bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the association between organic acids and phenotypic alterations of avian pathogenic Escherichia coli
Authors: Fallata Ghaith , Wall Doanl 
Published: July 2020

The excessive use of antibiotics in agriculture is routinely described as a major contributor to bacterial resistance. Globally, antibiotics are widely used as growth supplements in livestock. This has led to concerns regarding human-use antibiotics in food and food-producing animals. Lately, organic acids (OAs) such as propionic acid (PA) and formic acid (FA) have been increasingly used as alternative antimicrobials or preservatives instead of antibiotics. These are particularly efficient at removing salmonella.
Recently, we have shown that exposure of a Crohn’s Disease associated bacterial pathotype, Adherent-invasive Escherichia coli (AIEC), to PA significantly alters its phenotype resulting in increased adhesion and invasion of epithelial cells and increased persistence through biofilm formation. AIEC are both evolutionarily and phylogenetically related to avian pathogenic Escherichia coli (APEC), however the virulence mechanisms of APEC in poultry remain unclear. The widespread use of OAs as growth supplements and antimicrobials in the poultry industry is a rising concern due to the ability of OAs to alter the bacterial pathotype. In this study, we examined the effect of FA on the phenotype of APEC. We observed that following FA-exposure, APEC showed an increased ability to adhere to and invade human intestinal epithelial cells and form better biofilms both aerobically and anaerobically. Worryingly, these isolates also showed an increased resistance to several antibiotics. These results suggest that the increasing use of alternative antimicrobial such as FA in the poultry industry may lead to APEC strains that are increasingly virulent towards human cells with a potential for increased horizontal transmission
Cell surface lipid composition and hydrophobicity governs tuberculosis evolution and pathogenicity
Authors: Minnikin David 
Published: July 2020

The evolution of tubercle bacilli correlates closely with changes in cell envelope surface lipid composition (Donoghue et al.
Diversity 2017, 9:46; Jankute et al.
Scientific Reports 2017, 7:1315). Smooth, hydrophilic “Mycobacterium canettii” is the first recognisable member of the Mycobacterium tuberculosis complex, but it has reduced pathogenicity and poor aerosol transmission. In contrast, rough M. tuberculosis is very hydrophobic and readily spread in aerosols. Starting from hydrophilic surface lipids in environmental Mycobacterium kansasii, intermediate “M. canettii” adds hydrophobic lipids but retains overall cell hydrophilicity. Eliminating hydrophilic lipooligosaccharides (LOSs) and phenolic glycolipids (PGLs) from “M. canettii” leads to M. tuberculosis with a refined selection of hydrophobic lipids, namely phthiocerol dimycocerosates (PDIMs), pentaacyl trehaloses (PATs) and sulfoglycolipids (SGLs). The relative hydrophobicity of M. tuberculosis is double that of representatives of M. kansasii and “M. canettii”.
The above changes have implications both for the onset of tuberculosis and pinpointing evolutionary hosts. Tuberculosis has not been found in Homo sapiens during the Late Pleistocene, but megafauna are the most likely hosts; characteristic bone lesions have been validated by TB DNA amplification and lipid biomarkers in bison metacarpals up to 17,000 years old. Late Pleistocene enhanced TB hydrophobicity and aerosolisation may have produced megafaunal pandemics, with extinction of bison, mastodons and contemporary taxa. The oldest H. sapiens tuberculosis is from the “Fertile Crescent” back to 9-11ka BP at the start of the Holocene. Naïve humans arriving “Out of Africa” may have encountered newly virulent tubercle bacilli of megafaunal origin, recently refined through a distinct “bottleneck”.
Characterising the role of Proline Tyrosine Kinase 2 during Adherent-invasive Escherichia coli infection of macrophages
Authors: Li Xiang , Ormsby Michael , Wall Donal 
Published: July 2020

