The Role of Adipocytes and Adipocyte‐Like Cells in the Severity of COVID‐19 Infections

Coronavirus disease‐2019 (COVID‐19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), demonstrates high morbidity and mortality caused by development of a severe acute respiratory syndrome connected with extensive pulmonary fibrosis. In this Perspective, we argue that adipocytes and adipocyte‐like cells, such as pulmonary lipofibroblasts, may play an important role in the pathogenic response to SARS‐CoV‐2. Expression of angiotensin‐converting enzyme 2 (the functional receptor for SARS‐CoV) is upregulated in adipocytes of patients with obesity and diabetes, which turns adipose tissue into a potential target and viral reservoir. This may explain why obesity and diabetes are potential comorbidities for COVID‐19 infections. Similar to the recently established adipocyte‐myofibroblast transition, pulmonary lipofibroblasts located in the alveolar interstitium and closely related to classical adipocytes demonstrate the ability to transdifferentiate into myofibroblasts that play an integral part of pulmonary fibrosis. This may significantly increase the severity of the local response to SARS‐CoV‐2 in the lung. To reduce the severity and mortality associated with COVID‐19, we propose to probe for the clinical response to thiazolidinediones, peroxisome proliferator activated receptor γ agonists that are well‐known antidiabetic drugs. Thiazolidinediones are able to stabilize lipofibroblasts in their “inactive” state, preventing the transition to myofibroblasts and thereby reducing the development of pulmonary fibrosis and stimulating its resolution.     

Evaluating the effectiveness of retention forestry to enhance biodiversity in production forests of Central Europe using an interdisciplinary,multi‐scale approach

Retention forestry, which retains a portion of the original stand at the time of harvesting to maintain continuity of structural and compositional diversity, has been originally developed to mitigate the impacts of clear‐cutting. Retention of habitat trees and deadwood has since become common practice also in continuous‐cover forests of Central Europe. While the use of retention in these forests is plausible, the evidence base for its application is lacking, trade‐offs have not been quantified, it is not clear what support it receives from forest owners and other stakeholders and how it is best integrated into forest management practices. The Research Training Group ConFoBi (Conservation of Forest Biodiversity in Multiple‐use Landscapes of Central Europe) focusses on the effectiveness of retention forestry, combining ecological studies on forest biodiversity with social and economic studies of biodiversity conservation across multiple spatial scales. The aim of ConFoBi is to assess whether and how structural retention measures are appropriate for the conservation of forest biodiversity in uneven‐aged and selectively harvested continuous‐cover forests of temperate Europe. The study design is based on a pool of 135 plots (1 ha) distributed along gradients of forest connectivity and structure. The main objectives are (a) to investigate the effects of structural elements and landscape context on multiple taxa, including different trophic and functional groups, to evaluate the effectiveness of retention practices for biodiversity conservation; (b) to analyze how forest biodiversity conservation is perceived and practiced, and what costs and benefits it creates; and (c) to identify how biodiversity conservation can be effectively integrated in multi‐functional forest management. ConFoBi will quantify retention levels required across the landscape, as well as the socio‐economic prerequisites for their implementation by forest owners and managers. ConFoBi's research results will provide an evidence base for integrating biodiversity conservation into forest management in temperate forests.     

Evaluation of urinary 1-hydroxypyrene,S-phenylmercapturic acid,trans,trans-muconic acid, 3-methyladenine, 3-ethyladenine, 8-hydroxy-2′-deoxyguanosine and thioethers as biomarkers of exposure to cigarette smoke

