bluuebunny/crossref_metadata_2025_split huggingface dataset:
Streptococcus suisencodes multiple allelic variants of a phase-variable Type III DNA methyltransferase, ModS, that control distinct phasevarions
Authors: Tram Greg , Jen Freda E.-C. , Phillips Zachary N. , Timms Jamie , Husna Asma-Ul , Jennings Michael P. , Blackall Patrick J. , Atack John M. 
Published: January 2021

AbstractStreptococcus suisis a significant cause of bacterial meningitis in humans, particularly in S.E. Asia, and is a leading cause of respiratory and invasive disease in pigs. Phase-variable DNA methyltransferases, associated with Restriction-Modification (R-M) systems, are a source of epigenetic gene regulation, controlling the expression of multiple genes. These systems are known as phasevarions (phase-variable regulons), and have been characterised in many host-adapted bacterial pathogens. We recently described the presence of a Type III DNA methyltransferase inS. suis, ModS, which contains a simple sequence repeat (SSR) tract within the open reading frame of themodSgene, and which varied in length between individual strains. We also observed multiple allelic variants of themodSgene were present in a population ofS. suisisolates. Here, we demonstrate that a biphasic ON-OFF switching of expression occurs in the two most common ModS alleles, ModS1 and ModS2, and that switching is dependent on SSR tract length. Further, we show that ModS1 and ModS2 are active methyltransferases inS. suisusing Single-Molecule, Real Time (SMRT) sequencing. ON-OFF switching of each ModS allele results in the regulation of distinct phasevarions, with the ModS2 phasevarion impacting growth patterns and antibiotic resistance. This is the first demonstration of a phase-variable Type III DNA methyltransferase in a Gram-positive organism that controls a phasevarion. Characterising the phenotypic effects of phasevarions inS. suisis key to understanding pathogenesis and the development of future vaccines.ImportanceStreptococcus suisis a causative agent of meningitis, polyarthritis and polyserositis in swine, and is a major cause of zoonotic meningitis in humans. Here we investigate epigenetic gene regulation inS. suisby multiple phasevarions controlled by the phase-variable Type III DNA methyltransferase ModS. This is the first characterised example of a Type III R-M system regulating a phasevarion in a Gram-positive organism. We demonstrate that biphasic ON-OFF switching of ModS expression results in differences in bacterial growth and antibiotic resistance. Understanding the effects of ModS phase variation is required to determine the stably expressed antigenic repertoire ofS. suis, which will direct and inform the development of antimicrobial treatments and vaccines against this important pathogen.
Enhanced laterally resolved ToF-SIMS and AFM imaging of the electrically conductive structures in cable bacteria
Authors: Eachambadi Raghavendran Thiruvallur , Boschker Henricus T. S. , Franquet Alexis , Spampinato Valentina , Hidalgo-Martinez Silvia , Valcke Roland , Meysman Filip J. R. , Manca Jean V. 
Published: January 2021

ABSTRACTCable bacteria are electroactive bacteria that form a long, linear chain of ridged cylindrical cells. These filamentous bacteria perform centimeter-scale long-range electron transport through parallel, interconnected conductive pathways of which the detailed chemical and electrical properties are still unclear. Here, we combine ToF-SIMS (time of flight secondary ion mass spectrometry) and AFM (atomic force microscopy) to investigate the structure and composition of this naturally-occurring electrical network. The enhanced lateral resolution achieved allows differentiation between the cell body and the cell-cell junctions that contain a conspicuous cartwheel structure. Three ToF-SIMS modes were compared in the study of so-called fiber sheaths (i.e., the cell material that remains after removal of cytoplasm and membranes and which embeds the electrical network). Among these, fast imaging delayed extraction (FI-DE) was found to balance lateral and mass resolution, thus yielding multiple benefits in the study of structure-composition relations in cable bacteria: (i) it enables the separate study of the cell body and cell-cell junctions, (ii) by combining FI-DE with in-situ AFM, the depth of Ni-containing protein – key in the electrical transport – is determined with greater precision, and (iii) this combination prevents contamination, which is possible when using an ex-situ AFM. Our results imply that the interconnects in extracted fiber sheaths are either damaged during extraction, or that their composition is different from fibers, or both. From a more general analytical perspective, the proposed methodology of ToF-SIMS in FI-DE-mode combined within-situAFM holds great promise for studying the chemical structure of other biological systems.
Spatiotemporal organization of BamA governs the pattern of outer membrane protein distribution in growingEscherichia colicells
Authors: Mamou Gideon , Inns Patrick G. , Sun Dawei , Kaminska Renata , Housden Nicholas G. , Cohen-Khait Ruth , Miller Helen , Storek Kelly M. , Rutherford Steven T. , Payandeh Jian , Kleanthous Colin 
Published: January 2021

