bluuebunny/crossref_metadata_2025_split huggingface dataset:
A potential new paradigm of denitrification in pathogenic Neisseria
Authors: Bolton Jack , Djoko Karrera , Waldron Kevin 
Published: July 2020

Metals are bacterial nutrients. Upon infection by microorganisms, the animal host innate immune system typically reduces the availability of metals. In response, bacterial pathogens can activate pathways for metal uptaketo avoid metal starvation. This competition for metals at the host-pathogen interface is termed “nutritional immunity”.
We are interested in how the obligate human pathogen Neisseria gonorrhoeae acquires nutrient copper (Cu). This Gram-negative bacterium expresses several respiratory cuproenzymes that are required for growth and metabolism in both aerobic and anaerobic conditions. These cuproenzymes include the putative nitrous oxide reductase (NosZ). NosZ contains 12 Cu atoms per functional dimer and it catalyses the reduction of nitrous oxide (N2O) to dinitrogen (N2). This reduction is an intermediate step in the denitrification pathway, in which nitrite (NO2) is used as the terminal electron acceptor for respiration instead of O2. In this project, we will determine whether NosZ is expressed as a functional enzyme in N. gonorrhoeae. We will then examine how this enzyme acquires nutrient Cu and subsequently assembles its active site.
Given the rise in antibiotic resistance and the worldwide recognition of multidrug-resistant N. gonorrhoeae as a major threat to public health, we hope that a fundamental understanding of the physiology and metabolism of this organism will yield new strategies for anti-infectives, for instance by manipulating Cu availability at the site of infection.
Foot-and-mouth disease virus non-structural protein 3A modulates cellular innate immune responses to influence host tropism
Authors: Chakravarti Soumendu , Wright Caroline , Howes Emma , Kock Richard , Jackson Terry , Tuthill Toby 
Published: July 2020

The picornavirus foot-and-mouth disease virus (FMDV) is responsible for one of the most significant diseases of livestock, leading to large economic losses due to reduced productivity and trade embargoes for areas not certified as disease-free. The picornavirus non-structural protein 3A is involved in replication of the viral RNA genome and is implicated in host tropism of several picornaviruses. Deletions in the C-terminus of 3A have been observed in FMDV outbreaks specific for swine and such viruses are non-pathogenic in cattle. The mechanism for species specific attenuation of FMDV is unknown.
We have shown that FMDV containing a C-terminal deletion in 3A is attenuated in bovine cell culture and that the attenuated phenotype can be reversed by the JAK1/2 inhibitor Ruxolitinib (Rux), identifying a role for the induction of interferon stimulated genes (ISGs) in the restricted bovine tropism of the 3A-deleted virus.
Microwaves can reverse the tumour phenotype of human papillomavirus type 16 (HPV16)-positive keratinocytes in 3D cell culture models: a novel therapy for HPV-associated disease?
Authors: Epifano Ilaria , J. Conley Michaela , Stevenson Andrew , Doorbar John , V. Graham Sheila 
Published: July 2020

High-risk human papillomavirus (HPV) is the causative agent of benign, precancerous and cancerous lesions, in both anogenital and oropharyngeal sites. Increased expression of the viral oncoproteins E6 and E7 are responsible for tumour progression. The treatment of these precancerous and cancerous lesions is invasive, painful and with long-term side effects. Localised microwaves have been used successfully in the clinic for the treatment of verrucas, which are caused by low-risk HPV genotypes (>75% success rate versus >33% for cryotherapy). Moreover, local hyperthermia is known to have anti-tumour effects.
Ten-second microwave treatment of 3D in vitro-grown cervical tumour tissues (HPV16-positive SiHa cell) resulted in cell death in the treated zone while the tissue integrity was disrupted in the adjacent area. Microwaves induced apoptosis (induction of cleaved caspase 3) and autophagy (induction of LC3) and inhibited cell proliferation (loss of Ki67 and MCM2) in the entire tissue. Furthermore, HPV16 E6 and E7 expression was reduced in cells in the treated and transition zones, with subsequent induction of expression of the apoptosis-regulator, p53 over a 24 hour period following microwave treatment. Thermal stress, identified with the Heat Shock Protein 70 (HSP70) and translational stress identified by G3BP expression, was observed in the transition zone.
In conclusion, we demonstrate that the microwave treatment induces cell stress pathways and inhibits HPV oncoprotein expression that causes tumour progression. Induction of apoptosis and reduced cell proliferation suggest a reversal of the cervical tumour phenotype in the 3D tissues.
Design of stable Enterovirus 71 virus like particles (VLPs) as a potential approach to vaccine development
Authors: Martyna Agnieszka , Fox Helen , Macadam Andrew 
Published: July 2020

