Synthesis and evaluation of antibacterial and antibiofilm agents based on phenylamino-substituted 1,4-benzoquinones.

Aim: This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens.Materials & methods: The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and p-substituted anilines, were assessed for their antimicrobial activity through both in vitro and in silico analyses.Results: Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against Pseudomonas aeruginosa, with minimum inhibitory concentrations ranging from 16 to 128 µg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant Staphylococcus aureus ranging from 64 to 128 µg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features.Conclusion: The 6-AQs 19g and 19f showed a promising antimicrobial profile, indicating their potential as new therapeutic options.

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Back to the future: Forgotten protocols for optimizing the isolation of arthropod haemocytes.

Consideration is given to previous and more recent protocols for harvesting arthropod haemocytes from Galleria, Drosophila, mosquitoes, Limulus and crustaceans. The optimal harvesting of these cells is essential for meaningful studies of invertebrate immunity in vitro. The results of such experiments, however, have often been flawed due to a lack of understanding of the fragile nature of arthropod haemocytes on exposure to bacterial lipopolysaccharides, resulting in the aggregation and loss of cell types during haemolymph clotting. This article emphasizes that although there are similarities between mammalian neutrophils and arthropod haemocytes, the protocols required for the successful harvesting of these cells vary significantly. The various stages for the successful harvesting of arthropod haemocytes are described in detail and should provide invaluable advice to those requiring both high cell viability and recovery of the different cell types for subsequent experimentation.

Immune Reactions of Vector Insects to Parasites and Pathogens.

This overview initially describes insect immune reactions and then brings together present knowledge of the interactions of vector insects with their invading parasites and pathogens. It is a way of introducing this Special Issue with subsequent papers presenting the latest details of these interactions in each particular group of vectors. Hopefully, this paper will fill a void in the literature since brief descriptions of vector immunity have now been brought together in one publication and could form a starting point for those interested and new to this important area. Descriptions are given on the immune reactions of mosquitoes, blackflies, sandflies, tsetse flies, lice, fleas and triatomine bugs. Cellular and humoral defences are described separately but emphasis is made on the co-operation of these processes in the completed immune response. The paper also emphasises the need for great care in extracting haemocytes for subsequent study as appreciation of their fragile nature is often overlooked with the non-sterile media, smearing techniques and excessive centrifugation sometimes used. The potential vital role of eicosanoids in the instigation of many of the immune reactions described is also discussed. Finally, the priming of the immune system, mainly in mosquitoes, is considered and one possible mechanism is presented.

Potential for redistribution of post-moult habitat for Eudyptes penguins in the Southern Ocean under future climate conditions.

Anthropogenic climate change is resulting in spatial redistributions of many species. We assessed the potential effects of climate change on an abundant and widely distributed group of diving birds, Eudyptes penguins, which are the main avian consumers in the Southern Ocean in terms of biomass consumption. Despite their abundance, several of these species have undergone population declines over the past century, potentially due to changing oceanography and prey availability over the important winter months. We used light-based geolocation tracking data for 485 individuals deployed between 2006 and 2020 across 10 of the major breeding locations for five taxa of Eudyptes penguins. We used boosted regression tree modelling to quantify post-moult habitat preference for southern rockhopper (E. chrysocome), eastern rockhopper (E. filholi), northern rockhopper (E. moseleyi) and macaroni/royal (E. chrysolophus and E. schlegeli) penguins. We then modelled their redistribution under two climate change scenarios, representative concentration pathways RCP4.5 and RCP8.5 (for the end of the century, 2071-2100). As climate forcings differ regionally, we quantified redistribution in the Atlantic, Central Indian, East Indian, West Pacific and East Pacific regions. We found sea surface temperature and sea surface height to be the most important predictors of current habitat for these penguins; physical features that are changing rapidly in the Southern Ocean. Our results indicated that the less severe RCP4.5 would lead to less habitat loss than the more severe RCP8.5. The five taxa of penguin may experience a general poleward redistribution of their preferred habitat, but with contrasting effects in the (i) change in total area of preferred habitat under climate change (ii) according to geographic region and (iii) the species (macaroni/royal vs. rockhopper populations). Our results provide further understanding on the regional impacts and vulnerability of species to climate change.

Reaching the Final Endgame for Constant Waves of COVID-19.

