In the original version of the published article, Constantine Godellas was mistakenly omitted from the Author list and Author Contributions statement. Constantine Godellas has been added as the 29th ...Author, and is affiliated with Loyola University Medical Center, Maywood, IL, United States. The author contributions statement has been updated as follows: “Author Contributions Statement: Judy C. Boughey conducted the review of current protocols, led the effort to establish new I-SPY standards and was the principal author of the manuscript. Laura Esserman co-led the review and standardization processes. Michael D. Alvarado, Rachael B. Lancaster, Fraser Symmans, W, Rita Mukhtar, Jasmine Wong, Cheryl Ewing, David Potter, Todd Tuttle, Tina Hieken, Jodi Carter, James Jakub, Henry Kaplan, Claire Buchanan, Nora Jaskowiak, Husain Sattar, Jeffrey Mueller, Rita Nanda, Claudine Isaacs, Paula Pohlmann, Filipa Lynce, Eleni Tousimis, Jay Zeck, M. Catherine Lee, Julie Lang, Paulette Mhawech-Fauceglia, Roshni Rao, Bret Taback, Margaret Chen, Kevin Kalinsky, Hanina Hibshoosh, Brigid Killelea, Constantine Godellas, and Tara Sanft provided medical and scientific expertise/opinion towards the development of I-SPY standards. Jane Perlmutter provided the patient advocate’s perspective in these discussions. All I-SPY2 trial investigators participated in the review of current standards, had the opportunity to participate in and comment on proposed standards and the final manuscript. Gill Hirst and Smita Asare provided expertise on, conducted and analyzed surveys of I-SPY trial sites. Jeffrey B. Matthews provided significant input and editing throughout the manuscript development process. All authors reviewed manuscript drafts and signed off on the final manuscript. This has been corrected in the HTML and PDF version of the article.
Considerable evidence now exists to support an important role for the E-cadherin-mediated cell-cell adhesion pathway as a suppressor of the invasive phenotype in adenocarcinoma cells. Previous ...studies have found that this pathway is frequently aberrant in prostate cancers, particularly those that are likely to metastasize. In this study, we report on the effects of re-establishment of this pathway in a prostate cancer cell line, PC-3, in which this adhesion system is dysfunctional by virtue of a deletion of the gene that codes for alpha-catenin, an E-cadherin-associated protein necessary for normal E-cadherin function. Re-expression of alpha-catenin was accomplished either by transfection of PC-3 cells with a copy of the alpha-catenin cDNA under the control of a heterologous promoter or by microcell-mediated transfer of chromosome 5, which contains the alpha-catenin gene and its normal regulatory elements. In both cases, re-expression of alpha-catenin is associated with a similar, dramatic alteration in cell morphology, whereby extensive cell-cell contact is observed. In the case of transfection of the cDNA, this expression is only transient, because the transfected cells either cease to proliferate or, more commonly, revert to the parental phenotype with concomitant cessation of alpha-catenin expression. In contrast, cells containing one or more copies of microcell-transferred chromosome 5 express alpha-catenin in a stable manner and continue to proliferate. Upon injection into nude mice, these latter cells are no longer tumorigenic, or form only slowly growing tumors with greatly extended doubling times when compared to the parental PC-3 cells. During passage in culture, clones that contain only one transferred copy of chromosome 5 reproducibly revert to the parental phenotype. This reversion is associated with loss of the chromosome 5 region containing the alpha-catenin gene and consequent loss of alpha-catenin expression, as well as re-emergence of tumorigenicity. Transfer of chromosome 5 into prostate cancer cells that are E-cadherin negative does not result in either morphological transformation or suppression of tumorigenicity, suggesting that these effects of alpha-catenin expression are dependent upon concomitant expression of E-cadherin. These data demonstrate the tumor suppressive ability of chromosome 5 in the PC-3 prostate cancer cells and suggest that re-expression of alpha-catenin with resultant restoration of E-cadherin function plays a critical role in this process.
Warner and Ewing attempt to illuminate the struggle that women faced in achieving success as scientists while hampered not only by society's expectations of their behavior in mixed compnay but also ...by the physical constraints of confining dress. Sporting rubber hip boots and rain jackets, women scientists were often the subject of ridicule and disdain in the late 19th and early 20th centuries.
