Health beyond medicine. A planetary theory extension.

In Niklas Luhmann's vision of the modern functionally differentiated society, health presents one of the essential function systems, along with politics, law, economy and science. While he devoted much effort to elaborating the theoretical foundations of the latter function systems, his work on the health system was relatively sparse. This research gap has been rendered particularly acute by the recent COVID-19 crisis. In reconstructing and updating the Luhmannian analysis of this system, this article presents a three-dimensional concept of organic, psychic and social health and highlights the risks raised by a potential overexpansion of the health concept to the planetary level. The most important of these risks is shown to be the potential rise of totalitarian social control that exceeds classical forms of medical social control. The proposed argument not only contributes to the public criticism of the political responses to the COVID-19 crisis but also fills in some missing pieces of Luhmann's seminal elaboration of the health system.

A High-Throughput Continuous Spectroscopic Assay to Measure the Activity of Natural Product Methyltransferases.

Natural product methyltransferases (NPMTs) represent an emerging class of enzymes that can be of great use for the structural and functional diversification of bioactive compounds, such as the strategic modification of C-, N-, O- and S-moieties. To assess the activity and the substrate scope of the ever-expanding repertoire of NPMTs, a simple, fast, and robust assay is needed. Here, we report a continuous spectroscopic assay, in which S-adenosyl-L-methionine-dependent methylation is linked to NADH oxidation through the coupled activities of S-adenosyl-L-homocysteine (SAH) deaminase and glutamate dehydrogenase. The assay is highly suitable for a high-throughput evaluation of small molecule methylation and for determining the catalytic parameters of NPMTs under conditions that remove the potent inhibition by SAH. Through the modular design, the assay can be extended to match the needs of different aspects of methyltransferase cascade reactions and respective applications.

The Great Reset. Restratification for lives, livelihoods, and the planet.

In reviewing the Great Reset, an initiative launched by the World Economic Forum (WEF) in response to the global coronavirus crisis, this perspective article considers the scenario of an epochal transition from capitalism to "restorism". To facilitate the observation of underlying trends and assumptions, a systems-theoretical framework is developed for the observation of both this Great Reset scenario and those scenarios that are by implication excluded by the WEF vision. It is thus shown that the "shared goals" advocated by the WEF would converge to a transition from a modern pluralist to a "new-normative" order stratified to the primacy of individual, institutional, and planetary health. In discussing sociological implications of this transition, a vision emerges of a new digitally enhanced medieval era where health plays the role once played by religion. In this restorist scenario of a neo-medieval world health society, the emergence of new social strata corresponding to different levels of purity, infection, or pollution would be a probable consequence. The paper concludes that idea of deliberately caused great resets and other control illusions nurtured by the WEF initiative are barely smarter than and spur what the UN Secretary-General refers to as "wild conspiracy theories".

East of nature. Accounting for the environments of social sciences.

At the core of ecological economics is the image of the economy as an open system embedded in the natural environment whose carrying capacity is limited. The present paper revisits this image by drawing upon the constructivist implications of Luhmann's social systems theory. To Luhmann, the modern society consists of a multitude of social systems each bringing forth and observing their own environments. If the Luhmannian vision is accepted, then ecological economics can be said to privilege the observational perspective of natural sciences. The unfortunate consequence of this privileging is the underestimation of a broad range of multidimensional sustainability risks which are foregrounded by the numerous alternative observational perspectives which are just as legitimate. It is argued that, rather than relativizing the sustainability concerns of the modern ecological economics, the Luhmannian perspective generalizes and radicalizes them. In doing so, the latter perspective opens new possibilities not only for navigating these risks but also for envisioning new resources and solutions.

The evolution of female-biased genital diversity in bedbugs (Cimicidae).

