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At least 1,711 records · Page 95

All sources NASA NTRS DOE OSTI

DOE OSTI2022

Global decline in ocean memory over the 21st century

Ocean memory, the persistence of ocean conditions, is a major source of predictability in the climate system beyond weather time scales. We show that ocean memory, as measured by the year-to-year persistence of sea surface temperature anomalies, is projected to steadily decline in the coming decades over much of the globe. This global decline in ocean memory is predominantly driven by shoaling of the upper-ocean mixed layer depth in response to global surface warming, while thermodynamic and dynamic feedbacks can contribute substantially regionally. As the mixed layer depth shoals, stochastic forcing becomes more effective in driving sea surface temperature anomalies, increasing high-frequency noise at the expense of persistent signals. Reduced ocean memory results in shorter lead times of skillful persistence-based predictions of sea surface thermal conditions, which may present previously unknown challenges for predicting climate extremes and managing marine biological resources under climate change.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2021

Two-color, intracavity pump–probe, cavity ringdown spectroscopy

Here, we report a proof-of-principle demonstration of intracavity pump–probe, cavity ringdown (CRD) detection in a three-mirror, traveling-wave cavity. With cavity-enhanced pump power and probe absorption path length, the technique is a generally applicable, high-sensitivity, high-selectivity detection method. In our experiments, the pump radiation is switched off during every other probe ringdown, which allows uncorrelated measurements of analyte and background cavity decay rates. The net, two-color signal from the difference between the pump-on and pump-off decay rates is immune to empty-CRD drifts and spectral overlaps from non-target molecular transitions. The immunity to the ringdown drifts allows longer signal-averaging and, thus, higher detection sensitivity. The ability to compensate for the background absorption enhances the detection selectivity in spectrally congested regions. Our technique is well-suited for trace-detection in the mid-IR region, where pump–probe schemes based on strong rovibrational transitions can be applied. In this work, two-color CRD detection is implemented on a ladder-type, three-level system based on the N 2 O, ν 3 = 1 ← 0, P(19) (pump) and ν 3 = 2 ← 1, R(18) (probe), rovibrational transitions. By frequency-locking two-quantum cascade lasers to the p-polarization (pump, Finesse = 5280) and s-polarization (probe, Finesse = 67 700) cavity modes, we achieve high intracavity pump power (36 W) and high probe ringdown rates (>2 kHz). The observed two-color spectra are simulated by a density-matrix, three-level system model that is solved under the constraints of the cavity resonance conditions. In addition to its background compensation capability, experimental flexibility in the selection of pump–probe schemes and signal insensitivity to intracavity laser power are further features that enhance the utility of our technique for mid-IR trace-detection.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2018

TLR4/NF-κB axis induces fludarabine resistance by suppressing TXNIP expression in acute myeloid leukemia cells

Highlights: • THP-1 cells highly express the Toll-like receptor 4 (TLR4). • THP-1 cells overcome fludarabine (FA)-induced cytotoxicity by LPS treatment. • TLR4/NF-κB signaling regulates LPS-induced cell survival under FA treatment. • TXNIP is crucial for FA-induced cytotoxicity and TLR4/NF-κB-mediated FA resistance. Overcoming drug resistance is one of key issues in treating refractory acute myeloid leukemia (AML). The Toll-like receptor 4 (TLR4) signaling pathway is involved in many aspects of biological functions of AML cells, including the regulation of pro-inflammatory cytokine products, myeloid differentiation, and survival of AML cells. Thus, targeting TLR4 of AML patients for therapeutic purposes should be carefully addressed. In this regard, we investigated the possible role of TLR4 as a regulatory factor against fludarabine (FA) cytotoxicity activity. Here, we identified the differential expression of TLR4 and CD14 receptors in AML cell lines and examined their relationship to FA sensitivity. We found that the stimulation of TLR4 with lipopolysaccharide (LPS) in a TLR4-expressing cell line, THP-1, increased cell viability under FA treatment condition and showed that TLR4 stimulation overcame FA sensitivity through the activation of NF-κB, which subsequently upregulated several anti-apoptotic genes. The inhibition of TLR4/NF-κB signaling could partially or completely reverse LPS-induced cell survival under FA treatment conditions. Interestingly, we found that the expression of thioredoxin-interacting protein (TXNIP), a well-known tumor suppressor, was induced by FA treatment; however, it was suppressed by LPS treatment. Furthermore, the expression level of TXNIP was critical for FA-induced cytotoxicity or LPS-induced FA resistance of THP-1 cells. Our data suggest that TXNIP plays an important role in FA-induced cytotoxicity and TLR4/NF-κB-mediated FA resistance of AML cells. Therefore, TXNIP may be a potential therapeutic target for AML treatment.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

