bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical investigation into effect of self-healing composite microcapsules thickness and diameter on their failure strength
Authors: Pittala Raj Kumar , B. Satish Ben , Chokka Syam Kumar , Prasad Niranjan
Published: April 2021

Purpose

Microcapsule-embedded autonomic healing materials have the ability to repair microcracks when they come into contact with the crack by releasing the healing agent. The microcapsules with specific shape and thickness effect in releasing healing agent to the cracked surfaces. Thus, the purpose of this paper is to know the load bearing capacity of the self-healing microcapsules and the stresses developed in the material.

Design/methodology/approach

In the present study, self-healing microcapsule is modelled and integrated with the polymer matrix composite. The aim of the present study is to investigate failure criteria of Poly (methyl methacrylate) microcapsules by varying the shell thickness, capsule diameter and loading conditions. The strength of the capsule is evaluated by keeping the shell thickness as constant and varying the capsule diameter. Uniformly distributed pressure loads were applied on the capsule-reinforced polymer matrix composite to assess the failure strength of capsules and composite.

Findings

It is observed from the results that the load required to break the capsules is increasing with the increase in capsule diameter. The failure strength of microcapsule with 100 µm diameter and 5 µm thickness is observed as 255 MPa. For an applied load range of 40–160 N/mm2 on the capsules embedded composite, the maximum stress developed in the capsules is observed as 308 MPa.

Originality/value

Failure strengths of microcapsules and stresses developed in the microcapsule-reinforced polymer composites were evaluated.
Three dimensional modelling of aluminum foam through computed tomography scan technique
Authors: Sahu Sonika , Ukey Piyush D. , Kumar Narendra , Singh Ravi Pratap , Ansari Mohd. Zahid
Published: April 2021

Purpose

This study aims to generate different three-dimensional (3D) foam models using computer tomography (CT) scan and solid continuum techniques. The generated foam models were used to study deformation mechanism and the elastic-plastic behaviour with the existing experimental foam behaviour.

Design/methodology/approach

CT scan model was generated by combing 2D images of foam in MIMICS software. Afterwards, it was imported in ABAQUS/CAE software. However, solid continuum model was generated in ABAQUS/CAE software by using crushable foam properties. Then, the generated foam models were sets boundary conditions for a compression test.

Findings

CT scans capture the actual morphology of foam sample which may directly an image based finite element foam model. The sectional views of both the models were used to observe deformation mechanism on compression. The real compressive behaviour of foam was visualised in CT-Scan foam model. It was observed that CT-scan model was the more accurate modelling method than crushable foam model.

Originality/value

The internal structure of foam is very complex and difficult to analyse. Therefore, CT-scanning may be the accurate method for capturing the macro-level detailing of foam structure. A CT-scan foam model can be used for multiple times for mechanical analysis using a simulation software, which may reduce the manufacturing and the experimental cost and time.
Shifting baselines: Physiological legacies contribute to the response of reef corals to frequent heatwaves
Authors: Wall Christopher B. , Ricci Contessa A. , Wen Alexandra D. , Ledbetter Bren E. , Klinger Delania E. , Mydlarz Laura D. , Gates Ruth D. , Putnam Hollie M.
Published: April 2021

Global climate change is altering coral reef ecosystems. Notably, marine heatwaves are producing widespread coral bleaching events that are increasing in frequency, with projections for annual bleaching events on reefs worldwide by mid‐century.

Responses of corals to elevated seawater temperatures are modulated by abiotic factors (e.g. environmental regimes) and dominant Symbiodiniaceae endosymbionts that can shift coral traits and contribute to physiological legacy effects on future response trajectories. It is critical, therefore, to characterize shifting physiological and cellular states driven by these factors and evaluate their influence on in situ bleaching (and recovery) events. We use back‐to‐back bleaching events (2014, 2015) in Hawai'i to characterize the cellular and organismal phenotypes of Montipora capitata corals dominated by heat‐sensitive Cladocopium or heat‐tolerant Durusdinium Symbiodiniaceae at two reef sites.

Despite fewer degree heating weeks in the first‐bleaching event relative to the second (7 vs. 10), M. capitata bleaching severity was greater [bleached cover: ~70% (2014) vs. 50% (2015)] and environmental history (site effects) on coral phenotypes were more pronounced. Symbiodiniaceae affected bleaching responses, but immunity and antioxidant activity was similar in all corals, despite differences in bleaching phenotypes.

We demonstrate that repeat bleaching triggers cellular responses that shift holobiont multivariate phenotypes. These perturbed multivariate phenotypes constitute physiological legacies, which set corals on trajectories (positive and/or negative) that influence future coral performance. Collectively, our data support the need for greater tracking of stress response in a multivariate context to better understand the biology and ecology of corals in the Anthropocene.

A free Plain Language Summary can be found within the Supporting Information of this article.
Sodium addition increases leaf herbivory and fungal damage across four grasslands
Authors: Welti Ellen A. R. , Kaspari Michael
Published: April 2021

Sodium (Na) is an essential element for all animals, but not for plants. Soil Na supplies vary geographically. Animals that primarily consume plants thus have the potential to be Na limited and plants that uptake Na may be subject to higher rates of herbivory, but their high Na content also may attract beneficial partners such as pollinators and seed dispersers.

