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  • Mice  (205)
  • Scientific Community  (162)
  • Development  (66)
  • American Association for the Advancement of Science (AAAS)  (433)
  • Institute of Physics
  • 2015-2019  (433)
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  • 1
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-10
    Description: Author: Beverly A. Purnell
    Keywords: Development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 2
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-06-03
    Description: Two teams have developed innovative new applications of the popular genome-editing method CRISPR. One of the groups has used it to mark and trace cells in a developing animal. In the method's first test, described online today in Science, the researchers reveal that many tissues and organs in adult zebrafish form from just a few embryonic cells. Other researchers are already looking to adapt the method to mice, or to exploit it to trace the evolution of tumors. The second group found a way to use CRISPR-guided mutations to record a cell's history—for example, the environmental signals that influence it. Author: Kai Kupferschmidt
    Keywords: Development
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  • 3
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-09-03
    Description: Author: Valda Vinson
    Keywords: Development
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  • 4
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-07-27
    Keywords: Scientific Community
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-07-27
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-14
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-03
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Description: Mutations in the fragile X mental retardation 1 gene ( FMR1 ) cause the most common inherited human autism spectrum disorder. FMR1 influences messenger RNA (mRNA) translation, but identifying functional targets has been difficult. We analyzed quiescent Drosophila oocytes, which, like neural synapses, depend heavily on translating stored mRNA. Ribosome profiling revealed that FMR1 enhances rather than represses the translation of mRNAs that overlap previously identified FMR1 targets, and acts preferentially on large proteins. Human homologs of at least 20 targets are associated with dominant intellectual disability, and 30 others with recessive neurodevelopmental dysfunction. Stored oocytes lacking FMR1 usually generate embryos with severe neural defects, unlike stored wild-type oocytes, which suggests that translation of multiple large proteins by stored mRNAs is defective in fragile X syndrome and possibly other autism spectrum disorders.
    Keywords: Development
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  • 9
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Keywords: Development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 11
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-17
    Keywords: Development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 12
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-24
    Keywords: Development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 13
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-21
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 14
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-21
    Keywords: Development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 15
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-28
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 16
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-28
    Keywords: Development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 17
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-12
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 18
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-12
    Keywords: Development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 19
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-21
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 20
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-21
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 21
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-21
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 22
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-13
    Description: The way science is represented to the public can influence understanding and expectations, frame policy debates, and affect the implementation and use of emerging technologies. Inaccurate representations of research may, for example, lead to public confusion about the readiness of a technology for clinical application. As a result, the issue of science “hype”—in which the state of scientific progress, the degree of certainty in models or bench results, or the potential applications of research are exaggerated—is receiving increased attention from the popular press, the research community, and scientific societies (1). In newly issued guidelines on the ethical conduct of human pluripotent stem cell research and clinical translation (2), the International Society for Stem Cell Research (ISSCR) explicitly recognizes and confronts the issue of science hype. By placing a clear obligation on researchers, the ISSCR hopes to make balance in public representations of research a norm associated with scientific integrity. The focus on public communication, which is new to this version of the guidelines, is the result of both specific concerns regarding how stem cell research has been portrayed in the public sphere and the growing recognition that researchers play an important role in the science communication process. Authors: Timothy Caulfield, Douglas Sipp, Charles E. Murry, George Q. Daley, Jonathan Kimmelman
    Keywords: Scientific Community
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  • 23
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-05-20
    Description: A preprint is a complete scientific manuscript (often one also being submitted to a peer-reviewed journal) that is uploaded by the authors to a public server without formal review. After a brief inspection to ensure that the work is scientific in nature, the posted scientific manuscript can be viewed without charge on the Web. Thus, preprint servers facilitate the direct and open delivery of new knowledge and concepts to the worldwide scientific community before traditional validation through peer review (1, 2). Although the preprint server arXiv.org has been essential for physics, mathematics, and computer sciences for over two decades, preprints are currently used minimally in biology. Authors: Jeremy M. Berg, Needhi Bhalla, Philip E. Bourne, Martin Chalfie, David G. Drubin, James S. Fraser, Carol W. Greider, Michael Hendricks, Chonnettia Jones, Robert Kiley, Susan King, Marc W. Kirschner, Harlan M. Krumholz, Ruth Lehmann, Maria Leptin, Bernd Pulverer, Brooke Rosenzweig, John E. Spiro, Michael Stebbins, Carly Strasser, Sowmya Swaminathan, Paul Turner, Ronald D. Vale, K. VijayRaghavan, Cynthia Wolberger
    Keywords: Scientific Community
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    Electronic ISSN: 1095-9203
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  • 24
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-29
    Description: The field of physical anthropology recently has been convulsed by several high profile cases of alleged sexual harassment, and by a survey of field scientists showing that harassment during fieldwork is common. So when physical anthropologists gathered last week at their annual meeting, reducing such problems was high on the agenda. But how to change the culture of a discipline? Meeting organizers and advocates offered a menu of actions to battle harassment, from symbolic to concrete. All meeting registrants were required to agree to the American Association of Physical Anthropologists's code of ethics, and panels and workshops offered specific suggestions to women describing incidents of harassment and discrimination. Authors: Ann Gibbons, Elizabeth Culotta
    Keywords: Scientific Community
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  • 25
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2016-04-01
    Description: The generation of a mature egg, or oocyte, is essential for fertility. The oocyte requires the production of considerable quantities of messenger RNA (mRNA), protein, and organelles during its formation, a store needed for the subsequent development of the fertilized egg. In some species, these components are provided by neighboring cells called nurse cells (1). The role of nurse cells during oocyte development has been well studied in the fruit fly, Drosophila melanogaster, but it has been unclear if mammalian species also have nurse cells. On page 95 of this issue, Lei and Spradling (2) provide evidence for nurse cells during mouse oogenesis, adding to our understanding of mammalian oocyte development and raising hope for new infertility treatments. Author: Melissa E. Pepling
    Keywords: Development
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  • 26
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-19
    Keywords: Development
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 27
    Publication Date: 2018-10-19
    Description: Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell–like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (approximately 4 months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming—genome-wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA methylation in hPSCs—and acquire an immediate precursory state for meiotic recombination. Furthermore, the inactive X chromosome shows a progressive demethylation and reactivation, albeit partially. These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis.
    Keywords: Development
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  • 28
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Scientific Community
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    Electronic ISSN: 1095-9203
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  • 29
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-02
    Keywords: Scientific Community
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    Electronic ISSN: 1095-9203
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  • 30
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-14
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 31
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-16
    Keywords: Scientific Community
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  • 32
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-30
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 33
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-30
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 34
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-12-07
    Keywords: Scientific Community
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  • 35
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Keywords: Scientific Community
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    Electronic ISSN: 1095-9203
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  • 36
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-08-10
    Keywords: Scientific Community
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
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  • 37
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-07
    Keywords: Scientific Community
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    Electronic ISSN: 1095-9203
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  • 38
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-07
    Keywords: Development
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  • 39
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-14
    Keywords: Scientific Community
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    Electronic ISSN: 1095-9203
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  • 40
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-04-20
    Keywords: Development
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  • 41
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-05-11
    Keywords: Scientific Community
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  • 42
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-05-25
    Keywords: Development
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  • 43
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-01
    Keywords: Scientific Community
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  • 44
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-01
    Keywords: Scientific Community
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    Electronic ISSN: 1095-9203
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  • 45
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-01
