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As the globe gets more urbanised, the question about how natural biodiversity is structured in cities becomes increasingly pertinent. To contribute to an answer, we studied species richness and spatio-temporal structure of bees in a North European metropolitan area. A gradient of 13 sites in the city of Aarhus, Denmark, was censused from April to September 2016. Forty species, i.e. 29 solitary species (40 % of all individuals), ten Bombus species (28 %), and Apis mellifera (32 %), were sampled monthly in pan traps. (i) Information about species traits was extracted from the literature, and trait values were correlated and used to characterize the fauna. Most were soil-nesters, pollen generalists, and common. (ii) Habitat diversity within five concentric circles with trap at the centre and radii from 50 m to 1000 m was related to bee α diversity. The relationship was significant only within 1,000 m for all bees and for bumblebees. Solitary bee diversity was uncorrelated with habitat diversity at all spatial levels. (iii) Spatio-temporal structure was analysed as two networks, one for bees linked to sites, and one for bees linked to months. Link patterns were analysed for levels of nestedness, modularity, and spatio-temporal β diversity. The two networks were weakly and non-significantly nested, but strongly modular, being composed of five and four modules of co-occurring bees, respectively. (iv) Finally, we studied total β diversity, βTOTAL, being the sum of species turnover, βTURN, and species loss/gain or nestedness, βNEST. For both site and season, βTURN was higher than βNEST, and site βTOTAL was higher than season βTOTAL. One reason for this metacommunity structure may be a high spatio-temporal habitat patchiness, sustaining a rich biodiversity. Thus, a few large areas may not compensate for the loss of several small patches. Consequently, establishment of many green, even small habitats is recommended.

Liquid biopsy (LBx) provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity and clonal evolution.

Objectives Currently, gout management, particularly urate-lowering therapy (ULT), is often suboptimal. Nurses successfully manage various diseases including gout. As gout prevalence is rising, and rheumatologists and general practitioners face shortages, a new approach is imperative. This real-life prospective cohort study evaluated the effectiveness of nurse-led care employing a treat-to-target strategy for gout management over a 2-year period.Methods All consecutively confirmed gout patients were included. The nurse-led clinic provided a structured treatment plan with consultations, patient leaflets, telephone contacts and laboratory monitoring. After a year of nurse-led care, patients transitioned to continued care in general practice. Follow-up data were complete through registries. The primary outcome was achieving target p-urate levels (

Abstract Stingless bees are important pollinators in tropical forests. Yet, we know little about their foraging behavior (e.g., their nutritional requirements or their floral sources visited for resource collection). Many stingless bees not only depend vitally on pollen and nectar for food but also on resin for nest building and/or defense. However, it is unclear whether the large effort devoted to collecting resin as a non‐food resource by certain stingless bees affects their foraging behavior. Therefore, in this study, we analyzed differences in foraging patterns (i.e., foraging activity, proportion of collected resources, and specialization in plants visited) and resource nutritional composition (i.e., sucrose amount in nectar and amino acids in pollen) of seven different stingless bee species (eleven wild colonies) in north‐western Ecuador with a particular focus on the role of resin collection. We found that species with a high resin intake tended to be more active than species with a low resin intake. The foragers per minute invested for pollen collection were similar across all species. Sucrose intake per minute differed between some species but was not affected by increased resin intake. Interestingly, high and low resin collectors partly differed in the plants visited for pollen collection. Pollen amino acid profiles largely, but not completely, overlapped between the two resin collection groups. Our findings show that the foraging patterns and plant choices of stingless bees may vary depending on their resin intake, highlighting the need for more research focusing on resin collection and use by stingless bees.

Stingless bees (Meliponini) are a ubiquitous and diverse element of the pantropical melittofauna, and have significant cultural and economic importance. This review outlines their diversity, and provides identification keys based on external morphology, brief accounts for each of the recognized genera, and an updated checklist of all living and fossil species. In total there are currently 605 described extant species in 45 extant genera, and a further 18 extinct species in nine genera, seven of which are extinct. A new fossil genus, Adactylurina Engel, gen. nov., is also described for a species in Miocene amber from Ethiopia. In addition to the systematic review, the biology of stingless bees is summarized with an emphasis on aspects related to their nesting biology and architecture.

In this first field survey of an entire bee fauna for any part of Peru, we report a total of 1796 bees belonging to 181 species or morphospecies in four families. The taxonomic impediment was pronounced with only 80 species of 181 that could be named. With such a high proportion of undetermined species, it is not possible to adequately compare pollinator communities across different studies, assess historical changes or analyze endemism patterns to document ecology, behavior and evolution of the species and genera. This information is required to provide a sound basis for policymakers to protect habitats for the conservation of native pollinators.

