A method for forming efficient, ultrathin GaN light‐emitting diodes (LEDs) and for their assembly onto foreign substances is reported. The LEDs have lateral dimensions ranging from ∼1 mm × 1 mm to ...∼25 μm × 25 μm. Quantitative experimental and theoretical studies show the benefits of small device geometry on thermal management, for both continuous and pulsed‐mode operation, the latter of which suggests the potential use of these technologies in bio‐integrated contexts.
Listeria monocytogenes, a foodborne pathogen that causes listeriosis with high fatality rate, exhibits multidrug resistance (MDR) known to be progressively increasing. Alternative antibacterial ...strategies are in high demand for treating this well-known pathogen. Anti-biofilm and anti-virulence strategies are being explored as novel approaches to treat bacterial infections. In this study, one rare antibacterial named setomimycin was isolated from Streptomyces cyaneochromogenes, which showed potent antibacterial activity against L. monocytogenes. Next, the inhibition of biofilm formation and listeriolysin O (LLO) production against L. monocytogenes were investigated at sub-minimal inhibitory concentrations (sub-MICs) of setomimycin alone or combined with kanamycin and amikacin. Crystal violet staining confirmed that setomimycin combining with kanamycin or amikacin could dramatically reduce biofilm formation against L. monocytogenes at sub-MICs, which was further evaluated by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In the meantime, sub-MICs of setomimycin could significantly suppress the secretion of LLO. Furthermore, the transcription of genes associated with biofilms and main virulence factors, such as LLO, flagellum, and metalloprotease, were suppressed by setomimycin at sub-MICs. Hence, the study provided a deep insight into setomimycin as an alternative antibacterial agent against L. monocytogenes.
•HV backscatter coefficients of PALSAR-2 model mangrove AGB at high accuracy.•The model performance using k-fold CV was found at R2 of 0.89.•The model performance using LLO CV stood at R2 of ...0.88.•High LLO CV model performance overrules spatial overfitting.•Mangrove AGB saturation was found at a relatively high level at around 217 tons ha−1.
Accurate estimation of forest aboveground biomass (AGB) using remote sensing is a requisite for monitoring, reporting and verification (MRV) system of the United Nations Programme on Reducing Emissions from Deforestation and Forest Degradation. However, attaining high accuracy remains a great challenge in the diverse tropical forests. Among available technologies, l-band Synthetic Aperture Radar (SAR) estimates AGB with reasonably high accuracy in the terrestrial tropical forests. Nevertheless, the accuracy is relatively low in the mangrove forests. In this context, the study was carried out to model and map AGB using backscatter coefficients of Advanced Land Observing Satellite-2 (ALOS-2) Phased Array l-band SAR-2 (PALSAR-2) in part of the restored mangrove forest at Mahakam Delta, Indonesia. PALSAR-2 data was acquired with image scene observation during the peak low tide on 30 July 2018 from Japan Aerospace Exploration Agency. The forest parameters namely tree height and diameter at breast height were measured from 71 field plots in September-October 2018. The parameters were used in mangrove allometry to calculate the field AGB. Finally, HV polarized backscatter coefficients of PALSAR-2 were used to model AGB using linear regression. The model demonstrated a comparatively high performance using three distinct methods viz. independent validation (R2 of 0.89 and RMSE of 23.16 tons ha−1), random k-fold cross validation (R2 of 0.89 and RMSE of 24.59 tons ha−1) and leave location out cross validation (LLO CV) (R2 of 0.88 and RMSE of 24.05 tons ha−1). The high accuracy of the LLO CV indicates no spatial overfitting in the model. Thus, the model based on LLO CV was used to map AGB in the study area. This is the first study that successfully obtains high accuracy in modeling AGB in the mangrove forest. Therefore, it offers a significant contribution to the MRV mechanism for monitoring mangrove forests in the tropics and sub-tropics.
Wearable electronic devices with next‐generation biocompatible, mechanical, ultraflexible, and portable sensors are a fast‐growing technology. Hardware systems enabling artificial neural networks ...while consuming low power and processing massive in situ personal data are essential for adaptive wearable neuromorphic edging computing. Herein, the development of an ultraflexible artificial‐synaptic array device with concrete‐mechanical cyclic endurance consisting of a novel heterostructure with an all‐solid‐state 2D MoS2 channel and LiSiOx (lithium silicate) is demonstrated. Enabled by the sequential fabrication process of all layers, by excluding the transfer process, artificial van der Waals devices combined with the 2D‐MoS2 channel and LiSiOx solid electrolyte exhibit excellent neuromorphic synaptic characteristics with a nonlinearity of 0.55 and asymmetry ratio of 0.22. Based on the excellent flexibility of colorless polyimide substrates and thin‐layered structures, the fabricated flexible neuromorphic synaptic devices exhibit superior long‐term potentiation and long‐term depression cyclic endurance performance, even when bent over 700 times or on curved surfaces with a diameter of 10 mm. Thus, a high classification accuracy of 95% is achieved without any noticeable performance degradation in the Modified National Institute of Standards and Technology. These results are promising for the development of personalized wearable artificial neural systems in the future.
