Clostridium sordellii genome analysis reveals plasmid localized toxin genes encoded within pathogenicity loci

Background

Clostridium sordellii can cause severe infections in animals and humans, the latter associated with trauma, toxic shock and often-fatal gynaecological infections. Strains can produce two large clostridial cytotoxins (LCCs), TcsL and TcsH, related to those produced by Clostridium difficile, Clostridium novyi and Clostridium perfringens, but the genetic basis of toxin production remains uncharacterised.

Results

Phylogenetic analysis of the genome sequences of 44 strains isolated from human and animal infections in the UK, US and Australia placed the species into four clades. Although all strains originated from animal or clinical disease, only 5 strains contained LCC genes: 4 strains contain tcsL alone and one strain contains tcsL and tcsH. Four toxin-positive strains were found within one clade. Where present, tcsL and tcsH were localised in a pathogenicity locus, similar to but distinct from that present in C. difficile. In contrast to C. difficile, where the LCCs are chromosomally localised, the C. sordellii tcsL and tcsH genes are localised on plasmids. Our data suggest gain and loss of entire toxigenic plasmids in addition to horizontal transfer of the pathogenicity locus. A high quality, annotated sequence of ATCC9714 reveals many putative virulence factors including neuraminidase, phospholipase C and the cholesterol-dependent cytolysin sordellilysin that are highly conserved between all strains studied.

Conclusions

Genome analysis of C. sordellii reveals that the LCCs, the major virulence factors, are localised on plasmids. Many strains do not contain the LCC genes; it is probable that in several of these cases the plasmid has been lost upon laboratory subculture. Our data are consistent with LCCs being the primary virulence factors in the majority of infections, but LCC-negative strains may precipitate certain categories of infection. A high quality genome sequence reveals putative virulence factors whose role in virulence can be investigated.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1613-2) contains supplementary material, which is available to authorized users.     

Lighting during grow-out and <Emphasis Type="Italic">Salmonella</Emphasis> in broiler flocks

Background  

Lighting is used during conventional broiler grow-out to modify bird behaviour to reach the goals of production and improve bird welfare. The protocols for lighting intensity vary. In a field study, we evaluated if the lighting practices impact the burden of Salmonella in broiler flocks.     

Long‐range quantitative PCR for determining inactivation of adenovirus 2 by ultraviolet light

Aims

An extra‐long‐range quantitative PCR (LR‐qPCR) method was developed for estimating genome damage to adenovirus 2 caused by UV irradiation. The objective was to use LR‐qPCR as a rapid method to determine adenovirus UV inactivation.

Methods

The LR‐qPCR consisted of two steps: a long‐range PCR (up to 10 kb fragment) and a real‐time, quantitative (q) PCR for quantifying the products of the first PCR. We evaluated LR‐qPCR with adenovirus irradiated with medium‐pressure (MP, polychromatic emission) and low‐pressure (LP, 254 nm) mercury vapour lamps and compared results with cell culture infectivity.

Results

Using LR‐qPCR, a fragment of 6 kb estimated DNA damage in a linear relationship to doses between 0 and 20 mJ cm^?2, and a 1‐kb fragment related linearly to doses between 20 and 100 mJ cm^?2. The LR‐qPCR results for the 6‐kb fragment were similar to infectivity assays results for adenovirus exposed to MP UV. For adenovirus irradiated with LP lamps, LR‐qPCR results for the shorter fragment size (1 kb) were similar to reduction in viral infectivity. No difference was observed between 10 and 6 kb LR‐qPCR results.

Conclusion

The LR‐qPCR can be used as a tool for estimating DNA damage caused by UV in adenovirus. The LR‐qPCR results were related to reduction in viral infectivity.

Significance and Impact of the Study

The use of LR‐qPCR to determine DNA damage and estimate inactivation of adenovirus 2 from UV disinfection allows for same‐day results compared with >7 days required for cell culture. This accelerates adenovirus inactivation results for the water industry where adenovirus is used as a representative virus for crediting UV systems. This PCR approach provides a framework that can be used for other viral viability assays using the inhibition of amplification of viral nucleic acid after pretreatments, such as propidium monoazide, and for cellular biology studies of DNA damage.     

Impact assessment in SLCA: sorting the sLCIA methods according to their outcomes

Background, aims, and scope  

Social Life Cycle Assessment (SLCA) is a tool assessing the social aspects of products and services. This article is a step forward from the Guidelines and wishes to clarify the different impact assessment (IA) methods covered in the Guidelines and how these different methods would provide different types of information regarding the social aspects of the product system.     

The Use of P63 Immunohistochemistry for the Identification of Squamous Cell Carcinoma of the Lung

Introduction

While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples.

Methods

With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC.

Results

The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs.

Conclusions

P63 IHC is useful for the identification of lung SCCs.     

