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Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
Das schmalblättrige Weideröschen, Epilobium angustifolium, zählt in Mitteleuropa zu den charakteristischen Pionierpflanzen auf Kahlschlagflächen und Waldrändern. Durch seine lange Blütezeit (Juni bis September) ist es für viele Blütenbesucher eine wichtige Pollen- und Nektarressource im ansonsten blütenarmen Spätsommer (MAURITZIO & SCHÄFER 1994). Zu seinen häufigsten Blütenbesuchern zählt die solitär lebende oligolektische Blattschneiderbiene Megachile lapponica. Sie sammelt Pollen nur an Pflanzen der Gattung Epilobium und bevorzugt dabei das schmalblättrige Weidenröschen (WESTRICH 1989). Aber auch Honigbienen, Apis mellifera, sind oft in großer Menge an diesen Blüten anzutreffen. Sie nutzen E. angustifolium vorwiegend als Nektarquelle (MAURITZIO & SCHÄFER 1994), sammeln aber auch Pollen auf den Blüten. Bei starkem Beflug durch die Honigbienen könnte es daher zu einer Verknappung der Ressource Pollen kommen. Dies könnte dazu führen, dass die Wildbienenweibchen für ihre Sammelflüge mehr Zeit und Energie aufwenden müssen. Im kritischen Fall einer Konkurrenz sollte auch die Aufzuchtrate und somit die Fitness von M. lapponica betroffen sein, deren Larven fast ausschließlich mit Epilobium-Pollen verpflegt werden. Auf einer Kahlschlagfläche im Kottenforst (Bonn) sollte untersucht werden, welche Insekten an den Blüten des schmalblättrigen Weidenröschens Pollen und/oder Nektar sammeln und welche Blütenbesucher gleichzeitig auch Blütenbestäuber sind. Vor allem aber sollte die Frage geklärt werden, ob es durch die Honigbiene zur Konkurrenz um den Pollen kommt.
Nitro fatty acids (NFAs) are endogenously generated lipid mediators deriving from reactions of unsaturated electrophilic fatty acids with reactive nitrogen species. Furthermore, Mediterranean diets can be a source of NFA. These highly electrophilic fatty acids can undergo Michael addition reaction with cysteine residues, leading to post-translational modifications (PTM) of selected regulatory proteins. Such modifications are capable of changing target protein function during cell signaling or in biosynthetic pathways. NFA target proteins include the peroxisome proliferator-activated receptor γ (PPAR-γ), the pro-inflammatory and tumorigenic nuclear factor-κB (NF-κB) signaling pathway, the pro-inflammatory 5-lipoxygenases (5-LO) biosynthesis pathway as well as soluble epoxide hydrolase (sEH), which is essentially involved in the regulation of vascular tone. In several animal models of inflammation and cancer, the therapeutic efficacy of well-tolerated NFA has been demonstrated. This has already led to clinical phase II studies investigating possible therapeutic effects of NFA in subjects with pulmonary arterial hypertension. Albeit Michael acceptors feature a broad spectrum of bioactivity, they have for a rather long time been avoided as drug candidates owing to their presumed unselective reactivity and toxicity. However, targeted covalent modification of regulatory proteins by Michael acceptors became recognized as a promising approach to drug discovery with the recent FDA approvals of the cancer therapeutics, afatanib (2013), ibrutinib (2013), and osimertinib (2015). Furthermore, the Michael acceptor, neratinib, a dual inhibitor of the human epidermal growth factor receptor 2 and epidermal growth factor receptor, was recently approved by the FDA (2017) and by the EMA (2018) for the treatment of breast cancer. Finally, a number of further Michael acceptor drug candidates are currently under clinical investigation for pharmacotherapy of inflammation and cancer. In this review, we focus on the pharmacology of NFA and other Michael acceptor drugs, summarizing their potential as an emerging class of future antiphlogistics and adjuvant in tumor therapeutics.