AbstractThe outer membrane (OM) of Gram-negative bacteria is a robust protective barrier that excludes major classes of antibiotics. The assembly, integrity and functioning of the OM is dependent on β-barrel outer membrane proteins (OMPs), the insertion of which is catalyzed by BamA, the core component of the β-barrel assembly machine (BAM) complex. Little is known about BamA in the context of its native OM environment. Here, using high-affinity fluorescently-labelled antibodies in combination with diffraction-limited and super-resolution fluorescence microscopy, we uncover the spatial and temporal organization of BamA in liveEscherichia coliK-12 cells. BamA is clustered into ~150 nm diameter islands that contain an average of 10-11 BamA molecules, in addition to other OMPs, and are distributed throughout the OM and which migrate to the poles during growth. In stationary phase cells, BamA is largely confined to the poles. Emergence from stationary phase coincides with new BamA-containing islands appearing on the longitudinal axis of cells, suggesting they are not seeded by pre-existing BamAs but initiate spontaneously. Consistent with this interpretation, BamA-catalyzed OMP biogenesis is biased towards non-polar regions. Cells ensure the capacity for OMP biogenesis is uniformly distributed during exponential growth, even if the growth rate changes, by maintaining an invariant density of BamA-containing OMP islands (~9 islands/μm2) that only diminishes as cells enter stationary phase, the latter change governing what OMPs predominate as cells become quiescent. We conclude that OMP distribution inE. coliis driven by the spatiotemporal organisation of BamA which varies with the different phases of growth.SignificanceThe integrity and functioning of the outer membrane (OM) of Gram-negative bacteria depends on the β-barrel assembly machinery (BAM). Although the structure and the mechanism of the complex have been widely explored, little information exists about the organization of the BAM complex and how it dictates protein distribution in the OM. Here, we utilized highly specific monoclonal antibodies to study the spatiotemporal organization of BamA, the key component of this complex. We reveal that BAM organization is dynamic and tightly linked to the cell’s growth phase. We further discover that the rate of BAM facilitated OMP biogenesis is significantly reduced near the poles. In turn, these features govern the biogenesis patterns and the distribution of OMPs on the cell surface.
Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro
Authors: Lee Ming-Cheng , Chen Yin-Kai , Hsu Yih-Jen , Lin Bor-Ru 
Published: January 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a vast number of infections and fatalities worldwide. As the development and safety validation of effective vaccines are ongoing, drug repurposing is most efficient approach to search FDA approved agents against coronavirus disease 2019 (COVID-19). In the present study, we found that endogenous ACE2 expressions could be detected in H322M and Calu-3 cell lines, as well as their ACE2 mRNA and protein expressions were suppressed by pyrrolidine dithiocarbamate (PDTC), a NF-kappa B inhibitor, in dose- and time-dependent manners. Moreover, N-acetyl-cysteine (NAC) pretreatment reversed PDTC-induced ACE2 suppression, as well as the combined treatment of hydrogen peroxide and knockdown of p50 subunit of NF-kappa B by siRNA reduced ACE2 expression in H322M cells. In addition, anthelmintic drug triclabendazole and antiprotozoal drug emetine, repurposed drugs of NF-kappa B inhibitor, also inhibited ACE2 mRNA and protein expressions in H322M cells. Moreover, zinc supplement augmented the suppressive effects of triclabendazole and emetine on ACE2 suppression in H322M and Calu-3 cells. Taken together, these results indicate that ACE2 expression is modulated by reactive oxygen species (ROS) and NF-kappa B signal in human lung cell lines, and zinc combination with triclabendazole or emetine has the clinical potential for the prevention and treatment of COVID-19.
Fitness cost of vancomycin-resistantEnterococcus faeciumplasmids associated with hospital infection outbreaks
Authors: Tedim Ana P. , Lanza Val F. , Rodríguez Concepción M. , Freitas Ana R. , Novais Carla , Peixe Luísa , Baquero Fernando , Coque Teresa M. 
Published: January 2021

