Hydrogen chloride is produced as a by-product in industrial processes on a million-ton scale. Since HCl is inherently dangerous, its storage and transport are avoided by, e.g., on-site electrolysis providing H2 and Cl2 which usually requires complex cell designs and PFAS-based membranes. Here we report a complementary approach to safely store 0.61 kilogram HCl per kilogram storage material [NEt3Me]Cl forming the bichloride [NEt3Me][Cl(HCl)n]. Although HCl release is possible from this ionic liquid by heat or vacuum, the bichloride can be used directly to produce base chemicals like vinyl chloride. Alternatively, [NEt3Me][Cl(HCl)n] is electrolyzed under anhydrous conditions using a membrane-free cell to generate H2 and the corresponding chlorination agent [NEt3Me][Cl(Cl2)n], enabling the combination of these ionic liquids for the production of base chemicals.
Weniger anzeigenDer Berufsverband Deutscher Psychologinnen und Psychologen (BDP) und die Deutsche Gesellschaft für Psychologie (DGPs) bilden seit 1964 eine Föderation. Als Föderation haben die beiden Vereinigungen die deutsche Psychologie in internationalen Verbänden vertreten und die Reform des Psychologiestudiums sowie die Professionalisierung des Psychologieberufs in Deutschland mitgestaltet. Dabei sind BDP und DGPs selbständige Vereinigungen geblieben, welche auch voneinander abweichende fachpolitische Positionen einnehmen konnten.
Weniger anzeigenChris Hann's essay serves as a valuable intervention against the tendency to normalize primordial ethnonationalism following the full-scale Russian invasion. It is not immune to the common pitfalls and omissions in the writings of many authors whose point of criticism is aimed primarily at the role of Western elites in the conflict within and around Ukraine. But surely, Hann's core argument contains essential truths. Many social scientists have contributed to the construction of a theoretically shallow, methodologically nationalist, and culturally essentializing narrative. It is a telling fact that someone engaging the discussion has to begin with some basic facts of Ukrainian national identity formation, such as its diversity, or has to remind that the interests of the Western ruling classes in the war do not necessarily coincide with the interests of the Ukrainian subaltern classes, or that those are also likely to diverge from the interests and ideologies of their own comprador middle classes calling themselves “civil society.”
Weniger anzeigenAs the robust maximum likelihood 𝜒2 goodness-of-fit test had been found to yield inflated type-I error rates for certain two-level confirmatory factor analysis (CFA) models, a new correction for the test was implemented in Mplus version 8.7. In this simulation study, we inspected whether the corrected test statistics follow the expected 𝜒2 distributions when applying more complex two-level models for multitrait-multimethod data with varying sample sizes and correlations within trait factors. Investigating rejection rates and probability-probability plots, we found that the new correction markedly and sufficiently reduced previously inflated rejection rates in conditions with within-trait correlations equal to 1, 100 between-level units, and 10 or 20 within-level units. In other conditions, rejection rates were hardly affected or not sufficiently reduced by the new correction. While in most conditions, 2 within-level units did not suffice, 5 within-level units and 250 between-level units were enough to yield correct rejection rates given within-trait correlations did not exceed 0.80. Correlations above 0.80 required larger sample sizes. In planning studies with multilevel CFA models, researchers should be aware that sample size requirements for likelihood-based model fit evaluations can depend on several different factors and might consider conducting Monte Carlo simulations tailored to their specific modeling conditions.
Weniger anzeigenThe successful advancement of xenotransplantation has led to the development of highly sensitive detection systems for the screening of potentially zoonotic viruses in donor pigs and preventing their transmission to the recipient. To validate these methods, genetically modified pigs generated for xenotransplantation, numerous minipigs and other pig breeds have been tested, thereby increasing our knowledge concerning the pig virome and the distribution of pig viruses. Of particular importance are the porcine cytomegalovirus, a porcine roseolovirus (PCMV/PRV) and the hepatitis E virus genotype 3 (HEV3). PCMV/PRV has been shown to reduce the survival time of pig transplants in non-human primates and was also transmitted in the first pig heart transplantation to a human patient. The main aim of this study was to determine the sensitivities of our methods to detect PCMV/PRV, HEV3, porcine lymphotropic herpesvirus-1 (PLHV-1), PLHV-2, PLHV-3, porcine circovirus 2 (PCV2), PCV3, PCV4 and porcine parvovirus 1 (PPV1) and to apply the methods to screen indigenous Greek black pigs. The high number of viruses found in these animals allowed for the evaluation of numerous detection methods. Since porcine endogenous retroviruses (PERVs) type A and B are integrated in the genome of all pigs, but PERV-C is not, the animals were screened for PERV-C and PERV-A/C. Our detection methods were sensitive and detected PCMV/PRV, PLHV-1, PLHV-1, PLHV-3, PVC3 and PERV-C in most animals. PPV1, HEV3, PCV4 and PERV-A/C were not detected. These data are of great interest since the animals are healthy and resistant to diseases.