Composite effects of gene determinants on the translation speed and density of ribosomes

Background  

Translation is a central process of life, and its regulation is crucial for cell growth. In this article, focusing on two model organisms, Escherichia coli and Saccharomyces cerevisiae, we study how three major local features of a gene's coding sequence (its adaptation to the tRNA pool, its amino acid charge, and its mRNA folding energy) affect its translation elongation.     

Enhancing the Perceived Threat of Vehicle Approach to Deer

ABSTRACT In North America and Europe, deer (Cervidae)—vehicle collisions (DVCs) are common and result not only in injury and death to the animals involved, but also human injury and property damage. Given that most DVCs occur during crepuscular periods, we questioned whether the perceived threat to deer posed by vehicle approach could be enhanced. We hypothesized that a vehicle-based lighting system that better complements peak visual capabilities of deer at night relative to standard tungsten-halogen (TH) lighting alone would elicit a greater flight-initiation distance (FID) by free-ranging white-tailed deer (Odocoileus virginianus). Our lighting system comprised 2 TH lamps and one Xenarc high-intensity discharge (HID) lamp. We defined an a priori logistic model comprising 4 variables potentially explaining deer FID relative to vehicle approach: 1) starting distance of the approach, 2) lighting treatment, 3) season, and 4) deer group size. Deer exposed to the combination of TH lamps and constant illumination of the HID lamp exhibited a mean (SD) FID of 136 (127) m. In contrast, deer exposed to TH lamps only initiated flight on average at 116 (127) m, and those exposed to the combination of TH lamps and the HID lamp pulsed at 2 Hz exhibited a mean FID of 89 (98) m. We contend that the pulsing of the HID lamp while TH lamps were illuminated resulted in consistent loss (over approx. 0.5-sec intervals) of a portion of the image on approach, possibly interfering with sensory information relative to the position of the potential threat. In contrast, the combination of TH lamps and constant illumination of the HID lamp contributed (P = 0.033) to the probability of a FID ≥94 m. We suggest, therefore, that deer FID can be increased by combining currently available TH and HID lamps, or use of HID lamps alone, to enhance detection of an approaching vehicle at night. Also, we encourage research into new lamp designs to better complement deer visual capabilities as well as continued research to quantify deer FID in response to vehicle approach at night and lamp-specific properties that can enhance deer detection of the vehicle.     

Non-Visual Effects of Light on Melatonin,Alertness and Cognitive Performance: Can Blue-Enriched Light Keep Us Alert?

Background

Light exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range. Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance.

Methods

Sixteen healthy young men were studied in a balanced cross-over design with light exposure of 3 different light settings (compact fluorescent lamps with light of 40 lux at 6500K and at 2500K and incandescent lamps of 40 lux at 3000K) during 2 h in the evening.

Results

Exposure to light at 6500K induced greater melatonin suppression, together with enhanced subjective alertness, well-being and visual comfort. With respect to cognitive performance, light at 6500K led to significantly faster reaction times in tasks associated with sustained attention (Psychomotor Vigilance and GO/NOGO Task), but not in tasks associated with executive function (Paced Visual Serial Addition Task). This cognitive improvement was strongly related with attenuated salivary melatonin levels, particularly for the light condition at 6500K.

Conclusions

Our findings suggest that the sensitivity of the human alerting and cognitive response to polychromatic light at levels as low as 40 lux, is blue-shifted relative to the three-cone visual photopic system. Thus, the selection of commercially available compact fluorescent lights with different colour temperatures significantly impacts on circadian physiology and cognitive performance at home and in the workplace.     

A graphical representation for consequential life cycle assessment of future technologies. Part 1: methodological framework

Purpose  

To construct future visions of how innovative technologies should be used in the envisioned sustainable society while being aware of system-wide environmental impacts, consequential life cycle assessment (c-LCA) is useful. To systematically evaluate the technologies being aware of uncertainties in choice of technologies made in the future, in this article, we propose a novel graphical representation for theoretical range of impacts that contain results from c-LCA studies. This approach allows analyses of the consequences of the technology introduction without conducting detailed modeling of consequences.     

Influence of degree correlations on network structure and stability in protein-protein interaction networks

Background  

The existence of negative correlations between degrees of interacting proteins is being discussed since such negative degree correlations were found for the large-scale yeast protein-protein interaction (PPI) network of Ito et al. More recent studies observed no such negative correlations for high-confidence interaction sets. In this article, we analyzed a range of experimentally derived interaction networks to understand the role and prevalence of degree correlations in PPI networks. We investigated how degree correlations influence the structure of networks and their tolerance against perturbations such as the targeted deletion of hubs.     

