Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune ...

Biochemistry and Molecular Biology of Flaviviruses

The respiratory system undergoes a diversity of structural, biochemical, and functional changes necessary for adaptation to air breathing at birth. To identify the heterogeneity of pulmonary cell types and dynamic changes in gene expression mediating adaptation to respiration, here we perform single cell RNA analyses of mouse lung on postnatal day 1. Using an iterative cell type identification strategy we unbiasedly identify the heterogeneity of murine pulmonary cell types. We identify distinct populations of epithelial, endothelial, mesenchymal, and immune cells, each containing distinct subpopulations. Furthermore we compare temporal changes in RNA expression patterns before and after birth to identify signaling pathways selectively activated in specific pulmonary cell types, including activation of cell stress and the unfolded protein response during perinatal adaptation of the lung. The present data provide a single cell view of the adaptation to air breathing after birth.

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Single Cell RNA Analysis Identifies Cellular Heterogeneity and Adaptive Responses of the Lung at Birth

The endoplasmic reticulum (ER) supports biosynthesis of proteins with diverse transmembrane domain (TMD) lengths and hydrophobicity. Features in transmembrane domains such as charged residues in ion channels are often functionally important, but could pose a challenge during cotranslational membrane insertion and folding. Our systematic proteomic approaches in both yeast and human cells revealed that the ER membrane protein complex (EMC) binds to and promotes the biogenesis of a range of multipass transmembrane proteins, with a particular enrichment for transporters. Proximity-specific ribosome profiling demonstrates that the EMC engages clients cotranslationally and immediately following clusters of TMDs enriched for charged residues. The EMC can remain associated after completion of translation, which both protects clients from premature degradation and allows recruitment of substrate-specific and general chaperones. Thus, the EMC broadly enables the biogenesis of multipass transmembrane proteins containing destabilizing features, thereby mitigating the trade-off between function and stability.

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The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins.

Epithelial cell dysfunction has emerged as a central component of the pathophysiology of diffuse parenchymal diseases including idiopathic pulmonary fibrosis (IPF). Alveolar type 2 (AT2) cells represent a metabolically active lung cell population important for surfactant biosynthesis and alveolar homeostasis. AT2 cells and other distal lung epithelia, like all eukaryotic cells, contain an elegant quality control network to respond to intrinsic metabolic and biosynthetic challenges imparted by mutant protein conformers, dysfunctional subcellular organelles, and dysregulated telomeres. Failed AT2 quality control components (the ubiquitin-proteasome system, unfolded protein response, macroautophagy, mitophagy, and telomere maintenance) result in diverse cellular endophenotypes and molecular signatures including ER stress, defective autophagy, mitochondrial dysfunction, apoptosis, inflammatory cell recruitment, profibrotic signaling, and altered progenitor function that ultimately converge to drive downstream fibrotic remodeling in the IPF lung. As this complex network becomes increasingly better understood, opportunities will emerge to identify targets and therapeutic strategies for IPF.

/pdf/contributions-of-alveolar-epithelial-cell-quality-control-to-55zmg7abrf.pdf

Contributions of alveolar epithelial cell quality control to pulmonary fibrosis

The eukaryotic endoplasmic reticulum (ER) membrane contains essential complexes that oversee protein biogenesis and lipid metabolism, impacting nearly all aspects of cell physiology. The ER membrane protein complex (EMC) is a newly described transmembrane domain (TMD) insertase linked with various phenotypes, but whose clients and cellular responsibilities remain incompletely understood. We report that EMC deficiency limits the cellular boundaries defining cholesterol tolerance, reflected by diminished viability with limiting or excessive extracellular cholesterol. Lipidomic and proteomic analyses revealed defective biogenesis and concomitant loss of the TMD-containing ER-resident enzymes sterol-O-acyltransferase 1 (SOAT1) and squalene synthase (SQS, also known as FDFT1), which serve strategic roles in the adaptation of cells to changes in cholesterol availability. Insertion of the weakly hydrophobic tail-anchor (TA) of SQS into the ER membrane by the EMC ensures sufficient flux through the sterol biosynthetic pathway while biogenesis of polytopic SOAT1 promoted by the EMC provides cells with the ability to store free cholesterol as inert cholesteryl esters. By facilitating insertion of TMDs that permit essential mammalian sterol-regulating enzymes to mature accurately, the EMC is an important biogenic determinant of cellular robustness to fluctuations in cholesterol availability.This article has an associated First Person interview with the first author of the paper.

