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At least 1,081 records · Page 60

An Interaction Library for the FcεRI Signaling Network

Antigen receptors play a central role in adaptive immune responses. Although the molecular networks associated with these receptors have been extensively studied, we currently lack a systems-level understanding of how combinations of non-covalent interactions and post-translational modifications are regulated during signaling to impact cellular decision-making. To fill this knowledge gap, it will be necessary to formalize and piece together information about individual molecular mechanisms to form large-scale computational models of signaling networks. To this end, we have developed an interaction library for signaling by the high-affinity IgE receptor, FcεRI. The library consists of executable rules for protein–protein and protein–lipid interactions. This library extends earlier models for FcεRI signaling and introduces new interactions that have not previously been considered in a model. Thus, this interaction library is a toolkit with which existing models can be expanded and from which new models can be built. As an example, we present models of branching pathways from the adaptor protein Lat, which influence production of the phospholipid PIP 3 at the plasma membrane and the soluble second messenger IP 3 . We find that inclusion of a positive feedback loop gives rise to a bistable switch, which may ensure robust responses to stimulation above a threshold level. In addition, the library is visualized to facilitate understanding of network circuitry and identification of network motifs.

59 BASIC BIOLOGICAL SCIENCES↗

Extracellular ATP acts as a damage-associated molecular pattern (DAMP) signal in plants

As sessile organisms, plants have evolved effective mechanisms to protect themselves from environmental stresses. Damaged (i.e., wounded) plants recognize a variety of endogenous molecules as danger signals, referred to as damage-associated molecular patterns (DAMPs). ATP is among the molecules that are released by cell damage, and recent evidence suggests that ATP can serve as a DAMP. Although little studied in plants, extracellular ATP is well known for its signaling roles in animals, including acting as a DAMP during the inflammatory response and wound healing. If ATP acts outside the cell, then it is reasonable to expect that it is recognized by a plasma membrane-localized receptor. Recently, DORN1, a lectin receptor kinase, was shown to recognize extracellular ATP in Arabidopsis. DORN1 is the founding member of a new purinoceptor subfamily, P2K (P2 receptor kinase), which is plant-specific. P2K1 (DORN1) is required for ATP-induced cellular responses (e.g., cytosolic Ca2+ elevation, MAPK phosphorylation, and gene expression). Genetic analysis of loss-of-function mutants and overexpression lines showed that P2K1 participates in the plant wound response, consistent with the role of ATP as a DAMP. In this review, we summarize past research on the roles and mechanisms of extracellular ATP signaling in plants, and discuss the direction of future research on extracellular ATP as a DAMP signal.

54 ENVIRONMENTAL SCIENCES↗

The Role of Sugar Signaling in Regulating Plant Fatty Acid Synthesis

Photosynthates such as glucose, sucrose, and some of their derivatives play dual roles as metabolic intermediates and signaling molecules that influence plant cell metabolism. Such sugars provide substrates for de novo fatty acid (FA) biosynthesis. However, compared with the well-defined examples of sugar signaling in starch and anthocyanin synthesis, until recently relatively little was known about the role of signaling in regulating FA and lipid biosynthesis. Recent research progress shows that trehalose 6-phosphate and 2-oxoglutarate (2-OG) play direct signaling roles in the regulation of FA biosynthesis by modulating transcription factor stability and enzymatic activities involved in FA biosynthesis. Specifically, mechanistic links between sucrose non-fermenting−1–related protein kinase 1 (SnRK1)–mediated trehalose 6-phosphate (T6P) sensing and its regulation by phosphorylation of WRI1 stability, diacylglycerol acyltransferase 1 (DGAT1) enzyme activity, and of 2-OG–mediated relief of inhibition of acetyl-CoA carboxylase (ACCase) activity by protein PII are exemplified in detail in this review.