Atmospheric effects on the laser-driven avalanche-based remote detection of radiation

Here, the effect of realistic atmospheric conditions on mid-IR (λ = 3.9 µm) and long-wave-IR (λ = 10 µm) laser-induced avalanche breakdown for the remote detection of radioactive material is examined experimentally and with propagation simulations. Our short-range in-lab mid-IR laser experiments show a correlation between increasing turbulence level and a reduced number of breakdown sites associated with a reduction in the portion of the focal volume above the breakdown threshold. Simulations of propagation through turbulence are in excellent agreement with these measurements and provide code validation. We then simulate propagation through realistic atmospheric turbulence over a long range (0.1–1 km) in the long-wave-IR regime (λ = 10 µm). The avalanche threshold focal volume is found to be robust even in the presence of strong turbulence, only dropping by ~50% over a propagation length of ~0.6 km. We also experimentally assess the impact of aerosols on avalanche-based detection, finding that, while background counts increase, a useful signal is extractable even at aerosol concentrations 10 5 times greater than what is typically observed in atmospheric conditions. Our results show promise for the long-range detection of radioactive sources under realistic atmospheric conditions.

54 ENVIRONMENTAL SCIENCES↗

NASA NTRS2003

Investigation of Overlap Correction Techniques for Application in the Micro-Pulse Lidar Network (MPLNET)

The Micro-Pulse Lidar NETwork (MPLNET) is comprised of micro-pulse lidars (MPL) stationed around the globe to provide measurements of aerosol and cloud vertical distribution on a continuous basis. MPLNET sites are co-located with sunphotometers in the AErosol Robotic NETwork (AERONET) to provide joint measurements of aerosol optical depth, size, and other inherent optical properties. The IPCC 2001 report discusses . the importance of obtaining routine measurements of aerosol vertical structure, especially for absorbing aerosols. MPLNET provides exactly this sort of measurement, including calculation of aerosol extinction profiles, in a near real-time basis for all sites in the network. In order to obtain aerosol profiles, near range signal returns (0-6 km) must be accurately measured by the MPL. This measurement is complicated by the instrument s overlap range: Le., the minimum distance at which returning signals are completely in the instrument s field-of-view (FOV). Typical MPL overlap distances are large, between 5 - 6 km, due to the narrow FOV of the MPL receiver. A function describing the MPL overlap must be determined and used to correct signals in this range. Currently, overlap functions for MPLNET are determined using horizontal MPL measurements along a path with 10-1 5 km clear line-of-sight and a homogenous atmosphere. These conditions limit the location and ease in which successful overlaps can be obtained. Furthermore, the current MPLNET process of correcting for overlap increases the uncertainty and bias error for the near range signals and the resulting aerosol extinction profiles. To address these issues, an alternative overlap correction method using a small-diameter, wide FOV receiver is being considered for potential use in MPLNET. The wide FOV receiver has a much shorter overlap distance and will be used to calculate the overlap function of the MPL receiver. This approach has a significant benefit in that overlap corrections could be obtained without the need for horizontal measurements. A review of both overlap methods is presented, including a discussion of the impact on reducing the uncertainty and bias error in MPLNET aerosol profiles.