The crossview scheme of the flexible artificial synapse array provides a comprehensive view of the device's architecture. Photograph and crossview scheme of flexible artificial synapse array device present a detailed visual representation. The long‐term potentiation and long‐term depression characteristic curves show according to the pulse numbers. The normalized conductance plot of bended device with strain (Ɛ) of 0%, 0.08%, 0.13%, and 0.25% shows how the device's conductance changes in response to bending. The recognition accuracy of the network for bending radius is a measurement of how accurately the device can identify different bending radious.
Pathogenic bacteria rely on secreted virulence factors to cause disease in susceptible hosts. However, in Gram-positive bacteria, the mechanisms underlying secreted protein activation and regulation ...post-membrane translocation remain largely unknown. Using proteomics, we identified several proteins that are dependent on the secreted chaperone PrsA2. We followed with phenotypic, biochemical, and biophysical assays and computational analyses to examine the regulation of a detected key secreted virulence factor, listeriolysin O (LLO), and its interaction with PrsA2 from the bacterial pathogen
(
). Critical to
virulence is internalization by host cells and the subsequent action of the cholesterol-dependent pore-forming toxin, LLO, which enables bacterial escape from the host cell phagosome. Since
is a Gram-positive organism, the space between the cell membrane and wall is solvent exposed. Therefore, we hypothesized that the drop from neutral to acidic pH as the pathogen is internalized into a phagosome is critical to regulating the interaction of PrsA2 with LLO. Here, we demonstrate that PrsA2 directly interacts with LLO in a pH-dependent manner. We show that PrsA2 protects and sequesters LLO under neutral pH conditions where LLO can be observed to aggregate. In addition, we identify molecular features of PrsA2 that are required for interaction and ultimately the folding and activity of LLO. Moreover, protein-complex modeling suggests that PrsA2 interacts with LLO via its cholesterol-binding domain. These findings highlight a mechanism by which a Gram-positive secretion chaperone regulates the secretion, stability, and folding of a pore-forming toxin under conditions relevant to host cell infection.
is a ubiquitous food-borne pathogen that can cause severe disease to vulnerable populations. During infection,
relies on a wide repertoire of secreted virulence factors including the LLO that enables the bacterium to invade the host and spread from cell to cell. After membrane translocation, secreted factors must become active in the challenging bacterial cell membrane-wall interface. However, the mechanisms required for secreted protein folding and function are largely unknown.
encodes a chaperone, PrsA2, that is critical for the activity of secreted factors. Here, we show that PrsA2 directly associates and protects the major
virulence factor, LLO, under conditions corresponding to the host cytosol, where LLO undergoes irreversible denaturation. Additionally, we identify molecular features of PrsA2 that enable its interaction with LLO. Together, our results suggest that
and perhaps other Gram-positive bacteria utilize secreted chaperones to regulate the activity of pore-forming toxins during infection.
Background and Purpose
L. monocytogenes remain a leading cause of foodborne infection. Listeriolysin O (LLO), an indispensable virulence determinant involved in diverse pathogenic mechanisms of L. ...monocytogenes infection, represents a promising therapeutic target. In this study, we sought to identify an effective inhibitor of LLO pore formation and its mechanism of action in the treatment of L. monocytogenes infection.
Experimental Approach
Haemolysis assays were carried out to screen an effective LLO inhibitor. The interaction between candidate and LLO was investigated using surface plasmon resonance and molecular docking. The effect of candidate on LLO‐mediated cytotoxicity, barrier disruption and immune response were investigated. Finally, the in vivo effect of candidate on mice challenged with L. monocytogenes was examined.
Key results
Amentoflavone, a natural flavone present in traditional Chinese herbs, effectively inhibited LLO pore formation by engaging the residues Lys93, Asp416, Tyr469 and Lys505 in LLO. Amentoflavone dose‐dependently reduced L. monocytogenes‐induced cell injury in an LLO‐dependent manner. In the Caco‐2 monolayer model, amentoflavone maintained the integrity of the epithelial barrier exposed to LLO. Amentoflavone inhibited the inflammatory response evoked by L. monocytogenes in an LLO‐dependent manner, and inhibition was attributed to ability to block perforation‐associated K+ efflux and Ca2+ influx. In the mouse infection model, amentoflavone treatment significantly reduced bacterial burden and pathological lesions in target organs, with a significant increase in survival rate.
Conclusions and Implications
Amentoflavone reduced the pathogenicity of L. monocytogenes by specifically inhibiting LLO pore formation, and this may represent a potential treatment for L. monocytogenes infection.
The gastrointestinal tract is coated by a thick layer of mucus that forms the front line of innate host defense. Mucus consists of high molecular weight glycoproteins called mucins that are ...synthesized and secreted by goblet cells and functions primarily to lubricate the epithelium and protect it from damage by noxious substances. Recent studies have also suggested the involvement of goblet cells and mucins in complex immune functions such as antigen presentation and tolerance. Under normal physiological conditions, goblet cells continually produce mucins to replenish and maintain the mucus barrier; however, goblet cell function can be disrupted by various factors that can affect the integrity of the mucus barrier. Some of these factors such as microbes, microbial toxins and cytokines can stimulate or inhibit mucin production and secretion, alter the chemical composition of mucins or degrade the mucus layer. This can lead to a compromised mucus barrier and subsequently to various pathological conditions like chronic inflammatory diseases. Insight into how these factors modulate the mucus barrier in the gut is necessary in order to develop strategies to combat these disorders.