To test for the effects of Na biogeochemistry on herbivory, we conducted distributed Na press experiments (monthly Na application across the growing season) in four North American grasslands.

Na addition increased soil and plant Na concentrations at all sites. Grasses in Na addition plots had significantly higher herbivore damage by leaf miners and fungal pathogens than those in control plots. Forbs with higher foliar Na concentrations had significantly more chewing insect herbivore and fungal damage.

While no pattern was evident across all species, several forb species had higher Na concentrations in inflorescences compared to leaves, suggesting they may allocate Na to attract beneficial partners.

The uptake of Na by plants, and animal responses, has implications for the salinification in the Anthropocene. Increased use of road salt, irrigation with saline groundwater, rising sea levels and increasing temperatures and evapotranspiration rates with climate change can all increase inputs of Na into terrestrial ecosystems.

Our results suggest increasing terrestrial Na availability will benefit insect herbivores and plant fungal pathogens.

A free Plain Language Summary can be found within the Supporting Information of this article.
Diffraction separation by variational mode decomposition
Authors: Lin Peng , Zhao Jingtao , Peng Suping , Cui Xiaoqin
Published: April 2021

Diffracted wavefields with superior illumination encode key geologic information about small‐scale geologic discontinuities or inhomogeneities in the subsurface and thus possess great potential for high‐resolution imaging. However, the weak diffracted wavefield is easily masked by the dominant reflected data. Diffraction separation from specular reflected data still plays an important role and plays a major role in diffraction imaging implementation. To solve this problem, a new diffraction‐separation method is proposed that uses variational mode decomposition to suppress reflected data and separate diffracted wavefields in the common‐offset or poststack domains. The variational mode decomposition algorithm targets reflected wavefield by decomposing seismic data into an ensemble of band‐limited intrinsic mode functions representing linear and strong reflected data. This method is based on the principle of energy sparsity and can utilize the kinematic and dynamic differences between reflected and diffracted wavefields to effectively predict linear reflected data. Synthetic and field data examples using complex body geometries demonstrate the effectiveness and performance of the proposed method in enhancing diffracted wavefield and attenuating reflected data as well as increasing the signal‐to‐noise ratio, which helps to clearly image small‐scale subwavelength geologic structures.
The microbiota of intertidal macroalgae Fucus distichus is site‐specific and resistant to change following transplant
Authors: Davis Katherine M. , Mazel Florent , Parfrey Laura Wegener
Published: April 2021

It is unclear how host‐associated microbial communities will be affected by future environmental change. Characterizing how microbiota differ across sites with varying environmental conditions and assessing the stability of the microbiota in response to abiotic variation are critical steps towards predicting outcomes of environmental change. Intertidal organisms are valuable study systems because they experience extreme variation in environmental conditions on tractable timescales such as tide cycles and across small spatial gradients in the intertidal zone. Here we show a widespread intertidal macroalgae, Fucus distichus, hosts site‐specific microbiota over small (meters to kilometres) spatial scales. We demonstrate stability of site‐specific microbial associations by manipulating the host environment and microbial species pool with common garden and reciprocal transplant experiments. We hypothesized that F. distichus microbiota would readily shift to reflect the contemporary environment due to selective filtering by abiotic conditions and/or colonization by microbes from the new environment or nearby hosts. Instead, F. distichus microbiota was stable for days after transplantation in both the laboratory and field. Our findings expand the current understanding of microbiota dynamics on an intertidal foundation species. These results may also point to adaptations for withstanding short‐term environmental variation, in hosts and/or microbes, facilitating stable host–microbial associations.
Astrobiology of life on Earth
Authors: Hallsworth John E. , Mancinelli Rocco L. , Conley Catharine A. , Dallas Tiffany D. , Rinaldi Teresa , Davila Alfonso F. , Benison Kathleen C. , Rapoport Alexander , Cavalazzi Barbara , Selbmann Laura , Changela Hitesh , Westall Frances , Yakimov Michail M. , Amils Ricardo , Madigan Michael T.
Published: April 2021

Astrobiology is mistakenly regarded by some as a field confined to studies of life beyond Earth. Here, we consider life on Earth through an astrobiological lens. Whereas classical studies of microbiology historically focused on various anthropocentric sub‐fields (such as fermented foods or commensals and pathogens of crop plants, livestock and humans), addressing key biological questions via astrobiological approaches can further our understanding of all life on Earth. We highlight potential implications of this approach through the articles in this Environmental Microbiology special issue ‘Ecophysiology of Extremophiles’. They report on the microbiology of places/processes including low‐temperature environments and chemically diverse saline‐ and hypersaline habitats; aspects of sulphur metabolism in hypersaline lakes, dysoxic marine waters, and thermal acidic springs; biology of extremophile viruses; the survival of terrestrial extremophiles on the surface of Mars; biological soils crusts and rock‐associated microbes of deserts; subsurface and deep biosphere, including a salticle formed within Triassic halite; and interactions of microbes with igneous and sedimentary rocks. These studies, some of which we highlight here, contribute to our understanding of the spatiotemporal reach of Earth'sfunctional biosphere, and the tenacity of terrestrial life. Their findings will help set the stage for future work focused on the constraints for life, and how organisms adapt and evolve to circumvent these constraints.
Distinctive role of fluG in the adaptation of Beauveria bassiana to insect‐pathogenic lifecycle and environmental stresses
Authors: Guo Chong‐Tao , Peng Han , Tong Sen‐Miao , Ying Sheng‐Hua , Feng Ming‐Guang
Published: April 2021

