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https://www.readbyqxmd.com/read/28222515/meta-analysis-of-parkinson-s-disease-and-alzheimer-s-disease-revealed-commonly-impaired-pathways-and-dysregulation-of-nrf2-dependent-genes
#1
Qian Wang, Wen-Xing Li, Shao-Xing Dai, Yi-Cheng Guo, Fei-Fei Han, Jun-Juan Zheng, Gong-Hua Li, Jing-Fei Huang
Many lines of evidence suggest that Parkinson's disease (PD) and Alzheimer's disease (AD) have common characteristics, such as mitochondrial dysfunction and oxidative stress. As the underlying molecular mechanisms are unclear, we perform a meta-analysis with 9 microarray datasets of PD studies and 7 of AD studies to explore it. Functional enrichment analysis revealed that PD and AD both showed dysfunction in the synaptic vesicle cycle, GABAergic synapses, phagosomes, oxidative phosphorylation, and TCA cycle pathways, and AD had more enriched genes...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28220253/myd88-in-mycobacterium-tuberculosis-infection
#2
EDITORIAL
Jorge L Cervantes
MyD88 adaptor protein mediates numerous biologically important signal transduction pathways in innate immunity. MyD88 signaling fosters bacterial containment and is necessary to raise an adequate innate and acquired immune response to Mycobacterium tuberculosis (Mtb). The phagosome is a crucial cellular location not only for Mtb replication, but it is also where components of the Myddosome and inflammasome are recruited. Besides its function as a TLR-adaptor protein, MyD88 may help stabilizing cytosolic receptors that are recruited to the phagosome...
February 20, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28210928/bacterial-resistance-to-arsenic-protects-against-protist-killing
#3
Xiuli Hao, Xuanji Li, Chandan Pal, Jon Hobman, D G Joakim Larsson, Quaiser Saquib, Hend A Alwathnani, Barry P Rosen, Yong-Guan Zhu, Christopher Rensing
Protists kill their bacterial prey using toxic metals such as copper. Here we hypothesize that the metalloid arsenic has a similar role. To test this hypothesis, we examined intracellular survival of Escherichia coli (E. coli) in the amoeba Dictyostelium discoideum (D. discoideum). Deletion of the E. coli ars operon led to significantly lower intracellular survival compared to wild type E. coli. This suggests that protists use arsenic to poison bacterial cells in the phagosome, similar to their use of copper...
February 16, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28202687/oxidized-phagosomal-nox2-is-replenished-from-lysosomes
#4
Ilse Dingjan, Peter T A Linders, Luuk van den Bekerom, Maksim V Baranov, Partho Halder, Martin Ter Beest, Geert van den Bogaart
In dendritic cells, the NADPH oxidase 2 (NOX2) is recruited to the phagosomal membrane during antigen uptake. NOX2 produces reactive oxygen species (ROS) in the lumen of the phagosome which kill ingested pathogens, delay antigen breakdown and alter the peptide repertoire for presentation to T cells. How the integral membrane component of NOX2, cytochrome b558, traffics to phagosomes is incompletely understood. In this study, we show in dendritic cells derived from human blood-isolated monocytes that cytochrome b558 is initially recruited to the phagosome from the plasma membrane during phagosome formation...
February 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28192437/species-dependent-impact-of-helminth-derived-antigens-on-human-macrophages-infected-with-mycobacterium-tuberculosis-direct-effect-on-the-innate-anti-mycobacterial-response
#5
Naomi Aira, Anna-Maria Andersson, Susmita K Singh, Derek M McKay, Robert Blomgran
BACKGROUND: In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. PRINCIPAL FINDINGS: We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb...
February 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28191879/visualizing-the-early-stages-of-phagocytosis
#6
Ali Rashidfarrokhi, Veronica Richina, Fikadu G Tafesse
The mammalian body is equipped with various layers of mechanisms that help to defend itself from pathogen invasions. Professional phagocytes of the immune system - such as neutrophils, dendritic cells, and macrophages - retain the innate ability to detect and clear such invading pathogens through phagocytosis(1). Phagocytosis involves choreographed events of membrane reorganization and actin remodeling at the cell surface(2)(,)(3). Phagocytes successfully internalize and eradicate foreign molecules only when all stages of phagocytosis are fulfilled...
February 3, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28183269/transcriptome-profilings-of-two-tall-fescue-festuca-arundinacea-cultivars-in-response-to-lead-pb-stress
#7
Huiying Li, Tao Hu, Erick Amombo, Jinmin Fu
BACKGROUND: Lead (Pb) is one of the most toxic heavy metal environmental pollutants. Tall fescue is an important cold season turf grass which can tolerate and accumulate substantial amount of Pb. To estimate genes related to Pb response and the molecular mechanism associated with Pb tolerance and accumulation, we analyzed the transcriptome of tall fescue in response to Pb treatment. RESULTS: RNA-sequencing was performed in two tall fescue cultivars, Pb tolerant Silverado and Pb sensitive AST7001...
