bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the transcriptome and long non-coding RNAs but not the methylome occur in human cells exposed to Borrelia burgdorferi
Authors: Berthold Anne , Lloyd Vett 
Published: July 2022

AbstractLyme disease, caused by infection with members of the Lyme borreliosis group of Borrelia spirochete bacteria, is increasing in frequency and distribution worldwide. This spread is driven by the expansion of ticks, vectors of these pathogens. Epigenetics may be involved in the interaction between mammalian host, tick, and bacterial pathogen, but is still poorly understood. Next-generation sequencing (NGS) allows the study of host response at the transcriptomic and methylomic scale.We tested the effect of the Borrelia burgdorferi strain B31 on a human primary cell line (HUVEC) and an immortalized cell line (HEK-293) for 72 h, a time consistent with the duration of tick feeding and host cell exposure to B. burgdorferi. RNA and DNA were extracted from cells and used for RNA-seq and Enzymatic-Methyl-seq (EM-seq). Differential expression and Reactome pathway enrichment analysis were performed. More significantly differentially expressed genes (a total of 69) were found in HUVECs compared to HEK-293 (a total of 8). Borrelia burgdorferi exposure significantly induced genes in the interferon, cytokine, and other immune response signaling in HUVECs. In HEK-293, pre-NOTCH processing in Golgi was identified as a significant pathway. Other significant genes suggest extracellular matrix binding and interaction in HEK-293. Data comparison with other transcriptomic studies of human cells exposed to B. burgdorferi revealed a small overlap in genes identified in HUVEC, but no overlap for HEK-293. No significant methylation changes were detected in HUVECs or HEK-293 exposed to B. burgdorferi. However, two long non-coding RNAs and a pseudogene were deregulated in response to B. burgdorferi in HUVEC suggesting that other epigenetic mechanisms may be initiated by infection.This is the first study examining the transcriptome and methylome of human cells exposed to B. burgdorferi for 72 h and so contributes to the description of early-stage B. burgdorferi infection at the cellular level.
REST: A method for restoring signals and revealing individual macromolecule states in cryo-ET
Authors: Zhang Haonan , Li Yan , Liu Yanan , Li Dongyu , Wang Lin , Song Kai , Bao Keyan , Zhu Ping 
Published: July 2022

AbstractCryo-electron tomography (cryo-ET) is widely used to explore the 3D density of biomacromolecules. However, the heavy noise and missing wedge effect prevent directly visualizing and analyzing the 3D reconstructions. Here, we introduced REST, a deep learning strategy-based method to establish the relationship between low-quality and high-quality density and transfer this knowledge to restore signals in cryo-ET. Experimental results on purified ribosome and recombinant nucleosome datasets showed that REST had outstanding performance in denoising and compensating the missing wedge. The application in dynamic nucleosome structures suggests that REST has the capability to reveal individual macromolecules which present different conformations without subtomogram averaging. Moreover, REST could greatly improve the reliability of particle picking. These advantages enable REST to be a powerful tool for the straightforward interpretation of target macromolecules by visual inspection of the density and of a broad range of other applications in cryo-ET, such as segmentation, particle picking, and subtomogram averaging.
Competition between phage-resistance mechanisms determines the outcome of bacterial co-existence
Authors: Rendueles Olaya , de Sousa Jorge A.M. , Rocha Eduardo P.C. 
Published: July 2022