Despite intramuscular vaccines saving millions of lives, constant devastating waves of SARS-CoV-2 infections continue. The elimination of COVID-19 is challenging, but necessary in order to avoid millions more people who would suffer from long COVID if we fail. Our paper describes rapidly advancing and innovative therapeutic strategies for the early stage of infection with COVID-19 so that tolerating continuing cycles of infection should be unnecessary in the future. These therapies include new vaccines with broader specificities, nasal therapies and antiviral drugs some targeting COVID-19 at the first stage of infection and preventing the virus entering the body in the first place. Our article describes the advantages and disadvantages of each of these therapeutic options which in various combinations could eventually prevent renewed waves of infection. Finally, important consideration is given to political, social and economic barriers that since 2020 hindered vaccine application and are likely to interfere again with any COVID-19 endgame.

Foraging range scales with colony size in high-latitude seabirds.

Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals.1-4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony.1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony.5,6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment.6 Using tracking data from murres (Uria spp.), the world's most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size0.33 during the chick-rearing stage, consistent with Ashmole's halo theory.1,2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole's version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species.

Urinary Volatile Organic Compound Testing in Fast-Track Patients with Suspected Colorectal Cancer.

Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. A prospective, multi-center, observational feasibility study was performed across three sites. Patients referred to NHS fast-track pathways for potential CRC provided a urine sample that underwent Gas Chromatography-Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS), and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. 558 patients participated with 23 (4%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity = 0.878, specificity = 0.882, AUROC = 0.896) but it is labour intensive. Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified suggesting VOC analysis may have future utility as a triage tool.

Evaluation of Biological Activities of Quinone-4-oxoquinoline Derivatives against Pathogens of Clinical Importance.

BACKGROUND: Microbial resistance has become a worldwide public health problem and may lead to morbidity and mortality in affected patients. OBJECTIVES: Therefore, this work aimed to evaluate the antibacterial activity of quinone-4- oxoquinoline derivatives. METHODS: These derivatives were evaluated against Gram-positive and Gram-negative bacteria by their antibacterial activity, anti-biofilm, and hemolytic activities and in silico assays. RESULTS: The quinone-4-oxoquinoline derivatives presented broad-spectrum antibacterial activities and, in some cases, were more active than commercially available reference drugs. These compounds also inhibited bacterial adhesion, and the assays revealed seven non-hemolytic derivatives. The derivatives seem to cause damage to the bacterial cell membrane, and those containing the carboxyl group at the C-3 position of the 4-quinolonic nucleus were more active than those containing a carboxyethyl group. CONCLUSION: The isoquinoline-5,8-dione nucleus also favored antimicrobial activity. The study showed that the target of the derivatives must be a non-conventional hydrophobic allosteric binding pocket on the DNA gyrase enzyme.

Overview of paratransgenesis as a strategy to control pathogen transmission by insect vectors.

This article presents an overview of paratransgenesis as a strategy to control pathogen transmission by insect vectors. It first briefly summarises some of the disease-causing pathogens vectored by insects and emphasises the need for innovative control methods to counter the threat of resistance by both the vector insect to pesticides and the pathogens to therapeutic drugs. Subsequently, the state of art of paratransgenesis is described, which is a particularly ingenious method currently under development in many important vector insects that could provide an additional powerful tool for use in integrated pest control programmes. The requirements and recent advances of the paratransgenesis technique are detailed and an overview is given of the microorganisms selected for genetic modification, the effector molecules to be expressed and the environmental spread of the transgenic bacteria into wild insect populations. The results of experimental models of paratransgenesis developed with triatomines, mosquitoes, sandflies and tsetse flies are analysed. Finally, the regulatory and safety rules to be satisfied for the successful environmental release of the genetically engineered organisms produced in paratransgenesis are considered.

Individual repeatability of avian migration phenology: A systematic review and meta-analysis.

