Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. ...Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157-165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV.DOI:http://dx.doi.org/10.7554/eLife.00049.001.
Fibrosis can develop in most organs and causes organ failure. The most common type of lung fibrosis is known as idiopathic pulmonary fibrosis, in which fibrosis starts at the lung periphery and then ...progresses toward the lung center, eventually causing respiratory failure. Little is known about the mechanisms underlying the pathogenesis and periphery-to-center progression of the disease. Here we discovered that loss of Cdc42 function in alveolar stem cells (AT2 cells) causes periphery-to-center progressive lung fibrosis. We further show that Cdc42-null AT2 cells in both post-pneumonectomy and untreated aged mice cannot regenerate new alveoli, resulting in sustained exposure of AT2 cells to elevated mechanical tension. We demonstrate that elevated mechanical tension activates a TGF-β signaling loop in AT2 cells, which drives the periphery-to-center progression of lung fibrosis. Our study establishes a direct mechanistic link between impaired alveolar regeneration, mechanical tension, and progressive lung fibrosis.
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•Impaired alveolar regeneration results in sustained elevated tension on alveoli•Elevated mechanical tension activates a TGF-β signaling loop in AT2 cells•The impacts of mechanical tension on alveoli are not uniformly distributed•Mechanical tension-activated TGF-β signaling is essential for fibrosis progression
By investigating links between impaired alveolar regeneration and progressive pulmonary fibrosis, Wu et al. found that the periphery-to-center progression of the most common type of lung fibrosis is driven by sustained elevated mechanical tension that activates a TGF-β signaling loop in alveolar stem cells.
Enteroendocrine cells (EEs) in the intestinal epithelium have important endocrine functions, yet this cell lineage exhibits great local and regional variations that have hampered detailed ...characterization of EE subtypes. Through single-cell RNA-sequencing analysis, combined with a collection of peptide hormone and receptor knockin strains, here we provide a comprehensive analysis of cellular diversity, spatial distribution, and transcription factor (TF) code of EEs in adult Drosophila midgut. We identify 10 major EE subtypes that totally produced approximately 14 different classes of hormone peptides. Each EE on average co-produces approximately 2–5 different classes of hormone peptides. Functional screen with subtype-enriched TFs suggests a combinatorial TF code that controls EE cell diversity; class-specific TFs Mirr and Ptx1 respectively define two major classes of EEs, and regional TFs such as Esg, Drm, Exex, and Fer1 further define regional EE identity. Our single-cell data should greatly facilitate Drosophila modeling of EE differentiation and function.
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•Single-cell analysis reveals 10 EE subtypes in Drosophila midgut•Most EEs produce approximately 2–5 peptide hormone classes•The spatial distribution of EE subtypes along the length of midgut is determined•TF code analysis and functional screens identify EE subtype regulators
Through single-cell RNA-sequencing analysis and functional screens, Guo et al. provide a comprehensive characterization of the cellular diversity, spatial distribution, and transcription factor code of enteroendocrine cells in adult Drosophila midgut.
Heterochromatin Protein 1 (HP1) is a conserved chromosomal protein in eukaryotic cells that has a major role in directing heterochromatin formation, a process that requires co-transcriptional gene ...silencing mediated by small RNAs and their associated argonaute proteins. Heterochromatin formation requires erasing the active epigenetic mark, such as H3K4me2, but the molecular link between HP1 and H3K4 demethylation remains unclear. In a fertility screen in female
, we identified
(
), which functions in the stem cell niche, downstream of Piwi, to support germline stem cell differentiation. Moreover,
acts as a suppressor of position effect variegation, and is required for silencing telomeric transposons in the germline. Biochemically, Ova acts to link the H3K4 demethylase dLsd1 to HP1a for local histone modifications. Therefore, our study provides a molecular connection between HP1a and local H3K4 demethylation during HP1a-mediated gene silencing that is required for ovary development, transposon silencing, and heterochromatin formation.
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
•Triple-layer scales occur in both the fine-grained and coarse-grained specimens.•Fine-grained specimens possess the thicker outer layer and the discrete inner layer.•Fine-grained specimens possess ...the shallower Te permeation along grain boundaries.•Fine-grained specimens possess the shallower Cr3Te4 existence along grain boundaries.•Fine-grained specimens provide more paths for the outward diffusion of Cr.
The effects of grain size on the tellurium corrosion behaviors have been investigated systematically in GH3535 alloy. After the exposure to Te vapor, the triple-layer scales, which consist of Ni3Te2, Cr3Te4, MnTe, M6C carbides and Fe-riched γ phase, occur in both the fine-grained and coarse-grained specimens. The thicker outer layer, the more discrete inner layer, the shallower Te permeation and Cr3Te4 existence along grain boundaries can be observed in the fine-grained specimens. By comparing the Gibbs free energies and calculating the effective diffusion coefficients, the tellurization mechanism and the role of grain size were discussed.
