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https://www.readbyqxmd.com/read/29346416/decoding-the-network-of-trypanosoma-brucei-proteins-that-determines-sensitivity-to-apolipoprotein-l1
#1
Rachel B Currier, Anneli Cooper, Hollie Burrell-Saward, Annette MacLeod, Sam Alsford
In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative agents of human African trypanosomiasis), T. b. brucei is lysed by apolipoprotein-L1 (apoL1)-containing human serum trypanolytic factors (TLF), rendering it non-infectious to humans. While the mechanisms of TLF1 uptake, apoL1 membrane integration, and T. b. gambiense and T. b. rhodesiense apoL1-resistance have been extensively characterised, our understanding of the range of factors that drive apoL1 action in T. b. brucei is limited...
January 18, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29346349/early-treatment-of-siv-macaques-with-an-%C3%AE-4%C3%AE-7-mab-alters-virus-distribution-and-preserves-cd4-t-cells-in-later-stages-of-infection
#2
P J Santangelo, C Cicala, S N Byrareddy, K T Ortiz, D Little, K E Lindsay, S Gumber, J J Hong, K Jelicic, K A Rogers, C Zurla, F Villinger, A A Ansari, A S Fauci, J Arthos
Integrin α4β7 mediates the trafficking of leukocytes, including CD4+ T cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is implicated in HIV and SIV mediated chronic immune activation and leads to irreversible damage to the immune system. We employed an immuno-PET/CT imaging technique to evaluate the impact of an anti-integrin α4β7 mAb alone or in combination with ART, on the distribution of both SIV infected cells and CD4+ cells in rhesus macaques infected with SIV. We determined that α4β7 mAb reduced viral antigen in an array of tissues of the lung, spleen, axillary, and inguinal lymph nodes...
December 20, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29345574/role-of-cd73-in-disease-promising-prognostic-indicator-and-therapeutic-target
#3
Jiayin Yang, Xiaohong Liao, Jerry Yu, Ping Zhou
CD73, also known as ecto-5'-nucleotidase (eN, NT5E, EC3.13.5), is the rate-limiting enzyme for adenosine generation and is expressed on multiple cells. Its expression is significantly influenced by hypoxia and inflammatory factors. During inflammation, CD73 protects endothelial barrier function and inhibits leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory phenotype). In addition, CD73 is expressed on Treg cells and mediates immune suppression through adenosine. CD73 serves as an essential regulator for the immunity and inflammation...
January 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29345456/pre-occupation-of-empty-carriers-decreases-endo-lysosome-escape-and-reduces-the-protein-delivery-efficiency-of-mesoporous-silica-nanoparticles
#4
Wenqing Li, Liping Sun, Yiqiu Xia, Si-Jie Hao, Gong Cheng, Zhigang Wang, Yuan Wan, Chuandong Zhu, Hongzhang He, Si-Yang Zheng
Endo/lysosome escape is a major challenge in nanoparticles-based protein delivery for cancer therapy. To enhance endo/lysosomal escape and increase the efficacy of proteins delivery, current strategies mainly focuses on destroying endo/lysosomes by employing modified nanoparticles, such as pH-sensitive polyplexes, cell-penetrating peptides, and photosensitive molecules. Herein, we hypothesize that pre-treatment with empty nanocarriers might make endo/lysosomes occupied and affect the endo/lysosomal escape of subsequent protein delivery by nanocarriers...
January 18, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29344585/hereditary-folate-malabsorption-due-to-a-mutation-in-the-external-gate-of-the-proton-coupled-folate-transporter-slc46a1
#5
Srinivas Aluri, Rongbao Zhao, Charlotte Lubout, Susanna M I Goorden, Andras Fiser, I David Goldman
Hereditary folate malabsorption (HFM) is an autosomal recessive disorder characterized by impaired intestinal folate absorption and impaired folate transport across the choroid plexus due to loss of function of the proton-coupled folate transporter (PCFT-SLC46A1). We report a novel mutation, causing HFM, affecting a residue located in the 11th transmembrane helix within the external gate. The mutant N411K-PCFT was stable, trafficked to the cell membrane, and had sufficient residual activity to characterize the transport defect and the structural requirements at this site for gate function...
