13,719 research outputs found
Triggering of human monocyte activation through CD69, a member of the natural killer cell gene complex family of signal transducing receptors
No full textMitomiRs in human inflamm-aging: A hypothesis involving miR-181a, miR-34a and miR-146a
No full textMitochondria are intimately involved in the aging process. The decline of autophagic clearance during aging affects the equilibrium between mitochondrial fusion and fission, leading to a build-up of dysfunctional mitochondria, oxidative stress, chronic low-grade inflammation, and increased apoptosis rates, the main hallmarks of aging. Current research suggests that a large number of microRNAs (miRs or miRNAs) are differentially expressed during cell aging. Other lines of evidence indicate that several miRs likely share in "inflamm-aging", an aging-related state characterized by systemic chronic inflammation that in turn provides a biological background favoring susceptibility to age-related diseases and disabilities. Interestingly, miRs can modulate mitochondrial activity, and a discrete miR set has recently been identified in mitochondria of different species and cell types (mitomiRs). Here we show that some mitomiRs (let7b, mir-146a, -133b, -106a, -19b, -20a, -34a, -181a and -221) are also among the miRs primarily involved in cell aging and in inflamm-aging. Of note, Ingenuity Pathway Analysis (IPA) of aging-related mitomiR targets has disclosed a number of resident mitochondrial proteins playing large roles in energy metabolism, mitochondrial transport and apoptosis. Among these, Bcl-2 family members - which are critically involved in maintaining mitochondrial integrity - may play a role in controlling mitochondrial function and dysfunction during cellular aging, also considering that Bcl-2, the master member of the family, is an anti-oxidant and anti-apoptotic factor and regulates mitochondrial fission/fusion and autophagy. This intriguing hypothesis is supported by several observations: i) in endothelial cells undergoing replicative senescence (HUVECs), a well-established model of cell senescence, miR-146a, miR-34a, and miR-181a are over-expressed whereas their target Bcl-2 is down-regulated; ii) IPA of the miR-146a, miR-34a and miR-181a network shows that they are closely linked to each other, to Bcl-2 and to mitochondria; and iii) miR-146a, miR-34a, and miR-181a are involved in important cell functions (growth, proliferation, death, survival, maintenance) and age-related diseases (cancer, skeletal and muscle disorders, neurological, cardiovascular and metabolic diseases). In conclusion several aging-related mitomiRs may play a direct role in controlling mitochondrial function by regulating mitochondrial protein expression. Their modulation could thus mediate the loss of mitochondrial integrity and function in aging cells, inducing or contributing to the inflammatory response and to age-related diseases
Triggering of human monocyte activation through CD69, a member of the natural killer cell gene complex family of signal transducing receptors.
No full textThe expression and function of CD69, a member of the natural killer cell gene complex family of signal transducing receptors, was investigated on human monocytes. CD69 was found expressed on all peripheral blood monocytes, as a 28- and 32-kD disulfide-linked dimer. Molecular crosslinking of CD69 receptors induced extracellular Ca2+ influx, as revealed by flow cytometry. CD69 cross-linking resulted also in phospholipase A2 activation, as detected by in vivo arachidonic acid release measurement from intact cells and by direct in vitro measurement of enzymatic activity using radiolabeled phosphatidylcholine vesicles. Prostaglandin E 2 alpha, 6-keto-prostaglandin F 1 alpha, and leukotriene B-4 were detected by radioimmunoassay in supernatants from CD69-stimulated monocytes, suggesting the activation of both cyclooxygenase and lipoxygenase pathways after CD69 stimulation. CD69 cross-linking, moreover, was able to induce strong nitric oxide (NO) production from monocytes, as detected by accumulation of NO oxydixed derivatives, and cyclic GMP. It is important to note that NO generation was responsible for CD69-mediated increase in spontaneous cytotoxicity against L929 murine transformed fibroblast cell line and induction of redirected cytotoxicity towards P815 FcRII(+) murine mastocytoma cell line. These data indicate that CD69 can act as a potent stimulatory molecule on the surface of human peripheral blood monocytes
Mr. Melvin J. Collier, RWWL AUC, June 2011
No full textThis video is a conversation with Mr. Melvin J. Collier. Mr. Collier talks about his book, "From Mississippi to Africa: A Journey of Discovery". Daniel Le, AUC Woodruff Library, is the interviewer
Attenuation of Listeria monocytogenes Virulence by Cannabis sativa L. Essential Oil
No full textAnti-virulence strategies are being explored as a novel approach to combat pathogens. Such strategies include inhibition of surface adhesion, tissue invasion, toxin production, and/or interference with the gene regulation of other virulence traits. Listeria monocytogenes, the causative agent of listeriosis, is a facultative intracellular food pathogen characterized by a wide distribution in the environment. Its ability to persist within biofilms and to develop resistance to sanitizers is the cause of significant problems in food processing plants and of steep costs for the food industry. In humans, the treatment of listeriosis is hampered by the intracellular location of listeriae and the poor intracellular penetration of some antibiotics. Eleven L. monocytogenes isolates from patients who were diagnosed with invasive listeriosis in Italy in 2014–2016 were studied. This in vitro and in vivo study explored the antibacterial and anti-virulence properties of a steam-distilled essential oil of Cannabis sativa L., which is being intensively investigated for its high content in powerful bioactive phytochemicals. Susceptibility experiments demonstrated a moderate bactericidal activity of the essential oil (Minimum Bactericidal Concentration > 2048 μg/mL). Assessment of the effects of sublethal concentrations of the essential oil on L. monocytogenes virulence traits demonstrated a significant action on motility. Listeriae were non-motile after exposure to the essential oil. Light and scanning electron microscopy documented aggregates of listeriae with the flagella trapped inside the cluster. Real-time RT-PCR experiments showed downregulation of flagellar motility genes and of the regulatory gene prfA. The ability to form biofilm and to invade Caco-2 cells was also significantly reduced. Galleria mellonella larvae infected with L. monocytogenes grown in presence of sublethal concentrations of the essential oil showed much higher survival rates compared with controls, suggesting that the extract inhibited tissue invasion. Food contamination with L. monocytogenes is a major concern for the food industry, particularly for plants making ready-to-eat and processed food. The present work provides a baseline in the study of the anti-virulence properties of the C. sativa essential oil against L. monocytogenes. Further studies are needed to understand if it could be used as an alternative agent for the control of L. monocytogenes in food processing plants
From Oxidative Stress Damage to Pathways, Networks, and Autophagy via MicroRNAs.