    Keywords: Development
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    Electronic ISSN: 1095-9203
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  • 46
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-19
    Keywords: Scientific Community
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  • 47
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-19
    Keywords: Development
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  • 48
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Scientific Community
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  • 49
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Scientific Community
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  • 50
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Scientific Community
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  • 51
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Scientific Community
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  • 52
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-10-26
    Keywords: Scientific Community
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  • 53
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-09
    Keywords: Scientific Community
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  • 54
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-16
    Keywords: Scientific Community
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  • 55
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-11-23
    Keywords: Scientific Community
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  • 56
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-07-06
    Keywords: Scientific Community
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  • 57
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-07-20
    Keywords: Scientific Community
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  • 58
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-06-29
    Keywords: Development
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  • 59
    Publication Date: 2015-09-01
    Description: Glycerophospholipids, the structural components of cell membranes, have not been considered to be spatial cues for intercellular signaling because of their ubiquitous distribution. We identified lyso-phosphatidyl-beta-D-glucoside (LysoPtdGlc), a hydrophilic glycerophospholipid, and demonstrated its role in modality-specific repulsive guidance of spinal cord sensory axons. LysoPtdGlc is locally synthesized and released by radial glia in a patterned spatial distribution to regulate the targeting of nociceptive but not proprioceptive central axon projections. Library screening identified the G protein-coupled receptor GPR55 as a high-affinity receptor for LysoPtdGlc, and GPR55 deletion or LysoPtdGlc loss of function in vivo caused the misallocation of nociceptive axons into proprioceptive zones. These findings show that LysoPtdGlc/GPR55 is a lipid-based signaling system in glia-neuron communication for neural development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guy, Adam T -- Nagatsuka, Yasuko -- Ooashi, Noriko -- Inoue, Mariko -- Nakata, Asuka -- Greimel, Peter -- Inoue, Asuka -- Nabetani, Takuji -- Murayama, Akiho -- Ohta, Kunihiro -- Ito, Yukishige -- Aoki, Junken -- Hirabayashi, Yoshio -- Kamiguchi, Hiroyuki -- New York, N.Y. -- Science. 2015 Aug 28;349(6251):974-7. doi: 10.1126/science.aab3516.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Lipid Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Sendai, Miyagi 980-8578, Japan. Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. ; Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan. ; Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. ; Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Sendai, Miyagi 980-8578, Japan. Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), 1-7-1 Otemachi, Chiyoda, Tokyo 100-0004, Japan. ; RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. kamiguchi@brain.riken.jp hirabaya@riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26315437" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/*physiology ; Chick Embryo ; Coculture Techniques ; Ganglia, Spinal/*cytology/physiology ; Gene Knockout Techniques ; Glycerophospholipids/analysis/metabolism/*physiology ; Glycolipids/analysis/*physiology ; Mice ; Nerve Growth Factor/pharmacology ; Neuroglia/*physiology ; Nociceptors/*physiology ; Receptor, trkA/metabolism ; Receptor, trkC/metabolism ; Receptors, Cannabinoid/genetics/*physiology ; Spinal Cord/*cytology/*embryology ; Tissue Culture Techniques
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  • 60
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-11-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dajani, Rana -- New York, N.Y. -- Science. 2015 Nov 27;350(6264):1043. doi: 10.1126/science.350.6264.1043-b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology and Biotechnology, Hashemite University, Zarqa, Jordan. rdajani@hu.edu.jo.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26612944" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Art ; Equipment Reuse ; Fibroblasts ; Gloves, Protective ; Jordan ; Laboratories ; Mice ; Recycling/*methods ; United States
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  • 61
    Publication Date: 2015-11-14
    Description: The RNA-guided CRISPR-associated protein Cas9 is used for genome editing, transcriptional modulation, and live-cell imaging. Cas9-guide RNA complexes recognize and cleave double-stranded DNA sequences on the basis of 20-nucleotide RNA-DNA complementarity, but the mechanism of target searching in mammalian cells is unknown. Here, we use single-particle tracking to visualize diffusion and chromatin binding of Cas9 in living cells. We show that three-dimensional diffusion dominates Cas9 searching in vivo, and off-target binding events are, on average, short-lived (〈1 second). Searching is dependent on the local chromatin environment, with less sampling and slower movement within heterochromatin. These results reveal how the bacterial Cas9 protein interrogates mammalian genomes and navigates eukaryotic chromatin structure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Knight, Spencer C -- Xie, Liangqi -- Deng, Wulan -- Guglielmi, Benjamin -- Witkowsky, Lea B -- Bosanac, Lana -- Zhang, Elisa T -- El Beheiry, Mohamed -- Masson, Jean-Baptiste -- Dahan, Maxime -- Liu, Zhe -- Doudna, Jennifer A -- Tjian, Robert -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Nov 13;350(6262):823-6. doi: 10.1126/science.aac6572.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of California, Berkeley, CA, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. ; Laboratoire Physico-Chimie Curie, Institut Curie, Centre National de la Recherche Scientifique UMR 168, Paris, France. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. ; Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Laboratoire Physico-Chimie Curie, Institut Curie, Centre National de la Recherche Scientifique UMR 168, Paris, France. ; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu. ; Department of Chemistry, University of California, Berkeley, CA, USA. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Innovative Genomics Initiative, University of California, Berkeley, CA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Transcriptional Imaging Consortium, Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA. Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA. Li Ka Shing Biomedical and Health Sciences Center, University of California, Berkeley, CA, USA. liuz11@janelia.hhmi.org doudna@berkeley.edu jmlim@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26564855" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; Bacterial Proteins/chemistry/*metabolism ; *CRISPR-Cas Systems ; Chromatin/chemistry/*metabolism/ultrastructure ; Clustered Regularly Interspaced Short Palindromic Repeats ; *DNA Cleavage ; Endonucleases/chemistry/*metabolism ; *Genetic Engineering ; Genome ; Mice ; Single-Cell Analysis
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  • 62
    Publication Date: 2015-03-07
    Description: Human higher cognition is attributed to the evolutionary expansion and elaboration of the human cerebral cortex. However, the genetic mechanisms contributing to these developmental changes are poorly understood. We used comparative epigenetic profiling of human, rhesus macaque, and mouse corticogenesis to identify promoters and enhancers that have gained activity in humans. These gains are significantly enriched in modules of coexpressed genes in the cortex that function in neuronal proliferation, migration, and cortical-map organization. Gain-enriched modules also showed correlated gene expression patterns and similar transcription factor binding site enrichments in promoters and enhancers, suggesting that they are connected by common regulatory mechanisms. Our results reveal coordinated patterns of potential regulatory changes associated with conserved developmental processes during corticogenesis, providing insight into human cortical evolution.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426903/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426903/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reilly, Steven K -- Yin, Jun -- Ayoub, Albert E -- Emera, Deena -- Leng, Jing -- Cotney, Justin -- Sarro, Richard -- Rakic, Pasko -- Noonan, James P -- 099175/Z/12/Z/Wellcome Trust/United Kingdom -- DA023999/DA/NIDA NIH HHS/ -- F32 GM106628/GM/NIGMS NIH HHS/ -- GM094780/GM/NIGMS NIH HHS/ -- NS014841/NS/NINDS NIH HHS/ -- P30 CA016359/CA/NCI NIH HHS/ -- R01 DA023999/DA/NIDA NIH HHS/ -- R01 GM094780/GM/NIGMS NIH HHS/ -- T32 GM007223/GM/NIGMS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Mar 6;347(6226):1155-9. doi: 10.1126/science.1260943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. ; Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. ; Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA. Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA. james.noonan@yale.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745175" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/*growth & development ; Enhancer Elements, Genetic/*genetics ; *Epigenesis, Genetic ; *Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Humans ; Macaca mulatta ; Mice ; Organogenesis/*genetics ; Promoter Regions, Genetic/*genetics ; Rats
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  • 63
    Publication Date: 2015-01-03
    Description: Adipocytes have been suggested to be immunologically active, but their role in host defense is unclear. We observed rapid proliferation of preadipocytes and expansion of the dermal fat layer after infection of the skin by Staphylococcus aureus. Impaired adipogenesis resulted in increased infection as seen in Zfp423(nur12) mice or in mice given inhibitors of peroxisome proliferator-activated receptor gamma. This host defense function was mediated through the production of cathelicidin antimicrobial peptide from adipocytes because cathelicidin expression was decreased by inhibition of adipogenesis, and adipocytes from Camp(-/-) mice lost the capacity to inhibit bacterial growth. Together, these findings show that the production of an antimicrobial peptide by adipocytes is an important element for protection against S. aureus infection of the skin.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318537/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318537/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Ling-juan -- Guerrero-Juarez, Christian F -- Hata, Tissa -- Bapat, Sagar P -- Ramos, Raul -- Plikus, Maksim V -- Gallo, Richard L -- AR052728/AR/NIAMS NIH HHS/ -- DK096828/DK/NIDDK NIH HHS/ -- GM055246/GM/NIGMS NIH HHS/ -- HHSN272201000020C/PHS HHS/ -- P01 HL107150/HL/NHLBI NIH HHS/ -- R01 AI052453/AI/NIAID NIH HHS/ -- R01 AI083358/AI/NIAID NIH HHS/ -- R01 AI116576/AI/NIAID NIH HHS/ -- R01 AR064781/AR/NIAMS NIH HHS/ -- R01 AR067273/AR/NIAMS NIH HHS/ -- R01-AR067273/AR/NIAMS NIH HHS/ -- R01AI052453/AI/NIAID NIH HHS/ -- R25 GM055246/GM/NIGMS NIH HHS/ -- T32 GM007198/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 Jan 2;347(6217):67-71. doi: 10.1126/science.1260972.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Dermatology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA. ; Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA. Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA. ; Nomis Foundation Laboratories for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, San Diego, La Jolla, CA 92037, USA. ; Division of Dermatology, University of California, San Diego (UCSD), La Jolla, CA 92093, USA. rgallo@ucsd.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25554785" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3-L1 Cells ; Adipocytes/*immunology/microbiology ; Adipogenesis/immunology ; Animals ; Antimicrobial Cationic Peptides/immunology ; Cathelicidins/genetics/*immunology ; DNA-Binding Proteins/genetics/immunology ; Dermis/*immunology/microbiology ; Host-Pathogen Interactions/immunology ; Mice ; Mice, Mutant Strains ; Staphylococcal Skin Infections/*immunology ; Staphylococcus aureus/*immunology ; Transcription Factors/genetics/immunology
