Crataegus Extract WS®1442 Stimulates Cardiomyogenesis and Angiogenesis From Stem Cells: A Possible New Pharmacology for Hawthorn?

Extracts from the leaves and flowers of Crataegus spp. (i.e., hawthorn species) have been traditionally used with documented preclinical and clinical activities in cardiovascular medicine. Based on reported positive effects on heart muscle after ischemic injury and the overall cardioprotective profile, the present study addressed potential contributions of Crataegus extracts to cardiopoietic differentiation from stem cells. The quantified Crataegus extract WS®1442 stimulated cardiomyogenesis from murine and human embryonic stem cells (ESCs). Mechanistically, this effect was found to be induced by promoting differentiation of cardiovascular progenitor cell populations but not by proliferation. Bioassay-guided fractionation, phytochemical and analytical profiling suggested high-molecular weight ingredients as the active principle with at least part of the activity due to oligomeric procyanidines (OPCs) with a degree of polymerization between 3 and 6 (DP3–6). Transcriptome profiling in mESCs suggested two main, plausible mechanisms: These were early, stress-associated cellular events along with the modulation of distinct developmental pathways, including the upregulation of brain-derived neurotrophic factor (BDNF) and retinoic acid as well as the inhibition of transforming growth factor β/bone morphogenetic protein (TGFβ/BMP) and fibroblast growth factor (FGF) signaling. In addition, WS®1442 stimulated angiogenesis ex vivo in Sca-1+ progenitor cells from adult mice hearts. These in vitro data provide evidence for a differentiation promoting activity of WS®1442 on distinct cardiovascular stem/progenitor cells that could be valuable for therapeutic heart regeneration after myocardial infarction. However, the in vivo relevance of this new pharmacological activity of Crataegus spp. remains to be investigated and active ingredients from bioactive fractions will have to be further characterized

Bathymetric Mapping Of The Seafloor - A German Contribution To Completing The Map By 2030, Cruise No. MSM88/1 + MSM88/2, November 28, 2019 - January 14, 2020, Mindelo (Cabo Verde) - Mindelo (Cabo Verde) - Bridgetown (Barbados)

Despite over 100 years of acoustic seabed mapping, only around 15% of the seafloor has ever been directly mapped and little of the mapping performed has been systematic or over larger areas. The result is that our knowledge of seafloor structure is rudimentary and our understanding of the processes which form them has, in principle, advanced little since the advent of plate tectonics. Societally, the seafloor plays a vital role in humanity’s "life support system", for example providing habitat for marine organisms, stimulating mixing of ocean water as part of the overturning circulation system and increasingly being the site of industrial installations. It is scientifically and societally imperative that we bring the level of knowledge of the surface of our planet up to that of bodies like Moon and Mars that are mapped with a resolution better than 100 m per pixel. It is also essential that the data are made freely available to all to support research and conservation. The aim of this cruise was to map previously uncharted part of the tropical Atlantic using the ship’s multibeam system and to provide the data to global open databases as well as to acquire magnetic gradient data along the same tracks. Magnetic anomalies from so-called Oceanic Core Complexes challenged the conventional view that marine magnetic anomalies arose in the upper, extrusive layer of the oceanic crust, because the crust has been stripped away at these complexes. We therefore collected magnetic data simultaneously to the multibeam data in order to constrain the interpretation of the observed seabed morphology

Protocol for a multicentre cross-sectional, longitudinal ambulatory clinical trial in rheumatoid arthritis and Parkinson's disease patients analysing the relation between the gut microbiome, fasting and immune status in Germany (ExpoBiome).

