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Author Gajer, P.; Brotman, R.M.; Bai, G.; Sakamoto, J.; Schutte, U.M.E.; Zhong, X.; Koenig, S.S.K.; Fu, L.; Ma, Z.S.; Zhou, X.; Abdo, Z.; Forney, L.J.; Ravel, J. file  url
Title Temporal dynamics of the human vaginal microbiota Type Journal Article
Year 2012 Publication Science Translational Medicine Abbreviated Journal Sci Transl Med  
Volume 4 Issue 132 Pages 132ra52  
Keywords Bacteria/classification/genetics; Female; Humans; Magnetic Resonance Spectroscopy; Metabolome; Metabolomics; Metagenome/genetics/*physiology; Models, Biological; Phylogeny; Time Factors; Vagina/*microbiology; Microbiome  
Abstract Elucidating the factors that impinge on the stability of bacterial communities in the vagina may help in predicting the risk of diseases that affect women's health. Here, we describe the temporal dynamics of the composition of vaginal bacterial communities in 32 reproductive-age women over a 16-week period. The analysis revealed the dynamics of five major classes of bacterial communities and showed that some communities change markedly over short time periods, whereas others are relatively stable. Modeling community stability using new quantitative measures indicates that deviation from stability correlates with time in the menstrual cycle, bacterial community composition, and sexual activity. The women studied are healthy; thus, it appears that neither variation in community composition per se nor higher levels of observed diversity (co-dominance) are necessarily indicative of dysbiosis.  
Call Number Serial 2175  
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Author Xu, W.; Chi, L.; Xu, R.; Ke, Y.; Luo, C.; Cai, J.; Qiu, M.; Gozal, D.; Liu, R. file  url
Title Increased production of reactive oxygen species contributes to motor neuron death in a compression mouse model of spinal cord injury Type Journal Article
Year 2005 Publication Spinal Cord Abbreviated Journal Spinal Cord  
Volume 43 Issue 4 Pages 204-213  
Keywords Animals; Apoptosis/physiology; Blotting, Western/methods; Caspase 3; Caspases/metabolism; Cell Count/methods; Cytochromes c/metabolism; DNA, Single-Stranded/metabolism; Disease Models, Animal; Female; Guanine/*analogs & derivatives/metabolism; Immunohistochemistry/methods; In Situ Nick-End Labeling/methods; Lac Operon/physiology; Lipid Peroxidation/physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Molecular; Motor Neurons/*pathology; NF-kappa B/genetics; Peroxidases; Proto-Oncogene Proteins c-fos/metabolism; Reactive Oxygen Species/*metabolism; Spinal Cord Injuries/genetics/*metabolism/*pathology/physiopathology; Staining and Labeling/methods; Superoxide Dismutase/genetics; Superoxide Dismutase-1; Time Factors  
Abstract STUDY DESIGN: Experimental laboratory investigation of the role and pathways of reactive oxygen species (ROS)-mediated motor neuron cell death in a mouse model of compression spinal cord injury. OBJECTIVES: To analyze ROS-mediated oxidative stress propagation and signal transduction leading to motor neuron apoptosis induced by compression spinal cord injury. SETTING: University of Louisville Health Science Center. METHODS: Adult C57BL/6J mice and transgenic mice overexpressing SOD1 were severely lesioned at the lumbar region by compression spinal cord injury approach. Fluorescent oxidation, oxidative response gene expression and oxidative stress damage markers were used to assay spinal cord injury-mediated ROS generation and oxidative stress propagation. Biochemical and immunohistochemical analyses were applied to define the ROS-mediated motor neuron apoptosis resulted from compression spinal cord injury. RESULTS: ROS production was shown to be elevated in the lesioned spinal cord as detected by fluorescent oxidation assays. The early oxidative stress response markers, NF-kappaB transcriptional activation and c-Fos gene expression, were significantly increased after spinal cord injury. Lipid peroxidation and nucleic acid oxidation were also elevated in the lesioned spinal cord and motor neurons. Cytochrome c release, caspase-3 activation and apoptotic cell death were increased in the spinal cord motor neuron cells after spinal cord injury. On the other hand, transgenic mice overexpressing SOD1 showed lower levels of steady-state ROS production and reduction of motor neuron apoptosis compared to that of control mice after spinal cord injury. CONCLUSION: These data together provide direct evidence to demonstrate that the increased production of ROS is an early and likely causal event that contributes to the spinal cord motor neuron death following spinal cord injury. Thus, antioxidants/antioxidant enzyme intervention combined with other therapy may provide an effective approach to alleviate spinal cord injury-induced motor neuron damage and motor dysfunction.  