ABSTRACTMany bacterial species carry multiple prophages. Despite their potential cost, these elements can provide multiple fitness advantages to the host, such as the elimination of direct competitors. However, the long-term efficiency of prophage induction to displace competitors has received little attention. We experimentally coevolved a polylysogenic Klebsiella pneumoniae strain (ST14) with a phage-sensitive strain (BJ1) in several environments resulting in different phage pressures. We then followed the adaptation process and the emergence of resistance. After 30 days, population yield remained stable, and although BJ1 was present in all conditions, its frequency was higher when phage pressure was stronger. Resistance to phages emerged quickly through mutations that prevent capsule biosynthesis. In contrast to our expectation, lysogenic conversion was rare and costly because new BJ1 lysogens exhibited exacerbated death rates and were easily outcompeted. Unexpectedly, the adaptation process changed at longer time scales, where BJ1 populations adapted by fine-tuning the production of capsule, reducing the ability of phage to absorb, while remaining capsulated. These resistant clones are pan-resistant to a large panel of phages. Most intriguingly, some clones exhibited transient non-genetic resistance to phages. Our experimental and modelling results highlight the diversity, dynamics and competition between phage-resistance mechanisms during coevolution and how these are driven by phage pressure.
What drives mixed-species shoaling among wild zebrafish? Role of predators, food access, abundance of conspecifics and kin familiarity
Authors: Mukherjee Ishani , Bhat Anuradha 
Published: July 2022

AbstractMixed-species groups commonly occur across a wide range of faunal communities and are known to provide several benefits to members. While zebrafish have often been observed to form mixed-species shoals with coexisting species, the factors determining their occurrence is not yet understood. Using laboratory-based experiments, we decipher the main ecological drivers of mixed-species shoaling in these tropical fish communities. Shoals comprising zebrafish (Danio rerio), flying barbs (Esomus danricus) and whitespots (Aplocheilus panchax) were collected from a stagnant canal at Haringhata (West Bengal, India). Experiments to assess foraging efficiency were conducted where single or mixed-species shoals (comprising 5 individuals) were given low or high amounts of food. Shoal choice experiments were also conducted to assess the preferences of test subjects (zebrafish individuals) for forming associations based on shoal composition and familiarity. Results from experiments on feeding efficiency revealed that foraging time varied substantially among the shoal types (i.e., single or mixed-species), and was dependent on the quantity of food available, but not linked to the body size of species composing the shoal. The choice experiments to examine preference for associations revealed that under predator risk, zebrafish associate more with mixed shoals, and showed comparable associations to shoals differing in the abundance of conspecifics. Furthermore, we found that zebrafish preferred to associate with familiar conspecific over unfamiliar mixed and unfamiliar conspecific shoals. Therefore, equitable food consumption in mixed shoals, greater association to mixed shoals in presence of predator and familiarity were found to be important drivers for choosing mixed-species shoaling by zebrafish.
Integrative HDX-MS enables quantification of the conformational landscape of the sugar transporter XylE
Authors: Jia Ruyu , Bradshaw Richard T. , Calvaresi Valeria , Politis Argyris 
Published: July 2022

AbstractA yet unresolved challenge in structural biology is to quantify conformational states of proteins underpinning function. This challenge is particularly acute for membrane proteins owing to the difficulties in stabilising them for in vitro studies. To address this challenge, we present here an integrative strategy that combines hydrogen-deuterium exchange mass spectrometry (HDX-MS) with ensemble modelling. We benchmark our strategy on wild type and mutant conformers of XylE, a prototypical member of the ubiquitous Major Facilitator Superfamily (MFS) of transporters. Next, we apply our strategy to quantify conformational ensembles of XylE embedded in different lipid environments and identify key lipid contacts that modulate protein conformations. Further application of our integrative strategy to substrate-bound and inhibitor-bound ensembles, allowed us to unravel protein-ligand interactions contributing to the alternating access mechanism of secondary transport in atomistic detail. Overall, our study highlights the potential of integrative HDX-MS modelling to capture, accurately quantify and subsequently visualise co-populated states of membrane proteins in association with mutations and diverse substrates and inhibitors.For Table of Content Only
Separation of heterogeneous Aggregatibacter actinomycetemcomitans outer membrane vesicles reveals that toxin sorting is driven by surface-associated DNA
Authors: Nice Justin B. , Collins Shannon M. , Agro Samuel M. J. , Sinani Anxhela , Moros Spencer D. , Pasch Leah M. , Brown Angela C. 
Published: July 2022

