A curated collection of Klebsiella metabolic models reveals variable substrate usage and gene essentiality

2021 ◽  
Author(s):  
Jane Hawkey ◽  
Ben Vezina ◽  
Jonathan Monk ◽  
Louise M Judd ◽  
Taylor Harshegyi ◽  
...  
Keyword(s):  
Control Strategies ◽  
Single Gene ◽  
Multi Drug Resistance ◽  
Growth Data ◽  
Gene Deletions ◽  
Diverse Range ◽  
Metabolic Models ◽  
Species Specific ◽  
Healthcare Associated ◽  
The Impact

The Klebsiella pneumoniae species complex (KpSC) is a set of seven Klebsiella taxa which are found in a variety of niches, and are an important cause of opportunistic healthcare- associated infections in humans. Due to increasing rates of multi-drug resistance within the KpSC, there is a growing interest in better understanding the biology and metabolism of these organisms to inform novel control strategies. We collated 37 sequenced KpSC isolates isolated from a variety of niches, representing all seven taxa. We generated strain-specific genome scale metabolic models (GEMs) for all 37 isolates and simulated growth phenotypes on 511 distinct carbon, nitrogen, sulphur and phosphorus substrates. Models were curated and their accuracy assessed using matched phenotypic growth data for 94 substrates (median accuracy of 96%). We explored species-specific growth capabilities and examined the impact of all possible single gene deletions on growth in 145 core carbon substrates. These analyses revealed multiple strain-specific differences, within and between species and highlight the importance of selecting a diverse range of strains when exploring KpSC metabolism. This diverse set of highly accurate GEMs could be used to inform novel drug design, enhance genomic analyses, and identify novel virulence and resistance determinants. We envisage that these 37 curated strain-specific GEMs, covering all seven taxa of the KpSC, provide a valuable resource to the Klebsiella research community.

scholarly journals Targeting a coatomer protein complex-I gene via RNA interference results in effective lethality in the pollen beetle Brassicogethes aeneus

2020 ◽  
Author(s):  
Jonathan Willow ◽  
Silva Sulg ◽  
Clauvis Nji Tizi Taning ◽  
Ana Isabel Silva ◽  
Olivier Christiaens ◽  
...  
Keyword(s):  
Rna Interference ◽  
Control Strategies ◽  
Dietary Exposure ◽  
Pyrethroid Insecticides ◽  
Pollen Beetle ◽  
Nontarget Organisms ◽  
Brassicogethes Aeneus ◽  
Development Of Resistance ◽  
Species Specific ◽  
The Impact

AbstractThe pollen beetle Brassicogethes aeneus is a serious pest of oilseed rape (Brassica napus) in Europe. Management of this pest has grown difficult due to B. aeneus’s development of resistance to pyrethroid insecticides, as well as the pressure to establish control strategies that minimise the impact on nontarget organisms. RNA interference represents a nucleotide sequence-based, and thus potentially species-specific, approach to agricultural pest control. The present study examined the efficacy of targeting the coatomer gene coatomer subunit alpha (αCOP), via both microinjection and dietary exposure to exogenous complementary dsRNA, on αCOP-silencing and subsequent mortality in B. aeneus. Beetles injected with dsRNA targeting αCOP (at 0.14 µg/mg) showed 88% and 100% mortality at 6 and 10 days post-injection, respectively; where by the same time after dietary exposure, 43%–89% mortality was observed in the 3 µg dsRNA/µL treatment, though the effect was concentration-dependent. Thus, the effect was significant for both delivery routes. In working towards RNA-based management of B. aeneus, future studies should include αCOP as a target of interest.

scholarly journals Analysis of the Contribution of cyp51 Genes to Azole Resistance in Aspergillus Section Nigri with the CRISPR-Cas9 Technique

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Alba Pérez-Cantero ◽  
Adela Martin-Vicente ◽  
Josep Guarro ◽  
Jarrod R. Fortwendel ◽  
Javier Capilla
Keyword(s):  
Single Gene ◽  
Transcriptional Response ◽  
Azole Resistance ◽  
Gene Deletions ◽  
Content Type ◽  
Ergosterol Content ◽  
Expression Studies ◽  
Gene Expression Studies ◽  
Induced Changes ◽  
The Impact

