Further Antibacterial Geranium macrorrhizum L. Metabolites and Synthesis of Epoxygermacrones

4,5‐ and 1,10‐Epoxygermacrones were isolated from the essential oil of aerial parts of Geranium macrorrhizum L. (Geraniaceae). The structures of the epoxy derivatives were deduced from their 1D‐ and 2D‐NMR spectra, molecular modeling, and confirmed by synthesis starting from germacrone. The epoxy compounds were screened for their antimicrobial activities by a microdilution assay, which revealed high activities of both compounds against Bacillus subtilis (minimum inhibitory concentrations (M/Cs) determined were 4.3 and 43 nmol/ml for 1,10‐ and 4,5‐epoxygermacrone, resp.) and Pseudomonas aeruginosa (0.043 and 0.855 μmol/ml for 1,10‐ and 4,5‐epoxygermacrone, resp.). The discovery and observed activity of the two epoxides fills the gap in our knowledge of the active principles in this highly renowned ethnomedicinal plant species.     

(Un)Targeted Metabolomics in Asteraceae: Probing the Applicability of Essential‐Oil Profiles of Senecio L. (Senecioneae) Taxa in Chemotaxonomy

The possible applicability of (un)targeted metabolomics (volatile metabolites) for revealing taxonomic/evolutionary relationships among Senecio L. species (Asteraceae; tribe Senecioneae) was explored. Essential‐oil compositional data of selected Senecio/Senecioneae/Asteraceae taxa (93 samples in total) were mutually compared by means of multivariate statistical analysis (MVA), i.e., agglomerative hierarchical clustering and principal component analysis. The MVA input data set included the very first compositional data on the essential oil extracted from the aerial parts of S. viscosus L. as well as on four different Serbian populations of S. vernalis Waldst . & Kit . (oils from aerial parts and roots; eight samples in total). This metabolomic screening of Senecio/Senecioneae/Asteraceae species (herein presented results and data from the literature) pointed to short‐chain alk‐1‐enes (e.g., oct‐1‐ene, non‐1‐ene, and undec‐1‐ene), with up to now restricted general occurrence in Plantae, as characteristic chemotaxonomic markers/targets for future metabolomic studies of Senecio/Senecioneae taxa. The MVA additionally showed that the evolution of the terpene metabolism (volatile mono‐ and sesquiterpenoids) within the Asteraceae tribe Senecioneae was not genera specific. However, the MVA did confirm plant‐organ specific production/accumulation of volatiles within S. vernalis and suggested the existence of at least two volatile chemotypes for this species.     

Selective Use of Sequential Digital Dermoscopy Imaging Allows a Cost Reduction in the Melanoma Detection Process: A Belgian Study of Patients with a Single or a Small Number of Atypical Nevi

Background

Dermoscopy is a technique which improves melanoma detection. Optical dermoscopy uses a handheld optical device to observe the skin lesions without recording the images. Sequential digital dermoscopy imaging (SDDI) allows storage of the pictures and their comparison over time. Few studies have compared optical dermoscopy and SDDI from an economic perspective.

Objective

The present observational study focused on patients with one-to-three atypical melanocytic lesions, i.e. lesions considered as suspicious by optical dermoscopy. It aimed to calculate the “extra-costs” related to the process of melanoma detection. These extra-costs were defined as the costs of excision and pathology of benign lesions and/or the costs of follow-up by SDDI. The objective was to compare these extra-costs when using optical dermoscopy exclusively versus optical dermoscopy with selective use of SDDI.

Methods

In a first group of patients, dermatologists were adequately trained in optical dermoscopy but worked without access to SDDI. They excised all suspicious lesions to rule out melanoma. In a second group, the dermatologists were trained in optical and digital dermoscopy. They had the opportunity of choosing between immediate excision or follow-up by SDDI (with delayed excision if significant change was observed). The comparison of extra-costs in both groups was made possible by a decision tree model and by the division of the extra-costs by the number of melanomas diagnosed in each group. Belgian official tariffs and charges were used.

Results

The extra-costs in the first and in the second group were respectively €1,613 and €1,052 per melanoma excised. The difference was statistically significant.

Conclusions

Using the Belgian official tariffs and charges, we demonstrated that the selective use of SDDI for patients with one-to-three atypical melanocytic lesions resulted in a significant cost reduction.     

Impacts of Land Cover Data Selection and Trait Parameterisation on Dynamic Modelling of Species’ Range Expansion

Dynamic models for range expansion provide a promising tool for assessing species’ capacity to respond to climate change by shifting their ranges to new areas. However, these models include a number of uncertainties which may affect how successfully they can be applied to climate change oriented conservation planning. We used RangeShifter, a novel dynamic and individual-based modelling platform, to study two potential sources of such uncertainties: the selection of land cover data and the parameterization of key life-history traits. As an example, we modelled the range expansion dynamics of two butterfly species, one habitat specialist (Maniola jurtina) and one generalist (Issoria lathonia). Our results show that projections of total population size, number of occupied grid cells and the mean maximal latitudinal range shift were all clearly dependent on the choice made between using CORINE land cover data vs. using more detailed grassland data from three alternative national databases. Range expansion was also sensitive to the parameterization of the four considered life-history traits (magnitude and probability of long-distance dispersal events, population growth rate and carrying capacity), with carrying capacity and magnitude of long-distance dispersal showing the strongest effect. Our results highlight the sensitivity of dynamic species population models to the selection of existing land cover data and to uncertainty in the model parameters and indicate that these need to be carefully evaluated before the models are applied to conservation planning.     