Listeria monocytogenes (Lm), a foodborne bacterium, can infect people and has a high fatality rate in immunocompromised individuals. Listeriolysin O (LLO), the primary virulence factor of Lm, is ...critical in regulating the pathogenicity of Lm. This review concludes that LLO may either directly or indirectly activate a number of host cell viral pathophysiology processes, such as apoptosis, pyroptosis, autophagy, necrosis and necroptosis. We describe the invasion of host cells by Lm and the subsequent removal of Lm by CD8 T cells and CD4 T cells upon receipt of the LLO epitopes from major histocompatibility complex class I (MHC-I) and major histocompatibility complex class II (MHC-II). The development of several LLO-based vaccines that make use of the pore-forming capabilities of LLO and the immune response of the host cells is then described. Finally, we conclude by outlining the several natural substances that have been shown to alter the three-dimensional conformation of LLO by binding to particular amino acid residues of LLO, which reduces LLO pathogenicity and may be a possible pharmacological treatment for Lm.
Oral D-galactose supplementation in PGM1-CDG Wong, Sunnie Yan-Wai; Gadomski, Therese; van Scherpenzeel, Monique ...
Genetics in medicine,
11/2017, Letnik:
19, Številka:
11
Journal Article
Recenzirano
Odprti dostop
PurposePhosphoglucomutase-1 deficiency is a subtype of congenital disorders of glycosylation (PGM1-CDG). Previous casereports in PGM1-CDG patients receiving oral D-galactose (D-gal) showed clinical ...improvement. So far no systematic in vitro and clinical studies have assessed safety and benefits of D-gal supplementation. In a prospective pilot study, we evaluated the effects of oral D-gal in nine patients.MethodsD-gal supplementation was increased to 1.5 g/kg/day (maximum 50 g/day) in three increments over 18 weeks. Laboratory studies were performed before and during treatment to monitor safety and effect on serum transferrin-glycosylation, coagulation, and liver and endocrine function. Additionally, the effect of D-gal on cellular glycosylation was characterized in vitro.ResultsEight patients were compliant with D-gal supplementation. No adverse effects were reported. Abnormal baseline results (alanine transaminase, aspartate transaminase, activated partial thromboplastin time) improved or normalized already using 1 g/kg/day D-gal. Antithrombin-III levels and transferrin-glycosylation showed significant improvement, and increase in galactosylation and whole glycan content. In vitro studies before treatment showed N-glycan hyposialylation, altered O-linked glycans, abnormal lipid-linked oligosaccharide profile, and abnormal nucleotide sugars in patient fibroblasts. Most cellular abnormalities improved or normalized following D-gal treatment. D-gal increased both UDP-Glc and UDP-Gal levels and improved lipid-linked oligosaccharide fractions in concert with improved glycosylation in PGM1-CDG.ConclusionOral D-gal supplementation is a safe and effective treatment for PGM1-CDG in this pilot study. Transferrin glycosylation and ATIII levels were useful trial end points. Larger, longer-duration trials are ongoing.
A Li-rich layered oxide (LLO) cathode with morphology-dependent electrochemical performance with the composition Li1.23Mn0.538Ni0.117Co0.114O2 in three different microstructural forms, namely, ...randomly shaped particles, platelets, and nanofibers, is synthesized through the solid-state reaction (SSR-LLO), hydrothermal method (HT-LLO), and electrospinning process (ES-LLO), respectively. Even though the cathodes possess different morphologies, structurally they are identical. The elemental dispersion studies using energy-dispersive X-ray spectroscopy mapping in scanning transmission electron microscopy show uniform distribution of elements. However, SSR-LLO and ES-LLO nanofibers show slight Co-rich regions. The electrochemical studies of LLO cathodes are evaluated in terms of charging/discharging, C-rate capability, and cyclic stability performances. A high reversible capacity of 275 mA h g–1 is achieved in the fibrous LLO cathode which also demonstrates good high-rate capability (80 mA h g–1 at 10 C-rate). These capacities and rate capabilities are superior to those of SSR-LLO 210.5 mA h g–1 (0.1 C-rate) and 4 mA h g–1 (3 C-rate) and HT-LLO 242 mA h g–1 (0.1 C-rate) and 22 mA h g–1 (10 C-rate) cathodes. The ES-LLO cathode exhibits 88% capacity retention after 100 cycles at 1 C-rate. A decrease in voltage on cycling is found to be common in all three cathodes; however, minimal voltage decay and capacity loss are observed in ES-LLO upon cycling. Well-connected small LLO particles constituting fibrous microstructural forms in ES-LLO provide an enhanced electrolyte/cathode interfacial area and reduced diffusion path length for Li+. This, in turn, facilitates superior electrochemical performance of the electrospun Co-low LLO cathode suitable for quick charge battery applications.
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