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  • 64
    Publication Date: 2015-04-11
    Description: Protein phosphorylation regulates virtually all biological processes. Although protein kinases are popular drug targets, targeting protein phosphatases remains a challenge. Here, we describe Sephin1 (selective inhibitor of a holophosphatase), a small molecule that safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively bound and inhibited the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis. Thus, regulatory subunits of phosphatases are drug targets, a property exploited here to safely prevent two protein misfolding diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490275/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490275/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Indrajit -- Krzyzosiak, Agnieszka -- Schneider, Kim -- Wrabetz, Lawrence -- D'Antonio, Maurizio -- Barry, Nicholas -- Sigurdardottir, Anna -- Bertolotti, Anne -- 309516/European Research Council/International -- MC_U105185860/Medical Research Council/United Kingdom -- R01-NS55256/NS/NINDS NIH HHS/ -- Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2015 Apr 10;348(6231):239-42. doi: 10.1126/science.aaa4484.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. ; Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milan, Italy. ; Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK. aberto@mrc-lmb.cam.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25859045" target="_blank"〉PubMed〈/a〉
    Keywords: Amyotrophic Lateral Sclerosis/drug therapy/metabolism/pathology ; Animals ; Cells, Cultured ; Charcot-Marie-Tooth Disease/drug therapy/metabolism/pathology ; Disease Models, Animal ; Endoplasmic Reticulum Stress/drug effects ; Enzyme Inhibitors/metabolism/pharmacokinetics/*pharmacology/toxicity ; Guanabenz/*analogs & derivatives/chemical ; synthesis/metabolism/pharmacology/toxicity ; HeLa Cells ; Humans ; Mice ; Mice, Transgenic ; Molecular Targeted Therapy ; Phosphorylation ; Protein Folding ; Protein Phosphatase 1/*antagonists & inhibitors ; Proteostasis Deficiencies/*drug therapy/*prevention & control ; Signal Transduction
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  • 65
    Publication Date: 2015-05-02
    Description: Werner syndrome (WS) is a premature aging disorder caused by WRN protein deficiency. Here, we report on the generation of a human WS model in human embryonic stem cells (ESCs). Differentiation of WRN-null ESCs to mesenchymal stem cells (MSCs) recapitulates features of premature cellular aging, a global loss of H3K9me3, and changes in heterochromatin architecture. We show that WRN associates with heterochromatin proteins SUV39H1 and HP1alpha and nuclear lamina-heterochromatin anchoring protein LAP2beta. Targeted knock-in of catalytically inactive SUV39H1 in wild-type MSCs recapitulates accelerated cellular senescence, resembling WRN-deficient MSCs. Moreover, decrease in WRN and heterochromatin marks are detected in MSCs from older individuals. Our observations uncover a role for WRN in maintaining heterochromatin stability and highlight heterochromatin disorganization as a potential determinant of human aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494668/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494668/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Weiqi -- Li, Jingyi -- Suzuki, Keiichiro -- Qu, Jing -- Wang, Ping -- Zhou, Junzhi -- Liu, Xiaomeng -- Ren, Ruotong -- Xu, Xiuling -- Ocampo, Alejandro -- Yuan, Tingting -- Yang, Jiping -- Li, Ying -- Shi, Liang -- Guan, Dee -- Pan, Huize -- Duan, Shunlei -- Ding, Zhichao -- Li, Mo -- Yi, Fei -- Bai, Ruijun -- Wang, Yayu -- Chen, Chang -- Yang, Fuquan -- Li, Xiaoyu -- Wang, Zimei -- Aizawa, Emi -- Goebl, April -- Soligalla, Rupa Devi -- Reddy, Pradeep -- Esteban, Concepcion Rodriguez -- Tang, Fuchou -- Liu, Guang-Hui -- Belmonte, Juan Carlos Izpisua -- F32 AG047770/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 5;348(6239):1160-3. doi: 10.1126/science.aaa1356. Epub 2015 Apr 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. ; Diagnosis and Treatment Center for Oral Disease, the 306th Hospital of the PLA, Beijing, China. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; College of Life Sciences, Peking University, Beijing 100871, China. ; The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Universidad Catolica San Antonio de Murcia, Campus de los Jeronimos s/n, 30107 Guadalupe, Murcia, Spain. ; Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing 100871, China. Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing 100871, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. The Center for Anti-aging and Regenerative Medicine, Shenzhen University, Shenzhen 518060, China. Center for Molecular and Translational Medicine (CMTM), Beijing 100101, China. Beijing Institute for Brain Disorders, Beijing 100069, China. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu. ; Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ghliu@ibp.ac.cn tangfuchou@pku.edu.cn belmonte@salk.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25931448" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*metabolism ; Animals ; *Cell Aging ; Cell Differentiation ; Centromere/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; DNA-Binding Proteins/metabolism ; Epigenesis, Genetic ; Exodeoxyribonucleases/genetics/*metabolism ; Gene Knockout Techniques ; HEK293 Cells ; Heterochromatin/chemistry/*metabolism ; Humans ; Membrane Proteins/metabolism ; Mesenchymal Stromal Cells/*metabolism ; Methyltransferases/genetics/metabolism ; Mice ; Models, Biological ; RecQ Helicases/genetics/*metabolism ; Repressor Proteins/genetics/metabolism ; Werner Syndrome/genetics/*metabolism
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  • 66
    Publication Date: 2015-06-13
    Description: Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Yongyou -- Desai, Amar -- Yang, Sung Yeun -- Bae, Ki Beom -- Antczak, Monika I -- Fink, Stephen P -- Tiwari, Shruti -- Willis, Joseph E -- Williams, Noelle S -- Dawson, Dawn M -- Wald, David -- Chen, Wei-Dong -- Wang, Zhenghe -- Kasturi, Lakshmi -- Larusch, Gretchen A -- He, Lucy -- Cominelli, Fabio -- Di Martino, Luca -- Djuric, Zora -- Milne, Ginger L -- Chance, Mark -- Sanabria, Juan -- Dealwis, Chris -- Mikkola, Debra -- Naidoo, Jacinth -- Wei, Shuguang -- Tai, Hsin-Hsiung -- Gerson, Stanton L -- Ready, Joseph M -- Posner, Bruce -- Willson, James K V -- Markowitz, Sanford D -- 1P01CA95471-09/CA/NCI NIH HHS/ -- 5P30 CA142543-03/CA/NCI NIH HHS/ -- P01 CA095471/CA/NCI NIH HHS/ -- P30 CA043703/CA/NCI NIH HHS/ -- P30 CA142543/CA/NCI NIH HHS/ -- P30 DK020572/DK/NIDDK NIH HHS/ -- P30 DK097948/DK/NIDDK NIH HHS/ -- P50 CA130810/CA/NCI NIH HHS/ -- P50 CA150964/CA/NCI NIH HHS/ -- R01 CA127590/CA/NCI NIH HHS/ -- R25 CA148052/CA/NCI NIH HHS/ -- R25CA148052/CA/NCI NIH HHS/ -- U54 HL119810/HL/NHLBI NIH HHS/ -- U54HL119810/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):aaa2340. doi: 10.1126/science.aaa2340.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Gastroenterology, Haeundae Paik Hospital, Inje University, Busan 612896, South Korea. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Surgery, Busan Paik Hospital, and Paik Institute of Clinical Research and Ocular Neovascular Research Center, Inje University, Busan, South Korea. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. ; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Family Medicine, University of Michigan, Ann Arbor MI 48109, USA. ; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. ; Proteomics Center, Case Western Reserve University, Cleveland, OH 44106, USA. ; Department of Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. ; Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, USA. ; College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA. ; Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Case Medical Center, University Hospitals of Cleveland, Cleveland, OH 44106, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu. ; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. sxm10@cwru.edu james.willson@utsouthwestern.edu slg5@cwru.edu joseph.ready@utsouthwestern.edu bruce.posner@utsouthwestern.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068857" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Transplantation ; Colitis/enzymology/prevention & control ; Dinoprostone/metabolism ; Enzyme Inhibitors/chemistry/pharmacology ; Hematopoiesis/drug effects ; Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors/genetics/*physiology ; Liver Regeneration/drug effects ; Mice ; Mice, Knockout ; Prostaglandins/*metabolism ; Pyridines/chemistry/pharmacology ; Regeneration/drug effects/genetics/*physiology ; Thiophenes/chemistry/pharmacology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 67
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-05-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bilbe, Graeme -- New York, N.Y. -- Science. 2015 May 29;348(6238):974-6. doi: 10.1126/science.aaa3683. Epub 2015 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Drugs for Neglected Diseases Initiative, 15 Chemin Louis Dunant, 1202 Geneva, Switzerland. gbilbe@dndi.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26023124" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiprotozoal Agents/adverse effects/*chemistry/therapeutic use ; Chagas Disease/drug therapy/transmission ; Disease Models, Animal ; *Drug Design ; Euglenozoa Infections/*drug therapy/transmission ; Humans ; Kinetoplastida/*drug effects ; Leishmaniasis/drug therapy/transmission ; Mice ; Neglected Diseases/*drug therapy ; Trypanosoma cruzi/drug effects ; Trypanosomiasis, African/drug therapy/transmission
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 68
    Publication Date: 2015-06-13
    Description: During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richiardi, Jonas -- Altmann, Andre -- Milazzo, Anna-Clare -- Chang, Catie -- Chakravarty, M Mallar -- Banaschewski, Tobias -- Barker, Gareth J -- Bokde, Arun L W -- Bromberg, Uli -- Buchel, Christian -- Conrod, Patricia -- Fauth-Buhler, Mira -- Flor, Herta -- Frouin, Vincent -- Gallinat, Jurgen -- Garavan, Hugh -- Gowland, Penny -- Heinz, Andreas -- Lemaitre, Herve -- Mann, Karl F -- Martinot, Jean-Luc -- Nees, Frauke -- Paus, Tomas -- Pausova, Zdenka -- Rietschel, Marcella -- Robbins, Trevor W -- Smolka, Michael N -- Spanagel, Rainer -- Strohle, Andreas -- Schumann, Gunter -- Hawrylycz, Mike -- Poline, Jean-Baptiste -- Greicius, Michael D -- IMAGEN consortium -- 93558/Medical Research Council/United Kingdom -- R01 MH085772-01A1/MH/NIMH NIH HHS/ -- R01NS073498/NS/NINDS NIH HHS/ -- U54 EB020403/EB/NIBIB NIH HHS/ -- Department of Health/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1241-4. doi: 10.1126/science.1255905. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. Laboratory of Neurology and Imaging of Cognition, Department of Neuroscience, University of Geneva, Geneva, Switzerland. jonas.richiardi@unige.ch greicius@stanford.edu. ; Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. ; The War Related Illness and Injury Study Center, VA Palo Alto Health Care System, Palo Alto, CA, USA. Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. ; Advanced MRI Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. ; Cerebral Imaging Centre, Douglas Mental Health University Institute, Montreal, Canada. Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Canada. ; Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. ; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. ; Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Department of Psychiatry, Universite de Montreal, Centre Hospitalier Universitaire (CHU) Ste Justine Hospital, Montreal, Canada. ; Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Neurospin, Commissariat a l'Energie Atomique et aux Energies Alternatives, Paris, France. ; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany. ; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland. Departments of Psychiatry and Psychology, University of Vermont, Burlington, VT, USA. ; School of Physics and Astronomy, University of Nottingham, Nottingham, UK. ; Institut National de la Sante et de la Recherche Medicale, INSERM Unit 1000 "Neuroimaging and Psychiatry," University Paris Sud, Orsay, France. INSERM Unit 1000 at Maison de Solenn, Assistance Publique Hopitaux de Paris (APHP), Cochin Hospital, University Paris Descartes, Sorbonne Paris Cite, Paris, France. ; Rotman Research Institute, University of Toronto, Toronto, Canada. School of Psychology, University of Nottingham, Nottingham, UK. ; The Hospital for Sick Children, University of Toronto, Toronto, Canada. ; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. ; Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK. ; Department of Psychiatry and Psychotherapy, and Neuroimaging Center, Technische Universitat Dresden, Dresden, Germany. ; Department of Psychopharmacology, Central Institute of Mental Health, Faculty of Clinical Medicine Mannheim, Mannheim, Germany. ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. Medical Research Council (MRC) Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, UK. ; Allen Institute for Brain Science, Seattle, WA, USA. ; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA. ; Functional Imaging in Neuropsychiatric Disorders Laboratory, Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA. jonas.richiardi@unige.ch greicius@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068849" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Animals ; Brain/metabolism/*physiology ; Female ; Gene Expression ; Humans ; Ion Channels/*genetics ; Magnetic Resonance Imaging ; Male ; Mice ; Nerve Net/metabolism/*physiology ; Neural Pathways/metabolism/physiology ; Polymorphism, Genetic ; Rest/*physiology ; Synapses/metabolism/physiology ; *Transcriptome ; Young Adult
