bluuebunny/crossref_metadata_2025_split huggingface dataset:
Taking charge: Using electrochemical impedance spectroscopy to quantify biofilm formation in Pseudomonas spp.
Authors: Riordan Lily , Dunphy Raymond , Lasserre Perrine , Corrigan Damion , McCormick Christopher , Murray Paul , Duncan Katherine 
Published: July 2020

The opportunistic pathogen, Pseudomonas aeruginosa, is infamous for its ability to rapidly form biofilms (<24 h) in inhospitable environments and the development of antimicrobial resistance (AMR). It has been seen to have resistance to nearly all known antibiotics, including last-line antibiotics colistin and carbapenems. AMR is currently considered one of the biggest threats to human health, causing 700,000 deaths annually, expected to rise to 10 million deaths per year by 2050. P. aeruginosa, alongside other opportunistic pathogens, has been implicated in infections following various surgical procedures. Such infections compromise patient recovery and, when a medical implant is present a biofilm can develop that will ultimately require a complex revision surgery to remove the infection.
In this study, impedance spectroscopy and differential pulse voltammetry were carried out in parallel to measure electrochemical and impedance properties of bacteria, allowing for identification and quantification of pyoverdine and pyocyanin; bacterial metabolites. Three Pseudomonas spp. (P. aeruginosa, P. fluorescens and P. putida) were assayed in liquid culture at OD600. The sensor was standardised with pyoverdine and pyocyanin, with an electrochemical reading taken every 30 minutes up to 4 hours. This assay was repeated with Pseudomonas spp. growing in biofilms in LB broth, with a screen-printed electrode as the solid surface. Readings were then used to correlate metabolite production to biofilm production in each Pseudomonas sp. Pyoverdine correlated with biofilm formation for all three assayed Pseudomonas, with variation in the quantity of metabolite produced between species. This allows the two metabolites to be used as indicators of biofilm mass on devices and surfaces.
Bifidobacterium adolescentis shows potential to strengthen host defence against gastrointestinal infection via inhibition of the opportunistic pathogen Candida albicans and stimulation of human-isolated macrophages killing capacity in vitro
Authors: Ricci Liviana , Mackie Joanna , Lenardon Megan D. , Jukes Caitlin , Hegazy Ahmed N. , Brown Alistair J.P. , Duncan Sylvia H. , Walker Alan W. 
Published: July 2020

The human gut microbiota enhances the host’s resistance to enteric pathogens via colonisation resistance, a phenomenon that is driven by multiple mechanisms, such as production of antimicrobial metabolites and activation of host immune responses. However, there is limited information on how individual gut bacterial species, particularly many of the dominant anaerobes, might impact the host’s defence.
This study investigated the potential of specific human gut isolates to bolster the host’s resistance to infection. First, by antagonising the opportunistic fungal pathogen Candida albicans, and secondly, by modulating the killing capacity of human-isolated macrophages in vitro.
Co-culturing C. albicans with faecal microbiota from different healthy individuals revealed varying levels of fungal inhibition. In vitro assays with a panel of representative human gut anaerobes confirmed that culture supernatants from certain bacterial isolates, in particular of Bifidobacterium adolescentis, significantly inhibited C. albicans growth. Mechanistic studies revealed that microbial fermentation acids including acetate and lactate, in combination with the associated decrease in pH, were strong drivers of this inhibitory activity.
In the second in vitro assay, human-isolated macrophages were exposed to bacterial supernatants, and subsequently tested for their capacity to eliminate adherent-invasive Escherichia coli. Among the gut anaerobes tested, B. adolescentis was revealed to exert the strongest immunostimulatory and killing effect when compared to the unstimulated macrophages control.

