bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immature/transitional B-cell expansion is associated with bone loss in HIV-infected individuals with severe CD4+ T-cell lymphopenia
Authors: Titanji Kehmia , Ofotokun Ighovwerha , Weitzmann M. Neale 
Published: July 2020

Background:
Antiretroviral therapy (ART) has led to a significant decline in HIV-related morbidity and mortality in people living with HIV (PLWH). PLWH however experience non-AIDS ageing-associated comorbidities, including decreased bone mass and osteoporosis, earlier and more severely, than uninfected people. We previously reported that total B-cell production of the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL) was elevated in PLWH, concurrent with a decrease in total B-cell production of RANKL's physiological moderator Osteoprotegerin (OPG). The resulting increased total B-cell RANKL/OPG ratio was significantly associated with bone loss in the appendicular (long bones), but not axial (spine) skeletons of PLWH. A role for immature/transitional B cells (BImm) in HIV-induced bone loss has not been reported.

Methods:
BImm frequency was determined by flow cytometry; plasma IL-7 was quantified by ELISA and bone mineral density (BMD) measured by dual X-ray absorptiometry (DXA) in a cross-sectional study of 62 ART-naive HIV-infected and 58 HIV-negative individuals.

Results:
BImm expansion correlated with the total B-cell RANKL/OPG ratio in HIV-infected individuals and inversely with BMD at the total hip, femoral neck and the lumbar spine, and with IL-7.

Conclusion:
These data suggest that BImm contribute to the increased B-cell RANKL/OPG ratio in PLWH, and reveal a previously unrecognized link between BImm expansion and HIV-induced bone loss in the axial and appendicular skeletons of severely immunocompromised HIV-infected individuals. BImm expansion may be a novel biomarker for screening patients at risk of osteoporosis.
Influence of hepatitis C virus co-infection and hepatitis C virus treatment on risk of chronic kidney disease in HIV-positive persons
Authors: Mocroft Amanda , Ryom Lene , Oprea Cristiana , Li Qiuju , Rauch Andri , Boesecke Christoph , Uzdaviniene Vilma , Sedlacek Dalibor , Llibre Josep M. , Lacombe Karine , Nielsen Lars N. , Florence Eric , Aho Inka , Chkhartishvili Nikoloz , Szlavik János , Dragovic Gordana , Leen Clifford , Sambatakou Helen , Staub Therese , Laguno Montse , Elinav Hila , Tomažič Janez , Peters Lars 
Published: July 2020

Background:
Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study.

Methods:
HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m2] between HCV strata.

Results:
Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2–10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46–0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47–0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65–1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49–1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results.

Conclusion:
This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.
The use of wound dressings as a means to alter the composition of biofilms in a chronic wound model
Authors: Nedelea Gabriela , Maddocks Sarah 
Published: July 2020

It is estimated that £5 billion are invested yearly into chronic wound management by the NHS. Whilst the demand for treatment rises every year, it has become harder to treat wounds given the burden of antimicrobial resistance. Chronic wounds can easily become harbouring grounds for polymicrobial biofilms in which species interact in specific ways.
This study assessed the interactions between two commonly co-isolated chronic wound pathogens: Pseudomonas aeruginosa (ATCC 9027) and Staphylococcus aureus (EMRSA 15), whose biofilm relation initiates a Gram-negative shift. During this phenomenon, P. aeruginosa takes over the majority of the bacterial community, at the detriment of S. aureus. The Gram-negative shift marks the turning point from an acute to a chronic wound. The pH of a chronic wound is typically alkaline, and it was hypothesised that topical dressings with an acidic pH could disrupt the onset of the Gram negative shift, and therefore chronicity. Six different topical dressings with low pH were used in achronic wound model to assess their ability to reverse or delay the Gram-negative shift. It was found that they did not have an impact on the onset of the Gram-negative shift, despite their low pH values. However, the lower the pH of the dressings, the more frequently small colony variant (SCV) bacteria were observed in the biofilm. SCVs are known for causing persistent or chronic infections. It was therefore concluded that low pH dressings alone may not be favourable for managing chronic wound infection.
Digital Outreach: Promoting a global understanding of antimicrobial resistance (AMR)
Authors: Shaw Michael 
Published: July 2020