Abstract Sowing flower strips along field edges is a widely adopted method for conserving pollinating insects in agricultural landscapes. To maximize the effect of flower strips given limited resources, we need spatially explicit tools that can prioritize their placement, and for identifying plant species to include in seed mixtures. We sampled bees and plant species as well as their interactions in a semi‐controlled field experiment with roadside/field edge pairs with/without a sown flower strip at 31 sites in Norway and used a regional spatial model of solitary bee species richness to test if the effect of flower strips on bee species richness was predictable from the modelled solitary bee species richness. We found that sites with flower strips were more bee species rich compared to sites without flower strips and that this effect was greatest in areas that the regional solitary bee species richness model had identified to be particularly important for bees. Spatial models revealed that even within small landscapes there were pronounced differences between field edges in the predicted effect of sowing flower strips. Of the plant species that attracted the most bee species, the majority mainly attracted bumblebees and only few species also attracted solitary bees. Considering both the taxonomic diversity of bees and the species richness of bees attracted by plants we suggest that seed mixes containing Hieracium spp. such as Hieracium umbellatum, Pilosella officinarum, Taraxacum spp., Trifolium repens, Lotus corniculatus, Stellaria graminea and Achillea millefolium would provide resources for diverse bee communities in our region. Spatial prediction models of bee diversity can be used to identify locations where flower strips are likely to have the largest effect and can thereby provide managers with an important tool for prioritizing how funding for agri‐environmental schemes such as flower strips should be allocated. Such flower strips should contain plant species that are attractive to both solitary and bumblebees, and do not need to be particularly plant species rich as long as the selected plants complement each other.

We describe and figure a distinctive new species of the bee genus Andinopanurgus Gonzalez and Engel (Andrenidae, Protandrenini) from Apurímac and Cusco in southern Peru. Andinopanurgus vargasllosai Gonzalez and Alvarado, n. sp., occurs at elevations above 4000 m in the Central Andes and is the second species of this genus in Peru. The new species possesses terga with semi-translucent distal margins, a unique feature among Andinopanurgus, and it combines morphological features of the two species groups previously recognized in the genus. To facilitate its recognition, we provide an updated key to species of Andinopanurgus.

Abstract Species of Symphrasinae (Neuroptera: Mantispidae) are ectoparasitoids of larvae and pupae of holometabolous insects, primarily of Hymenoptera in their larval stages. Herein we present the third case of an association between the mantidfly genus Anchieta Navás, 1909 with the order Hymenoptera. The hymenopteran species attacked by the as of yet undescribed species of Anchieta is Montezumia dimidiata Saussure, 1852 (Vespidae: Eumeninae), a predacious wasp that constructs mud nests. The association was observed in Peruvian Amazonia (near Tarapoto, San Martín), after rearing the mantidflies from a wasp nest. The biology and mimicry pattern with stingless bees of the reared Anchieta species is discussed.

Consumers are responsible for almost 50 percent of food waste. Consumer-focused interventions are crucial to achieve many Sustainable Development Goals (SDGs), especially SDG 12.3. There are many factors that cause food waste, and these can be prevented by changing the consumption behavior of adults. Mobile apps are seen as promising tools to change consumer behavior for ensuring more sustainable food consumption. This study describes the development process and examines the perceived quality of MySusCof, an app intended to reduce the food waste of consumers. The uMARS scale was used for collecting data from consumers. Within the scope of the study, two studies were conducted to examine the development process of the application and to determine the user reactions to the mobile application. Results show that gamification elements with hedonic and social components, as well as functional aspects, are important features for user engagement and perceived impact. The qualitative results also supported the user experience in both hedonic and functional value and role of mobile apps to lead behavior change. This study serves as a guideline for future developers of mobile apps intended to lead consumers to a more sustainable food consumption.

A recurrent concern in nature conservation is the potential competition for forage plants between wild bees and managed honey bees. Specifically, that the highly sophisticated system of recruitment and large perennial colonies of honey bees quickly exhaust forage resources leading to the local extirpation of wild bees. However, different species of bees show different preferences for forage plants. We here summarize known forage plants for honey bees and wild bee species at national scale in Denmark. Our focus is on floral resources shared by honey bees and wild bees, with an emphasis on both threatened wild bee species and foraging specialist species. Across all 292 known bee species from Denmark, a total of 410 plant genera were recorded as forage plants. These included 294 plant genera visited by honey bees and 292 plant genera visited by different species of wild bees. Honey bees and wild bees share 176 plant genera in Denmark. Comparing the pairwise niche overlap for individual bee species, no significant relationship was found between their overlap and forage specialization or conservation status. Network analysis of the bee-plant interactions placed honey bees aside from most other bee species, specifically the module containing the honey bee had fewer links to any other modules, while the remaining modules were more highly inter-connected. Despite the lack of predictive relationship from the pairwise niche overlap, data for individual species could be summarized. Consequently, we have identified a set of operational parameters that, based on a high foraging overlap (>70%) and unfavorable conservation status (Vulnerable+Endangered+Critically Endangered), can guide both conservation actions and land management decisions in proximity to known or suspected populations of these species.

