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  • 1
    Publication Date: 1970-12-01
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
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  • 2
    Publication Date: 2014-12-18
    Description: We analyze the variability of mean age of air (AoA) and of the local effects of the stratospheric residual circulation and eddy mixing on AoA within the framework of the isentropic zonal mean continuity equation. AoA for the period 1988–2013 has been simulated with the Lagrangian chemistry transport model CLaMS driven by ERA-Interim winds and diabatic heating rates. Model simulated AoA in the lower stratosphere shows good agreement with both in-situ observations and satellite observations from MIPAS (Michelson Interferometer for Passive Atmospheric Sounding), even regarding interannual variability and changes during the last decade. The interannual variability throughout the lower stratosphere is largely affected by the QBO-induced circulation and mixing anomalies, with year-to-year AoA changes of about 0.5 years. The decadal 2002–2012 change shows decreasing AoA in the lowest stratosphere, below about 450 K. Above, AoA increases in the NH and decreases in the SH. Mixing appears to be crucial for understanding AoA variability, with local AoA changes resulting from a close balance between residual circulation and mixing effects. Locally, mixing increases AoA at low latitudes (40S-40N) and decreases AoA at higher latitudes. Strongest mixing occurs below about 500 K, consistent with the separation between shallow and deep circulation branches. The effect of mixing integrated along the air parcel path, however, significantly increases AoA globally, except in the polar lower stratosphere. Changes of local effects of residual circulation and mixing during the last decade are supportive of a strengthening shallow circulation branch in the lowest stratosphere and a southward shifting circulation pattern above.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 3
    Publication Date: 2012-04-15
    Description: Binding of the catalytic divalent ion to the ternary DNA polymerase β/gapped DNA/dNTP complex is thought to represent the final step in the assembly of the catalytic complex and is consequently a critical determinant of replicative fidelity. We have analyzed the effects of Mg 2+ and Zn 2+ on the conformational activation process based on NMR measurements of [methyl- 13 C]methionine DNA polymerase β. Unexpectedly, both divalent metals were able to produce a template base-dependent conformational activation of the polymerase/1-nt gapped DNA complex in the absence of a complementary incoming nucleotide, albeit with different temperature thresholds. This conformational activation is abolished by substituting Glu295 with lysine, thereby interrupting key hydrogen bonds necessary to stabilize the closed conformation. These and other results indicate that metal-binding can promote: translocation of the primer terminus base pair into the active site; expulsion of an unpaired pyrimidine, but not purine, base from the template-binding pocket; and motions of polymerase subdomains that close the active site. We also have performed pyrophosphorolysis studies that are consistent with predictions based on these results. These findings provide new insight into the relationships between conformational activation, enzyme activity and polymerase fidelity.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2016-03-01
    Description: Formation of the mature HIV-1 reverse transcriptase (RT) p66/p51 heterodimer requires subunit-specific processing of the p66/p66' homodimer precursor. Since the ribonuclease H (RH) domain contains an occult cleavage site located near its center, cleavage must occur either prior to folding or subsequent to unfolding. Recent NMR studies have identified a slow, subunit-specific RH domain unfolding process proposed to result from a residue tug-of-war between the polymerase and RH domains on the functionally inactive, p66' subunit. Here, we describe a structural comparison of the isolated RH domain with a domain swapped RH dimer that reveals several intrinsically destabilizing characteristics of the isolated domain that facilitate excursions of Tyr427 from its binding pocket and separation of helices B and D. These studies provide independent support for the subunit-selective RH domain unfolding pathway in which instability of the Tyr427 binding pocket facilitates its release followed by domain transfer, acting as a trigger for further RH domain destabilization and subsequent unfolding. As further support for this pathway, NMR studies demonstrate that addition of an RH active site-directed isoquinolone ligand retards the subunit-selective RH' domain unfolding behavior of the p66/p66' homodimer. This study demonstrates the feasibility of directly targeting RT maturation with therapeutics.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 5
    Publication Date: 2013-10-16
    Description: [1]  Soot particles are a major absorber of shortwave radiation in the atmosphere. The mass absorption cross section is an essential quantity to describe this light absorption process. This work presents new experimental data on the mass absorption cross section of soot particles in the troposphere over Central Europe. Mass absorption cross sections were derived as the ratio between the light absorption coefficient determined by multi angle absorption photometry (MAAP), and the soot mass concentration determined by Raman spectroscopy. The Raman method is sensitive to graphitic structures present in the particle samples, and was calibrated in the laboratory using Printex ® 90 model particles. M ass absorption cross sections were determined for a number of seven observation sites, ranging between 3.9 and 7.4 m 2 g − 1 depending on measurement site and observational period. The highest values were found in a continentally aged air mass in winter, where soot particles were assumed to be mainly internally mixed . Our values are in the lower range of previously reported values, possibly due to instrumental differences to the former photometer and mass measurements. Overall, a value of 5.3 m 2 g − 1 from orthogonal regression over all samples is considered to be representative for the soot mass absorption cross section in the troposphere over Central Europe.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
    Publication Date: 2013-12-12
    Description: The major allergen domain (MA) is widely distributed in insects. The crystal structure of a single Bla g 1 MA revealed a novel protein fold in which the fundamental structure was a duplex of two subsequences (monomers), which had diverged over time. This suggested that the evolutionary origin of the MA structure may have been a homodimer of this smaller subsequence. Using publicly available genomic data, the distribution of the basic unit of this class of proteins was determined to better understand its evolutionary history. The duplication and divergence is examined at three distinct levels of resolution: 1) within the orders Diptera and Hymenoptera, 2) within one genus Drosophila , and 3) within one species Aedes aegypti . Within the family Culicidae, we have found two separate occurrences of monomers as independent genes. The organization of the gene family in A. aegypti shows a common evolutionary origin for its monomer and several closely related MAs. Molecular modeling of the A. aegypti monomer with the unique Bla g 1 fold confirms the distant evolutionary relationship and supports the feasibility of homodimer formation from a single monomer. RNAseq data for A. aegypti confirms that the monomer is expressed in the mosquito similar to other A. aegypti MAs after a blood meal. Together, these data support the contention that the detected monomer shares similar functional characteristics to related MAs in other insects. An extensive search for this domain outside of Insecta confirms that the MAs are restricted to insects.