The upstream developmental activation (UDA) pathway comprises three fluG‐cored cascades (fluG‐flbA, fluG‐flbE/B/D and fluG‐flbC) that activate the key gene brlA of central developmental pathway (CDP) to initiate conidiation in aspergilli. However, the core role of fluG remains poorly understood in other fungi. Here, we report distinctive role of fluG in the insect‐pathogenic lifecycle of Beauveria bassiana. Disruption of fluG resulted in limited conidiation defect, which was mitigated with incubation time and associated with time‐course up‐regulation/down‐regulation of all flb and CDP genes and another fluG‐like gene (BBA_06309). In ΔfluG, increased sensitivities to various stresses correlated with repression of corresponding stress‐responsive genes. Its virulence through normal cuticle infection was attenuated greatly due to blocked secretion of cuticle‐degrading enzymes and delayed formation of hyphal bodies (blastospores) to accelerate proliferation in vivo and host death. In submerged ΔfluG cultures mimicking insect haemolymph, largely increased blastospore production concurred with drastic up‐regulation of the CDP genes brlA and abaA, which was associated with earlier up‐regulation of most flb genes in the cultures. Our results unveil an essentiality of fluG for fungal adaptation to insect‐pathogenic lifecycle and suggest the other fluG‐like gene to act as an alternative player in the UDA pathway of B. bassiana.
Seasonal dynamics of natural Ostreococcus viral infection at the single cell level using VirusFISH
Authors: Castillo Yaiza M. , Forn Irene , Yau Sheree , Morán Xosé Anxelu G. , Alonso‐Sáez Laura , Arandia‐Gorostidi Néstor , Vaqué Dolors , Sebastián Marta
Published: April 2021

Ostreococcus is a cosmopolitan marine genus of phytoplankton found in mesotrophic and oligotrophic waters, and the smallest free‐living eukaryotes known to date, with a cell diameter close to 1 μm. Ostreococcus has been extensively studied as a model system to investigate viral–host dynamics in culture, yet the impact of viruses in naturally occurring populations is largely unknown. Here, we used Virus Fluorescence in situ Hybridization (VirusFISH) to visualize and quantify viral‐host dynamics in natural populations of Ostreococcus during a seasonal cycle in the central Cantabrian Sea (Southern Bay of Biscay). Ostreococcus were predominantly found during summer and autumn at surface and 50 m depth, in coastal, mid‐shelf and shelf waters, representing up to 21% of the picoeukaryotic communities. Viral infection was only detected in surface waters, and its impact was variable but highest from May to July and November to December, when up to half of the population was infected. Metatranscriptomic data available from the mid‐shelf station unveiled that the Ostreococcus population was dominated by the species O. lucimarinus. This work represents a proof of concept that the VirusFISH technique can be used to quantify the impact of viruses on targeted populations of key microbes from complex natural communities.
Special roles for efflux systems in iron homeostasis of non‐siderophore‐producing cyanobacteria
Authors: Liu Ling‐Mei , Li Ding‐Lan , Deng Bin , Wang Xin‐Wei , Jiang Hai‐Bo
Published: April 2021

In oligotrophic oceans, low bioavailability of Fe is a key factor limiting primary productivity. However, excessive Fe in cells leads to the Fenton reaction, which is toxic to cells. Cyanobacteria must strictly maintain intracellular Fe homeostasis. Here, we knocked out a series of genes encoding efflux systems in Synechocystis sp. PCC 6803, and found eight genes that are required for high Fe detoxification. Unexpectedly, the HlyBD‐TolC efflux system plays an important role in the adaptation of Synechocystis under Fe‐deficient conditions. Mutants of HlyD and TolC grew worse than the wild‐type strain under low‐Fe conditions and showed significantly lower intracellular Fe contents than the wild‐type strain. We excluded the possibility that the low Fe sensitivity of the HlyBD‐TolC mutants was caused by a loss of the S‐layer, the main extracellular protein secreted via this efflux system. Inactivation of the HlyD protein influenced type IV pili formation and direct inactivation of type IV pili related genes affected the adaptation to low‐Fe conditions. HlyBD‐TolC system is likely involved in the formation of type IV pili and indirectly influenced Fe acquisition. Our findings suggest that efflux system in non‐siderophore‐producing cyanobacteria can facilitate Fe uptake and help cells adapt to Fe‐deficient conditions via novel pathways.
Termite mounds reduce soil microbial diversity by filtering rare microbial taxa
Authors: Chen Qing‐Lin , Hu Hang‐Wei , Yan Zhen‐Zhen , Li Chao‐Yu , Nguyen Bao‐Anh Thi , Zheng Yong , Zhu Yong‐Guan , He Ji‐Zheng
Published: April 2021