We have previously described the design of stable and immunogenic polio virus-like particles (VLPs) (Fox, et al. 2017) as an alternative approach to vaccine production. Unlike current polio vaccines, recombinantly-expressed VLP vaccines are non-infectious so would pose no risk of accidental escape from production plants, threatening eradication. To do this we devised a pipeline for the identification of stabilising mutations which could then be combined in a single construct to produce suitable particles; this strategy may have applications for other enterovirus vaccines.
Enterovirus 71 (EV71) is one of causative agents of hand, foot and mouth disease which is usually mild but in some cases neurological and systemic complications may occur. Recently there have been several outbreaks with significant mortality in South East Asia as well as increasing numbers of reports of outbreaks in Europe. VLP vaccines might be a useful alternative to inactivated vaccines currently in use or development.
EV71, like poliovirus, produces empty particles that are antigenically different from the virion. If, like poliovirus, these empty particles are less immunogenic than the virion, it would be necessary to stabilise them in the native conformation. We are attempting to do this (1) by incorporating modifications that proved successful in the context of poliovirus and (2) by identifying new candidate mutations using an analogous pipeline. Here we will report the characterisation of a range of different modifications that have stabilising and de-stabilising effects on EV71 particles as well as unexpected effects on morphogenesis.
Investigating the coding capacity of rotaviruses using a newly developed reverse genetics system
Authors: Lee Ola , Min Lee Hui , Maria Pinto Rute , Digard Paul , Gaunt Eleanor 
Published: July 2020

Bovine rotavirus (RV) infection causes severe diarrhoea in young dairy calves and has a significant economic impact on livestock production as a result of high morbidity and mortality caused. Development of technologies to engineer infectious RV using an entirely plasmid-based reverse genetics (RG) system has proven challenging. A breakthrough was made when Kanaiand co-authors (PNAS, 2017)developed a plasmid-only-based RG system for the simian RV strain SA11.We are currently developing an analogous RG system for the bovine RF RV strain. Having parallel systems for different RV strains will help to validate phenotypic changes induced by site-directed mutagenesis (SDM) within the RV genome.
The coding capacity of the 11-segmented dsRNA RV genome has been largely unexplored. Using bioinformatic analyses, we have identified four segments with up to five putative alternative initiation codons which are in moderate or strong Kozak context. Furthermore, some occur in segments for which the canonical start codon occurs within 15 nucleotides of the start of the segment, further suggesting the possibility of alternative translation start sites to generate coding diversity. We are now applying our RG systems to investigate RV coding capacity using TnT transcription assays, radiolabelling and SDM.
Strategies for glycan acquisition by Bacteroidetes in the soil: The carbohydrate enzymology of Chitinophaga pinensis
Authors: Lu Zijia , Inman Annie , Ergenlioglu Irem , Rämgård Carl , Sara McKee Lauren 
Published: July 2020