The ER membrane protein complex promotes biogenesis of sterol-related enzymes maintaining cholesterol homeostasis.

Recent advances in radio-frequency negative dielectric metamaterials by designing heterogeneous composites

Adaptation to respiration at birth depends upon the synthesis of pulmonary surfactant, a lipid-protein complex that reduces surface tension at the air-liquid interface in the alveoli and prevents lung collapse during the ventilatory cycle. Herein, we demonstrated that the gene encoding a subunit of the endoplasmic reticulum membrane complex, EMC3, also known as TMEM111 (Emc3/Tmem111), was required for murine pulmonary surfactant synthesis and lung function at birth. Conditional deletion of Emc3 in murine embryonic lung epithelial cells disrupted the synthesis and packaging of surfactant lipids and proteins, impaired the formation of lamellar bodies, and induced the unfolded protein response in alveolar type 2 (AT2) cells. EMC3 was essential for the processing and routing of surfactant proteins, SP-B and SP-C, and the biogenesis of the phospholipid transport protein ABCA3. Transcriptomic, lipidomic, and proteomic analyses demonstrated that EMC3 coordinates the assembly of lipids and proteins in AT2 cells that is necessary for surfactant synthesis and function at birth.

/pdf/emc3-coordinates-surfactant-protein-and-lipid-homeostasis-4svagasjy0.pdf

EMC3 coordinates surfactant protein and lipid homeostasis required for respiration

Znhit1 controls meiotic initiation in male germ cells by coordinating with Stra8 to activate meiotic gene expression.

Tailing direct Z-scheme photocatalyst is a prominent avenue to combat the challenges of environmental pollution and energy crisis. Herein, a direct Z-scheme composite of g-C3N4/TiO2 (CN/T) decorated with CdS (CdS/CN/T) is fabricated by a hydrothermal method. Compared with the binary and pristine photocatalysts, the CdS/CN/T ternary presents enhanced photocatalystic activity for the pollutants removal and H2 evolution under visible/solar light irradiation. 100% reduction of Cr(VI) within 20 min under solar light irradiation and 290 μmol h−1 g−1 evolution rate of H2 are achieved over the CdS/CN/T photocatalyst. The boosted photocatalytic activity is mainly ascribed to the synergistic interaction among CdS, g-C3N4, and TiO2, which endows them with larger specific surface area, higher light absorption capacity, and direct Z-scheme interface. Moreover, the as-developed photocatalyst is highly stable. This work offers a strategy of constructing g-C3N4-based direct Z-scheme photocatalysts for improving visible light photocatalytic performance.

Enhanced visible light absorption CdS-decorated direct Z-scheme g-C3N4/TiO2 for improved photocatalysis and hydrogen generation

Tailing direct Z-scheme photocatalyst is a prominent avenue to combat the challenges of environmental pollution and energy crisis. Herein, a direct Z-scheme composite of g-C_3N_4/TiO_2 (CN/T) decorated with CdS (CdS/CN/T) is fabricated by a hydrothermal method. Compared with the binary and pristine photocatalysts, the CdS/CN/T ternary presents enhanced photocatalystic activity for the pollutants removal and H_2 evolution under visible/solar light irradiation. 100% reduction of Cr(VI) within 20 min under solar light irradiation and 290 μmol h^−1 g^−1 evolution rate of H_2 are achieved over the CdS/CN/T photocatalyst. The boosted photocatalytic activity is mainly ascribed to the synergistic interaction among CdS, g-C_3N_4, and TiO_2, which endows them with larger specific surface area_, higher light absorption capacity, and direct Z-scheme interface. Moreover, the as-developed photocatalyst is highly stable. This work offers a strategy of constructing g-C_3N_4-based direct Z-scheme photocatalysts for improving visible light photocatalytic performance. Graphical abstract

Meina Huang

Papers

Recent advances in radio-frequency negative dielectric metamaterials by designing heterogeneous composites

EMC3 coordinates surfactant protein and lipid homeostasis required for respiration

Znhit1 controls meiotic initiation in male germ cells by coordinating with Stra8 to activate meiotic gene expression.

Enhanced visible light absorption CdS-decorated direct Z-scheme g-C3N4/TiO2 for improved photocatalysis and hydrogen generation

Enhanced visible light absorption CdS-decorated direct Z-scheme g-C_3N_4/TiO_2 for improved photocatalysis and hydrogen generation