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Mediator And Complex

Yuji Masuda, Satoshi Mitsuyuki, Rie Kanao, Asami Hishiki, Hiroshi Hashimoto, Chikahide Masutani
DNA-damage tolerance protects cells via at least two sub-pathways regulated by proliferating cell nuclear antigen (PCNA) ubiquitination in eukaryotes: translesion DNA synthesis (TLS) and template switching (TS), which are stimulated by mono- and polyubiquitination, respectively. However, how cells choose between the two pathways remains unclear. The regulation of ubiquitin ligases catalyzing polyubiquitination, such as helicase-like transcription factor (HLTF), could play a role in the choice of pathway. Here, we demonstrate that the ligase activity of HLTF is stimulated by double-stranded DNA via HIRAN domain-dependent recruitment to stalled primer ends...
October 18, 2018: Nucleic Acids Research
Alessandra Pierangeli, Carolina Scagnolari, Guido Antonelli
Respiratory syncytial virus (RSV) is the most common cause of infant hospitalization and causes a high burden of disease in the elderly, too. This enveloped negative-stranded RNA virus has been recently reclassified in the Pneumoviridae family. Infections of the respiratory cells happens when the two major surface glycoproteins, G and F, take contact with the cell receptor CX3CR1 and mediate entry by fusion, respectively. Viral mRNA transcription, genomic RNA synthesis and nucleocapsid formation occur in large cytoplasmic inclusion bodies to avoid recognition by the host innate immune response...
October 18, 2018: Minerva Pediatrica
Clément Lepori, Elise Bernoud, Régis Guillot, Sven Tobisch, Jérôme Hannedouche
A comprehensive mechanistic study by means of complementary experimental and computational approaches of the exo-cyclohydroamination of primary aminoalkenes mediated by the recently reported β-diketiminatoiron(II) complex B is presented. Kinetic analysis of the cyclisation of 2,2-diphenylpent-4-en-1-amine (1a) catalysed by B revealed a first-order dependence of the rate on both aminoalkene and catalyst concentrations and a primary KIE (kH/kD) of 2.7 (90 °C). Eyring analysis afforded ΔH‡ = 22.2 kcal.mol-1, ΔS‡ = -13...
October 18, 2018: Chemistry: a European Journal
Mang Mang Sang, Fu Lei Liu, Yang Wang, Ren Jie Luo, Xiao Xian Huan, Ling Fei Han, Zhong Tao Zhang, Feng Feng, Wei Qu, Wenyuan Liu, Feng Zheng
Gambogic acid (GA) is a naturally derived potent anticancer agent with extremely poor biocompatibility. In the present study, a novel of redox/pH dual-responsive multifunctional magnetic complex micelle (sPEG/HA/CSO-SS-Hex/Fe3 O4 /GA), which consisted of a reducible hexadecanol-modified chitosan oligosaccharide polymer micelle (CSO-SS-Hex) coated with hyaluronic acid (HA) and DCA grafted sheddable PEG-PLL (sPEG) copolymers and loaded with gambogic acid (GA) and Fe3 O4 nanoparticles were developed for parenteral delivery for the treatment of triple negative breast cancer (TNBC)...
November 2018: Drug Delivery
X Zhao, F Q Yu, X J Huang, B Y Xu, Y L Li, X Y Zhao, H F Guo, B Luan
Asthma is a respiratory disease that affects people of all walks of life, and is a hotspot of continuous research, with significant manpower and resources invested in its study. Airway remodeling is an important associated pathological change, and a mark of the irreversible damage produced by asthma. It involves compositional and functional changes in the cells of the airway walls, leading to reversible structural changes, and complicating treatment. Airway remodeling is mediated by different inflammatory pathways which have been targeted for treatment, with good results...
