Photobiomodulation in Animal Models of Ageing and Alzheimer’s Disease

Photobiomodulation refers to low-intensity light therapy, utilising wavelengths in the near-infrared region of the electromagnetic spectrum to elicit biological effects. The principle aim of this investigation was to explore signalling pathways initiated by IR1072, with particular focus on heat shock proteins (HSPs), a family of proteins known to target cellular aggregates which are involved in the maintenance of cellular homeostasis. This was further examined by exploring the role of age and sex in the magnitude of biological effects induced. Another aim of this study was to explore the cytoprotective potential of IR1072 in conjunction with Alzheimer’s disease-related insults. The results of this study show chronic IR1072 exposure altered the expression of a number of HSPs in both CD-1 and TASTPM mice; including HSP105, HSP70, HSP27, and αB crystallin. The magnitude of effect differed with age and sex of CD-1 and TASTPM mice respectively; these differences coincided with altered endogenous activity of electron transport chain components. Acute exposure of CAD neuronal cultures provided significant neuroprotection against oxidative-stress and β-amyloid insults. Further characterisation of the CD-1 and TASTPM strains during ageing was established. CD-1 mice demonstrated reduced TARP γ2 with age, which may underlie learning deficits that become apparent during ageing. Chronic IR1072 exposure significantly increased TARP γ2 in 7 and 13 month old CD-1 mice, perhaps explaining improved working-memory reported following IR1072 exposure. Acute treatments of CD-1 mice altered Complex I and II activity in mitochondria. Chronic IR1072 exposure Caenorhabditis elegans was shown to consistently extend lifespan. This model system aided in establishing pathways essential for biological effects of IR1072, demonstrating the importance of HSF1 driven pathways, in particular those requiring HSP70. In conclusion, this research revealed mechanisms initiated by photobiomodulation at IR1072 that act to re-establish homeostasis, profoundly reduce amyloid load, prevent cell stress and cell death

High-throughput sequencing of the chicken gut microbiome

The chicken ($Gallus$ $gallus$ $domesticus$) is the most abundant and widely distributed livestock animal with a global population of over 21 bill ion. A newly hatched broiler chick increases its body weight by 25% overnight and 50-fold over five weeks. The symbiotic, complex and variable community of the microbiome forms an important part of the gastrointestinal tract (gut). It is involved in gut development, biochemistry, immunology, physiology and non-specific resistance to infection. This study investigated the chicken gut microbiota using high-throughput 16S rRNA sequencing and culture-based techniques. There was specific interest in the proventriculus of which there is limited research currently in the literature and the caecum because it contains the highest density of bacterial cells in the gut at 10$^1$$^1$ per gram. The results showed no significant difference in the first stages of the gut which shared a low-diversity microbiota dominated by a few $Lactobacillus$ species. The microbiota becomes more diverse in the latter pa1ts of the small intestine where $C/ostridiales$ and $Enterobacteriaceae$ were present in higher numbers. The caecum was the most diverse organ with the majority of species belonging to Ruminococcaceae, Lachnospiraceae and $Alistipes$. A number of novel species were isolated from the chicken gut and six of these were whole-genome sequenced

Promoting Cross Border Investing By Business Angels in the European Union

The supply of entrepreneurial finance in Europe is constrained by the geographical fragmentation of its capital market. The need to facilitate more cross-border investing by business angels – the main source of early stage finance–is recognized. A study of business angels on the island of Ireland identifies three constraints on cross-border investing: (1) lack of information on cross-border investment opportunities; (2) the preference of angels to invest locally; and (3) tax incentives that are only available for investments in the angel’s own country. Increasing cross-border investment requires mechanisms that build relationships between business angels in different countries

A sensitive method for the recovery of Escherichia coli serogroup O55 including Shiga toxin-producing variants for potential use in outbreaks

AIM: Shiga toxin-producing Escherichia coli (STEC) cause bloody diarrhoea, kidney failure and occasionally death. However, identifying the source of infection caused by STEC other than serogroup O157 is hampered by availability of sensitive methods for detecting these pathogens. In this study we developed novel tools for detecting E. coli O55 that is potentially associated with human outbreaks. METHOD AND RESULTS: Overall specificity of immuno-magnetic separation (IMS) beads coated with anti-O55 serum was good with exception of cross reactivity with E. coli O22 and O23, which was eliminated using an O55 specific PCR. Limit of detection for E. coli O55 using O55-IMS-beads in spiked cattle faeces was on average 50 CFU ml-1 (range 1-90), and improved to <10 CFU ml-1 using the O55 specific PCR, following IMS on samples enriched for 2h with E. coli O55. Application of these tools to test cattle faeces collected on-farm allowed the isolation of O55:H19, which through whole genome sequencing was compared to STEC O55:H7 human outbreak strains. CONCLUSION: These tools provide a sensitive method which could be used to screen samples for STEC O55, whether environmental or human clinical. SIGNIFICANCE AND IMPACT OF THE STUDY: Several human outbreaks reported in England were caused by STEC O55:H7. Tools developed here could assist in identification of the environmental source for these isolates, which has not yet been established. This article is protected by copyright. All rights reserved

Draft Genome Sequences of Six Novel Bacterial Isolates from Chicken Ceca

The chicken is the most common domesticated animal and the most abundant bird in the world. However, the chicken gut is home to many previously uncharacterized bacterial taxa. Here, we report draft genome sequences from six bacterial isolates from chicken ceca, all of which fall outside any named species

Molecular characterization of extended spectrum cephalosporin resistant Escherichia coli isolated from livestock and in-contact humans in Southeast Nigeria

