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https://www.readbyqxmd.com/read/29331806/unifying-in%C3%A2-vitro-and-in%C3%A2-vivo-ivt-mrna-expression-discrepancies-in-skeletal-muscle-via-mechanotransduction
#1
Sushma M Bhosle, Kristin H Loomis, Jonathan L Kirschman, Emmeline L Blanchard, Daryll A Vanover, Chiara Zurla, Damien Habrant, Darin Edwards, Patrick Baumhof, Bruno Pitard, Philip J Santangelo
The translational efficiency of an in vitro transcribed (IVT) mRNA was measured upon delivery to primary skeletal muscle cells and to a mouse model system, towards the development of a predictive in vitro assay for the screening and validation of intramuscular mRNA-based vaccines. When IVT mRNA was delivered either naked or complexed with novel aminoglycoside-based delivery vehicles, significant differences in protein expression in vitro and in vivo were observed. We hypothesized that this previously anticipated discrepancy was due to differences in the mechanism of IVT mRNA endosomal entry and release following delivery...
January 6, 2018: Biomaterials
https://www.readbyqxmd.com/read/29331581/identification-and-characterization-of-arginine-finger-like-motifs-and-endosome-lysosome-basolateral-sorting-signals-within-ectopically-expressed-cira-a-coxiella-burnetii-type-iv-secreted-effector-protein
#2
Mary M Weber, Robert Faris, Erin J van Schaik, James E Samuel
Coxiella burnetii is an obligate intracellular pathogen that replicates in an endolysosome-like compartment termed the Coxiella-containing vacuole (CCV). Formation of this unique replicative niche requires delivery of bacterial effector proteins into the host cytosol where they mediate crucial interactions with the host. We previously identified an essential Dot/Icm effector, CirA that is required for intracellular replication and CCV formation. Furthermore, CirA was shown to stimulate the GTPase activity of RhoA in vitro...
January 10, 2018: Microbes and Infection
https://www.readbyqxmd.com/read/29331069/cellular-membrane-trafficking-machineries-utilized-by-the-hepatitis-viruses
#3
REVIEW
Jun Inoue, Masashi Ninomiya, Tooru Shimosegawa, Mark A McNiven
While the life cycles of hepatitis viruses (hepatitis A, B, C, D, and E viruses) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses 'hijack' the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are well known as a leading cause of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating HCV patients have recently been made, patients with HBV continue to require life-long treatment, which makes a thorough understanding of the HBV life cycle essential...
January 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29330675/recognizing-conserved-non-canonical-localization-patterns-of-toll-like-receptors-in-tissues-and-across-species
#4
REVIEW
Glenn Hamonic, J Alex Pasternak, Heather L Wilson
Toll-like receptors (TLR) 1, 2, 4, 5 and 6 were originally characterized as exclusively expressed on the cell surface and TLR 3, 7, 8 and 9 were said to be localized to the endosomes. However, continued research in this area shows that TLR localization may be altered across cell-types, and in response to stimulation, age or disease. Mucosal surfaces must remain tolerant to the commensal flora and thus intracellular or basal lateral localization of TLRs at mucosal surfaces may be necessary to prevent induction of an inflammatory response to commensal flora while still allowing the possibility for the receptors to prime an immune response when a pathogen has crossed the epithelial barrier...
