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  • Elsevier  (1,429,696)
  • American Institute of Physics (AIP)  (154,286)
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  • 1
    Call number: QZ269:203(3)
    Keywords: Radiation Oncology / methods ; Neoplasms / radiotherapy
    Pages: xxviii, 713 p. : ill.
    Edition: 3rd ed.
    ISBN: 9780128141281
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  • 2
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    München : Elsevier
    Call number: WN180:10(5)
    Pages: ix, 141 p. : ill.
    Edition: 5. Aufl.
    ISBN: 9783437422973
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  • 3
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    Amsterdam : Elsevier
    Call number: QZ200:575(3)/2
    Keywords: Neoplasms ; DKFZ-publications
    Notes: Contributor: Michael Baumann
    Pages: xl, 577 p. : ill.
    Edition: 3rd ed.
    ISBN: 9780128124840
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  • 4
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    München : Elsevier
    Call number: QZ269:204(3)
    Keywords: Neoplasms / radiotherapy ; Radiotherapy
    Pages: xxviii, 419 p. : ill.
    Edition: 3. Aufl.
    ISBN: 9783437232923
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  • 5
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    Amsterdam : Elsevier
    Call number: QZ200:575(3)/1
    Keywords: Neoplasms ; DKFZ-publications
    Notes: Contributor: Michael Baumann
    Pages: xl, 585 p. : ill.
    Edition: 3rd ed.
    ISBN: 9780128124840
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  • 6
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    Amsterdam : Elsevier
    Call number: QZ200:575(3)/3
    Keywords: Neoplasms ; DKFZ-publications
    Notes: Contributor: Michael Baumann
    Pages: xl, 605 p. : ill.
    Edition: 3rd ed.
    ISBN: 9780128124840
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  • 7
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    Elsevier
    Publication Date: 2018-05-28
    Description: Publication date: 1 August 2018 Source: NeuroImage, Volume 176
    Print ISSN: 1053-8119
    Electronic ISSN: 1095-9572
    Topics: Medicine , Psychology
    Published by Elsevier
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  • 8
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    Elsevier
    Publication Date: 2018-05-28
    Description: Publication date: September 2018 Source: NeuroImage, Volume 178 Author(s): Hanna Keren, Gang Chen, Brenda Benson, Monique Ernst, Ellen Leibenluft, Nathan A. Fox, Daniel S. Pine, Argyris Stringaris Reward Prediction Errors (RPEs), defined as the difference between the expected and received outcomes, are integral to reinforcement learning models and play an important role in development and psychopathology. In humans, RPE encoding can be estimated using fMRI recordings, however, a basic measurement property of RPE signals, their test-retest reliability across different time scales, remains an open question. In this paper, we examine the 3-month and 3-year reliability of RPE encoding in youth (mean age at baseline = 10.6 ± 0.3 years), a period of developmental transitions in reward processing. We show that RPE encoding is differentially distributed between the positive values being encoded predominantly in the striatum and negative RPEs primarily encoded in the insula. The encoding of negative RPE values is highly reliable in the right insula, across both the long and the short time intervals. Insula reliability for RPE encoding is the most robust finding, while other regions, such as the striatum, are less consistent. Striatal reliability appeared significant as well once covarying for factors, which were possibly confounding the signal to noise ratio. By contrast, task activation during feedback in the striatum is highly reliable across both time intervals. These results demonstrate the valence-dependent differential encoding of RPE signals between the insula and striatum, and the consistency of RPE signals or lack thereof, during childhood and into adolescence. Characterizing the regions where the RPE signal in BOLD fMRI is a reliable marker is key for estimating reward-processing alterations in longitudinal designs, such as developmental or treatment studies.
    Print ISSN: 1053-8119
    Electronic ISSN: 1095-9572
    Topics: Medicine , Psychology
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  • 9
    Publication Date: 2018-05-19
    Description: Publication date: Available online 18 May 2018 Source: Methods Author(s): James Birch, Danny Axford, James Foadi, Arne Meyer, Annette Eckardt, Yvonne Thielmann, Isabel Moraes Integral membrane proteins are among the most fascinating and important biomolecules as they play a vital role in many biological functions. Knowledge of their atomic structures is fundamental to the understanding of their biochemical function and key in many drug discovery programs. However, over the years, structure determination of integral membrane proteins has proven to be far from trivial, hence they are underrepresented in the protein data bank. Low expression levels, insolubility and instability are just a few of the many hurdles one faces when studying these proteins. X-ray crystallography has been the most used method to determine atomic structures of membrane proteins. However, the production of high quality membrane protein crystals is always very challenging, often seen more as art than a rational experiment. Here we review valuable approaches, methods and techniques to successful membrane protein crystallisation.
    Print ISSN: 1046-2023
    Topics: Biology , Medicine
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  • 10
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    Elsevier
    Publication Date: 2018-05-19
    Description: Publication date: 17 May 2018 Source: Molecular Cell, Volume 70, Issue 4 Author(s): Andrew Chatr-aryamontri, Almer van der Sloot, Mike Tyers The ubiquitin-proteasome system controls the stability of myriad protein substrates via short sequence motifs called degrons. Studies by Koren et al. (2018) and Lin et al. (2018) have uncovered a broad new class of degrons located at the extreme C terminus of substrates. Teaser The ubiquitin-proteasome system controls the stability of myriad protein substrates via short sequence motifs called degrons. Studies by Koren et al. (2018) and Lin et al. (2018) have uncovered a broad new class of degrons located at the extreme C terminus of substrates.
    Print ISSN: 1097-2765
    Electronic ISSN: 1097-4164
    Topics: Biology , Medicine
    Published by Elsevier on behalf of Cell Press.
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  • 11
    Publication Date: 2018-05-19
    Description: Publication date: 17 May 2018 Source: Molecular Cell, Volume 70, Issue 4 Author(s): Sophie Gay, Daniele Piccini, Christopher Bruhn, Sara Ricciardi, Paolo Soffientini, Walter Carotenuto, Stefano Biffo, Marco Foiani Cell survival to replication stress depends on the activation of the Mec1 ATR -Rad53 checkpoint response that protects the integrity of stalled forks and controls the origin firing program. Here we found that Mad2, a member of the spindle assembly checkpoint (SAC), contributes to efficient origin firing and to cell survival in response to replication stress. We show that Rad53 and Mad2 promote S-phase cyclin expression through different mechanisms: while Rad53 influences Clb5,6 degradation, Mad2 promotes their protein synthesis. We found that Mad2 co-sediments with polysomes and modulates the association of the translation inhibitor Caf20 4E-BP with the translation machinery and the initiation factor eIF4E. This Mad2-dependent translational regulatory process does not depend on other SAC proteins. Altogether our observations indicate that Mad2 has an additional function outside of mitosis to control DNA synthesis and collaborates with the Mec1-Rad53 regulatory axis to allow cell survival in response to replication stress. Graphical abstract Teaser Here, Gay et al. show that, in addition to its well-established role in the spindle checkpoint, Mad2 promotes translation of S-phase cyclin mRNAs. This S-phase role of Mad2 is critical for cell survival following replication stress.
    Print ISSN: 1097-2765
    Electronic ISSN: 1097-4164
    Topics: Biology , Medicine
    Published by Elsevier on behalf of Cell Press.
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  • 12
    Publication Date: 2018-05-19
    Description: Publication date: 17 May 2018 Source: Molecular Cell, Volume 70, Issue 4 Author(s): Kotaro Tsuboyama, Hisashi Tadakuma, Yukihide Tomari Loading of small RNAs into Argonaute, the core protein in RNA silencing, requires the Hsp70/Hsp90 chaperone machinery. This machinery also activates many other clients, including steroid hormone receptors and kinases, but how their structures change during chaperone-dependent activation remains unclear. Here, we utilized single-molecule Förster resonance energy transfer (smFRET) to probe the conformational changes of Drosophila Ago2 mediated by the chaperone machinery. We found that empty Ago2 exists in various closed conformations. The Hsp70 system (Hsp40 and Hsp70) and the Hsp90 system (Hop, Hsp90, and p23) together render Ago2 into an open, active form. The Hsp70 system, but not the Hsp90 system alone, is sufficient for Ago2 to partially populate the open form. Instead, the Hsp90 system is required to extend the dwell time of Ago2 in the open state, which must be transiently primed by the Hsp70 system. Our data uncover distinct and coordinated actions of the chaperone machinery, where the Hsp70 system expands the structural ensembles of Ago2 and the Hsp90 system captures and stabilizes the active form. Graphical abstract Teaser It remains unclear how the Hsp70/Hsp90 chaperone machinery modulates the structure of client proteins for their activation. Tsuboyama et al. utilized single-molecule FRET to show the chaperone-assisted dynamic conformational changes of Argonaute during small RNA loading, revealing distinct yet coordinated actions of the Hsp70 and Hsp90 systems.
