Metabolic control of stemness and differentiation

Prove crescenti evidenziano un ruolo fondamentale per il metabolismo nella fisiologia delle cellule staminali e nella specifica del lignaggio [1, 2]. Il metabolismo, infatti, non è più considerato solo una fonte di energia né un endpoint della regolazione genica. Invece, i metaboliti e l'ambiente nutritivo sono attori attivi nel determinare la segnalazione intracellulare e le attività enzimatiche e di conseguenza modulatori del destino delle cellule staminali. Inoltre, gli intermedi metabolici del metabolismo cellulare regolano i meccanismi epigenetici, comprese le modificazioni degli istoni, la metilazione del DNA e gli RNA non codificanti, modulando in tal modo il paesaggio e lo staminali dell'epigenoma globale [3]. Questo numero speciale riunisce 9 documenti per evidenziare i recenti sviluppi nel campo.Increasing evidence highlights a pivotal role for metabolism in stem cell physiology and lineage specification [1, 2]. Metabolism, indeed, is no longer considered merely an energy source nor an endpoint of gene regulation. Instead, metabolites and the nutrient environment are active players in determining intracellular signaling and enzymatic activities and consequently modulators of stem cell fate. Moreover, metabolic intermediates of cellular metabolism regulate epigenetic mechanisms, including histone modifications, DNA methylation, and noncoding RNAs, thereby modulating the global epigenome landscape and stemness [3]. This special issue brings together 9 papers to highlight recent developments in the field

SMYD3: An Oncogenic Driver Targeting Epigenetic Regulation and Signaling Pathways

SMYD3 is a member of the SMYD lysine methylase family and plays an important role in the methylation of various histone and non-histone targets. Aberrant SMYD3 expression contributes to carcinogenesis and SMYD3 upregulation was proposed as a prognostic marker in various solid cancers. Here we summarize SMYD3-mediated regulatory mechanisms, which are implicated in the pathophysiology of cancer, as drivers of distinct oncogenic pathways. We describe SMYD3-dependent mechanisms affecting cancer progression, highlighting SMYD3 interplay with proteins and RNAs involved in the regulation of cancer cell proliferation, migration and invasion. We also address the effectiveness and mechanisms of action for the currently available SMYD3 inhibitors. The findings analyzed herein demonstrate that a complex network of SMYD3-mediated cytoplasmic and nuclear interactions promote oncogenesis across different cancer types. These evidences depict SMYD3 as a modulator of the transcriptional response and of key signaling pathways, orchestrating multiple oncogenic inputs and ultimately, promoting transcriptional reprogramming and tumor transformation. Further insights into the oncogenic role of SMYD3 and its targeting of different synergistic oncogenic signals may be beneficial for effective cancer treatment

Dynamic recruitment of NF-Y and histone acetyltransferases on cell-cycle promoters

Regulation of transcription during the cell-cycle is under the control of E2 factors (E2Fs), often in cooperation with nuclear factor Y (NF-Y), a histone-like CCAAT-binding trimer. NF-Y is paradigmatic of a constitutive, ubiquitous factor that pre-sets the promoter architecture for other regulatory proteins to access it. We analyzed the recruitment of NF-Y, E2F1/4/6, histone acetyltransferases, and histone deacetylase (HDAC) 1/3/4 to several cell-cycle promoters by chromatin immunoprecipitation assays in serum-starved and restimulated NIH3T3 cells. NF-Y binding is not constitutive but timely regulated in all promoters tested, being displaced when promoters are repressed. p300 association correlates with activation, and it is never found in the absence of NF-Y, whereas PCAF/hGCN5 is often found before NF-Y association. E2F4 and E2F6, together with HDACs, are bound to repressed promoters, including the G(2)/M Cyclin B2. As expected, an inverse relationship between HDACs association and histones H3/H4 acetylation is observed. Blocking cells in G(1) with the cyclin-dependent kinase 2 inhibitor R-roscovitine confirms that NF-Y is bound to G(1)/S but not to G(2)/M promoters in G(1). These data indicate that following the release of E2Fs/HDACs, a hierarchy of PCAF-NF-Y-p300 interactions and H3-H4 acetylations are required for activation of cell-cycle promoters

Towards a new protocol for field measurements of greenhouse gases from wastewater treatment plant