Technology allows educators to reach a global audience without amassing a large carbon footprint. The Skype in the Classroom programme from Microsoft enables me to spark curiosity and engage a wide range of students in dialogue to explore global issues, in particular, the threat of antimicrobial resistance, while supporting me to develop my skills as an educator. Through a multi-disciplinary approach, I employ Skype in the Classroom as a future-proof, powerful tool in our arsenal against the evolving microbial threat. We are not only responsible for teaching the next generation of scientists, but also the next generation of thought-leaders and professionals, who will work collaboratively towards our common goals.
Antimicrobial resistance is one of the grand challenges of the 21st century, and global connectivity is one of the best solutions to promoting better understanding of this threat. The Skype in the Classroom programme has allowed me to teach sessions to students in Norway, India, Brazil, Miami, Florida and Puerto Rico, with students ranging from 10 to 18 years old. I use skype and Teams to deliver online lessons in an accessible way, starting with the scope of the problem, covering the technical detail of how resistance emerges and is spread, and looking at some of the newest approaches to tackling AMR. Using a ‘challenge-based-learning’ approach, we discuss how different professionals and roles within society can contribute to the issue. This makes the class applicable to students with a wide range of backgrounds, including those without a keen interest in science.
The investigation of microbial induced calcium carbonate precipitation for soil improvement
Authors: Haystead Jamie , Dade-Robertson Martyn , Arnardottir Thora , Christgen Beate , Zhang Meng 
Published: July 2020

Weak and unstable soils can limit the building of new infrastructure. Current soil strengthening techniques such as chemical grouting have detrimental effects on the environment from greenhouse gas production, soil pH modification and groundwater contamination. Microbial-induced calcium carbonate precipitation (MICCP) is a technique that utilises the ability of bacteria to precipitate calcium carbonate, which can be used for a variety of applications including binding adjacent soil particles and filling the pore spaces of soils to increase their mechanical properties. A commonly used bacterium is Sporosarcina pasteurii. A range of factors influences MICCP which presents challenges with process optimisation. Some studies have made use of computational models to predict biocementation at a larger scale, however aspects of models are based on assumption of conditions instead of experimental data.
An aim of this project is to investigate urease activity in S. pasteurii by comparing different growth media, growth stages, pH and temperatures. Ureolysis kinetics of S. pasteurii will be investigated at different urea and calcium chloride concentrations in liquid media. Finally, the biocementation of S. pasteurii in sand syringe setups will also be investigated to compare the effects of changing influencing factors such as growth stage and cell concentration of S. pasteurii, sand particle size, cementation media concentration, duration between cementation media applications and overall number of cementation treatments. Experimental work will be particularly focused towards gaps in the experimental data used in computational models, to help improve these models and bring MICCP biocementation closer to commercial use.
The role of air pollution and bacteria in COPD
Authors: Faye Purser Lillie , Purves Jo , Corscadden Louise , Selley Liza , S. Monks Paul , M. Ketley Julian , W. Andrew Peter , Barer Michael , Brightling Christopher , A. Morrissey Julie 
Published: July 2020

Air pollution is the single largest environmental health risk worldwide. Particulate matter (PM) air pollution is released as a result of fossil fuel combustion and vehicle motion, breaking and tyre wear. It has been shown that exposure to PM can cause increased levels of respiratory disease, including the exacerbation of COPD, which is frequently associated with bacterial infection. Despite this, the effects of air pollution exposure on COPD associated respiratory bacteria, includingHaemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae are largely unknown. Our recent publication was the first to document that as well as damaging the host, PM has a direct impact on bacteria that can cause respiratory infections. We showed that exposure to black carbon (BC), an important component of PM, results in alterations in biofilm structure in both Streptococcus pneumoniae and Staphylococcus aureus, and increases dissemination of colonising S. pneumoniaein in vivo models.
Following on from this work, we aim to determine how BC impacts the growth, behaviour and virulence of bacteria associated with the COPD exacerbation, including non-typeable Haemophilus influenzaeand Moraxella catarrhalis. Current data show that BC exposure is decreasing the biofilm forming ability of NTHistrains 162 and 375. M. catarrhalis strain M61 biofilm formation is also decreased in the presence of BC, while its growth rate is increased. In addition, pre-exposing NTHi375 cells to BC, prior to infection of A549 cells, increases their ability to adhere to human epithelial cells. This suggests that the frequency of bacterial infection induced COPD exacerbation may be altered in patients from highly polluted areas.
Molecular identification of ticks and tick borne pathogens in Nigerian Dogs: A public health threat
Authors: Apaa Ternenge , Dunham Stephen , Tarlinton Rachael 
Published: July 2020