Changes in phenology and distribution are being widely reported for many migratory species in response to shifting environmental conditions. Understanding these changes and the situations in which they occur can be aided by understanding consistent individual differences in phenology and distribution and the situations in which consistency varies in strength or detectability. Studies tracking the same individuals over consecutive years are increasingly reporting migratory timings to be a repeatable trait, suggesting that flexible individual responses to environmental conditions may contribute little to population-level changes in phenology and distribution. However, how this varies across species and sexes, across the annual cycle and in relation to study (tracking method, study design) and/or ecosystem characteristics is not yet clear. Here, we take advantage of the growing number of publications in movement ecology to perform a phylogenetic multilevel meta-analysis of repeatability estimates for avian migratory timings to investigate these questions. Of 2,433 reviewed studies, 54 contained suitable information for meta-analysis, resulting in 177 effect sizes from 47 species. Individual repeatability of avian migratory timings averaged 0.414 (95% confidence interval: 0.3-0.5) across landbirds, waterbirds and seabirds, suggesting consistent individual differences in migratory timings is a common feature of migratory systems. Timing of departure from the non-breeding grounds was more repeatable than timings of arrival at or departure from breeding grounds, suggesting that conditions encountered on migratory journeys and outcome of breeding attempts can influence individual variation. Population-level shifts in phenology could arise through individual timings changing with environmental conditions and/or through shifts in the numbers of individuals with different timings. Our findings suggest that, in addition to identifying the conditions associated with individual variation in phenology, exploring the causes of between-individual variation will be key in predicting future rates and directions of changes in migratory timings. We therefore encourage researchers to report the within- and between- individual variance components underpinning the reported repeatability estimates to aid interpretation of migration behaviour. In addition, the lack of studies in the tropics means that levels of repeatability in less strongly seasonal environments are not yet clear.

Investigation of urinary volatile organic compounds as novel diagnostic and surveillance biomarkers of bladder cancer.

BACKGROUND: The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers. METHODS: Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis. RESULTS: The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10-7-2.8 × 10-2). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80). CONCLUSIONS: Urinary VOC analysis could aid the diagnosis and surveillance of UBC.

Individual consistency in migration strategies of a tropical seabird, the Round Island petrel.

BACKGROUND: In migratory species, the extent of within- and between-individual variation in migratory strategies can influence potential rates and directions of responses to environmental changes. Quantifying this variation requires tracking of many individuals on repeated migratory journeys. At temperate and higher latitudes, low levels of within-individual variation in migratory behaviours are common and may reflect repeated use of predictable resources in these seasonally-structured environments. However, variation in migratory behaviours in the tropics, where seasonal predictability of food resources can be weaker, remains largely unknown. METHODS: Round Island petrels (Pterodroma sp.) are tropical, pelagic seabirds that breed all year round and perform long-distance migrations. Using multi-year geolocator tracking data from 62 individuals between 2009 and 2018, we quantify levels of within- and between-individual variation in non-breeding distributions and timings. RESULTS: We found striking levels of between-individual variation in at-sea movements and timings, with non-breeding migrations to different areas occurring across much of the Indian Ocean and throughout the whole year. Despite this, repeat-tracking of individual petrels revealed remarkably high levels of spatial and temporal consistency in within-individual migratory behaviour, particularly for petrels that departed at similar times in different years and for those departing in the austral summer. However, while the same areas were used by individuals in different years, they were not necessarily used at the same times during the non-breeding period. CONCLUSIONS: Even in tropical systems with huge ranges of migratory routes and timings, our results suggest benefits of consistency in individual migratory behaviours. Identifying the factors that drive and maintain between-individual variation in migratory behaviour, and the consequences for breeding success and survival, will be key to understanding the consequences of environmental change across migratory ranges.

The role of allochrony in influencing interspecific differences in foraging distribution during the non-breeding season between two congeneric crested penguin species.

Mechanisms promoting coexistence between closely related species are fundamental for maintaining species diversity. Mechanisms of niche differentiation include allochrony which offsets the peak timing of resource utilisation between species. Many studies focus on spatial and temporal niche partitioning during the breeding season, few have investigated the role allochrony plays in influencing interspecific segregation of foraging distribution and ecology between congeneric species during the non-breeding season. We investigated the non-breeding migrations of Snares (Eudyptes robustus) and Fiordland penguins (Eudyptes pachyrhynchus), closely related species breeding between 100-350 km apart whose migration phenology differs by two months. Using light geolocation tracking, we examined the degree of overlap given the observed allochrony and a hypothetical scenario where the species commence migration simultaneously. We found that Fiordland penguins migrated to the Sub-Antarctic Frontal Zone and Polar Frontal Zone in the austral autumn whereas Snares penguins disperse westwards staying north of the Sub-Tropical Front in the austral winter. Our results suggest that allochrony is likely to be at the root of segregation because the relative profitability of the different water masses that the penguins forage in changes seasonally which results in the two species utilising different areas over their core non-breeding periods. Furthermore, allochrony reduces relatively higher levels of spatiotemporal overlap during the departure and arrival periods, when the close proximity of the two species' colonies would cause the birds to congregate in similar areas, resulting in high interspecific competition just before the breeding season. Available evidence from other studies suggests that the shift in phenology between these species has arisen from adaptive radiation and phenological matching to the seasonality of local resource availability during the breeding season and reduced competitive overlap over the non-breeding season is likely to be an incidental outcome.