The objective was to evaluate the utility of urinary 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (S-PMA), trans,trans-muconic acid (t,t-MA), 3-methyladenine (3-MeAd), 3-ethyladenine (3-EtAd), 8-hydroxy-2′-deoxyguanosine (8-OHdG) and thioethers as biomarkers for assessing the exposure in adult smokers who switched from smoking conventional cigarettes to candidate potential reduced exposure products (PREP) or who stopped smoking. Two electrically heated smoking systems (EHCSS) were used as prototype cigarettes that have significant reductions in a number of mainstream smoke constituents as measured by smoking machines relative to those from conventional cigarettes. Urine samples were collected from a randomized, controlled, forced-switching study in which 110 adult smokers of a conventional cigarette brand (CC1) were randomly assigned to five study groups. The groups included the CC1 smoking group, a lower-tar conventional cigarette (CC2) smoking group, EHCSS1 group, EHCSS2 group and a no smoking group that were monitored for 8 days. Biomarkers were measured at baseline and day 8. The daily excretion levels of these biomarkers were compared among the groups before and after switching, and the relationships between the daily excretion levels of these biomarkers and cigarette smoking-related exposure were investigated using Pearson product-moment correlation and multiple regression analyses. It was concluded that under controlled study conditions: (1) 1-OHP, S-PMA and t,t-MA are useful biomarkers that could differentiate exposure between smoking conventional and EHCSS cigarettes or between smoking conventional cigarettes and no smoking; between S-PMA and t,t-MA, the former appeared to be more sensitive; (2) 3-MeAd could only differentiate between smoking conventional cigarettes and no smoking; the results for 3-EtAd were not conclusive because contradictory results were observed; (3) 8-OHdG had a questionable association with smoking and therefore the utility of this biomarker for smoking-related exposure could not be established; and (4) urinary excretion of thioethers as a biomarker lacked sensitivity to demonstrate a clear dose–response relationship in conventional cigarette smokers, although it could differentiate the excretion levels between those subjects who smoked a conventional cigarette and those who stopped smoking.     

Biomonitoring of environmental tobacco smoke (ETS)-related exposure to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)

The exposure of non-smokers to the tobacco-specific N-nitrosamine 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a rodent lung carcinogen, was determined in the air of various indoor environments as well as by biomonitoring of non-smokers exposed to environmental tobacco smoke (ETS) under real-life conditions using the urinary NNK metabolites 4-(N-methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and [4-(N-methylnitrosamino)-1-(3-pyridyl)but-1-yl]-beta-O-D-glucosiduronic acid (NNAL-Gluc). NNK was not detectable (<0.5 ng m^-3) in 11 rooms in which smoking did not occur. The mean NNK concentration in 19 rooms in which smoking took place was 17.5 (2.4-50.0) ng m^-3. The NNK levels significantly correlated with the nicotine levels (r=0.856; p< 0.0001). Of the 29 non-smokers investigated, 12 exhibited no detectable NNAL and NNAL-Gluc excretion (<3 pmol day) in their urine. The mean urinary excretion of NNAL and NNAL-Gluc of the 17 remaining non-smokers was 20.3 (<3-63.2) and 22.9 (<3-90.0) pmol day^-1, respectively. Total NNAL excretion (NNAL+NNAL-Gluc) in all non-smokers investigated significantly correlated with the amount of nicotine on personal samplers worn during the week prior to urine collection (r=0.88; <0.0001) and with the urinary cotinine levels (r=0.40; p=0.038). No correlation was found between NNAL excretion and the reported extent of ETS exposure. Average total NNAL excretion in the non-smokers with detectable NNAL levels was 74 times less than in 20 smokers who were also investigated. The cotinine/total NNAL ratios in urine of smokers (9900) and non-smokers (9300) were similar. This appears to be at variance with the ratios of the corresponding precursors (nicotine/NNK) in mainstream smoke (16400) and ETS (1000). Possible reasons for this discrepancy are discussed. The possible role of NNK as a lung carcinogen in non-smokers is unclear, especially since NNK exposure in non-smokers is several orders of magnitude lower than the ordinary exposure to exogenous and endogenous N-nitrosamines and the role of NNK as a human lung carcinogen is not fully understood.     