Weniger anzeigenThe repertoire of currently available antiviral drugs spans therapeutic applications against a number of important human pathogens distributed worldwide. These include cases of the pandemic severe acute respiratory coronavirus type 2 (SARS-CoV-2 or COVID-19), human immunodeficiency virus type 1 (HIV-1 or AIDS), and the pregnancy- and posttransplant-relevant human cytomegalovirus (HCMV). In almost all cases, approved therapies are based on direct-acting antivirals (DAAs), but their benefit, particularly in long-term applications, is often limited by the induction of viral drug resistance or side effects. These issues might be addressed by the additional use of host-directed antivirals (HDAs). As a strong input from long-term experiences with cancer therapies, host protein kinases may serve as HDA targets of mechanistically new antiviral drugs. The study demonstrates such a novel antiviral strategy by targeting the major virus-supportive host kinase CDK7. Importantly, this strategy focuses on highly selective, 3D structure-derived CDK7 inhibitors carrying a warhead moiety that mediates covalent target binding. In summary, the main experimental findings of this study are as follows: (1) the in vitro verification of CDK7 inhibition and selectivity that confirms the warhead covalent-binding principle (by CDK-specific kinase assays), (2) the highly pronounced antiviral efficacies of the hit compounds (in cultured cell-based infection models) with half-maximal effective concentrations that reach down to picomolar levels, (3) a particularly strong potency of compounds against strains and reporter-expressing recombinants of HCMV (using infection assays in primary human fibroblasts), (4) additional activity against further herpesviruses such as animal CMVs and VZV, (5) unique mechanistic properties that include an immediate block of HCMV replication directed early (determined by Western blot detection of viral marker proteins), (6) a substantial drug synergism in combination with MBV (measured by a Loewe additivity fixed-dose assay), and (7) a strong sensitivity of clinically relevant HCMV mutants carrying MBV or ganciclovir resistance markers. Combined, the data highlight the huge developmental potential of this host-directed antiviral targeting concept utilizing covalently binding CDK7 inhibitors.
Weniger anzeigenMutations in activin-like kinase 2 (ALK2), e.g., ALK2-R206H, induce aberrant signaling to SMAD1/5/8, leading to Fibrodysplasia Ossificans Progressiva (FOP). In spite of extensive studies, the underlying mechanism is still unclear. Here, we quantified the homomeric and heteromeric interactions of ACVR2A, ACVR2B, ALK2-WT, and ALK2-R206H by combining IgG-mediated immobilization of one receptor with fluorescence recovery after photobleaching (FRAP) measurements on the lateral diffusion of a co-expressed receptor. ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. ALK2-WT, but not ALK2-R206H, exhibited homomeric complexes unaffected by ActA. ACVR2B formed ActA-enhanced heterocomplexes with ALK2-R206H or ALK2-WT, while ACVR2A interacted mainly with ALK2-WT. The extent of the homomeric complex formation of ACVR2A or ACVR2B was reflected in their ability to induce the oligomerization of ALK2-R206H and ALK2-WT. Thus, ACVR2B, which forms dimers without ligand, induced ActA-independent ALK2-R206H clustering but required ActA for enhancing the oligomerization of the largely dimeric ALK2-WT. In contrast, ACVR2A, which undergoes homodimerization in response to ActA, required ActA to induce ALK2-R206H oligomerization. To investigate whether these interactions are translated into signaling, we studied signaling by the FOP-inducing hyperactive ALK2-R206H mutant, with ALK2-WT signaling as control. The activation of SMAD1/5/8 signaling in cells expressing ALK2-R206H alone or together with ACVR2A or ACVR2B was measured by blotting for pSMAD1/5/8 and by transcriptional activation assays using BRE-Luc reporter. In line with the biophysical studies, ACVR2B activated ALK2-R206H without ligand, while activation by ACVR2A was weaker and required ActA. We propose that the homodimerization of ACVR2B or ACVR2A dictates their ability to recruit ALK2-R206H into higher complexes, enabling the homomeric interactions of ALK2-R206H receptors and, subsequently, their activation.