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  • 69
    Publication Date: 2015-05-16
    Description: PIWI-interacting RNAs (piRNAs) protect the animal germ line by silencing transposons. Primary piRNAs, generated from transcripts of genomic transposon "junkyards" (piRNA clusters), are amplified by the "ping-pong" pathway, yielding secondary piRNAs. We report that secondary piRNAs, bound to the PIWI protein Ago3, can initiate primary piRNA production from cleaved transposon RNAs. The first ~26 nucleotides (nt) of each cleaved RNA becomes a secondary piRNA, but the subsequent ~26 nt become the first in a series of phased primary piRNAs that bind Piwi, allowing piRNAs to spread beyond the site of RNA cleavage. The ping-pong pathway increases only the abundance of piRNAs, whereas production of phased primary piRNAs from cleaved transposon RNAs adds sequence diversity to the piRNA pool, allowing adaptation to changes in transposon sequence.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545291/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545291/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Bo W -- Wang, Wei -- Li, Chengjian -- Weng, Zhiping -- Zamore, Phillip D -- GM62862/GM/NIGMS NIH HHS/ -- GM65236/GM/NIGMS NIH HHS/ -- HG007000/HG/NHGRI NIH HHS/ -- R01 GM065236/GM/NIGMS NIH HHS/ -- R37 GM062862/GM/NIGMS NIH HHS/ -- U41 HG007000/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 15;348(6236):817-21. doi: 10.1126/science.aaa1264.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. ; RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. zhiping.weng@umassmed.edu phillip.zamore@umassmed.edu. ; RNA Therapeutics Institute, Howard Hughes Medical Institute, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. zhiping.weng@umassmed.edu phillip.zamore@umassmed.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977554" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Argonaute Proteins/genetics/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*metabolism ; Endoribonucleases/genetics/*metabolism ; Female ; Germ Cells/metabolism ; Male ; Metabolic Networks and Pathways ; Mice ; Ovary/metabolism ; Peptide Initiation Factors/genetics/*metabolism ; *RNA Cleavage ; RNA, Guide/*metabolism ; RNA, Small Interfering/biosynthesis/*metabolism ; *Retroelements ; Testis/metabolism
    Print ISSN: 0036-8075
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  • 70
    Publication Date: 2015-04-18
    Description: Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rinkevich, Yuval -- Walmsley, Graham G -- Hu, Michael S -- Maan, Zeshaan N -- Newman, Aaron M -- Drukker, Micha -- Januszyk, Michael -- Krampitz, Geoffrey W -- Gurtner, Geoffrey C -- Lorenz, H Peter -- Weissman, Irving L -- Longaker, Michael T -- GM07365/GM/NIGMS NIH HHS/ -- R01 GM087609/GM/NIGMS NIH HHS/ -- U01 HL099776/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 17;348(6232):aaa2151. doi: 10.1126/science.aaa2151.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Ludwig Center for Cancer Stem Cell Biology and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu. ; Institute for Stem Cell Biology and Regenerative Medicine, Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. ryuval@stanford.edu irv@stanford.edu longaker@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25883361" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage/genetics ; Cell Separation/*methods ; Cicatrix/metabolism/*pathology ; Disease Models, Animal ; Embryonic Development ; Embryonic Stem Cells/cytology ; Fibroblasts/cytology/pathology/*physiology ; Gene Expression ; Homeodomain Proteins/genetics ; Mice ; Mouth/injuries/pathology/surgery ; Skin/injuries/*pathology ; Translational Medical Research ; *Wound Healing
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  • 71
    Publication Date: 2015-11-07
    Description: The sense of smell allows chemicals to be perceived as diverse scents. We used single-neuron RNA sequencing to explore the developmental mechanisms that shape this ability as nasal olfactory neurons mature in mice. Most mature neurons expressed only one of the ~1000 odorant receptor genes (Olfrs) available, and at a high level. However, many immature neurons expressed low levels of multiple Olfrs. Coexpressed Olfrs localized to overlapping zones of the nasal epithelium, suggesting regional biases, but not to single genomic loci. A single immature neuron could express Olfrs from up to seven different chromosomes. The mature state in which expression of Olfr genes is restricted to one per neuron emerges over a developmental progression that appears to be independent of neuronal activity involving sensory transduction molecules.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanchate, Naresh K -- Kondoh, Kunio -- Lu, Zhonghua -- Kuang, Donghui -- Ye, Xiaolan -- Qiu, Xiaojie -- Pachter, Lior -- Trapnell, Cole -- Buck, Linda B -- DP2 HD088158/DP/NCCDPHP CDC HHS/ -- R01 DC009324/DC/NIDCD NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1251-5. doi: 10.1126/science.aad2456. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98115, USA. Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98115, USA. ; Departments of Mathematics, Molecular and Cell Biology, and Electrical Engineering and Computer Sciences, University of California-Berkeley, Berkeley, CA 94720, USA. ; Department of Genome Sciences, University of Washington, Seattle, WA 98115, USA. coletrap@uw.edu lbuck@fhcrc.org. ; Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. coletrap@uw.edu lbuck@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541607" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cyclic Nucleotide-Gated Cation Channels/genetics ; *Gene Expression Regulation, Developmental ; Genetic Loci ; Genetic Markers ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/*metabolism ; Neurogenesis/*genetics ; Olfactory Mucosa/innervation ; Olfactory Receptor Neurons/*metabolism ; Receptors, Odorant/*genetics ; Sequence Analysis, RNA ; Single-Cell Analysis ; Smell/*genetics ; Transcriptome
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  • 72
    Publication Date: 2015-08-22
    Description: Plasma membrane depolarization can trigger cell proliferation, but how membrane potential influences mitogenic signaling is uncertain. Here, we show that plasma membrane depolarization induces nanoscale reorganization of phosphatidylserine and phosphatidylinositol 4,5-bisphosphate but not other anionic phospholipids. K-Ras, which is targeted to the plasma membrane by electrostatic interactions with phosphatidylserine, in turn undergoes enhanced nanoclustering. Depolarization-induced changes in phosphatidylserine and K-Ras plasma membrane organization occur in fibroblasts, excitable neuroblastoma cells, and Drosophila neurons in vivo and robustly amplify K-Ras-dependent mitogen-activated protein kinase (MAPK) signaling. Conversely, plasma membrane repolarization disrupts K-Ras nanoclustering and inhibits MAPK signaling. By responding to voltage-induced changes in phosphatidylserine spatiotemporal dynamics, K-Ras nanoclusters set up the plasma membrane as a biological field-effect transistor, allowing membrane potential to control the gain in mitogenic signaling circuits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687752/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687752/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhou, Yong -- Wong, Ching-On -- Cho, Kwang-jin -- van der Hoeven, Dharini -- Liang, Hong -- Thakur, Dhananiay P -- Luo, Jialie -- Babic, Milos -- Zinsmaier, Konrad E -- Zhu, Michael X -- Hu, Hongzhen -- Venkatachalam, Kartik -- Hancock, John F -- R01 NS081301/NS/NINDS NIH HHS/ -- R01NS081301/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Aug 21;349(6250):873-6. doi: 10.1126/science.aaa5619.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. ; Department of Diagnostic and Biomedical Sciences, Dental School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA. ; Department of Neuroscience, University of Arizona, Tucson, AZ 85721, USA. ; Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Program in Cell and Regulatory Biology, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. ; Department of Integrative Biology and Pharmacology, Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. Program in Cell and Regulatory Biology, University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030, USA. john.f.hancock@uth.tmc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26293964" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Membrane/metabolism/*physiology ; Cricetinae ; Drosophila melanogaster ; Fibroblasts ; *Membrane Potentials ; Mice ; Neurons ; Phosphatidylinositol 4,5-Diphosphate/*metabolism ; Phosphatidylserines/*metabolism ; Signal Transduction ; ras Proteins/*metabolism
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  • 73
    Publication Date: 2015-09-12
    Description: The function of neural circuits depends on the generation of specific classes of neurons. Neural identity is typically established near the time when neurons exit the cell cycle to become postmitotic cells, and it is generally accepted that, once the identity of a neuron has been established, its fate is maintained throughout life. Here, we show that network activity dynamically modulates the properties of fast-spiking (FS) interneurons through the postmitotic expression of the transcriptional regulator Er81. In the adult cortex, Er81 protein levels define a spectrum of FS basket cells with different properties, whose relative proportions are, however, continuously adjusted in response to neuronal activity. Our findings therefore suggest that interneuron properties are malleable in the adult cortex, at least to a certain extent.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702376/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702376/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dehorter, Nathalie -- Ciceri, Gabriele -- Bartolini, Giorgia -- Lim, Lynette -- del Pino, Isabel -- Marin, Oscar -- 103714MA/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 Sep 11;349(6253):1216-20. doi: 10.1126/science.aab3415.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Centre for Developmental Neurobiology, Medical Research Council, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, UK. Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas and Universidad Miguel Hernandez, 03550 Sant Joan d'Alacant, Spain. ; Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas and Universidad Miguel Hernandez, 03550 Sant Joan d'Alacant, Spain. ; MRC Centre for Developmental Neurobiology, Medical Research Council, New Hunt's House, Guy's Campus, King's College London, London SE1 1UL, UK. Instituto de Neurociencias, Consejo Superior de Investigaciones Cientificas and Universidad Miguel Hernandez, 03550 Sant Joan d'Alacant, Spain. oscar.marin@kcl.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26359400" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/cytology/metabolism/*physiology ; DNA-Binding Proteins/genetics/*metabolism ; Interneurons/cytology/metabolism/*physiology ; Mice ; Mice, Mutant Strains ; Mitosis ; Mutation ; Nerve Net/cytology/metabolism/*physiology ; Transcription Factors/genetics/*metabolism ; *Transcription, Genetic
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  • 74
    Publication Date: 2015-02-01