September 2018: Journal of Biological Regulators and Homeostatic Agents
Cristina Agliardi, Franca Rosa Guerini, Milena Zanzottera, Giulio Riboldazzi, Roberta Zangaglia, Andrea Sturchio, Carlo Casali, Cherubino Di Lorenzo, Brigida Minafra, Raffaello Nemni, Mario Clerici
Parkinson's disease (PD) is a α-synucleinopathy in which intracellular aggregates of α-synuclein (α-syn) result in neurodegeneration and in the impairment of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex-mediated release of neurotransmitters. SNAP25 is a SNARE complex component: its concentration is increased in the cerebrospinal fluid of PD patients and this is related to the severity of cognitive and motor symptoms. Five SNAP25 single-nucleotide polymorphisms (SNPs) that modulate gene expression and were described to play a role in neurologic conditions (rs363050, rs363039, rs363043, rs3746544, and rs1051312) were analyzed in a cohort of 412 sporadic Italian PD patients and 1103 healthy controls (HC) in order to identify possible correlation with the disease...
October 17, 2018: Molecular Neurobiology
L Brustolin, C Nardon, N Pettenuzzo, N Zuin Fantoni, S Quarta, F Chiara, A Gambalunga, A Trevisan, L Marchiò, P Pontisso, D Fregona
In this paper, we focused on the analysis of the effects mediated by different cyclic dithiocarbamic ligands (DTC) on three classes of antiproliferative coordination compounds, namely, Ru(iii) complexes with the general formulae [Ru(DTC)3] and [Ru2(DTC)5]Cl, and the neutral Cu(ii) derivatives of the type [Cu(DTC)2]. In particular, we present the synthesis and characterization of a library of total 23 coordination compounds containing Ru(iii) or Cu(ii) as the biologically-active metal center and two or more dithiocarbamato (DTC) ligands derived from cyclic amines (aliphatic or aromatic)...
October 18, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
Chuancheng Jia, Marjan Famili, Marco Carlotti, Yuan Liu, Peiqi Wang, Iain M Grace, Ziying Feng, Yiliu Wang, Zipeng Zhao, Mengning Ding, Xiang Xu, Chen Wang, Sung-Joon Lee, Yu Huang, Ryan C Chiechi, Colin J Lambert, Xiangfeng Duan
Molecular transistors operating in the quantum tunneling regime represent potential electronic building blocks for future integrated circuits. However, due to their complex fabrication processes and poor stability, traditional molecular transistors can only operate stably at cryogenic temperatures. Here, through a combined experimental and theoretical investigation, we demonstrate a new design of vertical molecular tunneling transistors, with stable switching operations up to room temperature, formed from cross-plane graphene/self-assembled monolayer (SAM)/gold heterostructures...
October 2018: Science Advances
Emil Lou, Edward Zhai, Akshat Sarkari, Snider Desir, Phillip Wong, Yoshie Iizuka, Jianbo Yang, Subbaya Subramanian, James McCarthy, Martina Bazzaro, Clifford J Steer
Intercellular communication is vital to the ecosystem of cancer cell organization and invasion. Identification of key cellular cargo and their varied modes of transport are important considerations in understanding the basic mechanisms of cancer cell growth. Gap junctions, exosomes, and apoptotic bodies play key roles as physical modalities in mediating intercellular transport. Tunneling nanotubes (TNTs)-narrow actin-based cytoplasmic extensions-are unique structures that facilitate direct, long distance cell-to-cell transport of cargo, including microRNAs, mitochondria, and a variety of other sub cellular components...
2018: Frontiers in Cell and Developmental Biology
Arjanneke F van de Merbel, Geertje van der Horst, Maaike H van der Mark, Janneke I M van Uhm, Erik J van Gennep, Peter Kloen, Lijkele Beimers, Rob C M Pelger, Gabri van der Pluijm
Urological malignancies, including prostate and bladder carcinoma, represent a major clinical problem due to the frequent occurrence of therapy resistance and the formation of incurable distant metastases. As a result, there is an urgent need for versatile and predictive disease models for the assessment of the individualized drug response in urological malignancies. Compound testing on ex vivo cultured patient-derived tumor tissues could represent a promising approach. In this study, we have optimized an ex vivo culture system of explanted human prostate and bladder tumors derived from clinical specimens and human cancer cell lines xenografted in mice...