The rise in antimicrobial resistance (AMR) in bacteria is reducing therapeutic options for livestock and human health, with a paucity of information globally. To fill this gap, a One-Health approach was taken by sampling livestock on farms (n = 52), abattoir (n = 8), and animal markets (n = 10), and in-contact humans in Southeast Nigeria. Extended spectrum cephalosporin (ESC)-resistant (ESC-R) Escherichia coli was selectively cultured from 975 healthy livestock faecal swabs, and hand swabs from in-contact humans. Antimicrobial susceptibility testing (AST) was performed on all ESC-R E. coli. For isolates showing a multi-drug resistance (MDR) phenotype (n = 196), quantitative real-time PCR (qPCR) was performed for confirmation of extended-spectrum β-lactamase (ESBL) and carbapenemase genes. Whole-genome sequencing (WGS) was performed on a subset (n = 157) for detailed molecular characterisation. The results showed ESC-R E. coli was present in 41.2% of samples, with AST results indicating 48.8% of isolates were phenotypically MDR. qPCR confirmed presence of ESBL genes, with bla(CTX-M) present in all but others in a subset [bla(TEM) (62.8%) and bla(SHV) (0.5%)] of isolates; none harboured transferable carbapenemase genes. Multi-locus sequence typing identified 34 Sequence Types (ST) distributed among different sampling levels; ST196 carrying bla(CTX-M-55) was predominant in chickens. Large numbers of single nucleotide polymorphisms (SNPs) in the core genome of isolates, even within the same clade by phylogenetic analysis, indicated high genetic diversity. AMR genotyping indicated the predominant bla(CTX-M) variant was bla(CTX-M-15) (87.9%), although bla(CTX-M-55), bla(CTX-M-64,) and bla(CTX-M-65) were present; it was notable that bla(CTX-M-1), common in livestock, was absent. Other predominant AMR genes included: sul2, qnrS1, strB, bla(TEM-1b), tetA-v2, and dfrA14, with prevalence varying according to host livestock species. A bla(CTX-M-15) harbouring plasmid from livestock isolates in Ebonyi showed high sequence identity to one from river/sewage water in India, indicating this ESBL plasmid to be globally disseminated, being present beyond the river environment. In conclusion, ESC-R E. coli was widespread in livestock and in-contact humans from Southeast Nigeria. WGS data indicated the isolates were genetically highly diverse, probably representing true diversity of wild type E. coli; they were likely to be MDR with several harbouring bla(CTX-M-15.) Surprisingly, human isolates had highest numbers of AMR genes and pigs the least

Melatonin limits paclitaxel-induced mitochondrial dysfunction in vitro and protects against paclitaxel-induced neuropathic pain in the rat

Acknowledgements Thank you to Professor Ahmet Hoke (Johns Hopkins, Baltimore, USA) for the gift of DRG cells; and to Professor Patrick M. Dougherty (MD Anderson Cancer Center, Texas, USA) for sharing his expertise in the rat model. Funding The study was funded by the Association of Anaesthetists of Great Britain and Ireland, the British Journal of Anaesthesia/Royal College of Anaesthetists and the Melville Trust.Peer reviewedPublisher PD

Molecular characterization of extended spectrum cephalosporin resistant Escherichia coli isolated from livestock and in-contact humans in Southeast Nigeria

The rise in antimicrobial resistance (AMR) in bacteria is reducing therapeutic options for livestock and human health, with a paucity of information globally. To fill this gap, a One-Health approach was taken by sampling livestock on farms (n = 52), abattoir (n = 8), and animal markets (n = 10), and in-contact humans in Southeast Nigeria. Extended spectrum cephalosporin (ESC)-resistant (ESC-R) Escherichia coli was selectively cultured from 975 healthy livestock faecal swabs, and hand swabs from in-contact humans. Antimicrobial susceptibility testing (AST) was performed on all ESC-R E. coli. For isolates showing a multi-drug resistance (MDR) phenotype (n = 196), quantitative real-time PCR (qPCR) was performed for confirmation of extended-spectrum β-lactamase (ESBL) and carbapenemase genes. Whole-genome sequencing (WGS) was performed on a subset (n = 157) for detailed molecular characterisation. The results showed ESC-R E. coli was present in 41.2% of samples, with AST results indicating 48.8% of isolates were phenotypically MDR. qPCR confirmed presence of ESBL genes, with blaCTX-M present in all but others in a subset [blaTEM (62.8%) and blaSHV (0.5%)] of isolates; none harboured transferable carbapenemase genes. Multi-locus sequence typing identified 34 Sequence Types (ST) distributed among different sampling levels; ST196 carrying blaCTX-M-55 was predominant in chickens. Large numbers of single nucleotide polymorphisms (SNPs) in the core genome of isolates, even within the same clade by phylogenetic analysis, indicated high genetic diversity. AMR genotyping indicated the predominant blaCTX-M variant was blaCTX-M-15 (87.9%), although blaCTX-M-55, blaCTX-M-64, and blaCTX-M-65 were present; it was notable that blaCTX-M-1, common in livestock, was absent. Other predominant AMR genes included: sul2, qnrS1, strB, blaTEM-1b, tetA-v2, and dfrA14, with prevalence varying according to host livestock species. A blaCTX-M-15 harbouring plasmid from livestock isolates in Ebonyi showed high sequence identity to one from river/sewage water in India, indicating this ESBL plasmid to be globally disseminated, being present beyond the river environment. In conclusion, ESC-R E. coli was widespread in livestock and in-contact humans from Southeast Nigeria. WGS data indicated the isolates were genetically highly diverse, probably representing true diversity of wild type E. coli; they were likely to be MDR with several harbouring blaCTX-M-15. Surprisingly, human isolates had highest numbers of AMR genes and pigs the least