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Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Many of the skills and resources associated with botanic gardens and arboreta, including plant taxonomy, horticulture, and seed bank management, are fundamental to ecological restoration efforts, yet ...few of the world's botanic gardens are involved in the science or practice of restoration. Thus, we examined the potential role of botanic gardens in these emerging fields. We believe a reorientation of certain existing institutional strengths, such as plant-based research and knowledge transfer, would enable many more botanic gardens worldwide to provide effective science-based support to restoration efforts. We recommend botanic gardens widen research to include ecosystems as well as species, increase involvement in practical restoration projects and training practitioners, and serve as information hubs for data archiving and exchange.Original Abstract: Resumen:Muchas de las habilidades y recursos asociados con los jardines botanicos y viveros, incluyendo la taxonomia de plantas, la horticultura y el manejo de banco de semillas, son fundamentales para los esfuerzos de restauracion ecologica. Por lo tanto, examinamos el papel potencial de los jardines botanicos en estos campos emergentes. Consideramos que una reorientacion de ciertas potenciales institucionales existentes, como la investigacion botanica y la transferencia de conocimiento permitirian que muchos jardines botanicos alrededor del mundo proporcionen un apoyo efectivo y basado en la ciencia a los esfuerzos de restauracion. Recomendamos que los jardines botanicos amplien su investigacion para incluir ecosistemas y especies, incrementen la participacion en proyectos de restauracion practica asi como la capacitacion de practicantes, y funcionen como centros de informacion para el almacenamiento e intercambio de datos.
Many of the skills and resources associated with botanic gardens and arboreta, including plant taxonomy, horticulture, and seed bank management, are fundamental to ecological restoration efforts, yet ...few of the world's botanic gardens are involved in the science or practice of restoration. Thus, we examined the potential role of botanic gardens in these emerging fields. We believe a reorientation of certain existing institutional strengths, such as plant-based research and knowledge transfer, would enable many more botanic gardens worldwide to provide effective science-based support to restoration efforts. We recommend botanic gardens widen research to include ecosystems as well as species, increase involvement in practical restoration projects and training practitioners, and serve as information hubs for data archiving and exchange. Resumen: Muchas de las habilidades y recursos asociados con los jardines botánicos y viveros, incluyendo la taxonomía de plantas, la horticultura y el manejo de banco de semillas, son fundamentales para los esfuerzos de restauración ecológica. Por lo tanto, examinamos el papel potencial de los jardines botánicos en estos campos emergentes. Consideramos que una reorientación de ciertas potenciales institucionales existentes, como la investigación botánica y la transferencia de conocimiento permitirían que muchos jardines botánicos alrededor del mundo proporcionen un apoyo efectivo y basado en la ciencia a los esfuerzos de restauración. Recomendamos que los jardines botánicos amplíen su investigación para incluir ecosistemas y especies, incrementen la participación en proyectos de restauración práctica así como la capacitación de practicantes, y funcionen como centros de información para el almacenamiento e intercambio de datos. PUBLICATION ABSTRACT
The human immunodeficiency virus (HIV) epidemic is an important medical problem. Although combination drug regimens have produced dramatic decreases in viral load, current therapies do not provide a ...cure for HIV infection. We have used structure-based design and combinatorial medicinal chemistry to identify potent and selective HIV-1 reverse transcriptase (RT) inhibitors that may work by a mechanism distinct from that of current HIV drugs. The most potent of these compounds (compound
4, 2-naphthalenesulfonic acid, 4-hydroxy-7-5-hydroxy-6-(4-cinnamylphenyl)azo-7-sulfo-2-naphthalenylaminocarbonylamino-3-(4-cinnamylphenyl)azo, disodium salt) has an IC
50 of 90
nM for inhibition of polymerase chain extension, a
K
d of 40
nM for inhibition of DNA–RT binding, and an IC
50 of 25–100
nM for inhibition of RNaseH cleavage. The parent compound (
1) was as effective against 10 nucleoside and non-nucleoside resistant HIV-1 RT mutants as it was against the wild-type enzyme. Compound
4 inhibited HIV-1 RT and murine leukemia virus (MLV) RT, but it did not inhibit T
4 DNA polymerase, T
7 DNA polymerase, or the Klenow fragment at concentrations up to 200
nM. Finally, compound
4 protected cells from HIV-1 infection at a concentration more than 40 times lower than the concentration at which it caused cellular toxicity.
We sequenced the amino-terminal third of the histone H3 and H4 genes and the intergenic region from Ichthyophthirius multifiliis. Fourteen recombinant clones of 646 bp were sequenced and the level of ...sequence variation detected among these clones was similar to that reported among closely related species of Tetrahymena and to levels of sequence variation detected within other ciliates. The intergenic region is 417 bp and approximately 92% AT rich, making it the longest and most AT-rich ciliate H3/H4 intergenic region yet identified. Similar to Tetrahymena, the intergenic region of Ichthyophthirius contains two CCAAT regions arranged in a complementary orientation. A neighbor-joining tree was constructed based on nucleotide sequence variation among H4 genes to evaluate evolutionary relationships within and among six classes of Ciliophora. The single shortest neighbor-joining tree depicted a sister-group relationship of Ichthyophthirius with taxa of Tetrahymenina, thereby supporting monophyly of Oligohymenophorea.
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