29 research outputs found
Determining nuclear shape: The role of farnesylated nuclear membrane proteins
No full textChanges in nuclear morphology are observed in diverse developmental processes as well as in pathological conditions. Modification of nuclear membrane and nuclear lamina protein levels results in altered nuclear shapes, as it has been demonstrated in experimental systems ranging from yeast to human cells. The important role of nuclear membrane components in regulating nuclear morphology is additionally highlighted by the abnormally shaped nuclei observed in diseases where nuclear lamina proteins are mutated. Even though the effect of nuclear envelope components on nuclear shape has been thoroughly described, not much is known about the molecular mechanisms that govern these events. In addition to the known role of intermediate filament formation by lamins, here we discuss several mechanisms that might alone or in combination participate in the regulation of nuclear shape observed upon modification of the levels of nuclear membrane and lamina proteins. Based on recent work with the two farnesylated nuclear membrane Drosophila proteins, kugelkern and lamin Dm0, we propose that the direct interaction of farnesylated nuclear membrane proteins with the phospholipid bilayer leads to nuclear envelope deformation. In addition to this mechanism, we suggest that the interaction of nuclear membrane and lamina proteins with cytoskeletal elements and chromatin, and modifications in lipid biosynthesis might also be involved in the formation of abnormally shaped nuclei
Farnesylated Nuclear Proteins Kugelkern and Lamin Dm0 Affect Nuclear Morphology by Directly Interacting with the Nuclear Membrane
No full textNuclear shape changes are observed during a variety of developmental processes, pathological conditions, and ageing. The mechanisms underlying nuclear shape changes in the above-mentioned situations have mostly remained unclear. To address the molecular mechanism behind nuclear shape changes, we analyzed how the farnesylated nuclear envelope proteins Kugelkern and lamin Dm0 affect the structure of the nuclear membrane. We found that Kugelkern and lamin Dm0 affect nuclear shape without requiring filament formation or the presence of a classical nuclear lamina. We also could show that the two proteins do not depend on a group of selected inner nuclear membrane proteins for their localization to the nuclear envelope. Surprisingly, we found that farnesylated Kugelkern and lamin Dm0 protein constructs change the morphology of protein-free liposomes. Based on these findings, we propose that farnesylated proteins of the nuclear membrane induce nuclear shape changes by being asymmetrically inserted into the phospholipid bilayer via their farnesylated C-terminal part
Technological Transformations and Global Value Chains: Strategic Challenges for Europe and Its Territory
No full textOver the past decade, Europe faced multiple challenges that have already caused structural changes in the way regional growth patterns have been taking place. Among many, these challenges include a substantial restructuring of Global Value Chains, with a reversal of the process of offshoring production towards the EU, and the technological transformations induced by the pervasive diffusion of Industry 4.0 and the digital service economy. Both challenges exert effects that are ex ante expected to be intertwined with other driving forces, most notably related to the structural changes associated with the COVID-19 restrictions, and the presently ongoing Russia-Ukraine conflict. Thus, the well-entangled nature of these challenges makes it hard to separate out their net impacts at the local level. The aim of this paper is to simulate the net effects of technological transformations and global value chains, and isolate their local effects on GDP growth, thanks to a regional macro-econometric forecasting model, called MAcroeconometric, Social, Sectoral, Territorial model in its fifth version (MASST5). Results are presented against the backdrop of a reference scenario, modeling both the long-run trends characterizing the EU economy over the past decade, as well as the long-lasting consequences of both COVID-19 restrictions, and the presently ongoing Russia-Ukraine conflict. Results hint at a remarkable spatial heterogeneity of the impacts of these challenges, both in absolute terms, as well as in terms of regional disparities
Structured Methods for reproducible science
No full textAbstract Detailed and accurate documentation of the reagents, tools and methods used in a study is key for reproducible science. However, the information provided in the Materials and Methods section is not always sufficiently detailed to allow for the adoption of methodologies across laboratories. Substantial time and effort, as well as extensive correspondence with the authors of a published paper, is often required in order to obtain all the relevant information related to a particular technique. Even after following a trail of references that frequently lead to a paper published decades ago, it is sometimes impossible to find a sufficiently detailed description of a technique “performed as described before”