Berkoff, Timothy A.↗

DOE OSTI2013

PROPERTIES OF DIFFUSE INTERSTELLAR BANDS AT DIFFERENT PHYSICAL CONDITIONS OF THE INTERSTELLAR MEDIUM

Diffuse interstellar bands (DIBs) can trace different conditions of the interstellar medium (ISM) along the sightline toward the observed stars. A small survey was made in optical wavelengths, producing high-resolution and high signal-to-noise spectra. We present measurements of 19 DIBs' properties in 50 sightlines toward hot stars, distributed at a variety of galactic coordinates and interstellar reddening. Equivalent widths were obtained by fitting asymmetric Gaussian and variable continua to DIBs. Conditions of the ISM were calculated from eight atomic and molecular interstellar lines. Two distinctly different types of DIBs were identified by carefully comparing correlation coefficients between DIBs and reddening and by different behavior in UV-shielded ({zeta}) and nonshielded ({sigma}) sightlines. A ratio of DIBs at 5780 A and 5797 A proved to be reliable enough to distinguish between two different sightline types. Based on the linear relations between DIB equivalent width and reddening for {sigma} and {zeta} sightlines, we divide DIBs into type I (where both linear relations are similar) and type II (where they are significantly different). The linear relation for {zeta} type sightlines always shows a higher slope and larger x-intercept parameter than the relation for {sigma} sightlines. Scatter around the linear relation is reduced after the separation, but it does not vanish completely. This means that UV shielding is the dominant factor of the DIB equivalent width versus reddening relation shape for {zeta} sightlines, but in {sigma} sightlines other physical parameters play a major role. No similar dependency on gas density, electron density, or turbulence was observed. A catalog of all observed interstellar lines is made public.

79 ASTRONOMY AND ASTROPHYSICS↗

NASA NTRS1996

Assimilation of Geosat Altimetric Data in a Nonlinear Shallow-Water Model of the Indian Ocean by Adjoint Approach. Part II: Some Validation and Interpretation of the Assimilated Results: Some Validation and Interpretation of the Assimilated Results - Part 2

This paper examines the results of assimilating Geosat sea level variations relative to the November 1986-November 1988 mean reference, in a nonlinear reduced-gravity model of the Indian Ocean, Data have been assimilated during one year starting in November 1986 with the objective of optimizing the initial conditions and the yearly averaged reference surface. The thermocline slope simulated by the model with or without assimilation is validated by comparison with the signal, which can be derived from expandable bathythermograph measurements performed in the Indian Ocean at that time. The topography simulated with assimilation on November 1986 is in very good agreement with the hydrographic data. The slopes corresponding to the South Equatorial Current and to the South Equatorial Countercurrent are better reproduced with assimilation than without during the first nine months. The whole circulation of the cyclonic gyre south of the equator is then strongly intensified by assimilation. Another assimilation experiment is run over the following year starting in November 1987. The difference between the two yearly mean surfaces simulated with assimilation is in excellent agreement with Geosat. In the southeastern Indian Ocean, the correction to the yearly mean dynamic topography due to assimilation over the second year is negatively correlated to the one the year before. This correction is also in agreement with hydrographic data. It is likely that the signal corrected by assimilation is not only due to wind error, because simulations driven by various wind forcings present the same features over the two years. Model simulations run with a prescribed throughflow transport anomaly indicate that assimilation is rather correcting in the interior of the model domain for inadequate boundary conditions with the Pacific.

Greiner, Eric↗

NASA NTRS2018

Detecting Early Warning Signals of Tree Mortality in Boreal North America Using Multiscale Satellite Data

Increasing tree mortality from global change drivers such as drought and biotic infestations is a widespread phenomenon, including in the boreal zone where climate changes and feedbacks to the Earth system are relatively large. Despite the importance for science and management communities, our ability to forecast tree mortality at landscape to continental scales is limited. However, two independent information streams have the potential to inform and improve mortality forecasts: repeat forest inventories and satellite remote sensing. Time series of tree-level growth patterns indicate that productivity declines and related temporal dynamics often precede mortality years to decades before death. Plot-level productivity, in turn, has been related to satellite-based indices such as the Normalized difference vegetation index (NDVI). Here we link these two data sources to show that early warning signals of mortality are evident in several NDVI-based metrics up to 24 years before death. We focus on two repeat forest inventories and three NDVI products across western boreal North America where productivity and mortality dynamics are influenced by periodic drought. These data sources capture a range of forest conditions and spatial resolution to highlight the sensitivity and limitations of our approach. Overall, results indicate potential to use satellite NDVI for early warning signals of mortality. Relationships are broadly consistent across inventories, species, and spatial resolutions, although the utility of coarse-scale imagery in the heterogeneous aspen parkland was limited. Longer-term NDVI data and annually remeasured sites with high mortality levels generate the strongest signals, although we still found robust relationships at sites remeasured at a typical 5 year frequency. The approach and relationships developed here can be used as a basis for improving forest mortality models and monitoring systems.