Weniger anzeigenAntimicrobial resistance (AMR) is considered one of the greatest threats to both human and animal health. Efforts to address AMR include implementing antimicrobial stewardship programs and introducing alternative treatment options. Nevertheless, effective treatment of infectious diseases caused by bacteria will still require the identification and development of new antimicrobial agents. Eight different natural products were tested for antimicrobial activity against seven pathogenic bacterial species (Brachyspira sp., Chlamydia sp., Clostridioides sp., Mannheimia sp., Mycobacterium sp., Mycoplasma sp., Pasteurella sp.). In a first pre-screening, most compounds (five out of eight) inhibited bacterial growth only at high concentrations, but three natural products (celastramycin A [CA], closthioamide [CT], maduranic acid [MA]) displayed activity at concentrations <2 µg/mL against Pasteurella sp. and two of them (CA and CT) also against Mannheimia sp. Those results were confirmed by testing a larger collection of isolates encompassing 64 Pasteurella and 56 Mannheimia field isolates originating from pigs or cattle, which yielded MIC90 values of 0.5, 0.5, and 2 µg/mL against Pasteurella and 0.5, 4, and >16 µg/mL against Mannheimia for CA, CT, and MA, respectively. CA, CT, and MA exhibited higher MIC50 and MIC90 values against Pasteurella isolates with a known AMR phenotype against commonly used therapeutic antimicrobial agents than against isolates with unknown AMR profiles. This study demonstrates the importance of whole-cell antibacterial screening of natural products to identify promising scaffolds with broad- or narrow-spectrum antimicrobial activity against important Gram-negative veterinary pathogens with zoonotic potential
Weniger anzeigenDue to the increasing risk of extreme events caused by climate change (i.e., floods, fires and hurricanes) or wars, European veterinary public health may need some improvement. Utilizing a mix of qualitative (participatory observation) and quantitative methods (Internet mining), we analyzed the Greek media’s responses to the millennial flood in Thessaly (September 2023), focusing on animal health (including wild, companion animals and livestock) and public sentiment towards epizootic/epidemic threats. The study revealed a gap in crisis management plans regarding veterinary-related issues, emphasizing the need for comprehensive emergency response strategies. Our findings show how (i) the lay referral system is projecting the perception of epidemic threats into the population; (ii) the emotional load of images of animal carcasses is misused by media creators aiming for a big audience; and (iii) pets’ owners are creating online communities for the searching and treatment of their pets. Our results stress the importance of integrating crisis communication in consecutive phases of the discourse, such as the following: (i) weather change; (ii) acute flood; (iii) recovery; and (iv) outbreaks, into veterinary practices to better prepare for such disasters.
Weniger anzeigenFact-checking has been granted a pivotal role in mitigating the effects of online disinformation, but its effectiveness has nonetheless been questioned (Lee and Shin Citation2019). Like any persuasive communication, fact checkers depend on their recipients perceiving both their messages and them as credible (Lombardi, Seyranian, and Sinatra Citation2014; Lombardi, Nussbaum, and Sinatra Citation2016). This study investigates the role of the perceived credibility of the fact checker as possible detriment to the effectiveness of fact-checking efforts by means of an online survey-embedded experiment. Results show that the perceived credibility of the fact checker and fact-checking messages is best explained by normative expectations of the roles of fact checkers and trust in traditional media. Some users perceive fact checkers as elite power structures in journalism or, in other words, as collaborative-facilitators for state propaganda (Hanitzsch and Vos Citation2018; see also Fawzi Citation2020). Further, low trust in media and politics predicts perceived credibility of disinformation better than political partisanship. The findings suggest that fact checkers should be more transparent and proactive in communicating their motives and identities. Further implications are discussed.