A graphical representation for consequential life cycle assessment of future technologies—Part 2: two case studies on choice of technologies and evaluation of technology improvements

Purpose  

To construct future visions of how innovative technologies should be used in the envisioned sustainable society while being aware of system-wide environmental impacts, consequential life cycle assessment (c-LCA) is useful. To systematically evaluate the technologies being aware of uncertainties in the choice of technologies made in the future, in this article, we propose a novel graphical representation for theoretical range of impacts that contain results from c-LCA studies. This approach allows analyses of the consequences of technology introduction without conducting a detailed modeling of consequences.     

Practitioners' use of life cycle costing with environmental costs—a Swedish study

Purpose  

The aim of this paper is to describe life cycle costing (LCC) practices in some Swedish organisations, investigate probable changes and determine whether and how environmental costs (internal and/or external) are considered in current LCC.     

A geometric and algebraic view of MHC-peptide complexes and their binding properties

Background  

Major histocompatibility complex (MHC) molecules present peptides to T lymphocytes. It is of critical biological and medical importance to elucidate how different MHC alleles bind to a specific set of peptides.     

An agent based approach to the potential for rebound resulting from evolution of residential lighting technologies

Purpose

More energy efficient lighting options, such as compact fluorescent bulbs and light emitting diodes are predicted to significantly reduce the amount of energy used for lighting. Such forecasts are predicated on the assumption of light saturation and do not take into account the potential for economic rebound. The potential of the rebound effect to reduce or negate predicted energy savings is explored here.

Methods

This work uses an agent-based model with a cellular automata approach to study the impact of rebound on the consumption of residential light and associated energy use, using three lighting technologies, and a time span from 2012 to 2030. Agents, representative of households, select between three lighting options using a multiplicative utility function and a probabilistic choice mechanism. Agents then decide whether to consume more light and potentially more energy based on the lighting technology selected and personal preferences. The agents are heterogeneous in nature, consisting of seven typologies, with their characteristics informed through survey data.

Results and discussion

The results of the model indicate that although the consumption of light may increase, overall changes in the consumption of energy compared to 2012 levels will be minor. If the consumption of light is held steady, assuming saturation, then there is the potential for the adoption of energy-efficient lighting to result in significant energy savings. However, if the rebound effect occurs, there will be a decrease in the consumption of energy for lighting as consumers adopt more energy efficient options. Overtime as the consumption of light continues to increase, those savings will largely be eroded.

Conclusions

This study suggests that the adoption of energy-efficient lighting in itself will not reduce the overall consumption of energy for lighting on a long-term scale although it may be successful in doing so in the short-term. The rebound effect will greatly reduce the projected energy savings from more efficient lighting technologies, with potential for direct rebound to exceed 100 %. In order for the quantity of energy utilized in residential lighting to decrease, solutions beyond that of efficiency gains must be considered.     

Outer membrane vesicle-mediated release of cytolethal distending toxin (CDT) from Campylobacter jejuni

Background  

Background: Cytolethal distending toxin (CDT) is one of the well-characterized virulence factors of Campylobacter jejuni, but it is unknown how CDT becomes surface-exposed or is released from the bacterium to the surrounding environment.     

The clinical meaningfulness of ADAS-Cog changes in Alzheimer's disease patients treated with donepezil in an open-label trial

Background  

In 6-month anti-dementia drug trials, a 4-point change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is held to be clinically important. We examined how this change compared with measures of clinical meaningfulness.     

Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors

Background  

The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) evolved from a common ancestor. Still not completely understood is how specificity for glucocorticoids (e.g. cortisol) and mineralocorticoids (e.g. aldosterone) evolved in these receptors.     

Predicting functional upstream open reading frames in Saccharomyces cerevisiae

Background  

Some upstream open reading frames (uORFs) regulate gene expression (i.e., they are functional) and can play key roles in keeping organisms healthy. However, how uORFs are involved in gene regulation is not yet fully understood. In order to get a complete view of how uORFs are involved in gene regulation, it is expected that a large number of experimentally verified functional uORFs are needed. Unfortunately, wet-experiments to verify that uORFs are functional are expensive.     

Carton for beverage—A decade of process efficiency improvements enhancing its environmental profile

Purpose  

Chain efficiency is currently a key issue for evaluating the sustainability of products and processes. Thus, the objective of this study was to evaluate how the overall efficiency process improvement carried out in the upstream manufacturing chain of LPB (Liquid Packaging Board) has affected the environmental profile over the last 10 years.     

Distance measurements via the morphogen gradient of Bicoid in <Emphasis Type="Italic">Drosophila</Emphasis> embryos

Background  

Patterning along the anterior-posterior (A-P) axis in Drosophila embryos is instructed by the morphogen gradient of Bicoid (Bcd). Despite extensive studies of this morphogen, how embryo geometry may affect gradient formation and target responses has not been investigated experimentally.