Phosphorylation-facilitated sumoylation of MEF2C negatively regulates its transcriptional activity

BACKGROUND: Sumoylation has emerged as an important posttranslational regulatory mechanism for transcription factors and cofactors. Sumoylation of many transcription factors represses their transcriptional activities. The myocyte enhancer factor 2 (MEF2) family of transcription factors plays an important role in regulating gene expression during myogenesis and has been recently shown to be sumoylated. RESULTS: Consistent with earlier reports, we show that sumoylation of MEF2C at K391 inhibits its transcriptional activity. Sumoylation of MEF2C does not block its DNA-binding activity. A small C-terminal fragment of MEF2C containing K391, referred to as delta-N2-MEF2C, is efficiently sumoylated and, when targeted to DNA, represses transcription at neighbouring promoters. Because delta-N2-MEF2C lacks the binding site for class II histone deacetylases (HDACs), this result suggests that sumoylation of MEF2C may help to recruit transcriptional repressors other than these HDACs. Intriguingly, we show that phosphorylation of S396 in MEF2C, a residue in close proximity to the major sumoylation site (K391) and known to be phosphorylated in vivo, enhances sumoylation of delta- N2-MEF2C in vitro. The S396A mutation reduces sumoylation of MEF2C in vivo and enhances the transcription activity of MEF2C in reporter assays. CONCLUSION: We propose that phosphorylation of MEF2C at S396 facilitates its sumoylation at K391, which in turn recruits yet unidentified co-repressors to inhibit transcription. Our studies further suggest that sumoylation motifs containing a phosphorylated serine or an acidic residue at the +5 position might be more efficiently sumoylated

Rooting Cuttings of Northern Red Oak (Quercus rubra L.)

Several techniques have been used experimentally to vegetatively propagate northern red oak (Quercus rubra L.), including: 1) rooting juvenile softwood cuttings in intermittent mist, 2) rooting shoots originating from mature buds grafted onto juvenile root stocks, and 3) in vitro shoot proliferation of juvenile or mature shoots followed by in vitro rooting. Of these techniques, rooting juvenile softwood cuttings has provided the most consistent results for northern red oak (NRO). Juvenility (or at least the associated ability to form adventitious roots) disappears rapidly among progressive flushes of growth in NRO seedlings. Decreased rooting has been reported for NRO shoots obtained from progressive flushes of growth produced within a growing season, as well as shoots representing flushes obtained from successive seasons of growth. However, as with many other tree species, the process of maturation in NRO can be slowed by pruning to encourage juvenile shoot production. Optimizing the number of juvenile cuttings produced from each stock plant is necessary for efficient rooted cutting production systems. In addition, rooting conditions must be determined for the shoots produced under these pruning regimes. Two NRO rooted cutting studies are currently being conducted at NCSU. The objective of the first study is to evaluate the effects of stock plant pruning location, diameter, and age on new shoot production. Treatments include pruning first-year seedlings, as well as one-, two-, and three-year-old seedlings to the base of the first, second, third, or fourth flush of growth produced during the first growing season. The objective of the second study is to evaluate the ability of the shoots produced in the first study to form adventitious roots. Treatments include three rooting hormone levels (0.5%, 1%, and 1.5% IBA) and a control (45% EtOH). Preliminary results from both studies will be presented.Papers and abstracts from the 27th Southern Forest Tree Improvement Conference held at Oklahoma State University in Stillwater, Oklahoma on June 24-27, 2003

Applied nanotechnologies in anticoagulant therapy: from anticoagulants to coagulation test performance of drug delivery systems

Heparin-based delivery systems have been explored to improve their therapeutic efficacy and to reduce toxicity for different administration routes. Regardless of the applied drug delivery system (DDS), the evaluation of anticoagulant performance is instrumental for the development of a suitable DDS. The understanding of the range of anticoagulant assays, together with their key applications and limitations, is essential both within the context of scientific research and for clinical usage. This review provides an overview of the current anticoagulant therapy and discusses the advantages and limitations of currently available anticoagulant assays. We also discuss studies involving low-molecular-weight heparin (LMWH)-based nanocarriers with emphasis on their anticoagulation performance. Conventional anticoagulants have been used for decades for the treatment of many diseases. Direct oral anticoagulants have overcome some limitations of heparins and vitamin K antagonists. However, the lack of an accurate laboratory assessment, as well as the lack of a factor xaban (Xa) inhibitor reversal agent, remains a major problem associated with these anticoagulants. LMWHs represent anticoagulant agents with noteworthy efficacy and safety, and they have been explored to improve their outcomes with various nanocarriers through several administration routes. The main problems related to LMWHs have been surmounted, and improved efficiency may be achieved through the use of DDSs.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and the European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

How strange are compact star interiors ?

We discuss a Nambu--Jona-Lasinio (NJL) type quantum field theoretical approach to the quark matter equation of state with color superconductivity and construct hybrid star models on this basis. It has recently been demonstrated that with increasing baryon density, the different quark flavors may occur sequentially, starting with down-quarks only, before the second light quark flavor and at highest densities also the strange quark flavor appears. We find that color superconducting phases are favorable over non-superconducting ones which entails consequences for thermodynamic and transport properties of hybrid star matter. In particular, for NJL-type models no strange quark matter phases can occur in compact star interiors due to mechanical instability against gravitational collapse, unless a sufficiently strong flavor mixing as provided by the Kobayashi-Maskawa-'t Hooft determinant interaction is present in the model. We discuss observational data on mass-radius relationships of compact stars which can put constraints on the properties of dense matter equation of state.Comment: 7 pages, 2 figures, to appear in the Proceedings of the International Conference SQM2009, Buzios, Rio de Janeiro, Brazil, Sep.27-Oct.2, 200

Two possible source regions for Central Greenland last glacial dust

Dust in Greenland ice cores is used to reconstruct the activity of dust-emitting regions and atmospheric circulation. However, the source of dust material to Greenland over the last glacial period is the subject of considerable uncertainty. Here we use new clay mineral and <10 µm Sr–Nd isotopic data from a range of Northern Hemisphere loess deposits in possible source regions alongside existing isotopic data to show that these methods cannot discriminate between two competing hypothetical origins for Greenland dust: an East Asian and/or central European source. In contrast, Hf isotopes (<10 µm fraction) of loess samples show considerable differences between the potential source regions. We attribute this to a first-order clay mineralogy dependence of Hf isotopic signatures in the finest silt/clay fractions, due to absence of zircons. As zircons would also be absent in Greenland dust, this provides a new way to discriminate between hypotheses for Greenland dust sources