ABSTRACT: Meliponiculture and associated honey production are activities with a great potential for general use and commercialization in the Peruvian Amazon. Lack of management techniques and limited knowledge of honey quality are two factors which may hinder the implementation of meliponiculture. The present study was conducted in three communities in the Peruvian Amazon where the production and physicochemical and microbiological characteristics of honey from Melipona eburnea were evaluated at 90 days following transfer from natural to rational hives. Honey from M. eburnea was also compared with the 90-day-old honey from Melipona grandis, Melipona illota, and Melipona titania. In addition, 180-day-old honey from M. eburnea was sampled and compared with the younger 90-day-old honey. The production of honey varied from 900 to 1400 mL/colony/3 months for M. eburnea. When moisture and total sugars among the different species of Melipona were compared, no significant differences were observed. Neither were there significant differences between the M. eburnea honey at 90 and 180 days of maturation. Microbiological analyses for both treatments had values

There is a global concern over insect declines, including both species loss and population declines. In particular, declines of species, such as bees that anchor trophic interactions and shoulder many of the essential ecosystem services, have been the focus of broad public concern. However, our understanding of what characterizes those species that are lost because of declines over long periods is limited by a scarcity of comparative studies. We here compare the species composition from a collection of bees sampled over two decades (2000–2019) from the island of Lolland in Denmark, with a collection also sampled over two decades (1900–1919), but a century ago by Jørgensen and his contemporaries. We further test if (1) the probability that bee species that were sampled a century ago are also found today depends on their degree of floral specialization; (2) and use information from pollen samples from bees from the historical records to assess if certain floral resources have been lost. In total, 203 species were recorded in the two periods, but less than half, 92 species, occurred in both sampling periods. A total of 174 species of bees were recorded from 1900–1919, and 121 species were recorded from 2000–2019, including 29 species not reported in 1900–1919. Notably, we report a reduction in the species composition among forage specialist bees from 26.4% to 15.7% of the bee fauna, a consistent and highly significant decline both when correcting for parasitic and social species. Pollen swabs from bees collected in the first period, 1900–1919, did not identify any plants that are not available today but documented a series of plants that were important to bees back then. These plants are still common today, such as Taraxacum and Salix. Our findings highlight the importance of local and historical faunistic studies, such as that of Jørgensen, who was a resident schoolteacher on the island of Lolland in southern Denmark, for documenting how changes over time affect the species composition in bee communities.

Heme oxygenase (HO) breaks down heme, the iron-containing, oxygen-carrying constituent of red blood cells, yielding biliverdin, iron (II) ions, and carbon monoxide (CO). Among the isoenzymes cloned to date, only HO-1 can be induced by a panoply of stimuli linked by their ability to provoke oxidative stress. HO-1 induction protects against cell death in experimental models associated with ischemia/reperfusion or inflammation, making the gene a promising target for critical care medicine. Induction of HO-1 may confer protection by controlling intracellular levels of toxic heme, or by anti-inflammatory, anti-apoptotic, and blood flow-maintaining effects of its by-products biliverdin and CO. Although protective effects of upregulation of HO-1 have been reported for a variety of cells and tissues, evidence suggests that the protective action may be restricted to a rather narrow threshold of overexpression. In addition, there is substantial variation in gene expression depending on transcriptional control mechanisms such as a microsatellite length polymorphism. Genetic variability and the required use of cytotoxic inducers are hurdles for purposeful targeting of HO-1 gene expression in critical care, while administration of by-products of the pathway seems feasible at present. [ABSTRACT FROM AUTHOR]

Objective: Platelet-activating factor (PAF) is a potent proinflammatory mediator in systemic inflammation and sepsis and is inactivated by the enzyme PAF-acetylhydrolase (PAF-AH). Recently, a large phase III clinical trial using recombinant PAF-AH to treat patients with severe sepsis was performed but failed to reduce 28-day mortality rate. To get more information on the activity of PAF-AH in sepsis, we repeatedly measured its activity in plasma in critically ill patients compared with healthy controls.Design: Retrospective cohort study.Setting: Intensive care unit.Patients: Two hundred thirty-one patients who were admitted to an operative intensive care unit within 1 yr were enrolled and evaluated daily for American College of Chest Physicians/Society of Critical Care Medicine criteria. PAF-AH activity was measured as the release of [H]-acetate from [H]-acetyl-PAF.Interventions: Analysis of plasma samples.Measurements and Main Results: At the day of admission, PAF-AH activity of patients was below controls but markedly increased over time. Higher activities were seen in patients with severe sepsis or septic shock compared with those without organ failure. With respect to the clinical outcome, lower values were found in nonsurvivors only as long as they had not developed organ failure. In severe sepsis/septic shock, values of nonsurvivors exceeded those of survivors. PAF-AH activity was positively correlated with plasma levels of inflammatory mediators such as neopterine and tumor necrosis factor-alpha but not with acute phase reactants such as C-reactive protein, interleukin-6, or PCT. In addition, parenteral nutrition with lipid emulsions was seemingly associated with low PAF-AH activity compared with enteral nutrition.Conclusion: The data indicate severity- and time-dependent changes in PAF-AH activity and may help to explain the failure of recombinant PAF-AH treatment strategies that were not based on activity measurements. [ABSTRACT FROM AUTHOR]