    Print ISSN: 1097-2765
    Electronic ISSN: 1097-4164
    Topics: Biology , Medicine
    Published by Elsevier on behalf of Cell Press.
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  • 13
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    Elsevier
    Publication Date: 2018-05-28
    Description: Publication date: Available online 26 May 2018 Source: Trends in Biochemical Sciences Author(s): Jack G. Salway Hans Kornberg wrote a paper entitled ‘Krebs and his trinity of cycles' commenting that every school biology student knows of the Krebs cycle, but few know that Krebs discovered two other cycles. These are (i) the ornithine cycle (urea cycle), (ii) the citric acid cycle (tricarboxylic acid or TCA cycle), and (iii) the glyoxylate cycle that was described by Krebs and Kornberg. Ironically, Kornberg, codiscoverer of the ‘glyoxylate cycle’, overlooked a fourth Krebs cycle – (iv) the uric acid cycle.
    Print ISSN: 0968-0004
    Electronic ISSN: 0968-0004
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 14
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    Elsevier
    Publication Date: 2018-05-28
    Description: Publication date: Available online 26 May 2018 Source: Trends in Microbiology Author(s): Cecily R. Wood, Lydia E. Mack, Luis A. Actis Acinetobacter baumannii adapts to different environmental conditions by expressing complex regulatory circuitry. Recent studies revealed that this circuitry includes regulatory factors that control the emergence of distinct bacterial subpopulations, which are critical for the capacity of this pathogen to persist in medical settings and cause infections in compromised hosts.
    Print ISSN: 0966-842X
    Electronic ISSN: 1878-4380
    Topics: Biology
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  • 15
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    Elsevier
    Publication Date: 2018-05-28
    Description: Publication date: Available online 26 May 2018 Source: Trends in Immunology Author(s): Timon E. Adolph, Christoph Grander, Alexander R. Moschen, Herbert Tilg The intestinal and hepatobiliary tract exhibits host-specific commensal colonization. The resident microbiota has emerged as a key player in intestinal and hepatic diseases. Alcoholic and nonalcoholic fatty liver diseases (ALD/NAFLD), primary sclerosing cholangitis (PSC), liver cirrhosis, and some of their clinical complications, such as hepatic encephalopathy (HE), have been linked to a microbial signature, as also observed for severe liver inflammation in alcoholic hepatitis. In turn, the liver impacts, and communicates with, the microbiota through hepatic mediators, such as bile acids or inflammatory signals. Therefore, a liver–microbiome bidirectional crosstalk appears to be critical in health and various liver diseases and could be therapeutically targeted, such as by fecal microbiota transplantation.
    Print ISSN: 1471-4906
    Electronic ISSN: 1471-4981
    Topics: Medicine
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  • 16
    Publication Date: 2018-05-28
    Description: Publication date: Available online 26 May 2018 Source: Virus Research Author(s): Min Feng, Jianjia Zhang, Weifan Xu, Haiping Wang, Xiangshuo Kong, Xiaofeng Wu Bombyx mori nucleopolyhedrovirus (BmNPV) is a leading cause of silkworm mortality and economic loss to sericulture. The entry of BmNPV budded virus (BV) into host cells is a fundamental process required for the initiation of infection. However, our understanding of the mechanism of virus entry is limited and it is unclear whether BV enter BmN cells via clathrin-mediated endocytosis. In this study, we found that BV enter BmN cells through a low-pH-dependent endocytosis pathway. Inhibition assays, transmission electron microscopy (TEM) analysis, and small interfering RNAs (siRNAs) knockdown assays revealed that BV entry into BmN cells is mediated by clathrin-dependent endocytosis. Moreover, after treated with dynasore, an inhibitor of dynamin, BmNPV entry was markedly reduced, indicating that dynamin also participates in the efficient internalization of BmNPV. In addition, suppression of Rab5, Rab7 or Rab11 through siRNAs demonstrated that BV requires early and late endosomes for endocytosis in infection of BmN cells. Taken together, BmNPV uses a clathrin- and dynamin-mediated endocytic pathway into BmN cells that requires participation of Rab5 and Rab7 but not Rab11.
    Print ISSN: 0168-1702
    Electronic ISSN: 1872-7492
    Topics: Medicine
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  • 17
    Publication Date: 2018-05-28
    Description: Publication date: Available online 26 May 2018 Source: Trends in Microbiology Author(s): Leigh K. Harris, Julie A. Theriot An immediately observable feature of bacteria is that cell size and shape are remarkably constant and characteristic for a given species in a particular condition, but vary quantitatively with physiological parameters such as growth rate, indicating both genetic and environmental regulation. However, despite decades of research, the molecular mechanisms underlying bacterial morphogenesis have remained incompletely characterized. We recently demonstrated that a wide range of bacterial species exhibit a robust surface area to volume ratio (SA/V) homeostasis. Because cell size, shape, and SA/V are mathematically interconnected, if SA/V is indeed the natural variable that cells actively monitor, this finding has critical implications for our understanding of bacterial morphogenesis, placing fundamental constraints on the sizes and shapes that cells can adopt. In this Opinion article we discuss the broad implications that this novel perspective has for the field of bacterial growth and morphogenesis.
    Print ISSN: 0966-842X
    Electronic ISSN: 1878-4380
    Topics: Biology
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  • 18
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Yuka Maya, Wataru Narasaki, Yoshiaki Maeda, Mitsuhito Ota
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 19
    Publication Date: 2018-05-29
    Description: Publication date: May 2018 Source: Gynecologic Oncology, Volume 149, Issue 2 Author(s): Cornelia L. Trimble
    Print ISSN: 0090-8258
    Electronic ISSN: 1095-6859
    Topics: Medicine
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  • 20
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Hong-Tao Tie, Rui Shi
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 21
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Sairam Parthasarathy
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 22
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Arka Chatterjee, Mark A. Law
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 23
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Muthiah Vaduganathan, Arman Qamar, Ankur Gupta, Navkaranbir Bajaj, Harsh B. Golwala, Ambarish Pandey, Deepak L. Bhatt
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 24
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Muthiah Vaduganathan, Arman Qamar, Ankur Gupta, Navkaranbir Bajaj, Harsh B. Golwala, Ambarish Pandey, Deepak L. Bhatt
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 25
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Tomoyuki Kawada
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 26
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Abhilash Koratala, Mayanka Kamboj
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 27
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Martin Windpessl
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 28
    Publication Date: 2018-05-29
    Description: Publication date: Available online 28 May 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Marisa R. Adelman, Howard T. Sharp
    Print ISSN: 0002-9378
    Electronic ISSN: 1097-6868
    Topics: Medicine
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  • 29
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Lisa L. Kirkland, Erin Shaughnessy
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 30
    Publication Date: 2018-05-29
    Description: Publication date: Available online 28 May 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Gillian E. Hanley, Janice S. Kwon, Sarah J. Finlayson, David G. Huntsman, Dianne Miller, Jessica N. McAlpine Background Recent evidence has suggested that the fallopian tube may often be the site of origin for the most common and lethal form of ovarian cancer. As a result, many Colleges of Obstetrics & Gynecology, including ACOG, are recommending surgical removal of the fallopian tube (bilateral salpingectomy) at the time of other gynecologic surgeries (particularly hysterectomy and tubal sterilization) in women at general population risk for ovarian cancer, collectively referred to as opportunistic salpingectomy (OS). Objectives Previous research using hospital data has indicated good perioperative safety of opportunistic salpingectomy, but no data on minor complications has been presented. Herein we examine whether women undergoing OS are at increased risk of minor complications following surgery. Study Design We identified all women in British Columbia (BC) who underwent OS between 2008 and 2014 and examined all physician visits in the two weeks post discharge from the hospital. We compared women undergoing OS at hysterectomy with women undergoing hysterectomy alone and women undergoing OS for sterilization with women undergoing tubal ligation. We examined visits for surgical infection, surgical complication, orders for lab tests and orders for imaging (x-ray, ultrasound or CT scan) and whether women undergoing OS were more likely to fill a prescription for an antibiotic or analgesic in the two weeks following discharge from hospital. We calculated adjusted odds ratios for these outcomes adjusting for other gynecologic conditions, surgical approach and patient age. Results We included 49,275 women who had undergone a hysterectomy alone, a hysterectomy with OS, hysterectomy with bilateral salpingo-oophorectomy, a tubal ligation, or an OS for sterilization. In women undergoing OS, there was no increased risk for physician visits for surgical infection, surgical complication, ordering a lab test or ordering imaging in the two weeks post discharge. There was no increased risk of filling a prescription for an antibiotic. However, women undergoing OS were at approximately 20% increased odds of filling a prescription for an analgesic in the two weeks post discharge from hospital (aOR=1.23; 95%CI 1.15, 1.32 for hysterectomy with OS and aOR=1.21; 95%CI 1.14, 1.29 for OS for sterilization). Conclusions We report no differences in minor complications between women undergoing OS and women undergoing hysterectomy alone or tubal ligation, except for a slightly increased likelihood of filling a prescription analgesic medication in the immediate two weeks post discharge.
