythraea population and the shared surface protein repeat may indicate an association between these bacteria.IMPORTANCE CPR bacteria are generally predicted to be symbionts due to their extensive biosynthetic deficits. Although monophyletic, they are not monolithic in terms of their lifestyles. The organism described here appears to have evolved an unusual metabolic platform not reliant on glucose or pentose sugars. Its biology appears to be centered around bacterial host-derived compounds and/or cell detritus. Amino acids likely provide building blocks for nucleic acids, peptidoglycan, and protein synthesis. We resolved an unusual repeat region that would be invisible without genome curation. The nucleotide sequence is apparently under strong diversifying selection, but the amino acid sequence is under stabilizing selection. The amino acid repeat also occurs in a surface protein of a coexisting bacterium, suggesting colocation and possibly interdependence

Radio Galaxy Zoo: Cosmological Alignment of Radio Sources

We study the mutual alignment of radio sources within two surveys, FIRST and TGSS. This is done by producing two position angle catalogues containing the preferential directions of respectively $30\,059$ and $11\,674$ extended sources distributed over more than $7\,000$ and $17\,000$ square degrees. The identification of the sources in the FIRST sample was performed in advance by volunteers of the Radio Galaxy Zoo project, while for the TGSS sample it is the result of an automated process presented here. After taking into account systematic effects, marginal evidence of a local alignment on scales smaller than $2.5\deg$ is found in the FIRST sample. The probability of this happening by chance is found to be less than $2$ per cent. Further study suggests that on scales up to $1.5\deg$ the alignment is maximal. For one third of the sources, the Radio Galaxy Zoo volunteers identified an optical counterpart. Assuming a flat $\Lambda$CDM cosmology with $\Omega_m = 0.31, \Omega_\Lambda = 0.69$, we convert the maximum angular scale on which alignment is seen into a physical scale in the range $[19, 38]$ Mpc $h_{70}^{-1}$. This result supports recent evidence reported by Taylor and Jagannathan of radio jet alignment in the $1.4$ deg$^2$ ELAIS N1 field observed with the Giant Metrewave Radio Telescope. The TGSS sample is found to be too sparsely populated to manifest a similar signal

Combined analysis of microbial metagenomic and metatranscriptomic sequencing data to assess in situ physiological conditions in the premature infant gut.

Microbes alter their transcriptomic profiles in response to the environment. The physiological conditions experienced by a microbial community can thus be inferred using meta-transcriptomic sequencing by comparing transcription levels of specifically chosen genes. However, this analysis requires accurate reference genomes to identify the specific genes from which RNA reads originate. In addition, such an analysis should avoid biases in transcript counts related to differences in organism abundance. In this study we describe an approach to address these difficulties. Sample-specific meta-genomic assembled genomes (MAGs) were used as reference genomes to accurately identify the origin of RNA reads, and transcript ratios of genes with opposite transcription responses were compared to eliminate biases related to differences in organismal abundance, an approach hereafter named the "diametric ratio" method. We used this approach to probe the environmental conditions experienced by Escherichia spp. in the gut of 4 premature infants, 2 of whom developed necrotizing enterocolitis (NEC), a severe inflammatory intestinal disease. We analyzed twenty fecal samples taken from four premature infants (4-6 time points from each infant), and found significantly higher diametric ratios of genes associated with low oxygen levels in samples of infants later diagnosed with NEC than in samples without NEC. We also show this method can be used for examining other physiological conditions, such as exposure to nitric oxide and osmotic pressure. These study results should be treated with caution, due to the presence of confounding factors that might also distinguish between NEC and control infants. Nevertheless, together with benchmarking analyses, we show here that the diametric ratio approach can be applied for evaluating the physiological conditions experienced by microbes in situ. Results from similar studies can be further applied for designing diagnostic methods to detect NEC in its early developmental stages