Objective. Rheumatoid arthritis (RA) and periodontal disease (PD) are common chronic, immunoinflammatory, destructive, and progressive diseases; however, the correlations between those two are not yet widely discussed. The purpose of this study was to evaluate the relationship between the selected demographic and clinical parameters of RA patients and oral health status parameters, on the basis of self-assessment. Materials and Methods. Three hundred patients under treatment were included in the study. Questionnaires were completed by 164 out of 300 patients. Results. A total of 100 females and 64 males took part in the study, with a mean age of 65 ± 11.1 years. In younger patients, the disease activity score (DAS28) was higher, and it was associated with pain or discomfort in the oral cavity and with difficulties in toothbrushing. Discomfort or pain in the oral cavity was to a significant extent associated with the poor gingival state, gingival bleeding, and difficulties in biting or chewing. Conclusions. In RA patients, difficulties in biting or chewing, discomfort or pain in oral cavity, feeling of the presence of movable teeth, and gingival bleeding are indications of periodontal infection. Maintaining awareness of oral health and RA is a key issue in the simultaneous management of proper oral care and RA due to the mutual influence of those two factors.

Abstract The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (https://www.nhm.ac.uk/our-science/our-work/biodiversity/predicts.html)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.

For a retrospective period of 110 years between 1901 and 2010 (observed data), and for the subsequent future period between 2011 and 2100 we calculated the phenological development (bud burst, harvest ripeness), and in particular the spring frost risk (frost after bud burst), as one important derived variable for grapevine (Vitis vinifera L. cv Riesling) for the whole of Germany. For the future climate we included two different scenarios (RCP8.5, RCP2.6) each of them containing a triple set with minimum, medium and maximum temperature increase. The time period between 1981 and 2010 as the last three decades in the observed data was chosen as reference. In general we found an acceleration of the phenological development (all main phases) mainly beginning in the late 1980s. For the three-decade period between 2031 and 2060 this acceleration will reach 11±3$11\pm3$ days in the RCP8.5-scenario. The acceleration for the other stages behaved similarly and results in an earlier harvest ripeness of 13±1$13\pm1$ days. Since a warmer spring in general leads to earlier bud burst, but does not reduce the risk of frost events during this period in the same manner, changes in the risk of spring frost damage were relatively small. For the coming decades this risk will not decrease for all traditional German viticultural regions in the RCP8.5-scenarios; on the contrary, our results suggest it is likely to increase. The results showed an increasing spring frost risk not only for the debated “upcoming” potential viticultural areas in eastern Germany, an effect which will partly also reach the southernmost viticultural areas. This effect in northern and eastern Germany is due to earlier bud burst together with the stronger continental influence, but for the southern and western regions of Germany is mainly due to the even earlier bud burst. This could modify the regionally nuanced character of German wines.

Background: Patients with psoriatic arthritis are at high cardiovascular risk. Marine n-3 polyunsaturated fatty acids (PUFA) may reduce the incidence of cardiovascular disease. The aim of this study was to investigate the effect of marine n-3 PUFA on cardiac autonomic function and vascular function in patients with psoriatic arthritis. Methods: The study was conducted as a randomized, double-blind, placebo-controlled trial, where 145 patients with psoriatic arthritis were supplemented with 3 g of n-3 PUFA or olive oil (control) daily for 24 weeks. Blood pressure, heart rate, HRV, central blood pressure, pulse wave velocity (PWV) and fatty acid composition of granulocytes, were determined. Results: At baseline we found a significant difference in the HRV parameter RR when comparing subjects with the highest vs the lowest fish intake (p = 0.03). After supplementation for 24 weeks there was a trend towards an increase in RR (p= 0.13) and decrease in heart rate (p = 0.12) comparing the n-3 PUFA group with the control group. However, per-protocol analysis (performed on participants who completed the trial with a good compliance) showed significantly increased RR (p = 0.01) and lowered heart rate (p = 0.01) in the n-3 PUFA supplemented patients compared to controls. Blood pressure, PWV and central blood pressure did not change after supplementation with n-3 PUFA. Conclusions: Marine n-3 PUFA increased HRV in patients with psoriatic arthritis which may suggest a protective effect of n-3 PUFA against cardiovascular disease in this population.