    Print ISSN: 0002-9378
    Electronic ISSN: 1097-6868
    Topics: Medicine
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  • 31
    Publication Date: 2018-05-29
    Description: Publication date: Available online 28 May 2018 Source: American Journal of Obstetrics and Gynecology Author(s): David Priver
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    Electronic ISSN: 1097-6868
    Topics: Medicine
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  • 32
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: The American Journal of Medicine, Volume 131, Issue 6 Author(s): Saeid Safiri, Ahad Ashrafi-Asgarabad
    Print ISSN: 0002-9343
    Electronic ISSN: 1555-7162
    Topics: Medicine
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  • 33
    Publication Date: 2018-05-29
    Description: Publication date: Available online 28 May 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Christopher P. Chung, Stephen J. Lee, Mark T. Wakabayashi
    Print ISSN: 0002-9378
    Electronic ISSN: 1097-6868
    Topics: Medicine
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  • 34
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: August 2018 Source: Biomaterials, Volume 174
    Print ISSN: 0142-9612
    Electronic ISSN: 1878-5905
    Topics: Biology , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Medicine
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  • 35
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: June 2018 Source: Cancer Treatment Reviews, Volume 67
    Print ISSN: 0305-7372
    Electronic ISSN: 1532-1967
    Topics: Medicine
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  • 36
    Publication Date: 2018-05-29
    Description: Publication date: July 2018 Source: Computer Methods and Programs in Biomedicine, Volume 161 Author(s): Hsuan-Chia Yang, Md. Mohaimenul Islam, Yu-Chuan (Jack) Li
    Print ISSN: 0169-2607
    Electronic ISSN: 1872-7565
    Topics: Biology , Medicine
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  • 37
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: July 2018 Source: Computer Methods and Programs in Biomedicine, Volume 161
    Print ISSN: 0169-2607
    Electronic ISSN: 1872-7565
    Topics: Biology , Medicine
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  • 38
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: 2018 Source: Current Topics in Developmental Biology, Volume 130
    Print ISSN: 0070-2153
    Electronic ISSN: 1557-8933
    Topics: Biology , Medicine
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  • 39
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: 2018 Source: Current Topics in Developmental Biology, Volume 130
    Print ISSN: 0070-2153
    Electronic ISSN: 1557-8933
    Topics: Biology , Medicine
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  • 40
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: 2018 Source: Current Topics in Developmental Biology, Volume 130
    Print ISSN: 0070-2153
    Electronic ISSN: 1557-8933
    Topics: Biology , Medicine
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  • 41
    Publication Date: 2018-05-29
    Description: Publication date: July 2018 Source: Computer Methods and Programs in Biomedicine, Volume 161 Author(s): Hung-Jr Shiu, Bor-Sing Lin, Chien-Hung Huang, Pei-Ying Chiang, Chin-Laung Lei
    Print ISSN: 0169-2607
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    Topics: Biology , Medicine
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  • 42
    Publication Date: 2018-05-29
    Description: Publication date: 2018 Source: Current Topics in Developmental Biology, Volume 130 Author(s): Bette J. Dzamba, Douglas W. DeSimone Extracellular matrices (ECMs) are structurally and compositionally diverse networks of collagenous and noncollagenous glycoproteins, glycosaminoglycans, proteoglycans, and associated molecules that together comprise the metazoan matrisome. Proper deposition and assembly of ECM is of profound importance to cell proliferation, survival, and differentiation, and the morphogenesis of tissues and organ systems that define sequential steps in the development of all animals. Importantly, it is now clear that the instructive influence of a particular ECM at various points in development reflects more than a simple summing of component parts; cellular responses also reflect the dynamic assembly and changing topology of embryonic ECM, which in turn affect its biomechanical properties. This review highlights recent advances in understanding how biophysical features attributed to ECM, such as stiffness and viscoelasticity, play important roles in the sculpting of embryonic tissues and the regulation of cell fates. Forces generated within cells and tissues are transmitted both through integrin-based adhesions to ECM, and through cadherin-dependent cell–cell adhesions; the resulting short- and long-range deformations of embryonic tissues drive morphogenesis. This coordinate regulation of cell–ECM and cell–cell adhesive machinery has emerged as a common theme in a variety of developmental processes. In this review we consider select examples in the embryo where ECM is implicated in setting up tissue barriers and boundaries, in resisting pushing or pulling forces, or in constraining or promoting cell and tissue movement. We reflect on how each of these processes contribute to morphogenesis.
    Print ISSN: 0070-2153
    Electronic ISSN: 1557-8933
    Topics: Biology , Medicine
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  • 43
    Publication Date: 2018-05-29
    Description: Publication date: 2018 Source: Current Topics in Developmental Biology, Volume 130 Author(s): Robert P. Mecham, Francesco Ramirez The extracellular matrix (ECM) is a highly heterogeneous mixture of macromolecules capable of self-assembling into tissue-specific suprastructures that constitute the architectural elements supporting organ function. Contrary to the traditional view of being a static scaffold that supports tissue integrity along with cell adhesion and migration, the ECM is an inherently dynamic system that specifies cellular function and defines the limits and patterns of tissue organization. Throughout evolution, the composition and organization of the ECM have changed to accommodate basic and new tissue functions, both in terms of providing structural support and integrating multivalent signals to cells. In this review, we will highlight some of these bidirectional cell–matrix interactions that guide the development of a mechanically compliant vascular system. Specifically, we will focus on studies that have investigated how ECM composition and physical properties influence cell fate decisions associated with vascular tissue development and homeostasis and implicitly, vascular disease.
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  • 44
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    Publication Date: 2018-05-29
    Description: Publication date: 2018 Source: Current Topics in Developmental Biology, Volume 130 Author(s): Eveline S. Litscher, Paul M. Wassarman
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    Electronic ISSN: 1557-8933
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  • 45
    Publication Date: 2018-05-30
    Description: Publication date: Available online 29 May 2018 Source: The International Journal of Biochemistry & Cell Biology Author(s): Eng-Soon Khor, Pooi-Fong Wong Accumulation of senescent endothelial cells can contribute to endothelium dysfunction. Suppression of MTOR signaling has been shown to delay senescence but the mechanism that underpins this effect, particularly one that involves miRNAs, remains to be further defined. This study sought to identify miRNAs involved in MTORC1-mediated inhibition of replicative senescence in endothelial cells. Pre-senescent HUVECs were prolonged treated with low dose rapamycin (1 nM), an MTOR inhibitor. Rapamycin treatment down-regulated the phosphorylated MTOR, RPS6 and 4EBP1 expressions, which confirmed MTORC1 suppression. Prolonged low dose rapamycin treatment has significantly reduced the percentage of senescence-associated beta galactosidase (SA-β gal) positively stained senescent cells and P16INK4 A expression in these cells. On the contrary, the percentage of BrdU-labelled proliferating cells has significantly increased. RPTOR, a positive regulator of MTORC1 was knockdown using RPTOR siRNA to inhibit MTORC1 activation. RPTOR knockdown was evidenced by significant suppressions of RPTOR mRNA and protein expression levels. In these cells, the expression of miR-107 was down-regulated whereas miR-145-5p and miR-217 were up-regulated. Target gene prediction revealed PTEN as the target of miR-107 and this was confirmed by biotin pull-down assay. Over-expression of miR-107 has decreased PTEN expression, increased MTORC1 activity, induced cell cycle arrest at G0/G1 phase and up-regulated P16INK4 A expression but mitigated tube formation. Collectively, our findings revealed that delayed endothelial replicative senescence caused by the inhibition of MTORC1 activation could be modulated by miR-107 via its influence on PTEN.