Termites are ubiquitous insects in tropical and subtropical habitats, and some of them construct massive nests (‘mounds’), which substantially promote substrate heterogeneity by altering soil properties. Yet, the role of termite nesting process in regulating the distribution and diversity of soil microbial communities remains poorly understood, which introduces uncertainty in predictions of ecosystem functions of termite mounds in a changing environment. Here, by using amplicon sequencing, we conducted a survey of 134 termite mounds across >1500 km in northern Australia and found that termite mounds significantly differed from bulk soils in the microbial diversity and community compositions. Compared with bulk soils, termite nesting process decreased the microbial diversity and the relative abundance of rare taxa. Rare taxa had a narrower habitat niche breadth than dominant taxa and might be easier to be filtered by the potential intensive microbial competition during the nesting processes. We further demonstrated that the shift in pH induced by termite nesting process was a major driver shaping the microbial community profiles in termite mounds. Together, our work provides novel evidence that termite nesting is an important process in regulating soil microbial diversity, which advances our understanding of the functioning of termite mounds.
Discovery of inhibitors of Pseudomonas aeruginosa virulence through the search for natural‐like compounds with a dual role as inducers and substrates of efflux pumps
Authors: Laborda Pablo , Alcalde‐Rico Manuel , Chini Andrea , Martínez José L. , Hernando‐Amado Sara
Published: April 2021

Multidrug efflux pumps are ancient elements encoded in every genome, from bacteria to humans. In bacteria, in addition to antibiotics, efflux pumps extrude a wide range of substrates, including quorum sensing signals, bacterial metabolites, or plant‐produced compounds. This indicates that their original functions may differ from their recently acquired role in the extrusion of antibiotics during human infection. Concerning plant‐produced compounds, some of them are substrates and inducers of the same efflux pump, suggesting a coordinated plant/bacteria coevolution. Herein we analyse the ability of 1243 compounds from a Natural Product‐Like library to induce the expression of P. aeruginosa mexCD‐oprJ or mexAB‐oprM efflux pumps' encoding genes. We further characterized natural‐like compounds that do not trigger antibiotic resistance in P. aeruginosa and that act as virulence inhibitors, choosing those that were not only inducers but substrates of the same efflux pump. Four compounds impair swarming motility, exotoxin secretion through the Type 3 Secretion System (T3SS) and the ability to kill Caenorhabditis elegans, which might be explained by the downregulation of genes encoding flagellum and T3SS. Our results emphasize the possibility of discovering new anti‐virulence drugs by screening natural or natural‐like libraries for compounds that behave as both, inducers and substrates of efflux pumps.
Identifying Linguistic Markers of CEO Hubris: A Machine Learning Approach
Authors: Akstinaite Vita , Garrard Peter , Sadler‐Smith Eugene
Published: April 2021

This paper explores the potential of machine learning for recognizing and analysing linguistic markers of hubris in CEO speech. This research is based on three assumptions: hubris is associated with potentially destructive leader behaviours; linguistic utterances are a way of distinguishing between leaders who are likely to exhibit such behaviours; identifying hubris at‐a‐distance using machine learning techniques provides a reliable, automated and scalable method for the identification and prevention of destructive outcomes emanating from CEO hubris. Using machine learning techniques, we analysed spoken utterances from a sample of hubristic CEOs and compared them with non‐hubristic CEOs. We found that machine learning algorithms have the ability to identify automatically hubristic versus non‐hubristic speech patterns. One of the main implications of this study is building a foundation for future studies that are interested in the application of machine learning in the fields of hubristic and other forms of destructive leadership, and in the study of the role that language plays in management and organizations more generally. We discuss the implications of automated data extraction and analysis for the prediction of CEOs’, and other employees’, category membership, intentions and behaviours. We offer recommendations for how hubristic and destructive leadership in organizations can be managed and curtailed more effectively, thereby obviating their negative consequences.
Humanitarianism, securitization, and containment in Jordan's Za'atari Refugee Camp
Authors: Pasha Suraina
Published: April 2021

Through a case study on Za'atari, the largest Syrian refugee camp in Jordan, this paper critically explores a contemporary example of intersection between local and global humanitarian and securitization processes in refugee governance. The paper argues that Syrian refugees have been subjected to humanitarian care and securitized treatment, with their construction in terms of potential threat to State security interests spiking in correlation with insecurities over the expansion of the “Islamic State” (IS). The paper tracks the suit of measures implemented by the host Jordanian State, with the support of the United Nations High Commissioner for Refugees (UNHCR), to produce docile refugee subjects of “humanitarian government” in a closed camp. It notes how the UNHCR invariably augments and extends the remit of Jordanian State power at the expense of refugee rights, in the name of ensuring refugee and aid worker security and the effectiveness of the aid operation. The camp plays a critical role in a performative politics of containment targeting local and global audiences.
Postmortem submersion interval (PMSI) estimation from the microbiome of sus scrofa bone in a freshwater lake
Authors: Cartozzo Claire , Singh Baneshwar , Swall Jenise , Simmons Tal
Published: April 2021