peer reviewed[en] INTRODUCTION: Chronic inflammatory diseases like rheumatoid arthritis (RA) and neurodegenerative disorders like Parkinson's disease (PD) have recently been associated with a decreased diversity in the gut microbiome, emerging as key driver of various diseases. The specific interactions between gut-borne microorganisms and host pathophysiology remain largely unclear. The microbiome can be modulated by interventions comprising nutrition.The aim of our clinical study is to (1) examine effects of prolonged fasting (PF) and time-restricted eating (TRE) on the outcome parameters and the immunophenotypes of RA and PD with (2) special consideration of microbial taxa and molecules associated with changes expected in (1), and (3) identify factors impacting the disease course and treatment by in-depth screening of microorganisms and molecules in personalised HuMiX gut-on-chip models, to identify novel targets for anti-inflammatory therapy. METHODS AND ANALYSIS: This trial is an open-label, multicentre, controlled clinical trial consisting of a cross-sectional and a longitudinal study. A total of 180 patients is recruited. For the cross-sectional study, 60 patients with PD, 60 patients with RA and 60 healthy controls are recruited at two different, specialised clinical sites. For the longitudinal part, 30 patients with PD and 30 patients with RA undergo 5-7 days of PF followed by TRE (16:8) for a period of 12 months. One baseline visit takes place before the PF intervention and 10 follow-up visits will follow over a period of 12 months (April 2021 to November 2023). ETHICS AND DISSEMINATION: Ethical approval was obtained to plan and conduct the trial from the institutional review board of the Charité-Universitätsmedizin Berlin (EA1/204/19), the ethics committee of the state medical association (Landesärztekammer) of Hessen (2021-2230-zvBO) and the Ethics Review Panel (ERP) of the University of Luxembourg (ERP 21-001 A ExpoBiome). The results of this study will be disseminated through peer-reviewed publications, scientific presentations and social media. TRIAL REGISTRATION NUMBER: NCT04847011

CP2K: An electronic structure and molecular dynamics software package - Quickstep: Efficient and accurate electronic structure calculations

CP2K is an open source electronic structure and molecular dynamics software package to perform atomistic simulations of solid-state, liquid, molecular, and biological systems. It is especially aimed at massively parallel and linear-scaling electronic structure methods and state-of-the-art ab initio molecular dynamics simulations. Excellent performance for electronic structure calculations is achieved using novel algorithms implemented for modern high-performance computing systems. This review revisits the main capabilities of CP2K to perform efficient and accurate electronic structure simulations. The emphasis is put on density functional theory and multiple post–Hartree–Fock methods using the Gaussian and plane wave approach and its augmented all-electron extension

An archaeal compound as a driver of Parkinson’s disease pathogenesis

Patients with Parkinson’s disease (PD) exhibit differences in their gut microbiomes compared to healthy individuals. Although differences have most commonly been described in the abundances of bacterial taxa, changes to viral and archaeal populations have also been observed. Mechanistic links between gut microbes and PD pathogenesis remain elusive but could involve molecules that promote α-synuclein aggregation. Here, we show that 2-hydroxypyridine (2-HP) represents a key molecule for the pathogenesis of PD. We observe significantly elevated 2-HP levels in faecal samples from patients with PD or its prodrome, idiopathic REM sleep behaviour disorder (iRBD), compared to healthy controls. 2-HP is correlated with the archaeal species Methanobrevibacter smithii and with genes involved in methane metabolism, and it is detectable in isolate cultures of M. smithii. We demonstrate that 2-HP is selectively toxic to transgenic α-synuclein overexpressing yeast and increases α-synuclein aggregation in a yeast model as well as in human induced pluripotent stem cell derived enteric neurons. It also exacerbates PD-related motor symptoms, α-synuclein aggregation, and striatal degeneration when injected intrastriatally in transgenic mice overexpressing human α-synuclein. Our results highlight the effect of an archaeal molecule in relation to the gut-brain axis, which is critical for the diagnosis, prognosis, and treatment of PD.

Entwicklung neuer multitargeting Kinaseinhibitoren zur Bekämpfung der Alzheimerschen Erkrankung