heat↗

DOE OSTI2018

Angiotensin II type 1 receptor-associated protein regulates carotid intimal hyperplasia through controlling apoptosis of vascular smooth muscle cells

Highlights: • ATRAP as a negative regulator of AT1 receptor plays an inhibitory role in VSMCs proliferation both in vitro and in vivo. • ATRAP triggers the marked apoptosis of VSMCs in balloon-injuried carotid arteries and depresses neointimal formation. • ATRAP induces VSMCs apoptosis through the influence of the PI3K/Akt signaling pathway. Intimal hyperplasia is the main cause of restenosis after carotid artery injury, and the underlying mechanism involves the proliferation and migration of vascular smooth muscle cells (VSMCs). Angiotensin II Type 1 Receptor-Associated Protein (ATRAP) has been reported to withstand intimal hyperplasia by inhibiting VSMCs proliferation and migration; however, whether the beneficial effect of ATRAP associates with VSMCs apoptosis remains unclarified. We demonstrated that the adenoviral-mediated overexpression of ATRAP induced VSMC apoptosis, alleviating the balloon injury-induced neointima formation in rats. Under the condition of Angiotensin-II stimulation, ATRAP overexpression induced the apoptosis of rat VSMCs by depressing the PI3K-Akt signaling; whereas up-regulation of Akt by PTEN inhibitor abolished the apoptotic death. Thus, ATRAP regulates carotid intimal hyperplasia through controlling the PI3K-Akt signal-mediated VSMCs apoptosis.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Comparison of mode-locking regimes in a holmium fibre laser

A comparison has been performed for two mode-locking regimes in an all-fibre holmium laser: locking due to nonlinear polarisation rotation (NPR) and hybrid mode-locking (NPR with application of single-walled carbon nanotubes). The characteristics of pulsed lasing in both regimes are investigated. Pulsed lasing is obtained at wavelengths of 2072 and 2082 nm, with FWHM values of 3.7 and 3.3 nm, respectively. The pulse width in both cases does not exceed 1.5 ps. The pulse energies in the NPR mode-locking and hybrid mode-locking regimes are 0.4 and 0.3 nJ, respectively. It is shown that the signal-to-noise ratio in the case of hybrid mode-locking is 3 dB better than that implemented under conditions of NPR mode-locking. A possibility of self-starting a laser system by applying hybrid mode-locking is indicated. (paper)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DOE OSTI2023

Seismoacoustic Analysis of the Large Surface Explosion Coupling Experiment Using a Large- N Seismic Array

Seismoacoustic signals at local distance (<~10 km) are widely used as important constraints on source parameters for near-surface events, yet the seismoacoustic wave generation and energy partitioning are not fully understood. Spatially dense sensors could provide observations in high resolution to capture the full wavefield for better understanding wave propagation and improving source estimation. Recently, spatially dense observations of the local seismoacoustic wavefield produced by a pair of 1-ton surface explosions have been recorded using a large-N seismic array. This large-N array consists of 446 geophones and covers an area of approximately 2×2.5 km 2 . The two surface explosions occur at the same location but at different times with different atmospheric conditions. Both seismic and air–ground coupled acoustic waves from the two surface explosions are well observed. Analyses of signals recorded by the large-N seismic array show different acoustic wave speed and amplitude for the two explosions. A strong spatial variability in acoustic wave speed and amplitude for each explosion is also observed. Finally, the observations suggest the important role of local atmosphere state on wave propagation and source estimation and demonstrate how the use of a large-N capability can improve characterization of the propagation medium and source.