B. adolescentis is known to be stimulated by dietary consumption of resistant starch andmay therefore represent an attractive target for the development of probiotic and prebiotic interventions tailored to enhancethe host’s natural defences against infection.
Air pollution induces an adaptive response in Staphylococcus aureus and alters host-pathogen interaction
Authors: Purves Jo , Corscadden Louise , Purser Lillie , Selley Liza , Monks Paul , Ketley Julian , Andrew Peter , Morrissey Julie 
Published: July 2020

Air pollution is a major global health problem, with around 91% of the world’s population living in areas that exceed the WHO air pollution guidelines. This complex mix of pollutants almost always includes particulate matter (PM), and this has the greatest impact on human health. PM exposure contributes to a range of diseases such as COPD, heart disease and respiratory infections. 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 Black Carbon (BC) exposure results in species-specific alterations in biofilm structure in both Streptococcus pneumoniae and Staphylococcus aureus, altered biofilm protectivity against antibiotic exposure, and S. pneumoniae bacterial colonisation in vivo.
Following on from this ground-breaking work, our current data show that the bacterial response to BC occurs at the genetic level, altering the transcription of key genes involved in biofilm formation, colonisation and virulence. Bacterial adhesion to and invasion of human epithelial cells is significantly increased when S. aureus are pre-exposed to BC prior to infection compared to naïve S. aureus cells. In a murine respiratory colonisation model, both S. aureus co-infected alongside BC, and crucially S. aureus pre-exposed to BC, show increased colonisation of the nasopharynx and lungs. These data suggest that the bacteria are responding and adapting to exposure to air pollution, and this has an impact on how the bacteria infect the host.
Regulation of Rhodobacter capsulatus gene transfer agent production
Authors: Duncan Ian , Sherlock David , Fogg Paul 
Published: July 2020

Horizontal gene transfer (HGT) enables the spread of antimicrobial resistance, virulence, metabolic and other genes conferring an advantage to the organism. HGT is enhanced in biofilms because of increased cell-cell contact (conjugation), and eDNA in the biofilm matrix causing development of competence and providing material for transformation. Production of the Rhodobacter capsulatus gene transfer agent (RcGTA), another mechanism of HGT, could also increase in biofilm as high cell density increases the proportion of GTA particles produced that encounter a target cell. RcGTA is a phage-like particle that packages ∼4.5 kb pieces of random DNA from the producing cell’s genome and transfers it to a recipient cell. Five loci comprise the RcGTA genome: a 15kb cluster containing most of the RcGTA structural genes, a cell lysis locus, two structural loci encoding head spikes and tail fibres, and a maturation/regulation locus that includes that master regulator, gafA.
I assayed RcGTA production using gene transfer bioassays and biofilm using a 96 well plate assay. I will present data showing that deletion of four GTA-related genes, including gafA itself, all lead to reduced biofilm production. All four gene knock-outs also strongly reduce GTA-mediated gene transfer, suggesting GTA production and biofilm are co-regulated. I will also present work to characterize GTA production in biofilms, for example by monitoring the transfer of fluorescent protein genes through confocal microscopy, and assessing how specific regulators control this process. Biofilms are ubiquitous in the environment so studying the spread of antimicrobial resistance genes by GTAs is important.
Human host cell entry restriction of Lassa and other arenaviruses
Authors: Stott Robert , Strecker Thomas , Foster Toshana 
Published: July 2020

Arenaviruses are the largest family of viral haemorrhagic fever causing viruses. They have worldwide distribution and are divided into Old World (OW) and New World (NW) viruses based on their phylogeny, geographical distribution and serological cross-reactivity. Endemic to West Africa and South America, these emerging RNA viruses jump the species barrier from their natural rodent hosts to humans, resulting in illnesses ranging from mild flu-like syndromes to severe and highly fatal haemorrhagic zoonoses. Recent increased frequency of outbreaks and associated high fatality rates of the most common arenavirus, Lassa, in Nigeria has emphasised that these viruses should no longer be treated as causes of sporadic epidemics. The immense impact of these outbreaks on human health is further exacerbated by the lack of vaccines and effective treatments and makes it imperative to understand the molecular basis of viral pathogenesis and immune evasion.
Virus entry is a key determinant of viral host range, cellular tropism and disease outcome, hence, targeting this step of the arenavirus lifecycle could have significant impact on the control of viral infection. Our data demonstrate for the first time a synergistic restriction activity against arenavirus entry by two cellular host factors known for their control of enveloped virus infections. This co-operative restriction activity appears to conserved and we have evidence that arenaviruses may have evolved strategies to escape inhibition, through entry receptor switching, thus alluding to an understanding of the dynamics of arenavirus infection and adaptations that the viruses have made to escape host restriction pressures.
Diverse mutational routes to the restoration of motility in a soil bacterium
Authors: Flanagan Louise , Horton James , Taylor Tiffany 
Published: July 2020

