Control of mammalian G protein signaling by N-terminal acetylation and the N-end rule pathway

Rgs2, a regulator of G proteins, lowers blood pressure by decreasing signaling through Gαq. Human patients expressing Met-Leu-Rgs2 (ML-Rgs2) or Met-Arg-Rgs2 (MR-Rgs2) are hypertensive relative to people expressing wild-type Met-Gln-Rgs2 (MQ-Rgs2). We found that wild-type MQ-Rgs2 and its mutant, MR-Rgs2, were destroyed by the Ac/N-end rule pathway, which recognizes Nα-terminally acetylated (Nt-acetylated) proteins. The shortest-lived mutant, ML-Rgs2, was targeted by both the Ac/N-end rule and Arg/N-end rule pathways. The latter pathway recognizes unacetylated N-terminal residues. Thus, the Nt-acetylated Ac-MX-Rgs2 (X = Arg, Gln, Leu) proteins are specific substrates of the mammalian Ac/N-end rule pathway. Furthermore, the Ac/N-degron of Ac-MQ-Rgs2 was conditional, and Teb4, an endoplasmic reticulum (ER) membrane-embedded ubiquitin ligase, was able to regulate G protein signaling by targeting Ac-MX-Rgs2 proteins for degradation through their N^α-terminal acetyl group

mHealth hyperspectral learning for instantaneous spatiospectral imaging of hemodynamics

Hyperspectral imaging acquires data in both the spatial and frequency domains to offer abundant physical or biological information. However, conventional hyperspectral imaging has intrinsic limitations of bulky instruments, slow data acquisition rate, and spatiospectral tradeoff. Here we introduce hyperspectral learning for snapshot hyperspectral imaging in which sampled hyperspectral data in a small subarea are incorporated into a learning algorithm to recover the hypercube. Hyperspectral learning exploits the idea that a photograph is more than merely a picture and contains detailed spectral information. A small sampling of hyperspectral data enables spectrally informed learning to recover a hypercube from an RGB image. Hyperspectral learning is capable of recovering full spectroscopic resolution in the hypercube, comparable to high spectral resolutions of scientific spectrometers. Hyperspectral learning also enables ultrafast dynamic imaging, leveraging ultraslow video recording in an off-the-shelf smartphone, given that a video comprises a time series of multiple RGB images. To demonstrate its versatility, an experimental model of vascular development is used to extract hemodynamic parameters via statistical and deep-learning approaches. Subsequently, the hemodynamics of peripheral microcirculation is assessed at an ultrafast temporal resolution up to a millisecond, using a conventional smartphone camera. This spectrally informed learning method is analogous to compressed sensing; however, it further allows for reliable hypercube recovery and key feature extractions with a transparent learning algorithm. This learning-powered snapshot hyperspectral imaging method yields high spectral and temporal resolutions and eliminates the spatiospectral tradeoff, offering simple hardware requirements and potential applications of various machine-learning techniques.Comment: This paper will appear in PNAS Nexu

Delineating transcriptional crosstalk between Mycobacterium avium subsp. paratuberculosis and human THP-1 cells at the early stage of infection via dual RNA-seq analysis

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, a chronic debilitating disease in ruminants. To control this disease, it is crucial to understand immune evasion and the mechanism of persistence by analyzing the early phase interplays of the intracellular pathogens and their hosts. In the present study, host-pathogen interactions at the transcriptomic level were investigated in an in vitro macrophage infection model. When differentiated human THP-1 cells were infected with MAP, the expression of various genes associated with stress responses and metabolism was altered in both host and MAP at 3 h post-infection. MAP upregulates stress-responsive global gene regulators, such as two-component systems and sigma factors, in response to oxidative and cell wall stress. Downstream genes involved in type VII secretion systems, cell wall synthesis (polyketide biosynthesis proteins), and iron uptake were changed in response to the intracellular environment of macrophages. On the host side, upregulation of inflammatory cytokine genes was observed along with pattern recognition receptor genes. Notably, alterations in gene sets involved in arginine metabolism were observed in both the host and MAP, along with significant downregulation of NOS2 expression. These observations suggest that the utilization of metabolites such as arginine by intracellular MAP might affect host NO production. Our dual RNA-seq data can provide novel insights by capturing the global transcriptome with higher resolution, especially in MAP, thus enabling a more systematic understanding of host-pathogen interactions

Dwarf Galaxy Discoveries from the KMTNet Supernova Program III. the Milky-Way Analog NGC~2997 Group

We present the discovery of 48 new and the analysis of 55, including 7 previously discovered, dwarf galaxy candidates around the giant spiral galaxy NGC~2997 using deep $BVI$ images from the KMTNet Supernova Program. Their $V$-band central surface brightness and total absolute magnitudes range between 20.3--26.7 mag arcsec$^{-2}$ and --(8.02--17.69) mag, respectively, while the $I$-band effective radii are between 0.14 and 2.97 kpc. We obtain $\alpha$ $\simeq$ --1.43 $\pm$ 0.02 for the faint-end slope of their luminosity function, comparable to previously measured values but shallower than theoretical predictions based on $\Lambda$CDM models. The distance-independent distributions of their mass and color from the host galaxy NGC~2997 suggest that the group could be dynamically young, prior to the development of significant mass segregation or radial color gradients. The systematically bluer colors of the brighter candidates than the fainter ones indicate higher star formation activities in brighter members. We suggest that the higher-mass dwarf galaxies in the group have maintained star-formation activities by effectively retaining gas content, while environmental quenching is only effective for the lower-mass galaxies. The interpretation of early evolutionary stage of this group is also consistent with the overall morphological distribution of the dwarf galaxy candidates showing a lack of morphologically evolved candidates but a plethora of irregularly shaped ones. Our detection rate of dwarf galaxy candidates in the NGC~2997 group and their inferred star formation activities are largely comparable to those found in Milky Way analog systems from the SAGA survey within the magnitude limit M$_{V}$ $\lesssim$ --13 mag, as well as those found in the ELVES survey