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    Electronic ISSN: 1878-5875
    Topics: Biology , Chemistry and Pharmacology , Medicine
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  • 46
    Publication Date: 2018-05-30
    Description: Publication date: 8 June 2018 Source: Journal of Molecular Biology, Volume 430, Issue 12 Author(s): Abbas Abou-Hamdan, Laura Belot, Aurélie Albertini, Yves Gaudin Graphical abstract
    Print ISSN: 0022-2836
    Electronic ISSN: 1089-8638
    Topics: Biology
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  • 47
    Publication Date: 2018-05-29
    Description: Publication date: Available online 24 May 2018 Source: Structure Author(s): Saurav Mallik, Sudip Kundu To find additional structural constraints (besides disordered segments) that regulate protein half-life in the cell, we herein assess the influence of native topology of monomeric and sequestration of oligomeric proteins into multimeric complexes in yeast, human, and mouse. Native topology acts as a molecular marker of globular protein's mechanical resistance and consequently captures their half-life variations on genome scale. Sequestration into multimeric complexes elongates oligomeric protein half-life in the cell, presumably by burying ubiquitinoylation sites and disordered segments required for proteasomal recognition. The latter effect is stronger for proteins associated with multiple complexes and for those binding early during complex self-assembly, including proteins that oligomerize with large proportions of surface buried. After gene duplication, diversification of topology and sequestration into non-identical sets of complexes alter half-lives of paralogous proteins during the course of evolution. Thus, native topology and sequestration into multimeric complexes reflect designing principles of proteins to regulate their half-lives. Graphical abstract Teaser Mallik and Kundu show that native topology of monomeric proteins and sequestration of oligomeric proteins into macromolecular complexes influence their half-lives in the cell and during the course of evolution, presumably by burying ubiquitinoylation sites and disordered segments. The findings provide insights into the design principles of biological macromolecules.
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  • 48
    Publication Date: 2018-05-29
    Description: Publication date: Available online 24 May 2018 Source: Structure Author(s): Sojin An, Philipp Koldewey, Jennifer Chik, Lakxmi Subramanian, Uhn-Soo Cho The Mis18 complex, composed of Mis16, Eic1, and Mis18 in fission yeast, selectively deposits the centromere-specific histone H3 variant, CENP-A Cnp1 , at centromeres. How the intact Mis18 holo-complex oligomerizes and how Mis16, a well-known ubiquitous histone H4 chaperone, plays a centromere-specific role in the Mis18 holo-complex, remain unclear. Here, we report the stoichiometry of the intact Mis18 holo-complex as (Mis16) 2 :(Eic1) 2 :(Mis18) 4 using analytical ultracentrifugation. We further determine the crystal structure of Schizosaccharomyces pombe Mis16 in complex with the C-terminal portion of Eic1 (Eic1-CT). Notably, Mis16 accommodates Eic1-CT through the binding pocket normally occupied by histone H4, indicating that Eic1 and H4 compete for the same binding site, providing a mechanism for Mis16 to switch its binding partner from histone H4 to Eic1. Thus, our analyses not only determine the stoichiometry of the intact Mis18 holo-complex but also uncover the molecular mechanism by which Mis16 plays a centromere-specific role through Eic1 association. Graphical abstract Teaser Using structural, biochemical, and genetic approaches, An et al. unravel the oligomeric state of the fission yeast Mis18 holo-complex and the molecular mechanism by which Mis16 performs its centromere-specific function upon binding to Eic1.
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  • 49
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    Publication Date: 2018-05-29
    Description: Publication date: Available online 24 May 2018 Source: Structure Author(s): Joshua Matthew Allen Bullock, Neeladri Sen, Konstantinos Thalassinos, Maya Topf Modeling macromolecular assemblies with restraints from crosslinking mass spectrometry (XL-MS) tends to focus solely on distance violation. Recently, we identified three different modeling features inherent in crosslink data: (1) expected distance between crosslinked residues; (2) violation of the crosslinker's maximum bound; and (3) solvent accessibility of crosslinked residues. Here, we implement these features in a scoring function. cMNXL, and demonstrate that it outperforms the commonlyused crosslink distance violation. We compare the different methods of calculating the distance between crosslinked residues, which shows no significant change in performance when using Euclidean distance compared with the solvent-accessible surface distance. Finally, we create a combined score that incorporates information from 3D electron microscopy maps as well as crosslinking. This achieves, on average, better results than either information type alone and demonstrates the potential of integrative modeling with XL-MS and low-resolution cryoelectron microscopy. Graphical abstract Teaser Bullock et al. present a scoring function for modeling protein complexes based on crosslink data (cMNXL) that outperforms other functions currently in use. They also combine this method with a 3D-EM fitting score to create a combined scoring function that outperforms each score alone.
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  • 50
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    Publication Date: 2018-05-29
    Description: Publication date: Available online 17 May 2018 Source: Structure Author(s): Raffaele Raucci, Elodie Laine, Alessandra Carbone Several models estimating the strength of the interaction between proteins in a complex have been proposed. By exploring the geometry of contact distribution at protein-protein interfaces, we provide an improved model of binding energy. Local interaction signal analysis (LISA) is a radial function based on terms describing favorable and non-favorable contacts obtained by density functional theory, the support-core-rim interface residue distribution, non-interacting charged residues and secondary structures contribution. The three-dimensional organization of the contacts and their contribution on localized hot-sites over the entire interaction surface were numerically evaluated. LISA achieves a correlation of 0.81 (and a root-mean-square error of 2.35 ± 0.38 kcal/mol) when tested on 125 complexes for which experimental measurements were realized. LISA's performance is stable for subsets defined by functional composition and extent of conformational changes upon complex formation. A large-scale comparison with 17 other functions demonstrated the power of the geometrical model in the understanding of complex binding. Graphical abstract Teaser Local interaction signal analysis (LISA) is an empirical function designed to estimate protein-protein binding affinities. Its comprehensive model of protein interactions describes strength, favorable/unfavorable character, and geometric distribution of interatomic contacts. It also accounts for the non-interacting surface and secondary structures contributions. It enables to identify “hot-sites” at the interface.
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  • 51
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    Publication Date: 2018-05-29
    Description: Publication date: Available online 10 May 2018 Source: Structure Author(s): Alberto Bartesaghi, Cecilia Aguerrebere, Veronica Falconieri, Soojay Banerjee, Lesley A. Earl, Xing Zhu, Nikolaus Grigorieff, Jacqueline L.S. Milne, Guillermo Sapiro, Xiongwu Wu, Sriram Subramaniam The advent of direct electron detectors has enabled the routine use of single-particle cryo-electron microscopy (EM) approaches to determine structures of a variety of protein complexes at near-atomic resolution. Here, we report the development of methods to account for local variations in defocus and beam-induced drift, and the implementation of a data-driven dose compensation scheme that significantly improves the extraction of high-resolution information recorded during exposure of the specimen to the electron beam. These advances enable determination of a cryo-EM density map for β-galactosidase bound to the inhibitor phenylethyl β-D-thiogalactopyranoside where the ordered regions are resolved at a level of detail seen in X-ray maps at ∼ 1.5 Å resolution. Using this density map in conjunction with constrained molecular dynamics simulations provides a measure of the local flexibility of the non-covalently bound inhibitor and offers further opportunities for structure-guided inhibitor design. Graphical abstract Teaser Bartesaghi et al. report methods to account for radiation damage and local changes in defocus and image drift, enabling visualization of atomic resolution features in a cryo-EM density map of inhibitor-bound β-galactosidase, and measuring of local flexibility of the bound inhibitor using constrained molecular dynamics simulations.
