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Cell plasticity

Max D Wellenstein, Karin E de Visser
Owing to their tremendous diversity and plasticity, immune cells exert multifaceted functions in tumor-bearing hosts, ranging from anti-tumor to pro-tumor activities. Tumor immune landscapes differ greatly between and within cancer types. Emerging evidence suggests that genetic aberrations in cancer cells dictate the immune contexture of tumors. Here, we review the current understanding of the mechanisms whereby common drivers of tumorigenesis modulate the tumor immune milieu. We discuss these findings in the context of clinical observations and examine how cancer-cell-intrinsic properties can be exploited to maximize the benefit of immunomodulatory therapies...
March 20, 2018: Immunity
Manami Yamashita, Shin-Ya Kawaguchi, Tetsuya Hori, Tomoyuki Takahashi
Synaptic efficacy plays crucial roles in neuronal circuit operation and synaptic plasticity. Presynaptic determinants of synaptic efficacy are neurotransmitter content in synaptic vesicles and the number of vesicles undergoing exocytosis at a time. Bursts of presynaptic firings depress synaptic efficacy, mainly due to depletion of releasable vesicles, whereas recovery from strong depression is initiated by endocytic vesicle retrieval followed by refilling of vesicles with neurotransmitter. We washed out presynaptic cytosolic GABA to induce a rundown of IPSCs at cerebellar inhibitory cell pairs in slices from rats and then allowed fast recovery by elevating GABA concentration using photo-uncaging...
March 20, 2018: Cell Reports
Xu Zheng, Ali Beyzavi, Joanna Krakowiak, Nikit Patel, Ahmad S Khalil, David Pincus
Clonal populations of cells exhibit cell-to-cell variation in the transcription of individual genes. In addition to this noise in gene expression, heterogeneity in the proteome and the proteostasis network expands the phenotypic diversity of a population. Heat shock factor 1 (Hsf1) regulates chaperone gene expression, thereby coupling transcriptional noise to proteostasis. Here we show that cell-to-cell variation in Hsf1 activity is an important determinant of phenotypic plasticity. Budding yeast cells with high Hsf1 activity were enriched for the ability to acquire resistance to an antifungal drug, and this enrichment depended on Hsp90, a known phenotypic capacitor and canonical Hsf1 target...
March 20, 2018: Cell Reports
Luna Jammal, Ben Whalley, Edi Barkai
Training rats in a complex olfactory discrimination task results in acquisition of 'rule learning' (learning how to learn), a term describing the capability to perform the task superbly. Such rule learning results in strengthening of both excitatory and inhibitory synaptic connections between neurons in the piriform cortex. Moreover, intrinsic excitability is also enhanced throughout the pyramidal neuron population. Surprisingly, the cortical network retains its stability under these long-term modifications...
March 21, 2018: Journal of Neurophysiology
Saori Furuta, Gang Ren, Jian-Hua Mao, Mina J Bissell
How mammalian tissues maintain their architecture and tissue-specificity is poorly understood. Previously, we documented both the indispensable role of the extracellular matrix (ECM) protein, laminin-111 (LN1), in the formation of normal breast acini, and the phenotypic reversion of cancer cells to acini-like structures in 3-dimensional (3D) gels with inhibitors of oncogenic pathways. Here, we asked how laminin (LN) proteins integrate the signaling pathways necessary for morphogenesis. We report a surprising reciprocal circuitry comprising positive players: laminin-5 (LN5), nitric oxide (NO), p53, HOXD10 and three microRNAs (miRNAs) - that are involved in the formation of mammary acini in 3D...
March 21, 2018: ELife
Ma Cristina Acosta-García, Israel Morales-Reyes, Anabel Jiménez-Anguiano, Nikola Batina, N P Castellanos, R Godínez-Fernández
This paper shows the simultaneous recording of electrical activity and the underlying ionic currents by using a gold substrate to culture NG108-15 cells. Cells grown on two different substrates (plastic Petri dishes and gold substrates) were characterized quantitatively through scanning electron microscopy (SEM) as well as qualitatively by optical and atomic force microscopy (AFM). No significant differences were observed between the surface area of cells cultured on gold substrates and Petri dishes, as indicated by measurements performed on SEM images...
February 2018: Heliyon
Tenpei Akita, Kazushi Aoto, Mitsuhiro Kato, Masaaki Shiina, Hiroki Mutoh, Mitsuko Nakashima, Ichiro Kuki, Shin Okazaki, Shinichi Magara, Takashi Shiihara, Kenji Yokochi, Kaori Aiba, Jun Tohyama, Chihiro Ohba, Satoko Miyatake, Noriko Miyake, Kazuhiro Ogata, Atsuo Fukuda, Naomichi Matsumoto, Hirotomo Saitsu
Objective: α ( CAMK2A ) and β ( CAMK2B ) isoforms of Calcium/calmodulin-dependent protein kinase II (CaMKII) play a pivotal role in neuronal plasticity and in learning and memory processes in the brain. Here, we explore the possible involvement of α - and β -CaMKII variants in neurodevelopmental disorders. Methods: Whole-exome sequencing was performed for 976 individuals with intellectual disability, developmental delay, and epilepsy. The effect of CAMK2A and CAMK2B variants on CaMKII structure and firing of neurons was evaluated by computational structural analysis, immunoblotting, and electrophysiological analysis...