ABSTRACT Cyp51 contribution to azole resistance has been broadly studied and characterized in Aspergillus fumigatus, whereas it remains poorly investigated in other clinically relevant species of the genus, such as those of section Nigri. In this work, we aimed to analyze the impact of cyp51 genes (cyp51A and cyp51B) on the voriconazole (VRC) response and resistance of Aspergillus niger and Aspergillus tubingensis. We generated CRISPR-Cas9 cyp51A and cyp51B knockout mutants from strains with different genetic backgrounds and diverse patterns of azole susceptibility. Single-gene deletions of cyp51 genes resulted in 2- to 16-fold decreases of the VRC MIC values, which were below the VRC epidemiological cutoff value (ECV) established by the Clinical and Laboratory Standards Institute (CLSI), irrespective of their parental strains’ susceptibilities. Gene expression studies in the tested species confirmed that cyp51A participates more actively than cyp51B in the transcriptional response of azole stress. However, ergosterol quantification revealed that both enzymes comparably impact the total ergosterol content within the cell, as basal- and VRC-induced changes to ergosterol content were similar in all cases. These data contribute to our understanding of Aspergillus azole resistance, especially in non-A. fumigatus species.

‘Feral’ and ‘wild’-type methicillin-resistantStaphylococcus aureusin the United Kingdom

2009 ◽  
Vol 138 (5) ◽  
pp. 655-665 ◽  
Author(s):  
R. MILLER ◽  
A. S. WALKER ◽  
K. KNOX ◽  
D. WYLLIE ◽  
J. PAUL ◽  
...  
Keyword(s):  
Control Strategies ◽  
Acute Hospital ◽  
Wild Type ◽  
Gene Testing ◽  
The United Kingdom ◽  
Mrsa Strains ◽  
Healthcare Associated ◽  
The Impact ◽  
Panton Valentine Leukocidin

SUMMARYCirculation of methicillin-resistantStaphylococcus aureus(MRSA) outside hospitals could alter the impact of hospital-based control strategies. We investigated two groups of cases (each matched to controls with MRSA): 61 ‘community cases’ not in acute hospital in the year before MRSA isolation; and 21 cases with ciprofloxacin-sensitive (CipS) MRSA. Multi-locus sequence typing,spa-typing and Panton–Valentine leukocidin gene testing were performed and demographics obtained. Additional questionnaires were completed by community case GPs. Community cases comprised 6% of Oxfordshire MRSA. Three community cases had received no regular healthcare or antibiotics: one was infected with CipS. Ninety-one percent of community cases had healthcare-associated sequence type (ST)22/36; CipS MRSA cases had heterogeneous STs but many had recent healthcare exposure. A substantial minority of UK MRSA transmission may occur outside hospitals. Hospital strains are becoming ‘feral’ or persisting in long-term carriers in the community with regular healthcare contacts; those with recent healthcare exposure may nevertheless acquire non-hospital epidemic MRSA strains in the community.

Book Review

2014 ◽  
Vol 11 (3) ◽  
pp. 387-390
Author(s):  
Antonina Levatino
Keyword(s):  
Control Strategies ◽  
Human Mobility ◽  
Diverse Range ◽  
Transnational Mobility ◽  
Migration Management ◽  
Nation States ◽  
Migration Control ◽  
Political Economic ◽  
Controversial Nature

Martin Geiger & Antoine Pécoud (eds.), Disciplining the Transnational Mobility of People, Palgrave Macmillan, 2013, 271 pp., (ISBN 978-1-137-26306-3).In the last decades a very diverse range of initiatives have been undertaken in order to intensify and diversify the ways human mobility is managed and restricted. This trend towards a ‘diversification’ of the migration control strategies stems from the increased awareness by the nation-states of the profoundly controversial nature of the migration management enterprise because of its political, economic, social and moral implications.

