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  • 1
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The stx genes of many Shiga toxin-encoding Escherichia coli (STEC) strains are encoded by prophages of the λ bacteriophage family. In the genome of the Stx1-encoding phage H-19B, the stx1AB genes are found ≈ 1 kb downstream of the late phage promoter, pR′, but are known to be regulated by the associated iron-regulated promoter, pStx1. Growth of H-19B lysogens in low iron concentrations or in conditions that induce the prophage results in increased Stx1 production. Although the mechanism by which low iron concentration induces Stx1 production is well understood, the mechanisms by which phage induction enhances toxin production have not been extensively characterized. The studies reported here identify the factors that contribute to Stx1 production after induction of the H-19B prophage. We found that replication of the phage genome, with the associated increase in stx1AB copy number, is the most quantitatively important mechanism by which H-19B induction increases Stx1 production. Three promoters are shown to be involved in stx1AB transcription after phage induction, the iron-regulated pStx1 and the phage-regulated pR and pR′ promoters, the relative importance of which varies with environmental conditions. Late phage transcription initiating at the pR′ promoter, contrary to previous findings in the related Stx2-encoding phage φ361, was found to be unnecessary for high-level Stx1 production after phage induction. Finally, we present evidence that phage-mediated lysis regulates the quantity of Stx1 produced by determining the duration of Stx1 accumulation and provides a mechanism for Stx1 release. By amplifying stx1AB copy number, regulating stx1AB transcription and allowing for Stx1 release, the biology of the Stx-encoding phages contributes greatly to the production of Stx, the principal virulence factor of STEC.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7357
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The normal state resistivity of high temperature superconductors can be probed in the region below T c by suppressing the superconducting state in high magnetic fields. Here we present the normal state properties of YBa 2 Cu 3 O x thin films in the underdoped regime and the normal state resistance of La 2-x Sr x CuO 4 thin films under epitaxial strain, measured below T c by applying pulsed fields up to 60 T. We interpret these data in terms of the recently proposed 1D quantum transport model with the 1D paths corresponding to the charge stripes.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2014-05-29
    Description: BACKGROUND Younger survivors (YS) of breast cancer often report more survivorship symptoms such as fatigue, depression, sexual difficulty, and cognitive problems than older survivors (OS). This study sought to determine the effect of breast cancer and age at diagnosis on quality of life (QoL) by comparing 3 groups: 1) YS diagnosed at age 45 years or before, 2) OS diagnosed between 55 and 70, and 3) for the YSs, age-matched controls (AC) of women not diagnosed with breast cancer. METHODS Using a large Eastern Cooperative Oncology Group (ECOG) database, 505 YS were recruited who were aged 45 years or younger when diagnosed and 622 OS diagnosed at 55 to 70 years of age. YS, OS, and AC were compared on physical, psychological, social, spiritual, and overall QoL variables. RESULTS Compared to both AC and to OS, YS reported more depressive symptoms ( P  = .005) and fatigue ( P  〈 .001), poorer self-reported attention function ( P  〈 .001), and poorer sexual function ( P  〈 .001) than either comparison group. However, YS also reported a greater sense of personal growth ( P  〈 .001) and perceived less social constraint ( P  〈 .001) from their partner than AC. CONCLUSIONS YS reported worse functioning than AC relative to depression, fatigue, attention, sexual function, and spirituality. Perhaps even more important, YS fared worse than both AC and OS on body image, anxiety, sleep, marital satisfaction, and fear of recurrence, indicating that YS are at greater risk for long-term QoL problems than survivors diagnosed at a later age. Cancer 2014. © 2014 American Cancer Society .
    Print ISSN: 0008-543X
    Electronic ISSN: 1097-0142
    Topics: Biology , Medicine
    Published by Wiley-Blackwell on behalf of The American Cancer Society.
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  • 4
    Publication Date: 2015-09-08
    Description: The International Prognostic Score (IPS-7) is the most commonly used risk stratification tool for advanced Hodgkin lymphoma (HL), however recent studies suggest the IPS-7 is less discriminating due to improved outcomes with contemporary therapy. We evaluated the seven variables for IPS-7 recorded at study entry for 854 patients enrolled on Eastern Cooperative Oncology Group 2496 trial. Univariate and multivariate Cox models were used to assess their prognostic ability for freedom from progression (FFP) and overall survival (OS). The IPS-7 remained prognostic however its prognostic range has narrowed. On multivariate analysis, two factors (age, stage) remained significant for FFP and three factors (age, stage, haemoglobin level) for OS. An alternative prognostic index, the IPS-3, was constructed using age, stage and haemoglobin level, which provided four distinct risk groups [FFP ( P  = 0·0001) and OS ( P  〈 0·0001)]. IPS-3 outperformed the IPS-7 on risk prediction for both FFP and OS by model fit and discrimination criteria. Using reclassification calibration, 18% of IPS-7 low risk patients were re-classified as intermediate risk and 13% of IPS-7 intermediate risk patients as low risk. For patients with advanced HL, the IPS-3 may provide a simpler and more accurate framework for risk assessment in the modern era. Validation of these findings in other large data sets is planned.