Studies have implicated that Adherent-invasive Escherichia coli (AIEC) in the aetiology of Crohn’s Disease (CD), a chronic inflammatory bowel disease (IBD). CD-associated AIEC are characterised by an ability to adhere to and invade intestinal epithelial cells and replicate intracellularly in macrophages. This occurs as AIEC form vacuoles within phagolysosomes, preventing macrophage-mediated killing. However, little is known about the interaction of macrophage proteins with AIEC.
In this study, we used an in vitro infection model to identify macrophage proteins associated with AIEC intracellular replication. We identified the importance of proline-rich tyrosine kinase 2 (PYK2) in AIEC infection. PYK2 is widely expressed in epithelial cells and hematopoietic cells and plays essential roles in tumorigenesis and tumour progression. PYK2 is also overexpressed in patients with intestinal and colorectal cancer (CRC). CRC is one of the major long-term complications of IBD, especially in patients with long disease duration, a large extent of colitis, and uncontrolled inflammation. Moreover, PYK2 has been identified as an IBD risk loci via large scale genome-wide association studies.
Our in vitro models have demonstrated that the addition of PYK2 inhibitor PF-431396 during infection results in a significant decrease in intracellular replication of AIEC. This has been quantified using fluorescence immunostaining and imaging flow cytometry. These results suggest that PYK2 may play a role in intracellular bacteria survive and replication. Our future work aims to further understand the relationship between PYK2, AIEC and CD.
Explosive intron expansion and fickle rDNA copies within plastid genomes of Euglenophyta
Authors: Maciszewski Kacper , Karnkowska Anna 
Published: July 2020

Several eukaryotic lineages gained the ability of photosynthesis by acquiring plastids in the events of primary endosymbiosis with cyanobacteria, or secondary endosymbiosis with plastid-bearing eukaryotes. Plastids possess genomes (ptDNA) with genetic contents considerably reduced as a result of gene losses and transfers to the host’s nucleus. Still, ptDNA encodes components of various metabolic processes, including photosynthesis. Plastid genomes usually retain quadripartite structure with two rDNA-bearing inverted repeats, but the reason for its conservation, and the consequences of its decline, have not been fully understood.
As the model group to study plastid genome evolution, we chose euglenids (Euglenophyta), whose ancestor acquired the secondary plastid by endosymbiosis with a green alga. The organization of ptDNA in this lineage is rather diverse: we have shown that loss of one repeat occurred at least three times, while some species in the genus Euglena possess tandemly repeated rDNA copies. The ptDNA of euglenids is also intron-rich, but we did not confirm the previously proposed strong correlation between the prevalence of introns and quantity of maturases.
Although euglenophytes are predominantly photosynthetic, a few of them lost their photosynthetic capabilities independently. Thus far, only Euglena longa has been shown to possess vestigial plastids with reduced genome; we observed that another strain lost its plastid genome completely. Currently, we are investigating the loss and retention of metabolic functions in the plastids of other non-photosynthetic euglenophytes. This, along with investigation of ptDNA structure, will bring new insights into the evolutionary processes shaping the diversity of eukaryotic plastids.
Investigating the mechanisms of BK polyomavirus egress and virus-host interactions
Authors: Ho Sophia , Caller Laura , Beale Rupert , Crump Colin 
Published: July 2020

BK polyomavirus (BKPyV) is a small, non-enveloped dsDNA virus that infects 70-90% of the world's population and causes a lifelong, silently persistent infection. In immunocompromised individuals, BKPyV replication can result in serious pathology. Bone marrow transplant patients can develop a haemorrhagic cystitis, and in kidney transplant patients BKPyV replication can provoke a nephropathy that leads to deterioration of allograft function and eventual loss of the transplanted organ. There are currently no antiviral treatments with clinical efficacy against BKPyV associated nephropathy.
While the life cycles of non-enveloped viruses are often assumed to require cell lysis to release progeny virions, we have evidence to suggest that BKPyV exits the cell via non-lytic means using an unconventional secretory pathway. We have investigated the effects of knocking out cellular genes thought to be involved in unconventional secretory pathways that bypass the Golgi apparatus on the release of BKPyV. We observe decreased BKPyV release from cells that have undergone CRISPR-mediated knockout of Golgi Reassembly Stacking Protein (GORASP) 1 or 2. Investigation of BKPyV-induced changes to the plasma membrane of infected cells demonstrated increased cell surface expression of transmembrane proteins normally resident in the endoplasmic reticulum. This appears to be inhibited by the knockout of GORASP1 or 2, suggesting that virions and ER markers are secreted via a common pathway in infected cells. These experiments are uncovering novel virus-host interactions that, when targeted, could help prevent BKPyV-associated nephropathy and allograft loss.
Characterisation and identification of STEC O157 pathogenicity using machine learning
Authors: Khatun Suniya , J. Dallman Timothy , Jenkins Claire 
Published: July 2020