Novel Applications of Nanotechnology in Controlling HIV and HSV Infections

2020 ◽  
Vol 12 ◽  
Author(s):  
Sai Akilesh M ◽  
Ashish Wadhwani
Keyword(s):  
Drug Delivery ◽  
Viral Infections ◽  
Polymeric Nanoparticles ◽  
Volume Ratio ◽  
Fold Increase ◽  
Multi Drug Resistance ◽  
Health Crisis ◽  
Pharmaceutical Properties ◽  
Simplex Virus ◽  
The Impact

: Infectious diseases have been prevalent since many decades and viral pathogens have caused global health crisis and economic meltdown on a devastating scale. High occurrence of newer viral infections in the recent years, in spite of the progress achieved in the field of pharmaceutical sciences defines the critical need for newer and more effective antiviral therapies and diagnostics. The incidence of multi-drug resistance and adverse effects due to the prolonged use of anti-viral therapy is also a major concern. Nanotechnology offers a cutting edge platform for the development of novel compounds and formulations for biomedical applications. The unique properties of nano-based materials can be attributed to the multi-fold increase in the surface to volume ratio at the nano-scale, tunable surface properties of charge and chemical moieties. Idealistic pharmaceutical properties such as increased bioavailability and retention times, lower toxicity profiles, sustained release formulations, lower dosage forms and most importantly, targeted drug delivery can be achieved through the approach of nanotechnology. The extensively researched nano-based materials are metal and polymeric nanoparticles, dendrimers and micelles, nano-drug delivery vesicles, liposomes and lipid based nanoparticles. In this review article, the impact of nanotechnology on the treatment of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus (HSV) viral infections during the last decade are outlined.

The Oxford Handbook of Adult Cognitive Disorders

2019 ◽  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Neurodevelopmental Disorders ◽  
Brain Aging ◽  
Cognitive Disorders ◽  
Diverse Range ◽  
Medical Specialties ◽  
Psychiatric Illnesses ◽  
Medical Disorders ◽  
The Impact

The prevalence of cognitive impairment caused by neurodegenerative diseases and other neurologic disorders associated with aging is expected to rise dramatically between now and year 2050, when the population of Americans aged 65 or older will nearly double. Cognitive impairment also commonly occurs in other neurologic conditions, as well as in non-neurologic medical disorders (and their treatments), idiopathic psychiatric illnesses, and adult neurodevelopmental disorders. Cognitive impairment can thus infiltrate all aspects of healthcare, making it necessary for clinicians and clinical researchers to have an integrated knowledge of the spectrum of adult cognitive disorders. The Oxford Handbook of Adult Cognitive Disorders is meant to serve as an up-to-date, scholarly, and comprehensive volume covering most diseases, conditions, and injuries resulting in impairments in cognitive function in adults. Topics covered include normal cognitive and brain aging, the impact of medical disorders (e.g., cardiovascular, liver, pulmonary) and psychiatric illnesses (e.g., depression and bipolar disorder) on cognitive function, adult neurodevelopmental disorders (e.g., Down Syndrome, Attention Deficit/Hyperactivity Disorder), as well as the various neurological conditions (e.g., Alzheimer’s disease, chronic traumatic encephalopathy, concussion). A section of the Handbook is also dedicated to unique perspectives and special considerations for the clinicians and clinical researchers, covering topics such as cognitive reserve, genetics, diversity, and neuroethics. The target audience of this Handbook includes: (1) clinicians, particularly psychologists, neuropsychologists, neurologists (including behavioral and cognitive neurologists), geriatricians, and psychiatrists (including neuropsychiatrists), who provide clinical care and management for adults with a diverse range of cognitive disorders; (2) clinical researchers who investigate cognitive outcomes and functioning in adult populations; and (3) graduate level students and post-doctoral trainees studying psychology, clinical neuroscience, and various medical specialties.

scholarly journals Power Hardware-in-the-Loop-Based Performance Analysis of Different Converter Controllers for Fast Active Power Regulation in Low-Inertia Power Systems

Energies ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 3274
Author(s):  
Jose Rueda Torres ◽  
Zameer Ahmad ◽  
Nidarshan Veera Kumar ◽  
Elyas Rakhshani ◽  
Ebrahim Adabi ◽  
...  
Keyword(s):  
Performance Evaluation ◽  
Power Systems ◽  
Real Time ◽  
Control Strategies ◽  
Active Power ◽  
Power Electronic ◽  
Hardware In The Loop ◽  
Digital Controllers ◽  
Power Regulation ◽  
The Impact