While many studies have developed microbial succession‐based models for the prediction of postmortem interval (PMI) in terrestrial systems, similar well‐replicated long‐term decomposition studies are lacking for aquatic systems. Therefore, this study sought to identify temporal changes in bacterial community structure associated with porcine skeletal remains (n = 198) for an extended period in a fresh water lake. Every ca. 250 ADD, one cage, containing 5 ribs and 5 scapulae, was removed from the lake for a total of nineteen collections. Water was also sampled at each interval. Variable region 4 (V4) of 16S rDNA was amplified and sequenced for all collected samples using Illumina MiSeq FGx Sequencing platform; resulting data were analyzed with the mothur (v1.39.5) and R (v3.6.0). Bacterial communities associated with ribs differed significantly from those associated with scapulae. This difference was mainly attributed to Clostridia, Holophagae, and Spirochaete relative abundances. For each bone type, α‐diversity increased with ADD; similarly, β‐diversity bacterial community structure changed significantly with ADD and were explained using environmental parameters and inferred functional pathways. Models developed using 24 rib and 34 scapula family‐level taxa allowed the prediction of PMSI with root mean square error of 522.97 ADD (~57 days) and 333.8 ADD (~37 days), respectively.
Combination of nitrous oxide and the modified inflation‐deflation method for identifying the intersegmental plane in segmentectomy: A randomized controlled trial
Authors: Yang Wenjing , Liu Zicheng , Yang Chun , Liu Shijiang , Guo Minna , Wen Wei , Wang Jun , Liu Cunming , Zhu Quan
Published: April 2021

Background

During thoracoscopic segmentectomy, accurately and rapidly identifying the intersegmental plane (ISP) is of great importance. This study aimed to investigate the effect and safety of a nitrous oxide (N2O)/oxygen (O2) inspired mixture on the appearance time of the ISP (TISP) via the modified inflation‐deflation method.

Methods

A total of 65 participants who underwent segmentectomy were randomized into three groups: 75% N2O (n = 24), 50% N2O (n = 23) or 0% N2O (n = 18). The 75% N2O group received a gas mixture of N2O/O2 (Fio2 = 0.25), the 50% N2O group received N2O/O2 (Fio2 = 0.5), and the 0% N2O group received 100% oxygen during lung expansion. The appearance time of satisfactory and ideal planes was recorded. Furthermore, arterial blood gas at breathing room air, one‐lung ventilation (OLV) before lung expansion, 5 and 15 min after lung expansion were also recorded.

Results

TISP was significantly shorter in the 75% N2O group (320.2 ± 65.9 s) compared with that of the 50% N2O group (552.4 ± 88.9 s, p < 0.001) and the 0% N2O group (968.3 ± 85.5 s, p < 0.001), while the 50% N2O group was shorter than that of the 0% N2O group (p < 0.001). Arterial oxygenation was significantly improved in the 0% N2O group only after lung expansion, before which there were no differences in mean PaO2 values among groups.

Conclusions

The use of N2O in the inspired gas mixture during lung expansion is an applicable strategy to rapidly identify the ISP via the modified inflation‐deflation method without any adverse effect on OLV related arterial oxygenation during segmentectomy.
Density‐dependent age of first reproduction as a key factor for population dynamics: stable breeding populations mask strong floater declines in a long‐lived raptor
Authors: Katzenberger Jakob , Gottschalk Eckhard , Balkenhol Niko , Waltert Matthias
Published: April 2021

The age at which individuals reproduce for the first time is a key demographic factor impacting population dynamics and is subject to substantial variation across animal populations. There is also widespread empirical evidence that age of first reproduction responds to changes in population density over time, especially for long‐lived birds and mammals. The density dependence in age of first reproduction has profound impacts on the size of the non‐breeding (‘floater’) part of the population. A better understanding of floater dynamics in raptor populations is urgently needed for comprehensive assessments of conservation status and management. We use the European near‐endemic red kite Milvus milvus, a long‐lived raptor of conservation concern, as an example to investigate total population dynamics with an age‐structured demographic model. Using published estimates of survival and reproduction, we model the red kite population in Germany over four decades, considering also density dependence in the age of first reproduction in different model scenarios. Based on the literature and the results of our simulations, we show that age of first reproduction for the red kite most likely responds non‐linearly to density and that this general feedback mechanism should regularly be considered in demographic simulations. Our model results have far‐reaching implications for the conservation status of the red kite, as they highlight a drastic decrease of juvenile and non‐breeding individuals in the population over time – driven both by declining vital rates and a density‐dependent shift towards a younger age of first breeding. This process is not visible when judged only by the size of the breeding population, which our model estimates to be of similar size today as in the 1980s. The total red kite population reconstructed for Germany, however, seems diminished to nearly 50% of its former size.
High‐dimensional analysis defines multicytokine T‐cell subsets and supports a role for IL‐21 in atopic dermatitis
Authors: Czarnowicki Tali , Kim Hyun Je , Villani Axel P. , Glickman Jacob , Duca Ester Del , Han Joseph , Pavel Ana B. , Lee Brian H. , Rahman Adeeb H. , Merad Miriam , Krueger James G. , Guttman‐Yassky Emma
Published: April 2021

Background

Flow cytometry is a well‐accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad‐scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients’ comprehensive profiling, critical for leveraging new targeted treatments, is not available. IL‐21 may be involved in inflammatory skin diseases but its role in AD is not well established.

Methods

We studied T‐cell polarization in the blood of 20 moderate‐to‐severe AD and 15 controls. Using CyTOF and an unsupervised analysis, we measured the frequencies and mean metal intensities of activated polar CD4+/CD8+ T‐cell subsets. Immunohistochemistry, immunofluorescence, and qRT‐PCR were used to analyze skin samples.