Shiga toxin-producing Escherichia coli O157: H7 (STEC) is a zoonotic pathogen that is globally dispersed, causing severe gastroenteritis when transmitted from ruminants to humans through direct or indirect contact with animals, their environment or contaminated food. Symptoms are varied in severity; from mild to bloody diarrhoea with more serious sequalae including hemolytic uremic syndrome (HUS) which can be fatal. Although there is compelling evidence that the Shiga toxin sub-type is a key predictor of disease severity, differences in virulence potential of strains with the same Shiga toxin profile are often observed. In this study, we employ machine learning algorithms to explore the relationship between the STEC genome with clinical outcome.
Kmer-counts of variable length (9-100 base pair) from 1148 isolates of STEC O157:H7, representing two years of routine surveillance in England, were matched to their respective clinical outcome data. A Random Forest classifier was developed and validated with the objective of inferring the clinical symptoms associated with a given STEC genome. Clinical outcomes were categorised into asymptomatic, diarrhoea, bloody diarrhoea and HUS. The model correctly classified 160 out of 190 cases of bloody diarrhoea, 81 out of 128 cases of diarrhoea and 7 out of 12 cases of HUS, with average AUC ROC score of 90%. Kmers deemed important for distinct classification were characterised and matches related to Shiga toxin 2a phage integration and excision genes and adhesion and transporter proteins were identified. This is consistent with reported virulence factors in the literature, supporting this approach of de novo pathogen characterisation.
Interreg 2 seas Project: Health For Dairy Cows, H4DC
Authors: A. Ribeiro Claudia , Pinto Pedro , J. Warren Christopher , Vlandas Alexis , Vuylsteke Isabelle , Canniere Evi , Dellevoet Martine , Roemen Janine , Bourgeois Anne , Leruste Helene , Roblin Maud , Windal Feryal , Benhabiles Halim , Hammouma O. , Deweer Caroline , Robinson Gary 
Published: July 2020

Cryptosporidium spp. are microbial parasites that infect the gastrointestinal tract of humans and many animals, causing cryptosporidiosis, a disease characterised by acute watery diarrhoea. In dairy farms, C. parvum is the most common species in calves, leading to high mortality rate, stunted growth, and consequently high economic losses. Trade between farms and breeding centres is a major risk factor in the spread of such parasites, posing a threat to other farms worldwide as well as to human health. This problem is aggravated by the lack of good breeding practices, efficient detection tools, and lack of effective anti-cryptosporidial drugs.
To address cryptosporidiosis in dairy farms, we have established the ‘Health For Dairy Cows (H4DC)’ consortium in order to tackle some of the aforementioned issues.
Herein, we will present preliminary data from a 3-step strategy:
1)Dissemination of pilot farms in France, Belgium, The Netherlands and England. This collaboration will serve to test the effect of new husbandry practices in the occurrence of Cryptosporidium, which will aim to decrease Cryptosporidium incidence and ultimately decrease the economic burden of cryptosporidiosis.
2)These pilot farms will later be used as testing-grounds of the low-cost and easy-to-use in-situ C. parvum detection tool that will be developed during this project.
3)Development of a cell-based drug-screening system which will be used to screen various drugs and compounds for anti-Cryptosporidium activity.
Finally, data from these findings will be used to establish model and strategies in order to transfer the developed technologies to both farmers and biotech/pharmaceutical companies.
The complete sequence, annotation and comparative analysis of the Escherichia coli IncFII family plasmid pMccB17, encoding biosynthetic and immunity functions for the antimicrobial peptide microcin B17
Authors: Ajeigbe Mayokun , Bingle Lewis 
Published: July 2020