Restoration of a phenotype following insertion of a crippling mutation gives us insights into the adaptability of an organism. Mutational routes to the restoration of phenotypes can be diverse. Deletion of the master regulator (fleQ) for flagellar synthesis genes renders Pseudomonas fluorescens immotile, but after being put under strong selection to swim, it reliably re-evolves motility.
In order to uncover how the immotile bacteria regain their ability to swim they are inoculated into swimming agar plates and sampled from the leading edge of the motile zone. These samples are sequenced at a range single locus sites, predicted to be where causative mutations for the restoration of motility will be found (as indicated from previous research).
In the engineered immotile strain Pf0-2x, a huge variety of mutations, consisting of SNPs, multi-codon deletions, and frameshifts are observed across all candidate loci. In a complex environment (LB) 50% of initial restorative mutations occur in glnA, a glutamine synthetase gene. In a minimal media environment (M9) 45% of these mutations occur in ntrB, a gene for a kinase that forms part of a two component system. These findings contrast strongly with similar work in the related P. fluorescens strain SBW25, where the same SNP is repeatedly found across all environments. Interestingly, this SNP has never been seen in Pf0-2x.
These results highlight how preferential mutational routes can vary across environments, and that strain-to-strain differences can have a major impact types of mutations that are uncovered and selected for by evolution.
Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas
Authors: Hu Xin , Estecio Marcos R. , Chen Runzhe , Reuben Alexandre , Wang Linghua , Fujimoto Junya , Carrot-Zhang Jian , McGranahan Nicholas , Ying Lisha , Fukuoka Junya , Chow Chi-Wan , Pham Hoa , Godoy Myrna C.B. , Carter Brett W. , Behrens Carmen , Zhang Jianhua , Antonoff Mara B. , Sepesi Boris , Lu Yue , Pass Harvey , Kadara Humam , Scheet Paul , Vaporciyan Ara A. , Heymach John V. , Wistuba Ignacio I. , Lee J. Jack , Futreal P. Andrew , Su Dan , Issa Jean-Pierre J. , Zhang Jianjun 
Published: July 2020

ABSTRACTThe evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8+ T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and allelic imbalance burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas.
Effects of environmental factors on severity and mortality of COVID-19
Authors: Kifer Domagoj , Bugada Dario , Villar-Garcia Judit , Gudelj Ivan , Menni Cristina , Sudre Carole , Vučković Frano , Ugrina Ivo , Lorini Luca F , Posso Margarita , Bettinelli Silvia , Ughi Nicola , Maloberti Alessandro , Epis Oscar , Giannattasio Cristina , Rossetti Claudio , Kalogjera Livije , Peršec Jasminka , Ollivere Luke , Ollivere Benjamin J , Yan Huadong , Cai Ting , Aithal Guruprasad P. , Steves Claire J , Kantele Anu , Kajova Mikael , Vapalahti Olli , Sajantila Antti , Wojtowicz Rafal , Wierzba Waldemar , Krol Zbigniew , Zaczynski Artur , Zycinska Katarina , Postula Marek , Lukšić Ivica , Čivljak Rok , Markotić Alemka , Brachmann Johannes , Markl Andreas , Mahnkopf Christian , Murray Benjamin , Ourselin Sebastien , Valdes Ana M. , Horcajada Juan P , Castells Xavier , Pascual Julio , Allegri Massimo , Primorac Dragan , Spector Tim D. , Barrios Clara , Lauc Gordan 
Published: July 2020