Call Number Serial 2145  
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Author Leach, L.; Samuel, A.G. file  url
Title Lexical configuration and lexical engagement: when adults learn new words Type Journal Article
Year 2007 Publication Cognitive Psychology Abbreviated Journal Cogn Psychol  
Volume 55 Issue 4 Pages 306-353  
Keywords Adult; Humans; Retention (Psychology); Semantics; Time Factors; *Verbal Learning; *Vocabulary  
Abstract People know thousands of words in their native language, and each of these words must be learned at some time in the person's lifetime. A large number of these words will be learned when the person is an adult, reflecting the fact that the mental lexicon is continuously changing. We explore how new words get added to the mental lexicon, and provide empirical support for a theoretical distinction between what we call lexical configuration and lexical engagement. Lexical configuration is the set of factual knowledge associated with a word (e.g., the word's sound, spelling, meaning, or syntactic role). Almost all previous research on word learning has focused on this aspect. However, it is also critical to understand the process by which a word becomes capable of lexical engagement--the ways in which a lexical entry dynamically interacts with other lexical entries, and with sublexical representations. For example, lexical entries compete with each other during word recognition (inhibition within the lexical level), and they also support the activation of their constituents (top-down lexical-phonemic facilitation, and lexically-based perceptual learning). We systematically vary the learning conditions for new words, and use separate measures of lexical configuration and engagement. Several surprising dissociations in behavior demonstrate the importance of the theoretical distinction between configuration and engagement.  
Call Number Serial 1967  
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Author Ling, L.L.; Schneider, T.; Peoples, A.J.; Spoering, A.L.; Engels, I.; Conlon, B.P.; Mueller, A.; Schaberle, T.F.; Hughes, D.E.; Epstein, S.; Jones, M.; Lazarides, L.; Steadman, V.A.; Cohen, D.R.; Felix, C.R.; Fetterman, K.A.; Millett, W.P.; Nitti, A.G.; Zullo, A.M.; Chen, C.; Lewis, K. file  url
Title A new antibiotic kills pathogens without detectable resistance Type Journal Article
Year 2015 Publication Nature Abbreviated Journal Nature  
Volume 517 Issue 7535 Pages 455-459  
Keywords Animals; Anti-Bacterial Agents/biosynthesis/chemistry/isolation & purification/*pharmacology; Betaproteobacteria/chemistry/genetics; Biological Products/chemistry/isolation & purification/pharmacology; Cell Wall/chemistry/drug effects/metabolism; Depsipeptides/biosynthesis/chemistry/isolation & purification/*pharmacology; Disease Models, Animal; *Drug Resistance, Microbial/genetics; Female; Mice; Microbial Sensitivity Tests; Microbial Viability/*drug effects; Molecular Sequence Data; Multigene Family/genetics; Mycobacterium tuberculosis/cytology/*drug effects/genetics; Peptidoglycan/biosynthesis; Staphylococcal Infections/drug therapy/microbiology; Staphylococcus aureus/chemistry/cytology/*drug effects/genetics; Teichoic Acids/biosynthesis; Time Factors  
Abstract Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.  
Call Number Serial 1893  
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Author Ito, H.; Wate, R.; Zhang, J.; Ohnishi, S.; Kaneko, S.; Ito, H.; Nakano, S.; Kusaka, H. file  url
Title Treatment with edaravone, initiated at symptom onset, slows motor decline and decreases SOD1 deposition in ALS mice Type Journal Article
Year 2008 Publication Experimental Neurology Abbreviated Journal Exp Neurol  
Volume 213 Issue 2 Pages 448-455  
Keywords Amyotrophic Lateral Sclerosis/*drug therapy/*enzymology; Animals; Antipyrine/administration & dosage/*analogs & derivatives; Female; Humans; Male; Mice; Mice, Transgenic; Motor Skills/*drug effects/*physiology; Motor Skills Disorders/drug therapy/enzymology; Superoxide Dismutase/genetics/*metabolism; Superoxide Dismutase-1; Time Factors  
Abstract Edaravone is a free-radical scavenger, an agent being widely used for cerebral ischemia in Japan. To evaluate its efficacy for possible treatment of amyotrophic lateral sclerosis (ALS), we performed a randomized blind trial in ALS model mice. After identification of the clinical onset in each female G93A mutant SOD1 transgenic mouse, we intraperitoneally administered multiple doses of edaravone to the mice and observed their motor symptoms. We also counted the number of lumbar motoneurons, determined the 3-nitrotyrosine/tyrosine ratio, and evaluated the abnormal SOD1 aggregation in the spinal cord at the 10th day after the edaravone injection. Edaravone significantly slowed the motor decline of the transgenic mice. The remaining motoneurons were significantly preserved in the higher-dose edaravone-administered group, and the 3-nitrotyrosine/tyrosine ratios were reduced dose-dependently. Intriguingly, the area of abnormal SOD1 deposition in the spinal cord was significantly decreased in the higher-dose edaravone-administered group. Our results indicate that edaravone was effective to slow symptom progression and motor neuron degeneration in the ALS model mice. These favorable actions might be attributable to the yet unidentified mechanism responsible for reducing the deposition of mutant SOD1.  
Call Number Serial 1838  
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