Microcin B17 (Mcb17) is a ribosomally synthesized and post-translationally modified peptide (RiPP), produced by Escherichia coli, that inhibits bacterial DNA gyrase in a similar way to quinolones. The Mcb17 operon, consisting of seven genes encoding biosynthetic and immunity/export functions, was originally found on a plasmid, pMccB17. This circular plasmid, previously known as pRYC17, was originally found in Escherichia coli strain LP17, isolated from the intestinal tract of a healthy newborn at Hospital La Paz, Spain and was transferred by conjugation to E. coli K-12 [Baquero et al. (1978) J. Bacteriol. 135: 342]. pMccB17 is a low copy number IncFII plasmid in the same incompatibility group as R100 and R1. Not much is known about this plasmid aside from the facts that it carries the Mcb17 operon, does not possess any conventional antibiotic resistance markers and its size was estimated to be approximately 70 kb.
We extracted the plasmid from E. coli K-12 strain RYC1000 [pMccB17] and sequenced it twice using an Illumina short-read method, firstly together with the host bacterial chromosome, then plasmid DNA was purified and sequenced separately. PCR primers were designed to close the single remaining gap via Sanger sequencing. The resulting complete sequence has 83 predicted genes, initially identified by Prokka and subsequently manually reannotated using BLAST. Comparison to other IncFII plasmids shows a large proportion of shared genes, especially in the conjugative plasmid backbone. However, pMccB17 which is a MOBF12 plasmid lacks transposable elements and in addition to the Mcb17 operon, this plasmid carries 25 genes of unknown function.
The investigation of virus-driven intrahepatic cholangiocarcinoma through dysregulated hepatic differentiation
Authors: Kilvington Alexandria , Matthews Laura , Griffin Stephen 
Published: July 2020

Intrahepatic Cholangiocarcinoma (iCCA), bile duct cancer, is increasing in incidence worldwide. Infection with hepatitis C virus (HCV) is a known risk factor for developing iCCA. Recent studies of HCV associated hepatocellular carcinoma (HCC) have demonstrated that HCV infection induces oncogenic gene expression patterns resulting from altered epigenetic profiles. Importantly, whilst ∼90% of patients treated with new direct acting antivirals (DAAs) attain a sustained virological response, the risk of HCC and other malignancies is not reduced by the same extent as previous interferon therapies. We, and others, have shown that this may be related to an imprinted gene expression pattern persisting post-treatment.
The cellular origin of primary liver cancers can vary due to liver cell plasticity. However, the incidence of mixed iCCA-HCC tumour phenotypes and the dual iCCA/HCC risk associated with HCV infection led us to hypothesise that virus-infected hepatic progenitor cells (HPC) might be the source of virus-driven malignancies. Accordingly, we demonstrated that adult HPCs were susceptible to HCV infection ex vivo. Moreover, models of hepatic differentiation revealed that HCV disrupts this process via hijacking the HIPPO signalling pathway with oncogenic hallmarks persisting following viral cure.
To explore HCV-induced alterations during cholangiocyte-specific differentiation, we have chosen to exploit the immortalised non-transformed HPC line, HepaRG and induced pluripotent stem cell derived HPCs. We will describe endeavours to develop a robust model of HCV-mediated perturbation of cholangiocyte-specific differentiation in order to identify new treatments that complement DAA therapy in order to eliminate the risk of malignancy.
Characterization of a multi-modular bacterial enzyme with binding and hydrolysis activities on fungal cell wall components: Insights into bacterial-fungal interactions in the soil
Authors: Lu Zijia , Inman Annie , Kask Josefin , Sara McKee Lauren 
Published: July 2020

Bacteria from the phylum Bacteroidetes is known as good degraders because of their abilities in secreting glycoside hydrolases (GHs). As a member in Bacteroidetes, Chitinophaga pinensis is capable to hydrolyze several glycans (McKee et al., 2019). We found that a multi-modular CAZyme produced by C. pinensis contains not only two GHs but also two uncharacterized domains. Although it is common for CAZmes to have non-catalytic modules like carbohydrate-binding domains (CBMs), the domains in this protein are uncommon, and their functions unknown.
Our enzyme contains five domains – a GH5_46 enzyme, a GH18 enzyme, two non-identical uncharacterized domains, and a Por C-terminal secretion domain. I have shown that the GH5 can specifically degrade pustulan (β-1,6-glucan), and is the only β-1,6-glucanase found in its sub-family. The GH18 is a chitinase that reacts with β-chitin. Interestingly, the two uncharacterized domains both bind polysaccharides, and improve enzyme stability. However, they do not necessarily bind the same glycan as their GH partners. Our result demonstrates how two distinct polysaccharide-degrading modules within one protein can cooperate. We also discuss the impact of the binding domains on the GH activity.
We anticipate our research can stimulate the exploration of β-1,6-glucanase activity in family GH5, and expand the database of carbohydrate specificities in bacteria. The two unusual binding domains we have characterized suggest an unexplored aspect of bacterial physiology in the soil.
References:
McKee, L.S., et al., 2019. Focused metabolism of β-Glucans by the soil Bacteroidetes species Chitinophaga pinensis. Appl. Environ. Microbiol., 85(2), pp.e02231-18.
Novel intraoperative online functional mapping of somatosensory finger representations for targeted stimulating electrode placement
Authors: McMullen David P. , Thomas Tessy M. , Fifer Matthew S. , Candrea Daniel N. , Tenore Francesco V. , Nickl Robert W. , Pohlmeyer Eric A. , Coogan Christopher , Osborn Luke E. , Schiavi Adam , Wojtasiewicz Teresa , Gordon Chad , Cohen Adam B. , Ramsey Nick F. , Schellekens Wouter , Bensmaia Sliman J. , Cantarero Gabriela L. , Celnik Pablo A. , Wester Brock A. , Anderson William S. , Crone Nathan E. 
Published: July 2020