58 GEOSCIENCES↗

DOE OSTI2024

Highly cascaded first-order fiber Bragg gratings in highly multimode optical fibers for distributed temperature sensing under harsh environment conditions

This study presents a pioneering technique for fabricating highly cascaded first-order fiber Bragg gratings (FBGs) using a femtosecond laser-assisted point-by-point inscription method in highly multimode optical fibers, specifically Sapphire crystalline fiber, and pure silica coreless fiber. Notably, it marks the first successful demonstration of a distributed array comprising 10 FBGs within highly multimode fibers. This achievement is facilitated by a high-power laser technique that yields larger reflectors characterized by a Gaussian intensity profile. These first-order FBGs offer various advantages, including enhanced reflectivity, reduced fabrication time, and simplified spectral characteristics, enhancing their accessibility for interpretation when contrasted with higher-order FBGs. In addition to that it encompasses a comprehensive analysis of the robustness and efficacy of these FBGs, with particular emphasis on their ability to endure extreme temperatures. These FBGs demonstrate an advantageous capability for localized multi-point temperature monitoring, reaching temperatures up to 1500°C with sapphire crystalline fiber and 1100°C with pure silica coreless fiber. This resilience makes them suitable for deployment in harsh environmental conditions. This innovative approach substantially broadens the potential applications of highly multimode optical fibers, particularly in the arena of sensing and communication, where challenges related to thermal gradients and harsh environments prevail. Furthermore, these groundbreaking first-order FBGs signify a substantial advancement in the realm of distributed temperature sensing, offering supreme capabilities for temperature monitoring and signal stability. As such, our work holds the promise of a substantial impact on industries and applications that demand unwavering reliability under extreme conditions.

47 OTHER INSTRUMENTATION↗

DOE OSTI2016

A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses La Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Signal amplification in a solid-state sensor through asymmetric many-body echo

Electronic spins of nitrogen–vacancy centres in diamond constitute a promising system for micro- and nanoscale magnetic sensing, because of their operation under ambient conditions, ease of placement in close proximity to sensing targets and biological compatibility. At high densities, the electronic spins interact through dipolar coupling, which typically limits but can also potentially enhance sensing performance. Here we report the experimental demonstration of many-body signal amplification in a solid-state, room-temperature quantum sensor. Our approach uses time-reversed two-axis-twisting interactions, engineered through dynamical control of the quantization axis and Floquet engineering in a two-dimensional ensemble of nitrogen–vacancy centres. We observe that optimal amplification occurs when the backward evolution time equals twice the forward evolution time, in sharp contrast to the conventional Loschmidt echo. These observations can be understood as resulting from an underlying time-reversed mirror symmetry of the microscopic dynamics, providing key insights into signal amplification and opportunities for practical entanglement-enhanced quantum sensing.

quantum information↗

DOE OSTI2016

Interpreting the CMB aberration and Doppler measurements: boost or intrinsic dipole?

The aberration and Doppler coupling effects of the Cosmic Microwave Background (CMB) were recently measured by the Planck satellite. The most straightforward interpretation leads to a direct detection of our peculiar velocity β, consistent with the measurement of the well-known dipole. In this paper we discuss the assumptions behind such interpretation. We show that Doppler-like couplings appear from two effects: our peculiar velocity and a second order large-scale effect due to the dipolar part of the gravitational potential. We find that the two effects are exactly degenerate but only if we assume second-order initial conditions from single-field Inflation. Thus, detecting a discrepancy in the value of β from the dipole and the Doppler couplings implies the presence of a primordial non-Gaussianity. We also show that aberration-like signals likewise arise from two independent effects: our peculiar velocity and lensing due to a first order large-scale dipolar gravitational potential, independently on Gaussianity of the initial conditions. In general such effects are not degenerate and so a discrepancy between the measured β from the dipole and aberration could be accounted for by a dipolar gravitational potential. Only through a fine-tuning of the radial profile of the potential it is possible to have a complete degeneracy with a boost effect. Finally we discuss that we also expect other signatures due to integrated second order terms, which may be further used to disentangle this scenario from a simple boost.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2015