ABSTRACTBackgroundVancomycin resistance is mostly associated withEnterococcus faeciumdue to Tn1546-vanAlocated on narrow- and broad-host plasmids of various families. The study’s aim was to analyse the effects of acquiring Tn1546-plasmids with proven epidemicity in different bacterial host backgrounds.MethodsWidespread Tn1546-plasmids of different families RepA_N (n=5), Inc18 (n=4) and/or pHTβ (n=1), and prototype plasmids RepA_N (pRUM) and Inc18 (pRE25, pIP501) were analysed. Plasmid transferability and fitness cost were assessed usingE. faecium(GE1, 64/3) andEnterococcus faecalis(JH2-2/FA202/UV202) recipient strains. Growth curves (Bioscreen C) and Relative Growth Rates were obtained in presence/absence of vancomycin. Plasmid stability was analysed (300 generations). Whole genome sequencing (Illumina-MiSeq) of non-evolved and evolved strains (GE1/64/3 transconjugants, n=49) was performed. SNP calling (breseq software) of non-evolved strains was used for comparison.ResultsAll plasmids were successfully transferred to differentE. faeciumclonal backgrounds. Most Tn1546-plasmids and Inc18 and RepA_N prototypes reduced host fitness (−2%-18%) while the cost of Tn1546expression varied according to the Tn1546-variant and the recipient strain (9-49%). Stability of Tn1546-plasmids was documented in all cases, often with loss of phenotypic resistance and/or partial plasmid deletions. Point mutations and/or indels associated with essential bacterial functions were observed on the chromosome of evolved strains, some of them linked to increased fitness.ConclusionsThe stability ofE. faeciumTn1546-plasmids in the absence of selective pressure and the high intra-species conjugation rates might explain the persistence of vancomycin resistance inE. faeciumpopulations despite the significant burden they might impose on bacterial host strains.
Inversion of explosive source land seismic data to determine source signature parameters
Authors: Ziolkowski Anton 
Published: January 2021

ABSTRACTIn seismic land exploration, where terrain conditions limit the use of vibrator sources, explosive sources are the preferred choice, and in situations where low‐frequency energy is essential, explosive is the preferred source, because it contains energy down to DC (0 Hz). I present a new method to estimate the source time functions of explosion source seismic data, using a modified acquisition method, data processing, modelling and inversion. Two shots of different sizes are fired into the same geophone spread with source–receiver geometry arranged such that the Green's functions are essentially the same. The spectral ratio of corresponding seismic traces is then the spectral ratio of the source time functions. A corresponding synthetic ratio filter is calculated from Blake's explosion source model for the sources within each pair. Each modelled source is defined by five parameters: the minimum radius a of the elastic zone, the internal pressure p0 at a, the density of the rock ρ and two elastic constants for an isotropic rock, the P‐wave velocity c and Poisson's ratio σ. A grid search finds the source parameters that minimise the difference between the measured and synthetic filters for each source pair, thus yielding the two source time functions, but not their absolute amplitudes. Deconvolution of the shot records within each pair for the minimum‐phase source time functions recovers the estimated earth impulse response gathers, convolved only with the response of the recording system. The improved knowledge of the source signature is then helpful in subsequent processing, especially for reverse time migration, full waveform inversion and amplitude‐versus‐offset analysis. I consider shots at different depths in the same shot hole and shots at the same depth in different shot holes. The former configuration minimises differences in geophone coupling, and, in operations, quality control procedures must be met. There is considerable variation in recovered source parameters from place to place, caused by variations in charge size, soil or rock properties and source coupling.
Carl von Clausewitz and his Philosophy of War: The Evolution of a Reputation, 1831–2021
Authors: GERALD HUGHES R. 
Published: January 2021