Results

Examining 24 surface, intracellular markers, and transcription factors, we identified six CD4+ and five CD8+ T‐cell metaclusters. A CD4+ skin‐homing IL‐13+monocytokine and a novel IL‐13+IL‐21+ multicytokine metaclusters were increased in AD vs. controls (p < .01). While IL‐13 signature characterized both clusters, levels were significantly higher in the IL‐21+ group. Both clusters correlated with AD severity (r = 0.49, p = .029). Manual gating corroborated these results and identified additional multicytokine subsets in AD. Immunohistochemistry and immunofluorescence, validated by mRNA expression, displayed significantly increasedIL‐21 counts and colocalization with IL‐13/IL‐4R in AD skin.

Conclusion

A multicytokine signature characterizes moderate‐to‐severe AD, possibly explaining partial therapeutic responses to one cytokine targeting, particularly in severe patients. Prominent IL‐21 signature in blood and skin hints for a potential pathogenic role of IL‐21 in AD.
Is there a role for glucagon‐like peptide‐1 receptor agonists in the treatment of male infertility?
Authors: Cannarella Rossella , Calogero Aldo E. , Condorelli Rosita A. , Greco Emanuela A. , Aversa Antonio , La Vignera Sandro
Published: April 2021

Glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) are novel anti‐hyperglycemic drugs efficacious on glucose control, weight loss, and cardiovascular prevention. These drugs may also be effective in modulating testicular function. In fact, they increase serum testosterone levels in diabetic and/or obese patients with functional hypogonadism on a dysmetabolic basis. Although part of this effect can be ascribed to weight loss, some evidence suggests that there is a direct effect at the testicular level. Indeed, human Leydig, Sertoli, and germ cells express GLP1 receptors. GLP1‐RAs improve sperm metabolism, motility, and insulin secretion in vitro. Likewise, GLP1‐RAs exert positive effects on the metabolism of human Sertoli cells in vitro. Finally, GLP1 is secreted by mouse Leydig cells and this suggests the presence of a paracrine mechanism by which these cells could support the metabolism of Sertoli cells. Therefore, the widespread use of GLP1‐RAs in clinical practice may reveal an important role in the management of male infertility in obese and/or diabetic patients given the negative impact of these diseases on testicular steroidogenesis and spermatogenesis. This should suggest the design of randomized controlled studies aimed at evaluating the effects of these drugs on testicular function.
Macrophage activation in stellate ganglia contributes to lung injury‐induced arrhythmogenesis in male rats
Authors: Hong Juan , Adam Ryan J. , Gao Lie , Hahka Taija , Xia Zhiqiu , Wang Dong , Nicholas Thomas A. , Zucker Irving H. , Lisco Steven J. , Wang Han‐Jun
Published: April 2021

Aim

Patients suffering from acute lung injury (ALI) are at high risk of developing cardiac arrhythmias. We hypothesized that stellate ganglia (SG) neural inflammation contributes to ALI‐induced arrhythmia.

Methods

We created an ALI rat model using a single tracheal instillation of bleomycin (2.5 mg/kg), with saline as a sham control. We recorded ECGs by implanted radiotelemetry in male bleomycin and sham rats treated with and without oral minocycline (20 mg/kg/d), an anti‐inflammatory drug that inhibits microglia/macrophage activation. The SG neuronal excitability was assessed by electrophysiology experiments.

Results

ECG data showed that bleomycin‐exposed rats exhibited significantly more spontaneous premature ventricular contractions (PVCs) from 1‐ to 3‐week post‐induction compared with sham rats, which was mitigated by chronic oral administration of minocycline. The bleomycin‐exposed rats displayed a robust increase in both the number of Iba1‐positive macrophages and protein expression of interferon regulatory factor 8 in the SG starting as early at 1‐week post‐exposure and lasted for at least 4 weeks, which was largely attenuated by minocycline. Heart rate variability analysis indicated autonomic imbalance during the first 2‐week post‐bleomycin, which was significantly attenuated by minocycline. Electrical stimulation of the decentralized SG triggered more PVCs in bleomycin‐exposed rats than sham and bleomycin + minocycline rats. Patch‐clamp data demonstrated enhanced SG neuronal excitability in the bleomycin‐exposed rats, which was attenuated by minocycline. Co‐culture of lipopolysaccharide (LPS)‐pretreated macrophages with normal SG neurons enhanced SG neuronal excitability.

Conclusion

Macrophage activation in the SG contributes to arrhythmogenesis in bleomycin‐induced ALI in male rats.
Population pharmacokinetics and probability of target attainment in patients with sepsis under renal replacement therapy receiving continuous infusion of meropenem: Sustained low‐efficiency dialysis and continuous veno‐venous haemodialysis
Authors: Westermann Isabella , Gastine Silke , Müller Carsten , Rudolph Wiebke , Peters Frank , Bloos Frank , Pletz Mathias , Hagel Stefan
Published: April 2021

Aims

To describe the population pharmacokinetics (PK) and probability of target attainment (PTA) of continuous infusion (CI) of meropenem in septic patients receiving renal replacement therapy (RRT).