Future electrical power systems will be dominated by power electronic converters, which are deployed for the integration of renewable power plants, responsive demand, and different types of storage systems. The stability of such systems will strongly depend on the control strategies attached to the converters. In this context, laboratory-scale setups are becoming the key tools for prototyping and evaluating the performance and robustness of different converter technologies and control strategies. The performance evaluation of control strategies for dynamic frequency support using fast active power regulation (FAPR) requires the urgent development of a suitable power hardware-in-the-loop (PHIL) setup. In this paper, the most prominent emerging types of FAPR are selected and studied: droop-based FAPR, droop derivative-based FAPR, and virtual synchronous power (VSP)-based FAPR. A novel setup for PHIL-based performance evaluation of these strategies is proposed. The setup combines the advanced modeling and simulation functions of a real-time digital simulation platform (RTDS), an external programmable unit to implement the studied FAPR control strategies as digital controllers, and actual hardware. The hardware setup consists of a grid emulator to recreate the dynamic response as seen from the interface bus of the grid side converter of a power electronic-interfaced device (e.g., type-IV wind turbines), and a mockup voltage source converter (VSC, i.e., a device under test (DUT)). The DUT is virtually interfaced to one high-voltage bus of the electromagnetic transient (EMT) representation of a variant of the IEEE 9 bus test system, which has been modified to consider an operating condition with 52% of the total supply provided by wind power generation. The selected and programmed FAPR strategies are applied to the DUT, with the ultimate goal of ascertaining its feasibility and effectiveness with respect to the pure software-based EMT representation performed in real time. Particularly, the time-varying response of the active power injection by each FAPR control strategy and the impact on the instantaneous frequency excursions occurring in the frequency containment periods are analyzed. The performed tests show the degree of improvements on both the rate-of-change-of-frequency (RoCoF) and the maximum frequency excursion (e.g., nadir).

scholarly journals Estimating asymptomatic, undetected and total cases for the COVID-19 outbreak in Wuhan: a mathematical modeling study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xi Huo ◽  
Jing Chen ◽  
Shigui Ruan
Keyword(s):  
Disease Transmission ◽  
Large Scale ◽  
Transmission Rate ◽  
Control Strategies ◽  
Herd Immunity ◽  
Antibody Prevalence ◽  
Screening Process ◽  
Vaccination Programs ◽  
Prevalence Level ◽  
The Impact

Abstract Background The COVID-19 outbreak in Wuhan started in December 2019 and was under control by the end of March 2020 with a total of 50,006 confirmed cases by the implementation of a series of nonpharmaceutical interventions (NPIs) including unprecedented lockdown of the city. This study analyzes the complete outbreak data from Wuhan, assesses the impact of these public health interventions, and estimates the asymptomatic, undetected and total cases for the COVID-19 outbreak in Wuhan. Methods By taking different stages of the outbreak into account, we developed a time-dependent compartmental model to describe the dynamics of disease transmission and case detection and reporting. Model coefficients were parameterized by using the reported cases and following key events and escalated control strategies. Then the model was used to calibrate the complete outbreak data by using the Monte Carlo Markov Chain (MCMC) method. Finally we used the model to estimate asymptomatic and undetected cases and approximate the overall antibody prevalence level. Results We found that the transmission rate between Jan 24 and Feb 1, 2020, was twice as large as that before the lockdown on Jan 23 and 67.6% (95% CI [0.584,0.759]) of detectable infections occurred during this period. Based on the reported estimates that around 20% of infections were asymptomatic and their transmission ability was about 70% of symptomatic ones, we estimated that there were about 14,448 asymptomatic and undetected cases (95% CI [12,364,23,254]), which yields an estimate of a total of 64,454 infected cases (95% CI [62,370,73,260]), and the overall antibody prevalence level in the population of Wuhan was 0.745% (95% CI [0.693%,0.814%]) by March 31, 2020. Conclusions We conclude that the control of the COVID-19 outbreak in Wuhan was achieved via the enforcement of a combination of multiple NPIs: the lockdown on Jan 23, the stay-at-home order on Feb 2, the massive isolation of all symptomatic individuals via newly constructed special shelter hospitals on Feb 6, and the large scale screening process on Feb 18. Our results indicate that the population in Wuhan is far away from establishing herd immunity and provide insights for other affected countries and regions in designing control strategies and planing vaccination programs.

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