Global warming has changed the range of tick species and the tick borne diseases (TBDs) they carry; there is an increasing need to assess the risk and impact of TBDs. This study focused on TBDs of Dogs in Nigeria, where despite a large burden of ticks and TBDs there is little data on the prevalence of either for veterinarians and human health professionals to make informed decisions regarding treatment and control.
Most existing studies on cattle have indicated that Anaplasma, Babesia, Theileria, Ehrlichia, Hepatozoon and Candidatus Neoehrlichia species are present in Nigeria. However, dogs kept in much closer contact with their owners, may represent a higher risk of zoonotic TBDs transmission. This study used a combination of morphological and molecular identification of ticks and tick borne pathogens, and IDEXX 4Dx kits for pathogen antibody detection from canine blood, we examined 93 dogs to date.
Rhipicephalus sanguineus was the most abundant tick found on Nigerian dogs. Babesia species were the most abundant tick borne pathogen, followed by Ehrlichia species. This study serves as the first report of Babesia microti like species, Theileria parva, Babesia bovis, Anaplasma phagocytophilium and Ehrlichia chaffeensis in Nigerian dogs. There was no evidence of Borrelia Burgdorferi sensu lato nor Dirofilaria species in Nigerian dogs. The presence of Babesia microti and Anaplasma phagocytophilium is a direct public threat. Further testing of additional 200 dog samples and multivariate modelling of demographic risk factors, will enable us develop treatment and control guidelines for TBDs for Nigerian Veterinarians and Dog owners.
Characterisation of Burkholderia prophages and discovery of a novel inducible phage from B. vietnamiensis G4 that is widely distributed across the species
Authors: Weiser Rebecca , Ling Zhong , Otter Ashley , Mullins Alex , Mahenthiralingam Eshwar 
Published: July 2020

Burkholderia species have environmental, industrial and medical significance, and are important opportunistic pathogens in individuals with cystic fibrosis (CF). Approximately 10% of Burkholderia genomes (6-9 Mb) are horizontally acquired material, representing a rich source of mobile genetic elements including prophages. There is limited research on Burkholderia bacteriophages, their contributions to genome evolution, virulence and antimicrobial resistance, or biotechnological and therapeutic applications. We investigated prophage carriage in Burkholderia and aimed to isolate and characterise inducible bacteriophages from B. vietnamiensis.

Burkholderia genomes were screened for prophages using PHASTER. Prophage genomes were compared using MASH and visualised with ProgressiveMauve. Phylogenomics was used to assess the distribution of prophages across B. vietnamiensis strains. Spontaneously induced phages were characterised to determine linkage between prophage regions and isolated phages, bacteriophage morphology and host range.
Prophage carriage across 456 Burkholderia strains (spanning 43 species) was high; 716 intact prophages were discovered and polylysogeny was common. In B. vietnamiensis alone, 115 prophages were identified from 81 strains, with evidence of shared prophage carriage between related and diverse strains. Three novel inducible phages were isolated from B. vietnamiensis strain G4 and their genomic origins localised putatively. One phage (vB_BvM-G4P1; family Myoviridae) had inhibitory activity against multiple strains of 5 B. cepacia complex species, including species prevalent in CF infections.
Prophages are numerous in Burkholderia genomes and contribute to strain diversity. There is huge potential for further investigation into the functional implications of prophage carriage and its impact on genome evolution, in addition to the isolation of novel bacteriophages.
Molecular detection of Mycoplasma amphoriforme and Ureaplasma spp. from patient samples previously investigated for Mycoplasma pneumoniae infection
Authors: Rehman Safi , Maddocks Sarah , Afshar Baharak , Day Jessica , Chalker Victoria , Beeton Michael 
Published: July 2020

M. amphorifrome(MAM), is a novel pathogen associated with chronic respiratory tract infections in immunocompromised patients, but prevalence in immunocompetent patients is not established. Ureaplasma spp. are a known cause of hyperammonaemia in lung transplant patients. To date, their prevalence has been well documented in neonatal lungs but observations in adults is lacking.
161 samples were obtained from Public Health England, submitted previously for M. pnuemoniae (MPN) investigation, which were screened for MAM using quantitative PCR. MAM positive samples were then screened for macrolide resistance using 23s rRNA (domain V) PCR amplification and Sanger-sequencing. The 161 samples were also screened for Ureaplasma spp. using conventional PCR involving different primer sets for initial screening and subsequent differentiation between Ureaplasma spp. by targeting a variable region.
10 of 161 samples were found positive for MAM (6.2%), all of which were found to be genotypically macrolide susceptible and 9/10 positives were isolated from males. Three of the total positives were previously identified to be MPN positives. None of the samples taken during the summer months had any MAM DNA detected. Five of the 161 samples tested positive for U. parvum (3.1%), 3/5 of which were from isolated from males.
These data suggest that MAM maybe an emerging pathogen that can cause persistent respiratory infections. The lungs may represent a possible reservoir for U. parvum and source for donor-derived lung infections. Further investigation is required into the prevalence of these organisms.
Comparing the innate and humoral immune responses of different chicken lines to Infectious Bronchitis Virus (IBV) infection
Authors: Dowell Isaac , Steyn Angela , Keep Sarah , Bickerton Erica , Hammond John 
Published: July 2020