January 9, 2018: Blood Advances
https://www.readbyqxmd.com/read/29343549/intracellular-vesicle-trafficking-plays-an-essential-role-in-mitochondrial-quality-control
#6
Mike Gerards, Giuseppe Cannino, Jose M González de Cózar, Howard T Jacobs
The Drosophila gene products Bet1, Slh and CG10144, predicted to function in intracellular vesicle trafficking, were previously found to be essential for mitochondrial nucleoid maintenance. Here we show that Slh and Bet1 co-operate to maintain mitochondrial functions. In their absence, mitochondrial content, membrane potential and respiration became abnormal, accompanied by mitochondrial proteotoxic stress, but without direct effects on mtDNA. Immunocytochemistry showed that both Slh and Bet1 are localized at the Golgi, together with a proportion of Rab5-positive vesicles...
January 17, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29343516/stat3-mediated-alterations-in-lysosomal-membrane-protein-composition
#7
Bethan Lloyd-Lewis, Caroline C Krueger, Timothy J Sargeant, Michael E D'Angelo, Michael J Deery, Renata Feret, Julie A Howard, Kathryn S Lilley, Christine J Watson
Lysosome function is essential in cellular homeostasis. In addition to its recycling role, the lysosome has recently been recognised as a cellular signalling hub. We have shown in mammary epithelial cells, both in vivo and in vitro, that signal transducer and activator of transcription 3 (Stat3) modulates lysosome biogenesis and can promote the release of lysosomal proteases that culminates in cell death. To further investigate the impact of Stat3 on lysosomal function, we have conducted a proteomic screen of changes in lysosomal membrane protein components induced by Stat3 using an iron nanoparticle enrichment strategy...
January 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29343411/consequence-of-enhanced-lc3-trafficking-for-a-live-attenuated-m-tuberculosis-vaccine
#8
Stefan Köster, Thais Klevorn, Kadamba Papavinasasundaram, Christopher M Sassetti, Cynthia Portal-Celhay, Jennifer A Philips
Development of a new vaccine against tuberculosis is urgently needed. Recent work has demonstrated that two related LC3-associated trafficking pathways, autophagy and LC3-associated phagocytosis (LAP), enhance antigen presentation and might play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3-trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3-trafficking than M. tuberculosis, which may help explain its limited efficacy. To determine whether enhanced LC3-trafficking can improve efficacy of a live, attenuated M...
January 15, 2018: Vaccine
https://www.readbyqxmd.com/read/29342872/human-cytomegalovirus-nuclear-capsids-associate-with-the-core-nuclear-egress-complex-and-the-viral-protein-kinase-pul97
#9
Jens Milbradt, Eric Sonntag, Sabrina Wagner, Hanife Strojan, Christina Wangen, Tihana Lenac Rovis, Berislav Lisnic, Stipan Jonjic, Heinrich Sticht, William J Britt, Ursula Schlötzer-Schrehardt, Manfred Marschall
The nuclear phase of herpesvirus replication is regulated through the formation of regulatory multi-component protein complexes. Viral genomic replication is followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The latter has been studied intensely pointing to the formation of a viral core nuclear egress complex (NEC) that recruits a multimeric assembly of viral and cellular factors for the reorganization of the nuclear envelope. To date, the mechanism of the association of human cytomegalovirus (HCMV) capsids with the NEC, which in turn initiates the specific steps of nuclear capsid budding, remains undefined...
January 13, 2018: Viruses
https://www.readbyqxmd.com/read/29342457/the-von-hippel-lindau-gene-is-required-to-maintain-renal-proximal-tubule-and-glomerulus-integrity-in-zebrafish-larvae
#10
Ellen van Rooijen, Glenn van de Hoek, Ive Logister, Henry Ajzenberg, Nine V A M Knoers, Freek van Eeden, Emile E Voest, Stefan Schulte-Merker, Rachel H Giles
BACKGROUND: von Hippel-Lindau (VHL) disease is characterized by the development of benign and malignant tumours in many organ systems, including renal cysts and clear cell renal cell carcinoma. It is not completely understood what underlies the development of renal pathology, and the use of murine Vhl models has been challenging due to limitations in disease conservation. We previously described a zebrafish model bearing inactivating mutations in the orthologue of the human VHL gene. METHODS: We used histopathological and functional assays to investigate the pronephric and glomerular developmental defects in vhl mutant zebrafish, supported by human cell culture assays...
