92 results match your criteria: "Biomedical Sciences Research Centre Alexander Fleming[Affiliation]"
Cancers (Basel)
January 2021
Biomedical Sciences Research Centre "Alexander Fleming", Institute of Bioinnovation, 34 Fleming Str., 16672 Vari-Athens, Greece.
Beyond the conventional perception of solid tumours as mere masses of cancer cells, advanced cancer research focuses on the complex contributions of tumour-associated host cells that are known as "tumour microenvironment" (TME). It has been long appreciated that the tumour stroma, composed mainly of blood vessels, cancer-associated fibroblasts and immune cells, together with the extracellular matrix (ECM), define the tumour architecture and influence cancer cell properties. Besides soluble cues, that mediate the crosstalk between tumour and stroma cells, cell adhesion to ECM arises as a crucial determinant in cancer progression.
View Article and Find Full Text PDFImmunity
March 2021
Institute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University Magdeburg, Germany; Health Campus Immunology, Infectiology and Inflammation, Otto-von-Guericke-University, Magdeburg, Germany. Electronic address:
Tissue resident mast cells (MCs) rapidly initiate neutrophil infiltration upon inflammatory insult, yet the molecular mechanism is still unknown. Here, we demonstrated that MC-derived tumor necrosis factor (TNF) was crucial for neutrophil extravasation to sites of contact hypersensitivity-induced skin inflammation by promoting intraluminal crawling. MC-derived TNF directly primed circulating neutrophils via TNF receptor-1 (TNFR1) while being dispensable for endothelial cell activation.
View Article and Find Full Text PDFAlthough Tau accumulation is clearly linked to pathogenesis in Alzheimer's disease and other Tauopathies, the mechanism that initiates the aggregation of this highly soluble protein remains largely unanswered. Interestingly, Tau can be induced to form fibrillar filaments by oxidation of its two cysteine residues, generating an intermolecular disulfide bond that promotes dimerization and fibrillization. The recently solved structures of Tau filaments revealed that the two cysteine residues are not structurally equivalent since Cys-322 is incorporated into the core of the fibril, whereas Cys-291 projects away from the core to form the fuzzy coat.
View Article and Find Full Text PDFFront Mol Neurosci
October 2020
Biomedical Sciences Research Centre "Alexander Fleming", Institute for Fundamental Biomedical Research, Vari, Greece.
Hyperphosphorylated Tau protein is the main component of the neurofibrillary tangles, characterizing degenerating neurons in Alzheimer's disease and other Tauopathies. Expression of human Tau protein in Drosophila CNS results in increased toxicity, premature mortality and learning and memory deficits. Herein we use novel transgenic lines to investigate the contribution of specific phosphorylation sites previously implicated in Tau toxicity.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2020
Institute for Fundamental Biomedical Research, Biomedical Sciences Research Centre "Alexander Fleming," 16672 Vari, Greece
Adv Exp Med Biol
April 2020
Institute for Fundamental Biomedical Research, Biomedical Sciences Research Centre "Alexander Fleming", Vari, Greece.
Tauopathies are a heterogeneous group of neurodegenerative dementias involving perturbations in the levels, phosphorylation or mutations of the neuronal microtubule-binding protein Tau. Tauopathies are characterized by accumulation of hyperphosphorylated Tau leading to formation of a range of aggregates including macromolecular ensembles such as Paired Helical filaments and Neurofibrilary Tangles whose morphology characterizes and differentiates these disease states. Why nonphysiological Tau proteins elude the surveillance normal proteostatic mechanisms and eventually form these macromolecular assemblies is a central mostly unresolved question of cardinal importance for diagnoses and potential therapeutic interventions.
View Article and Find Full Text PDFNat Immunol
January 2020
Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.
Regulatory T (T) cells accumulate into tumors, hindering the success of cancer immunotherapy. Yet, therapeutic targeting of T cells shows limited efficacy or leads to autoimmunity. The molecular mechanisms that guide T cell stability in tumors remain elusive.
View Article and Find Full Text PDFNat Commun
September 2019
Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, QC, H3G1Y6, Canada.
The master posttranscriptional regulator HuR promotes muscle fiber formation in cultured muscle cells. However, its impact on muscle physiology and function in vivo is still unclear. Here, we show that muscle-specific HuR knockout (muHuR-KO) mice have high exercise endurance that is associated with enhanced oxygen consumption and carbon dioxide production.