Hymenoptera exhibit an incredible diversity of phenotypes, the result of ~240 million years of evolution and the primary subject of more than 250 years of research. Here we describe the history, development, and utility of the Hymenoptera Anatomy Ontology (HAO) and its associated applications. These resources are designed to facilitate accessible and extensible research on hymenopteran phenotypes. Outreach with the hymenopterist community is of utmost importance to the HAO project, and this paper is a direct response to questions that arised from project workshops. In a concerted attempt to surmount barriers of understanding, especially regarding the format, utility, and development of the HAO, we discuss the roles of homology, “preferred terms”, and “structural equivalency”. We also outline the use of Universal Resource Identifiers (URIs) and posit that they are a key element necessary for increasing the objectivity and repeatability of science that references hymenopteran anatomy. Pragmatically, we detail a mechanism (the “URI table”) by which authors can use URIs to link their published text to the HAO, and we describe an associated tool (the “Analyzer”) to derive these tables. These tools, and others, are available through the HAO Portal website (http://portal.hymao.org). We conclude by discussing the future of the HAO with respect to digital publication, cross-taxon ontology alignment, the advent of semantic phenotypes, and community-based curation.

Callosphecodes Friese, 1909, a synonym or perhaps subgenus of Sphecodes Latreille, 1804, is known on the basis of one female of Sphecodes ralunensis (Friese, 1909) from New Britain and one female and one male of a similar species, Sphecodes manskii (Rayment, 1935) from northeastern Australia. The male is here described for the first time and the females of the two species are compared for the first time. In spite of considerable collecting, only these three specimens have appeared in over a century. Descriptions and illustrations are provided.

The first checklist to the 225 genera and 1169 reported species-group taxa of aculeate wasps of Peru is presented. The list is based on a literature survey and examination of Peruvian entomological collections and include locality references for each taxon. Bibliographic references for the identification of families, genera, and species are provided when available. The occurrence data are published in addition as a downloadable file (doi: 10.3897/zookeys.15.196.app.2.ds, doi: 10.3897/zookeys.15.196.app.3.ds, and 10.3897/zookeys.15.196.app.4.ds) and were uploaded onto GBIF infrastructure simultaneously with the publication process. The following new combinations are proposed: Ancistroceroides cirrifer (Zavattari, 1912), Ancistrocerus epicus (Zavattari, 1912), and Stenodynerus corallineipes (Zavattari, 1912).

Our grasp of biodiversity is fine-tuned through the process of revisionary taxonomy. If species do exist in nature and can be discovered with available techniques, then we expect these revisions to converge on broadly shared interpretations of species. But for the primarily arctic bumblebees of the subgenus Alpinobombus of the genus Bombus, revisions by some of the most experienced specialists are unusual for bumblebees in that they have all reached different conclusions on the number of species present. Recent revisions based on skeletal morphology have concluded that there are from four to six species, while variation in colour pattern of the hair raised questions as to whether at least seven species might be present. Even more species are supported if we accept the recent move away from viewing species as morphotypes to viewing them instead as evolutionarily independent lineages (EILs) using data from genes. EILs are recognised here in practice from the gene coalescents that provide direct evidence for their evolutionary independence. We show from fitting both general mixed Yule/coalescent (GMYC) models and Poisson-tree-process (PTP) models to data for the mitochondrial COI gene that there is support for nine species in the subgenus Alpinobombus. Examination of the more slowly evolving nuclear PEPCK gene shows further support for a previously unrecognised taxon as a new species in northwestern North America. The three pairs of the most morphologically similar sister species are separated allopatrically and prevented from interbreeding by oceans. We also find that most of the species show multiple shared colour patterns, giving the appearance of mimicry among parts of the different species. However, reconstructing ancestral colour-pattern states shows that speciation is likely to have cut across widespread ancestral polymorphisms, without or largely without convergence. In the particular case of Alpinobombus, morphological, colour-pattern, and genetic groups show little agreement, which may help to explain the lack of agreement among previous taxonomic revisions.

High tree species richness in the western Amazon has been attributed to heterogeneous soils, which harbor edaphic specialist trees. While rapid transitions in tree communities are well documented across these variable soils few studies have investigated the role of habitat heterogeneity in structuring animal communities. Stingless bees are taxonomically diverse and important natural pollinators in Neotropical forests. However, little is known about their community structuring at local scales in naturally heterogeneous environments. We systematically sampled stingless bee communities found across three paired sites that included adjacent patches of white-sand and non-white-sand forest in the lowland Amazonian region of Loreto, Peru. We sought to understand: (1) How stingless bee species richness and abundance differs among white-sand and non-white-sand habitats and (2) The relative influence of fine scale geographic distance and habitat type in structuring stingless bee communities. We found that species richness did not differ between habitats and that species abundances were highest in white-sand habitats. Community analyses for sampling sites pooled across all months demonstrated that location and soil type played a significant role in structuring bee communities and that community turnover may be more strongly influenced by distance in white-sand habitats than non-white sand habitats. Our results suggest that distance and habitat play an important role in driving stingless bee community turnover at fine scales and that the interaction between habitat and geographic distance may promote higher stingless bee community turnover in white-sand habitats than non-white sand habitats.

