Summary The androgen receptor (AR) is required for castration resistant prostate cancer (CRPC) progression, but the function and disease relevance of AR-bound enhancers remain unclear. Here, we identify a group of AR-regulated enhancer RNAs (e.g. PSA eRNA) that are upregulated in CRPC cells, patient-derived xenografts (PDX) and patient tissues. PSA eRNA binds to CYCLIN T1, activates P-TEFb and promotes cis and trans target gene transcription by increasing serine-2 phosphorylation of RNA polymerase II (Pol II-Ser2p). We define an HIV-1 TAR RNA-like (TAR-L) motif in PSA eRNA that is required for CYCLIN T1 binding. Using TALEN-mediated gene editing we further demonstrate that this motif is essential for increased Pol II-Ser2p occupancy levels and CRPC cell growth. We have uncovered a P-TEFb activation mechanism and reveal altered eRNA expression that is related to abnormal AR function and may potentially be a therapeutic target in CRPC.
The cell envelope of a marine pseudomonad as seen in thin section by electron microscopy has the double-membrane structure typical of other gram-negative bacteria. Cells washed with a solution containing Na+, K+, and Mg++ at their concentrations in the growth medium, when suspended briefly in 0.5 M sucrose, lost 13% of their hexosamine in a form nonsedimentable by centrifugation at 73,000 x g. Since the resulting cells in thin section appeared unchanged, it was concluded that the material released was derived from a nonstaining, loosely bound outer layer. This same layer could be removed from the cells by washing with 0.5 M NaCI. A second nonsedimentable fraction was released after successive suspension of the cells in 0.5 M sucrose. Since this material was released only when the outer doubletrack structure had broken, it was concluded that it arose from a layer immediately underlying the latter layer. The three layers differed in their content of hexosamine and protein. None of the layers released contained muramic or diaminopimelic acid. The cell form remaining was rod shaped and appeared in thin section to be bounded only by its cytoplasmic membrane. This form contained all the muramic and diaminopimelic acid in the cell. Treatment with lysozyme released the muramic and diaminopimelic acid and converted the rod form to a protoplast, indicating that in the rod form (mureinoplast) a thin layer of peptidoglycan is located on the outside surface of the cytoplasmic membrane. Thus, five separate layers have been detected in the cell envelope of this marine pseudomonad.
Issued as Macdonald College Journal Series Number 520. 9 transformations of matter, would have very little point (76). Most of the experiments undertaken in attempting to settle the question have dealt with the temperature range and halophilic nature of bacteria from the sea. Marine bacteria were found to be generally more psychrophilic in character than terrestrial species and to prefer seawater or 3 7% NaCl to freshwater in the medium for growth. Evidence was presented, however, to indicate that these physiological properties were unstable. Baars (2), for instance, reported success in interconverting, by training procedures, three varieties of sulfate-reducing bacteria which, on the basis of temperature range, salt range, and habitat, had been regarded as separate species. ZoBell and Rittenberg (92) found that chitinoclastic bacteria from the sea, after prolonged laboratory cultivation or acclimatization procedures, developed the ability to grow in freshwater media. This change was accompanied by a widening of the temperature range for growth. Reports on the stability of the halophilic character of marine bacteria have been particularly
Analysis of the number of citations within a given specialty provides information on the classic publications of that specialty. The goals of this study were to identify the 50 most cited articles on rotator cuff repair and to analyze various characteristics of these articles. The ISI Web of Science (Thomson Reuters, Philadelphia, Pennsylvania) was used to conduct a search for the term rotator cuff repair. The 50 most cited articles were retrieved, and the following objective characteristics of each article were recorded: number of times cited, citation density, journal, country of origin, and language. The following subjective characteristics of each article were also recorded: article type (clinical vs basic science), article subtype, and level of evidence for clinical articles. Of the 50 most cited articles on rotator cuff repair, the number of citations ranged from 138 to 677 (mean, 232±133 citations) and citation density ranged from 3.8 to 53.5 citations per year (mean, 16.9±9.2 citations per year). The articles were published between 1974 and 2011, with most of the articles published in the 2000s (29 articles), followed by the 1990s (16 articles). The articles originated from 8 countries, with the United States accounting for 30 articles (60%). Overall, 66% of the articles were clinical and 34% were basic science. The most common article subtype was the clinical case series (48%). Of the 33 clinical articles, 24 (73%) were level IV. Among the 50 most cited articles on rotator cuff repair, the case series was the most common article subtype, showing the effect that publication of preliminary outcomes and new surgical techniques has had on surgeons performing rotator cuff repair. [Orthopedics. 2016; 39(6):e1045-e1051.].
When cells of a marine pseudomonad were washed and suspended in 0.5 M sucrose, they retained their rod shape, but thin sections, when examined in an electron microscope, revealed that the outer layer of the cell wall had separated a considerable distance from the cytoplasmic membrane. Treatment of such cells with lysozyme alone produced no obvious change, but treatment with ethylenediaminetetraacetic acid (EDTA) alone caused the outer wall to disappear. A combination of EDTA and lysozyme resulted in the rapid formation of spheres essentially free from hexosamine and indistinguishable from protoplasts of gram-positive bacteria. When cells were washed with 0.5 M NaCl and then suspended in 0.5 m sucrose, they also retained their rod shape, but in this case the outer layer separated from the cells completely and could be recovered from the suspending medium. Such cells were converted to protoplasts by the action of lysozyme alone. Cells washed and finally suspended in 0.5 M NaCl, when treated with EDTA and lysozyme, slowly became spherical. Thin sections revealed typical spheroplasts of gram-negative bacteria in which the outer wall remained intact. Protoplasts took up a-aminoisobutyric acid by a Na+-dependent process. When certain species of gram-positive bacteria are treated with lysozyme, the entire outer wall of the cell is removed and the resulting osmotically sensitive structure is bounded only by its cytoplasmic membrane. Such a structure is referred to as a protoplast (3). Gram-negative bacteria are more resistant to the action of lysozyme and are converted to osmotically sensitive forms by this enzyme only if auxiliary agents or procedures are employed. The latter include heat treatment of the cells (L. E. Myerholtz and S. E. Hartsell, Bacteriol. Proc., p. 34, 1952), freezing and thawing (Ii), the addition of ethylenediaminetetraacetic acid (EDTA) in tris(hydroxymethyl)aminomethane (Tris) buffer (17), and plasmolysis (2). Such auxiliary treatments appear to increase the penetrability of the outer layers of the cell wall, permitting lysozyme to reach andattack the underlying mucopeptide 1 lssued as Macdonald College Journal Series No.
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