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  • 52
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    Publication Date: 2018-05-29
    Description: Publication date: Available online 3 May 2018 Source: Structure Author(s): Egor Svidritskiy, Andrei A. Korostelev Translation termination ensures proper lengths of cellular proteins. During termination, release factor (RF) recognizes a stop codon and catalyzes peptide release. Conformational changes in RF are thought to underlie accurate translation termination. However, structural studies of ribosome termination complexes have only captured RFs in a conformation that is consistent with the catalytically active state. Here, we employ a hyper-accurate RF1 variant to obtain crystal structures of 70S termination complexes that suggest a structural pathway for RF1 activation. We trapped RF1 conformations with the catalytic domain outside of the peptidyl-transferase center, while the codon-recognition domain binds the stop codon. Stop-codon recognition induces 30S decoding-center rearrangements that precede accommodation of the catalytic domain. The separation of codon recognition from the opening of the catalytic domain suggests how rearrangements in RF1 and in the ribosomal decoding center coordinate stop-codon recognition with peptide release, ensuring accurate translation termination. Graphical abstract Teaser Accurate translation termination defines the lengths of cellular proteins, ensuring proteome integrity. Release factors recognize a stop codon and hydrolyze peptidyl-tRNA, releasing the newly made protein from the ribosome. Here, 70S termination structures capture release factor RF1 in pre-accommodation-like conformations, shedding light on the mechanism of termination accuracy.
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  • 53
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: 1 May 2018 Source: Structure, Volume 26, Issue 5 Author(s): Jianhong Zhou, A. Keith Dunker In this issue of Structure , Tsirigotaki et al. (2018) use bioinformatics and biophysical tools to demonstrate that many secreted proteins form long-lived, loosely packed folding intermediates. This delayed folding correlates with elevated disorder and reduced hydrophobicity compared to structured cytosolic proteins and is often stabilized by signal peptides by yet to be determined mechanisms. Teaser In this issue of Structure , Tsirigotaki et al. (2018) use bioinformatics and biophysical tools to demonstrate that many secreted proteins form long-lived, loosely packed folding intermediates. This delayed folding correlates with elevated disorder and reduced hydrophobicity compared to structured cytosolic proteins and is often stabilized by signal peptides by yet to be determined mechanisms.
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  • 54
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    Elsevier
    Publication Date: 2018-05-29
    Description: Publication date: 1 May 2018 Source: Structure, Volume 26, Issue 5 Author(s): Neil R. Lloyd, Deborah S. Wuttke Pot1 is the shelterin component responsible for the protection of the single-stranded DNA (ssDNA) overhang at telomeres in nearly all eukaryotic organisms. The C-terminal domain of the DNA-binding domain, Pot1pC, exhibits non-specific ssDNA recognition, achieved through thermodynamically equivalent alternative binding conformations. Given this flexibility, it is unclear how specificity for ssDNA over RNA, an activity required for biological function, is achieved. Examination of the ribose-position specificity of Pot1pC shows that ssDNA specificity is additive but not uniformly distributed across the ligand. High-resolution structures of several Pot1pC complexes with RNA-DNA chimeric ligands reveal Pot1pC discriminates against RNA by utilizing non-compensatory binding modes that feature significant rearrangement of the binding interface. These alternative conformations, accessed through both ligand and protein flexibility, recover much, but not all, of the binding energy, leading to the observed reduction in affinities. These findings suggest that intermolecular interfaces are remarkably sophisticated in their tuning of specificity toward flexible ligands. Graphical abstract Teaser Lloyd et al. determine the nucleotide-position specificity of the C-terminal domain of S. pombe Pot1 for ssDNA over ssRNA and report three ligand-bound structures that reveal RNA-chimeric ligands bind in a widely utilized non-compensatory binding mode that features significant rearrangement of the binding interface to achieve thermodynamically equivalent binding.
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  • 55
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    Publication Date: 2018-05-29
    Description: Publication date: 1 May 2018 Source: Structure, Volume 26, Issue 5 Author(s): Johan Hattne, Dan Shi, Calina Glynn, Chih-Te Zee, Marcus Gallagher-Jones, Michael W. Martynowycz, Jose A. Rodriguez, Tamir Gonen Micro-crystal electron diffraction (MicroED) combines the efficiency of electron scattering with diffraction to allow structure determination from nano-sized crystalline samples in cryoelectron microscopy (cryo-EM). It has been used to solve structures of a diverse set of biomolecules and materials, in some cases to sub-atomic resolution. However, little is known about the damaging effects of the electron beam on samples during such measurements. We assess global and site-specific damage from electron radiation on nanocrystals of proteinase K and of a prion hepta-peptide and find that the dynamics of electron-induced damage follow well-established trends observed in X-ray crystallography. Metal ions are perturbed, disulfide bonds are broken, and acidic side chains are decarboxylated while the diffracted intensities decay exponentially with increasing exposure. A better understanding of radiation damage in MicroED improves our assessment and processing of all types of cryo-EM data. Graphical abstract Teaser The scattered electrons in a cryo-EM measurement provide the information necessary to determine the atomic structure, but inevitably damage the sample. Radiation damage must be controlled to avoid compromising the result. Here, the relationship between exposure and damage is assessed in two different crystalline samples.
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  • 56
    Publication Date: 2018-05-29
    Description: Publication date: Available online 27 May 2018 Source: Seminars in Cancer Biology Author(s): Giuseppe Curigliano In gynecological cancers tumor infiltrating lymphocytes and upregulation of immune-related gene signatures have been associated with a better prognosis. Knowledge of tumor immunogenicity and associated gene signatures suggests that the tumor immune landscape is a key determinant to define patient prognosis and potentially to predict response to immune-checkpoint inhibitors. The aim of this review is to give an overview of immune gene signatures across gynecology histological cancer types, defining their prognostic and potential predictive role. In the current review we will present data on these gene signatures, on immunohistochemical features and their potential importance to select patients potentially eligible to trials with immune-checkpoint inhibitors.
    Print ISSN: 1044-579X
    Electronic ISSN: 1096-3650
    Topics: Medicine
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  • 57
    Publication Date: 2018-05-29
    Description: Publication date: July 2018 Source: Virology, Volume 520 Author(s): Tony L. Goldberg, Victoria L. Clyde, Annette Gendron-Fitzpatrick, Samuel D. Sibley, Roberta Wallace Gyroviruses are small, single stranded DNA viruses in the family Anelloviridae . In chickens, the type virus (chicken anemia virus; CAV) causes epidemic disease in poultry flocks worldwide. In 2007 and 2008, young crested screamers ( Chauna torquata ) at a zoo in Wisconsin, USA, died of neurologic disease with clinical and pathological features resembling CAV infection. Conventional diagnostics were negative, but molecular analyses revealed coinfection of an affected bird with three variants of a novel Gyrovirus lineage, GyV10. Analysis of ten additional screamers from this and another zoo revealed infection in all but one bird, with co-infections and persistent infections common. The association between GyV10 (“screamer anemia virus,” provisionally) and the disease remains unproven, but certain immunological and neurologic features of the syndrome would expand the known pathologic consequences of Gyrovirus infection. To control the virus, autogenous vaccines, environmental decontamination, and management strategies to limit vertical and horizontal transmission might prove effective.
    Print ISSN: 0042-6822
    Electronic ISSN: 1096-0341
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  • 58
    Publication Date: 2018-05-30
    Description: Publication date: Available online 29 May 2018 Source: American Journal of Obstetrics and Gynecology Author(s): Eva Maria Rehbinder, Karin C. Lødrup Carlsen, Anne Cathrine Staff, Inga Leena Angell, Linn Landrø, Katarina Hilde, Peter Gaustad, Knut Rudi Background The “sterile womb” paradigm is debated. Recent evidence suggests that the offspring’s first microbial encounter is before birth in term uncomplicated pregnancies. The establishment of a healthy microbiota early in life might be crucial for reducing the burden of diseases later in life. Objective We aimed to investigate the presence of a microbiota in sterilely collected amniotic fluid in uncomplicated pregnancies at term in the Preventing Atopic Dermatitis and Allergies in children (PreventADALL) study cohort. Study Design Amniotic fluid was randomly sampled at cesarean sections in pregnant women in one out of three study sites included in the PreventADALL study. From 65 pregnancies at term, where amniotic fluid was successfully sampled, we selected 10 from elective (planned, without ongoing labour) cesarean sections with intact amniotic membranes (non-ROM group) and all 14 with prior rupture of membranes (ROM group) were included as positive controls. Amniotic fluid was analysed by culture-independent and culture-dependent techniques. Results The median (min-max) concentration of prokaryotic DNA (16S rRNA gene copies/ml; ddPCR) was low for the non-ROM group (664 (544-748)) – corresponding to the negative controls (596 (461-679)), while the ROM group had more than 10-fold higher levels (7700 (1066-251430)) (p = 0.0001, by Mann-Whitney U-test). Furthermore, bacteria were detected in 50 % of the ROM samples by anaerobic culturing, while none of the non-ROM samples showed bacterial growth. Sanger sequencing of the ROM samples identified bacterial strains that are commonly part of the vaginal flora and/or associated with intrauterine infections. Conclusion We conclude that fetal development in uncomplicated pregnancies occurs in the absence of an amniotic fluid microbiota and that the offspring microbial colonization starts after uterine contractions and rupture of amniotic membrane.