2018: Frontiers in Oncology
Clément Pierre, Florent Guillebaud, Coraline Airault, Nathalie Baril, Rym Barbouche, Etienne Save, Stéphanie Gaigé, Bruno Bariohay, Michel Dallaporta, Jean-Denis Troadec
Chronic low-grade inflammation is known to be linked to obesity, and to occur in the early stages of the disease. This mechanism is complex and involves numerous organs, cells, and cytokines. In this context, inflammation of white adipose tissue seems to play a key role in the development of obesity. Because of its properties, prostaglandin E2 (PGE2), an emblematic inflammatory mediator, has been proposed as an actor linking inflammation and obesity. Indeed, PGE2 is involved in mechanisms that are dysregulated in obesity such as lipolysis and adipogenesis...
2018: Frontiers in Physiology
Bárbara B Garrido-Suárez, Gabino Garrido, Marian Castro-Labrada, Zenia Pardo-Ruíz, Addis Bellma Menéndez, Evelyn Spencer, Jozi Godoy-Figueiredo, Sergio H Ferreira, René Delgado-Hernández
The present study reproduces chronic post-ischemia pain (CPIP), a model of complex regional pain syndrome type I (CRPS-I), in rats to examine the possible transient and long-term anti-allodynic effect of mangiferin (MG); as well as its potential beneficial interactions with some standard analgesic drugs and sympathetic-mediated vasoconstriction and vasodilator agents during the earlier stage of the pathology. A single dose of MG (50 and 100 mg/kg, p.o.) decreased mechanical allodynia 72 h post-ischemia-reperfusion (I/R)...
2018: Frontiers in Pharmacology
Whitby V I Eagle, Daniel K Yeboah-Kordieh, Matthew G Niepielko, Elizabeth R Gavis
Specification and development of Drosophila germ cells depend on molecular determinants within the germ plasm, a specialized cytoplasmic domain at the posterior of the embryo. Localization of numerous mRNAs to the germ plasm occurs by their incorporation, as single-transcript ribonucleoprotein (RNP) particles, into complex RNP granules called polar granules. Incorporation of mRNAs into polar granules is followed by recruitment of additional like-transcripts to form discrete homotypic clusters. The cis -acting localization signals that target mRNAs to polar granules and promote homotypic clustering remain largely uncharacterized...
October 17, 2018: Development
Kaiyuan Wu, Lingdi Wang, Yong Chen, Mehdi Pirooznia, Komudi Singh, Sarah Wälde, Ralph H Kehlenbach, Iain Scott, Marjan Gucek, Michael N Sack
Although GCN5L1 facilitates mitochondrial protein acetylation and controls endosomal-lysosomal trafficking mechanisms underpinning these disparate effects are unclear. As microtubule acetylation modulates endosome-lysosome trafficking we reasoned that exploring the role of GCN5L1 in this biology may enhance our understanding of GCN5L1-mediated protein acetylation. We show that α-tubulin acetylation is reduced in GCN5L1 knockout hepatocytes and restored by GCN5L1 reconstitution. Furthermore, GCN5L1 binds to the alpha-tubulin acetyltransferase αTAT1 and GCN5L1 mediated α-tubulin acetylation is αTAT1-dependent...
October 17, 2018: Journal of Cell Science
Damian A Almiron Bonnin, Matthew C Havrda, Mark A Israel
Cellular secretion is an important mediator of cancer progression. Secreted molecules in glioma are key components of complex autocrine and paracrine pathways that mediate multiple oncogenic pathologies. In this review, we describe tumor cell secretion in high-grade glioma and highlight potential novel therapeutic opportunities. Cancer Res; 78(21); 1-9. ©2018 AACR.