January 12, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29330463/effective-photo-enhancement-of-cellular-activity-of-fluorophore-octaarginine-antisense-pna-conjugates-correlates-with-singlet-oxygen-formation-endosomal-escape-and-chromophore-lipophilicity
#5
Reza Yarani, Takehiko Shiraishi, Peter E Nielsen
Photochemical internalization (PCI) is a cellular drug delivery method based on the generation of light-induced reactive oxygen species (ROS) causing damage to the endosomal membrane and thereby resulting in drug release to the cytoplasm. In our study a series of antisense fluorophore octaarginine peptide nucleic acid (PNA) conjugates were investigated in terms of PCI assisted cellular activity. It is found that tetramethylrhodamine and Alexa Fluor 555 conjugated octaarginine PNA upon irradiation exhibit more than ten-fold increase in antisense activity in the HeLa pLuc705 luciferase splice correction assay...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29326436/p66shc-deficiency-enhances-cxcr4-and-ccr7-recycling-in-cll-b-cells-by-facilitating-their-dephosphorylation-dependent-release-from-%C3%AE-arrestin-at-early-endosomes
#6
Laura Patrussi, Nagaja Capitani, Francesca Cattaneo, Noemi Manganaro, Alessandra Gamberucci, Federica Frezzato, Veronica Martini, Andrea Visentin, Pier Giuseppe Pelicci, Mario M D'Elios, Livio Trentin, Gianpietro Semenzato, Cosima T Baldari
Neoplastic cell traffic abnormalities are central to the pathogenesis of chronic lymphocytic leukemia (CLL). Enhanced CXC chemokine receptor-4 (CXCR4) and chemokine receptor-7 (CCR7) recycling contributes to the elevated surface levels of these receptors on CLL cells. Here we have addressed the role of p66Shc, a member of the Shc family of protein adaptors the expression of which is defective in CLL cells, in CXCR4/CCR7 recycling. p66Shc reconstitution in CLL cells reduced CXCR4/CCR7 recycling, lowering their surface levels and attenuating B-cell chemotaxis, due to their accumulation in Rab5+ endosomes as serine-phosphoproteins bound to β-arrestin...
January 12, 2018: Oncogene
https://www.readbyqxmd.com/read/29326080/light-triggerable-formulations-for-the-intracellular-controlled-release-of-biomolecules
#7
REVIEW
Miguel M Lino, Lino Ferreira
New therapies based on the use of biomolecules [e.g., proteins, peptides, and non-coding (nc)RNAs] have emerged during the past few years. Given their instability, adverse effects, and limited ability to cross cell membranes, delivery systems are required to fully reveal their biological potential. Sophisticated nanoformulations responsive to light offer an excellent opportunity for the controlled release of these biomolecules, enabling the control of timing, duration, location, and dosage. In this review, we discuss the design principles for the delivery of biomolecules, in particular proteins and RNA-based therapeutics, by light-triggerable formulations...
January 8, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29325023/the-extending-spectrum-of-npc1-related-human-disorders-from-niemann-pick-c1-disease-to-obesity
#8
Amel Lamri, Marie Pigeyre, William S Garver, David Meyre
The Niemann-Pick C1 (NPC1) protein regulates the transport of cholesterol and fatty acids from late endosomes / lysosomes and has a central role in maintaining lipid homeostasis. NPC1 loss-of-function mutations in humans cause NPC1 disease, a rare autosomal-recessive lipid-storage disorder characterized by progressive and lethal neurodegeneration, liver and lung failure, due to cholesterol infiltration. In humans, genome wide association studies (GWAS) and post-GWAS reports highlight the implication of common variants in NPC1 in adult-onset obesity, body fat mass, and type 2 diabetes...
January 9, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29324305/caveolin-mediated-endocytosis-of-the-chlamydia-m278-outer-membrane-peptide-encapsulated-in-poly-lactic-acid-poly-ethylene-glycol-nanoparticles-by-mouse-primary-dendritic-cells-enhances-specific-immune-effectors-mediated-by-mhc-class-ii-and-cd4-t-cells
#9
Saurabh Dixit, Rajnish Sahu, Richa Verma, Skyla Duncan, Guillermo H Giambartolomei, Shree R Singh, Vida A Dennis
We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules...