Most ecological networks are analysed as static structures, where all observed species and links are present simultaneously. However, this is over-simplified, because networks are temporally dynamical. We resolved an arctic, entire-season plant-flower visitor network into a temporal series of 1-day networks and compared the properties with its static equivalent based on data pooled over the entire season. Several properties differed. The nested link pattern in the static network was blurred in the dynamical version, because the characteristic long nestedness tail of flower-visitor specialists got stunted in the dynamical networks. This tail comprised a small food web of pollinators, parasitoids and hyper-parasitoids. The dynamical network had strong time delays in the transmission of direct and indirect effects among species. Twenty percent of all indirect links were impossible in the dynamical network. Consequently, properties and thus also robustness of ecological networks cannot be deduced from the static topology alone.

Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive impairment. We closely mimicked SAE in a murine peritoneal contamination and infection (PCI) model. We found long-lasting synaptic pathology in the hippocampus including defective long-term synaptic plasticity, reduction of mature neuronal dendritic spines, and severely affected excitatory neurotransmission. Genes related to synaptic signaling, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and members of the transcription-regulatory EGR gene family, were downregulated. At the protein level, ARC expression and mitogen-activated protein kinase signaling in the brain were affected. For targeted rescue we used adeno-associated virus-mediated overexpression of ARC in the hippocampus in vivo. This recovered defective synaptic plasticity and improved memory dysfunction. Using the enriched environment paradigm as a non-invasive rescue intervention, we found improvement of defective long-term potentiation, memory, and anxiety. The beneficial effects of an enriched environment were accompanied by an increase in brain-derived neurotrophic factor (BDNF) and ARC expression in the hippocampus, suggesting that activation of the BDNF-TrkB pathway leads to restoration of the PCI-induced reduction of ARC. Collectively, our findings identify synaptic pathomechanisms underlying SAE and provide a conceptual approach to target SAE-induced synaptic dysfunction with potential therapeutic applications to patients with SAE., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Sepsis is defined by life-threatening organ dysfunction mediated by the host’s response to infection. This can result in septic dyslipidemia, which is involved in the neutralization of pathogen-related lipids. Knowledge of the regulatory mechanisms of septic dyslipidemia is incomplete. The cytokine betatrophin/Angiopoietin-like protein 8 (ANGPTL8) plays a role in the regulation of triacylglyceride metabolism, though its function in septic dyslipidemia remains unknown. Sixty-six patients were enrolled in a cross-sectional study. Circulating concentrations and adipose tissue (AT) mRNA expression of betatrophin/ANGPTL8 were studied in patients suffering from peritoneal sepsis. Insulin-resistant individuals and subjects without metabolic derangement/systemic inflammation were enrolled as controls. All underwent open abdominal surgery. Circulating betatrophin/ANGPTL8 was analyzed by an enzyme-linked immunosorbent assay and AT mRNA expression levels were assessed by real-time PCR. Standard laboratory analyses including lipid electrophoresis were evaluated. Sepsis patients showed pronounced septic dyslipidemia (p < 0.05 for all major lipid classes). Despite comparable betatrophin/ANGPTL8 mRNA expression in AT (p = 0.24), we found significantly increased circulating betatrophin/ANGPTL8 with septic dyslipidemia (p = 0.009). Expression levels of betatrophin/ANGPTL8 in AT correlated with circulating concentrations in both control groups (r = 0.61; p = 0.008 and r = 0.43; p = 0.034), while this association was undetectable in sepsis. After stratification, betatrophin/ANGPTL8 remained associated with hypertriacylglyceridemia (p < 0.05)., Competing Interests: All authors declare no conflict of interest with regards to the herein reported data.

Loss of active synapses and alterations in membrane lipids are crucial events in physiological aging as well as in neurodegenerative disorders. Both are related to the abnormal aggregation of amyloid-beta (Aβ) species, generally known as amyloidosis. There are two major known human Aβ species: Aβ (1-40) and Aβ (1-42) . However, which of these species have more influence on active synapses and membrane lipids is still poorly understood. Additionally, the time-dependent effect of Aβ species on alterations in membrane lipids of hippocampal neurones and glial cells remains unknown. Therefore, our study contributes to a better understanding of the role of Aβ species in the loss of active synapses and the dysregulation of membrane lipids in vitro. We showed that Aβ (1-40) or Aβ (1-42) treatment influences membrane lipids before synaptic loss appears and that the loss of active synapses is not dependent on the Aβ species. Our lipidomic data analysis showed early changes in specific lipid classes such as sphingolipid and glycerophospholipid neurones. Our results underscore the potential role of lipids as a possible early diagnostic biomarker in amyloidosis-related disorders.

We provide a descriptive characterization of the unfolded protein response (UPR) in skeletal muscle of human patients with peritoneal sepsis and a sepsis model of C57BL/6J mice. Patients undergoing open surgery were included in a cross-sectional study and blood and skeletal muscle samples were taken. Key markers of the UPR and cluster of differentiation 68 (CD68) as surrogate of inflammatory injury were evaluated by real-time PCR and histochemical staining. CD68 mRNA increased with sepsis in skeletal muscle of patients and animals (p < 0.05). Mainly the inositol-requiring enzyme 1α branch of the UPR was upregulated as shown by elevated X-box binding-protein 1 (XBP1u) and its spliced isoform (XBP1s) mRNA (p < 0.05, respectively). Increased expression of Gadd34 indicated activation of PRKR-Like Endoplasmic Reticulum Kinase (PERK) branch of the UPR, and was only observed in mice (p < 0.001) but not human study subjects. Selected cell death signals were upregulated in human and murine muscle, demonstrated by increased bcl-2 associated X protein mRNA and TUNEL staining (p < 0.05). In conclusion we provide a first characterization of the UPR in skeletal muscle in human sepsis., (© 2022. The Author(s).)

Circulating phospholipids have been considered as biomarkers and therapeutic targets in multiple disorders. Atopic dermatitis (AD) is the most common inflammatory skin disease. Although there are numerous studies having addressed stratum corneum lipids in the context of epidermal barrier, little is known about the circulating lipids in patients with AD. In this study, we explored the changes of serum phospholipids in AD using liquid chromatography coupled to tandem mass spectrometry and sought serum lipids' contribution to clinical status. Several serum levels of phospholipids were altered in the AD group (n = 179) compared with that in healthy controls (n = 47) and patients without AD with atopic comorbidities (n = 22); lipids exhibiting the apparent changes included increased sphingosine, multiple variants of phosphatidylcholine, and decreased ceramide (16:0) in patients with AD. Moreover, serum levels of sphingosine correlated with the severity of AD, and sphingosine and ceramide(16:0) were also detected as the risk-increasing effect and risk-reduction effect of AD, respectively. In summary, alterations in the serum concentration of phospholipids are seen in patients with AD. Although more detailed investigations will be needed to evaluate the significance of the changes in circulating lipids in AD, these findings can provide, to our knowledge, previously unreported insight into AD's pathogenesis and therapeutic strategies., (© 2021 The Authors.)

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients., (© 2021 The Author(s).)

Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA-approved drugs. Here, we report the activation of sphingomyelinase-ceramide pathway in 23 intensive care patients with severe COVID-19. We observed an increase of circulating activity of sphingomyelinase with subsequent derangement of sphingolipids in serum lipoproteins and from red blood cells (RBC). Consistent with increased ceramide levels derived from the inert membrane constituent sphingomyelin, increased activity of acid sphingomyelinase (ASM) accurately distinguished the patient cohort undergoing intensive care from healthy controls. Positive correlational analyses with biomarkers of severe clinical phenotype support the concept of an essential pathophysiological role of ASM in the course of SARS-CoV-2 infection as well as of a promising role for functional inhibition with anti-inflammatory agents in SARS-CoV-2 infection as also proposed in independent observational studies. We conclude that large-sized multicenter, interventional trials are now needed to evaluate the potential benefit of functional inhibition of this sphingomyelinase in critically ill patients with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Abusukhun, Winkler, Pöhlmann, Moerer, Meissner, Tampe, Hofmann-Winkler, Bauer, Gräler and Claus.)

Background: The complement factor D (CFD) exerts a regulatory role during infection. However, its physiological function in coagulopathy and its impact on the course of an infection remains unclear., Materials: Wild-type and CFD-deficient mice (n = 91) were subjected to cecal ligation and puncture to induce sepsis. At several time points, markers of coagulation and the host-immune response were determined. Furthermore, in patients (n = 79) with sepsis or SIRS, CFD levels were related to clinical characteristics, use of antiplatelet drugs and outcome., Results: Septic CFD-deficient mice displayed higher TAT complexes (p = 0.02), impaired maximal clot firmness, but no relevant platelet drop and reduced GPIIb/IIIa surface expression on platelets (p = 0.03) compared to septic wild-type mice. In humans, higher CFD levels (non-survivors, 5.0 µg/ml to survivors, 3.6 µg/ml; p = 0.015) were associated with organ failure (SOFA score: r = 0.33; p = 0.003) and mortality (75% percentile, 61.1% to 25% percentile, 26.3%). CFD level was lower in patients with antiplatelet drugs (4.5-5.3 µg/ml) than in patients without., Conclusion: In mice, CFD is linked to pronounced platelet activation, depicted by higher GPIIb/IIIa surface expression in wild-type mice. This might be of clinical importance since high CFD plasma concentrations were also associated with increased mortality in sepsis patients., (© 2021. The Author(s).)

Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may benefit of hydrocortisone treatment depending on their individual immune response. We performed an exploratory analysis of the database from the international randomized controlled clinical trial Corticosteroid Therapy of Septic Shock (CORTICUS) employing machine learning to a panel of 137 variables collected from the Berlin subcohort comprising 83 patients including demographic and clinical measures, organ failure scores, leukocyte counts and levels of circulating cytokines. The identified theranostic marker was validated against data from a cohort of the Hellenic Sepsis Study Group (HSSG) ( n = 246), patients enrolled in the clinical trial of Sodium Selenite and Procalcitonin Guided Antimicrobial Therapy in Severe Sepsis (SISPCT, n = 118), and another, smaller clinical trial (Crossover study, n = 20). In addition, in vitro blood culture experiments and in vivo experiments in mouse models were performed to assess biological plausibility. A low serum IFNγ/IL10 ratio predicted increased survival in the hydrocortisone group whereas a high ratio predicted better survival in the placebo group. Using this marker for a decision rule, we applied it to three validation sets and observed the same trend. Experimental studies in vitro revealed that IFNγ/IL10 was negatively associated with the load of (heat inactivated) pathogens in spiked human blood and in septic mouse models. Accordingly, an in silico analysis of published IFNγ and IL10 values in bacteremic and non-bacteremic patients with the Systemic Inflammatory Response Syndrome supported this association between the ratio and pathogen burden. We propose IFNγ/IL10 as a molecular marker supporting the decision to administer hydrocortisone to patients in septic shock. Prospective clinical studies are necessary and standard operating procedures need to be implemented, particularly to define a generic threshold. If confirmed, IFNγ/IL10 may become a suitable theranostic marker for an urging clinical need., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 König, Kolte, Ahlers, Oswald, Krauss, Roell, Sommerfeld, Dimopoulos, Tsangaris, Antoniadou, Jaishankar, Bogatsch, Löffler, Rödel, Garcia-Moreno, Tuchscherr, Sprung, Singer, Brunkhorst, Oppert, Gerlach, Claus, Coldewey, Briegel, Giamarellos-Bourboulis, Keh and Bauer.)

Breakdown of the inert and constitutive membrane building block sphingomyelin to the highly active lipid mediator ceramide by extracellularly active acid sphingomyelinase is tightly regulated during stress response and opens the gate for invading pathogens, triggering the immune response, development of remote organ failure, and tissue repair following severe infection. How do one enzyme and one mediator manage all of these affairs? Under physiological conditions, the enzyme is located in the lysosomes and takes part in the noiseless metabolism of sphingolipids, but following stress the protein is secreted into circulation. When secreted, acid sphingomyelinase (ASM) is able to hydrolyze sphingomyelin present at the outer leaflet of membranes to ceramide. Its generation troubles the biophysical context of cellular membranes resulting in functional assembly and reorganization of proteins and receptors, also embedded in highly conserved response mechanisms. As a consequence of cellular signaling, not only induction of cell death but also proliferation, differentiation, and fibrogenesis are affected. Here, we discuss the current state of the art on both the impact and function of the enzyme during host response and damage control. Also, the potential role of lysosomotropic agents as functional inhibitors of this upstream alarming cascade is highlighted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chung and Claus.)

Scientific Background: Sphingolipids are a highly diverse group of lipids with respect to physicochemical properties controlling either structure, distribution, or function, all of them regulating cellular response in health and disease. Mass spectrometry, on the other hand, is an analytical technique characterizing ionized molecules or fragments thereof by mass-to-charge ratios, which has been prosperingly developed for rapid and reliable qualitative and quantitative identification of lipid species. Parallel to best performance of in-depth chromatographical separation of lipid classes, preconditions of precise quantitation of unique molecular species by preprocessing of biological samples have to be fulfilled. As a consequence, "lipid profiles" across model systems and human individuals, esp. complex (clinical) samples, have become eminent over the last couple of years due to sensitivity, specificity, and discriminatory capability. Therefore, it is significance to consider the entire experimental strategy from sample collection and preparation, data acquisition, analysis, and interpretation. Areas Covered: In this review, we outline considerations with clinical (i.e., human) samples with special emphasis on sample handling, specific physicochemical properties, target measurements, and resulting profiling of sphingolipids in biomedicine and translational research to maximize sensitivity and specificity as well as to provide robust and reproducible results. A brief commentary is also provided regarding new insights of "clinical sphingolipidomics" in translational sepsis research. Expert Opinion: The role of mass spectrometry of sphingolipids and related species ("sphingolipidomics") to investigate cellular and compartment-specific response to stress, e.g., in generalized infection and sepsis, is on the rise and the ability to integrate multiple datasets from diverse classes of biomolecules by mass spectrometry measurements and metabolomics will be crucial to fostering our understanding of human health as well as response to disease and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Claus and Graeler.)