Identification and characterization of a new potent inhibitor targeting CtBP1/BARS in melanoma cells.

Background: The C-terminal-binding protein 1/brefeldin A ADP-ribosylation substrate (CtBP1/BARS) acts both as an oncogenic transcriptional co-repressor and as a fission inducing protein required for membrane trafficking and Golgi complex partitioning during mitosis, hence for mitotic entry. CtBP1/BARS overexpression, in multiple cancers, has pro-tumorigenic functions regulating gene networks associated with "cancer hallmarks" and malignant behavior including: increased cell survival, proliferation, migration/invasion, epithelial-mesenchymal transition (EMT). Structurally, CtBP1/BARS belongs to the hydroxyacid-dehydrogenase family and possesses a NAD(H)-binding Rossmann fold, which, depending on ligands bound, controls the oligomerization of CtBP1/BARS and, in turn, its cellular functions.

The Golgi checkpoint: Golgi unlinking during G2 is necessary for spindle formation and cytokinesis.

Entry into mitosis requires not only correct DNA replication but also extensive cell reorganization, including the separation of the Golgi ribbon into isolated stacks. To understand the significance of pre-mitotic Golgi reorganization, we devised a strategy to first block Golgi segregation, with the consequent G2-arrest, and then force entry into mitosis. We found that the cells forced to enter mitosis with an intact Golgi ribbon showed remarkable cell division defects, including spindle multipolarity and binucleation.

In Vitro Methods to Investigate the Disassembly of the Golgi Ribbon During the G2-M Transition of the Cell Cycle.

The Golgi complex is the central hub of the secretory pathway. In mammalian cells, it is formed by stacks of flattened cisternae organized in a continuous membrane system, the Golgi ribbon, located near the centrosome. During G2, the Golgi ribbon is disassembled into isolated stacks that, at the onset of mitosis, are further fragmented into small tubular-vesicular clusters that disperse throughout the cytoplasm.

Structural Organization and Function of the Golgi Ribbon During Cell Division.

The Golgi complex has a central role in the secretory traffic. In vertebrate cells it is generally organized in polarized stacks of cisternae that are laterally connected by membranous tubules, forming a structure known as Golgi ribbon. The steady state ribbon arrangement results from a dynamic equilibrium between formation and cleavage of the membrane tubules connecting the stacks.

Evolving dynamic self-adaptation policies of mHealth systems for long-term monitoring.

Tele-rehabilitation can complement traditional rehabilitation therapies by providing valuable information that can help in the evaluation, monitoring, and treatment of patients. Many patient tele-monitoring systems that integrate wearable technology are emerging as an effective tool for the long-term surveillance of rehabilitation progression, enabling continuous sampling of patient real-time movement in a non-invasive way, without affecting the normal daily activity of the outpatient, who, therefore, will not need to make frequent clinic visits. One of the main challenges of tele-rehabilitation systems is to pay special attention to the diversity of dysfunctions in patients by offering devices with customized behaviours adaptable to the physical conditions of each patient at the different stages of the rehabilitation therapy.

The Golgi ribbon: mechanisms of maintenance and disassembly during the cell cycle.

The Golgi complex (GC) has an essential role in the processing and sorting of proteins and lipids. The GC of mammalian cells is composed of stacks of cisternae connected by membranous tubules to create a continuous network, the Golgi ribbon, whose maintenance requires several core and accessory proteins. Despite this complex structural organization, the Golgi apparatus is highly dynamic, and this property becomes particularly evident during mitosis, when the ribbon undergoes a multistep disassembly process that allows its correct partitioning and inheritance by the daughter cells.

Organelle Inheritance Control of Mitotic Entry and Progression: Implications for Tissue Homeostasis and Disease.

The Golgi complex (GC), in addition to its well-known role in membrane traffic, is also actively involved in the regulation of mitotic entry and progression. In particular, during the G2 phase of the cell cycle, the Golgi ribbon is unlinked into isolated stacks. Importantly, this ribbon cleavage is required for G2/M transition, indicating that a "Golgi mitotic checkpoint" controls the correct segregation of this organelle.

GRASP65 controls Golgi position and structure during G2/M transition by regulating the stability of microtubules.