View Article and Find Full Text PDFAlthough the involvement of pathological tau in neurodegenerative dementias is indisputable, its physiological roles have remained elusive in part because its abrogation has been reported without overt phenotypes in mice and This was addressed using the recently described and Mi{MIC} mutants and focused on molecular and behavioral analyses. Initially, we show that tau (dTau) loss precipitates dynamic cytoskeletal changes in the adult CNS and translation upregulation. Significantly, we demonstrate for the first time distinct roles for dTau in adult mushroom body (MB)-dependent neuroplasticity as its downregulation within α'β'neurons impairs habituation.
View Article and Find Full Text PDFBio Protoc
June 2019
Division of Neuroscience, Institute of Basic Biomedical Research, Biomedical Sciences Research Centre "Alexander Fleming", Vari, Greece.
Habituation is the process whereby perceptual changes alter the value of environmental stimuli, enabling salience filtering. This behavioral response decrement is a form of non-associative learning, where the subject learns about the stimulus and does not involve sensory adaptation, sensory or motor fatigue. The range of behavioral responses in led to the development of a number of habituation paradigms addressing various sensory modalities.
View Article and Find Full Text PDFInt J Mol Sci
April 2019
Centre de Recherche en Transplantation et Immunologie, Institut National de la Santé Et de la Recherche Médicale (INSERM), Université de Nantes, 44000 Nantes, France.
Antigen-presenting cells (APCs) including dendritic cells (DCs) play a critical role in the development of autoimmune diseases by presenting self-antigen to T-cells. Different signals modulate the ability of APCs to activate or tolerize autoreactive T-cells. Since the expression of heme oxygenase-1 (HO-1) by APCs has been associated with the tolerization of autoreactive T-cells, we hypothesized that HO-1 expression might be altered in APCs from autoimmune-prone non-obese diabetic (NOD) mice.
View Article and Find Full Text PDFExpert Opin Drug Discov
March 2019
a Division of Neuroscience , Biomedical Sciences Research Centre "Alexander Fleming", Vari , Greece.
Drosophila melanogaster offers a powerful expedient and economical system with facile genetics. Because of the high sequence and functional conservation with human disease-associated genes, it has been cardinal in deciphering disease mechanisms at the genetic and molecular level. Drosophila are amenable to and respond well to pharmaceutical treatment which coupled to their genetic tractability has led to discovery, repositioning, and validation of a number of compounds.
View Article and Find Full Text PDFElife
December 2018
Division of Neuroscience, Biomedical Sciences Research Centre "Alexander Fleming", Vari, Greece.
Unlabelled: Habituation is the process that enables salience filtering, precipitating perceptual changes that alter the value of environmental stimuli. To discern the neuronal circuits underlying habituation to brief inconsequential stimuli, we developed a novel olfactory habituation paradigm, identifying two distinct phases of the response that engage distinct neuronal circuits. Responsiveness to the continuous odor stimulus is maintained initially, a phase we term habituation latency and requires Rutabaga Adenylyl-Cyclase-depended neurotransmission from GABAergic Antennal Lobe Interneurons and activation of excitatory Projection Neurons (PNs) and the Mushroom Bodies.
View Article and Find Full Text PDFJ Stem Cell Res Ther
July 2018
National and Kapodistrian University of Athens, School of Medicine, Department of Pediatrics, Athens, Greece.
The cerebellum, a derivative of the hindbrain, plays a crucial role in balance and posture as well as in higher cognitive and locomotive processes. Cerebellar development is initiated during the segmental phase of hindbrain formation. Here, we describe the phenotype, of a single surviving adult conditional mouse mutant mouse, in which Sox2 function is ablated in embryonic radial glial cells by means of hGFAP-CRE.
View Article and Find Full Text PDFNeurobiol Dis
April 2019
Division of Neuroscience, Biomedical Sciences Research Centre "Alexander Fleming", 34 Fleming str, Vari 16672, Greece. Electronic address:
Accumulation of normal or mutant human Tau isoforms in Central Nervous System (CNS) neurons of vertebrate and invertebrate models underlies pathologies ranging from behavioral deficits to neurodegeneration that broadly recapitulate human Tauopathies. Although some functional differences have begun to emerge, it is still largely unclear whether normal and mutant Tau isoforms induce differential effects on the synaptic physiology of CNS neurons. We use the oligosynaptic Giant Fiber System in the adult Drosophila CNS to address this question and reveal that 3R and 4R isoforms affect distinct synaptic parameters.