ABSTRACTBackgroundMost respiratory viruses show pronounced seasonality, but for SARS-CoV-2 this still needs to be documented.MethodsWe examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application.FindingsMeta-analysis of the mortality risk in seven European hospitals estimated odds ratios per one day increase in the admission date to be 0.981 (0.973-0.988, p<0.001) and per increase in ambient temperature of one degree Celsius to be 0.854 (0.773-0.944, p=0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to Intensive Care Unit and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time.InterpretationSeverity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.
Impact of COVID-19 Second Wave on Healthcare Networks in the United States
Authors: Hassan Emad M. , Mahmoud Hussam 
Published: July 2020

AbstractThe risk of overwhelming healthcare systems from a second wave of COVID-19 is yet to be quantified. Here, we investigate the impact of different reopening scenarios of states around the U.S. on COVID-19 hospitalized cases and the risk of overwhelming the healthcare system while considering resources at the county level. We show that the second wave might involve an unprecedented impact on the healthcare system if an increasing number of the population becomes susceptible and/or if the various protective measures are discontinued. Furthermore, we explore the ability of different mitigation strategies in providing considerable relief to the healthcare system. The results can aid healthcare planners, policymakers, and state officials in making decisions on additional resources required and on when to return to normalcy.One Sentence SummaryA second wave of COVID-19 will have an unprecedented impact on the healthcare system.
Revisiting Role of Bilateral Ligation of Internal Iliac Arteries and Preperitoneal Pelvic Packing for Hemorrhage Control in Patients with Pelvic Injuries in Resource Constraint Settings
Authors: Bagaria Dinesh Kumar , Anwer Majid , Choudhary Narendra , kumar Abhinav , Priyadarshini Pratyusha , Banerjee Niladri , Alam Junaid , Gupta Amit , Mishra Biplab , Sagar Sushma , Kumar Subodh 
Published: July 2020

AbstractBackgroundSince the description of bilateral ligation of internal iliac arteries (BLIIA) and preperitoneal pelvic packing (PPP) for haemorrhage control in pelvic injury patients, multiple reports have been published advocating its use with acceptable outcomes. We analyzed our experience with this technique in a setting where the facility of hybrid Operating room for simultaneous angioembolisation is not available.Material and MethodsWe prospectively analysed data of sixty-six patients who presented in a state of unresponsive shock with pelvic fracture between January 2014 and September 2019. After initial resuscitation, they all underwent BLIIA with PPP as part of damage control surgery.ResultsOut of 66 patients, 55 were male. The mean age was 36.12 years. All patients sustained blunt trauma, with road traffic injuries being the most common mechanism involving 65 % of the patients followed by fall from height. The mean systolic blood pressure at the time of surgery was 77 ±34.46mm Hg. Median packed red blood cell transfusion in the first 24 hours was 8.5 units with IQR of 6-12. The hemorrhage related mortality was 48%.ConclusionBLIIA with PPP may be considered as a viable treatment option in hemodynamically unstable patients with pelvic injuries in resource constraint facilities.
Atomoxetine modulates the contribution of high- and low-level signals during free viewing of natural images in rhesus monkeys
Authors: Reynaud Amélie J. , Blini Elvio , Koun Eric , Macaluso Emiliano , Meunier Martine , Hadj-Bouziane Fadila 
Published: July 2020

