Neurochemical Architecture of the Central Complex Related to Its Function in the Control of Grasshopper Acoustic Communication

The central complex selects and coordinates the species- and situation-specific song production in acoustically communicating grasshoppers. Control of sound production is mediated by several neurotransmitters and modulators, their receptors and intracellular signaling pathways. It has previously been shown that muscarinic cholinergic excitation in the central complex promotes sound production whereas both GABA and nitric oxide/cyclic GMP signaling suppress its performance. The present immunocytochemical and pharmacological study investigates the question whether GABA and nitric oxide mediate inhibition of sound production independently. Muscarinic ACh receptors are expressed by columnar output neurons of the central complex that innervate the lower division of the central body and terminate in the lateral accessory lobes. GABAergic tangential neurons that innervate the lower division of the central body arborize in close proximity of columnar neurons and thus may directly inhibit these central complex output neurons. A subset of these GABAergic tangential neurons accumulates cyclic GMP following the release of nitric oxide from neurites in the upper division of the central body. While sound production stimulated by muscarine injection into the central complex is suppressed by co-application of sodium nitroprusside, picrotoxin-stimulated singing was not affected by co-application of this nitric oxide donor, indicating that nitric oxide mediated inhibition requires functional GABA signaling. Hence, grasshopper sound production is controlled by processing of information in the lower division of the central body which is subject to modulation by nitric oxide released from neurons in the upper division

A behavioral database for masked form priming

Reading involves a process of matching an orthographic input with stored representations in lexical memory. The masked priming paradigm has become a standard tool for investigating this process. Use of existing results from this paradigm can be limited by the precision of the data and the need for cross-experiment comparisons that lack normal experimental controls. Here, we present a single, large, high-precision, multicondition experiment to address these problems. Over 1,000 participants from 14 sites responded to 840 trials involving 28 different types of orthographically related primes (e.g., castfe–CASTLE) in a lexical decision task, as well as completing measures of spelling and vocabulary. The data were indeed highly sensitive to differences between conditions: After correction for multiple comparisons, prime type condition differences of 2.90 ms and above reached significance at the 5% level. This article presents the method of data collection and preliminary findings from these data, which included replications of the most widely agreed-upon differences between prime types, further evidence for systematic individual differences in susceptibility to priming, and new evidence regarding lexical properties associated with a target word’s susceptibility to priming. These analyses will form a basis for the use of these data in quantitative model fitting and evaluation and for future exploration of these data that will inform and motivate new experiments

Understanding, diagnosing, and treating Myalgic encephalomyelitis/chronic fatigue syndrome - State of the art: Report of the 2nd international meeting at the Charité fatigue center.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a devastating disease affecting millions of people worldwide. Due to the 2019 pandemic of coronavirus disease (COVID-19), we are facing a significant increase of ME/CFS prevalence. On May 11th to 12th, 2023, the second international ME/CFS conference of the Charité Fatigue Center was held in Berlin, Germany, focusing on pathomechanisms, diagnosis, and treatment. During the two-day conference, more than 100 researchers from various research fields met on-site and over 700 attendees participated online to discuss the state of the art and novel findings in this field. Key topics from the conference included: the role of the immune system, dysfunction of endothelial and autonomic nervous system, and viral reactivation. Furthermore, there were presentations on innovative diagnostic measures and assessments for this complex disease, cutting-edge treatment approaches, and clinical studies. Despite the increased public attention due to the COVID-19 pandemic, the subsequent rise of Long COVID-19 cases, and the rise of funding opportunities to unravel the pathomechanisms underlying ME/CFS, this severe disease remains highly underresearched. Future adequately funded research efforts are needed to further explore the disease etiology and to identify diagnostic markers and targeted therapies

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Is traffic safety improved through better engineering? : Investigation of risk compensation with the example of antilock brake systems