Rapid genitalia evolution is believed to be mainly driven by sexual selection. Recently, noncopulatory genital functions have been suggested to exert stronger selection pressure on female genitalia than copulatory functions. In bedbugs (Cimicidae), the impact of the copulatory function can be isolated from the noncopulatory impact. Unlike in other taxa, female copulatory organs have no function in egg-laying or waste-product expulsion. Males perform traumatic mating by piercing the female integument, thereby imposing antagonistic selection on females and suspending selection to morphologically match female genitalia. We found the location of the copulatory organ evolved rapidly, changing twice between dorsal and ventral sides, and several times along the anteroposterior and the left-right axes. Male genital length and shape varied much less, did not appear to follow the positional changes seen in females, and showed no evidence for coevolution. Female genitalia position evolved 1.5 times faster than male genital length and shape and showed little neutral or geographic signals. Instead, we propose that nonmorphological male traits, such as mating behavior, may drive female genitalia morphology in this taxon. Models of genitalia evolution may benefit from considering morphological genital responses to nonmorphological stimuli, such as male mating behavior or copulatory position.

Peptidomics-based phylogeny and biogeography of Mantophasmatodea (Hexapoda).

The insect order Mantophasmatodea was described in 2002. Prior to that time, several generations of entomologists had assumed that all major insect taxa were known; thus, its description was a sensation for zoologists. Since then, a surprising abundance and species diversity of this taxon have been found, particularly in the winter rainfall region of South Africa. To learn more about the evolutionary lineages, speciation, and biogeography of Mantophasmatodea, we applied an unusual peptidomics approach. We collected specimens of almost all known and novel taxa of these insects, developed methods for immediate sample preparation in the field, introduced peptide mass fingerprints for the unambiguous identification of taxa, and subsequently analyzed the most extensive data set on peptide hormones ever compiled for insect taxa. To account for intraspecific variation, we analyzed several individuals per putative species. Increased taxon sampling was preferred over a further increase in the number of characters to optimize the accuracy of phylogenetic analyses. The large data set made it possible to test the validity of using neuropeptide sequences, which coevolve with their respective receptors, to analyze phylogenetic relationships among closely related taxa. Altogether, the data from 71 populations of Mantophasmatodea were sufficient to clearly separate the major clades of Mantophasmatodea, including previously undescribed taxa such as Pachyphasma, Striatophasma, and Austrophasmatidae gen. et sp. nov. "RV." The data confirm the monophyly of Austrophasmatidae and show a relatively recent and extensive radiation in the winter rainfall region of South Africa but also suggest that the species-level diversification of Namibian Mantophasma is less marked than previously thought. We discuss the biogeographical and ecological factors that may have resulted in different regional patterns of endemism and species diversity in Mantophasmatodea. The unique development of the neuroendocrine capa-neurons in the ventral nervous system is described as synapomorphy of Mantophasmatodea + Grylloblattodea and is a further argument for a close relationship between these insect taxa.

Truth Tables, True Distinctions. Paradoxes of the Source Code of Science.

On the occasion of a growing popularity of paradox theory in management and organisation research, this article provides an introduction to the paradox of true distinctions, reports on its relevance to theory building, and presents a strategy to contain the paradox without resolving it. To this end, I draw on works by George Spencer Brown and Niklas Luhmann to contextualize theory within the paradox of observation in general and the paradox of scientific observation in particular. A special case of the paradox of scientific communication, paradox theory is then redefined as a scientific programme fascinated with the paradoxical nature of the basic operation of science. I conclude that further development work on the "source code" of science will provide "critical updates" on the opportunities and limits to metatheoretical extensions of theories of management, organisation, and society, including their digital transformation.

Contribution to the Cimicidae (Hemiptera: Heteroptera) fauna from Argentina: biology and geographical distribution.

The bed bug family Cimicidae (Hemiptera: Heteroptera) constitutes a group of specialized haematophagous ectoparasitic insects with about 110 species worldwide and 13 species in the Neotropics. Here we provide biological and faunistic observations for 4 out of the 8 species recorded in Argentina. Propicimex tucmatiani (Wygodzinsky, 1951) was recorded for the first time in the Province of Santa Fe and we provide the first barcode sequence for this species. Acanthocrios furnarii (Cordero & Vogelsang, 1928), a mainly ornithophilic species, has been found in a human apartment in Buenos Aires and was probably attacking humans. Bertilia valdiviana (Philippi, 1865) had been reported in 1950 in the Province of Ro Negro, we discuss its potential habitat and host association after visiting the only location where this species had been recorded so far in Argentina. Moreover, we provide some natural history data, i.e. developmental stages, sex ratio and feeding habit of the parrot parasite Cyanolicimex patagonicus Carpintero, Di Iorio, Masello & Turienzo, 2010 from a colony in El Condor (Province of Ro Negro).