Infectious Bronchitis Virus (IBV) is a gammacoronavirus that is prevalent in commercial chicken flocks, resulting in characteristic clinical signs including snicking, rales, decreased tracheal ciliary activity, reduced weight gain and reduced egg production. Preliminary results indicate that there is a different clinical response to IBV infection in different chicken lines. Therefore, we aim to determine whether there is a differential innate or humoral immune response to IBV between chicken lines.
A series of in vivo experiments were conducted comparing brown leghorns (Rhode Island Red, RIR (Roslin)) to white leghorns (from Valo and Ovagen). Trachea and bursa were collected from infected and control birds at four-, six- and fourteen-days post infection (dpi). There was a difference in snick rate and rales between the RIRs and the white leghorns (both lines). However, no difference was observed in ciliary activity. Viral load was determined by absolute quantification using qRT-PCR. The viral load in the trachea of RIRs was significantly lower (p<0.05) at 6 dpi compared to 4 dpi, unlike in Ovagen birds where there was no significant difference between the timepoints. Relative gene expression of IFN-α, IFN-β, IFN-γ, IL-6 and IL-1β in these tissues will be measuredby qRT-PCR. Serum was processed from whole blood collected at zero and ten dpi for use in IBV specific ELISAs which will measure antibody responses in the chicken lines. This project aims to explore immune responses against IBV as well as identifying the causes of variability in experimentation using chickens to investigate IBV infection.
Gene transfer agents: Another step towards a mechanistic understanding of expression
Authors: Sherlock David , Benn Millie , Fogg Paul 
Published: July 2020

Gene transfer agents (GTAs) are small viruses that package and transfer random pieces of the producing cell’s genome but are unable to transfer all the genes required for their own production. GTAs are able to spread any DNA in the host cell and so their potential impact upon bacterial evolution and antimicrobial resistance is immense.
Our discovery that the product of gene rcc01865 is a specific GTA activation factor (GafA) for the model Rhodobacter capsulatus GTA (RcGTA) and that GafA is essential for RcGTA production, has provided the link between GTA production and host regulatory pathways. However, while GafA has significantly improved our understanding of GTA regulation the complete mechanism is unclear. Our goal was to investigate the GafA mechanism of action in more detail. We demonstrate direct protein-protein interaction between GafA and the RNA polymerase omega subunit (RNAP Ω) using bacterial-two-hybrid and pull down assays. Further evidence for the interaction has come from random and site directed mutagenesis of gafA and targeted truncations. GafA mutants were also tested to assess their impact on RcGTA production. RNAP Ω is thought to recruit alternative sigma factors to the RNAP holoenzyme. Regions of GafA also share sequence homology with known sigma factor proteins, and we propose that GafA acts as an alternative sigma factor to co-ordinate expression of disparate RcGTA genes. Our results advance our understanding of this fascinating mode of horizontal gene transfer, not only in the model species but also in other potential GTA producing species that contain gafA homologues.
MORF: An online tool for exploring microbial cell responses using multi-omics analysis
Authors: Springthorpe Vicki , Leaman Rosalyn , Sifouna Despoina , Bennett Joyce , Thomas Gavin 
Published: July 2020

With continuing improvements and reducing costs of high-throughput technologies, microbiologists are increasingly collecting multi-omics datasets. However, the tools and techniques used to analyse these kinds of data are often highly specialised and require bioinformatics, statistics and often coding experience. Many studies also tend to report on a single aspect of the data whilst overlooking other potentially interesting phenomena. Consequently, many of these multi-omics data sets are not being used to their full potential. MORF was created as a solution to these problems by providing access to multi-omics datasets through an online interface which presents the data in a user-friendly and accessible way. No coding experience or specialist statistical knowledge is required, and users are free to explore the data using interactive graphics and simple analysis tools.
Here we demonstrate MORF using multi-omics datasets from two experiments using bacteria in industrial fermentation processes. First, Escherichia coli engineered to produce styrene, a valuable chemical used in the manufacture of polymers, and secondly a Clostridium which produces the biofuel butanol. A key outcome was the identification of targets believed to be involved in responding to membrane stress, which we identified using MORF’s differential gene and protein analysis tools. Work is underway to further characterise and engineer these targets to improve product yields. In conclusion, MORF provides a framework for omics analysis that can be applied to any organism or set of experimental conditions, and will help researchers and collaborators to make the most of their data.