Methods

Fifteen patients without RRT, 13 patients receiving sustained low‐efficiency dialysis and 12 patients receiving continuous veno‐venous haemodialysis were included. Population PK analysis with Monte Carlo simulations for different dosing regimens was performed. For minimum inhibitory concentration 2 mg/L was chosen. The target was set as 50% time ≥4× minimum inhibitory concentration.

Results

The PK of meropenem was best described by a 1‐compartment model with linear elimination. Serum creatinine, residual diuresis and time on RRT, with no difference between sustained low‐efficiency dialysis and continuous veno‐venous haemodialysis, were found to be significant covariates affecting clearance, explaining >20% of the clearance between subject variability. PTA analysis showed that in patients with RRT, 2 g/24 h, meropenem CI achieved a PTA of 95%. In patients without RRT, the target was achieved with 3 g/24 h CI or prolonged infusion of 1 g meropenem over 8 hours but not with bolus application of 1 g meropenem for 8 hours. Only 2 patients (both without RRT) had meropenem concentrations below the target level. However, approximately half of the patients with RRT receiving CI 3 g/24 h meropenem had toxic concentrations.

Conclusion

We found relevant PK variability for meropenem CI in septic patients with or without RRT, leading to a substantial risk for overdosing in patients with RRT. This finding highlights the strong demand for personalized dosing in critically ill patients.
Oxytocin and vasopressin: Signalling, behavioural modulation and potential therapeutic effects
Authors: Rae Mariana , Lemos Duarte Mariana , Gomes Ivone , Camarini Rosana , Devi Lakshmi A.
Published: April 2021

Oxytocin (OT) and vasopressin (AVP) are endogenous ligands for OT and AVP receptors in the brain and in the peripheral system. Several studies demonstrate that OT and AVP have opposite roles in modulating stress, anxiety and social behaviours. Interestingly, both peptides and their receptors exhibit high sequence homology which could account for the biased signalling interaction of the peptides with OT and AVP receptors. However, how and under which conditions this crosstalk occurs in vivo remains unclear. In this review we shed light on the complexity of the roles of OT and AVP, by focusing on their signalling and behavioural differences and exploring the crosstalk between the receptor systems. Moreover, we discuss the potential of OT and AVP receptors as therapeutic targets to treat human disorders, such as autism, schizophrenia and drug abuse.

LINKED ARTICLES

This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc
Apocynin prevents cigarette smoking‐induced loss of skeletal muscle mass and function in mice by preserving proteostatic signalling
Authors: Chan Stanley M. H. , Bernardo Ivan , Mastronardo Chanelle , Mou Kevin , De Luca Simone N. , Seow Huei Jiunn , Dobric Aleksandar , Brassington Kurt , Selemidis Stavros , Bozinovski Steven , Vlahos Ross
Published: April 2021

Background and Purpose

Skeletal muscle dysfunction is a major comorbidity of chronic obstructive pulmonary disease (COPD). This type of muscle dysfunction may be a direct consequence of oxidative insults evoked by cigarette smoke (CS) exposure. The present study examined the effects of a potent Nox inhibitor and reactive oxygen species (ROS) scavenger, apocynin, on CS‐induced muscle dysfunction.

Experimental Approach

Male BALB/c mice were exposed to either room air (sham) or CS generated from nine cigarettes per day, 5 days a week for 8 weeks, with or without the coadministration of apocynin (5 mg·kg−1, i.p.). C2C12 myotubes exposed to either hydrogen peroxide (H2O2) or water‐soluble cigarette smoke extract (CSE) with or without apocynin (500 nM) were used as an experimental model in vitro.

Key Results

Eight weeks of CS exposure caused muscle dysfunction in mice, reflected by 10% loss of muscle mass and 54% loss of strength of tibialis anterior which were prevented by apocynin administration. In C2C12 myotubes, direct exposure to H2O2 or CSE caused myofibre wasting, accompanied by ~50% loss of muscle‐derived insulin‐like growth factor (IGF)‐1 and two‐fold induction of Cybb, independent of cellular inflammation. Expression of myostatin and MAFbx, negative regulators of muscle mass, were up‐regulated under H2O2 but not CSE conditions. Apocynin treatment abolished CSE‐induced Cybb expression, preserving muscle‐derived IGF‐1 expression and signalling pathway downstream of mammalian target of rapamycin (mTOR), thereby preventing myofibre wasting.

Conclusion and Implications

Targeted pharmacological inhibition of Nox‐derived ROS may alleviate the lung and systemic manifestations in smokers with COPD.
Accuracy of static computer‐assisted implant placement in long span edentulous area by novice implant clinicians: A cross‐sectional in vitro study comparing fully‐guided, pilot‐guided, and freehand implant placement protocols
Authors: Abduo Jaafar , Lau Douglas
Published: April 2021

Background

To ensure accurate implant placement, surgical guides are used to control the steps of implant placement surgery.

Purpose

Evaluation of the accuracy of implant placement in long span edentulous area by novice implant clinicians according to fully‐guided (FG), pilot‐guided (PG), and freehand (FH) placement protocols.