Using in vivo animal models for studying SARS-CoV-2.

INTRODUCTION: The search for an animal model capable of reproducing the physiopathology of the COVID-19, and also suitable for evaluating the efficacy and safety of new drugs has become a challenge for many researchers. AREAS COVERED: This work reviews the current animal models for in vivo tests with SARS-CoV-2 as well as the challenges involved in the safety and efficacy trials. EXPERT OPINION: Studies have reported the use of nonhuman primates, ferrets, mice, Syrian hamsters, lagomorphs, mink, and zebrafish in experiments that aimed to understand the course of COVID-19 or test vaccines and other drugs. In contrast, the assays with animal hyperimmune sera have only been used in in vitro assays. Finding an animal that faithfully reproduces all the characteristics of the disease in humans is difficult. Some models may be more complex to work with, such as monkeys, or require genetic manipulation so that they can express the human ACE2 receptor, as in the case of mice. Although some models are more promising, possibly the use of more than one animal model represents the best scenario. Therefore, further studies are needed to establish an ideal animal model to help in the development of other treatment strategies besides vaccines.

Cold comfort: Arctic seabirds find refugia from climate change and potential competition in marginal ice zones and fjords.

Climate change alters species distributions by shifting their fundamental niche in space through time. Such effects may be exacerbated by increased inter-specific competition if climate alters species dominance where competitor ranges overlap. This study used census data, telemetry and stable isotopes to examine the population and foraging ecology of a pair of Arctic and temperate congeners across an extensive zone of sympatry in Iceland, where sea temperatures varied substantially. The abundance of Arctic Brünnich's guillemot Uria lomvia declined with sea temperature. Accessibility of refugia in cold water currents or fjords helped support higher numbers and reduce rates of population decline. Competition with temperate Common guillemots Uria aalge did not affect abundance, but similarities in foraging ecology were sufficient to cause competition when resources are limiting. Continued warming is likely to lead to further declines of Brünnich's guillemot, with implications for conservation status and ecosystem services.

Application of a solid-phase microextraction-gas chromatography-mass spectrometry/metal oxide sensor system for detection of antibiotic susceptibility in urinary tract infection-causing Escherichia coli - A proof of principle study.

PURPOSE: Antibiotic resistance is widespread throughout the world and represents a serious health concern. There is an urgent need for the development of novel tools for rapidly distinguishing antibiotic resistant bacteria from susceptible strains. Previous work has demonstrated that differences in antimicrobial susceptibility can be reflected in differences in the profile of volatile organic compounds (VOCs) produced by dissimilar strains. The aim of this study was to investigate the effect of the presence of cephalosporin antibiotics on the VOC profile of extended spectrum beta-lactamase (ESBL) and non-ESBL producing strains of Escherichia coli. MATERIAL AND METHODS: In this study, VOCs from strains of Escherichia coli positive and negative for the most commonly encountered ESBL, CTX-M in the presence of cephalosporin antibiotics were assessed using solid-phase microextraction (SPME) coupled with a combined gas chromatography-mass spectrometry/metal oxide sensor (GC-MS/MOS) system. RESULTS: Our proof-of-concept study allowed for distinguishing CTX-M positive and negative bacteria within 2 â€‹h after the addition of antibiotics. One MOS signal (RT: 22.6) showed a statistically significant three-way interaction (p â€‹= â€‹0.033) in addition to significant two-way interactions for culture and additive (p â€‹= â€‹0.046) plus time and additive (p â€‹= â€‹0.020). There were also significant effects observed for time (p â€‹= â€‹0.009), culture (p â€‹= â€‹0.030) and additive (p â€‹= â€‹0.028). No effects were observed in the MS data. CONCLUSIONS: The results of our study showed the potential of VOC analysis using SPME combined with a GC-MS/MOS system for the early detection of CTX-M-producing, antibiotic-resistant E. coli, responsible for urinary tract infections (UTIs).