59 BASIC BIOLOGICAL SCIENCES↗

Wounding rapidly alters transcription factor expression, hormonal signaling, and phenolic compound metabolism in harvested sugarbeet roots

Injuries sustained by sugarbeet (Beta vulgaris L.) roots during harvest and postharvest operations seriously reduce the yield of white sugar produced from stored roots. Although wound healing is critically important to reduce losses, knowledge of these processes is limited for this crop as well as for roots in other species. To better understand the metabolic signals and changes that occur in wounded roots, dynamic changes in gene expression were determined by RNA sequencing and the activity of products from key genes identified in this analysis were determined in the 0.25 to 24 h following injury. Nearly five thousand differentially expressed genes that contribute to a wide range of cellular and molecular functions were identified in wounded roots. Highly upregulated genes included transcription factor genes, as well as genes involved in ethylene and jasmonic acid (JA) biosynthesis and signaling and phenolic compound biosynthesis and polymerization. Enzyme activities for key genes in ethylene and phenolic compound biosynthesis and polymerization also increased due to wounding. Results indicate that wounding causes a major reallocation of metabolism in sugarbeet taproots. Although both ethylene and JA are likely involved in triggering wound responses, the greater and more sustained upregulation of ethylene biosynthesis and signaling genes relative to those of JA, suggest a preeminence of ethylene signaling in wounded sugarbeet roots. Changes in gene expression and enzymes involved in phenolic compound metabolism additionally indicate that barriers synthesized to seal off wounds, such as suberin or lignin, are initiated within the first 24 h after injury.

59 BASIC BIOLOGICAL SCIENCES↗

Lectin Receptor-like Kinase Signaling during Engineered Ectomycorrhiza Colonization

Mutualistic association can improve a plant’s health and productivity. G-type lectin receptor-like kinase (PtLecRLK1) is a susceptibility factor in Populus trichocarpa that permits root colonization by a beneficial fungus, Laccaria bicolor. Engineering PtLecRLK1 also permits L. bicolor root colonization in non-host plants similar to Populus trichocarpa. The intracellular signaling reprogramed by PtLecRLK1 upon recognition of L. bicolor to allow for the development and maintenance of symbiosis is yet to be determined. In this study, phosphoproteomics was utilized to identify phosphorylation-based relevant signaling pathways associated with PtLecRLK1 recognition of L. bicolor in transgenic switchgrass roots. Our finding shows that PtLecRLK1 in transgenic plants modifies the chitin-triggered plant defense and MAPK signaling along with a significant adjustment in phytohormone signaling, ROS balance, endocytosis, cytoskeleton movement, and proteasomal degradation in order to facilitate the establishment and maintenance of L. bicolor colonization. Moreover, protein–protein interaction data implicate a cGMP-dependent protein kinase as a potential substrate of PtLecRLK1.

ectomycorrhiza colonization↗

The Gravitational Wave Signal from Core-collapse Supernovae

We report on gravitational waves (GWs) from a set of 2D multigroup neutrino radiation hydrodynamic simulations of core-collapse supernovae (CCSNe). Our aim is to systematize the current knowledge about the post-bounce CCSN GW signal and recognize the templatable features that could be used by the ground-based laser interferometers. We demonstrate that, starting from ~400 ms after core bounce, the dominant GW signal represents the fundamental quadrupole (l = 2) oscillation mode (f-mode) of the proto–neutron star (PNS), which can be accurately reproduced by a linear perturbation analysis of the angle-averaged PNS profile. Before that, in the time interval between ~200 and ~400 ms after bounce, the dominant mode has two radial nodes and represents a g-mode. We associate the high-frequency noise in the GW spectrograms above the main signal with p-modes, while below the dominant frequency there is a region with very little power. The collection of models introduced here summarizes the dependence of the CCSN GW signal on the progenitor mass, equation of state, many-body corrections to the neutrino opacity, and rotation. Weak dependence of the dominant GW frequency on the progenitor mass motivates us to provide a simple fit for it as a function of time, which can be used as a prior when looking for CCSN candidates in the LIGO data.