AbstractAggregatibacter actinomycetemcomitans is a Gram-negative oral bacterium associated with localized aggressive periodontitis as well as some systemic diseases. The strains of A. actinomycetemcomitans most closely associated with periodontal disease tend to produce more of a secreted leukotoxin (LtxA) than isolates from healthy carriers, suggesting a key role for this toxin in disease progression. LtxA is secreted via a type 1 secretion system, from the bacterial cytosol across both the inner and outer membranes in a single step into the supernatant, where it is able to interact with host cells. Upon secretion, some of the toxin associates with the bacterial cell membrane, enabling its release in association with the surface of outer membrane vesicles (OMVs), small, spherical vesicles derived from the outer membrane. We have previously observed that the highly leukotoxic A. actinomycetemcomitans strain JP2 produces two populations of OMVs, a highly abundant population of small (<100 nm in diameter) OMVs, and a less abundant population of large (>300 nm in diameter) OMVs. Here, we have investigated the association of LtxA with the two populations of OMVs varying in size. Our results indicate that surface-associated DNA drives the selective sorting of LtxA to large OMVs.
Probabilities of HIV-1 bNAb development in healthy and chronically infected individuals
Authors: Kreer Christoph , Lupo Cosimo , Ercanoglu Meryem S. , Gieselmann Lutz , Spisak Natanael , Grossbach Jan , Schlotz Maike , Schommers Philipp , Gruell Henning , Dold Leona , Beyer Andreas , Nourmohammad Armita , Mora Thierry , Walczak Aleksandra M. , Klein Florian 
Published: July 2022

AbstractHIV-1 broadly neutralizing antibodies (bNAbs) are able to suppress viremia and prevent infection. Their induction by vaccination is therefore a major goal. However, in contrast to antibodies that neutralize other pathogens, HIV-1-specific bNAbs frequently carry uncommon molecular characteristics that might prevent their induction. Here, we performed unbiased sequence analyses of B cell receptor repertoires from 57 healthy and 46 chronically HIV-1- or HCV-infected individuals and learned probabilistic models to predict the likelihood of bNAb development. We formally show that lower probabilities for bNAbs are predictive of higher HIV-1 neutralization activity. Moreover, ranking of bNAbs by their probabilities allowed to identify highly potent antibodies with superior generation probabilities as preferential targets for vaccination approaches. Importantly, we found equal bNAb probabilities across infected and healthy donors. This implies that chronic infection is not a prerequisite for the generation of bNAbs, fostering the hope that HIV-1 vaccines can induce bNAb development in healthy individuals.Significance StatementWhile HIV-1 broadly neutralizing antibodies (bNAbs) can develop in chronically HIV-1-infected individuals, they could not yet be elicited by active vaccination. Here, we computationally demonstrate that HIV-1 bNAbs carry distinct sequence features making them unlikely outcomes of the antibody evolution. However, our approach allowed us to identify bNAbs with higher probabilities of being generated. These candidates can now serve as the most promising targets to be induced by vaccination. Moreover, we show that chronic infection has no influence on the probabilities of finding typical bNAb sequence features in the memory B cell compartment. Both findings are critical to design effective vaccination strategies.
A novel prion strain is responsible for the first case of chronic wasting disease in Finnish moose
Authors: Sun Julianna L. , Bian Jifeng , Kim Sehun , Crowell Jenna , Webster Bailey K. , Raisley Emma K. , Korpenfelt Sirkka-Liisa , Benestad Sylvie L. , Telling Glenn C. 
Published: July 2022