January 17, 2018: Nephron
https://www.readbyqxmd.com/read/29342287/to-the-brain-and-back-migratory-paths-of-dendritic-cells-in-multiple-sclerosis
#11
Maxime De Laere, Zwi N Berneman, Nathalie Cools
Migration of dendritic cells (DC) to the central nervous system (CNS) is a critical event in the pathogenesis of multiple sclerosis (MS). While up until now, research has mainly focused on the transmigration of DC through the blood-brain barrier, experimental evidence points out that also the choroid plexus and meningeal vessels represent important gateways to the CNS, especially in early disease stages. On the other hand, DC can exit the CNS to maintain immunological tolerance to patterns expressed in the CNS, a process that is perturbed in MS...
January 12, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29341790/postnatal-tendon-growth-and-remodeling-requires-platelet-derived-growth-factor-receptor-signaling
#12
Kristoffer B Sugg, James F Markworth, Nathaniel P Disser, Andrew M Rizzi, Jeffrey R Talarek, Dylan C Sarver, Susan V Brooks, Christopher L Mendias
Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in the fundamental biological activities of many cells that compose musculoskeletal tissues. However, little is known about the role of PDGFR signaling during tendon growth and remodeling in adult animals. Using the hindlimb synergist ablation model of tendon growth, our objectives were to determine the role of PDGFR signaling in the adaptation of tendons subjected to a mechanical growth stimulus, as well as to investigate the biological mechanisms behind this response...
December 13, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29341352/misregulation-of-membrane-trafficking-processes-in-human-nonalcoholic-steatohepatitis
#13
Anika L Dzierlenga, Nathan J Cherrington
Nonalcoholic steatohepatitis (NASH) remodels the expression and function of genes and proteins that are critical for drug disposition. This study sought to determine whether disruption of membrane protein trafficking pathways in human NASH contributes to altered localization of multidrug resistance-associated protein 2 (MRP2). A comprehensive immunoblot analysis assessed the phosphorylation, membrane translocation, and expression of transporter membrane insertion regulators, including several protein kinases (PK), radixin, MARCKS, and Rab11...
January 17, 2018: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29339490/structural-basis-of-sterol-recognition-and-nonvesicular-transport-by-lipid-transfer-proteins-anchored-at-membrane-contact-sites
#14
Junsen Tong, Mohammad Kawsar Manik, Young Jun Im
Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339412/the-sequence-specific-peptide-binding-activity-of-the-protein-sulfide-isomerase-agr2-directs-its-stable-binding-to-the-oncogenic-receptor-epcam
#15
M Aiman Mohtar, Lenka Hernychova, Robert O'Neill, Melanie Lawrence, Euan Murray, Borek Vojtesek, Ted R Hupp
AGR2 is an oncogenic endoplasmic reticulum (ER)-resident protein disulfide isomerase. AGR2 protein has a relatively unique property for a chaperone in that it can bind sequence-specifically to a specific peptide motif (TTIYY). A synthetic TTIYY-containing peptide column was used to affinity-purify AGR2 from crude lysates highlighting peptide selectivity in complex mixtures. Hydrogen-deuterium exchange mass spectrometry localized the dominant region in AGR2 that interacts with the TTIYY peptide to within a structural loop from amino acids 131-135 (VDPSL)...