December 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/29322087/the-endosomal-protein-endotubin-is-required-for-enterocyte%C3%A2-differentiation
#10
Christopher M Cox, Ruifeng Lu, Kaan Salcin, Jean M Wilson
Background & Aims: During late embryonic development and through weaning, enterocytes of the ileum are highly endocytic. Defects in endocytosis and trafficking are implicated in neonatal disease, however, the mechanisms regulating trafficking during the developmental period are incompletely understood. The apical endosomal protein endotubin (EDTB) is highly expressed in the late embryonic and neonatal ileum. In epithelial cells in vitro, EDTB regulates both trafficking of tight junction proteins and proliferation through modulation of YAP activity...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29321445/negative-regulation-of-b-cell-responses-and-self-tolerance-to-rna-related-lupus-self-antigen
#11
Takeshi Tsubata
The antibody response to RNA-related antigens such as Sm/RNP requires the endosomal RNA sensor TLR7, and this process is crucial in the development of systemic lupus erythematosus at least in animal models. The inhibitory B cell receptor CD72 is unique because it recognizes Sm/RNP and specifically inhibits the activation of Sm/RNP-reactive B cells by activating SH2-containing protein tyrosine phosphatase 1 (SHP-1). In the normal immune system, Sm/RNP-reactive B cells are tolerized by a unique mechanism that probably involves SHP-1...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/29321327/human-papillomavirus-16-infection-induces-vap-dependent-endosomal-tubulation
#12
Abida Siddiqa, Paola Massimi, David Pim, Justyna Broniarczyk, Lawrence Banks
Human Papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans-Golgi network and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317514/erratum-for-barouch-bentov-et-al-hepatitis-c-virus-proteins-interact-with-the-endosomal-sorting-complex-required-for-transport-escrt-machinery-via-ubiquitination-to-facilitate-viral-envelopment
#13
Rina Barouch-Bentov, Gregory Neveu, Fei Xiao, Melanie Beer, Elena Bekerman, Stanford Schor, Joseph Campbell, Jim Boonyaratanakornkit, Brett Lindenbach, Albert Lu, Yves Jacob, Shirit Einav
No abstract text is available yet for this article.
January 9, 2018: MBio
https://www.readbyqxmd.com/read/29317286/the-a-enth-domain-containing-protein-ateca4-is-an-adaptor-protein-involved-in-cargo-recycling-from-the-trans-golgi-network-early-endosome-to-the-plasma-membrane
#14
Hong Hanh Nguyen, Myoung Hui Lee, Kyungyoung Song, Gyeongik Ahn, Jihyeong Lee, Inhwan Hwang
Endocytosis and subsequent trafficking pathways are crucial for regulating the activity of plasma membrane-localized proteins. Depending on cellular and physiological conditions, the internalized cargoes are sorted at (and transported from) the trans-Golgi network/early endosome (TGN/EE) to the vacuole for degradation or recycled back to the plasma membrane. How this occurs at the molecular level remains largely elusive. Here we provide evidence that the ENTH domain-containing protein AtECA4 plays a crucial role in recycling cargoes from the TGN/EE to the plasma membrane...
January 6, 2018: Molecular Plant
https://www.readbyqxmd.com/read/29316441/budding-yeast-has-a-minimal-endomembrane-system
#15
Kasey J Day, Jason C Casler, Benjamin S Glick
The endomembrane system consists of the secretory and endocytic pathways, which communicate by transport to and from the trans-Golgi network (TGN). In mammalian cells, the endocytic pathway includes early, late, and recycling endosomes. In budding yeast, different types of endosomes have been described, but the organization of the endocytic pathway has remained unclear. We performed a spatial and temporal analysis of yeast endosomal markers and endocytic cargoes. Our results indicate that the yeast TGN also serves as an early and recycling endosome...
January 8, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29316035/transcription-factor-eb-tfeb-influences-invasion-and-migration-in-oral-squamous-cell-carcinomas
#16
Hiroshi Sakamoto, Kentaro Yamashita, Kuniaki Okamoto, Tomoko Kadowaki, Eiko Sakai, Masahiro Umeda, Takayuki Tsukuba
OBJECTIVE: Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and plays an important role in various cancers. However, the function of TFEB in oral squamous cell carcinomas has not been examined. The aim of this study was to elucidate the role of TFEB in oral squamous cell carcinomas. MATERIALS AND METHODS: Expression levels of TFEB were examined in six different human oral squamous carcinoma cells: HSC2, HSC3, HSC4, SAS, OSC20, and SCC25...