A sensitive and selective electrochemical dopamine (DA) sensor has been developed using gold nanoparticles decorated marimo-like graphene (Au NP/MG) as a modifier of the glassy carbon electrode ...(GCE). Marimo-like graphene (MG) was prepared by partial exfoliation on the mesocarbon microbeads (MCMB) through molten KOH intercalation. Characterization via transmission electron microscopy confirmed that the surface of MG is composed of multi-layer graphene nanowalls. The graphene nanowalls structure of MG provided abundant surface area and electroactive sites. Electrochemical properties of Au NP/MG/GCE electrode were investigated by cyclic voltammetry and differential pulse voltammetry techniques. The electrode exhibited high electrochemical activity towards DA oxidation. The oxidation peak current increased linearly in proportion to the DA concentration in a range from 0.02 to 10 μM with a detection limit of 0.016 μM. The detection selectivity was carried out with the presence of 20 μM uric acid in goat serum real samples. This study demonstrated a promising method to fabricate DA sensor-based on MCMB derivatives as electrochemical modifiers.
Signal recognition particle (SRP) is critical for delivering co-translational proteins to the bacterial inner membrane. Previously, we identified SRP suppressors in
Escherichia coli
that inhibit ...translation initiation and elongation, which provided insights into the mechanism of bypassing the requirement of SRP. Suppressor mutations tended to be located in regions that govern protein translation under evolutionary pressure. To test this hypothesis, we re-executed the suppressor screening of SRP. Here, we isolated a novel SRP suppressor mutation located in the Shine–Dalgarno sequence of the S10 operon, which partially offset the targeting defects of SRP-dependent proteins. We found that the suppressor mutation decreased the protein translation rate, which extended the time window of protein targeting. This increased the possibility of the correct localization of inner membrane proteins. Furthermore, the fidelity of translation was decreased in suppressor cells, suggesting that the quality control of translation was inactivated to provide an advantage in tolerating toxicity caused by the loss of SRP. Our results demonstrated that the inefficient protein targeting due to SRP deletion can be rescued through modulating translational speed and accuracy.
Intestinal stem cells (ISCs) are able to generate gut-specific enterocytes, as well as neural-like enteroendocrine cells. It is unclear how the tissue identity of the ISC lineage is regulated to ...confer cell-lineage fidelity. Here, we show that, in adult Drosophila midgut, loss of the transcriptional repressor Tramtrack in ISCs causes a self-renewal program switch to neural stem cell (NSC)-like, and that switch drives neuroendocrine tumor development. In Tramtrack-depleted ISCs, the ectopically expressed Deadpan acts as a major self-renewal factor for cell propagation, and Sequoia acts as a differentiation factor for the neuroendocrine phenotype. In addition, the expression of Sequoia renders NSC-specific self-renewal genes responsive to Notch in ISCs, thus inverting the differentiation-promoting function of Notch into a self-renewal role as in normal NSCs. These results suggest an active maintenance mechanism for the gut identity of ISCs, whose disruption may lead to an improper acquisition of NSC-like traits and tumorigenesis.
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•Depletion of ttk69 in fly ISCs causes a genome-wide program switch to NSC-like•The ectopically expressed NSC factor Dpn drives NET tumorigenesis•The ectopically expressed pan-neural factor Seq generates a neuroendocrine phenotype•Seq also converts the differentiation-promoting role of Notch into a self-renewal role
Li et al. show that the loss of a transcriptional repressor, Tramtrack, in adult Drosophila intestinal stem cells causes a self-renewal program switch to neural-stem-cell-like, which drives neuroendocrine tumor development.
Thermally conductive and electrically insulating polymer composites are ideal for applying in electrical or electronic fields as thermal management materials. Diamond nanomaterials have been used as ...an ideal thermal conductive filler due to their excellent intrinsic thermal conductivity. In this work, utilizing single-crystal nanodiamond (SCND) flakes as the thermally conductive filler, flexible cellulose nanofiber/single-crystal nanodiamond (CNF/SCND) flake composite films with high thermal conductivity were prepared by vacuum-assisted filtration. The strong hydrogen bonding interaction between CNF and SCND and the highly ordered stacking structure of SCND flake layers endowed the composite films with satisfactory flexibility and excellent heat dissipation performance. Compared with pure CNF film, a remarkable thermal conductivity enhancement of approximately 145.6 times and enhanced thermal conductivity (76.23 W m
−1
K
−1
) was achieved in our CNF/SCND composite films. In addition, the enhanced thermal conductivity and excellent mechanical strength, accompanied with excellent flexibility, can be attributed to the CNF/SCND films with low and medium filling content of SCND. This demonstrates that the CNF/SCND composite films are a promising candidate as a heat spreader to rapidly cool LED lamps or electronic devices.
A simple method was proposed to produce a flexible heat spreader with efficient thermal transportation performance.
Autism spectrum disorder (ASD) is a heterogeneous disorder characterized by different levels of repetitive and stereotypic behavior as well as deficits in social interaction and communication. In ...this current study, we explored the changes in cerebral neural activities in ASD. The purpose of this study is to investigate whether there exists a dysfunction of interactive information processing between the prefrontal cortex and posterior brain regions in ASD. We investigated the atypical connectivity and information flow between the prefrontal cortex and posterior brain regions in ASD utilizing the entropy connectivity (a kind of directional connectivity) method. Eighty-nine patients with ASD and 94 typical developing (TD) teenagers participated in this study. Two-sample t-tests revealed weakened interactive entropy connectivity between the prefrontal cortex and posterior brain regions. This result indicates that there exists interactive prefrontal-posterior underconnectivity in ASD, and this disorder might lead to less prior knowledge being used and updated. Our proposals highlighted that aforementioned atypical change might accelerate the deoptimization of brain networks in ASD.
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