February 10, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28177960/innate-immune-response-to-burkholderia-mallei
#8
Kamal U Saikh, Tiffany M Mott
PURPOSE OF REVIEW: Burkholderia mallei is a facultative intracellular pathogen that causes the highly contagious and often the fatal disease, glanders. With its high rate of infectivity via aerosol and recalcitrance toward antibiotics, this pathogen is considered a potential biological threat agent. This review focuses on the most recent literature highlighting host innate immune response to B. mallei. RECENT FINDINGS: Recent studies focused on elucidating host innate immune responses to the novel mechanisms and virulence factors employed by B...
February 7, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28174296/ncs1-regulates-ca2-dependent-focal-exocytosis-of-golgi-derived-vesicles-to-help-phagocytic-uptake-in-macrophages
#9
Nimi Vashi, Syed Bilal Ahmad Andrabi, Swapnil Ghanwat, Mrutyunjay Suar, Dhiraj Kumar
During phagocytic uptake by macrophages, role of Golgi apparatus was previously ruled out. Notably all such reports were limited to Fcγ-receptor mediated phagocytosis. Here we unravel a highly devolved mechanism for recruitment of Golgi-derived secretory vesicles during phagosome biogenesis, which was important for uptake of most cargos except IgG-coated ones. We report recruitment of Mannosidase-II positive Golgi-derived vesicles during uptake of diverse targets including latex beads, E. coli, Salmonella Typhimurium and Mycobacterium tuberculosis in human and mouse macrophages...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28142206/mycobacterium-tuberculosis-virulence-regulator-phop-interacts-with-alternative-sigma-factor-sige-during-acid-stress-response
#10
Roohi Bansal, Vijjamarri Anil Kumar, Ritesh Rajesh Sevalkar, Prabhat Ranjan Singh, Dibyendu Sarkar
The ability to sense acid stress and mount an appropriate adaptive response by M. tuberculosis, which adapts a long term residence in the macrophage phagosome remains one of the critical features that defines mycobacterial physiology and its intracellular location. To understand the mechanistic basis of adaptation of the intracellular pathogen, we studied global regulation of M. tuberculosis gene expression in response to acid stress. Although recent studies indicate a role for the virulence-associated phoP locus in pH-driven adaptation, in this study, we discovered a strikingly novel regulatory mechanism which controls acid-stress homeostasis...
January 31, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28137237/model-systems-for-pulmonary-infectious-diseases-paradigms-of-anthrax-and-tuberculosis
#11
Gunjan Arora, Richa Misra, Andaleeb Sajid
Robert Koch utilized animal model systems to put forward his postulates while discovering the etiological agents of anthrax and tuberculosis, Bacillus anthracis and Mycobacterium tuberculosis, respectively. After more than 130 years, we have achieved limited success towards understanding these two pestilences, which have propagated as scourge against humans. B. anthracis and M. tuberculosis are diverse organisms, which share a common evolutionary path in tropics. They adapt unique strategies to overcome unfavorable conditions and surpass the host defense mechanisms...
January 30, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28129089/activation-of-compensatory-pathways-via-rac2-in-the-absence-of-the-cdc42-effector-wiskott-aldrich-syndrome-protein-in-dendritic-cells
#12
Marisa A P Baptista, Lisa S Westerberg
There is extensive crosstalk between different Rho GTPases, including Cdc42, Rac1, and Rac2, and they can activate or inhibit the activity of each other. Dendritic cells express both Rac1 and Rac2. Due to posttranslational modification of lipid anchors, Rac1 localizes mainly to the plasma membrane whereas Rac2 localizes to the phagosomal membrane where it assembles the NADPH complex. Our recent study of primary immunodeficiency disease caused by mutations in the Cdc42 effector Wiskott-Aldrich syndrome protein (WASp) has shed light on the compensatory mechanisms between Rho GTPases and their effector proteins...
January 27, 2017: Small GTPases
https://www.readbyqxmd.com/read/28126902/the-monomeric-gtpase-rab35-regulates-phagocytic-cup-formation-and-phagosomal-maturation-in-entamoeba-histolytica
#13
Kuldeep Verma, Sunando Datta
One of the hallmarks of amoebic colitis is the detection of Entamoeba histolytica (Eh) trophozoites with ingested erythrocytes. Therefore, erythrophagocytosis is traditionally considered as one of the most important criteria to identify the pathogenic behavior of the amoebic trophozoites. Phagocytosis is an essential process for the proliferation and virulence of this parasite. Phagocytic cargo, upon internalization, follows defined trafficking route to amoebic lysosomal degradation machinery. Here, we demonstrated the role of EhRab35 in the early and late phase of erythrophagocytosis by the amoeba...