January 9, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29315333/cell-penetrating-peptide-driven-cre-recombination-in-porcine-primary-cells-and-generation-of-marker-free-pigs
#17
Qianqian Kang, Zhaolin Sun, Zhiyuan Zou, Ming Wang, Qiuyan Li, Xiaoxiang Hu, Ning Li
Cell-penetrating peptides (CPPs) have been increasingly used to deliver various molecules, both in vitro and in vivo. However, there are no reports of CPPs being used in porcine fetal fibroblasts (PFFs). The increased use of transgenic pigs for basic research and biomedical applications depends on the availability of technologies for efficient genetic-modification of PFFs. Here, we report that three CPPs (CPP5, TAT, and R9) can efficiently deliver active Cre recombinase protein into PFFs via an energy-dependent endocytosis pathway...
2018: PloS One
https://www.readbyqxmd.com/read/29313392/improved-intestinal-absorption-of-paclitaxel-by-mixed-micelles-self-assembled-from-vitamin-e-succinate-based-amphiphilic-polymers-and-their-transcellular-transport-mechanism-and-intracellular-trafficking-routes
#18
Xiaoyou Qu, Yang Zou, Chuyu He, Yuanhang Zhou, Yao Jin, Yunqiang Deng, Ziqi Wang, Xinru Li, Yanxia Zhou, Yan Liu
To ensure that antitumor drugs can be effectively transported across intestinal barrier and then quickly released in tumor cells, mixed polymeric micelles (Mix-PMs) were designed and fabricated by combining poly(2-ethyl-2-oxazoline)-vitamin E succinate (PEOz-VES) with TPGS1000 for enhancing intestinal absorption of paclitaxel. PEOz-VES exhibited an extremely low critical micelle concentration and negligible cytotoxicity. The Mix-PMs were characterized to have about 20 nm in diameter, uniform spherical morphology, high drug-loading content and sustained drug release profile with a retained pH-sensitivity...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29313030/poly-2-propylacrylic-acid-poly-lactic-co-glycolic-acid-blend-microparticles-as-a-targeted-antigen-delivery-system-to-direct-either-cd4-or-cd8-t-cell-activation
#19
Lirong Yang, Evelyn Bracho-Sanchez, Lawrence P Fernando, Jamal S Lewis, Matthew R Carstens, Craig L Duvall, Benjamin G Keselowsky
Poly(lactic-co-glycolic acid) (PLGA) based microparticles (MPs) are widely investigated for their ability to load a range of molecules with high efficiency, including antigenic proteins, and release them in a controlled manner. Micron-sized PLGA MPs are readily phagocytosed by antigen presenting cells, and localized to endosomes. Due to low pH and digestive enzymes, encapsulated protein cargo is largely degraded and processed in endosomes for MHC-II loading and presentation to CD4+ T cells, with very little antigen delivered into the cytosol, limiting MHC-I antigenic loading and presentation to CD8+ T cells...
June 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/29312605/overexpression-of-scamp3-is-an-indicator-of-poor-prognosis-in-hepatocellular-carcinoma
#20
Xinyuan Zhang, Jie Sheng, Yuhong Zhang, Yu Tian, Jie Zhu, Nan Luo, Congshu Xiao, Rongkuan Li
SCAMP3, an isoform of the secretory carrier membrane proteins (SCAMPs) family, is a membrane-trafficking protein involved in endosome transport. Previous microarray data showed that SCAMP3 mRNA is highly expressed in hepatocellular carcinoma (HCC). In this study, the expression and clinical significance of SCAMP3 in 100 pairs of HCC and adjacent normal tissue were investigated. siRNA transfection was performed to silence SCAMP3 expression in HCC cells. The MTS assay and flow cytometry were used to detect the proliferation, cell cycle progression of HCC cells...
December 12, 2017: Oncotarget
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