Acyltransferase families that act on thioesters: Sequences,structures, and mechanisms

Acyltransferases (AT) are enzymes that catalyze the transfer of acyl group to a receptor molecule. This review focuses on ATs that act on thioester-containing substrates. Although many ATs can recognize a wide variety of substrates, sequence similarity analysis allowed us to classify the ATs into fifteen distinct families. Each AT family is originated from enzymes experimentally characterized to have AT activity, classified according to sequence similarity, and confirmed with tertiary structure similarity for families that have crystallized structures available. All the sequences and structures of the AT families described here are present in the thioester-active enzyme (ThYme) database. The AT sequences and structures classified into families and available in the ThYme database could contribute to enlightening the understanding acyl transfer to thioester-containing substrates, most commonly coenzyme A, which occur in multiple metabolic pathways, mostly with fatty acids.     

Local genes for local bacteria: Evidence of allopatry in the genomes of transatlantic Campylobacter populations

The genetic structure of bacterial populations can be related to geographical locations of isolation. In some species, there is a strong correlation between geographical distance and genetic distance, which can be caused by different evolutionary mechanisms. Patterns of ancient admixture in Helicobacter pylori can be reconstructed in concordance with past human migration, whereas in Mycobacterium tuberculosis it is the lack of recombination that causes allopatric clusters. In Campylobacter, analyses of genomic data and molecular typing have been successful in determining the reservoir host species, but not geographical origin. We investigated biogeographical variation in highly recombining genes to determine the extent of clustering between genomes from geographically distinct Campylobacter populations. Whole‐genome sequences from 294 Campylobacter isolates from North America and the UK were analysed. Isolates from within the same country shared more recently recombined DNA than isolates from different countries. Using 15 UK/American closely matched pairs of isolates that shared ancestors, we identify regions that have frequently and recently recombined to test their correlation with geographical origin. The seven genes that demonstrated the greatest clustering by geography were used in an attribution model to infer geographical origin which was tested using a further 383 UK clinical isolates to detect signatures of recent foreign travel. Patient records indicated that in 46 cases, travel abroad had occurred <2 weeks prior to sampling, and genomic analysis identified that 34 (74%) of these isolates were of a non‐UK origin. Identification of biogeographical markers in Campylobacter genomes will contribute to improved source attribution of clinical Campylobacter infection and inform intervention strategies to reduce campylobacteriosis.     

Determinants and co‐expression of anti‐predator responses in amphibian tadpoles: a meta‐analysis

A wide range of taxa respond to perceived predation risk (PPR) through inducible defenses, and many prey are capable of responding both behaviorally and morphologically to the same risk event. In cases where multiple defenses confer protection by independent means (i.e. they are mechanistically independent) responses will either be co‐expressed, or the expression of one defense will limit the capacity (or need) to respond along another axis. Our ability to generate a broad understanding of these patters has been limited, in part, by difficulties in comparing results across studies that employ distinct experimental protocols. Using the extensive literature on tadpole responses to PPR, we conducted a meta‐analysis to identify the ecological and experimental determinants of inducible defence expression. We then assessed whether the magnitude of response to PPR along behavioural versus morphological response axes was positively, or negatively, correlated. The most commonly quantified responses to perceived risk in tadpoles included reductions in movement and swimming behaviour, and altered tail morphology. Our analyses reveal that tadpole behavioural responses are strongly influenced by prey family, predator taxon, evolutionary history with the predator (native versus non‐native), amount of prey consumed by the predator, and how perceived risk was manipulated (e.g. presence versus absence of alarm cues). Tail morphology was similarly influenced by these factors, but also whether the target prey was palatable to predators. Thus, our results identify ecological and experimental features that critically influence the observed effect size in tadpole responses to PPR. A positive correlation between behavioural and morphological responses in studies where both were measured indicates that trait co‐specialization is the predominant pattern of defense deployment in larval amphibians. This positive relationship suggests that survival tends to be maximized in tadpoles through equivalent co‐activation of multiple independent axes of protection, opposed to maximal expression along any single axis. Synthesis Our understanding of plastic responses to perceived predation risk (PPR) has benefited substantially from the vast amount of experimental work examining inducible defences in anuran tadpoles. Indeed this research has illustrated the wide variety of ways that prey animals can respond to the same risk event. We conducted a metaanalysis to identify the key ecological and experimental determinants of inducible defence expression. We then show that, in most cases, behavioural and morphological responses to PPR tend to be co‐expressed suggesting that responding along one axis (moving behaviour) does not limit their ability to respond along another distinct axis (tail morphology).     