    Print ISSN: 0007-1048
    Electronic ISSN: 1365-2141
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 5
    Publication Date: 2018-11-03
    Description: The enoyl-thioester reductase InhA catalyzes an essential step in fatty acid biosynthesis of Mycobacterium tuberculosis and is a key target of antituberculosis drugs to combat multidrug-resistant M. tuberculosis strains. This has prompted intense interest in the mechanism and intermediates of the InhA reaction. Here, using enzyme mutagenesis, NMR, stopped-flow spectroscopy, and LC–MS, we found that the NADH cofactor and the CoA thioester substrate form a covalent adduct during the InhA catalytic cycle. We used the isolated adduct as a molecular probe to directly access the second half-reaction of the catalytic cycle of InhA (i.e. the proton transfer), independently of the first half-reaction (i.e. the initial hydride transfer) and to assign functions to two conserved active-site residues, Tyr-158 and Thr-196. We found that Tyr-158 is required for the stereospecificity of protonation and that Thr-196 is partially involved in hydride transfer and protonation. The natural tendency of InhA to form a covalent C2-ene adduct calls for a careful reconsideration of the enzyme's reaction mechanism. It also provides the basis for the development of effective tools to study, manipulate, and inhibit the catalytic cycle of InhA and related enzymes of the short-chain dehydrogenase/reductase (SDR) superfamily. In summary, our work has uncovered the formation of a covalent adduct during the InhA catalytic cycle and identified critical residues required for catalysis, providing further insights into the InhA reaction mechanism important for the development of antituberculosis drugs.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
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  • 6
    Publication Date: 2022-05-26
    Description: Author Posting. © American Meteorological Society, 2021. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 34(5), (2021): 1767-1788, https://doi.org/10.1175/JCLI-D-19-1020.1.
    Description: Marine heatwaves along the coast of Western Australia, referred to as Ningaloo Niño, have had dramatic impacts on the ecosystem in the recent decade. A number of local and remote forcing mechanisms have been put forward; however, little is known about the depth structure of such temperature extremes. Utilizing an eddy-active global ocean general circulation model, Ningaloo Niño and the corresponding cold Ningaloo Niña events are investigated between 1958 and 2016, with a focus on their depth structure. The relative roles of buoyancy and wind forcing are inferred from sensitivity experiments. Composites reveal a strong symmetry between cold and warm events in their vertical structure and associated large-scale spatial patterns. Temperature anomalies are largest at the surface, where buoyancy forcing is dominant, and extend down to 300-m depth (or deeper), with wind forcing being the main driver. Large-scale subsurface anomalies arise from a vertical modulation of the thermocline, extending from the western Pacific into the tropical eastern Indian Ocean. The strongest Ningaloo Niños in 2000 and 2011 are unprecedented compound events, where long-lasting high temperatures are accompanied by extreme freshening, which emerges in association with La Niñas, that is more common and persistent during the negative phase of the interdecadal Pacific oscillation. It is shown that Ningaloo Niños during La Niña phases have a distinctively deeper reach and are associated with a strengthening of the Leeuwin Current, while events during El Niño are limited to the surface layer temperatures, likely driven by local atmosphere–ocean feedbacks, without a clear imprint on salinity and velocity.
    Description: The following support is gratefully acknowledged: the Feodor-Lynen Fellowship by the Alexander von Humboldt Foundation and the WHOI Postdoctoral Scholar program (to SR), the Office of Naval Research under project number N-00014-19-12646 (to GG), the James E. and Barbara V. Moltz Fellowship for Climate-Related Research (to CCU), and IndoArchipel from the Deutsche Forschungsgemeinschaft (DFG) as part of the Special Priority Program (SPP)-1889 “Regional Sea Level Change and Society” (SeaLevel) (for PW).
    Keywords: Ocean ; Australia ; Indian Ocean ; Extreme events ; General circulation models ; Ocean models
    Repository Name: Woods Hole Open Access Server
    Type: Article
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  • 7
    Publication Date: 2022-10-26
    Description: Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 47(22), (2020): e2020GL088692, doi:10.1029/2020GL088692.
    Description: Rapid increases in upper 700‐m Indian Ocean heat content (IOHC) since the 2000s have focused attention on its role during the recent global surface warming hiatus. Here, we use ocean model simulations to assess distinct multidecadal IOHC variations since the 1960s and explore the relative contributions from wind stress and buoyancy forcing regionally and with depth. Multidecadal wind forcing counteracted IOHC increases due to buoyancy forcing from the 1960s to the 1990s. Wind and buoyancy forcing contribute positively since the mid‐2000s, accounting for the drastic IOHC change. Distinct timing and structure of upper ocean temperature changes in the eastern and western Indian Ocean are linked to the pathway how multidecadal wind forcing associated with the Interdecadal Pacific Oscillation is transmitted and affects IOHC through local and remote winds. Progressive shoaling of the equatorial thermocline—of importance for low‐frequency variations in Indian Ocean Dipole occurrence—appears to be dominated by multidecadal variations in wind forcing.
    Description: This work was supported by the Alexander von Humboldt Foundation (CCU and SR), The Investment in Science Fund given primarily by WHOI Trustee and Corporation Members (CCU), James E. and Barbara V. Moltz Fellowship for climate‐related research (CCU), the ARC Centre of Excellence for Climate Extremes (CE170100023; CCU and MHE), ARC DP150101331 (CCU and MHE), and PW was supported through grant IndoArchipel from the Deutsche Forschungsgemeinschaft (DFG) as part of the Special Priority Program (SPP)‐1889”Regional Sea Level Change and Society” (SeaLevel).
    Description: 2021-04-26
    Keywords: Decadal variability ; Hiatus ; Indian Ocean ; Ocean heat content ; Ocean models ; Pacific Ocean
    Repository Name: Woods Hole Open Access Server
    Type: Article
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