    Description: When exposed to antigens, naive B cells differentiate into different types of effector cells: antibody-producing plasma cells, germinal center cells, or memory cells. Whether an individual naive B cell can produce all of these different cell fates remains unclear. Using a limiting dilution approach, we found that many individual naive B cells produced only one type of effector cell subset, whereas others produced all subsets. The capacity to differentiate into multiple subsets was a characteristic of clonal populations that divided many times and resisted apoptosis, but was independent of isotype switching. Antigen receptor affinity also influenced effector cell differentiation. These findings suggest that diverse effector cell types arise in the primary immune response as a result of heterogeneity in responses by individual naive B cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412594/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412594/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taylor, Justin J -- Pape, Kathryn A -- Steach, Holly R -- Jenkins, Marc K -- P01 AI035296/AI/NIAID NIH HHS/ -- P01AI035296/AI/NIAID NIH HHS/ -- P30 CA077598/CA/NCI NIH HHS/ -- R01 AI027998/AI/NIAID NIH HHS/ -- R01 AI039614/AI/NIAID NIH HHS/ -- R01AI036914/AI/NIAID NIH HHS/ -- R37AI027998/AI/NIAID NIH HHS/ -- T32 CA009138/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):784-7. doi: 10.1126/science.aaa1342. Epub 2015 Jan 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA. jtaylor3@fhcrc.org. ; Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. ; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98019, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25636798" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibody-Producing Cells/*immunology ; Antigens/immunology ; Apoptosis/*immunology ; B-Lymphocyte Subsets/*immunology ; B-Lymphocytes/*immunology ; Cell Differentiation ; *Immunity, Humoral ; Immunoglobulin Class Switching ; Mice ; Mice, Inbred C57BL
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  • 75
    Publication Date: 2015-06-13
    Description: Blood gas and tissue pH regulation depend on the ability of the brain to sense CO2 and/or H(+) and alter breathing appropriately, a homeostatic process called central respiratory chemosensitivity. We show that selective expression of the proton-activated receptor GPR4 in chemosensory neurons of the mouse retrotrapezoid nucleus (RTN) is required for CO2-stimulated breathing. Genetic deletion of GPR4 disrupted acidosis-dependent activation of RTN neurons, increased apnea frequency, and blunted ventilatory responses to CO2. Reintroduction of GPR4 into RTN neurons restored CO2-dependent RTN neuronal activation and rescued the ventilatory phenotype. Additional elimination of TASK-2 (K(2P)5), a pH-sensitive K(+) channel expressed in RTN neurons, essentially abolished the ventilatory response to CO2. The data identify GPR4 and TASK-2 as distinct, parallel, and essential central mediators of respiratory chemosensitivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, Natasha N -- Velic, Ana -- Soliz, Jorge -- Shi, Yingtang -- Li, Keyong -- Wang, Sheng -- Weaver, Janelle L -- Sen, Josh -- Abbott, Stephen B G -- Lazarenko, Roman M -- Ludwig, Marie-Gabrielle -- Perez-Reyes, Edward -- Mohebbi, Nilufar -- Bettoni, Carla -- Gassmann, Max -- Suply, Thomas -- Seuwen, Klaus -- Guyenet, Patrice G -- Wagner, Carsten A -- Bayliss, Douglas A -- HL074011/HL/NHLBI NIH HHS/ -- HL108609/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 12;348(6240):1255-60. doi: 10.1126/science.aaa0922. Epub 2015 Jun 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. ; Institute of Physiology, University of Zurich, Zurich, CH-8057, Switzerland. ; Institute of Veterinary Physiology, University of Zurich, Zurich, CH-8057, Switzerland. Centre de Recherche du CHU de Quebec, Departement de Pediatrie, Faculte de Medecine, Universite Laval, Quebec, QC, Canada. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. Department of Physiology, Hebei Medical University, Shijiazhuang, Hebei, 050017, China. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. School of Medical Sciences, University of New South Wales, New South Wales 2052, Australia. Department of Neurology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, USA. ; Novartis Institutes for Biomedical Research, Basel, CH-4002, Switzerland. ; Institute of Veterinary Physiology, University of Zurich, Zurich, CH-8057, Switzerland. ; Institute of Physiology, University of Zurich, Zurich, CH-8057, Switzerland. Wagnerca@access.uzh.ch bayliss@virginia.edu. ; Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. Wagnerca@access.uzh.ch bayliss@virginia.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26068853" target="_blank"〉PubMed〈/a〉
    Keywords: Acidosis, Respiratory/genetics/physiopathology ; Animals ; Carbon Dioxide/*physiology ; Female ; Gene Deletion ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Neurons/metabolism/physiology ; Potassium Channels, Tandem Pore Domain/genetics/*physiology ; Receptors, G-Protein-Coupled/antagonists & inhibitors/genetics/*physiology ; *Respiration ; Trapezoid Body/cytology/metabolism/*physiology
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  • 76
    Publication Date: 2015-03-07
    Description: Immune cells, including natural killer (NK) cells, recognize transformed cells and eliminate them in a process termed immunosurveillance. It is thought that tumor cells evade immunosurveillance by shedding membrane ligands that bind to the NKG2D-activating receptor on NK cells and/or T cells, and desensitize these cells. In contrast, we show that in mice, a shed form of MULT1, a high-affinity NKG2D ligand, causes NK cell activation and tumor rejection. Recombinant soluble MULT1 stimulated tumor rejection in mice. Soluble MULT1 functions, at least in part, by competitively reversing a global desensitization of NK cells imposed by engagement of membrane NKG2D ligands on tumor-associated cells, such as myeloid cells. The results overturn conventional wisdom that soluble ligands are always inhibitory and suggest a new approach for cancer immunotherapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deng, Weiwen -- Gowen, Benjamin G -- Zhang, Li -- Wang, Lin -- Lau, Stephanie -- Iannello, Alexandre -- Xu, Jianfeng -- Rovis, Tihana L -- Xiong, Na -- Raulet, David H -- R01 CA093678/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):136-9. doi: 10.1126/science.1258867. Epub 2015 Mar 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, and Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA. ; Center for Proteomics University of Rijeka Faculty of Medicine Brace Branchetta 20, 51000 Rijeka, Croatia. ; Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 115 Henning Building, University Park, PA 16802, USA. ; Department of Molecular and Cell Biology, and Cancer Research Laboratory, University of California at Berkeley, Berkeley, CA 94720, USA. raulet@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25745066" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/genetics/*immunology/pharmacology ; Histocompatibility Antigens Class I/genetics/*immunology/pharmacology ; Immunologic Surveillance ; Immunotherapy/methods ; Killer Cells, Natural/*immunology ; Ligands ; Lymphocyte Activation ; Melanoma, Experimental/immunology/therapy ; Mice ; NK Cell Lectin-Like Receptor Subfamily K/*immunology ; Neoplasms/*immunology/therapy ; Recombinant Proteins/genetics/immunology/pharmacology ; T-Lymphocytes/immunology
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  • 77
    Publication Date: 2015-10-17
    Description: Human skin relies on cutaneous receptors that output digital signals for tactile sensing in which the intensity of stimulation is converted to a series of voltage pulses. We present a power-efficient skin-inspired mechanoreceptor with a flexible organic transistor circuit that transduces pressure into digital frequency signals directly. The output frequency ranges between 0 and 200 hertz, with a sublinear response to increasing force stimuli that mimics slow-adapting skin mechanoreceptors. The output of the sensors was further used to stimulate optogenetically engineered mouse somatosensory neurons of mouse cortex in vitro, achieving stimulated pulses in accordance with pressure levels. This work represents a step toward the design and use of large-area organic electronic skins with neural-integrated touch feedback for replacement limbs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tee, Benjamin C-K -- Chortos, Alex -- Berndt, Andre -- Nguyen, Amanda Kim -- Tom, Ariane -- McGuire, Allister -- Lin, Ziliang Carter -- Tien, Kevin -- Bae, Won-Gyu -- Wang, Huiliang -- Mei, Ping -- Chou, Ho-Hsiu -- Cui, Bianxiao -- Deisseroth, Karl -- Ng, Tse Nga -- Bao, Zhenan -- New York, N.Y. -- Science. 2015 Oct 16;350(6258):313-6. doi: 10.1126/science.aaa9306.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Electrical Engineering, Stanford University, Stanford, CA, USA. ; Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA. ; Department of Bioengineering, Stanford University, Stanford, CA, USA. ; Department of Chemistry, Stanford University, Stanford, CA, USA. ; Department of Chemical Engineering, Stanford University, Stanford, CA, USA. ; Xerox Palo Alto Research Center, Palo Alto, CA, USA. ; Department of Chemical Engineering, Stanford University, Stanford, CA, USA. zbao@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472906" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cerebral Cortex/cytology/physiology ; Hand/anatomy & histology/innervation/physiology ; Humans ; In Vitro Techniques ; *Mechanoreceptors ; Mice ; *Neural Prostheses ; Optogenetics ; Pressure ; Skin/*innervation ; *Touch ; Transcutaneous Electric Nerve Stimulation/*methods ; Transistors, Electronic
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  • 78
    Publication Date: 2015-06-20
    Description: The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform "identification of direct RNA interacting proteins" (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors-including cohesins, condensins, topoisomerases, RNA helicases, chromatin remodelers, and modifiers-that synergistically repress Xi transcription. Inhibiting two or three interactors destabilizes silencing. Although Xist attracts some interactors, it repels architectural factors. Xist evicts cohesins from the Xi and directs an Xi-specific chromosome conformation. Upon deleting Xist, the Xi acquires the cohesin-binding and chromosomal architecture of the active X. Our study unveils many layers of Xi repression and demonstrates a central role for RNA in the topological organization of mammalian chromosomes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Minajigi, Anand -- Froberg, John E -- Wei, Chunyao -- Sunwoo, Hongjae -- Kesner, Barry -- Colognori, David -- Lessing, Derek -- Payer, Bernhard -- Boukhali, Myriam -- Haas, Wilhelm -- Lee, Jeannie T -- R01-DA-38695/DA/NIDA NIH HHS/ -- R03-MH97478/MH/NIMH NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 17;349(6245). pii: aab2276. doi: 10.1126/science.aab2276. Epub 2015 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA. ; Massachusetts General Hospital Cancer Center, Charlestown, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA, USA. ; Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA; Department of Genetics, Harvard Medical School, Boston, MA, USA. lee@molbio.mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089354" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphatases/metabolism ; Animals ; Cell Cycle Proteins/*metabolism ; Cells, Cultured ; Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA-Binding Proteins/metabolism ; Embryonic Stem Cells/metabolism ; Fibroblasts/metabolism ; Gene Knockdown Techniques ; Gene Silencing ; Mice ; Multiprotein Complexes/metabolism ; Nucleic Acid Conformation ; Proteomics ; RNA Helicases/metabolism ; RNA, Long Noncoding/*metabolism ; X Chromosome/chemistry/genetics/*metabolism ; *X Chromosome Inactivation
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  • 79
    Publication Date: 2015-01-13