January 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28120876/mycofactocin-associated-mycobacterial-dehydrogenases-with-non-exchangeable-nad-cofactors
#14
Daniel H Haft, Phillip G Pierce, Stephen J Mayclin, Amy Sullivan, Anna S Gardberg, Jan Abendroth, Darren W Begley, Isabelle Q Phan, Bart L Staker, Peter J Myler, Vasilios M Marathias, Donald D Lorimer, Thomas E Edwards
During human infection, Mycobacterium tuberculosis (Mtb) survives the normally bacteriocidal phagosome of macrophages. Mtb and related species may be able to combat this harsh acidic environment which contains reactive oxygen species due to the mycobacterial genomes encoding a large number of dehydrogenases. Typically, dehydrogenase cofactor binding sites are open to solvent, which allows NAD/NADH exchange to support multiple turnover. Interestingly, mycobacterial short chain dehydrogenases/reductases (SDRs) within family TIGR03971 contain an insertion at the NAD binding site...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28120110/identification-of-m2-macrophages-in-anterior-pituitary-glands-of-normal-rats-and-rats-with-estrogen-induced-prolactinoma
#15
Ken Fujiwara, Megumi Yatabe, Alimuddin Tofrizal, Depicha Jindatip, Takashi Yashiro, Ryozo Nagai
Macrophages are present throughout the anterior pituitary gland. However, the features and function of macrophages in the gland are poorly understood. Recent studies have indicated that there are two main macrophage classes: M1 (classically activated) and M2 (alternatively activated). In this study, we examine whether both M1 and M2 macrophages are present in the anterior pituitary gland of rats. Our findings indicate that macrophages that are positive for CD68 (a pan-macrophage marker) were localized near capillaries in rat anterior pituitary gland...
January 24, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28112722/myeloperoxidase-targets-oxidative-host-attacks-to-salmonella-and-prevents-collateral-tissue-damage
#16
Nura Schürmann, Pascal Forrer, Olivier Casse, Jiagui Li, Boas Felmy, Anne-Valérie Burgener, Nikolaus Ehrenfeuchter, Wolf-Dietrich Hardt, Mike Recher, Christoph Hess, Astrid Tschan-Plessl, Nina Khanna, Dirk Bumann
Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0...
January 23, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28109303/uptake-of-dna-by-cancer-cells-without-a-transfection-reagent
#17
Yanping Kong, Xianbo Zhang, Yongliang Zhao, Yanfang Xue, Ye Zhang
BACKGROUND: Cancer cells exhibit elevated levels of glucose uptake and may obtain pre-formed, diet-derived fatty acids from the bloodstream to boost their rapid growth; they may also use nucleic acid from their microenvironment. The study of processing nucleic acid by cancer cells will help improve the understanding of the metabolism of cancer. DNA is commonly packaged into a viral or lipid particle to be transferred into cells; this process is called transfection in laboratory. Cancer cells are known for having gene mutations and the evolving ability of endocytosis...
January 21, 2017: Biological Research
https://www.readbyqxmd.com/read/28096301/phosphoinositol-3-phosphate-acts-as-a-timer-for-reactive-oxygen-species-production-in-the-phagosome
#18
Zhi Min Song, Leïla Bouchab, Elodie Hudik, Romain Le Bars, Oliver Nüsse, Sophie Dupré-Crochet
Production of reactive oxygen species (ROS) in the phagosome by the NADPH oxidase is critical for mammalian immune defense against microbial infections and phosphoinositides are important regulators in this process. Phosphoinositol 3-phosphate (PI(3)P) regulates ROS production at the phagosome via p40(phox) by an unknown mechanism. This study tested the hypothesis that PI(3)P controls ROS production by regulating the presence of p40(phox) and p67(phox) at the phagosomal membrane. Pharmacologic inhibition of PI(3)P synthesis at the phagosome decreased the ROS production both in differentiated PLB-985 cells and human neutrophils...
January 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28095608/esx-1-and-phthiocerol-dimycocerosates-of-mycobacterium-tuberculosis-act-in-concert-to-cause-phagosomal-rupture-and-host-cell-apoptosis
#19
Jacques Augenstreich, Ainhoa Arbues, Roxane Simeone, Evert Haanappel, Alice Wegener, Fadel Sayes, Fabien Le Chevalier, Christian Chalut, Wladimir Malaga, Christophe Guilhot, Roland Brosch, Catherine Astarie-Dequeker
Although phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. Localized in the outer membrane of mycobacterial pathogens, DIM are predicted to interact with host cell membranes. Interaction with eukaryotic membranes is a property shared with another virulence factor of Mtb, the early secretory antigenic target EsxA (also known as ESAT-6). This small protein, which is secreted by the type VII secretion system ESX-1 (T7SS/ESX-1), is involved in phagosomal rupture and cell death induced by virulent mycobacteria inside host phagocytes...
January 17, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28095485/bordetella-parapertussis-circumvents-neutrophil-extracellular-bactericidal-mechanisms
#20
Juan Gorgojo, Emilia Scharrig, Ricardo M Gómez, Eric T Harvill, Maria Eugenia Rodríguez
B. parapertussis is a whooping cough etiological agent with the ability to evade the immune response induced by pertussis vaccines. We previously demonstrated that in the absence of opsonic antibodies B. parapertussis hampers phagocytosis by neutrophils and macrophages and, when phagocytosed, blocks intracellular killing by interfering with phagolysosomal fusion. But neutrophils can kill and/or immobilize extracellular bacteria through non-phagocytic mechanisms such as degranulation and neutrophil extracellular traps (NETs)...
2017: PloS One
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