Medicine and Health Sciences Commons^™

Coordinated Changes In Mrna Turnover, Translation, And Rna Processing Bodies In Bronchial Epithelial Cells Following Inflammatory Stimulation, Yuxin Zhai, Zhenping Zhong, Chyi-Ying A Chen, Zhenfang Xia, Ling Song, Michael R Blackburn, Ann-Bin Shyu

Journal Articles

Bronchial epithelial cells play a pivotal role in airway inflammation, but little is known about posttranscriptional regulation of mediator gene expression during the inflammatory response in these cells. Here, we show that activation of human bronchial epithelial BEAS-2B cells by proinflammatory cytokines interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) leads to an increase in the mRNA stability of the key chemokines monocyte chemotactic protein 1 and IL-8, an elevation of the global translation rate, an increase in the levels of several proteins critical for translation, and a reduction of microRNA-mediated translational repression. Moreover, using the BEAS-2B cell system and …

Increased Myocardial Susceptibility To Repetitive Ischemia With High-Fat Diet-Induced Obesity, Geeta D Thakker, Nikolaos G Frangogiannis, Pawel T Zymek, Saumya Sharma, Joe L Raya, Philip M Barger, Heinrich Taegtmeyer, Mark L Entman, Christie M Ballantyne

Journal Articles

Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol …

Poly(A)-Binding Protein-Interacting Protein 1 Binds To Eukaryotic Translation Initiation Factor 3 To Stimulate Translation, Yvan Martineau, Mélanie C Derry, Xiaoshan Wang, Akiko Yanagiya, Juan José Berlanga, Ann-Bin Shyu, Hiroaki Imataka, Kalle Gehring, Nahum Sonenberg

Journal Articles

Poly(A)-binding protein (PABP) stimulates translation initiation by binding simultaneously to the mRNA poly(A) tail and eukaryotic translation initiation factor 4G (eIF4G). PABP activity is regulated by PABP-interacting (Paip) proteins. Paip1 binds PABP and stimulates translation by an unknown mechanism. Here, we describe the interaction between Paip1 and eIF3, which is direct, RNA independent, and mediated via the eIF3g (p44) subunit. Stimulation of translation by Paip1 in vivo was decreased upon deletion of the N-terminal sequence containing the eIF3-binding domain and upon silencing of PABP or several eIF3 subunits. We also show the formation of ternary complexes composed of Paip1-PABP-eIF4G and …

Characterization Of The Inflammatory Cells In Ascending Thoracic Aortic Aneurysms In Patients With Marfan Syndrome, Familial Thoracic Aortic Aneurysms, And Sporadic Aneurysms, Rumin He, Dong-Chuan Guo, Wei Sun, Christina L Papke, Senthil Duraisamy, Anthony L Estrera, Hazim J Safi, Chul Ahn, L Maximilian Buja, Frank C Arnett, Jingwu Zhang, Yong-Jian Geng, Dianna M Milewicz

Journal Articles

OBJECTIVE: This study sought to characterize the inflammatory infiltrate in ascending thoracic aortic aneurysm in patients with Marfan syndrome, familial thoracic aortic aneurysm, or nonfamilial thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysms are associated with a pathologic lesion termed "medial degeneration," which is described as a noninflammatory lesion. Thoracic aortic aneurysms are a complication of Marfan syndrome and can be inherited in an autosomal dominant manner of familial thoracic aortic aneurysm.