Weniger anzeigenDas vietnamesische Berlin war lange Zeit hauptsächlich durch zwei Zuwanderungsgruppen gekennzeichnet: die vornehmlich aus Südvietnam geflüchteten sogenannten „Boatpeople“, die Ende der 1970er von der BRD im Rahmen von Kontingentvereinbarungen aufgenommen wurden und die einstigen Vertragsarbeiter*innen, die in den 1980er Jahren in die DDR kamen und nach der Wiedervereinigung zu einem großen Teil in Deutschland blieben. Seitdem wird die Zuwanderung aus Vietnam heterogener, seit Beginn der 2010er Jahre hat sie sich deutlich verstärkt. Diese ‚neue Migration‘, über die bisher kaum etwas bekannt ist, steht im Mittelpunkt der vorliegenden sozialanthropologischen Studie. Mittels eines qualitativen und anwendungsbezogenen ethnografischen ‚multi-sited‘ Ansatzes wurden die dieser Zuwanderung zugrundliegenden Push und Pull-Faktoren und die zentralen Migrationsstrategien untersucht. Daneben wurden die empirisch evidenten Probleme und Belastungen aus der Sicht von Migrant*innen sowie von Fachkräften aus u.a. der Sozialen Arbeit und der Verwaltung analysiert, um ein umfassendes Bild über die Lebenssituation nach Ankunft in Berlin zu erhalten. Ein besonderer Fokus liegt auf den spezifischen Herausforderungen, denen sich (werdende) Mütter und ihre Kinder sowie Auszubildende gegenübersehen.
Weniger anzeigenMolecular isomerization kinetics in liquid solvent depends on a complex interplay between the solvent friction acting on the molecule, internal dissipation effects (also known as internal friction), the viscosity of the solvent, and the dihedral free energy profile. Due to the absence of accurate techniques to directly evaluate isomerization friction, it has not been possible to explore these relationships in full. By combining extensive molecular dynamics simulations with friction memory-kernel extraction techniques we consider a variety of small, isomerising molecules under a range of different viscogenic conditions and directly evaluate the viscosity dependence of the friction acting on a rotating dihedral. We reveal that the influence of different viscogenic media on isomerization kinetics can be dramatically different, even when measured at the same viscosity. This is due to the dynamic solute-solvent coupling, mediated by time-dependent friction memory kernels. We also show that deviations from the linear dependence of isomerization rates on solvent viscosity, which are often simply attributed to internal friction effects, are due to the simultaneous violation of two fundamental relationships: the Stokes-Einstein relation and the overdamped Kramers prediction for the barrier-crossing rate, both of which require explicit knowledge of friction.
Weniger anzeigenHere, we demonstrate the beneficial effect of surfactant-producing pseudomonads on Pantoea eucalypti 299R. We conducted a series of experiments in environments of increasing complexity. P. eucalypti 299R (Pe299R), and Pseudomonas sp. FF1 (Pff1) or Pe299R and surfactant-production deficient Pseudomonas sp. FF1::ΔviscB (Pff1ΔviscB) were co-inoculated in broth, on swarming agar plates, and on plants. In broth, there were no differences in the growth dynamics of Pe299R when growing in the presence of Pff1 or Pff1ΔviscB. By contrast, on swarming agar plates, Pe299R was able to co-swarm with Pff1 which led to a significant increase in Pe299R biomass compared to Pe299R growing with Pff1ΔviscB or in monoculture. Finally in planta, and using the single-cell bioreporter for reproductive success (CUSPER), we found a temporally distinct beneficial effect of Pff1 on co-inoculated Pe299R subpopulations that did not occur in the presence of Pff1ΔviscB. We tested three additional surfactant-producing pseudomonads and their respective surfactant knockout mutants on PE299R on swarming agar showing similar results. This led us to propose a model for the positive effect of surfactant production during leaf colonization. Our results indicate that co-motility might be common during leaf colonization and adds yet another facet to the already manyfold roles of surfactants.
Weniger anzeigenPneumolysin (PLY) is a cholesterol-dependent cytolysin (CDC) from Streptococcus pneumoniae, the main cause for bacterial pneumonia. Liberation of PLY during infection leads to compromised immune system and cytolytic cell death. Here, we report discovery, development, and validation of targeted small molecule inhibitors of PLY (pore-blockers, PB). PB-1 is a virtual screening hit inhibiting PLY-mediated hemolysis. Structural optimization provides PB-2 with improved efficacy. Cryo-electron tomography reveals that PB-2 blocks PLY-binding to cholesterol-containing membranes and subsequent pore formation. Scaffold-hopping delivers PB-3 with superior chemical stability and solubility. PB-3, formed in a protein-templated reaction, binds to Cys428 adjacent to the cholesterol recognition domain of PLY with a KD of 256 nM and a residence time of 2000 s. It acts as anti-virulence factor preventing human lung epithelial cells from PLY-mediated cytolysis and cell death during infection with Streptococcus pneumoniae and is active against the homologous Cys-containing CDC perfringolysin (PFO) as well.