The mammalian Golgi apparatus is organized in the form of a ribbon-like structure positioned near the centrosome. Despite its multimodular organization, the Golgi complex is characterized by a prominent structural plasticity, which is crucial during essential physiological processes, such as the G2 phase of the cell cycle, during which the Golgi ribbon must be "unlinked" into isolated stacks to allow progression into mitosis. Here we show that the Golgi-associated protein GRASP65, which is well known for its role in Golgi stacking and ribbon formation, is also required for the organization of the microtubule cytoskeleton.

Mitotic inheritance of the Golgi complex and its role in cell division.

The Golgi apparatus plays essential roles in the processing and sorting of proteins and lipids, but it can also act as a signalling hub and a microtubule-nucleation centre. The Golgi complex (GC) of mammalian cells is composed of stacks connected by tubular bridges to form a continuous membranous system. In spite of this structural complexity, the GC is highly dynamic, and this feature becomes particularly evident during mitosis, when the GC undergoes a multi-step disassembly process that allows its correct partitioning and inheritance by daughter cells.

Alterations of Golgi organization in Alzheimer's disease: A cause or a consequence?

The Golgi apparatus is a central organelle of the secretory pathway involved in the post-translational modification and sorting of lipids and proteins. In mammalian cells, the Golgi apparatus is composed of stacks of cisternae organized in polarized manner, which are interconnected by membrane tubules to constitute the Golgi ribbon, located in the proximity of the centrosome. Besides the processing and transport of cargo, the Golgi complex is actively involved in the regulation of mitotic entry, cytoskeleton organization and dynamics, calcium homeostasis, and apoptosis, representing a signalling platform for the control of several cellular functions, including signalling initiated by receptors located at the plasma membrane.

Assays to Study the Fragmentation of the Golgi Complex During the G2-M Transition of the Cell Cycle.

The Golgi complex of mammalian cells is composed of stacks of flattened cisternae that are connected by tubules to form a continuous membrane system, also known as the Golgi ribbon. At the onset of mitosis, the Golgi ribbon is progressively fragmented into small tubular-vesicular clusters and it is reconstituted before completion of cytokinesis. The investigation of the mechanisms behind this reversible cycle of disassembly and reassembly has led to the identification of structural Golgi proteins and regulators.

A Software Product Line Process to Develop Agents for the IoT.

One of the most important challenges of this decade is the Internet of Things (IoT), which aims to enable things to be connected anytime, anyplace, with anything and anyone, ideally using any path/network and any service. IoT systems are usually composed of heterogeneous and interconnected lightweight devices that support applications that are subject to change in their external environment and in the functioning of these devices. The management of the variability of these changes, autonomously, is a challenge in the development of these systems.

The Neisseria meningitidis ADP-Ribosyltransferase NarE Enters Human Epithelial Cells and Disrupts Epithelial Monolayer Integrity.

Many pathogenic bacteria utilize ADP-ribosylating toxins to modify and impair essential functions of eukaryotic cells. It has been previously reported that Neisseria meningitidis possesses an ADP-ribosyltransferase enzyme, NarE, retaining the capacity to hydrolyse NAD and to transfer ADP-ribose moiety to arginine residues in target acceptor proteins. Here we show that upon internalization into human epithelial cells, NarE gains access to the cytoplasm and, through its ADP-ribosylating activity, targets host cell proteins.

JNK2 controls fragmentation of the Golgi complex and the G2/M transition through phosphorylation of GRASP65.

In mammalian cells, the Golgi complex is composed of stacks that are connected by membranous tubules. During G2, the Golgi complex is disassembled into isolated stacks. This process is required for entry into mitosis, indicating that the correct inheritance of the organelle is monitored by a 'Golgi mitotic checkpoint'.

Dynamic reconfiguration of security policies in wireless sensor networks.

Providing security and privacy to wireless sensor nodes (WSNs) is very challenging, due to the heterogeneity of sensor nodes and their limited capabilities in terms of energy, processing power and memory. The applications for these systems run in a myriad of sensors with different low-level programming abstractions, limited capabilities and different routing protocols. This means that applications for WSNs need mechanisms for self-adaptation and for self-protection based on the dynamic adaptation of the algorithms used to provide security.

iMuseumA: an agent-based context-aware intelligent museum system.

