WW domain-containing oxidoreductase promotes neuronal differentiation via negative regulation of glycogen synthase kinase 3β

WW domain-containing oxidoreductase (WWOX), a putative tumour suppressor, is suggested to be involved in the hyperphosphorylation of Alzheimer's Tau. Tau is a microtubule-associated protein that has an important role in microtubule assembly and stability. Glycogen synthase kinase 3β (GSK3β) has a vital role in Tau hyperphosphorylation at its microtubule-binding domains. Hyperphosphorylated Tau has a low affinity for microtubules, thus disrupting microtubule stability. Bioinformatics analysis indicated that WWOX contains two potential GSK3β-binding FXXXLI/VXRLE motifs. Immunofluorescence, immunoprecipitation and molecular modelling showed that WWOX interacts physically with GSK3β. We demonstrated biochemically that WWOX can bind directly to GSK3β through its short-chain alcohol dehydrogenase/reductase domain. Moreover, the overexpression of WWOX inhibited GSK3β-stimulated S396 and S404 phosphorylation within the microtubule domains of Tau, indicating that WWOX is involved in regulating GSK3β activity in cells. WWOX repressed GSK3β activity, restored the microtubule assembly activity of Tau and promoted neurite outgrowth in SH-SY5Y cells. Conversely, RNAi-mediated knockdown of WWOX in retinoic acid (RA)-differentiated SH-SY5Y cells inhibited neurite outgrowth. These results suggest that WWOX is likely to be involved in regulating GSK3β activity, reducing the level of phosphorylated Tau, and subsequently promoting neurite outgrowth during neuron differentiation. In summary, our data reveal a novel mechanism by which WWOX promotes neuronal differentiation in response to RA

BioTIME 2.0: Expanding and Improving a Database of Biodiversity Time Series

Motivation Here, we make available a second version of the BioTIME database, which compiles records of abundance estimates for species in sample events of ecological assemblages through time. The updated version expands version 1.0 of the database by doubling the number of studies and includes substantial additional curation to the taxonomic accuracy of the records, as well as the metadata. Moreover, we now provide an R package (BioTIMEr) to facilitate use of the database. Main Types of Variables Included The database is composed of one main data table containing the abundance records and 11 metadata tables. The data are organised in a hierarchy of scales where 11,989,233 records are nested in 1,603,067 sample events, from 553,253 sampling locations, which are nested in 708 studies. A study is defined as a sampling methodology applied to an assemblage for a minimum of 2 years. Spatial Location and Grain Sampling locations in BioTIME are distributed across the planet, including marine, terrestrial and freshwater realms. Spatial grain size and extent vary across studies depending on sampling methodology. We recommend gridding of sampling locations into areas of consistent size. Time Period and Grain The earliest time series in BioTIME start in 1874, and the most recent records are from 2023. Temporal grain and duration vary across studies. We recommend doing sample-level rarefaction to ensure consistent sampling effort through time before calculating any diversity metric. Major Taxa and Level of Measurement The database includes any eukaryotic taxa, with a combined total of 56,400 taxa. Software Format csv and. SQL

Fusionen und Übernahmen im Licht der Hybris – Überblick über den Forschungsstand

Eine hohe Anzahl von Fusionen und Übernahmen scheitert. Gleichwohl sind Fusionen und Übernahmen an der Tagesordnung. Als eine Erklärung hierfür wird die Hybris-Hypothese diskutiert, d.h. die These, dass sich Entscheidungsträger der aufnehmenden Unternehmen systematisch überschätzen. Um diese These zu testen und um gegebenenfalls Maßnahmen gegen Hybris zu ergreifen, sind verlässliche Indikatoren für Hybris erforderlich. Die Arbeit stellt die in der Literatur entwickelten Indikatoren vor und diskutiert deren Vor- und Nachteile. Although corporate acquisitions are ubiquitous a large number of M&A fails. One explanation for such failure is the hubris hypothesis for corporate takeovers. A decision maker affected with hubris (or overconfidence) will overestimate his abilities in raising potential synergies and is likely to make investment decisions destroying shareholder wealth. The growing literature on CEO hubris proposes various ways to measure hubris. We present these indicators and discuss possible advantages and drawbacks. (71 words) Schlüsselwörter Hybris - Mergers & Acquisitions Keywords Hubris - Mergers & Acquisitions JEL Classification G34 - M1

Ethical Issues in Public Health Practice in Michigan

Objectives. We sought to ascertain the types of ethical challenges public health practitioners face in practice and to identify approaches used to resolve such challenges

MAP1B regulates microtubule dynamics by sequestering EB1/3 in the cytosol of developing neuronal cells

MAP1B, a structural microtubule (MT)-associated protein highly expressed in developing neurons, plays a key role in neurite and axon extension. However, not all molecular mechanisms by which MAP1B controls MT dynamics during these processes have been revealed. Here, we show that MAP1B interacts directly with EB1 and EB3 (EBs), two core 'microtubule plus-end tracking proteins' (+TIPs), and sequesters them in the cytosol of developing neuronal cells. MAP1B overexpression reduces EBs binding to plus-ends, whereas MAP1B downregulation increases binding of EBs to MTs. These alterations in EBs behaviour lead to changes in MT dynamics, in particular overstabilization and looping, in growth cones of MAP1B-deficient neurons. This contributes to growth cone remodelling and a delay in axon outgrowth. Together, our findings define a new and crucial role of MAP1B as a direct regulator of EBs function and MT dynamics during neurite and axon extension. Our data provide a new layer of MT regulation: a classical MAP, which binds to the MT lattice and not to the end, controls effective concentration of core +TIPs thereby regulating MTs at their plus-ends. © 2013 European Molecular Biology Organization.Spanish Research Ministry (SAF2006-02424 and SAF2011-24841); CIBERNED; Comunidad de Madrid (S2010/BMD2331); Spanish Research Council (CSIC)Peer Reviewe