AbstractConcern is mounting over the global emergence, expanding host range, and uncertain zoonotic potential of chronic wasting disease (CWD), a fatal, infectious disease of cervids caused by prions. Our previous studies using genetically modified CWD-susceptible mice showed that Norwegian and North American CWD are caused by different prion strains. Here we investigated the properties of prions causing the first case of Finnish moose CWD. While Finnish and Norwegian moose CWD prions share characteristics that distinguish them from North American CWD including the inability to replicate in lymphoid tissues, common responses to variations at residue 226 of host prion protein, and overlapping central nervous system profiles, they also exhibit pronounced conformational variation which is consistent with strain differences between Finnish and Norwegian moose CWD. Our findings support the existence of a surprisingly diverse portfolio of emergent CWD strains in Nordic countries that is etiologically distinct from North American CWD.Summary linePrion strain properties from the first case of chronic wasting disease in a Finnish moose are similar but not identical to Norwegian cases, supporting a growing population of strains in Nordic countries.
An Open Microfluidic Coculture Model of Fibroblasts and Eosinophils to Investigate Mechanisms of Airway Inflammation
Authors: Zeng Yuting , Su Xiaojing , Takezawa Meg G. , Fichtinger Paul S. , Lee Ulri N. , Pippin Jeffery W. , Shankland Stuart J. , Lim Fang Yun , Denlinger Loren C. , Jarjour Nizar N. , Mathur Sameer K. , Sandbo Nathan , Berthier Erwin , Esnault Stephane , Bernau Ksenija , Theberge Ashleigh B. 
Published: July 2022

AbstractInteractions between fibroblasts and immune cells play an important role in tissue inflammation. Previous studies have found that eosinophils activated with interleukin-3 (IL-3) degranulate on aggregated immunoglobulin G (IgG) and release mediators that activate fibroblasts in the lung. However, these studies were done with eosinophil-conditioned media that have the capacity to investigate only one-way signaling from eosinophils to fibroblasts. Here, we demonstrate a coculture model of primary normal human lung fibroblasts (HLFs) and human blood eosinophils from patients with allergy and asthma using an open microfluidic coculture device. In our device, the two types of cells can communicate via two-way soluble factor signaling in the shared media while being physically separated by a half wall. Initially, we assessed the level of eosinophil degranulation by their release of eosinophil-derived neurotoxin (EDN). Next, we analyzed the inflammation-associated genes and soluble factors using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and multiplex immunoassays, respectively. Our results suggest an induction of a proinflammatory fibroblast phenotype of HLFs following the coculture with degranulating eosinophils, validating our previous findings. Additionally, we present a new result that indicate potential impacts of activated HLFs back on eosinophils. This open microfluidic coculture platform provides unique opportunities to investigate the intercellular signaling between the two cell types and their roles in airway inflammation and remodeling.
Lead exposure from general aviation emissions in the UK: a review and call for action
Authors: Mills Ashley , Peckham Stephen 
Published: July 2022

AbstractLeaded fuel emissions exposed a global population of children to lead and its profound health consequences. Recognition of its harms precipitated a global phase out and replacement with unleaded substitutes for road vehicles. Despite this widespread recognition and action, aviation fuel for piston engine aircraft still contains lead. Leaded aviation fuel (AVGAS100LL) contains 0.56g of tetraethyl lead per litre and this lead must be jettisoned from the engine during operation to prevent fouling. This action distributes lead and lead compounds into the air and soil around general aviation airports. This has been shown to increase the blood lead levels of children living nearby to clinically significant levels. Whilst this problem is recognised by the EPA in the U.S, it has received little attention in the UK. We provide a review of the situation in the UK with regard to the current policy and regulation framework. We analysed the UK’s general aviation airport fleet, general avation airport data, and GB residential address data. We estimate the unleaded-readiness of the UK aviation fleet and the current usage of fuels at UK general aviation airports. We provide a first order estimate of the number of residential addresses exposed to lead near general aviation airports. We find that the majority of aviation fuel sold in the UK is leaded and that there are 370721 residences within 4km of a general aviation airport at risk from exposure to lead emissions. Finally we present a path forward for regulation change and public health monitoring.
National statutory reporting: not even ticking the boxes? The quality of ‘Learning from Deaths’ reporting in Quality Accounts within the NHS in England 2017-2020
Authors: Brummell Z , Braun D , Hussein Z , Moonesinghe SR , Vindrola-Padros C 
Published: July 2022

