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Jeremiah J. Faith Jean-Frédéric Colombel Jeffrey I. Gordon 《Proceedings of the National Academy of Sciences of the United States of America》2015,112(3):633-640
It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA genes could be used to distinguish the three domains of life on Earth. During the past decade, 16S rDNA sequencing has enabled the now frequent enumeration of bacterial communities that populate the bodies of humans representing different ages, cultural traditions, and health states. A challenge going forward is to quantify the contributions of community members to wellness, disease risk, and disease pathogenesis. Here, we explore a theoretical framework for studies of the inheritance of bacterial strains and discuss the advantages and disadvantages of various study designs for assessing the contribution of strains to complex diseases. 相似文献
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Jerry R. Paugh Alba Alfonso-Garcia Andrew Loc Nguyen Jeffrey L. Suhalim Marjan Farid Sumit Garg Jeremiah Tao Donald J. Brown Eric O. Potma James V. Jester 《The ocular surface》2019,17(1):151-159
Purpose
This study examined whether hyperspectral stimulated Raman scattering (hsSRS) microscopy can detect differences in meibum lipid to protein composition of normal and evaporative dry eye subjects with meibomian gland dysfunction.Methods
Subjects were evaluated for tear breakup time (TBUT), staining, meibum expression and gland dropout. Expressed meibum was analyzed using SRS vibrational signatures in the CH stretching region (2800–3050?cm?1). Vertex component analysis and K-means clustering were used to group the spectral signatures into four fractions containing high lipid (G1) to high protein (G4).Results
Thirty-three subjects could be statistically analyzed using pooled meibum (13 with stable tear films (TBUTs?>?10?s) and 20 with unstable tear films (TBUTs?≤?10?s). Significant differences in meibum from subjects with unstable vs. stable TBUTs were found for the G1 fraction (medians 0.164 and 0.020, respectively; p?=?0.012) and the G2 fraction (medians 0.244 and 0.272, respectively; p?=?0.045). No differences were observed for the G3 and G4 fractions. Single orifice samples were not significantly different vs. pooled samples from the fellow eye, and eyelid sector samples (nasal, central and temporal) G2:G3 fractional components were not significantly different (p?=?0.449). Spearman analysis suggested a significant inverse correlation between G1 fraction and TBUT (R?=??0.351; p?=?0.045).Conclusions
hsSRS microscopy allows compositional analysis of expressed meibum from humans which correlated to changes in TBUT. These findings support the hypothesis that hsSRS may be useful in classifying meibum quality and evaluating the effects of therapy. 相似文献4.
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Luke Witherspoon Sean O'Reilly Jeremiah Hadwen Nafisa Tasnim Alex MacKenzie Faraz Farooq 《CTS Clinical and Translational Science》2015,8(4):298-304
Myotonic dystrophy type 1 (DM1) is caused by an expanded trinucleotide (CTG)n tract in the 3′ untranslated region (UTR) of the dystrophia myotonica protein kinase (DMPK) gene. This results in the aggregation of an expanded mRNA forming toxic intranuclear foci which sequester splicing factors. We believe down‐regulation of DMPK mRNA represents a potential, and as yet unexplored, DM1 therapeutic avenue. Consequently, a computational screen for agents which down‐regulate DMPK mRNA was undertaken, unexpectedly identifying the sodium channel blockers mexiletine, prilocaine, procainamide, and sparteine as effective suppressors of DMPK mRNA. Analysis of DMPK mRNA in C2C12 myoblasts following treatment with these agents revealed a reduction in the mRNA levels. In vivo analysis of CD1 mice also showed DMPK mRNA and protein down‐regulation. The role of DMPK mRNA suppression in the documented efficacy of this class of compounds in DM1 is worthy of further investigation. 相似文献
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Draper JM Xia Z Smith RA Zhuang Y Wang W Smith CD 《Molecular cancer therapeutics》2011,10(11):2052-2061
The ceramide/sphingosine-1-phosphate (S1P) rheostat has been hypothesized to play a critical role in regulating tumor cell fate, with elevated levels of ceramide inducing death and elevated levels of S1P leading to survival and proliferation. Ceramidases are key enzymes that control this rheostat by hydrolyzing ceramide to produce sphingosine and may also confer resistance to drugs and radiation. Therefore, ceramidase inhibitors have excellent potential for development as new anticancer drugs. In this study, we identify a novel ceramidase inhibitor (Ceranib-1) by screening a small molecule library and describe the synthesis of a more potent analogue (Ceranib-2). In a cell-based assay, both compounds were found to inhibit cellular ceramidase activity toward an exogenous ceramide analogue, induce the accumulation of multiple ceramide species, decrease levels of sphingosine and S1P, inhibit the proliferation of cells alone and in combination with paclitaxel, and induce cell-cycle arrest and cell death. In vivo, Ceranib-2 was found to delay tumor growth in a syngeneic tumor model without hematologic suppression or overt signs of toxicity. These data support the selection of ceramidases as suitable targets for anticancer drug development and provide the first nonlipid inhibitors of human ceramidase activity. 相似文献
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Adam N. Wallace Clifford G. Robinson Jeffrey Meyer Nam D. Tran Afshin Gangi Matthew R. Callstrom Samuel T. Chao Brian A. Van Tine Jonathan M. Morris Brian M. Bruel Jeremiah Long Robert D. Timmerman Jacob M. Buchowski Jack W. Jennings 《The oncologist》2015,20(10):1205-1215
The Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied.