Hu Etal Research Articles

From whence it came: Mitochondrial mRNA leaves, a protein returns

Small peptides have previously been reported to be encoded in mitochondrial rRNA and translated by cytosolic ribosomes. In this issue of Cell Metabolism, Hu etal. use mass spectrometry to identify a cytosolically translated protein, encoded instead in mitochondrial mRNA, that is surprisingly targeted back into the mitochondrial matrix.

Equation of state of partially ionized hydrogen and deuterium plasma revisited.

We present improved first-principle fermionic path integral Monte Carlo (PIMC) simulation results for a dense partially ionized hydrogen (deuterium) plasma, for temperatures in the range 15000K≤T≤400000K and densities 7×10^{-7}g/cm^{3}≤ρ_{H}≤0.085g/cm^{3} (1.4×10^{-6}g/cm^{3}≤ρ_{D}≤0.17g/cm^{3}), corresponding to 100≥r_{s}≥2, where r_{s}=r[over ¯]/a_{B} is the ratio of the mean interparticle distance to the Bohr radius. These simulations are based on the fermionic propagator PIMC (FP-PIMC) approach in the grand canonical ensemble [Filinov et al., Contrib. Plasma Phys. 61, e202100112 (2021)0863-104210.1002/ctpp.202100112] and fully account for correlation and quantum degeneracy and spin effects. For the application to hydrogen and deuterium, we develop a combination of the fourth-order factorization and the pair product ansatz for the density matrix. Moreover, we avoid the fixed node approximation that may lead to uncontrolled errors in restricted PIMC (RPIMC). Our results allow us to critically reevaluate the accuracy of the RPIMC simulations for hydrogen by Hu etal. [Phys. Rev. B 84, 224109 (2011)1098-012110.1103/PhysRevB.84.224109] and of various chemical models. The deviations are generally found to be small, but for the lowest temperature, T=15640K they reach several percent. We present detailed tables with our first principles results for the pressure and energy isotherms. We expect our updated results will serve as a valuable benchmark for comparison with other methods.

Into the Unknown: A Chemical Biology Approach Provides Mechanistic Insight into HCV Entry

In this issue of Cell Chemical Biology, Hu etal. (2020) demonstrate that chlorcyclizine blocks HCV fusion by targeting the putative fusion peptide on the viral envelope glycoprotein E1. The study provides new insights into the viral fusion machinery, presenting an opportunity to study novel antivirals against HCV.

AGK Unleashes CD8+ T Cell Glycolysis to Combat Tumor Growth

Elevated glycolytic metabolism is essential for CD8+ Tcell antitumor function, but cell-intrinsic factors modulating this process remain elusive. In this issue, Hu etal. (2019) show that the lipid kinase acylglycerol kinase (AGK) promotes the glycolytic and functional fitness of CD8+ Tcells by inactivating PTEN and boosting mTOR activity, thereby promoting antitumor activity.

The zinc fingers of the small optic lobes calpain bind polyubiquitin.

The small optic lobes (SOL) calpain is a highly conserved member of the calpain family expressed in the nervous system. A dominant negative form of the SOL calpain inhibited consolidation of one form of synaptic plasticity, non-associative facilitation, in sensory-motor neuronal cultures in Aplysia, presumably by inhibiting cleavage of protein kinase Cs (PKCs) into constitutively active protein kinase Ms (PKMs) (Hu etal. 2017a). SOL calpains have a conserved set of 5-6 N-terminal zinc fingers. Bioinformatic analysis suggests that these zinc fingers could bind to ubiquitin. In this study, we show that both the Aplysia and mouse SOL calpain (also known as Calpain 15) zinc fingers bind ubiquitinated proteins, and we confirm that Aplysia SOL binds poly- but not mono- or diubiquitin. No specific zinc finger is required for polyubiquitin binding. Neither polyubiquitin nor calcium was sufficient to induce purified Aplysia SOL calpain to autolyse or to cleave the atypical PKC to PKM invitro. In Aplysia, over-expression of the atypical PKC in sensory neurons leads to an activity-dependent cleavage event and an increase in nuclear ubiquitin staining. Activity-dependent cleavage is partially blocked by a dominant negative SOL calpain, but not by a dominant negative classical calpain. The cleaved PKM was stabilized by the dominant negative classical calpain and destabilized by a dominant negative form of the PKM stabilizing protein KIdney/BRAin protein. These studies provide new insight into SOL calpain's function and regulation. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/.

Crossroads of metabolism and CKD

Sensitive and useful biomarkers for predicting chronic kidney disease (CKD) and its prognosis are urgently needed. Using a nontargeted metabolomic approach, Hu etal. explored an established CKD cohort, Modification of Diet in Renal Disease, as well as a validation cohort, African American Study of Kidney Disease and Hypertension. They identified 3 serum metabolites (ribonate, fumarate, and allantoin) significantly associated with mortality in CKD even after statistical adjustment by multiple clinical covariates including glomerular filtration rate and urinary protein. Their finding develops a new aspect for diagnosing and predicting the prognosis of CKD.

T Cell LEGO: Identifying the Master Builders and What They Do

Understanding how cell fate decisions are made during cellular differentiation and the mechanisms that drive them is a holy grail of cell biology. In this issue of Immunity, Hu etal. (2018) and Johnson etal. (2018) demonstrate that key transcriptional regulators and global changes in nuclear architecture underlie differentiation decisions during Tcell development.

Modulating the Modulator: Regulation of Protein Methylation by Nitric Oxide

Protein methylation is an important modulator of signal transduction pathways, but methyltransferases themselves may also be modulated. Hu etal. (2017) demonstrate in this issue of Molecular Cell that S-nitrosylation selectively modulates enzymatic activity of a protein arginine methyltransferase vital to abiotic stress tolerance.

Epidermal Barrier Protects against Age-Associated Systemic Inflammation

Skin provides barrier protection for the body, but aging disrupts epidermal barrier function. Hu etal. show that disruption of the epidermal barrier increases serum cytokine levels partly because of increased cytokine production by the skin. They then show that restoring epidermal barrier function in aged mice reduces circulating levels of proinflammatory cytokines.

Inside the Chamber of Secrets of the Type III Secretion System

The bacterial type III secretion system is a specialized machine that injects effectors into eukaryotic cells to manipulate the host cell physiology. In this issue of Cell, Hu etal. use cryo-electron tomography to reveal an unprecedented level of details regarding the architecture of this machine and theconformational changes that occur during its assembly.

Regulated Degradation: Controlling the Stability of Autophagy Gene Transcripts

Autophagy is involved in diverse cellular functions through degradation of various intracellular constituents, and hence must be tightly controlled. A recent study by Hu etal. (2015) in Nature Cell Biology adds a new layer of autophagy regulation, involving Tor kinase-driven degradation of mRNAs encoding autophagy-related proteins.

Authors' reply

This is a reply to comments from Hu etal. regarding, of which there are three concerns. The first concern in the comments is a one-to-one mapping relationship between coupling paths in a transversal array network topology and coupling elements in a physical filter structure. In conclusion, it is not necessary to determine the order of parallel paths corresponding to physical structures, as shown. This is because resonators in parallel paths of a transversal array network topology represent eigenmode resonances appearing in coupled resonators. This physical understanding has already been presented in using an example of a direct-coupled waveguide filter. The viewpoint of the order in parallel paths may come from a conventional design method of direct-coupled resonator filters, where the one-to-one mapping relationships can be easily found because the filters are composed of physically separated resonators. On the other hand, multiple resonances of a multi-mode resonator cannot be divided into physical coupling elements. In such cases, the transversal array network topology is a powerful tool for multi-mode filter designs. Therefore, three multi-mode filters have been demonstrated as examples of applications of our proposed parameter-extraction technique. The second concern in the comments of Hu et al. is the treatment of stray couplings in the transversal array coupling network. The stray couplings such as undesired cross couplings need to be evaluated in conventional filter designs based on direct-coupled resonator filter synthesis theory in order to obtain a desired frequency response. In the transversal resonator array network, as pointed out in, such stray couplings are included into parallel paths of resonators. We think that this is one of the advantages of the transversal resonator array network since coupled-resonator filters may be designed without any decomposition of main and stray couplings. In the initial design step of a filter, a well-known design approach of coupled-resonator filters is useful for intuitive designs, but stray couplings are not taken into account in this design step. In the final design step, the introduction of a transversal coupling network may help the fine adjustments of structural parameters, because all couplings are considered in terms of eigenmodes. To verify this idea, further studies will be needed. A similar design methodology has already been provided. The third concern in the comments of Hu etal. is a reference-phase equation.

The taxonomic status ofMoschus moschiferus anhuiensis

Since the musk deer distributed in the Dabie Mountains, Anhui was defined asMoschus moschiferus anhuiensis, its status has been disputed based on researches of morphology and ecology. This study further probed into its taxonomic status with principal components analysis (PCA) on skull measurements and mtDNA cytochrome b sequences (367 bp) analysis so as to clear its status. It is concluded that the figure and skull in Anhui musk deer are different from other species, and DNA divergence between it and other species is 6.24%–7.90%, which belongs to inter-specific difference. Thus, the study defines this musk deer as one distinct species,Moschus anhuiensis (Wang, Huet al.)