The secretion of extracellular enzymes by soil microbes is rate-limiting in the global recycling of biomass. Fungi and bacteria compete and collaborate for nutrients in the soil, with wide ranging ecological impacts. Within soil microbiota, the Bacteroidetes tend to be a dominant bacterial phylum, just like in human and animal intestines. The enzymology of Bacteroidetes in the dynamic and competitive soil environment is under-explored compared to their cousins from the human and ruminant gut ecosystems. We are exploring carbohydrate binding and deconstruction by Chitinophaga pinensis. This species was isolated from the leaf litter of a pine forest, and our ongoing microbiological, biochemical, and proteomic analyses show that C. pinensis has a marked metabolic preference for carbohydrates (glycans) of microbial, rather than plant, origin. The species has a repertoire of enzymes that degrade components of the fungal cell wall, and we are characterising several important enzyme activities, including some with unusual substrate specificity.
Several features of the C. pinensis “cazome” make it note-worthy. In particular, there is a significantly reduced reliance on the Polysaccharide Utilisation Loci that define glycan acquisition in most well-studied gut symbiont Bacteroidetes. Instead, C. pinensis produces some large multi-modular enzymes that convey multiple complementary carbohydrate-binding and -degrading functions, and which are often secreted via the phylum-specific Type IX Secretion System.
This presentation will highlight our latest enzyme characterisation data, discussed in the context of the environmental functions of soil bacteria, as well as the use of enzymes for industrial biotechnology.
Luminore CopperTouch™ surface coating effectively inactivates SARS-CoV-2, Ebola, and Marburg viruses in vitro
Authors: Mantlo Emily K. , Paessler Slobodan , Seregin Alexey , Mitchell Alfred 
Published: July 2020

AbstractWe investigated the ability of Luminore CopperTouch™ copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral droplets exposed to copper surfaces for 30 min. The copper and copper–nickel surfaces inactivated 99.9% of the viral titer of both Ebola and Marburg viruses. The copper surfaces also inactivated 99% of SARS-CoV-2 titers in 2 hours to close to the limit of detection. These data add Ebolavirus, Marburgvirus, and SARS-CoV-2 (COVID-19) to the list of pathogens that can be inactivated by exposure to copper ions, validating Luminore CopperTouch™ technology (currently the only Environmental Protection Agency-registered cold spray antimicrobial surface technology) as an efficacious, cost-friendly tool to improve infection control in hospitals, long-term care facilities, schools, hotels, buses, trains, airports, and other highly trafficked areas.
Predicting outcomes of cross-sex hormone therapy in gender dysphoria based on pre-therapy resting-state brain connectivity
Authors: Moody Teena D , Feusner Jamie D , Reggente Nicco , Vanhoecke Jonathan , Holmberg Mats , Manzouri Amirhossein , Khorashad Behzad Sorouri , Savic Ivanka 
Published: July 2020

AbstractIndividuals with gender dysphoria experience serious distress due to incongruence between their gender identity and birth-assigned sex. Sociological, cultural, interpersonal, and biological factors are likely contributory, and for some individuals medical treatment such as cross-hormone therapy and gender affirming surgery can be helpful. Cross-hormone therapy can be effective for reducing body incongruence, but responses vary, and there is no reliable way to predict therapeutic outcomes. We used clinical and MRI data before cross-sex hormone therapy as features to train a machine learning model to predict individuals’ post-therapy body congruence (the degree to which photos of their bodies match their self-identities). Twenty-five trans women and trans men with gender dysphoria participated. The model significantly predicted post-therapy body congruence, with the highest predictive features coming from the fronto-parietal and cingulo-opercular networks. This study provides evidence that hormone therapy efficacy can be predicted from information collected before therapy and that patterns of functional brain connectivity may provide insights into body-brain effects of hormones, affecting one’s sense of body congruence. Results could help identify the need for personalized therapies in individuals predicted to have low body-self congruence after standard therapy.
Low-Dose Whole-Lung Radiation for COVID-19 Pneumonia
Authors: Hess Clayton B. , Buchwald Zachary S. , Stokes William , Nasti Tahseen H. , Switchenko Jeffrey M. , Weinberg Brent D. , Rouphael Nadine , Steinberg James P. , Godette Karen D. , Murphy David , Ahmed Rafi , Curran Walter J. , Khan Mohammad K. 
Published: July 2020