Emissions into the atmosphere of greenhouse gases (GHGs), i.e., carbon dioxide, methane and nitrous oxide from wastewater treatment plants are of increasing concern in the water industry. In order to produce useful and comparable information for monitoring, assessing and reporting GHG emissions from wastewater treatment plants, there is a crescent need for a general accepted methodology. This paper aims at proposing the first protocol for monitoring and accounting GHG emissions from wastewater treatment plants taking into account both direct and internal indirect emissions focusing on sections known to be major responsible of GHG emissions i.e. oxidation tanks and sludge digestion. The main novelties of the proposed protocol are: (i) direct and indirect internal emissions ascribed to aeration devices which are related each other, (ii) the monitoring of biogas composition in case of anaerobic digestion which affects GHG emissions offset due to biogas valorization systems and (iii) monitoring of non-aerated tanks

Interactions between p300 and multiple NF-Y trimers govern cyclin B2 promoter function

The CCAAT box is one of the most common elements in eukaryotic promoters and is activated by NF-Y, a conserved trimeric transcription factor with histone-like subunits. Usually one CCAAT element is present in promoters at positions between -60 and -100, but an emerging class of promoters harbor multiple NF-Y sites. In the triple CCAAT-containing cyclin B2 cell-cycle promoter, all CCAAT boxes, independently from their NF-Y affinities, are important for function. We investigated the relationships between NF-Y and p300. Chromatin immunoprecipitation analysis found that NF-Y and p300 are bound to the cyclin B2 promoter in vivo and that their binding is regulated during the cell cycle, positively correlating with promoter function. Cotransfection experiments determined that the coactivator acts on all CCAAT boxes and requires a precise spacing between the three elements. We established the order of in vitro binding of the three NF-Y complexes and find decreasing affinities from the most distal Y1 to the proximal Y3 site. Binding of two or three NF-Y trimers with or without p300 is not cooperative, but association with the Y1 and Y2 sites is extremely stable. p300 favors the binding of NF-Y to the weak Y3 proximal site, provided that a correct distance between the three CCAAT is respected. Our data indicate that the precise spacing of multiple CCAAT boxes is crucial for coactivator function. Transient association to a weak site might be a point of regulation during the cell cycle and a general theme of multiple CCAAT box promoters

Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins by JQ1 Unravels a Novel Epigenetic Modulation to Control Lipid Homeostasis

The homeostatic control of lipid metabolism is essential for many fundamental physiological processes. A deep understanding of its regulatory mechanisms is pivotal to unravel prospective physiopathological factors and to identify novel molecular targets that could be employed to design promising therapies in the management of lipid disorders. Here, we investigated the role of bromodomain and extraterminal domain (BET) proteins in the regulation of lipid metabolism. To reach this aim, we used a loss-of-function approach by treating HepG2 cells with JQ1, a powerful and selective BET inhibitor. The main results demonstrated that BET inhibition by JQ1 efficiently decreases intracellular lipid content, determining a significant modulation of proteins involved in lipid biosynthesis, uptake and intracellular trafficking. Importantly, the capability of BET inhibition to slow down cell proliferation is dependent on the modulation of cholesterol metabolism. Taken together, these data highlight a novel epigenetic mechanism involved in the regulation of lipid homeostasis

A testbed for flexible and energy-efficient resource management with virtualized LTE-A nodes

This paper describes the software architecture and the implementation of a fully operational testbed that demonstrates the benefits of flexible, dynamic resource allocation with virtualized LTE-A nodes. The testbed embodies and specializes the general software architecture devised within the Flex5Gware EU project, and focuses on two intelligent programs: the first one is a Global Scheduler, that coordinates radio resource allocation among interfering nodes; the second one is a Global Power Manager, which switches on/off nodes based on their expected and measured load over a period of minutes. The software framework is written using open-source software, and includes fast, scalable optimization algorithms at both components. Moreover, it supports virtualized BaseBand Units, implemented using OpenAir-Interface, that can run on physical and virtual machines. We present the results obtained via on-field measurements, that demonstrate the feasibility and benefits of our approach

Hippocampal and Amygdalar Volumes Changes in Drug Addicts: A Preliminary Study

Oral comunication for American Society of Neuroradiology 45th Annual Meeting. Chicago, June 9-14 200

Flexible dynamic Coordinated Scheduling in Virtual-RAN deployments

Using Coordinated Scheduling (CS), eNodeBs in a cellular network dynamically agree on which Resource Blocks (not) to use, so as to reduce the interference, especially for celledge users. This paper describes a software framework that allows dynamic CS to occur among a relatively large number of nodes, as part of a more general framework of network management devised within the Flex5Gware project. The benefits of dynamic CS, in terms of spectrum efficiency and resource saving, are illustrated by means of simulation and with live measurements on a prototype implementation using virtualized eNodeBs