    Description: The mechanical mismatch between soft neural tissues and stiff neural implants hinders the long-term performance of implantable neuroprostheses. Here, we designed and fabricated soft neural implants with the shape and elasticity of dura mater, the protective membrane of the brain and spinal cord. The electronic dura mater, which we call e-dura, embeds interconnects, electrodes, and chemotrodes that sustain millions of mechanical stretch cycles, electrical stimulation pulses, and chemical injections. These integrated modalities enable multiple neuroprosthetic applications. The soft implants extracted cortical states in freely behaving animals for brain-machine interface and delivered electrochemical spinal neuromodulation that restored locomotion after paralyzing spinal cord injury.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Minev, Ivan R -- Musienko, Pavel -- Hirsch, Arthur -- Barraud, Quentin -- Wenger, Nikolaus -- Moraud, Eduardo Martin -- Gandar, Jerome -- Capogrosso, Marco -- Milekovic, Tomislav -- Asboth, Leonie -- Torres, Rafael Fajardo -- Vachicouras, Nicolas -- Liu, Qihan -- Pavlova, Natalia -- Duis, Simone -- Larmagnac, Alexandre -- Voros, Janos -- Micera, Silvestro -- Suo, Zhigang -- Courtine, Gregoire -- Lacour, Stephanie P -- New York, N.Y. -- Science. 2015 Jan 9;347(6218):159-63. doi: 10.1126/science.1260318.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Centre for Neuroprosthetics, Institute of Microengineering and Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland. ; International Paraplegic Foundation Chair in Spinal Cord Repair, Centre for Neuroprosthetics and Brain Mind Institute, EPFL, Switzerland. Pavlov Institute of Physiology, St. Petersburg, Russia. ; International Paraplegic Foundation Chair in Spinal Cord Repair, Centre for Neuroprosthetics and Brain Mind Institute, EPFL, Switzerland. ; Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, EPFL, Lausanne, Switzerland. ; Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Centre for Neuroprosthetics, Institute of Microengineering and Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland. International Paraplegic Foundation Chair in Spinal Cord Repair, Centre for Neuroprosthetics and Brain Mind Institute, EPFL, Switzerland. ; School of Engineering and Applied Sciences, Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, MA, USA. ; Laboratory for Biosensors and Bioelectronics, Institute for Biomedical Engineering, University and ETH Zurich, Switzerland. ; Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, EPFL, Lausanne, Switzerland. The BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa 56025, Italy. ; International Paraplegic Foundation Chair in Spinal Cord Repair, Centre for Neuroprosthetics and Brain Mind Institute, EPFL, Switzerland. gregoire.courtine@epfl.ch stephanie.lacour@epfl.ch. ; Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronic Interfaces, Centre for Neuroprosthetics, Institute of Microengineering and Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne (EPFL), Switzerland. gregoire.courtine@epfl.ch stephanie.lacour@epfl.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25574019" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biocompatible Materials/therapeutic use ; Brain-Computer Interfaces ; Drug Delivery Systems/*methods ; *Dura Mater ; Elasticity ; Electric Stimulation/*methods ; Electrochemotherapy/*methods ; *Electrodes, Implanted ; Locomotion ; Mice ; Mice, Inbred Strains ; Motor Cortex/physiopathology ; Multimodal Imaging ; Neurons/physiology ; Paralysis/etiology/physiopathology/*therapy ; Platinum ; *Prostheses and Implants ; Silicon ; Spinal Cord/physiopathology ; Spinal Cord Injuries/complications/physiopathology/*therapy
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  • 80
    Publication Date: 2015-10-24
    Description: The immune system plays an important role in regulating tumor growth and metastasis. Classical monocytes promote tumorigenesis and cancer metastasis, but how nonclassical "patrolling" monocytes (PMo) interact with tumors is unknown. Here we show that PMo are enriched in the microvasculature of the lung and reduce tumor metastasis to lung in multiple mouse metastatic tumor models. Nr4a1-deficient mice, which specifically lack PMo, showed increased lung metastasis in vivo. Transfer of Nr4a1-proficient PMo into Nr4a1-deficient mice prevented tumor invasion in the lung. PMo established early interactions with metastasizing tumor cells, scavenged tumor material from the lung vasculature, and promoted natural killer cell recruitment and activation. Thus, PMo contribute to cancer immunosurveillance and may be targets for cancer immunotherapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanna, Richard N -- Cekic, Caglar -- Sag, Duygu -- Tacke, Robert -- Thomas, Graham D -- Nowyhed, Heba -- Herrley, Erica -- Rasquinha, Nicole -- McArdle, Sara -- Wu, Runpei -- Peluso, Esther -- Metzger, Daniel -- Ichinose, Hiroshi -- Shaked, Iftach -- Chodaczek, Grzegorz -- Biswas, Subhra K -- Hedrick, Catherine C -- F32 HL117533-02/HL/NHLBI NIH HHS/ -- R01 CA202987/CA/NCI NIH HHS/ -- R01 HL118765/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):985-90. doi: 10.1126/science.aac9407. Epub 2015 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. rhanna@lji.org hedrick@lji.org. ; Department of Molecular Biology and Genetics, Bilkent University, Ankara, Turkey. ; Izmir Biomedicine and Genome Center, Dokuz Eylul University, Izmir, Turkey. ; Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; Microscopy Core, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; Department of Functional Genomics and Cancer, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Universite de Strasbourg, Illkirch, France. ; Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. ; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26494174" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Immunologic Surveillance/*immunology ; Immunotherapy/methods ; Killer Cells, Natural/immunology ; Lung Neoplasms/*immunology/*secondary/therapy ; Mice ; Mice, Mutant Strains ; Monocytes/*immunology ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasms, Experimental/immunology/secondary ; Nuclear Receptor Subfamily 4, Group A, Member 1/genetics
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  • 81
    Publication Date: 2015-09-19
    Description: Prostate cancer is initially responsive to androgen deprivation, but the effectiveness of androgen receptor (AR) inhibitors in recurrent disease is variable. Biopsy of bone metastases is challenging; hence, sampling circulating tumor cells (CTCs) may reveal drug-resistance mechanisms. We established single-cell RNA-sequencing (RNA-Seq) profiles of 77 intact CTCs isolated from 13 patients (mean six CTCs per patient), by using microfluidic enrichment. Single CTCs from each individual display considerable heterogeneity, including expression of AR gene mutations and splicing variants. Retrospective analysis of CTCs from patients progressing under treatment with an AR inhibitor, compared with untreated cases, indicates activation of noncanonical Wnt signaling (P = 0.0064). Ectopic expression of Wnt5a in prostate cancer cells attenuates the antiproliferative effect of AR inhibition, whereas its suppression in drug-resistant cells restores partial sensitivity, a correlation also evident in an established mouse model. Thus, single-cell analysis of prostate CTCs reveals heterogeneity in signaling pathways that could contribute to treatment failure.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miyamoto, David T -- Zheng, Yu -- Wittner, Ben S -- Lee, Richard J -- Zhu, Huili -- Broderick, Katherine T -- Desai, Rushil -- Fox, Douglas B -- Brannigan, Brian W -- Trautwein, Julie -- Arora, Kshitij S -- Desai, Niyati -- Dahl, Douglas M -- Sequist, Lecia V -- Smith, Matthew R -- Kapur, Ravi -- Wu, Chin-Lee -- Shioda, Toshi -- Ramaswamy, Sridhar -- Ting, David T -- Toner, Mehmet -- Maheswaran, Shyamala -- Haber, Daniel A -- 2R01CA129933/CA/NCI NIH HHS/ -- EB008047/EB/NIBIB NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1351-6. doi: 10.1126/science.aab0917.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Urology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Center for Bioengineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. haber@helix.mgh.harvard.edu smaheswaran@mgh.harvard.edu. ; Massachusetts General Cancer Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. haber@helix.mgh.harvard.edu smaheswaran@mgh.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383955" target="_blank"〉PubMed〈/a〉
    Keywords: Androgen Antagonists/pharmacology/*therapeutic use ; Animals ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; Humans ; Male ; Mice ; Neoplastic Cells, Circulating/drug effects/*metabolism ; Phenylthiohydantoin/*analogs & derivatives/pharmacology/therapeutic use ; Prostate/drug effects/metabolism/pathology ; Prostatic Neoplasms/*drug therapy/*pathology ; Proto-Oncogene Proteins/genetics/metabolism ; RNA Splicing ; Receptors, Androgen/*genetics ; Sequence Analysis, RNA/methods ; Signal Transduction ; Single-Cell Analysis/methods ; Transcriptome ; Wnt Proteins/genetics/*metabolism ; Xenograft Model Antitumor Assays
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  • 82
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-12-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Travis, John -- New York, N.Y. -- Science. 2015 Dec 18;350(6267):1456-7. doi: 10.1126/science.350.6267.1456.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26680172" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria/genetics ; *CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; DNA/genetics ; Embryo, Mammalian ; Gene Targeting/*methods ; Genetic Engineering/*methods ; Genome/*genetics ; Humans ; Mice ; Organisms, Genetically Modified
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 83
    Publication Date: 2015-10-31
    Description: Light mechanical stimulation of hairy skin can induce a form of itch known as mechanical itch. This itch sensation is normally suppressed by inputs from mechanoreceptors; however, in many forms of chronic itch, including alloknesis, this gating mechanism is lost. Here we demonstrate that a population of spinal inhibitory interneurons that are defined by the expression of neuropeptide Y::Cre (NPY::Cre) act to gate mechanical itch. Mice in which dorsal NPY::Cre-derived neurons are selectively ablated or silenced develop mechanical itch without an increase in sensitivity to chemical itch or pain. This chronic itch state is histamine-independent and is transmitted independently of neurons that express the gastrin-releasing peptide receptor. Thus, our studies reveal a dedicated spinal cord inhibitory pathway that gates the transmission of mechanical itch.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700934/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700934/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bourane, Steeve -- Duan, Bo -- Koch, Stephanie C -- Dalet, Antoine -- Britz, Olivier -- Garcia-Campmany, Lidia -- Kim, Euiseok -- Cheng, Longzhen -- Ghosh, Anirvan -- Ma, Qiufu -- Goulding, Martyn -- NS072031/NS/NINDS NIH HHS/ -- NS072040/NS/NINDS NIH HHS/ -- NS080586/NS/NINDS NIH HHS/ -- NS086372/NS/NINDS NIH HHS/ -- P01 NS072040/NS/NINDS NIH HHS/ -- P30 NS072031/NS/NINDS NIH HHS/ -- R01 NS 067216/NS/NINDS NIH HHS/ -- R01 NS080586/NS/NINDS NIH HHS/ -- R01 NS086372/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):550-4. doi: 10.1126/science.aac8653.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA. ; Neurobiology Section, Division of Biological Sciences, University of California, San Diego, CA 92093, USA. ; Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA. Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China. ; Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA. goulding@salk.edu qiufu_ma@dfci.harvard.edu. ; Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. goulding@salk.edu qiufu_ma@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516282" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Hair/physiology ; Interneurons/*physiology ; Mechanoreceptors/physiology ; Mechanotransduction, Cellular/genetics/*physiology ; Mice ; Mice, Transgenic ; *Neural Inhibition ; Neuropeptide Y/genetics/physiology ; Pruritus/*physiopathology ; Skin/innervation ; Spinal Cord/*physiology ; *Synaptic Transmission
    Print ISSN: 0036-8075
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  • 84
    Publication Date: 2015-05-16
    Description: In animal gonads, PIWI-clade Argonaute proteins repress transposons sequence-specifically via bound Piwi-interacting RNAs (piRNAs). These are processed from single-stranded precursor RNAs by largely unknown mechanisms. Here we show that primary piRNA biogenesis is a 3'-directed and phased process that, in the Drosophila germ line, is initiated by secondary piRNA-guided transcript cleavage. Phasing results from consecutive endonucleolytic cleavages catalyzed by Zucchini, implying coupled formation of 3' and 5' ends of flanking piRNAs. Unexpectedly, Zucchini also participates in 3' end formation of secondary piRNAs. Its function can, however, be bypassed by downstream piRNA-guided precursor cleavages coupled to exonucleolytic trimming. Our data uncover an evolutionarily conserved piRNA biogenesis mechanism in which Zucchini plays a central role in defining piRNA 5' and 3' ends.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohn, Fabio -- Handler, Dominik -- Brennecke, Julius -- New York, N.Y. -- Science. 2015 May 15;348(6236):812-7. doi: 10.1126/science.aaa1039.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria. ; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr. Bohrgasse 3, 1030 Vienna, Austria. julius.brennecke@imba.oeaw.ac.at.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25977553" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*enzymology/genetics ; Endoribonucleases/genetics/*metabolism ; Evolution, Molecular ; Female ; Germ Cells/enzymology ; Male ; Mice ; Ovary/enzymology ; *RNA Cleavage ; RNA, Guide/*metabolism ; RNA, Small Interfering/biosynthesis/*metabolism ; RNA-Binding Proteins/genetics ; Testis/enzymology ; *Transcription, Genetic ; Uridine/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 85