In-vitro culture of human embryos with mechanical micro-vibration increases implantation rates.

The in-vitro culture of human embryos in a medium subjected to regular short intervals of mechanical agitation leads to increased development rates. This type of treatment tries to mimic conditions in nature whereby oviductal fluid is mechanically agitated by the epithelial cilia. This phenomenon can be explained by the fact that an embryo developing in vivo is naturally exposed to constant vibrations of around 6Hz with the periodically repeating increase to 20Hz. This review covers the history of this question and in this light offers an explanation through biological concept for one of the most recent developments in this area: in-vitro culture of human embryos with mechanical micro-vibration. The effect of mechanical micro-vibration on embryos during their in-vitro culture was examined. Pregnancy rates after the transfer of embryos in the group with in-vitro culture under mechanical vibration were increased.

Mechanical agitation during the in vitro culture of human pre-implantation embryos drastically increases the pregnancy rate.

BACKGROUND: The in vivo developing embryo is naturally exposed to constant vibrations of around 6 Hz, increasing to 20 Hz when the oviductal fluid is mechanically agitated by the cilia. This study examines the effects on viability of subjecting human pronuclear oocytes and embryos to mechanical agitation during their in vitro culture before transplantation. METHODS: Metaphase-II oocytes were ICSI/IVF with morphologically normal spermatozoa and then divided into two groups according to whether the cells underwent mechanical agitation (20 Hz over 5 seconds once per hour) of the culture medium (Group 2, n=23) or were cultured without mechanical agitation (Group 1, n=23). The fertilization rate of oocytes was recorded 18 hours later. Embryo development was monitored every day during the whole period of in vitro culture up to the embryo transfer on day 3, 4 or 5. RESULTS: Pregnancy rates after the transfer of 3 Day embryos in Group 1 and Group 2 were 50% and 80%, and of 5 Day embryos in Group 1 and Group 2 were 36% and 73%, respectively. CONCLUSIONS: The in vitro culture of human embryos in a medium subjected to regular short bursts of mechanical agitation drastically increases their development rate.

Bacterial Endotoxin Testing-Fast Endotoxin Masking Kinetics in the Presence of Lauryldimethylamine Oxide.

For release of parenteral drug products, bacterial endotoxin testing is one of a panel of necessary tests. In order to ensure the validity of such tests, various controls are performed, including demonstration of compendial method suitability or method qualification. In addition to compendial suitability testing, quality control (QC) sample hold-time studies are requested by authorities like the Food and Drug Administration (FDA) as described in "Guidance for Industry: Pyrogen and Endotoxins Testing." It is requested to be determine whether the ability to detect endotoxins can be affected by storage and handling of the sample to be tested. To accomplish these studies, endotoxin is introduced or spiked into the undiluted product and held for a certain period of time in process-representative containers. This time period reflects procedural maximum QC sample hold time from sampling until analysis. Inadequate detection of endotoxin can be caused by adsorption of endotoxin to container surfaces or molecular masking effects, in which the binding sites on the endotoxin molecules are prevented from triggering the enzymatic cascade necessary in the assay, are obscured. The endotoxin may form macromolecular structures, such as sheets or blebs, or the binding sites may otherwise be rendered unavailable due to the sample matrix composition. In either case, the endotoxin assay may yield falsely low results if and when masking occurs. In this work, the QC sample hold times of different in-process controls within the production process of a biopharmaceutical product were analyzed. One out of eight different samples showed a strong masking of endotoxin. Analysis of the sample composition revealed that either kifunensine, mycophenolic acid (MPA), or lauryl-N, N-dimethylamine oxide (LDAO) was responsible for masking. Further analysis clearly identified LDAO as the root cause for masking. A novel one-step mechanism for LDAO-induced endotoxin masking is proposed. The principle is similar to an already-proposed two-step mechanism for endotoxin masking, but the LDAO case combines these two steps: the disturbance of the salt bridges and hydrophobic interactions with LPS in one molecule. These molecular interactions occur quickly when both endotoxin and LDAO are present in the same matrix. Thus, depending on the masking agents, low endotoxin recovery (LER) can occur regardless of the QC sample hold duration.