Evidence for plasticity in the frequency of skipped breeding opportunities in common toads

Breeding is limited by energetic or environmental constraints and long-lived species sometimes skip breeding opportunities. Environmental conditions may vary considerably across the geographic and elevational range of a species and species that can respond through variation in life history strategies are likely to maintain populations at the extremes of their ranges. The decision to skip breeding enables animals to adjust life history to circumstances, and plasticity in behavior allows implementation of adjustments. Elevational patterns suggest that breeding may be limited physiologically at high elevations (e.g., greater probability of skipped breeding; resources and environmental conditions more variable) in contrast to low elevations (probability of skipping breeding lower; resources and environmental conditions more predictable). We estimated the probabilities of survival and skipped breeding in a high-elevation population of common toads and compared estimates to existing data for common toads at low elevations, and to another toad species inhabiting a similar high elevation environment. Female common toads at high elevations tend to have high probabilities of skipping breeding and survival relative to data for common toads at low elevations, and appear to use a similar strategy of skipping breeding in response to similar environmental constraints as other toads at high elevations. We provide evidence of variability in this aspect of life history for common toads. Understanding variation in life history within widely distributed species is critical. Knowing that certain life history strategies are employed on a continuum informs conservation efforts, especially as impacts of climate change are likely to be different depending on elevation.     

Spatio-temporal dynamics of endophyte diversity in the canopy of European ash (Fraxinus excelsior)

Leaf-inhabiting endophytic fungi of Fraxinus excelsior growing in a floodplain forest were isolated during 2008 to investigate vertical community structure, species richness and seasonal variation. The analysis of 848 fungal endophytes from 213 leaves resulted in 50 different species. In the understorey, infection density and species richness were higher than in the crowns of mature trees throughout the whole vegetation period. Within tree crowns, sun-exposed leaves of the top canopy exhibited the lowest infection rates. Most species were rare or absent in spring and in the light crowns and frequent in autumn and the understorey. However, some species, especially the two most frequent, Alternaria infectoria and A. alternata, deviated from these patterns. Young leaves were nearly free of endophytes. Apparently, the subsequent infection and establishment of fungi strongly depend on microclimatic parameters and leaf characters, which create highly variable spatial and temporal colonisation patterns within an individual tree.     

Green Rust Formation from the Bioreduction of γ –FeOOH (Lepidocrocite): Comparison of Several Shewanella Species

Green rusts are mixed ferrous/ferric hydroxides that typically form under weakly acidic to alkaline conditions in suboxic environments. The recent identification of green rusts as products of the reduction of Fe(III) oxides and oxyhydroxides by Shewanella putrefaciens, a dissimilatory iron-reducing bacterium (DIRB), suggests that green rusts may play a role in the redox cycling of Fe in many aquatic and terrestrial environments. We examined the potential for green rust formation resulting from the bioreduction of lepidocrocite(γ -FeOOH) by a series of Shewanella species (S. alga BrY, S. amazonensis SB2B, S. baltica OS155, S. denitrificans OS217T, S. loihica PV-4, S. oneidensis MR-1, S. putrefaciens ATCC 8071, S. putrefaciens CN32, S. saccharophilia, and Shewanella sp. ANA-3). All Shewanella species, with the exception of S. denitrificans OS217T, were able to couple the oxidation of formate to the reduction of Fe(III) in lepidocrocite; however there were significant differences among species with respect to the rate and extent of Fe(II) production. Despite these differences, green rust was the only Fe(II)-bearing solid phase formed under our experimental conditions, as indicated by X-ray diffraction, Mössbauer spectroscopy, and scanning electron microscopy. The formation of green rust by Shewanella species isolated from a wide range of habitats and possessing varied metabolic capabilities suggests that under favorable conditions biogenic green rusts may be formed by a diverse array of DIRB.     

Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development

An increased rate of lipid synthesis in cancerous tissues has long been recognised as an important aspect of the rewired metabolism of transformed cells. However, the contribution of lipids to cellular transformation, tumour development and tumour progression, as well as their potential role in facilitating the spread of cancerous cells to secondary sites, are not yet fully understood. In this article, we review the recent findings that support the importance of lipid synthesis and metabolism in tumorigenesis. Specifically, we explore the role of aberrant lipid biosynthesis in cancer cell migration and invasion, and in the induction of tumour angiogenesis. These processes are crucial for the dissemination of tumour cells and formation of metastases, which constitute the main cause of cancer mortality.