Es wurde empirisch geprüft, ob und in welchem Umfang Sicherheitsgewinne aufgrund fahrzeugtechnischer Maßnahmen durch entsprechend riskanteres Verhalten der Fahrer wieder aufgehoben (kompensiert) werden, wie es G. Wildes Risikohomöostasetheorie (RHT) postuliert, und auf welche Weise diese Kompensation erfolgt. Am Beispiel des Antiblockiersystems (ABS) wurden in Zusammenarbeit mit einem Münchner Taxiunternehmen fünf Untersuchungen an Taxifahrern durchgeführt: 1. Retrospektiv wurden 957 Unfälle (270 mit ABS) von 91 Taxen (21 mit ABS) im Zeitraum vom 01.01.81 bis 31.12.83 analysiert. Vier Erhebungen erfolgten von Juli 1985 bis Juni 1986 in einem Feldexperiment mit 10 Taxen ohne ABS: 2. Analyse sämtlicher Unfälle der beiden Fahrzeuggruppen. 3. Wiederholte Beobachtung des Fahrverhaltens der Fahrer durch als Fahrgast getarnte Beobachter. 4. Apparative Messung des Beschleunigungs- und Verzögerungsverhaltens der Fahrer. 5. Befragung der Fahrer zu Kenntnissen über Einstellungen und Meinungen zum und Erfahrungen mit ABS. Beide Unfallanalysen ergaben übereinstimmend, dass bestimmte Unfallarten (Unfälle mit Vollbremsung, durch Geschnittenwerden) mit ABS seltener auftraten als ohne. Dieser Sicherheitsgewinn wurde aber in beiden Analysen durch die Zunahme anderer Unfälle kompensiert, so dass die Gesamtunfallzahl beide Male gleich blieb. In der ersten Unfallanalyse war dies vor allem eine unspezifische Zunahme von Unfällen, deren Verursachung dem Unfallgegner der ABS-Taxen angelastet wurde. In der zweiten Untersuchung verursachten die ABS-Fahrer hingegen mehr Bagatellunfälle zum Beispiel beim Parken oder Rückwärtsfahren. In beiden Analysen nahmen ferner mit ABS Unfälle bei Glatteis zu. Während der Kompensationsprozess in der zweiten Unfallanalyse durch die weiteren Erhebungen auf geringere Aufmerksamkeit der ABS-Fahrer und Überschätzung der Wirkung des ABS zurückgeführt werden konnte, hatten die Fahrer der ersten Unfallanalyse das ABS eher aktiv zum schnelleren und riskanteren Vorwärtskommen genutzt. Die RHT konnte also durch die Untersuchungen nicht wiederlegt werden, Kompensation erfolgte auf vielfältige Art.An empirical study was undertaken as to whether and to what extent safety gains due to automotive engineering measures are offset or compensated, as claimed by G. Wilde in his theory of risk homoeostasis (RHT), and how the compensation is being achieved. The study concentrated on the antilock system (ALS) and was undertaken with the collaboration of a taxi company in Munich, carrying out five investigations on taxi drivers: (1) a retrospective analysis of 957 accidents involving 91 taxicabs (21 of which equipped with ALS) within the time period 01-01-81 to 31-12-83. Four surveys were made from July 1985 to June 1986 in a field experiment including ten taxicabs with and ten taxicabs without ALS: (2) analysis of all accidents of both groups of vehicles. (3) Repeated observations of driver behaviour by observers acting as passengers. (4) Monitoring the acceleration and deceleration behaviour of drivers by measuring instruments. (5) Questioning drivers about their knowledge of, attitudes to, opinions on and experience with ALS. The results of both accident analyses agreed in respect of the fact that certain types of accidents (accidents involving full braking, caused by cutting in sharply in front of the passed vehicle) occur less frequently with than without ALS. However, both analyses also revealed that this safety gain is off- set by an increase in other types of accidents so that the over-all number of accidents turned out to be the same in both analyses. The first accident analysis particularly revealed a nonspecific increase in accidents for which the opponents of the cabs with ALS were blamed. The second analysis revealed a higher number of minor accidents caused by the drivers of taxis with ALS, e.g. accidents while parking or reversing. Both analyses furthermore revealed an increase in accidents of cabs with ALS on black ice. Whereas the compensation effect revealed by the second accident analysis, as further investigations showed, had been due to reduced attention on the part of the drivers of ALS-equipped cars and to overestimating the effectiveness of ALS, the drivers in the first accident analysis were shown to have actively used the ad-vantage of ALS by trying to get on faster and taking higher risks. The result: the studies could not refute RHT. Compensation is achieved in many ways

Using the Polymeric Ouzo Effect for the Preparation of Polysaccharide-Based Nanoparticles

The polymeric ouzo effect, a nanoprecipitation process, is used for the preparation of polysaccharide-based nanoparticles. Dextran, pullulan, and starch were esterified with hydrophobic carboxylic acid anhydrides to obtain hydrophobic polysaccharides, which are insoluble in water. The additional introduction of methacroyl residues offers the possibility to cross-link the generated nanostructures, which become insoluble in organic solvents. To make use of the ouzo effect for the formation of nanoparticles, the polymer has to be soluble in an organic solvent, which is miscible with water. Here, acetone and THF were used. Immediately after the organic polymer solution is added to water, nanoparticles are generated. The size of the nanoparticles can be adjusted between 50 and 200 nm by changing the concentration of the initial polysaccharide solution. The degree of hydrophobic substitution was shown to have a very minor effect on the particle size. Dispersions with solids contents of up to 2% were obtained. Furthermore, the mechanical properties of the nanoparticles were investigated with force microscopy, and it was shown by fluorescence correlation spectroscopy that a fluorescent dye could be encapsulated in the nanoparticles by the applied nanoprecipitation procedure

Sialidase Fusion Protein as a Novel Broad-Spectrum Inhibitor of Influenza Virus Infection

Influenza is a highly infectious disease characterized by recurrent annual epidemics and unpredictable major worldwide pandemics. Rapid spread of the highly pathogenic avian H5N1 strain and escalating human infections by the virus have set off the alarm for a global pandemic. To provide an urgently needed alternative treatment modality for influenza, we have generated a recombinant fusion protein composed of a sialidase catalytic domain derived from Actinomyces viscosus fused with a cell surface-anchoring sequence. The sialidase fusion protein is to be applied topically as an inhalant to remove the influenza viral receptors, sialic acids, from the airway epithelium. We demonstrate that a sialidase fusion construct, DAS181, effectively cleaves sialic acid receptors used by both human and avian influenza viruses. The treatment provides long-lasting effect and is nontoxic to the cells. DAS181 demonstrated potent antiviral and cell protective efficacies against a panel of laboratory strains and clinical isolates of IFV A and IFV B, with virus replication inhibition 50% effective concentrations in the range of 0.04 to 0.9 nM. Mouse and ferret studies confirmed significant in vivo efficacy of the sialidase fusion in both prophylactic and treatment modes