79 ASTRONOMY AND ASTROPHYSICS↗

AI ensemble for signal detection of higher order gravitational wave modes of quasi-circular, spinning, non-precessing binary black hole mergers

We introduce spatiotemporal-graph models that concurrently process data from the twin advanced LIGO detectors and the advanced Virgo detector. We trained these AI classifiers with 2.4 million IMRPhenomXPHM waveforms that describe quasi-circular, spinning, non-precessing binary black hole mergers with component masses m{1,2}∈[3M⊙,50M⊙], and individual spins sz{1,2}∈[−0.9,0.9]; and which include the (ℓ,|m|)={(2,2),(2,1),(3,3),(3,2),(4,4)} modes, and mode mixing effects in the ℓ=3,|m|=2 harmonics. We trained these AI classifiers within 22 hours using distributed training over 96 NVIDIA V100 GPUs in the Summit supercomputer. We then used transfer learning to create AI predictors that estimate the total mass of potential binary black holes identified by all AI classifiers in the ensemble. We used this ensemble, 3 classifiers for signal detection and 2 total mass predictors, to process a year-long test set in which we injected 300,000 signals. This year-long test set was processed within 5.19 minutes using 1024 NVIDIA A100 GPUs in the Polaris supercomputer (for AI inference) and 128 CPU nodes in the ThetaKNL supercomputer (for post-processing of noise triggers), housed at the Argonne Leadership Computing Facility. These studies indicate that our AI ensemble provides state-of-the-art signal detection accuracy, and reports 2 misclassifications for every year of searched data. This is the first AI ensemble designed to search for and find higher order gravitational wave mode signals.

Tian, Minyang↗

Homeostasis of branched-chain amino acids is critical for the activity of TOR signaling in Arabidopsis

The target of rapamycin (TOR) kinase is an evolutionarily conserved hub of nutrient sensing and metabolic signaling. In plants, a functional connection of TOR activation with glucose availability was demonstrated, while it is yet unclear whether branched-chain amino acids (BCAAs) are a primary input of TOR signaling as they are in yeast and mammalian cells. Here, we report on the characterization of an Arabidopsis mutant over-accumulating BCAAs. Through chemical interventions targeting TOR and by examining mutants of BCAA biosynthesis and TOR signaling, we found that BCAA over-accumulation leads to up-regulation of TOR activity, which causes reorganization of the actin cytoskeleton and actin-associated endomembranes. Finally, we show that activation of TOR is concomitant with alteration of cell expansion, proliferation and specialized metabolism, leading to pleiotropic effects on plant growth and development. These results demonstrate that BCAAs contribute to plant TOR activation and reveal previously uncharted downstream subcellular processes of TOR signaling.

59 BASIC BIOLOGICAL SCIENCES↗

Structure of human Frizzled5 by fiducial-assisted cryo-EM supports a heterodimeric mechanism of canonical Wnt signaling

Frizzleds (Fzd) are the primary receptors for Wnt morphogens, which are essential regulators of stem cell biology, yet the structural basis of Wnt signaling through Fzd remains poorly understood. Here we report the structure of an unliganded human Fzd5 determined by single-particle cryo-EM at 3.7 Å resolution, with the aid of an antibody chaperone acting as a fiducial marker. We also analyzed the topology of low-resolution XWnt8/Fzd5 complex particles, which revealed extreme flexibility between the Wnt/Fzd-CRD and the Fzd-TM regions. Analysis of Wnt/β-catenin signaling in response to Wnt3a versus a ‘surrogate agonist’ that cross-links Fzd to LRP6, revealed identical structure-activity relationships. Thus, canonical Wnt/β-catenin signaling appears to be principally reliant on ligand-induced Fzd/LRP6 heterodimerization, versus the allosteric mechanisms seen in structurally analogous class A G protein-coupled receptors, and Smoothened. These findings deepen our mechanistic understanding of Wnt signal transduction, and have implications for harnessing Wnt agonism in regenerative medicine.

59 BASIC BIOLOGICAL SCIENCES↗

Blood pressure reprogramming adapter assists signal recording

Blood pressure reprogramming adapter separates the two components of a blood pressure signal, a dc pressure signal and an ac Korotkoff sounds signal, so that the Korotkoff sounds are recorded on one channel as received while the dc pressure signal is converted to FM and recorded on a second channel.

Vick, H. A.↗

Electronic signal generators: A compilation

Electronic signal generator data based on solid state concepts were simplified or refined to meet requirements, such as reliability, simplicity, fail-safe characteristics, and the capability of withstanding environmental extremes. Pulse generators, high voltage pulse generators, oscillators, analog signal generators, square wave signal generators, and special function signal generators are described.