In the shadows of snow leopards and the Himalayas: density and habitat selection of blue sheep in Manang,Nepal

There is a growing agreement that conservation needs to be proactive and pay increased attention to common species and to the threats they face. The blue sheep (Pseudois nayaur) plays a key ecological role in sensitive high‐altitude ecosystems of Central Asia and is among the main prey species for the globally vulnerable snow leopard (Panthera uncia). As the blue sheep has been increasingly exposed to human pressures, it is vital to estimate its population dynamics, protect the key populations, identify important habitats, and secure a balance between conservation and local livelihoods. We conducted a study in Manang, Annapurna Conservation Area (Nepal), to survey blue sheep on 60 transects in spring (127.9 km) and 61 transects in autumn (134.7 km) of 2019, estimate their minimum densities from total counts, compare these densities with previous estimates, and assess blue sheep habitat selection by the application of generalized additive models (GAMs). Total counts yielded minimum density estimates of 6.0–7.7 and 6.9–7.8 individuals/km² in spring and autumn, respectively, which are relatively high compared to other areas. Elevation and, to a lesser extent, land cover indicated by the normalized difference vegetation index (NDVI) strongly affected habitat selection by blue sheep, whereas the effects of anthropogenic variables were insignificant. Animals were found mainly in habitats associated with grasslands and shrublands at elevations between 4,200 and 4,700 m. We show that the blue sheep population size in Manang has been largely maintained over the past three decades, indicating the success of the integrated conservation and development efforts in this area. Considering a strong dependence of snow leopards on blue sheep, these findings give hope for the long‐term conservation of this big cat in Manang. We suggest that long‐term population monitoring and a better understanding of blue sheep–livestock interactions are crucial to maintain healthy populations of blue sheep and, as a consequence, of snow leopards.     

Conservation genetics of the yellow-bellied toad (Bombina variegata): population structure,genetic diversity and landscape effects in an endangered amphibian

Revealing patterns of genetic diversity and barriers for gene flow are key points for successful conservation in endangered species. Methods based on molecular markers are also often used to delineate conservation units such as evolutionary significant units and management units. Here we combine phylo-geographic analyses (based on mtDNA) with population and landscape genetic analyses (based on microsatellites) for the endangered yellow-bellied toad Bombina variegata over a wide distribution range in Germany. Our analyses show that two genetic clusters are present in the study area, a northern and a southern/central one, but that these clusters are not deeply divergent. The genetic data suggest high fragmentation among toad occurrences and consequently low genetic diversity. Genetic diversity and genetic connectivity showed a negative relationship with road densities and urban areas surrounding toad occurrences, indicating that these landscape features act as barriers to gene flow. To preserve a maximum of genetic diversity, we recommend considering both genetic clusters as management units, and to increase gene flow among toad occurrences with the aim of restoring and protecting functional meta-populations within each of the clusters. Several isolated populations with especially low genetic diversity and signs of inbreeding need particular short-term conservation attention to avoid extinction. We also recommend to allow natural gene flow between both clusters but not to use individuals from one cluster for translocation or reintroduction into the other. Our results underscore the utility of molecular tools for species conservation, highlight outcomes of habitat fragmentation onto the genetic structure of an endangered amphibian and reveal particularly threatened populations in need for urgent conservation efforts.

     

Expression of VEGFA‐regulating miRNAs and mortality in wet AMD

MicroRNAs (miRNAs) regulate gene expression; many of them act in the retinal pigment epithelium (RPE), and RPE degeneration is known to be a critical factor in age‐related macular degeneration (AMD). Repeated injections with anti‐VEGFA (vascular endothelial growth factor A) are the only effective therapy in wet AMD. We investigated the correlation between the expression of 18 miRNAs involved in the regulation of the VEGFA gene in serum of 76 wet AMD patients and 70 controls. Efficacy of anti‐VEGFA treatment was evaluated by counting the number of injections delivered up to 12 years. In addition, we compared the relative numbers of deaths in patient with AMD and control groups. We observed a decreased expression of miR‐34‐5p, miR‐126‐3p, miR‐145‐5p and miR‐205‐5p in wet AMD patients as compared with controls. These miRNAs are involved in the regulation of angiogenesis, cytoprotection and protein clearance. No miRNA was significantly correlated with the treatment outcome. Wet AMD patients had greater mortality than controls, and their survival was inversely associated with the number of anti‐VEGFA injections per year. No association was observed between miRNA expression and mortality. Our study emphasizes the need to clarify the role of miRNA regulation in AMD pathogenesis.     

Synthesis and Spectral Characterization of Asymmetric Azines Containing a Coumarin Moiety: The Discovery of New Antimicrobial and Antioxidant Agents

Nine unsymmetrical azines containing a coumarin moiety were prepared by the reaction of the hydrazone of 4‐hydroxy‐3‐acetylcoumarin with differently substituted aromatic aldehydes. The azines were fully spectrally characterized, including a complete assignment of ¹H‐ and ¹³C‐NMR resonances, and were assessed for their acute toxicities in the Artemia salina model. Their free radical scavenging activities were tested in the DPPH assay, and in vitro antimicrobial activities were determined against seven bacterial and two fungal strains. The azines containing a p‐hydroxyphenyl group were shown to be the most effective antimicrobial agents, and in the case of resistant strains of Staphylococcus aureus and Acinetobacter baumannii, the activity was comparable to that of chloramphenicol. The derivative having a 3,5‐dimethoxy‐4‐hydroxyphenyl group exhibited pronounced antioxidant power reacting rapidly and in 1 : 1 mol ratio with the DPPH radical.