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    Electronic ISSN: 1097-6868
    Topics: Medicine
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  • 59
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Tomonao Inobe, Masayuki Tsukamoto, Miyuki Nozaki Methods to induce proteasomal degradation of unwanted proteins are valuable in biomedical studies and thus receive increasing attention. For efficient degradation, the proteasome requires both a ubiquitin tag, which delivers substrates to the proteasome, and an unstructured region, where the proteasome engages the substrate for unfolding and degradation. We fused two degron components into a single molecule to create a fusion protein comprising ubiquitin and Rpn4-derived unstructured region. We demonstrated that the fusion protein retained its function to polyubiquitinate target proteins, thereby inducing more efficient proteasomal target degradation than wild-type ubiquitin in vitro and in cells. These results provide novel strategies for robust degradation enhancement of polyubiquitinated proteins.
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  • 60
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Seul-Gi Lee, Young Ae Joe Mesenchymal stromal/stem cells (MSCs) have been promising source for regenerative cell therapy in ischemic diseases. To improve efficacy of MSC therapy, various priming methods have been developed, and hypoxic priming has been reported to enhance therapeutic efficacy of MSCs by increasing secretion level of growth factors and cytokines. Recently, it has been reported that bone marrow MSCs primed with hypoxic condition show an increase of autophagy. Here, we addressed whether proangiogenic activity increased by hypoxic condition is associated with autophagy. Wharton's jelly derived MSCs primed with hypoxia showed increase of autophagy with increased hypoxia inducible factor-1α level, and conditioned medium (CM) derived from these cells showed increased levels of migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared to non-primed MSCs-derived CM. Pretreatment with autophagy inhibitor 3-methyladenine or chloroquine prior to exposure of hypoxia resulted in reduction of migration and tube formation of HUVECs. CM obtained under hypoxic condition from MSCs in which autophagy activity was inhibited by ATG5 and ATG7 siRNA treatment also showed decrease of migration and tube formation of HUVECs. Accordingly, secretion levels of angiogenin and VEGF that were markedly increased upon hypoxia exposure was decreased by ATG5/7 knockdown. Therefore, it may be suggested that autophagy plays an important role in hypoxia-driven enhancement of paracrine effect of MSCs.
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  • 61
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Shufan Zhang, Huixuan Wan, Peng Wang, Mengmeng Liu, Gongchen Li, Chunxue Zhang, Yao Sun Mesenchymal Stem Cells (MSCs) are self-renewing and multipotent stem cells which was investigated for diverse clinical applications. However, complex mechanism of MSCs fate determination is still not fully disclosed. Extracellular matrix (ECM) proteins contribute to maintain MSCs stemness by providing extracellular microenvironment. Increasing evidences show that ECM proteins could also regulate the fate of MSCs directly. Dentin matrix protein 1 (DMP1) is an ECM protein enrich in bone tissue and terminal cells, which well-known in promoting osteoblasts and osteocytes maturation, and facilitate mineralization. Recently, our experiment indicated that DMP1 was also expressed in MSCs of long bone. In present study, it is found that DMP1 expressed in Prx1 positive MSCs. And, DMP1 is down-regulated in early osteoblasts and up-regulated again in mature osteoblasts. DMP1 conditional knockout mice model under Prx1cre was generated to explore whether DMP1 regulates MSCs osteogenic differentiation. Specific ablation of DMP1 in Prx1 positive MSCs increased bone mass in vivo and promoted osteoblasts activity in vitro . This study provides a new understanding of DMP1's function in regulation of osteogenesis: not only an enhancer of bone formation, but also a negative regulator of MSCs differentiation in bone.
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  • 62
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Zhiyu Li, Qi Wu, Si Sun, Juan Wu, Juanjuan Li, Yimin Zhang, Changhua Wang, Jingping Yuan, Shengrong Sun Monocarboxylate transporters (MCTs) are transmembrane proteins that control the lactate metabolism and associated with poor prognosis in solid tumours including breast cancer (BC). This study aimed to evaluate the clinical and prognostic value of MCTs used by immunohistochemistry and quantum dots-based fluorescent imaging technique in BC and surrounding stroma with emphasis on the interaction between tumour and stroma. Moreover, the data from The Cancer Genome Atlas (TCGA) was analyzed to evaluate the association between MCTs mRNA expression and prognosis of breast cancer patients. Our study found that MCT1 overexpression was observed in hormone receptor-negative and high-proliferation subtypes. High expression of MCT1 and MCT4 in tumour tissues was associated with poor patient outcome; further the correlation between MCT1 expression and poor prognosis in breast cancer was further strengthened when combined with MCT4 overexpression in the adjacent adipose tissue. These results demonstrate that MCTs tend to play a role in the aggressive BC subtypes through the dynamic interaction between breast cancer cells and adipocytes, and developing therapeutics to block this interaction will be a promising strategy in cancer therapy.
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  • 63
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Norihiro Kotani, Yui Ida, Takanari Nakano, Izumi Sato, Ryusuke Kuwahara, Arisa Yamaguchi, Masahiro Tomita, Koichi Honke, Takayuki Murakoshi Close homolog of L1 (CHL1) and its truncated form mainly play crucial roles in mouse brain development and neural functions. Herein, we newly identified that truncated form of CHL1 is produced and released from lung tumor tissue in a mouse model expressing human EML4-ALK fusion gene. Both western blot and direct ELISA analysis revealed that mouse CHL1 level in serum (including serum extracellular vesicles) was significantly elevated in EML4-ALK transgenic mice. The correlation between the tumor size and the amount of CHL1 secretion could be examined in this study, and showed a significant positive correlation in a tumor size-dependent manner. Considering these results, the measurement of circulating CHL1 level may contribute to assess a tumor progression in human lung tumor patients.
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  • 64
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Feng Tian, Jiwei Wang, Haifeng Sun, Jianbo Yang, Peng Wang, Songlin Wan, Xuejin Gao, Li Zhang, Jieshou Li, Xinying Wang Parenteral nutrition (PN) is one of the basic therapies for patients with intestinal failure; however, hepatic steatosis associated with PN limits the long-term use of PN. N-3 polyunsaturated fatty acids (PUFAs) have been used to improve clinical outcomes of patients receiving PN; however, the mechanisms by which n-3 PUFAs ameliorate hepatic steatosis remain unclear. In the present study, C57BL/6J mice were randomly assigned to three treatment groups, namely, enteral nutrition (EN), n-3 PUFAs, and n-6 PUFAs. Additionally, MK 886 was used to inhibit PPAR-α. After 7 days of intervention, mice were sacrificed, and liver tissue and serum samples were collected. Results from liver weight and liver triglyceride measurements and Oil Red O staining showed that n-3 PUFAs significantly reduced the liver triglyceride levels. In addition, treatment with n-3 PUFAs resulted in a greater decrease in serum triglyceride and low-density lipoprotein cholesterol levels compared to n-6 PUFAs. The key enzymes involved in FA oxidation, namely, PPAR-α and CPT-1α, were significantly restored at both the mRNA and protein levels in the n-3 PUFAs group. However, the benefits of n-3 PUFAs in improving serum and liver TG levels were abolished when the PPAR-α/CPT-1α pathway was blocked by MK 886. The results of this study indicated that n-3 PUFAs ameliorated the PN-associated hepatic steatosis by activating the PPAR-α/CPT-1α pathway. The present study provided a reliable scientific basis supporting the potential beneficial effects of n-3 PUFAs for improving hepatic steatosis in patients receiving long-term parenteral nutrition.