METHODS: Full aortic segments were collected from patients undergoing elective repair with Marfan syndrome (n = 5), familial thoracic aortic aneurysm (n = 6), and thoracic aortic aneurysms (n …

Identification And Phenotypic Characterization Of A Second Collagen Adhesin, Scm, And Genome-Based Identification And Analysis Of 13 Other Predicted Mscramms, Including Four Distinct Pilus Loci, In Enterococcus Faecium, Jouko Sillanpää, Sreedhar R Nallapareddy, Vittal P Prakash, Xiang Qin, Magnus Höök, George M Weinstock, Barbara E Murray

Journal Articles

Attention has recently been drawn to Enterococcus faecium because of an increasing number of nosocomial infections caused by this species and its resistance to multiple antibacterial agents. However, relatively little is known about the pathogenic determinants of this organism. We have previously identified a cell-wall-anchored collagen adhesin, Acm, produced by some isolates of E. faecium, and a secreted antigen, SagA, exhibiting broad-spectrum binding to extracellular matrix proteins. Here, we analysed the draft genome of strain TX0016 for potential microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). Genome-based bioinformatics identified 22 predicted cell-wall-anchored E. faecium surface proteins (Fms), of which 15 …

388 A Structure Of Cytoplasmic Polyhedrosis Virus By Cryo-Electron Microscopy, Xuekui Yu, Lei Jin, Z Hong Zhou

Journal Articles

Cytoplasmic polyhedrosis virus (CPV) is unique within the Reoviridae family in having a turreted single-layer capsid contained within polyhedrin inclusion bodies, yet being fully capable of cell entry and endogenous RNA transcription. Biochemical data have shown that the amino-terminal 79 residues of the CPV turret protein (TP) is sufficient to bring CPV or engineered proteins into the polyhedrin matrix for micro-encapsulation. Here we report the three-dimensional structure of CPV at 3.88 A resolution using single-particle cryo-electron microscopy. Our map clearly shows the turns and deep grooves of alpha-helices, the strand separation in beta-sheets, and densities for loops and many bulky …

Clinical And Microbiological Aspects Of Linezolid Resistance Mediated By The Cfr Gene Encoding A 23s Rrna Methyltransferase, Cesar A Arias, Martha Vallejo, Jinnethe Reyes, Diana Panesso, Jaime Moreno, Elizabeth Castañeda, Maria V Villegas, Barbara E Murray, John P Quinn

Journal Articles

The cfr (chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first cfr-carrying human hospital isolate of linezolid and methicillin-resistant Staphylococcus aureus (designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of cfr was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the cfr gene. In addition to erm(B), …

Application Of In Vivo Induced Antigen Technology (Iviat) To Bacillus Anthracis, Sean M Rollins, Amanda Peppercorn, John S Young, Melissa Drysdale, Andrea Baresch, Margaret V Bikowski, David A Ashford, Conrad P Quinn, Martin Handfield, Jeffrey D Hillman, C Rick Lyons, Theresa M Koehler, Stephen B Calderwood, Edward T Ryan

Journal Articles

In vivo induced antigen technology (IVIAT) is an immuno-screening technique that identifies bacterial antigens expressed during infection and not during standard in vitro culturing conditions. We applied IVIAT to Bacillus anthracis and identified PagA, seven members of a N-acetylmuramoyl-L-alanine amidase autolysin family, three P60 family lipoproteins, two transporters, spore cortex lytic protein SleB, a penicillin binding protein, a putative prophage holin, respiratory nitrate reductase NarG, and three proteins of unknown function. Using quantitative real-time PCR comparing RNA isolated from in vitro cultured B. anthracis to RNA isolated from BALB/c mice infected with virulent Ames strain B. anthracis, we confirmed induced …

Messenger Rna Half-Life Measurements In Mammalian Cells, Chyi-Ying A Chen, Nader Ezzeddine, Ann-Bin Shyu

Journal Articles

The recognition of the importance of mRNA turnover in regulating eukaryotic gene expression has mandated the development of reliable, rigorous, and "user-friendly" methods to accurately measure changes in mRNA stability in mammalian cells. Frequently, mRNA stability is studied indirectly by analyzing the steady-state level of mRNA in the cytoplasm; in this case, changes in mRNA abundance are assumed to reflect only mRNA degradation, an assumption that is not always correct. Although direct measurements of mRNA decay rate can be performed with kinetic labeling techniques and transcriptional inhibitors, these techniques often introduce significant changes in cell physiology. Furthermore, many critical mechanistic …