A proteomic approach for studying insect phylogeny: CAPA peptides of ancient insect taxa (Dictyoptera, Blattoptera) as a test case.

BACKGROUND: Neuropeptide ligands have to fit exactly into their respective receptors and thus the evolution of the coding regions of their genes is constrained and may be strongly conserved. As such, they may be suitable for the reconstruction of phylogenetic relationships within higher taxa. CAPA peptides of major lineages of cockroaches (Blaberidae, Blattellidae, Blattidae, Polyphagidae, Cryptocercidae) and of the termite Mastotermes darwiniensis were chosen to test the above hypothesis. The phylogenetic relationships within various groups of the taxon Dictyoptera (praying mantids, termites and cockroaches) are still highly disputed. RESULTS: Tandem mass spectrometry of neuropeptides from perisympathetic organs was used to obtain sequence data of CAPA peptides from single specimens; the data were analysed by Maximum Parsimony and Bayesian Interference. The resulting cladograms, taking 61 species into account, show a topology which is in general agreement with recent molecular and morphological phylogenetic analyses, including the recent phylogenetic arrangement placing termites within the cockroaches. When sequence data sets from other neuropeptides, viz. adipokinetic hormones and sulfakinins, were included, the general topology of the cladogram did not change but bootstrap values increased considerably. CONCLUSION: This study represents the first comprehensive survey of neuropeptides of insects for solely phylogenetic purposes and concludes that sequences of short neuropeptides are suitable to complement molecular biological and morphological data for the reconstruction of phylogenetic relationships.

Bedbugs Evolved before Their Bat Hosts and Did Not Co-speciate with Ancient Humans.

All 100+ bedbug species (Cimicidae) are obligate blood-sucking parasites [1, 2]. In general, blood sucking (hematophagy) is thought to have evolved in generalist feeders adventitiously taking blood meals [3, 4], but those cimicid taxa currently considered ancestral are putative host specialists [1, 5]. Bats are believed to be the ancestral hosts of cimicids [1], but a cimicid fossil [6] predates the oldest known bat fossil [7] by >30 million years (Ma). The bedbugs that parasitize humans [1, 8] are host generalists, so their evolution from specialist ancestors is incompatible with the "resource efficiency" hypothesis and only partially consistent with the "oscillation" hypothesis [9-16]. Because quantifying host shift frequencies of hematophagous specialists and generalists may help to predict host associations when vertebrate ranges expand by climate change [17], livestock, and pet trade in general and because of the previously proposed role of human pre-history in parasite speciation [18-20], we constructed a fossil-dated, molecular phylogeny of the Cimicidae. This phylogeny places ancestral Cimicidae to 115 mya as hematophagous specialists with lineages that later frequently populated bat and bird lineages. We also found that the clades, including the two major current urban pests, Cimex lectularius and C. hemipterus, separated 47 mya, rejecting the notion that the evolutionary trajectories of Homo caused their divergence [18-21]. VIDEO ABSTRACT.

Co-speciation in bedbug Wolbachia parallel the pattern in nematode hosts.