January 16, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29339384/a-novel-inhibitor-of-the-lolcde-abc-transporter-essential-for-lipoprotein-trafficking-in-gram-negative-bacteria
#16
Nicholas N Nickerson, Christine C Jao, Yiming Xu, John Quinn, Elizabeth Skippington, Mary Kate Alexander, Anh Miu, Nicholas Skelton, Jessica V Hankins, Michael S Lopez, Christopher M Koth, Steven Rutherford, Mireille Nishiyama
The outer membrane is an essential structural component of Gram-negative bacteria that is composed of lipoproteins, lipopolysaccharides, phospholipids, and integral β-barrel membrane proteins. A dedicated machinery, called the Lol system, ensures proper trafficking of lipoproteins from the inner to the outer membrane. The LolCDE ABC transporter is the inner membrane component, which is essential for bacterial viability. Here, we report a novel pyrrolopyrimidinedione compound, G0507, which was identified in a phenotypic screen for inhibitors of E...
January 16, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29338048/ebola-virus-requires-a-host-scramblase-for-externalization-of-phosphatidylserine-on-the-surface-of-viral-particles
#17
Asuka Nanbo, Junki Maruyama, Masaki Imai, Michiko Ujie, Yoichiro Fujioka, Shinya Nishide, Ayato Takada, Yusuke Ohba, Yoshihiro Kawaoka
Cell surface receptors for phosphatidylserine contribute to the entry of Ebola virus (EBOV) particles, indicating that the presence of phosphatidylserine in the envelope of EBOV is important for the internalization of EBOV particles. Phosphatidylserine is typically distributed in the inner layer of the plasma membrane in normal cells. Progeny virions bud from the plasma membrane of infected cells, suggesting that phosphatidylserine is likely flipped to the outer leaflet of the plasma membrane in infected cells for EBOV virions to acquire it...
January 16, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29337303/pd-l1-on-host-cells-is-essential-for-pd-l1-blockade-mediated-tumor-regression
#18
Haidong Tang, Yong Liang, Robert A Anders, Janis M Taube, Xiangyan Qiu, Aditi Mulgaonkar, Xin Liu, Susan M Harrington, Jingya Guo, Yangchun Xin, Yahong Xiong, Kien Nham, William Silvers, Guiyang Hao, Xiankai Sun, Mingyi Chen, Raquibul Hannan, Jian Qiao, Haidong Dong, Hua Peng, Yang-Xin Fu
Programmed death-ligand 1 (PD-L1) expression on tumor cells is essential for T cell impairment, and PD-L1 blockade therapy has shown unprecedented durable responses in several clinical studies. Although higher expression of PD-L1 on tumor cells is associated with a better immune response after Ab blockade, some PD-L1-negative patients also respond to this therapy. In the current study, we explored whether PD-L1 on tumor or host cells was essential for anti-PD-L1-mediated therapy in 2 different murine tumor models...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337241/differential-effects-of-alzheimer-s-disease-a%C3%AE-40-and-42-on-endocytosis-and-intraneuronal-trafficking
#19
Rajesh S Omtri, Kevin Thompson, Xiojia Tang, Chaitanya C Gali, Ute Panzenboeck, Michael W Davidson, Krishna R Kalari, Karunya K Kadimalla
Anomalous neuronal accumulation of Aβ peptides was shown to affect synaptic transmission and contribute to neurodegeneration in Alzheimer's disease (AD) brain. Neuronal cells internalize amyloid beta (Aβ) peptides from the brain extracellular space even under normal physiological conditions, and these endocytotic pathways go awry during AD progression. We hypothesized that exposure to toxic Aβ species accumulating in AD brain contribute to perturbations in neuronal endocytosis. We have shown substantial down-regulation of KEGG endocytotic pathway genes in AD patient brain regions that accumulate Aβ compared to those in non-demented individuals...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29337233/tau-deficiency-down-regulated-transcription-factor-orthodenticle-homeobox-2-expression-in-the-dopaminergic-neurons-in-ventral-tegmental-area-and-caused-no-obvious-motor-deficits-in-mice
#20
Xiaolu Tang, Luyan Jiao, Meige Zheng, Yan Yan, Qi Nie, Ting Wu, Xiaomei Wan, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Huaibin Cai, Pingyi Xu, Jinhai Duan, Xian Lin
Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes are controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+, tau+/-, tau-/- mice. We found tau deficiency could not induce significant motor disorders...
January 11, 2018: Neuroscience
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