AbstractBackgroundSafety of whole-lung low-dose radiation therapy (LD-RT) for COVID-19 pneumonia has been established in two phase I trials. By focally dampening pulmonary cytokine hyperactivation, LD-RT may improve outcomes in hospitalized and oxygen-dependent COVID-19 patients.MethodsPatients with COVID-19 pneumonia were treated with 1.5 Gy whole-lung LD-RT, followed for 28 days or at least until hospital discharge, and compared to an age- and comorbidity-matched control cohort. COVID-19-positive patients eligible for this protocol were hospitalized, had radiographic consolidations, and required supplemental oxygen. Efficacy endpoints were time to clinical recovery, radiographic improvement, and serologic responses.ResultsTen patients received whole-lung LD-RT between April 24 and May 24, 2020 and were compared to ten matched control patients, of whom six received COVID-directed therapy. Median time to clinical recovery was 12 days for the control cohort vs 3 days for LD-RT (HR 2.9, p=0.05). Median time to hospital discharge (20 and 12 days, p=0.19), and intubation rates (40% and 10%, p=0.12) were shorter for the LD-RT cohort. The LD-RT cohort had faster radiographic improvement (p=0.03), even among patients with high COVID burden. Serologic recovery in specific hematologic, cardiac, hepatic, clotting, and inflammatory markers occurred more rapidly following LD-RT than among matched controls.ConclusionsStrong efficacy signals, including a 3-fold risk reduction in time to clinical improvement, were observed following LD-RT compared to matched patients receiving COVID-directed therapy for COVID-19 pneumonia. Given the global availability of radiation accelerators, ongoing international efforts to investigate the optimal role of LD-RT in COVID-19 pneumonia are justified.Clinical Trial RegistrationNCT04366791.
Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19 Related Mortality in the U.S.
Authors: Correa-Agudelo Esteban , Mersha Tesfaye B. , Hernández Andrés , Branscum Adam J. , MacKinnon Neil J. , Cuadros Diego F. 
Published: July 2020

ABSTRACTBackgroundThe role of health-related disparities including sociodemographic, environmental, and critical care capacity in the COVID-19 pandemic are poorly understood. In the present study, we characterized vulnerable populations located in areas at higher risk of COVID-19 related mortality and low critical healthcare capacity in the U.S.MethodsUsing Bayesian multilevel analysis and small area disease risk mapping, we assessed the spatial variation of COVID-19 related mortality risk for the U.S. in relation with healthcare disparities including race, ethnicity, poverty, air quality, and critical healthcare capacity.ResultsOverall, highly populated, regional air hub areas, and minorities had an increased risk of COVID-19 related mortality. We found that with an increase of only 1 ug/m3 in long term PM2.5 exposure, the COVID-19 mortality rate increased by 13%. Counties with major air hubs had 18% increase in COVID-19 related death compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average. These counties were primary located at the North- and South-Eastern regions of the country.ConclusionThe existing disparity in health and environmental risk factors that exacerbate the COVID-19 related mortality, along with the regional healthcare capacity, determine the vulnerability of populations to COVID-19 related mortality. The results from this study can be used to guide the development of strategies for the identification and targeting preventive strategies in vulnerable populations with a higher proportion of minority groups living in areas with poor air quality and low healthcare capacity.KEY POINTSQuestionWhat are the sociodemographic and environmental drivers of the heterogeneous distribution of the COVID-19 related mortality in the U.S., and what are the vulnerable areas at higher risk of COVID-19 related mortality and low critical healthcare capacity?FindingsHigher proportions of African American and Latino populations, as well as high levels of air pollution and airport connectivity were linked to higher risk of COVID-19 related mortality. Over 68% of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average.MeaningIn a time-limited response, the identification and targeting prevention efforts should focus in vulnerable populations located in high risk areas in which sociodemographic and environmental factors are exacerbating the burden of COVID-19 related deaths.
Multitask Learning over Shared Subspaces
Authors: Menghi Nicholas , Kacar Kemal , Penny Will 
Published: July 2020