Wolbachia bacteria, vertically transmitted intracellular endosymbionts, are associated with two major host taxa in which they show strikingly different symbiotic modes. In some taxa of filarial nematodes, where Wolbachia are strictly obligately beneficial to the host, they show complete within- and among-species prevalence as well as co-phylogeny with their hosts. In arthropods, Wolbachia usually are parasitic; if beneficial effects occurs, they can be facultative or obligate, related to host reproduction. In arthropods, the prevalence of Wolbachia varies within and among taxa, and no co-speciation events are known. However, one arthropod species, the common bedbug Cimex lectularius was recently found to be dependent on the provision of biotin and riboflavin by Wolbachia, representing a unique case of Wolbachia providing nutritional and obligate benefits to an arthropod host, perhaps even in a mutualistic manner. Using the presence of presumably functional biotin gene copies, our study demonstrates that the obligate relationship is maintained at least in 10 out of 15 species of the genera Cimex and Paracimex. The remaining five species harboured Wolbachia as well, demonstrating the first known case of 100% prevalence of Wolbachia among higher arthropod taxa. Moreover, we show the predicted co-cladogenesis between Wolbachia and their bedbug hosts, also as the first described case of Wolbachia co-speciation in arthropods.

Analyses of Synthetic N-Acyl Dopamine Derivatives Revealing Different Structural Requirements for Their Anti-inflammatory and Transient-Receptor-Potential-Channel-of-the-Vanilloid-Receptor-Subfamily-Subtype-1 (TRPV1)-Activating Properties.

We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for the activation of transient-receptor-potential channels of the vanilloid-receptor subtype 1 (TRPV1) and inhibition of inflammation. The potency of NOD in activating TRPV1 was significantly higher compared with those of variants in which the ortho-dihydroxy groups were acetylated, one of the hydroxy groups was omitted ( N-octanoyl tyramine), or the ester functionality consisted of a bulky fatty acid ( N-pivaloyl dopamine). Shortening of the amide linker (ΔNOD) slightly increased its potency, which was further increased when the carbonyl and amide groups (ΔNODR) were interchanged. With the exception of ΔNOD, the presence of an intact catechol structure was obligatory for the inhibition of VCAM-1 and the induction of HO-1 expression. Because TRPV1 activation and the inhibition of inflammation by N-acyl dopamines require different structural entities, our findings provide a framework for the rational design of TRPV1 agonists with improved anti-inflammatory properties.

Chemoenzymatic Synthesis of a Novel Borneol-Based Polyester.

Terpenes are a class of natural compounds that have recently moved into the focus as a bio-based resource for chemical production, owing to their abundance, their mostly cyclic structures, and the presence of olefin or single hydroxy groups. To apply this raw material in new industrial fields, a second hydroxy group is inserted into borneol by cytochrome P450cam (CYP101) enzymes in a whole-cell catalytic biotransformation with Pseudomonas putida KT2440. Next, a semi-continuous batch system was developed to produce 5-exo-hydroxyborneol with a final concentration of 0.54 g L-1 . The bifunctional terpene was then used for the synthesis of a bio-based polyester by a solvent-free polycondensation reaction. The resulting polymer showed a glass transition temperature of around 70 °C and a molecular weight in the range of 2000-4000 g mol-1 (Mw ). These results show that whole-cell catalytic biotransformation of terpenes could lead to bio-based, higher-functionalized monomers, which might be basic raw materials for different fields of application, such as biopolymers.

High genetic diversity of common toad (Bufo bufo) populations under strong natural fragmentation on a Northern archipelago.

The last decades have shown a surge in studies focusing on the interplay between fragmented habitats, genetic variation, and conservation. In the present study, we consider the case of a temperate pond-breeding anuran (the common toad Bufo bufo) inhabiting a naturally strongly fragmented habitat at the Northern fringe of the species' range: islands offshore the Norwegian coast. A total of 475 individuals from 19 populations (three mainland populations and 16 populations on seven adjacent islands) were genetically characterized using nine microsatellite markers. As expected for a highly fragmented habitat, genetic distances between populations were high (pairwise F st values ranging between 0.06 and 0.33), with however little differences between populations separated by ocean and populations separated by terrestrial habitat (mainland and on islands). Despite a distinct cline in genetic variation from mainland populations to peripheral islands, the study populations were characterized by overall high genetic variation, in line with effective population sizes derived from single-sample estimators which were on average about 20 individuals. Taken together, our results reinforce the notion that spatial and temporal scales of fragmentation need to be considered when studying the interplay between landscape fragmentation and genetic erosion.