Studying the role of dimerization in regulating the activity of Receptor Protein Tyrosine Phosphatase Sigma
No full textRPTP-sigma is a member of the LAR-RPTP subfamily that has been associated with neurite outgrowth and neuronal regeneration. In this study, it is reported that dimenzation, seems to play a role in the regulation of RPTP-sigma activity. RPTP-sigma forms homodimers in cells under physiological conditions and antibody induced dimerization of HA-tagged RPTP-sigma leads to changes in the localization of the protein from the plasma membrane to vesicles in the cytoplasm. Furthermore, when N1E-115 cells were used as an in vitro model for studying the effect of RPTP-sigma-dimerization on neurite outgrowth, it was observed that induction of dimerization of the phosphatase allows neurite outgrowth in conditions that are normally non permissive for differentiation of the cells, indicating that dimer formation probably inhibits RPTP-sigma activity. In order to provide useful tools for studying the signaling cascades regulated by the phosphatase, a series of tagged constructs of potential RPTP-sigma interacting proteins were made. Finally, potential interactions between RPTP-sigma and c-MET were investigated
Looking for “the one”: who is the “real” opinion leader in an agricultural cooperative?
No full textThe aim of the chapter is to answer a critical question: how do we identify an opinion leader portrait in agriculture (specifically in a cooperative)? A key point of concern is the profile of these people in terms of the leading features and some other characteristics which will help policy makers and local stakeholders to identify and use them in the agricultural extension work. In order to achieve the above-mentioned aim a field - case study - research was carried out in a typical Greek agricultural cooperative
Methods to drive systems biology forward
No full textAbstract The development of new methodologies has driven the expansion of systems biology over the past decades. Technological breakthroughs in sequencing, in quantitative proteomics, in single‐cell measurements, to name only a few, have each opened up whole new fields of research. To highlight the importance of new experimental and computational methodologies in enabling novel biological discoveries, we are pleased to announce the introduction of a new Methods section in Molecular Systems Biology ( http://msb.embopress.org/authorguide#methodsguide )
COPS: detecting co-occurrence and spatial arrangement of transcription factor binding motifs in genome-wide datasets.
No full textIn multi-cellular organisms, spatiotemporal activity of cis-regulatory DNA elements depends on their occupancy by different transcription factors (TFs). In recent years, genome-wide ChIP-on-Chip, ChIP-Seq and DamID assays have been extensively used to unravel the combinatorial interaction of TFs with cis-regulatory modules (CRMs) in the genome. Even though genome-wide binding profiles are increasingly becoming available for different TFs, single TF binding profiles are in most cases not sufficient for dissecting complex regulatory networks. Thus, potent computational tools detecting statistically significant and biologically relevant TF-motif co-occurrences in genome-wide datasets are essential for analyzing context-dependent transcriptional regulation. We have developed COPS (Co-Occurrence Pattern Search), a new bioinformatics tool based on a combination of association rules and Markov chain models, which detects co-occurring TF binding sites (BSs) on genomic regions of interest. COPS scans DNA sequences for frequent motif patterns using a Frequent-Pattern tree based data mining approach, which allows efficient performance of the software with respect to both data structure and implementation speed, in particular when mining large datasets. Since transcriptional gene regulation very often relies on the formation of regulatory protein complexes mediated by closely adjoining TF binding sites on CRMs, COPS additionally detects preferred short distance between co-occurring TF motifs. The performance of our software with respect to biological significance was evaluated using three published datasets containing genomic regions that are independently bound by several TFs involved in a defined biological process. In sum, COPS is a fast, efficient and user-friendly tool mining statistically and biologically significant TFBS co-occurrences and therefore allows the identification of TFs that combinatorially regulate gene expression