Relative growth and size at onset of sexual maturity of the brown crab,Cancer pagurus in the Isle of Man,Irish Sea

In this study, the relative growth, size–weight relationships and size at onset of maturity of the brown crab Cancer pagurus were investigated in the Isle of Man. For the analyses of relative growth and size at onset of maturity, the samples were collected seasonally between autumn 2012 and spring 2013 using several methods: pot surveys, dredge and trawl surveys, market surveys and shore surveys. Results showed that allometric growth occurred in the chelipeds of males (n?=?87) and in the abdomen of females (n?=?222). Four different measures of maturity (behavioural, functional, morphometric and physiological) were examined. With respect to the behavioural maturity, the smallest female crab found with a sperm plug measured 110?mm CW, whereas in terms of functional maturity the smallest ovigerous female had a CW of 134?mm. Based on direct observations of gonad maturity, 50% of females were mature at 108?mm CW, whereas 50% of males were mature at 89?mm CW. The size at the onset of maturity measurements of female and male C. pagurus based on gonad development is smaller than the current minimum landing size (130?mm), and therefore this suggests that the current minimum landing size is an adequate management measure.     

Investigation of optical attenuation imaging using optical coherence tomography for monitoring of scars undergoing fractional laser treatment

We demonstrate the use of the near‐infrared attenuation coefficient, measured using optical coherence tomography (OCT), in longitudinal assessment of hypertrophic burn scars undergoing fractional laser treatment. The measurement method incorporates blood vessel detection by speckle decorrelation and masking, and a robust regression estimator to produce 2D en face parametric images of the attenuation coefficient of the dermis. Through reliable co‐location of the field of view across pre‐ and post‐treatment imaging sessions, the study was able to quantify changes in the attenuation coefficient of the dermis over a period of ～20 weeks in seven patients. Minimal variation was observed in the mean attenuation coefficient of normal skin and control (untreated) mature scars, as expected. However, a significant decrease (13 ± 5%, mean ± standard deviation) was observed in the treated mature scars, resulting in a greater distinction from normal skin in response to localized damage from the laser treatment. By contrast, we observed an increase in the mean attenuation coefficient of treated (31 ± 27%) and control (27 ± 20%) immature scars, with numerical values incrementally approaching normal skin as the healing progressed. This pilot study supports conducting a more extensive investigation of OCT attenuation imaging for quantitative longitudinal monitoring of scars.

En face 2D OCT attenuation coefficient map of a treated immature scar derived from the pre‐treatment (top) and the post‐treatment (bottom) scans. (Vasculature (black) is masked out.) The scale bars are 0.5 mm.     

Induction of PrPSc-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease

The ongoing epidemic of chronic wasting disease (CWD) within cervid populations indicates the need for novel approaches for disease management. A vaccine that either reduces susceptibility to infection or reduces shedding of prions by infected animals, or a combination of both, could be of benefit for disease control. The development of such a vaccine is challenged by the unique nature of prion diseases and the requirement for formulation and delivery in an oral format for application in wildlife settings. To address the unique nature of prions, our group targets epitopes, termed disease specific epitopes (DSEs), whose exposure for antibody binding depends on disease-associated misfolding of PrP^C into PrP^Sc. Here, a DSE corresponding to the rigid loop (RL) region, which was immunogenic following parenteral vaccination, was translated into an oral vaccine. This vaccine consists of a replication-incompetent human adenovirus expressing a truncated rabies glycoprotein G recombinant fusion with the RL epitope (hAd5:tgG-RL). Oral immunization of white-tailed deer with hAd5:tgG-RL induced PrP^Sc-specific systemic and mucosal antibody responses with an encouraging safety profile in terms of no adverse health effects nor prolonged vector shedding. By building upon proven strategies of formulation for wildlife vaccines, these efforts generate a particular PrP^Sc-specific oral vaccine for CWD as well as providing a versatile platform, in terms of carrier protein and biological vector, for generation of other oral, peptide-based CWD vaccines.