Source record↗

Phase-lock demodulation of a PM signal contaminated with incidental AM

Signals from phase-modulated satellite transmitters usually exhibit some degree of incidental amplitude modulation. The effects of incidental AM are analyzed when this type of signal is demodulated by a phase-lock receiver which does not employ a limiter preceding the loop phase detector. The presence of incidental AM causes a reduction in the receiver output signal-to-noise ratio. The tolerable level of AM decreases in proportion to the phase modulation index Beta. For a square-wave modulating signal, a 1 db reduction results at the receiver PM channel output when Beta = 1 radian and the percentage of AM = 23, Beta = 1.2 radians and the percentage of AM = 16, or Beta = 1.5 radians and the percentage of AM = 4. Although only the PM channel of the receiver is used ordinarily, utilizing both the AM and PM channel by summing offers an improvement in S/N relative to the S/N ratio of the PM channel if the percentage of incidental AM is greater than fifteen.

Robinson, G. B.↗

Precision signal power measurement

Accurate estimation of signal power is an important Deep Space Network (DSN) consideration. Ultimately, spacecraft power and weight is saved if no reserve transmitter power is needed to compensate for inaccurate measurements. Spectral measurement of the received signal has proved to be an effective method of estimating signal power over a wide dynamic range. Furthermore, on-line spectral measurements provide an important diagnostic tool for examining spacecraft anomalies. Prototype equipment installed at a 64-m-diameter antenna site has been successfully used to make measurements of carrier power and sideband symmetry of telemetry signals received from the Mariner Mars 1971 spacecraft.

Winkelstein, R.↗

Satellite observations of whistler-mode signals in the conjugate region of a 200-kilohertz station.

Study of the signals recorded by a narrow-band (about 200 Hz) receiver at a broadcast station operating at 200 kHz and in the conjugate region of Ashkhabad. The latitude of the station is nearly low enough for propagation of a 200-kHz signal in the ducted whistler mode to the conjugate hemisphere along field lines terminating at the station. In the dawn-dusk orbital plane signals are indeed relatively often observed in the conjugate region, but the source of the signals and their path of propagation is not completely clear. The pattern of observations is consistent with propagation over the long magnetospheric path in field-aligned ducts spread in longitude near 22 deg invariant latitude, but an interpretation involving nonducted propagation is preferred, in which the occasionally high electric-field intensities encountered (greater than 10 microvolts/m) result from focusing effects or from propagation near the resonance angle.

Laaspere, T.↗

Phase shift keyed, pulse code modulated signal synchronizer

Signal is demodulated and synchronized by three loop circuits: ''Q'' loop uses quadrature signal to stabilize frequency; ''B'' loop acts on baseboard signal to stabilize phase; and decoding ''I'' loop acts on in-phase signal. Synchronizer may be used to eliminate false-lock.

Kobayashi, H. S.↗

Amplitude fading of simultaneous transionospheric L-band and VHF signals received at the geomagnetic equator

At Ancon, Peru, simultaneous observations of 1550-MHz and 136-MHz signals from the ATS 5 and Intelsat-1 spacecraft showed ionospheric fading as great as 27 db at 136 MHz and 6 db at 1550 MHZ. The observations were made on 48 days during the 1970 autumnal and 1971 vernal equinox periods. Comparison of the two frequencies, in respect to rates and depths of fades, is made. Statistical distributions of the received signal levels during ionospheric scintillation occurrences are presented which may be of use to communications system engineers with operational requirements in the equatorial regions. The distributions show that during expected periods of scintillation, the L band signal typically falls 1.1 db below the median for 1.0 percent of the time, and the VHF signal falls 11.5 db below the median for 1.0 percent of the time.

Sessions, W. B.↗

Video-signal improvement using comb filtering techniques.

Significant improvement in the signal-to-noise performance of television signals has been obtained through the application of comb filtering techniques. This improvement is achieved by removing the inherent redundancy in the television signal through linear prediction and by utilizing the unique noise-rejection characteristics of the receiver comb filter. Theoretical and experimental results describe the signal-to-noise ratio and picture-quality improvement obtained through the use of baseband comb filters and the implementation of a comb network as the loop filter in a phase-lock-loop demodulator. Attention is given to the fact that noise becomes correlated when processed by the receiver comb filter.

Arndt, G. D.↗