AbstractIntroductionRegulation through statutory reporting is used in healthcare internationally to improve accountability, quality of care and patient safety. Since 2017 within the National Health Service (NHS) in England NHS Secondary Care Trusts (NSCTs) are legally required to report annually both quantitative and qualitative information related to patient deaths within their care within their publicly available Quality Accounts as part of a countrywide patient safety programme: The Learning from Deaths (LfDs) programme.MethodAll LfDs reports published between 2017 (programme inception) and 2020 were reviewed and evaluated through a critical realist lens, quantitatively reported using descriptive statistics and qualitatively using reflexive thematic analysis.ResultsIn 2017/18 44% of NSCTs reported all six statutory elements of the LfDs reporting regulations, in 2019/20 35% of NSCTs were reporting this information. A small number of NSCTs did not report any parts of the LfDs regulatory requirements between 2017 and 2020. Multiple qualitative themes arose from this study suggesting problematic engagement with the LfDs programme, erroneous reporting accuracy and written communication.ConclusionsThe LfDs programme has to some extent reduced variation and improved consistency to the way that NSCTs identify, report and investigate deaths. However, three years into the LfDs programme the majority of NSCTs are not reporting as required by law. This makes the validity of National statutory reporting in Quality accounts within the NHS in England questionable as a regulatory process.
Strengthening Health System’s Capacity for Linkage to HIV Care for adolescent girls and young women and adolescent boys and young men in South Africa (SheS’Cap-Linkage): Protocol for a mixed methods study in KwaZulu-Natal, South Africa
Authors: Nicol Edward , Basera Wisdom , Lombard Carl , Jonas Kim , Ramraj Trisha , Govindasamy Darshini , Hlongwa Mbuzeleni , McClinton-Appollis Tracy , Mehlomakulu Vuyelwa , Naqvi Nuha , Bedford Jason , Drummond Jennifer , Cheyip Mireille , Dladla Sibongile , Pass Desiree , Funani Noluntu , Mathews Cathy 
Published: July 2022

AbstractIntroductionIn South Africa, HIV prevalence among adolescent girls and young women (AGYW) was 5.8% (15-19 years) and 15.6% (20-24 years) respectively in 2017. Amongst South African males, HIV prevalence in 2017 was 4.7% (15-19 years), 4.8% (20-24 years), 12.4% (25-29 years) and 18.4% (30-34 years). The National Department of Health adopted the universal test and treat (UTT) strategy in 2016, resulting in increases in same-day antiretroviral therapy initiations and linkage to care. Monitoring progress towards attainment of South Africa’s 95-95-95 targets amongst AGYW and adolescent boys and young men (ABYM) relies on high quality data to identify and address gaps in linkage to care. The purpose of this study is to provide evidence to guide efforts to improve linkage to, and retention in, HIV care among AGYW and ABYM in KwaZulu-Natal, in the context of the UTT strategy.Methods and analysisThis is a mixed methods study, which will be conducted in uMgungundlovu district of KwaZulu-Natal, over a 24-month period, in 22 purposively selected HIV testing and treatment service delivery points (SDPs). For the quantitative component, a sample size of 1100 participants will be recruited into the study. The qualitative component will include 30 participating patients who were successfully linked to care, 30 who were not, and 30 who have never tested for HIV. The questionnaire study population comprises of 231 healthcare providers and AGYW aged 15-24 years and ABYM aged 15-35 years old. Primary outcomes will be evaluated using a logistic regression model. A time to event analysis will also be conducted taking the study design into account. Quantitative data for outcome variables and process indicators will be summarized by domain evaluated with logistic regression to account for potential confounders. For qualitative data, manual thematic content analysis will be conducted.Ethics and disseminationThe protocol was approved by the South African Medical Research Council Health Research Ethics Committee (EC052-11/2020). Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer reviewed journal articles and research capacity building through research degrees.