Materials and methods

Maxillary surgical models with four missing teeth from the right first canine to the first molar were produced by 3‐dimensional printing. Fourteen clinicians new to implant dentistry participated in the study, and each one of them inserted one canine and one molar implant for every implant placement protocol. All implant placement steps were completed in phantom heads to simulate the clinical situation. To evaluate the accuracy, the implant vertical, horizontal platform, horizontal apex, angle, and interimplant distance deviations from the planned positions were calculated.

Results

With the exception of vertical deviation, the FG placement was clearly more accurate than the PG and FH placements for all the variables for canine and molar implants. The PG placement was significantly more accurate than the FH placement for the horizontal platform and apex deviations, and interimplant distance deviation. The FG placement did not show a significant impact of the location of the implant, or the horizontal deviations of the platform or the apex. The PG and FH placements showed increased deviation at the canine implant than the molar implant, and at the apex of the implants than the platform of the implants.

Conclusions

Within the limitations of this in vitro study, novice clinicians achieved a significantly more accurate implant position with FG placement, followed by PG and FH placements respectively. Therefore, a form of guided surgery is beneficial for novice clinicians.
British Rhinological Society Consensus Guidance on the use of biological therapies for chronic rhinosinusitis with nasal polyps
Authors: Hopkins Claire , McKenzie Jo‐Lyn , Anari Shahram , Carrie Sean , Ramakrishnan Yujay , Kara Naveed , Philpott Carl , Hobson Jonathan , Qureishi Ali , Stew Ben , Bhalla Raj , Gane Simon , Walker Abigail , Harries Phil , Hathorn Iain , Lund Valerie
Published: April 2021

Objectives

We set out to create Consensus Guidelines, based on current evidence and relative risks of adverse effects and the costs of different treatments, which reflect the views of the British Rhinological Society (BRS) Council on where the use of biologics should be positioned within treatment pathways for CRSwNP, specifically in the setting of the National Health Service (NHS).

Design

An expert panel of 16 members was assembled. A review of the literature and evidence synthesis was undertaken and circulated to the panel. We used the RAND/UCLA methodology with a multi‐step process to make recommendations on the use of biologics.

Setting

N/A.

Participants

N/A.

Results

Recommendations were made, based on underlying disease severity, prior treatments and co‐morbidities. A group of patients for whom biologics were considered an appropriate treatment option for CRSwNP was defined.

Conclusions

Although biologics are not currently available for the treatment of CRSwNP, the BRS Council have defined a group of patients who have higher rates of “failure” with current treatment pathways, higher resource use and are more likely to suffer with uncontrolled symptoms. We would urge NICE to consider approval of biologics for such indications without applying further restrictions on use.
An understanding of trust, identity, and power can enhance equitable and resilient conservation partnerships and processes
Authors: Dietsch Alia M. , Wald Dara M. , Stern Marc J. , Tully Brooke
Published: April 2021

Conservation practitioners regularly engage in partnerships and processes to develop and achieve important conservation goals aimed at alleviating the biodiversity crisis. These processes, and the partnerships needed for success, are subject to complex social dynamics that can result in negative outcomes if not well understood and addressed. As an illustration, a heavy reliance on authority‐based power in a conservation process could lead to alliances with some groups and alienation of others. Such ingroup/outgroup dynamics can prompt threats to one's identity and distrust of others, which may lead to disengagement or active blocking of progress toward goals (e.g., legal action). To support practitioners in addressing the biodiversity crisis, we review key concepts and theory from the literature in relation to how trust, identity, and power operate in the context of conservation partnerships and processes. We further offer a list of considerations for conservation practitioners seeking to co‐develop goals that are achievable, equitable, and responsive to the needs of diverse interests, as well as sustainable over time given shifting social and ecological conditions.
Increasing compliance with alcohol service laws in community sporting clubs in Australia
Authors: Kremer Peter , Crooks Nicholas , Rowland Bosco , Hall Jessica , Toumbourou John W.
Published: April 2021

Introduction

Many community sporting clubs in Australia sell alcohol, but many do not comply with laws that require verification of age and forbid underage alcohol sales. This study aimed to assess the effectiveness of an intervention that incorporated sales monitoring and community awareness raising to improve compliance with alcohol service regulations in community sporting clubs.

Methods

Non‐randomised community trial in ‘matched’ intervention and comparison communities. A total of 50 sporting clubs from two metropolitan and two regional areas in Victoria, Australia, were selected, and baseline and follow‐up purchase observations completed during 2018. Youth who looked underage were monitored as they attempted to purchase alcohol. Intervention clubs received feedback letters regarding staff sales behaviour. Other intervention actions included building awareness of underage supply of alcohol and media coverage of baseline observations.

Results

Observations were completed at 46 clubs (intervention = 24; comparison = 22) at baseline and 39 (intervention = 24; comparison = 15) at follow up. Compliance was low but improved at follow up for both groups for age verification (intervention +12.5%; comparison +8.5%) and non‐supply of alcohol (intervention +12.5%; comparison +10.6%); but no significant intervention effects were found.

Discussion and Conclusions

Findings indicated low compliance with age verification checks and underage alcohol sales laws at baseline. Promising improvements in compliance were observed at follow up; however, ‘spillover’ of intervention activities may have compromised ability to detect significant intervention effects. Further intervention effort and evaluation is recommended to encourage alcohol sales compliance in community sporting clubs.