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  • 65
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Mai Takizawa, Kazuki Harada, Kazuaki Nakamura, Takashi Tsuboi Astrocytes, a large population of glial cells, detect neurotransmitters and respond by increasing intracellular Ca 2+ concentration ([Ca 2+ ] i ) and releasing chemical molecules called gliotransmitters. Recently discovered Ca 2+ influx through transient receptor potential ankyrin 1 (TRPA1) channels is reported to cause spontaneous [Ca 2+ ] i increase in astrocytes. While several physiological functions of TRPA1-mediated spontaneous Ca 2+ signal have been revealed, relation with gliotransmitter release, especially peptide hormone exocytosis is largely unknown. We therefore explored the [Ca 2+ ] i and exocytosis dynamics in rat astrocyte cell line C6 cells and primary astrocytes. TRPA1-mediated spontaneous [Ca 2+ ] i transients were observed in both C6 cells and primary astrocytes. Total internal reflection fluorescence microscopy revealed that Venus-tagged brain-derived neurotrophic factor and neuropeptide Y were released spontaneously from astrocytes. Activation of TRPA1 channels enhanced the frequency of peptide hormone exocytosis, and inhibition of TRPA1 channels decreased the number of peptide hormone exocytosis. These results suggest that TRPA1-mediated spontaneous [Ca 2+ ] i increase modulates the spontaneous release of peptide hormones from astrocytes.
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  • 66
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Masaki Nishikawa, Hiroshi Kimura, Naomi Yanagawa, Morgan Hamon, Peter Hauser, Lifu Zhao, Oak D. Jo, Norimoto Yanagawa Kidney organoid is an emerging topic of importance for research in kidney development and regeneration. Conventional culture systems for kidney organoids reported thus far use culture media containing serum, which may compromise our understanding and the potential clinical applicability of the organoid system. In our present study, we tested two serum-free culture conditions and compared their suitability for the maintenance and growth of kidney organoids in culture. One of the serum-free culture conditions was the combination of keratinocytes serum free medium (KSFM) with knockout serum replacement (KSR) (KSFM + KSR), and the other was the combination of knockout DMEM/F12 (KD/F12) and KSR (KD/F12 + KSR). With cell aggregates derived from E12.5 mouse embryonic kidneys, we found that KD/F12 + KSR was superior to KSFM + KSR in promoting the growth of the aggregate with expansion of Six2 + nephron progenitor cells (NPC) and elaborated ureteric branching morphogenesis. With KD/F12 + KSR, we found that lower concentrations of KSR at 5–10% were superior to a higher concentration (20%) in promoting the growth of aggregates without affecting the expression levels of NPC marker genes. We also found that NPC in aggregates retained their differentiation potential to develop nephron tubules through mesenchyme-to-epithelial transition (MET), after being maintained in culture under these conditions for up to 7 days. In conclusion, we have identified a defined serum-free culture condition suitable for the maintenance and growth of kidney organoids that retain the differentiation potential to develop nephron structures. This defined serum-free culture condition may serve as a useful platform for further investigation of kidney organoids in vitro .
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  • 67
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Vladimir F. Lazarev, Elizaveta A. Dutysheva, Elena Y. Komarova, Elena R. Mikhaylova, Irina V. Guzhova, Boris A. Margulis Massive neuronal death caused by a neurodegenerative pathology or damage due to ischaemia or traumatic brain injury leads to the appearance of cytosolic proteins in the extracellular space. We found that one of the most abundant cellular polypeptides, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), appearing in the medium of dying cells or body fluids is able to form aggregates that are cytotoxic to adjacent cells. Since we previously showed that the hydrocortisone derivative RX624 can inhibit the ability of GAPDH to transport the enzyme complex with polyglutamine and reduce the cytotoxicity of the complex, we explored the effects of GAPDH on SH-SY5Y neuroblastoma cells. We found that the latter treated with particular forms of GAPDH molecules die with a high efficiency, suggesting that the exogenous enzyme does kill adjacent cells. RX624 prevented the interaction of exogenous GAPDH with the cell membrane and reduced the level of death by more than 10%. We also demonstrated the efficiency of RX624 treatment in a rat model of traumatic brain injury. The chemical blocked the formation of GAPDH aggregates in the brain, inhibited the cytotoxic effects of cerebrospinal fluid and rescued the motor function of injured rats. Importantly, RX624 treatment of rats had a similar effect as the intracranial injection of anti-GAPDH antibodies. Graphical abstract
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  • 68
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Kazuki Harada, Shoko Sada, Hidekazu Sakaguchi, Mai Takizawa, Rika Ishida, Takashi Tsuboi S -equol is one of gut bacterial metabolites produced from soybean isoflavone daizein. While S -equol is known to promote glucose-induced insulin secretion from pancreatic β cells, whether S -equol affects glucagon-like peptide-1 (GLP-1) secretion from enteroendoceine L cells remains unclear. Here we assessed the effect of S -equol on GLP-1 secretion from mouse enteroendocrine L cell line GLUTag cells. GLUTag cells expressed GPR30 and estrogen receptors, which are putative S -equol receptors. Application of S -equol induced an increase in intracellular Ca 2+ levels via GPR30. However, S -equol did not enhance GLP-1 exocytosis, and long-term treatment of S -equol suppressed GLP-1 secretion. Moreover, immunocytochemistry revealed that S -equol increased the density of cortical actin filaments via G 12/13 signaling under GPR30. These data suggest that S -equol prevents GLP-1 secretion as a result of competing regulation between Ca 2+ mobilization and actin reorganization.
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  • 69
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Nanaka Kaneshiro, Ryosuke Imaoka, Masato Komai, Taku Kashiyama, Takashi Sakurai, Takashi Uehara, Nobumasa Takasugi Amyloid-β precursor protein (APP) correlates with the pathogenesis of certain brain diseases, such as Alzheimer disease (AD). APP is cleaved by several enzymes to produce APP metabolites, including the amyloid beta peptide (Aβ), which accumulates in the brain of AD patients. However, the exact functions of APP metabolites remain elusive. In this study, using genome editing technology, we mutated juxta- and intra-membrane domains of murine APP in the mouse neuroblastoma cell line, Neuro2a. We identified several clones that expressed characteristic patterns of APP metabolites. Mutations in juxta- (deletion 673A), and intra-membrane (deletion 705-6LM) domains of APP, decreased overall levels of APP metabolites or decreased the level of α-secretase-cleaved carboxy-terminal fragment (αCTF), respectively. APP is known to influence neuronal differentiation; therefore, we used theses clones to dissect the function of APP metabolites during neuronal differentiation. One clone (CA), which expressed reduced levels of both FL-APP and αCTF, showed increased expression of the neuronal marker, β3-tubulin, and enhanced retinoic acid (RA)-induced neurite outgrowth. In contrast, a clone that expressed FL-APP, but was devoid of αCTF (CE), showed comparable expression of β3-tubulin and neurite outgrowth compared with normal Neuro2a cells. These data indicate that FL-APP is a suppressor of neurite outgrowth. Our data suggest a novel regulatory function of juxta- and intra-membrane domains on the metabolism and function of APP. Graphical abstract
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  • 70
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Wenyu Jiao, Yongchen Wang, Linghong Kong, Tao Ou-yang, Qing Meng, Qiang Fu, Zhenzhen Hu The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ 1-42 (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0.02μg/hemisphere) into rat hippocampus was administered for five consecutive days before Aβ 1-42 treatment. We found that Aβ 1-42 microinjection led to reduction of endogenous CART level in rat hippocampus. CART pretreatment improved the spatial memory and locomotor ability of AD rats. CART peptide decreased the Aβ 1-42 and Aβ production-associated enzyme BACE1 levels. Moreover, CART peptide attenuated the oxidative stress damage with a concrete manifestation of increased MDA as well as decreased T-SOD, GSH and ATP levels in the hippocampus of Aβ 1-42 -treated rat, which may be causatively implicated the activating of Nrf2/HO-1 signaling pathway. Furthermore, CART peptide attenuated neuronal apoptosis with decreased Bax, caspase-9 and caspase-3 levels and increased Bcl-2 level in rat hippocampus. Our results therefore indicate that CART peptide could serve as an antioxidant in early therapy for AD.
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  • 71
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Keita Kikuchi, Mahmoud Ben Othman, Kazuichi Sakamoto Probiotics such as Lactobacillus and Bifidobacterium improve the balance of intestinal microflora and have various physiological functions beneficial to human health. It is not always known whether the ingested microbial cells are viable- or killed. However, even sterilized bacterial cells are functional. Bacterial cell functions are strain-specific and their modes of action are still poorly understood. The aim of this study was to elucidate the roles of sterilized bifidobacteria in obesity and lipid metabolism. To this end, mice were orally ingested sterilized bacteria. Male C57BL/6J mice aged 7 wks were raised on a high-fat diet and received oral sterilized bifidobacteria for 4 wks. Although the amount of food they ingested did not change in response to bifidobacteria administration, both weight gain and epididymal body fat mass were significantly reduced. In addition, the elevated blood glucose, triglyceride, and total cholesterol levels observed in the mice on the high-fat diet all decreased in response to bifidobacteria treatment. Hepatic triglyceride levels also decreased. Furthermore, oral glucose tolerance and insulin resistance tests indicated that sterilized bifidobacteria improved glucose tolerance and diminished insulin resistance. Sterilized bifidobacteria also decreased blood lipopolysaccharides and altered intestinal flora. The present study indicates that in mice on a high-fat diet, sterilized bifidobacteria suppressed fat accumulation, improved insulin resistance, and lowered blood glucose levels.