Weniger anzeigenThe least squares linear filter, also called the Wiener filter, is a popular tool to predict the next element(s) of time series by linear combination of time-delayed observations. We consider observation sequences of deterministic dynamics, and ask: Which pairs of observation function and dynamics are predictable? If one allows for nonlinear mappings of time-delayed observations, then Takens’ well-known theorem implies that a set of pairs, large in a specific topological sense, exists for which an exact prediction is possible. We show that a similar statement applies for the linear least squares filter in the infinite-delay limit, by considering the forecast problem for invertible measure-preserving maps and the Koopman operator on square-integrable functions.
Weniger anzeigenIn this article I will try to highlight the importance of astrological teachings in some of the "magic recipes" of the Cyranides. The main aim is to understand the strategies used in the selection of animal products that determine their connection to certain astral bodies. It is precisely this connection that activates the astral force that ensures the effectiveness of the remedy. Secondly, based on the presence of certain animals in magical sources, I will try to decipher a series of seven enigmatic magical words, voces magicae, which seem to correspond to the secret names of the planets. The aim is to understand whether, thanks to the reference to the animal, it is possible to assign each of these vocabularies to a particular planet.
Weniger anzeigenTrait-based frameworks are promising tools to understand the functional consequences of community shifts in response to environmental change. The applicability of these tools to soil microbes is limited by a lack of functional trait data and a focus on categorical traits. To address this gap for an important group of soil microorganisms, we identify trade-offs underlying a fungal economics spectrum based on a large trait collection in 28 saprobic fungal isolates, derived from a common grassland soil and grown in culture plates. In this dataset, ecologically relevant trait variation is best captured by a three-dimensional fungal economics space. The primary explanatory axis represents a dense-fast continuum, resembling dominant life-history trade-offs in other taxa. A second significant axis reflects mycelial flexibility, and a third one carbon acquisition traits. All three axes correlate with traits involved in soil carbon cycling. Since stress tolerance and fundamental niche gradients are primarily related to the dense-fast continuum, traits of the 2nd (carbon-use efficiency) and especially the 3rd (decomposition) orthogonal axes are independent of tested environmental stressors. These findings suggest a fungal economics space which can now be tested at broader scales.
Weniger anzeigenThe increasing pressure on freshwater systems due to intensive anthropogenic use is a big challenge in central-northern Namibia and its catchment areas, the Kunene and the Kavango Rivers, and the Cuvelai-Etosha Basin, that provide water for more than 1 million people. So far, there is no comprehensive knowledge about the ecological status and only few knowledge about the water quality. Therefore, it is crucial to learn about the state of the ecosystem and the ecological effects of pollutants to ensure the safe use of these resources. The surface waters of the three systems were sampled, and three bioassays were applied on three trophic levels: algae, daphnia, and zebrafish embryos. Additionally, in vitro assays were performed to analyze mutagenicity (Ames fluctuation), dioxin-like potential (micro-EROD), and estrogenicity (YES) by mechanism-specific effects. The results show that acute toxicity to fish embryos and daphnia has mainly been detected at all sites in the three catchment areas. The systems differ significantly from each other, with the sites in the Iishana system showing the highest acute toxicity. At the cellular level, only weak effects were identified, although these were stronger in the Iishana system than in the two perennial systems. Algae growth was not inhibited, and no cytotoxic effects could be detected in any of the samples. Mutagenic effects and an estrogenic potential were detected at three sites in the Iishana system. These findings are critical in water resource management as the effects can adversely impact the health of aquatic ecosystems and the organisms within them.
Weniger anzeigenTropical theileriosis is an important protozoan tick-borne disease in cattle. Vaccination using attenuated schizont-infected cell lines is one of the methods used for controlling the disease. This study describes the production of attenuated schizont-infected cell lines from Egypt and an evaluation of its use as a vaccine to protect calves against clinical disease upon field challenge. Two groups of exotic and crossbred male calves were divided into vaccinated and control groups. The vaccinated groups were inoculated with 4 ml (1 × 106 cells/ml) of the attenuated cell line. Three weeks after vaccination, calves of both groups were transported to the New Valley Governorate (Egyptian oasis) where they were kept under field conditions and exposed to the natural Theileria annulata challenge. All animals in the control group showed severe clinical signs and died despite treatment with buparvaquone, which was administered after two days of persistent fever due to a severe drop in packed cell volume (PCV). Animals in the vaccinated group became seropositive without developing severe clinical signs other than transient fever. Post-mortem examinations revealed enlarged and fragile lymph nodes, spleen, and liver with necrosis and hemorrhages. These findings indicate that the Egyptian attenuated cell line was successful in protecting both exotic and crossbred animals against tropical theileriosis under field conditions.
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