No full textOxidative stress can alter the expression level of many microRNAs (miRNAs), but how these changes are integrated and related to oxidative stress responses is poorly understood. In this article, we addressed this question by using in silico tools. We reviewed the literature for miRNAs whose expression is altered upon oxidative stress damage and used them in combination with various databases and software to predict common gene targets of oxidative stress-modulated miRNAs and affected pathways. Furthermore, we identified miRNAs that simultaneously target the predicted oxidative stress-modulated miRNA gene targets. This generated a list of novel candidate miRNAs potentially involved in oxidative stress responses. By literature search and grouping of pathways and cellular responses, we could classify these candidate miRNAs and their targets into a larger scheme related to oxidative stress responses. To further exemplify the potential of our approach in free radical research, we used our explorative tools in combination with ingenuity pathway analysis to successfully identify new candidate miRNAs involved in the ubiquitination process, a master regulator of cellular responses to oxidative stress and proteostasis. Lastly, we demonstrate that our approach may also be useful to identify novel candidate connections between oxidative stress-related miRNAs and autophagy. In summary, our results indicate novel and important aspects with regard to the integrated biological roles of oxidative stress-modulated miRNAs and demonstrate how this type of in silico approach can be useful as a starting point to generate hypotheses and guide further research on the interrelation between miRNA-based gene regulation, oxidative stress signaling pathways, and autophagy
Interview Excerpt of Mr. Donald M. Crawford, Sr.
No full text(1948-2018) Donald Mitchell Crawford, Sr. (“DC”), musician, author, and educator, was born on May 24, 1948, and was a lifelong resident of Birmingham, AL. His father and mother owned and operated “C & S Charter Tours Bus Company,” the first black-owned bus company in the state of Alabama. Crawford was a 1966 graduate of Western Olin High School in Birmingham, AL. Crawford was an outstanding drum major, playing first chair alto saxophone under the tutelage of the late Amos F. Gordon, Sr. After high school, he received a music scholarship to Alabama State University (ASU) where he earned both his Bachelor’s and Master’s Degrees in Music Education and was later inducted into the “School of Music Hall of Fame” at ASU. He was the youngest ever inducted into the Alabama Jazz Hall of Fame. He was a veteran of the U.S. Army and performed with the 291 st and 283rd Army Band in Fort Bennett, GA. DC was Band Director at Jackson Olin High School and taught in the Birmingham School System for over thirty-five years. His love for music and performing lead him after his retirement to serve as Band Director for Miles College.
Crawford is the author of “The Wheels of the Birmingham Civil Rights Movement.” This book chronicles the lives of his late father and mother, Worcy and Christine Pride Crawford, and the role he and the company played in the Birmingham Civil Rights Movement
APOPTOTIC SIGNALING THROUGH CD95 (FAS/APO-1) ACTIVATES AN ACIDIC SPHINGOMYELINASE
No full textAbstract: Intracellular pathways leading from membrane receptor engagement to apoptotic cell death are still poorly characterized. We investigated the intracellular signaling generated after cross-linking of CD95 (Fas/Apo-1 antigen), a broadly expressed cell surface receptor whose engagement results in triggering of cellular apoptotic programs. DX2, a new functional anti-CD95 monoclonal antibody was produced by immunizing mice with human CD95-transfected L cells. Crosslinking of CD95 with DX2 resulted in the activation of a sphingomyelinase (SMase) in promyelocytic U937 cells, as well as in other human tumor cell lines and in CD95-transfected murine cells, as demonstrated by induction of in vivo sphingomyelin (SM) hydrolysis and generation of ceramide. Direct in vitro measurement of enzymatic activity within CD95-stimulated U937 cell extracts, using labeled SM vesicles as substrates, showed strong SMase activity, which required pH 5.0 for optimal substrate hydrolysis. Finally, all CD95-sensitive cell lines tested could be induced to undergo apoptosis after exposure to cell-permeant C-2-ceramide. These data indicate that CD95 cross-linking induces SM breakdown and ceramide production through an acidic SMase, thus providing the first information regarding early signal generation from CD95, and may be relevant in defining the biochemical nature of intracellular messengers leading to apoptotic cell death
Decitabine, differently from DNMT1 silencing, exert its antiproliferative activity through p21 upregulation in Malignant Pleural Mesothelioma (MPM) cells.
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