AbstractThis paper uses constructs from machine learning to define pairs of learning tasks that either shared or did not share a common subspace. Human subjects then learnt these tasks using a feedback-based approach. We found, as hypothesised, that subject performance was significantly higher on the second task if it shared the same subspace as the first. Additionally, accuracy was positively correlated over subjects learning same-subspace tasks, and negatively correlated for those learning different-subspace tasks. These results were compared to the behaviour of a Neural Network model trained using sequential Bayesian learning. Human performance was found to be consistent with a minimal capacity variant of this model. Networks with an increased representational capacity, and networks without Bayesian learning, did not show these transfer effects. We propose that the concept of shared subspaces provides a useful framework for the experimental study of human multitask and transfer learning.Author summaryHow does knowledge gained from previous experience affect learning of new tasks ? This question of “Transfer Learning” has been addressed by teachers, psychologists, and more recently by researchers in the fields of neural networks and machine learning. Leveraging constructs from machine learning, we designed pairs of learning tasks that either shared or did not share a common subspace. We compared the dynamics of transfer learning in humans with those of a multitask neural network model, finding that human performance was consistent with a minimal capacity variant of the model. Learning was boosted in the second task if the same subspace was shared between tasks. Additionally, accuracy between tasks was positively correlated but only when they shared the same subspace. Our results highlight the roles of subspaces, showing how they could act as a learning boost if shared, and be detrimental if not.
Long-term live imaging of epithelial organoids and corresponding multiscale analysis reveal high heterogeneity and identify core regulatory principles
Authors: Hof Lotta , Moreth Till , Koch Michael , Liebisch Tim , Kurtz Marina , Tarnick Julia , Lissek Susanna M. , Verstegen Monique M.A. , van der Laan Luc J.W. , Huch Meritxell , Matthäus Franziska , Stelzer Ernst H.K. , Pampaloni Francesco 
Published: July 2020

AbstractOrganoids are morphologically heterogeneous three-dimensional cell culture systems. To understand the cell organisation principles of their morphogenesis, we imaged hundreds of pancreas and liver organoids in parallel using light sheet and bright field microscopy for up to seven days. We quantified organoid behaviour at single-cell (microscale), individual-organoid (mesoscale), and entire-culture (macroscale) levels. At single-cell resolution, we monitored formation, monolayer polarisation and degeneration, and identified diverse behaviours, including lumen expansion and decline (size oscillation), migration, rotation and multi-organoid fusion. Detailed individual organoid quantifications lead to a mechanical 3D agent-based model. A derived scaling law and simulations support the hypotheses that size oscillations depend on organoid properties and cell division dynamics, which is confirmed by bright field macroscale analyses of entire cultures. Our multiscale analysis provides a systematic picture of the diversity of cell organisation in organoids by identifying and quantifying core regulatory principles of organoid morphogenesis.Graphical AbstractCreated withBioRender.com.
KHz-rate volumetric voltage imaging of the whole zebrafish heart
Authors: Sacconi L. , Silvestri L. , Rodríguez E.C. , Armstrong G.A.B. , Pavone F.S. , Shrier A. , Bub G. 
Published: July 2020

AbstractFast volumetric imaging is essential for understanding the function of excitable tissues such as those found in the brain and heart. Measuring cardiac voltage transients in tissue volumes with spatial and temporal resolutions needed to give insight to cardiac function has so far been impossible. We introduce a new imaging modality based on simultaneous illumination of multiple planes in the tissue and parallel detection with multiple cameras, avoiding compromises inherent in any scanning approach. The system enables imaging of voltage transients in-situ, allowing us, for the first time, to map voltage activity in the whole heart volume at KHz rates. The unprecedented spatio-temporal resolution of our method enabled the observation of novel dynamics of electrical propagation through the zebrafish atrioventricular canal.