October 17, 2018: Cancer Research
Sebastian Vogel, Taruna Arora, Xunde Wang, Laurel Mendelsohn, James Nichols, Darlene Allen, Arun S Shet, Christian A Combs, Zenaide M N Quezado, Swee Lay Thein
A key inflammatory mechanism recently identified in platelets involves the Nod-like receptor nucleotide-binding domain leucine-rich repeat containing protein 3 (NLRP3) and Bruton tyrosine kinase (BTK), which control activation of caspase-1 within inflammasome complexes. We investigated platelet caspase-1 activity in the context of sickle cell disease (SCD) directly in platelets isolated from SCD patients (n = 24) and indirectly by incubating platelets from healthy subjects with plasma obtained from SCD patients (n = 20), both in steady state and during an acute pain crisis (paired samples)...
October 23, 2018: Blood Advances
Li-Juan Yan, Xin-Hong Guo, Wei-Ping Wang, Yu-Rong Hu, Shao-Feng Duan, Ying Liu, Zhi Sun, Sheng-Nan Huang, Hui-Li Li
MicroRNA (miRNA) therapy, which was widely considered to treat a series of cancer, has been confronted with numerous obstacles to being delivered into target cells because of its easy biodegradation and instability. In this research, we successfully constructed 11-mercaptoundecanoic acid modified gold nanocages (AuNCs)/polyethyleneimine (PEI)/miRNA/hyaluronic acid (HA) complexes (abbreviated as AuNCs/PEI/miRNA/HA) using a layer-by-layer method for target-specific intracellular delivery of miRNA by HA receptor mediated endocytosis...
October 16, 2018: Current Cancer Drug Targets
Olga Simo-Servat, Cristina Hernández, Rafael Simó
BACKGROUND: Microvascular complications remain an important cause of morbidity in diabetic patients, and they are associated with a significant economic burden for healthcare systems. Vascular leakage is one of the earlier hallmarks in diabetic microvascular complications. Ezrin, radixin and moesin (ERM) proteins have recently been involved in vascular dysfunction under the effect of molecular mediators of diabetes complications. In this review we will present the available evidence regarding the role of these proteins in vascular leakage and their putative implication in diabetic microvascular complications...
October 16, 2018: Current Medicinal Chemistry
Matteo Biolatti, Valentina Dell'Oste, Sara Scutera, Francesca Gugliesi, Gloria Griffante, Marco De Andrea, Tiziana Musso, Santo Landolfo
Interleukin-1β (IL-1β) is a key effector of the inflammasome complex in response to pathogens and danger signals. Although it is well known that assembly of the inflammasome triggers proteolytic cleavage of the biologically inactive precursor pro-IL-1β into its mature secreted form, the mechanism by which human cytomegalovirus (HCMV) regulates IL-1β production via the inflammasome is still poorly understood. Here, we show that the infection of human foreskin fibroblasts (HFFs) with a mutant HCMV lacking the tegument protein pp65 (v65Stop) results in higher expression levels of mature IL-1β compared to its wild-type counterpart, suggesting that pp65 mediates HCMV immune evasion through downmodulation of IL-1β...
October 16, 2018: Viruses
Yukako Tatematsu, Qalbi Khan, Tomas Blanco, Jeffrey A Bair, Robin R Hodges, Sharmila Masli, Darlene A Dartt
Thrombospondin-1-deficient (TSP-1-/- ) mice are used as an animal model of Sjögren's Syndrome because they exhibit many of the symptoms associated with the autoimmune type of dry eye found in primary Sjögren's Syndrome. This type of dry eye is linked to the inflammation of the lacrimal gland, conjunctiva, and cornea, and is thought to involve dysfunction of the complex neuronal reflex arc that mediates tear production in response to noxious stimuli on the ocular surface. This study characterizes the structural and functional changes to the corneal nerves that are the afferent arm of this arc in young and older TSP-1-/- and wild type (WT) mice...
October 16, 2018: International Journal of Molecular Sciences
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