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  • 72
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Margarita Kublanovsky, Amir Aharoni, Dan Levy Protein lysine methyltransferases (PKMTs) catalyze the methylation of lysine residues on many different cellular proteins. Despite extensive biochemical and structural studies, focusing on PKMT active site-peptide interactions, little is known regarding how PKMTs recognize globular substrates. To examine whether these enzymes recognize protein substrates through interactions that take place outside of the active site, we have measured SETD6 and SETD7 activity with both protein and peptide RelA substrate. We have utilized the MTase-Glo™ methyltransferase assay to measure the activity of SETD6 and SETD7 with the different RelA substrates and calculated the Michaelis-Menten (MM) parameters. We found an up to ∼12-fold increase in K M of the PKMTs activity with RelA peptide relative to the respective full-length protein, emphasizing the significantly higher PKMT-protein interaction affinity. Examination of SETD6 and SETD7 activity toward the same RelA substrates highlight the similarity in substrate recognition for both PKMTs. Our results show that the interaction affinity of SETD6 and SETD7 with RelA is enhanced through interactions that occur outside of the active site leading to higher catalytic efficiency and specificity. These interactions can significantly vary depending on the PKMT and the specific methylation site on RelA. Overall, our results underline that PKMTs can recognize their substrates through docking interactions that occur out of the active site-peptide region for enhancing their activity and specificity in the cellular environment.
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  • 73
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Mikhail Skliar, Vasiliy S. Chernyshev, David M. Belnap, German V. Sergey, Samer M. Al-Hakami, Philip S. Bernard, Inge J. Stijleman, Rakesh Rachamadugu Exosomes are membrane nanovesicles implicated in cell-to-cell signaling in which they transfer their molecular cargo from the parent to the recipient cells. This role essentially depends on the exosomes' small size, which is the prerequisite for their rapid migration through the crowded extracellular matrix and into and out of circulation. Here we report much lower exosome mobility than expected from the size of their vesicles, implicate membrane proteins in a substantially impeded rate of migration, and suggest an approach to quantifying the impact. The broadly distributed excess hydrodynamic resistance provided by surface proteins produces a highly heterogeneous and microenvironment-dependent hindrance to exosome mobility. The implications of the findings on exosome-mediated signaling are discussed. Graphical abstract
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  • 74
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Junrong Wang, Cong Ye, Junbao Liu, Yubo Hu Increasing evidence has demonstrated the involvement of dysregulated long non-coding RNAs (lncRNAs) in chemoresistance acting as potential oncogenes or tumor suppressors in various cancers. Nevertheless, the profound molecular mechanisms of lncRNAs in ovarian cancer (OC) chemoresistance is not well elucidated. The objective of this work was to investigate the role and molecular mechanisms of urothelial carcinoma associated 1 (UCA1) in paclitaxel (PTX) resistance in OC. Our results indicated that UCA1 was significantly up-regulated in PTX-resistant OC cells (SKOV3/PTX and HeyA-8/PTX) compared with their parental cells (SKOV3 and HeyA-8). Functionally, UCA1 knockdown sensitized SKOV3/PTX and HeyA-8/PTX cells to PTX through enhancing PTX-induced apoptosis. Mechanistically, UCA1 silencing induced PTX sensitivity of SKOV3/PTX and HeyA-8/PTX cells by de-repressing ABCB1 through sponging miR-129. Collectively, our study elaborated a novel UCA1/miR-129/ABCB1 regulatory axis underlying PTX resistance of OC cells, providing a potential therapeutic target for OC.
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  • 75
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Kayo Masago, Yasuyuki Kihara, Keisuke Yanagida, Fumie Hamano, Shinsuke Nakagawa, Masami Niwa, Takao Shimizu Cerebral edema is a life-threatening neurological condition characterized by brain swelling due to the accumulation of excess fluid both intracellularly and extracellularly. Fulminant hepatic failure (FHF) develops cerebral edema by disrupting blood-brain barrier (BBB). However, the mechanisms by which mediator induces brain edema in FHF remain to be elucidated. Here, we assessed a linkage between brain edema and lysophosphatidic acid (LPA) signaling by utilizing an animal model of FHF and in vitro BBB model. Azoxymethane-treated mice developed FHF and hepatic encephalopathy, associated with higher autotaxin (ATX) activities in serum than controls. Using in vitro BBB model, LPA disrupted the structural integrity of tight junction proteins including claudin-5, occludin, and ZO-1. Furthermore, LPA decreased transendothelial electrical resistances in in vitro BBB model, and induced cell contraction in brain endothelial monolayer cultures, both being inhibited by a Rho-associated protein kinase inhibitor, Y-27632. The brain capillary endothelial cells predominantly expressed LPA 6 mRNA, whose knockdown blocked the LPA-induced endothelial cell contraction. Taken together, the up-regulation of serum ATX in hepatic encephalopathy may activate the LPA–LPA 6 –G 12/13 –Rho pathway in brain capillary endothelial cells, leading to enhancement of BBB permeability and brain edema. Graphical abstract
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  • 76
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Zhen-Hua Wu, Chen Lin, Chen-Chen Liu, Wei-Wei Jiang, Ming-Zhu Huang, Xin Liu, Wei-Jian Guo Dysregulation of microRNAs has been demonstrated to be involved in a variety of biological events related to cancer, including proliferation, metastasis, angiogenesis and immune escape. MiR-616-3p is located on the chromosome region 12q13.3, however, its potential role and clinical implications in gastric cancer remain poorly understood. The current study aimed to investigate the potential role of miR-616-3p in gastric cancer. The results showed that miR-616-3p was up-regulated in cancer tissues. Higher expression of miR-616-3p in tumor tissues also predicted poor prognosis. Furthermore, loss- and gain-of-function in vitro revealed that miR-616-3p promoted angiogenesis and EMT in gastric cancer cells. Mechanistically, further analysis demonstrated that the effects of miR-616-3p on metastasis and angiogenesis occurred through the down-regulation of PTEN, a direct target of miR-616-3p. We propose that the restoration of PTEN expression may block miR-616-3p-induced EMT and angiogenesis. Collectively, our findings suggest that the miR-616-3p-PTEN signaling axis might be a potential therapeutic target for gastric cancer.
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  • 77
    Publication Date: 2018-05-30
    Description: Publication date: 2 July 2018 Source: Biochemical and Biophysical Research Communications, Volume 501, Issue 4 Author(s): Ling He, Dijuan Meng, Shi-Hu Zhang, Yi Zhang, Zhengming Deng, Lian-Bao Kong Over-expression of the bromodomain and extraterminal (BET) family protein BRD4 is associated with hepatocellular carcinoma (HCC) progression. In the present study, we indentified a novel putative anti-BRD4 microRNA: microRNA-608 (“miR-608”). In HepG2 cells and primary human HCC cells, over-expression of miR-608, using a lentiviral construct, induced BRD4 downregulation and proliferation inhibition. Conversely, transfection of the miR-608 inhibitor increased BRD4 expression to promote HepG2 cell proliferation. Our results suggest that BRD4 is the primary target gene of miR-608 in HepG2 cells. shRNA-mediated knockdown or CRSIPR/Cas9-mediated knockout of BRD4 mimicked and overtook miR-608's actions in HepG2 cells. Furthermore, introduction of a 3′-untranslated region (3′-UTR) mutant BRD4 (UTR-A1718G) blocked miR-608-induced c-Myc downregulation and proliferation inhibition in HepG2 cells. In vivo , HepG2 xenograft tumor growth was significantly inhibited after expressing miR-608 or BRD4 CRSIPR/Cas9-KO construct. Importantly, BRD4 mRNA was upregulated in human HCC tissues, which was correlated with downregulation of miR-608. Together, we conclude that miR-608 inhibits HCC cell proliferation possibly via targeting BET family protein BRD4.
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  • 78