Currently, museums provide their visitors with interactive tour guide applications that can be installed in mobile devices and provide timely tailor-made multimedia information about exhibits on display. In this paper, we argue that mobile devices not only could provide help to visitors, but also to museum staff. Our goal is to integrate, within the same system, multimedia tour guides with the management facilities required by museums.

Cell and molecular biology of invadopodia.

The controlled degradation of the extracellular matrix is crucial in physiological and pathological cell invasion alike. In vitro, degradation occurs at specific sites where invasive cells make contact with the extracellular matrix via specialized plasma membrane protrusions termed invadopodia. Considerable progress has been made in recent years toward understanding the basic molecular components and their ultrastructural features; generating substantial interest in invadopodia as a paradigm to study the complex interactions between the intracellular trafficking, signal transduction, and cytoskeleton regulation machineries.

Faciogenital dysplasia protein (FGD1) regulates export of cargo proteins from the golgi complex via Cdc42 activation.

Mutations in the FGD1 gene are responsible for the X-linked disorder known as faciogenital dysplasia (FGDY). FGD1 encodes a guanine nucleotide exchange factor that specifically activates the GTPase Cdc42. In turn, Cdc42 is an important regulator of membrane trafficking, although little is known about FGD1 involvement in this process.

Invadopodia biogenesis is regulated by caveolin-mediated modulation of membrane cholesterol levels.

Invadopodia are proteolytically active protrusions formed by invasive tumoural cells when grown on an extracellular matrix (ECM) substratum. Clearly, invadopodia are specialized membrane domains acting as sites of signal transduction and polarized delivery of components required for focalized ECM degradation. For these reasons, invadopodia are a model to study focal ECM degradation by tumour cells.

Invadopodia: specialized tumor cell structures for the focal degradation of the extracellular matrix.

Invasive tumor-derived or transformed cells, cultured on a flat extracellular matrix substratum, extend specialized proteolytically active plasma membrane protrusions. These structures, termed invadopodia, are responsible for the focal degradation of the underlying substrate. Considerable progress has been made in recent years towards understanding the basic molecular components and regulatory circuits and the ultrastructural features of invadopodia.

Faciogenital dysplasia protein Fgd1 regulates invadopodia biogenesis and extracellular matrix degradation and is up-regulated in prostate and breast cancer.

Invadopodia are proteolytically active membrane protrusions that extend from the ventral surface of invasive tumoral cells grown on an extracellular matrix (ECM). The core machinery controlling invadopodia biogenesis is regulated by the Rho GTPase Cdc42. To understand the upstream events regulating invadopodia biogenesis, we investigated the role of Fgd1, a Cdc42-specific guanine nucleotide exchange factor.

Multiple regulatory inputs converge on cortactin to control invadopodia biogenesis and extracellular matrix degradation.

Invadopodia are proteolytically active protrusions formed by invasive tumoral cells when grown on an extracellular matrix (ECM) substratum. Although many molecular components have been defined, less is known of the formation and regulation of invadopodia. The multidomain protein cortactin, which is involved in the regulation of actin polymerisation, is one such component, but how cortactin is modulated to control the formation of invadopodia has not been elucidated.

Actin dynamics at sites of extracellular matrix degradation.

The degradation of extracellular matrix (ECM) by proteases is crucial in physiological and pathological cell invasion alike. In vitro, degradation occurs at specific sites where invasive cells make contact with the ECM via specialized plasma membrane protrusions termed invadopodia. Here we present an extensive morpho-functional analysis of invadopodia actively engaged in ECM degradation and show that they are actin comet-based structures, not unlike the well-known bacteria-propelling actin tails.

Invadopodia: a guided tour.

The controlled degradation of extracellular matrix is crucial in physiological and pathological cell invasion alike. In cultured cells, degradation occurs at specific sites where invasive cells make contact with the extracellular matrix via specialized plasma membrane protrusions termed invadopodia. Considerable progress has been made in recent years towards understanding the basic molecular components and the ultrastructural features of invadopodia.

Protein kinase D regulates basolateral membrane protein exit from trans-Golgi network.

Protein kinase D (PKD) binds to diacylglycerol (DAG) in the trans-Golgi network (TGN) and is activated by trimeric G-protein subunits beta gamma. This complex then regulates the formation of transport carriers in the TGN that traffic to the plasma membrane in non-polarized cells. Here we report specificity of different PKD isoforms in regulating protein trafficking from the TGN.