March 2018: Annals of Clinical and Translational Neurology
Mohit Kumar Jolly, Prakash Kulkarni, Keith Weninger, John Orban, Herbert Levine
It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms-those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease...
2018: Frontiers in Oncology
Laura Hidalgo-Garcia, Julio Galvez, M Elena Rodriguez-Cabezas, Per O Anderson
Inflammatory bowel disease (IBD) is a group of chronic inflammatory conditions of the gastrointestinal tract characterized by an exacerbated mucosal immune response. Macrophages play pivotal roles in the maintenance of gut homeostasis but they are also implicated in the pathogenesis of IBD. They are highly plastic cells and their activation state depends on the local environment. In the healthy intestine, resident macrophages display an M2 phenotype characterized by inflammatory energy, while inflammatory M1 macrophages dominate in the inflamed intestinal mucosa...
2018: Frontiers in Pharmacology
Victoria Shabardina, Tabea Kischka, Hanna Kmita, Yutaka Suzuki, Wojciech Makałowski
Amoebozoans are in many aspects interesting research objects, as they combine features of single-cell organisms with complex signaling and defense systems, comparable to multicellular organisms. Acanthamoeba castellanii is a cosmopolitan species and developed diverged feeding abilities and strong anti-bacterial resistance; Entamoeba histolytica is a parasitic amoeba, who underwent massive gene loss and its genome is almost twice smaller than that of A. castellanii . Nevertheless, both species prosper, demonstrating fitness to their specific environments...
2018: International Journal of Biological Sciences
Kathrin Kunz, Tanja Piller, Stefan Müller
The ubiquitin-related SUMO system controls many cellular signaling networks. In mammalian cells, three SUMO forms (SUMO1, SUMO2 and SUMO3) act as covalent modifiers of up to thousands of cellular proteins. SUMO conjugation affects cell function mainly by regulating the plasticity of protein networks. Importantly, the modification is reversible and highly dynamic. Cysteine proteases of the sentrin-specific protease (SENP) family reverse SUMO conjugation in mammalian cells. In this Cell Science at a Glance article and the accompanying poster, we will summarize how the six members of the mammalian SENP family orchestrate multifaceted deconjugation events to coordinate cell processes, such as gene expression, the DNA damage response and inflammation...
March 20, 2018: Journal of Cell Science
Richard K P Benninger, David J Hodson
Insulin-secreting β-cells are heterogeneous in their regulation of hormone release. While long known, recent technological advances and new markers have allowed the identification of novel subpopulations, improving our understanding of the molecular basis for heterogeneity. This includes specific subpopulations with distinct functional characteristics, developmental programs, abilities to proliferate in response to metabolic or developmental cues, and resistance to immune-mediated damage. Importantly, these subpopulations change in disease or aging, including in human disease...
April 2018: Diabetes
Mikkel Vestergaard Olesen, Casper René Gøtzsche, Søren Hofman Christiansen, David Paul Drucker Woldbye
OBJECTIVE: Electroconvulsive therapy (ECT) is regularly used to treat patients with severe major depression, but the mechanisms underlying the beneficial effects remain uncertain. Electroconvulsive stimulation (ECS) regulates diverse neurotransmitter systems and induces anticonvulsant effects, properties implicated in mediating therapeutic effects of ECT. Somatostatin (SST) is a candidate for mediating these effects because it is upregulated by ECS and exerts seizure-suppressant effects...
March 21, 2018: Acta Neuropsychiatrica
Kamila Szymanska, Krystyna Makowska, Slawomir Gonkowski
Bisphenol A, used in the production of plastic, is able to leach from containers into food and cause multidirectional adverse effects in living organisms, including neurodegeneration and metabolic disorders. Knowledge of the impact of BPA on enteric neurons is practically non-existent. The destination of this study was to investigate the influence of BPA at a specific dose (0.05 mg/kg body weight/day) and at a dose ten times higher (0.5 mg/kg body weight/day), given for 28 days, on the porcine ileum. The influence of BPA on enteric neuron immunoreactive to selected neuronal active substances, including substance P (SP), vasoactive intestinal polypeptide (VIP), galanin (GAL), vesicular acetylcholine transporter (VAChT-used here as a marker of cholinergic neurons), and cocaine- and amphetamine-regulated transcript peptide (CART), was studied by the double immunofluorescence method...