    Publication Date: 2015-10-24
    Description: Mammalian sleep comprises rapid eye movement (REM) sleep and non-REM (NREM) sleep. To functionally isolate from the complex mixture of neurons populating the brainstem pons those involved in switching between REM and NREM sleep, we chemogenetically manipulated neurons of a specific embryonic cell lineage in mice. We identified excitatory glutamatergic neurons that inhibit REM sleep and promote NREM sleep. These neurons shared a common developmental origin with neurons promoting wakefulness; both derived from a pool of proneural hindbrain cells expressing Atoh1 at embryonic day 10.5. We also identified inhibitory gamma-aminobutyric acid-releasing neurons that act downstream to inhibit REM sleep. Artificial reduction or prolongation of REM sleep in turn affected slow-wave activity during subsequent NREM sleep, implicating REM sleep in the regulation of NREM sleep.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hayashi, Yu -- Kashiwagi, Mitsuaki -- Yasuda, Kosuke -- Ando, Reiko -- Kanuka, Mika -- Sakai, Kazuya -- Itohara, Shigeyoshi -- New York, N.Y. -- Science. 2015 Nov 20;350(6263):957-61. doi: 10.1126/science.aad1023. Epub 2015 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai Tsukuba, Ibaraki 305-8575, Japan. Japan Science and Technology Agency (JST), PRESTO, 4-1-8 Honcho Kawaguchi, Saitama 332-0012, Japan. hayashi.yu.fp@u.tsukuba.ac.jp sitohara@brain.riken.jp. ; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai Tsukuba, Ibaraki 305-8575, Japan. ; Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan. ; Integrative Physiology of the Brain Arousal System, Lyon Neuroscience Research Center, INSERM U1028-CNRS UMR5292, School of Medicine, Claude Bernard University Lyon 1, F-69373 Lyon, France. ; Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan. hayashi.yu.fp@u.tsukuba.ac.jp sitohara@brain.riken.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26494173" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Brain Stem/cytology/physiology ; Cell Lineage ; Cell Separation ; Female ; Glutamates/metabolism ; Male ; Mice ; Mice, Transgenic ; Neurons/metabolism/*physiology ; Pons/cytology/physiology ; Rhombencephalon/*cytology/*embryology ; Sleep, REM/*physiology ; Wakefulness/*physiology ; gamma-Aminobutyric Acid
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 86
    Publication Date: 2015-03-21
    Description: Deterioration of adult stem cells accounts for much of aging-associated compromised tissue maintenance. How stem cells maintain metabolic homeostasis remains elusive. Here, we identified a regulatory branch of the mitochondrial unfolded protein response (UPR(mt)), which is mediated by the interplay of SIRT7 and NRF1 and is coupled to cellular energy metabolism and proliferation. SIRT7 inactivation caused reduced quiescence, increased mitochondrial protein folding stress (PFS(mt)), and compromised regenerative capacity of hematopoietic stem cells (HSCs). SIRT7 expression was reduced in aged HSCs, and SIRT7 up-regulation improved the regenerative capacity of aged HSCs. These findings define the deregulation of a UPR(mt)-mediated metabolic checkpoint as a reversible contributing factor for HSC aging.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447312/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447312/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mohrin, Mary -- Shin, Jiyung -- Liu, Yufei -- Brown, Katharine -- Luo, Hanzhi -- Xi, Yannan -- Haynes, Cole M -- Chen, Danica -- R01 AG040990/AG/NIA NIH HHS/ -- R01AG040061/AG/NIA NIH HHS/ -- T32 AG000266/AG/NIA NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1374-7. doi: 10.1126/science.aaa2361.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Biochemistry, Cell and Molecular Biology Allied Program, Weill Cornell Medical College, 1300 York Avenue, New York, NY, USA. ; Program in Metabolic Biology, Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720, USA. danicac@berkeley.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Aging ; *Cell Cycle Checkpoints ; Energy Metabolism ; HEK293 Cells ; Hematopoietic Stem Cells/metabolism/*physiology ; Humans ; Mice ; Mice, Mutant Strains ; Mitochondria/*metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Nuclear Respiratory Factor 1/*metabolism ; Protein Biosynthesis ; Sirtuins/genetics/*metabolism ; *Unfolded Protein Response
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  • 87
    Publication Date: 2015-09-19
    Description: Throughout life, neural stem cells (NSCs) generate neurons in the mammalian brain. Using photobleaching experiments, we found that during cell division in vitro and within the developing mouse forebrain, NSCs generate a lateral diffusion barrier in the membrane of the endoplasmic reticulum, thereby promoting asymmetric segregation of cellular components. The diffusion barrier weakens with age and in response to impairment of lamin-associated nuclear envelope constituents. Weakening of the diffusion barrier disrupts asymmetric segregation of damaged proteins, a product of aging. Damaged proteins are asymmetrically inherited by the nonstem daughter cell in embryonic and young adult NSC divisions, whereas in the older adult brain, damaged proteins are more symmetrically distributed between progeny. Thus, these data identify a mechanism of how damage that accumulates with age is asymmetrically distributed during somatic stem cell division.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Moore, D L -- Pilz, G A -- Arauzo-Bravo, M J -- Barral, Y -- Jessberger, S -- New York, N.Y. -- Science. 2015 Sep 18;349(6254):1334-8. doi: 10.1126/science.aac9868.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland. ; Biodonostia Health Research Institute, 20014 San Sebastian, Spain. IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain. ; Institute of Biochemistry, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland. ; Brain Research Institute, Faculty of Medicine and Science, University of Zurich, 8057 Zurich, Switzerland. jessberger@hifo.uzh.ch.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26383951" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Aging ; *Cell Division ; Diffusion ; Endoplasmic Reticulum/physiology/ultrastructure ; Intracellular Membranes/physiology/ultrastructure ; Lamin Type A/*metabolism ; Mice ; Neural Stem Cells/*cytology/*metabolism ; Photobleaching ; Prosencephalon/cytology/growth & development/metabolism ; Protein Transport
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  • 88
    Publication Date: 2015-05-30
    Description: Memory consolidation is the process by which a newly formed and unstable memory transforms into a stable long-term memory. It is unknown whether the process of memory consolidation occurs exclusively through the stabilization of memory engrams. By using learning-dependent cell labeling, we identified an increase of synaptic strength and dendritic spine density specifically in consolidated memory engram cells. Although these properties are lacking in engram cells under protein synthesis inhibitor-induced amnesia, direct optogenetic activation of these cells results in memory retrieval, and this correlates with retained engram cell-specific connectivity. We propose that a specific pattern of connectivity of engram cells may be crucial for memory information storage and that strengthened synapses in these cells critically contribute to the memory retrieval process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ryan, Tomas J -- Roy, Dheeraj S -- Pignatelli, Michele -- Arons, Autumn -- Tonegawa, Susumu -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2015 May 29;348(6238):1007-13. doi: 10.1126/science.aaa5542. Epub 2015 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. ; RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. tonegawa@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26023136" target="_blank"〉PubMed〈/a〉
    Keywords: Amnesia, Retrograde/chemically induced/*physiopathology ; Amygdala/chemistry/physiopathology ; Animals ; Conditioning, Classical ; Dendrites/chemistry/pathology/*physiology ; Dentate Gyrus/chemistry/pathology/physiopathology ; Fluorescent Dyes/analysis ; Luminescent Proteins/analysis ; Memory, Long-Term/*physiology ; Mice ; Neuronal Plasticity/physiology ; Protein Synthesis Inhibitors/pharmacology ; Staining and Labeling ; Synapses/physiology
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  • 89
    Publication Date: 2015-03-21
    Description: Neuronal excitation is regulated by energy metabolism, and drug-resistant epilepsy can be suppressed by special diets. Here, we report that seizures and epileptiform activity are reduced by inhibition of the metabolic pathway via lactate dehydrogenase (LDH), a component of the astrocyte-neuron lactate shuttle. Inhibition of the enzyme LDH hyperpolarized neurons, which was reversed by the downstream metabolite pyruvate. LDH inhibition also suppressed seizures in vivo in a mouse model of epilepsy. We further found that stiripentol, a clinically used antiepileptic drug, is an LDH inhibitor. By modifying its chemical structure, we identified a previously unknown LDH inhibitor, which potently suppressed seizures in vivo. We conclude that LDH inhibitors are a promising new group of antiepileptic drugs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sada, Nagisa -- Lee, Suni -- Katsu, Takashi -- Otsuki, Takemi -- Inoue, Tsuyoshi -- New York, N.Y. -- Science. 2015 Mar 20;347(6228):1362-7. doi: 10.1126/science.aaa1299.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. ; Department of Hygiene, Kawasaki Medical School, Kurashiki 701-0192, Japan. ; Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan. tinoue@pharm.okayama-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25792327" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anticonvulsants/chemistry/*pharmacology/therapeutic use ; Dioxolanes/chemistry/*pharmacology/therapeutic use ; Disease Models, Animal ; Enzyme Inhibitors/chemistry/*pharmacology/therapeutic use ; L-Lactate Dehydrogenase/*antagonists & inhibitors ; Membrane Potentials/drug effects ; Mice ; Mice, Inbred ICR ; Neurons/enzymology/physiology ; Patch-Clamp Techniques ; Safrole/chemistry/*pharmacology/therapeutic use ; Seizures/*drug therapy ; Subthalamic Nucleus/enzymology
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  • 90
    Publication Date: 2015-10-17
    Description: Research in the genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. Although the exact identity of many of the genes remains to be discovered, genes identified to date encode proteins that play roles in certain conserved pathways: protein synthesis, transcriptional and epigenetic regulation, and synaptic signaling. The next generation of research in neurodevelopmental disorders must address the neural circuitry underlying the behavioral symptoms and comorbidities, the cell types playing critical roles in these circuits, and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we can leverage the heterogeneity of neurodevelopmental disorders into precision medicine will the mechanism-based therapeutics for these disorders start to unlock success.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739545/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739545/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sahin, Mustafa -- Sur, Mriganka -- EF1451125/PHS HHS/ -- EY007023/EY/NEI NIH HHS/ -- MH085802/MH/NIMH NIH HHS/ -- NS090473/NS/NINDS NIH HHS/ -- P20 NS080199/NS/NINDS NIH HHS/ -- P30 HD018655/HD/NICHD NIH HHS/ -- U01 NS082320/NS/NINDS NIH HHS/ -- U54 NS092090/NS/NINDS NIH HHS/ -- U54NS092090/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2015 Nov 20;350(6263). pii: aab3897. doi: 10.1126/science.aab3897. Epub 2015 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉F. M. Kirby Center for Neurobiology, Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA. mustafa.sahin@childrens.harvard.edu msur@mit.edu. ; Simons Center for the Social Brain, Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. mustafa.sahin@childrens.harvard.edu msur@mit.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26472761" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autistic Disorder/drug therapy/genetics ; Behavior ; Brain/growth & development/metabolism ; Chromatin Assembly and Disassembly ; Clinical Trials as Topic ; Epigenesis, Genetic ; Genes ; *Genetic Predisposition to Disease ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Mutation ; Neural Pathways/metabolism ; Neurodevelopmental Disorders/*drug therapy/*genetics ; Precision Medicine/*methods ; Protein Biosynthesis/genetics ; Transcription, Genetic ; Translational Medical Research
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  • 91
    facet.materialart.