Das Gehirn von Alzheimerpatienten ist charakterisiert durch Aβ-Proteine und Neurofibrilläre Verwicklungen (NFTs). Die Agglomeration der NFTs korreliert mit einer erhöhten Konzentration an Proteinkinasen. Azoxafluorene können diese inhibieren und könnten somit eine therapeutische Lösung für AD darstellen. 52 neue Azoxafluorene mit Carbamid oder Oximether Seitenkette konnten synthetisiert werden. Auf Basis von VOIGTs Zweitschrittsynthese wurden die synthetisierten Nicotinamide und Nicotincarbaldehydoximether in 3,4-disubstituierte N-Acetyl-1,4-dihydropyridine mit Hilfe von Acetylchlorid, Kupfer-I-jodid, Lithiumchlorid und Phenylmagnesiumchlorid umgewandelt. Diese Verbindungen reagierten anschließend mit verschiedenen Chinonen in einer fünfprozentigen Perchlorsäurelösung zu tri- und tetrazyklischen Azoxafluorenen. Die neuen Verbindungen wurden an der CDK1, CDK2, ERK1, JNK3, GSK3β und Fyn wt getestet. Verbindung 23, 28, 33, 77, 88 zeigte dabei IC50 Werte von ein bis 40 μM. Docking Experimente von ausgewählten Verbindungen zeigten Wasserstoffbrücken und hydrophobe Wechselwirkungen mit den Zielstrukturen JNK3 und Fyn.The brain of Alzheimer Disease (AD) patients is characterized by Aβ proteins and neurofibrillary tangles (NFTs). The agglomeration of NFTs correlates with increased concentration of protein kinases. Azoxafluorenes can be inhibited this kinases and could be therapeutic solution for AD. So 52 new azoxafluorenes with carbamide or oxime ether residues are synthesized. On basis of two steps synthesis by VOIGT, the synthesized pyridinecarbamides and nicotinaldehyde oxime ethers were converted in 3,4-disubstituted N-acetyl-1,4-dihydropyridines by acetyl chloride, copper one iodide, lithium chloride and phenylmagnesium chloride. These intermediate compounds reacted with several quinones in a five percentage perchloric acid solution to give tricyclic and tetracyclic azoxafluorenes. The new compounds were tested on CDK1, CDK2, ERK1, JNK3, GSK3β and Fyn wt. The Compounds 23, 28, 33, 77, 88 showed activities with IC50 values of one to 40 μM. Dockings experiments of selected compounds showed hydrogen bonds and hydrophobic interactions with the target kinases JNK3 and Fyn

AtlantOS data products from multibeam EM122 data: Maria S. Merian cruise MSM43 (North Atlantic)

Processed multibeam raw data (quality assured) using QPS Fledermaus Pro and Qimera. Data products are bathymetric grids (50 m resolution). The data processing took place within AtlantOS Project. For map of track see doi:10.1594/PANGAEA.91200

AtlantOS data products from multibeam EM122 data: METEOR cruise M127 (Tropical Atlantic)

The multibeam raw data has been cleaned, quality assured and processed using QPS Qimera. Data products include ungridded soundings, bathymetric grids (150 m resolution), an area shapefile, a backscatter image (100 m resolution) as well as the ship track. The data processing and provision took place within the EU Horizon 2020 project AtlantOS - Optimising and Enhancing the Integrated Atlantic Ocean Observing Systems. For map of transit track see doi:10.1594/PANGAEA.86481

Understanding “understanding”: Presenting a richly annotated multimodal corpus of dyadic interaction

Schade L, Dallmann N, Türk O, Wagner P. Understanding “understanding”: Presenting a richly annotated multimodal corpus of dyadic interaction. In: Proceedings of INTERSPEECH 2024. 2024: 2040--2041.Understanding “understanding”: Presenting a richly annotated multimodal corpus of dyadic interaction Leonie Schade, Nico Dallmann, Olcay T ̈urk, Petra Wagner Bielefeld University, Germany [email protected] Abstract This paper presents the MUNDEX corpus (MUltimodal UNDerstanding of EXplanations) together with past and current investigations using its data. The corpus is constructed to observe the dynamics of co-constructed communication and the understanding of explanations on multiple modalities in dyadic interactions. These modalities are annotated on several levels, including orthographic transcriptions, acoustic information, annotations of head movement, gaze, manual gestures, and further non-verbal behaviour as well as discourse annotations. Present and past projects are also concerned with adding further to these annotations. The interlocutors’ level of understanding is currently investigated in regard to several verbal and non-verbal behaviour markers of both the explaining and listening side