View Article and Find Full Text PDFBiol Open
September 2018
Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA
MEF2 (myocyte enhancer factor 2) transcription factors are found in the brain and muscle of insects and vertebrates and are essential for the differentiation of multiple cell types. We show that in the fruit fly , MEF2 is essential for the formation of mushroom bodies in the embryonic brain and for the normal development of wings in the adult. In embryos mutant for , there is a striking reduction in the number of mushroom body neurons and their axon bundles are not detectable.
View Article and Find Full Text PDFNat Immunol
August 2018
Aristotle University of Thessaloniki, School of Biology, Department of Genetics, Development & Molecular Biology, Thessaloniki, Greece.
Proc Natl Acad Sci U S A
June 2018
Department of Immunology, Biomedical Sciences Research Centre "Alexander Fleming," 16672 Vari, Greece;
Mesenchymal cells in the microenvironment of cancer exert important functions in tumorigenesis; however, little is known of intrinsic pathways that mediate these effects. MAPK signals, such as from MAPKAPK2 (MK2) are known to modulate tumorigenesis, yet their cell-specific role has not been determined. Here, we studied the cell-specific role of MK2 in intestinal carcinogenesis using complete and conditional ablation of MK2.
View Article and Find Full Text PDFHum Mol Genet
July 2018
Division of Neuroscience, Biomedical Sciences Research Centre 'Alexander Fleming', Vari 16672, Greece.
Neurodegenerative dementias collectively known as Tauopathies involve aberrant phosphorylation and aggregation of the neuronal protein Tau. The largely neuronal 14-3-3 proteins are also elevated in the central nervous system (CNS) and cerebrospinal fluid of Tauopathy patients, suggesting functional linkage. We use the simplicity and genetic facility of the Drosophila system to investigate in vivo whether 14-3-3s are causal or synergistic with Tau accumulation in precipitating pathogenesis.
View Article and Find Full Text PDFActa Neuropathol Commun
November 2017
Univ. Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc, 59000, Lille, France.
Since the discovery of the microtubule-associated protein Tau (MAPT) over 40 years ago, most studies have focused on Tau's role in microtubule stability and regulation, as well as on the neuropathological consequences of Tau hyperphosphorylation and aggregation in Alzheimer's disease (AD) brains. In recent years, however, research efforts identified new interaction partners and different sub-cellular localizations for Tau suggesting additional roles beyond its standard function as microtubule regulating protein. Moreover, despite the increasing research focus on AD over the last decades, Tau was only recently considered as a promising therapeutic target for the treatment and prevention of AD as well as for neurological pathologies beyond AD e.
View Article and Find Full Text PDFeNeuro
September 2018
Division of Neuroscience, Biomedical Sciences Research Centre "Alexander Fleming," Vari 16672, Greece.
A remarkable feature of olfaction, and perhaps the hardest one to explain by shape-based molecular recognition, is the ability to detect the presence of functional groups in odorants, irrespective of molecular context. We previously showed that trained to avoid deuterated odorants could respond to a molecule bearing a nitrile group, which shares the vibrational stretch frequency with the CD bond. Here, we reproduce and extend this finding by showing analogous olfactory responses of to the chemically vastly different functional groups, thiols and boranes, that nevertheless possess a common vibration at 2600 cm.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2017
Division of Neuroscience, Biomedical Sciences Research Centre "Alexander Fleming," Vari 16672, Greece
Anesthesia-resistant memory (ARM) was described decades ago, but the mechanisms that underlie this protein synthesis-independent form of consolidated memory in remain poorly understood. Whether the several signaling molecules, receptors, and synaptic proteins currently implicated in ARM operate in one or more pathways and how they function in the process remain unclear. We present evidence that Drk, the ortholog of the adaptor protein Grb2, is essential for ARM within adult mushroom body neurons.
View Article and Find Full Text PDFeNeuro
September 2018
Neurobiology, University of Konstanz, Konstanz, 78457, Germany.
Several studies have attempted to test the vibrational hypothesis of odorant receptor activation in behavioral and physiological studies using deuterated compounds as odorants. The results have been mixed. Here, we attempted to test how deuterated compounds activate odorant receptors using calcium imaging of the fruit fly antennal lobe.
View Article and Find Full Text PDFNeurobiol Dis
September 2017
Centre for Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK. Electronic address:
Tau exists as six closely related protein isoforms in the adult human brain. These are generated from alternative splicing of a single mRNA transcript and they differ in the absence or presence of two N-terminal and three or four microtubule binding domains. Typically all six isoforms have been considered functionally similar.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2017
Departamento de Cristalografía y Biología Estructural, Instituto de Química Física Rocasolano, Spanish National Research Council, 28006 Madrid, Spain;