March 20, 2018: International Journal of Molecular Sciences
Leonardo Elia, Paolo Kunderfranco, Pierluigi Carullo, Marco Vacchiano, Floriana Maria Farina, Ignacio Fernando Hall, Stefano Mantero, Cristina Panico, Roberto Papait, Gianluigi Condorelli, Manuela Quintavalle
Adult vascular smooth muscle cells (VSMCs) possess the peculiar ability to de-differentiate in response to extracellular cues, such as vascular damage and inflammation. De-differentiated VSMCs are proliferative, migratory, and have decreased contractile capacity. VSMC dedifferentiation contributes not only to vascular repair, but also to cardiovascular pathologies, such as intimal hyperplasia/restenosis in coronary artery or peripheral vascular diseases and arterial aneurysm. We here demonstrate the role of ubiquitin-like, containing PHD and RING finger domains, 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity...
March 20, 2018: Journal of Clinical Investigation
Cemile Sonmez, Aysegul Atak Yucel, Turan Hilmi Yesil, Hamit Kucuk, Berna Sezgin, Ridvan Mercan, Ahmet Eftal Yucel, Gulderen Yanikkaya Demirel
Behcet's disease is a chronic multisystemic disease with remissions and relapses. Several studies have shown that immune mechanisms play an important role in the development of the disease. In order to assess the association of disease activity with IL-17A/F, IL-23, IL-12/23 (p40) and IL-35 expression, we aimed to investigate production of these cytokines in peripheral blood mononuclear cells (PBMCs) from Behcet's patients and normal controls. Furthermore, we included Systemic Lupus Erythematosus (SLE) as disease control to evaluate the specificity of our data for immunopathogenesis of BD...
March 20, 2018: Clinical Rheumatology
Ashley C Nelson, Stephanie B Williams, Stephanie S Pistorius, Hyun J Park, Taylor J Woodward, Andrew J Payne, J Daniel Obray, Samuel I Shin, Jennifer K Mabey, Scott C Steffensen
The neural mechanisms underlying alcohol dependence are not well-understood. GABAergic neurons in the ventral tegmental area (VTA) are a relevant target for ethanol. They are inhibited by ethanol at physiologically-relevant levels in vivo and display marked hyperexcitability during withdrawal. In the present study, we examined the effects of the GABA(A) receptor agonist muscimol on VTA neurons ex vivo following withdrawal from acute and chronic ethanol exposure. We used standard cell-attached mode electrophysiology in the slice preparation to evaluate the effects of muscimol on VTA GABA neuron firing rate following exposure to acute and chronic ethanol in male CD-1 GAD-67 GFP mice...
2018: Frontiers in Neuroscience
Hsin-Hao Yu, Nafiseh Atapour, Tristan A Chaplin, Katrina H Worthy, Marcello G P Rosa
Lesions of striate cortex (V1) trigger massive retrograde degeneration of neurons in the lateral geniculate nucleus (LGN). In primates, these lesions also lead to scotomas within which conscious vision is abolished. Mediation of residual visual capacity within these regions (blindsight) has been traditionally attributed to an indirect visual pathway to the extrastriate cortex, which involves the superior colliculus and pulvinar complex. However, recent studies have suggested that preservation of the LGN is critical for behavioral evidence of blindsight, raising the question of what type of visual information is channeled by remaining neurons in this structure...
March 19, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
David Kirkland, Paul Fowler
Trimethylolpropane triacrylate (TMPTA) is a trifunctional acrylate monomer which polymerizes rapidly when exposed to sources of free radicals. It is widely used as a reactive diluent and polymer building block in the formulation of overprint varnishes, inks and a variety of wood, plastic and metal coatings. TMPTA has been tested in a range of in vitro and in vivo genotoxicity tests. There is no clear evidence of induction of gene mutations by TMPTA in bacteria or mammalian cells in vitro, but there is evidence of clastogenicity from induction of small colony tk mutants in the mouse lymphoma assay, and also induction of micronuclei and chromosomal aberrations...
April 2018: Mutation Research
Chiara Assunta Pilato, Ilaria Stadiotti, Angela Serena Maione, Valentina Saverio, Valentina Catto, Fabrizio Tundo, Antonio Dello Russo, Claudio Tondo, Giulio Pompilio, Michela Casella, Elena Sommariva
A normal adult heart is composed of several different cell types, among which cardiac mesenchymal stromal cells represent an abundant population. The isolation of these cells offers the possibility of studying their involvement in cardiac diseases, and, in addition, provides a useful primary cell model to investigate biological mechanisms. Here, the method for the isolation of C-MSC from arrhythmogenic cardiomyopathy patients' bioptic samples is described. The endomyocardial biopsy sampling is guided in the right ventricular areas adjacent to the scar visualized by electro-anatomical mapping...
February 28, 2018: Journal of Visualized Experiments: JoVE
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