AbstractThis article is concerned with the evolution of the reputation of the Prussian soldier and philosopher of war, Carl von Clausewitz (1780–1831). It examines developments in debates about the reception, and relevance, of Clausewitz's work for strategic thought in both the historical and contemporary contexts. This article takes note of many of the misperceptions and misinterpretations directed at Clausewitz's work since his death. It argues that much of the criticism directed at Clausewitz is rooted in a visceral dislike of past proponents of Clausewitz for their aggressive and militaristic policies. An appreciation of this history is nevertheless useful for facilitating accurate interpretations of Clausewitz's work. Finally, the article argues that the notion of Clausewitz as advocate of militarism and aggressive war has been largely discredited. Indeed, in today's Federal Republic of Germany, the reformers masterminding the Wars of Liberation against Napoleon, of whom Clausewitz was one, and the resistance involved in the bomb plot of 20 July 1944, have now come to represent a useable historical tradition.
State of the Field: Material Culture
Authors: DYER SERENA 
Published: January 2021

AbstractThis article surveys the state of the field of material culture within the discipline of history. The study of material culture – the myriad layers of cultural meaning embedded within objects – has been adopted by historians from colleagues in anthropology, archaeology and museum studies, and continues to thrive as an interdisciplinary field in tandem with art history and literary studies. As inventive digital and embodied methodologies within material culture begin to shape the future of the field, this article takes the opportunity to reflect upon the opportunities and impediments presented to scholars of material culture. It elucidates the diverse and often unfamiliar vernaculars of material objects, and reflects upon future directions in the study of material culture.
The associations of medical marijuana policies with opioid‐related health care utilization
Authors: Jayawardhana Jayani , Fernandez Jose M. 
Published: January 2021

AbstractObjectiveTo examine the associations between medical marijuana policies and opioid‐related hospitalizations and emergency department visits.Data SourcesWe utilized quarterly rates of hospital discharge data from the Healthcare Cost and Utilization Project's (HCUP) Fast Stats Database from 2005 to 2016 along with state‐level sociodemographic data from US Census Bureau and Bureau of Labor Statistics and opioid‐related state health policy data from publicly available sources for the analysis.Study DesignAnalyses were carried out using a difference‐in‐differences regression approach. We estimate heterogeneous effects of medical marijuana policies such as initial policy, presence of active dispensary, and home cultivation on opioid‐related hospitalizations and emergency department visits related to opioids.Data Collection/Extraction MethodsPublicly available secondary data were collected, linked, and analyzed. Observations with missing values for explanatory variables were excluded from the analysis.Principal FindingsRegression results indicate that type of medical marijuana policy has varying effects on opioid‐related hospitalizations and emergency department visits. States that allow home cultivation of medical marijuana experienced significant positive associations with opioid‐related hospitalizations and emergency department visits, while no effect was observed with medical marijuana dispensaries. Moreover, recreational marijuana policies were positively associated with opioid‐related hospitalizations.ConclusionsThe findings indicate that the effects of medical marijuana policies on opioid‐related hospitalizations and emergency department visits vary depending on the type of medical marijuana policy. Our findings indicate that the implementation of home cultivation of marijuana is positively associated with hospitalizations and emergency department visits related to opioids, suggesting that easier access to marijuana among opioid users may result in adverse health conditions that need treatment.
Access block in Australian emergency departments 2017–2020
Authors: Richardson Drew B 
Published: January 2021

AbstractObjectiveTo describe Australian ED workload over the period 2017–2020 using data from twice annual Access Block Point Prevalence Studies, and to identify any impact of the COVID‐19 pandemic.MethodsRetrospective analysis of demand and occupancy data provided by the Australasian College for Emergency Medicine accredited EDs in voluntary surveys at the start of June and September 2017–2020. Hospitals answering all surveys were grouped and compared by jurisdiction and role delineation.ResultsA total of 121 EDs were eligible, 63% supplied complete occupancy data and 53% complete demand data. Between the June 2017 and 2019 surveys, mean daily ED presentations increased by 11.4% (P= 0.0003). The number being treated at 10.00 hours rose by 27.7% (P< 0.0001) and those experiencing access block (waiting for an inpatient bed, been in ED more than 8 h) rose by 46.1% (P= 0.001). Between the June 2019 and 2020 surveys, ED presentations fell by an average of 12.6% (P< 0.0001), ward admissions were almost unchanged (−6.0%,P= NS), and patients who did not wait to be seen fell by 57.8% (P< 0.0001). Major Paediatric Referral hospitals reported a 28% decrease in presentations. By September 2020, only the state of Victoria (ongoing state of emergency) and Major Paediatric Referral hospitals reported demand lower than 2019 or occupancy lower than 2018.ConclusionsOccupancy increased by more than demand 2017–2019, with some decrease in 2020: in June presentations were 12.7% lower than 2019, in September back to the normal range outside Victorian and Major Paediatric Referral hospitals. Future research needs to consider locality, role delineation and work practice change in comparing ED pandemic responses.
Juvenoids on aphids to prolong optimal stages
Authors: Lai Rongquan , Bai Jingjing , Gu Gang , Zhou Ting , Mi Yuee , Zhang Bang , Han Meng , Bai Jianbao 
Published: January 2021

