1,391 research outputs found
The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy.
Apolipoprotein A-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I central domain on HDL. The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of ApoA-I residues 99-163 on 9.6-nm reconstituted HDL was analyzed by EPR. In previous analyses, we examined residues 6-98 and 164-238 (of ApoA-I's 243 residues), and combining these findings with the current results, we have generated a full-length map of the backbone structure of reconstituted HDL-associated ApoA-I. Remarkably, given that the majority of ApoA-I's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a β-strand (residues 149-157). The significance of these nonhelical residues is discussed, along with the other features, in the context of ApoA-I function in contrast to recent models derived by other methods
Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation.
ObjectivePostprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL) and circulating lipopolysaccharide (LPS), has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation.Methods and resultsWe showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4.ConclusionPostprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation
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Nucleotide Sequence of xylE from the TOL pDK1 Plasmid and Structural Comparison with Isofunctional Catechol-2,3-Dioxygenase Genes from TOL pWW0 and NAH7
Article on the nucleotide sequence of xylE from the TOL pDK1 plasmid and structural comparison with isofunctional catechol-2,3-dioxygenase genes from TOL pWW0 and NAH7
Protective spin-labeled fluorenes maintain amyloid beta peptide in small oligomers and limit transitions in secondary structure
Alzheimer’s disease is characterized by the presence of extracellular plaques comprised of amyloid beta
(Aβ) peptides. Soluble oligomers of the Aβ peptide underlie a cascade of neuronal loss and dysfunction
associated with Alzheimer's disease. Single particle analyses of Aβ oligomers in solution by fluorescence
correlation spectroscopy (FCS) were used to provide real-time descriptions of how spin-labeled fluorenes
(SLFs; bi-functional small molecules that block the toxicity of Aβ) prevent and disrupt oligomeric
assemblies of Aβ in solution. Furthermore, the circular dichroism (CD) spectrum of untreated Aβ shows
a continuous, progressive change over a 24-hour period, while the spectrum of Aβ treated with SLF
remains relatively constant following initial incubation. These findings suggest the conformation of Aβ
within the oligomer provides a complementary determinant of Aβ toxicity in addition to oligomer growth
and size. Although SLF does not produce a dominant state of secondary structure in Aβ, it does induce a
net reduction in beta secondary content compared to untreated samples of Aβ. The FCS results, combined
with electron paramagnetic resonance spectroscopy and CD spectroscopy, demonstrate SLFs can inhibit
the growth of Aβ oligomers and disrupt existing oligomers, while retaining Aβ as a population of smaller,
yet largely disordered oligomers
A unified earthquake catalogue for the North Sea to derisk European CCS operations
Carbon capture and storage (CCS) technology is essential to European decarbonisation efforts, and several offshore CO2 storage projects are being developed in the North Sea. Understanding the geomechanical response to CO2 injection is key to both the pre-characterisation and operation of a storage reservoir. A thorough assessment of seismicity gives critical insights into the stress field and faulting around reservoirs, both key controls on the geomechanical response to injection. Seismicity also illuminates potential hydraulic pathways for leakage, be it directly by revealing the extent of faults, or indirectly through fractures imaged by measurements of seismic anisotropy. High quality seismicity data is critical to underpin all of these methods of analysis. This paper presents the most complete catalogue of seismicity in the North Sea to date. The combined data are enabling revised assessments of seismic hazard and leakage risk in the North Sea, as well as a better understanding of faulting and stress. This study shows the value of unifying disparate seismicity data, allowing for more accurate seismological analyses. These lay the foundation for better management of risks for not only geologic CO2 storage, but other offshore industries and infrastructure
Dynamic Scaling of Magnetic Flux Noise Near the KTB Transition in Overdamped Josephson Junction Arrays
We have used a dc Superconducting QUantum Interference Device to measure the
magnetic flux noise generated by the equilibrium vortex density fluctuations
associated with the Kosterlitz-Thouless-Berezinskii (KTB) transition in an
overdamped Josephson junction array. At temperatures slightly above the KTB
transition temperature, the noise is white for and scales as
for . Here , where is the correlation
length and is the dynamic exponent. Moreover, when all frequencies are
scaled by , data for different temperatures and frequencies collapse on
to a single curve. In addition, we have extracted the dynamic exponent and
found .Comment: 5 pages, LaTeX (REVTeX) format, requires epsfig and amstex style
files. 3 figures included. Tentatively scheduled for publication in Physical
Review Letters, 18 March, 199
Climate change adaptation in European river basins
This paper contains an assessment and standardized comparative analysis of the current water management regimes in four case-studies in three European river basins: the Hungarian part of the Upper Tisza, the Ukrainian part of the Upper Tisza (also called Zacarpathian Tisza), Alentejo Region (including the Alqueva Reservoir) in the Lower Guadiana in Portugal, and Rivierenland in the Netherlands. The analysis comprises several regime elements considered to be important in adaptive and integrated water management: agency, awareness raising and education, type of governance and cooperation structures, information management and—exchange, policy development and—implementation, risk management, and finances and cost recovery. This comparative analysis has an explorative character intended to identify general patterns in adaptive and integrated water management and to determine its role in coping with the impacts of climate change on floods and droughts. The results show that there is a strong interdependence of the elements within a water management regime, and as such this interdependence is a stabilizing factor in current management regimes. For example, this research provides evidence that a lack of joint/participative knowledge is an important obstacle for cooperation, or vice versa. We argue that there is a two-way relationship between information management and collaboration. Moreover, this research suggests that bottom-up governance is not a straightforward solution to water management problems in large-scale, complex, multiple-use systems, such as river basins. Instead, all the regimes being analyzed are in a process of finding a balance between bottom-up and top–down governance. Finally, this research shows that in a basin where one type of extreme is dominant—like droughts in the Alentejo (Portugal) and floods in Rivierenland (Netherlands)—the potential impacts of other extremes are somehow ignored or not perceived with the urgency they might deserv
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