AbstractVisuo-spatial attentional orienting is fundamental to selectively process behaviorally relevant information, depending on both low-level visual attributes of stimuli in the environment and higher-level factors, such as goals, expectations and prior knowledge. Growing evidence suggests an impact of the locus-coeruleus-norepinephrine (LC-NE) system in attentional orienting that depends on task-context. Nonetheless, most of previous studies used visual displays encompassing a target and various distractors, often preceded by cues to orient the attentional focus. This emphasizes the contribution of goal-driven processes, at the expense of other factors related to the stimulus content. Here, we aimed to determine the impact of NE on attentional orienting in more naturalistic conditions, using complex images and without any explicit task manipulation. We tested the effects of atomoxetine (ATX) injections, a NE reuptake inhibitor, on four monkeys during free viewing of images belonging to three categories: landscapes, monkey faces and scrambled images. Analyses of the gaze exploration patterns revealed, first, that the monkeys spent more time on each fixation under ATX compared to the control condition, regardless of the image content. Second, we found that, depending on the image content, ATX modulated the impact of low-level visual salience on attentional orienting. This effect correlated with the effect of ATX on the number and duration of fixations. Taken together, our results demonstrate that ATX adjusts the contribution of salience on attentional orienting depending on the image content, indicative of its role in balancing the role of stimulus-driven and top-down control during free viewing of complex stimuli.
miR6236, a microRNA suppressed by the anisotropic surface topography, regulates neuronal development and regeneration
Authors: Chen Yi-Ju , Huang Yung-An , Ho Chris T. , Yang Jinn-Moon , Chao Jui-I , Li Ming-Chia , Hwang Eric 
Published: July 2020

AbstractIt has been well studied that the surface topography affects the growth and development of neurons. However, the precise mechanism that the surface topography leads to cellular changes remains unknown. In this study, we created an anisotropic surface using nanodiamonds and discovered this surface topography accelerates the development of primary neurons from both the central and peripheral nervous systems. Using RNA sequencing technology, a previously uncharacterized microRNA (miR6236) was found to exhibit significant and the most substantial decrease when neurons are cultured on this nanodiamond surface. Gain- and loss-of-function assays confirm that miR6236 is the predominant molecule responsible for converting the surface topography into biological responses. We further demonstrate that the depletion of miR6236 can enhance neuroregeneration on inhibitory substrate, uncovering its therapeutic potential for promoting central nervous system regeneration.
Global Geographic and Temporal Analysis of SARS-CoV-2 Haplotypes Normalized by COVID-19 Cases during the Pandemic
Authors: Justo Arevalo Santiago , Zapata Sifuentes Daniela , Huallpa Robles Cesar , Landa Bianchi Gianfranco , Castillo Chavez Adriana , Garavito-Salini Casas Romina , Uceda-Campos Guillermo , Pineda Chavarria Roberto 
Published: July 2020

ABSTRACTSince the identification of SARS-CoV-2, a large number of genomes have been sequenced with unprecedented speed around the world. This marks a unique opportunity to analyze virus spreading and evolution in a worldwide context. Currently, there is not a useful haplotype description to help to track important and globally scattered mutations. Also, differences in the number of sequenced genomes between countries and/or months make it difficult to identify the emergence of haplotypes in regions where few genomes are sequenced but a large number of cases are reported. We propose an approach based on the normalization by COVID-19 cases of relative frequencies of mutations using all the available data to identify major haplotypes. Furthermore, we can use a similar normalization approach to tracking the temporal and geographic distribution of haplotypes in the world. Using 171 461 genomes, we identify five major haplotypes (OTUs) based on nine high-frequency mutations. OTU_3 characterized by mutations R203K and G204R is currently the most frequent haplotype circulating in four of the six continents analyzed. On the other hand, during almost all months analyzed, OTU_5 characterized by the mutation T85I in nsp2 is the most frequent in North America. Recently (since September), OTU_2 has been established as the most frequent in Europe. OTU_1, the ancestor haplotype is near to extinction showed by its low number of isolations since May. Also, we analyzed whether age, gender, or patient status is more related to a specific OTU. We did not find OTU’s preference for any age group, gender, or patient status. Finally, we discuss structural and functional hypotheses in the most frequently identified mutations, none of those mutations show a clear effect on the transmissibility or pathogenicity.