AbstractIn recent years, Aphidius gifuensis, a critical parasitoid, has been increasingly used to control Myzus persicae in tobacco. However, problems due to inconsistent emergence and insufficient numbers of A. gifuensis to control M. persicae have arisen in artificial reproduction. Here, we investigated the effects of the juvenoids ZR‐512, ZR‐777, ZR‐515, fenoxycarb and juvenile hormone (JH) III on the performance of M. persicae, the activities of molting enzymes and parasitism rates. The aim was to identify juvenoids that may prolong the ‘arrived too early’ optimal stages of M. persicae for A. gifuensis parasitism to address the problems mentioned above. The results showed that the developmental durations of 2nd‐ and 3rd‐instar nymphs of the parental (F0) and offspring (F1) generations of M. persicae were significantly prolonged by juvenoid treatment. The instar durations ranged from 4.00 to 13.67 h for the parental generation and from 8.00 to 32.00 h for the offspring. M. persicae lifespan was not significantly affected by the juvenoids, whereas fecundity was. Additionally, the phenoloxidase and chitinase contents and activities in M. persicae were significantly reduced by the juvenoids, whereas the parasitism rate of A. gifuensis on M. persicae was unaffected. Our study provides information that can help prolong the ‘arrived too early’ period of effective parasitism of M. persicae nymphs by A. gifuensis and thereby benefit the large‐scale artificial reproduction of A. gifuensis. These findings will enhance the biological control of M. persicae and highlight the mechanism by which juvenoids affect M. persicae development by regulating phenoloxidase or chitinase.
Tonsillitis as a possible predisposition to synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome
Authors: Xiang Yirong , Wang Yutong , Cao Yihan , Li Zhaohui , Xiong Dingkun , Wang Lun , Zhang Wen , Zeng Xiaofeng , Wang Yi , Li Chen 
Published: January 2021

AbstractAimTo present the prevalence of tonsillitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) patients, to compare the clinical characteristics and disease activities between SAPHO patients with and without tonsillitis and to preliminarily explore the efficacy of tonsillectomy in SAPHO syndrome.MethodA total of 58 SAPHO patients were included. Clinical data were collected, including demographic characteristics and acute phase reactants (erythrocyte sedimentation rate, high‐sensitivity C‐reactive protein). The visual analog scale (VAS), Palmoplantar Pustule Psoriasis Area Severity Index (PPPASI) and Nail Psoriasis Severity Index (NAPSI) were used to measure the severity of bone pain, skin lesions and nail lesions, respectively. Patients were referred to the otolaryngology department for tonsil examinations, including tonsil hypertrophy (grade ≥ 2), chronic congestion, inflammatory secretion and tonsil stones. The patients who underwent tonsillectomy were followed up after the surgery.ResultsA total of 67.2% of patients had tonsillitis. Patients with tonsillitis had markedly higher PPPASI (1.2 [0, 7.4] vs. 7.6 [1.75, 15.5], P = .018) and NAPSI (0 [0, 21] vs. 8 [3, 28], P = .032) scores. After tonsillectomy, the patients experienced significantly improved bone pain (VAS, 5 [4, 7] vs. 3 [1, 4], P = .034) and skin lesions (PPPASI, 16.2 [7.05, 18.35] vs 1.8 [0.7, 3.7], P = .028).ConclusionApproximately 2/3 of SAPHO patients had tonsillitis. Patients with tonsillitis had more severe skin and nail lesions. Tonsillectomy might be associated with improved bone and skin symptoms in SAPHO patients. Future prospective controlled studies are warranted.