    Electronic ISSN: 1759-6653
    Topics: Biology
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  • 7
    Publication Date: 2014-05-01
    Description: HIV-1 reverse transcriptase (RT), a critical enzyme of the HIV life cycle and an important drug target, undergoes complex and largely uncharacterized conformational rearrangements that underlie its asymmetric folding, dimerization and subunit-selective ribonuclease H domain (RH) proteolysis. In the present article we have used a combination of NMR spectroscopy, small angle X-ray scattering and X-ray crystallography to characterize the p51 and p66 monomers and the conformational maturation of the p66/p66' homodimer. The p66 monomer exists as a loosely structured molecule in which the fingers/palm/connection, thumb and RH substructures are connected by flexible (disordered) linking segments. The initially observed homodimer is asymmetric and includes two fully folded RH domains, while exhibiting other conformational features similar to that of the RT heterodimer. The RH' domain of the p66' subunit undergoes selective unfolding with time constant ~6.5 h, consistent with destabilization due to residue transfer to the polymerase' domain on the p66' subunit. A simultaneous increase in the intensity of resonances near the random coil positions is characterized by a similar time constant. Consistent with the residue transfer hypothesis, a construct of the isolated RH domain lacking the two N-terminal residues is shown to exhibit reduced stability. These results demonstrate that RH' unfolding is coupled to homodimer formation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
    Publication Date: 2012-11-04
    Description: HIV-1 reverse transcriptase (RT) contains a C-terminal ribonuclease H (RH) domain on its p66 subunit that can be expressed as a stable, although inactive protein. Recent studies of several RH enzymes demonstrate that substrate binding plays a major role in the creation of the active site. In the absence of substrate, the C-terminal helix E of the RT RNase H domain is dynamic, characterized by severe exchange broadening of its backbone amide resonances, so that the solution characterization of this region of the protein has been limited. Nuclear magnetic resonance studies of 13 C-labeled RH as a function of experimental conditions reveal that the 1 methyl resonance of Ile556, located in a short, random coil segment following helix E, experiences a large 13 C shift corresponding to a conformational change of Ile556 that results from packing of helix E against the central β-sheet. This shift provides a useful basis for monitoring the effects of various ligands on active site formation. Additionally, we report that the RNase H complexes formed with one or both divalent ions can be individually observed and characterized using diamagnetic Zn 2+ as a substitute for Mg 2+ . Ordering of helix E results specifically from the interaction with the lower affinity binding to the A divalent ion site.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 9
    Publication Date: 2017-11-08
    Description: Silicon is a keystone nutrient in the ocean for understanding climate change because of the importance of Southern Ocean diatoms in taking up CO 2 from the surface ocean–atmosphere system and sequestering carbon into the deep sea. Here we report on silicon isotopes and germanium-to-silicon ratios in giant glass spicules of deep-sea sponge Monorhaphis chuni over the past 17,000 years. In-situ measurements of Si isotopes and Ge concentrations show systematic variations from rim to center of the cross sections. When calibrated against seawater concentrations using data from modern spicule rims, sponge data indicate that dissolved silica concentrations in the deep Pacific were ~12 % higher during the early deglacial. These deep Pacific Ocean data help to fill an important global gap in paleo-nutrient records. Either continental sources supplied more silica to the deglacial ocean and/or biogenic silica burial was lower, both of which may have affected atmospheric CO 2 .
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 10
    Publication Date: 1969-06-01
    Print ISSN: 0014-2956
    Electronic ISSN: 1432-1033
    Topics: Biology , Chemistry and Pharmacology , Medicine
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