    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1188-90. doi: 10.1126/science.350.6265.1188.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785475" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/blood/genetics/*physiology ; Animals ; Biological Clocks/genetics/*physiology ; Biomarkers/blood/metabolism ; DNA/genetics ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Mice ; Rats ; Telomere Homeostasis
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 92
    Publication Date: 2015-02-14
    Description: The C-terminal region of Clostridium perfringens enterotoxin (C-CPE) can bind to specific claudins, resulting in the disintegration of tight junctions (TJs) and an increase in the paracellular permeability across epithelial cell sheets. Here we present the structure of mammalian claudin-19 in complex with C-CPE at 3.7 A resolution. The structure shows that C-CPE forms extensive hydrophobic and hydrophilic interactions with the two extracellular segments of claudin-19. The claudin-19/C-CPE complex shows no density of a short extracellular helix that is critical for claudins to assemble into TJ strands. The helix displacement may thus underlie C-CPE-mediated disassembly of TJs.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saitoh, Yasunori -- Suzuki, Hiroshi -- Tani, Kazutoshi -- Nishikawa, Kouki -- Irie, Katsumasa -- Ogura, Yuki -- Tamura, Atsushi -- Tsukita, Sachiko -- Fujiyoshi, Yoshinori -- New York, N.Y. -- Science. 2015 Feb 13;347(6223):775-8. doi: 10.1126/science.1261833.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. ; Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. ; Cellular and Structural Physiology Institute, Nagoya University, Chikusa, Nagoya 464-8601, Japan. Department of Basic Medical Science, Graduate School of Pharmaceutical Science, Nagoya University, Chikusa, Nagoya 464-8601, Japan. yoshi@cespi.nagoya-u.ac.jp.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25678664" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Claudins/*chemistry ; Enterotoxins/*chemistry ; Hydrophobic and Hydrophilic Interactions ; Mice ; Protein Structure, Secondary ; Tight Junctions/chemistry/*ultrastructure
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 93
    Publication Date: 2015-02-28
    Description: Ebola virus causes sporadic outbreaks of lethal hemorrhagic fever in humans, but there is no currently approved therapy. Cells take up Ebola virus by macropinocytosis, followed by trafficking through endosomal vesicles. However, few factors controlling endosomal virus movement are known. Here we find that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Disrupting TPC function by gene knockout, small interfering RNAs, or small-molecule inhibitors halted virus trafficking and prevented infection. Tetrandrine, the most potent small molecule that we tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. Therefore, TPC proteins play a key role in Ebola virus infection and may be effective targets for antiviral therapy.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550587/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4550587/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakurai, Yasuteru -- Kolokoltsov, Andrey A -- Chen, Cheng-Chang -- Tidwell, Michael W -- Bauta, William E -- Klugbauer, Norbert -- Grimm, Christian -- Wahl-Schott, Christian -- Biel, Martin -- Davey, Robert A -- R01 AI063513/AI/NIAID NIH HHS/ -- R01AI063513/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Feb 27;347(6225):995-8. doi: 10.1126/science.1258758.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Texas Biomedical Research Institute, San Antonio, TX, USA. ; The University of Texas Medical Branch, Galveston, TX, USA. ; Center for Integrated Protein Science Munich (CIPSM) at the Department of Pharmacy-Center for Drug Research, Ludwig-Maximilians-Universitat Munchen, Munich, Germany. ; Southwest Research Institute, San Antonio, TX, USA. ; Institute for Experimental and Clinical Pharmacology and Toxicology, Albert-Ludwigs-Universitat Freiburg, Freiburg, Germany. ; Texas Biomedical Research Institute, San Antonio, TX, USA. rdavey@txbiomed.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25722412" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antiviral Agents/*pharmacology/therapeutic use ; BALB 3T3 Cells ; Benzylisoquinolines/pharmacology/therapeutic use ; Calcium Channel Blockers/*pharmacology/therapeutic use ; Calcium Channels/genetics/*physiology ; Ebolavirus/drug effects/*physiology ; Female ; Gene Knockout Techniques ; HeLa Cells ; Hemorrhagic Fever, Ebola/drug therapy/*therapy/virology ; Humans ; Macrophages/drug effects/virology ; Mice ; *Molecular Targeted Therapy ; NADP/analogs & derivatives/metabolism ; RNA Interference ; Signal Transduction ; Verapamil/pharmacology/therapeutic use ; Virus Internalization/*drug effects
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 94
    Publication Date: 2015-07-04
    Description: Larger brains tend to have more folded cortices, but what makes the cortex fold has remained unknown. We show that the degree of cortical folding scales uniformly across lissencephalic and gyrencephalic species, across individuals, and within individual cortices as a function of the product of cortical surface area and the square root of cortical thickness. This relation is derived from the minimization of the effective free energy associated with cortical shape according to a simple physical model, based on known mechanisms of axonal elongation. This model also explains the scaling of the folding index of crumpled paper balls. We discuss the implications of this finding for the evolutionary and developmental origin of folding, including the newfound continuum between lissencephaly and gyrencephaly, and for pathologies such as human lissencephaly.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mota, Bruno -- Herculano-Houzel, Suzana -- New York, N.Y. -- Science. 2015 Jul 3;349(6243):74-7. doi: 10.1126/science.aaa9101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Instituto de Fisica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. ; Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Instituto Nacional de Neurociencia Translacional, INCT/MCT, Sao Paulo, Brazil. suzanahh@gmail.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26138976" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Count ; *Cerebral Cortex/cytology/embryology/pathology ; Humans ; Lissencephaly/*pathology ; Mice ; Models, Neurological ; Neurons/*cytology/pathology ; Rats ; Species Specificity
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 95
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-10-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Oct 30;350(6260):491-2. doi: 10.1126/science.350.6260.491.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26516259" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*physiology/ultrastructure ; Brain-Derived Neurotrophic Factor/pharmacology ; Memory, Long-Term/*physiology ; Mice ; Microscopy, Electron ; Nerve Net/*physiology/ultrastructure ; Neurons/drug effects/physiology ; Neurosciences ; Synapses/*physiology/ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 96
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-04-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mueller, Kristen L -- New York, N.Y. -- Science. 2015 Apr 3;348(6230):54-5. doi: 10.1126/science.348.6230.54.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25838372" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology/therapeutic use ; Humans ; Immunotherapy ; Mice ; Neoplasms/*immunology/*therapy ; Receptors, Antigen, T-Cell/antagonists & inhibitors/immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2015-04-25
    Description: Inflammatory CD4(+) T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. Although selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here, we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII(+) ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4(+) T cells in the intestine and suggest that this process is dysregulated in human IBD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449822/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449822/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hepworth, Matthew R -- Fung, Thomas C -- Masur, Samuel H -- Kelsen, Judith R -- McConnell, Fiona M -- Dubrot, Juan -- Withers, David R -- Hugues, Stephanie -- Farrar, Michael A -- Reith, Walter -- Eberl, Gerard -- Baldassano, Robert N -- Laufer, Terri M -- Elson, Charles O -- Sonnenberg, Gregory F -- DK071176/DK/NIDDK NIH HHS/ -- DP5 OD012116/OD/NIH HHS/ -- DP5OD012116/OD/NIH HHS/ -- UL1-RR024134/RR/NCRR NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2015 May 29;348(6238):1031-5. doi: 10.1126/science.aaa4812. Epub 2015 Apr 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. ; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ; Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA. ; Medical Research Council, Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. ; Department of Pathology and Immunology, University of Geneva Medical School, Geneva, Switzerland. ; Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, MN, USA. ; Institut Pasteur, Microenvironment and Immunity Unit, Paris, France. ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA. ; Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA. ; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Joan and Sanford I. Weill Department of Medicine, Gastroenterology Division, and Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. gfsonnenberg@med.cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25908663" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/immunology ; Autoimmunity ; Bacteria/*immunology ; CD4-Positive T-Lymphocytes/*immunology ; Colon/*microbiology ; Female ; Flagellin/genetics/immunology ; Histocompatibility Antigens Class II/*immunology ; Humans ; *Immunity, Innate ; Inflammatory Bowel Diseases/immunology/*microbiology ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred C57BL ; Symbiosis ; Thymus Gland/immunology
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Aug 7;349(6248):575-7. doi: 10.1126/science.349.6248.575.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26250665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*cytology ; Caenorhabditis elegans ; Cell Shape ; Humans ; Identity Crisis ; Interneurons/classification ; Mice ; Neuroanatomy/*methods ; Neurons/*classification ; Retina/cytology ; Silver Staining ; Visual Cortex/cytology
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  • 99
    Publication Date: 2015-03-31
    Description: Trypanosoma brucei, a causative agent of African Sleeping Sickness, constantly changes its dense variant surface glycoprotein (VSG) coat to avoid elimination by the immune system of its mammalian host, using an extensive repertoire of dedicated genes. However, the dynamics of VSG expression in T. brucei during an infection are poorly understood. We have developed a method, based on de novo assembly of VSGs, for quantitatively examining the diversity of expressed VSGs in any population of trypanosomes and monitored VSG population dynamics in vivo. Our experiments revealed unexpected diversity within parasite populations and a mechanism for diversifying the genome-encoded VSG repertoire. The interaction between T. brucei and its host is substantially more dynamic and nuanced than previously expected.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514441/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4514441/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mugnier, Monica R -- Cross, George A M -- Papavasiliou, F Nina -- AI085973/AI/NIAID NIH HHS/ -- R01 AI085973/AI/NIAID NIH HHS/ -- R01 AI097127/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Mar 27;347(6229):1470-3. doi: 10.1126/science.aaa4502.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY, USA. Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA. ; Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY, USA. Laboratory of Molecular Parasitology, The Rockefeller University, New York, NY, USA. papavasiliou@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25814582" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Antigenic Variation ; Host-Parasite Interactions/*immunology ; Humans ; Mice ; Mice, Inbred BALB C ; Trypanosoma brucei brucei/*immunology ; Trypanosomiasis, African/*immunology ; Variant Surface Glycoproteins, Trypanosoma/*immunology
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2015-03-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2015 Mar 13;347(6227):1186-7. doi: 10.1126/science.347.6227.1186.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25766212" target="_blank"〉PubMed〈/a〉
    Keywords: Alzheimer Disease/pathology/*therapy ; Animals ; Antineoplastic Agents/administration & dosage ; *Blood-Brain Barrier ; Brain/pathology ; Brain Neoplasms/drug therapy/*therapy ; Clinical Trials, Phase I as Topic ; Disease Models, Animal ; Humans ; Mice ; Microbubbles ; Plaque, Amyloid/pathology/therapy ; *Ultrasonic Therapy
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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