AbstractDefining eloquent cortex intraoperatively, traditionally performed by neurosurgeons to preserve patient function, can now help target electrode implantation for restoring function. Brain-machine interfaces (BMIs) have the potential to restore upper-limb motor control to paralyzed patients but require accurate placement of recording and stimulating electrodes to enable functional control of a prosthetic limb. Beyond motor decoding from recording arrays, precise placement of stimulating electrodes in cortical areas associated with finger and fingertip sensations allows for the delivery of sensory feedback that could improve dexterous control of prosthetic hands. In our study, we demonstrated the use of a novel intraoperative online functional mapping (OFM) technique with high-density electrocorticography (ECoG) to localize finger representations in human primary somatosensory cortex. In conjunction with traditional pre- and intraoperative targeting approaches, this technique enabled accurate implantation of stimulating microelectrodes, which was confirmed by post-implantation intra-cortical stimulation of finger and fingertip sensations. This work demonstrates the utility of intraoperative OFM and will inform future studies of closed-loop BMIs in humans.
Maternal and perinatal characteristics and outcomes of pregnancies complicated with COVID-19 in Kuwait
Authors: Ayed Amal , Embaireeg Alia , Benawath Asma , Al-Fouzan Wadha , Hammoud Majdeda , Al-Hathal Monif , Alzaidai Abeer , Ayed Mariam 
Published: July 2020

AbstractBackgroundIn late December of 2019, a novel coronavirus (SARS-CoV-2) was identified in the Chinese city Wuhan among a cluster of pneumonia patients. While it is known that pregnant women have reduced immunity and they are at risk for COVID-19 infection during the current pandemic, it is not clear if the disease manifestation would be different in pregnant women from non-pregnant women.ObjectivesTo describe the maternal and neonatal clinical features as well as outcome of pregnancies complicated with SARS-CoV-2 infection.MethodsIn this retrospective national-based study, we analyzed the medical records of all SARS-CoV-2 positive pregnant patients and their neonates who were admitted to New-Jahra Hospital, Kuwait, between March 15th 2020 and May 31st 2020. The outcomes of pregnancies were assessed until the end date of follow-up (June 15th 2020).ResultsA total of 185 pregnant women were enrolled with a median age of 31 years (interquartile range, IQR: 27.5-34), and median gestational age at diagnosis was 29 weeks (IQR: 18-34). The majority (88%) of the patients had mild symptoms, with fever (58%) being the most common presenting symptom followed by cough (50.6%). During the study period, 141 (76.2%) patients continued their pregnancy, 3 (1.6%) had a miscarriage, 1 (0.5%) had intrauterine fetal death and only 2 (1.1%) patients developed severe pneumonia and required intensive care. Most of the neonates were asymptomatic, and only 2 (5%) of them tested positive on day 5 by nasopharyngeal swab testing.ConclusionPregnant women do not appear to be at higher risk to the COVID-19 than the general population. The clinical features of pregnant women with SARS-CoV-2 infection were similar to those of the general population having SARS-CoV-2 infection. Favorable maternal and neonatal outcomes reinforce the existing evidence and may guide healthcare professionals in the management of pregnancies complicated with SARS-CoV-2 infection.