Reproducible Data Processing Research for the CABRI R.I.A. experiments Acoustic Emission signal analysis

The CABRI facility is an experimental nuclear reactor of the French Atomic Energy Commission (CEA) designed to study the behaviour of fuel rods at high burnup under Reactivity Initiated Accident (R.I.A.) conditions such as the scenario of a control rod ejection. During the experimental phase, the behaviour of the fuel element generates acoustic waves which can be detected by two microphones placed upstream and downstream from the test device. Studies carried out on the last fourteen tests showed the interest in carrying out temporal and spectral analyses on these signals by showing the existence of signatures which can be correlated with physical phenomena. We want presently to return to this rich data in order to have a new point of view by applying modern signal processing methods. Such an antecedent works resumption leads to some difficulties. Although all the raw data are accessible in the form of text files, analyses and graphics representations were not clear in reproducing from the former studies since the people who were in charge of the original work have left the laboratory and it is not easy when time passes, even with our own work, to be able to remember the steps of data manipulations and the exact setup. Thus we decided to consolidate the availability of the data and its manipulation in order to provide a robust data processing workflow to the experimentalists before doing any further investigations. To tackle this issue of strong links between data, treatments and the generation of documents, we adopted a Reproducible Research paradigm. We shall first present the tools chosen in our laboratory to implement this workflow and, then we shall describe the global perception carried out to continue the study of the Acoustic Emission signals recorded by the two microphones during the last fourteen CABRI R.I.A. tests. (authors)

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

NASA NTRS1980

Performance considerations of frequency-hopping multiple access

The basic system parameters of a frequency-hopping multiple-access system are investigated. Noncoherent binary FSK and M-ary FSK signal formats are studied in a random-access asynchronous environment. Both slow and fast frequency hopping are considered. Under relatively ideal conditions, the degradation in performance with respect to the number of users is determined. The dependence on performance due to hopping rate and bandwidth constraint is developed. It is shown, for example, that, for fast hopping, the optimum hopping rate is that which spreads the users' power over the entire available bandwidth during each baud time. This agrees with the basic spread spectrum philosophy of making the signal appear white over as wide a bandwidth as possible. The computational results describe the trade-off between the number of tones in M-ary FSK and the number of hops per symbol. Given a specified number of tones in the frequency-hopping system, the results describe the manner in which the system degrades as the number of users is increased.

Weber, C. L.↗

DOE OSTI2023

Genetic encoding of 3–nitro–tyrosine reveals the impacts of 14–3–3 nitration on client binding and dephosphorylation

14–3–3 proteins are central hub regulators of hundreds of phosphorylated “client” proteins. They are subject to over 60 post–translational modifications (PTMs), yet little is known how these PTMs alter 14–3–3 function and its ability to regulate downstream signaling pathways. An often neglected, but well–documented 14–3–3 PTM found under physiological and immune–stimulatory conditions is the conversion of tyrosine to 3–nitro–tyrosine at several Tyr sites, two of which are located at sites considered important for 14–3–3 function: Y130 (β–isoform numbering) is located in the primary phospho–client peptide–binding groove, while Y213 is found on a secondary binding site that engages with clients for full 14–3–3/client complex formation and client regulation. By genetically encoding 3–nitro–tyrosine, we sought to understand if nitration at Y130 and Y213 effectively modulated 14–3–3 structure, function, and client complexation. The 1.5 Å resolution crystal structure of 14–3–3 nitrated at Y130 showed the nitro group altered the conformation of key residues in the primary binding site, while functional studies confirmed client proteins failed to bind this variant of 14–3–3. But, in contrast to other client–binding deficient variants, it did not localize to the nucleus. Further, the 1.9 Å resolution structure of 14–3–3 nitrated at Y213 revealed unusual flexibility of its C–terminal α–helix resulting in domain swapping, suggesting additional structural plasticity though its relevance is not clear as this nitrated form retained its ability to bind clients. Collectively, our data suggest that nitration of 14–3–3 will alter downstream signaling systems, and if uncontrolled could result in global dysregulation of the 14–3–3 interactome.

14-3-3↗