Multiple subcutaneous granulomas and severe rhinitis after intradermal deposition of epoxy: a case report.

BACKGROUND: We present an unusual case of subcutaneous granulomas that also highlights the importance of assessing possible associations between exposure and symptoms early in the diagnostic approach to prevent further adverse health effects. Granulomas of the skin are seen in association with several diseases and after foreign body penetration of soft tissue, but have not been described after contact with epoxy. Epoxy resins are commonly used in paints and other protective coatings, including flooring materials. CASE PRESENTATION: We report a case of granulomatous inflammation in a 58-year-old man after accidental intradermal deposition of unhardened epoxy. Multiple subcutaneous nodules were present on his right forearm, from hand to elbow, for a period of 6 months after the incident. Biopsies and histological analysis showed a granulomatous inflammation without necrosis. Microscopic analysis of the biopsies did not show mycobacterium tuberculosis, other bacteria, or fungal elements. Standard patch testing was negative. The nodules disappeared gradually, but intense pruritus remained. The patient returned to exposure and developed severe work related rhinitis. CONCLUSIONS: This case report describes an unusual case of multiple subcutaneous granulomas after a small injury with an epoxy-contaminated tool. Initially no association between the granulomas and exposure was established and the patient returned to work and epoxy exposure. He subsequently developed severe work related rhinitis. The case highlights the challenges of establishing an association between exposure and dermal reactions and that exposure should be reduced or avoided when sensitisation to allergens may have occurred.

Tachykinin-related peptide precursors in two cockroach species.

Tachykinins and tachykinin-related peptides (TKRPs) play major roles in signaling in the nervous system and intestine of both invertebrates and vertebrates. Here we have identified cDNAs encoding precursors of multiple TKRPs from the cockroaches Leucophaea maderae and Periplaneta americana. All nine LemTKRPs that had been chemically isolated in earlier experiments could be identified on the precursor of L. maderae. Four previously unidentified LemTKRPs were found in addition on the precursor. The P. americana cDNA displayed an open reading frame very similar to that of L. maderae with 13 different TKRPs. MALDI-TOF mass spectra from tissues of both species confirms the presence of all the TKRPs encoded on the precursor plus two additional peptides that are cleavage products of the N-terminally extended TKRPs. A tissue-specific distribution of TKRPs was observed in earlier experiments at isolation from brain and midgut of L. maderae. Our data do not suggest a differential gene expression but a different efficacy in processing of LemTKRP-2 and Lem/PeaTKRP-3 in the brain and intestine, respectively. This results in a gut-specific accumulation of these extended peptides, whereas in the brain their cleavage products, LemTKRP-1 and LemTKRP-3(11-19), are most abundant. Mass spectrometric analysis demonstrated the occurrence of the different TKRPs in single glomeruli of the tritocerebrum and in cells of the optical lobe.

Spatiotemporal analysis of predation by carabid beetles (Carabidae) on nematode infected and uninfected slugs in the field.

The dynamics of predation on parasites within prey has received relatively little attention despite the profound effects this is likely to have on both prey and parasite numbers and hence on biological control programmes where parasites are employed. The nematode Phasmarhabditis hermaphrodita is a commercially available biological agent against slugs. Predation on these slugs may, at the same time, result in intraguild predation on slug-parasitic nematodes. This study describes, for the first time, predation by carabid beetles on slugs and their nematode parasites on both spatial and temporal scales, using PCR-based methods. The highest nematode infection levels were found in the slugs Deroceras reticulatum and Arion silvaticus. Numbers of infected slugs decreased over time and no infected slugs were found four months after nematode application. The density of the most abundant slug, the invasive Arion vulgaris, was positively related to the activity-density of the carabid beetle, Carabus nemoralis. Predation on slugs was density and size related, with highest predation levels also on A. vulgaris. Predation on A. vulgaris decreased significantly in summer when these slugs were larger than one gram. Predation by C. nemoralis on slugs was opportunistic, without any preferences for specific species. Intraguild predation on the nematodes was low, suggesting that carabid beetles such as C. nemoralis probably do not have a significant impact on the success of biological control using P. hermaphrodita.