2,468 research outputs found
Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin
Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society
Observationally constrained modeling of sound in curved ocean internal waves: Examination of deep ducting and surface ducting at short range
Author Posting. © Acoustical Society of America, 2011. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 130 (2011): 1173-1187, doi:10.1121/1.3605565.A study of 400 Hz sound focusing and ducting effects in a packet of curved nonlinear internal waves in shallow water is presented. Sound propagation roughly along the crests of the waves is simulated with a three-dimensional parabolic equation computational code, and the results are compared to measured propagation along fixed 3 and 6 km source/receiver paths. The measurements were made on the shelf of the South China Sea northeast of Tung-Sha Island. Construction of the time-varying three-dimensional sound-speed fields used in the modeling simulations was guided by environmental data collected concurrently with the acoustic data. Computed three-dimensional propagation results compare well with field observations. The simulations allow identification of time-dependent sound forward scattering and ducting processes within the curved internal gravity waves. Strong acoustic intensity enhancement was observed during passage of high-amplitude nonlinear waves over the source/receiver paths, and is replicated in the model. The waves were typical of the region (35 m vertical displacement). Two types of ducting are found in the model, which occur asynchronously. One type is three-dimensional modal trapping in deep ducts within the wave crests (shallow thermocline zones). The second type is surface ducting within the wave troughs (deep thermocline zones).Grants from the Office of Naval Research funded this
work. Use of the vessels Ocean Researcher I and Ocean
Researcher II in this experiment was funded by the Taiwan
National Science Council
Lessons Learned from Recent Failure and Incident Investigations of Composite Structures
During the past few decades, NASA Langley Research Center (LaRC) has supported several large-scale failure and incident investigations and numerous requests for engineering consultations. Although various extenuating circumstances contributed to each of these incidents, in all cases, the failure resulted from accumulation and/or propagation of damage that reduced the load carrying capability of the structure to a level below that which was needed to sustain structural loads. A brief overview of various failure and incident investigations supported by LaRC, including some of the computational and experimental methodologies that have been applied, is presented. An important outcome of many of these failure and incident investigations is the development of an improved understanding of not only the state-of-the-art in experimental and analytical methods but also the state-of-the-art in the design and manufacturing processes that may contribute to such failures. In order to provide insight into such large-scale investigations, a series of lessons learned were captured. Awareness of these lessons learned is highly beneficial to engineers involved in similar investigations. Therefore, it is prudent that the lessons learned are disseminated such that they can be built upon in other investigations and in ensuing research and development activities
Redox and Peroxidase Activities of the Hemoglobin Superfamily: Relevance to Health and Disease
Significance: Erythrocyte hemoglobin (Hb) and myocyte myoglobin, although primarily oxygen-carrying proteins,
have the capacity to do redox chemistry. Such redox activity in the wider family of globins now appears to have important
associations with the mechanisms of cell stress response. In turn, an understanding of such mechanisms in vivo may have
a potential in the understanding of cancer therapy resistance and neurodegenerative disorders such as Alzheimer’s.
Recent Advances: There has been an enhanced understanding of the redox chemistry of the globin superfamily
in recent years, leading to advances in development of Hb-based blood substitutes and in hypotheses relating to
specific disease mechanisms. Neuroglobin (Ngb) and cytoglobin (Cygb) have been linked to cell protection
mechanisms against hypoxia and oxidative stress, with implications in the onset and progression of neurodegenerative
diseases for Ngb and cancer for Cygb.
Critical Issues: Despite advances in the understanding of redox chemistry of globins, the physiological roles of
many of these proteins still remain ambiguous at best. Confusion over potential physiological roles may relate
to multifunctional roles for globins, which may be modulated by surface-exposed cysteine pairs in some
globins. Such roles may be critical in deciphering the relationships of these globins in human diseases.
Future Directions: Further studies are required to connect the considerable knowledge on the mechanisms of globin
redox chemistry in vitro with the physiological and pathological roles of globins in vivo. In doing so, new therapies
for neurodegenerative disorders and cancer therapy resistance may be targeted
Cochlear Implants in the Workplace: A Nationwide Survey
A nation wide survey of cochlear implant recipients was conducted to study how implants may impact people at work. Using a self-reporting questionnaire, recipients using four cochlear implant designs were surveyed about spoken communication on the job, overall job performance, job satisfaction, confidence in job retention and in seeking new employment, job promotion, and income. Of the implant recipients using their implants at work (106 people), the majority used their implants during all work hours and reported positive changes in their job situations. The survey results suggest that cochlear implants may help in mitigating functional limitations in the workplace resulting from profound hearing loss
Landscape Genetics of Raccoons (\u3ci\u3eProcyon lotor\u3c/i\u3e) Associated with Ridges and Valleys of Pennsylvania: Implications for Oral Rabies Vaccination Programs
Raccoons are the reservoir for the raccoon rabies virus variant in the United States. To combat this threat, oral rabies vaccination (ORV) programs are conducted in many eastern states. To aid in these efforts, the genetic structure of raccoons (Procyon lotor) was assessed in southwestern Pennsylvania to determine if select geographic features (i.e., ridges and valleys) serve as corridors or hindrances to raccoon gene flow (e.g., movement) and, therefore, rabies virus trafficking in this physiographic region. Raccoon DNA samples (n = 185) were collected from one ridge site and two adjacent valleys in southwestern Pennsylvania (Westmoreland, Cambria, Fayette, and Somerset counties). Raccoon genetic structure within and among these study sites was characterized at nine microsatellite loci. Results indicated that there was little population subdivision among any sites sampled. Furthermore, analyses using a model-based clustering approach indicated one essentially panmictic population was present among all the raccoons sampled over a reasonably broad geographic area (e.g., sites up to 36 km apart). However, a signature of isolation by distance was detected, suggesting that widths of ORV zones are critical for success. Combined, these data indicate that geographic features within this landscape influence raccoon gene flow only to a limited extent, suggesting that ridges of this physiographic system will not provide substantial long-term natural barriers to rabies virus trafficking. These results may be of value for future ORV efforts in Pennsylvania and other eastern states with similar landscapes
Improved fat water separation with water selective inversion pulse for inversion recovery-based cardiac MRI sequence
Effect of the distal histidine on the peroxidatic activity of monomeric cytoglobin
The reaction of hydrogen peroxide with ferric human cytoglobin and a number of distal histidine variants were studied. The peroxidase activity of the monomeric wildtype protein with an internal disulfide bond, likely to be the form of the protein in vivo, exhibits a high peroxidase-like activity above that of other globins such as myoglobin. Furthermore, the peroxidatic activity of wildtype cytoglobin shows increased resistance to radical-based degradation compared to myoglobin. The ferryl form of wildtype cytoglobin is unstable, but is able to readily oxidize substrates such as guaiacol. In contrast distal histidine mutants of cytoglobin (H81Y and H81V) show very low peroxidase activity but enhanced radical-induced degradation. Therefore, the weakly bound distal histidine appears to modulate ferryl stability and limit haem degradation. These data are consistent with a role of a peroxidase activity of cytoglobin in cell stress response mechanisms.</ns4:p
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