Enterohemorrhagic Escherichia coli (EHEC) induces changes to the intestinal cell cytoskeleton and formation of attaching and effacing lesions, characterized by the effacement of microvilli and then ...formation of actin pedestals to which the bacteria are tightly attached. Here, we use a Caenorhabditis elegans model of EHEC infection to show that microvillar effacement is mediated by a signalling pathway including mitotic cyclin-dependent kinase 1 (CDK1) and diaphanous-related formin 1 (CYK1). Similar observations are also made using EHEC-infected human intestinal cells in vitro. Our results support the use of C. elegans as a host model for studying attaching and effacing lesions in vivo, and reveal that the CDK1-formin signal axis is necessary for EHEC-induced microvillar effacement.
PurposeThe purpose of this study is to find evidence of the impact of intellectual capital on firm value, and, in turn, enhance the existing literature which lacks consensus on it. By employing some ...distinctive proxies for human capital, innovation capital, customer capital and process capital, this study might provide valuable information for firms to make strategic decisions.Design/methodology/approachThis study uses Tobin's Q to represent firm value and various variables to be the proxies for intellectual capitals. By utilizing firm-year observations, this study applies panel data models first, and then Petersen regression models for further investigation to enhance the robustness of the empirical results.FindingsFirm value is affected positively by the average net profit per employee as well as goodwill and intangible assets. This is because firms having employees with abundant knowledge will possess advantage for innovation, and the excellent reputation, a part of goodwill for oriental firms, would encourage people to consume and invest more.Research limitations/implicationsThe constraint of data resource is the main limitation. With the limited scales and as an emerging market of Taiwan Stock Exchange, it is not confirmed whether the results are appropriate for the developed markets. Nevertheless, firms should make efforts on developing intellectual capital and corporate governance for operating businesses with competitiveness and safety.Originality/valueSince capable employees enhance the innovation, innovation improves customer's satisfaction and good customer relationship increases the sales; this study illustrates that for expanding businesses, firms should make more efforts on developing intellectual capital.
Nowadays, with rapid development of technology and hardware, mobile devices have become an important part of people’s daily life. Although LTE (Long Term Evolution) had been developed stably and can ...support large scale communication services to mobile devices, the traffic offloading in core network and mobile devices is still an issue. Besides, the intensive collision between mobile devices is also an issue because they need to compete the finite network resources with each other. Mobile Edge Computing (MEC) is a promising technique applied to network edge, which can assist the edge device to offload the data traffic and decrease the gigantic computation effort through sending the complicated tasks to remote MEC before sending to core network. To solve the traffic and location issues, this paper proposed a channel selection scheme for MEC-assisted Device to Device communication Offloading (MD2DO) which can help the peered mobile devices to confirm the location of the mobile device and efficiently have Wi-Fi D2D through channel selection for traffic offloading. The simulation results proved that the MD2DO method decreases the collisions between the mobile devices through the efficiently channel selection and enhances the network performance.
Improper use of antibiotics has led to the global rise of drug-resistant biofilm bacteria. Thus, researchers have been increasingly interested in green materials that are highly biocompatible and ...have low toxicity. Here, nanogels (NGs) with imine bonds were synthesized by crosslinking kiwifruit-derived DNA's primary amine and aromatic aldehydes (cuminaldehyde, p-anisaldehyde, or vanillin) under water-in-hexane emulsion processes. Transmission electron microscope showed that the NGs had spherical geometry with an average particle size ranging from 40 to 140 nm and that the zeta potential indicated a negative charge. Additionally, the DNA-aromatic aldehyde NGs showed low cytotoxicity toward normal cell organoids and human RBCs in cell viability tests. These NGs were also tested against four pathogenic bacteria for various assays. DNA-vanillin (DNA-VA) NGs exhibited significant antibacterial effects against bacteria with very low inhibitory concentrations as seen in a minimum inhibitory concentration assay. Scanning electron microscope observation revealed that the bacteria were deformed, and immunoblotting detected intracellular groEL protein expression. In agreement with these results, DNA-aromatic aldehyde NGs successfully protected C. elegans from P. aeruginosa-induced lethality. These DNA NGs provided a multivalent 3D space for antibacterial aromatic aldehydes to tether, enhancing their interaction with the bacterial wall. These results offer a new direction for the development of novel antibiotics in the future.
Abstract
IEEE 802.11ah is a new protocol designed for Internet of Things (IoT). IEEE 802.11ah uses a hierarchical ID assignment schema and designs the corresponding channel access method such that ...stations can access channel alternatively through the four-level’s hierarchical channel access structure. Nevertheless, collisions still cannot be effectively avoided in a dense IOT networking environment using the legacy IEEE 802.11ah. The work proposed the registration-based situation-aware access extension (RSAE) control scheme to avoid collisions, decrease backoff’s waiting time and improve slot utilization through the following two ways: (i) in contrast to the traditional CSMA/CA protocol that generates the backoff time for the next channel access after the collision happened, registering the backoff time to AP for scheduling the next channel access before the collision happens; (ii) extending the channel accessing’s privilege of those stations that did not complete the data transmission/receiving in the current slot to the available time of the next slot. Comparing with the legacy IEEE 802.11ah, the performance evaluation of the proposed RSAE scheme shown that it still can have a better throughput and a lower collision rate when there is a bigger number of stations in a slot.
Autophagy is an evolutionarily conserved intracellular system that maintains cellular homeostasis by degrading and recycling damaged cellular components. The transcription factor HLH-30/TFEB-mediated ...autophagy has been reported to regulate tolerance to bacterial infection, but less is known about the bona fide bacterial effector that activates HLH-30 and autophagy. Here, we reveal that bacterial membrane pore-forming toxin (PFT) induces autophagy in an HLH-30-dependent manner in Caenorhabditis elegans. Moreover, autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans. These results demonstrate that autophagic pathways and autophagy are induced partly at the transcriptional level through HLH-30 activation and are required to protect metazoan upon PFT intoxication. Together, our data show a new and powerful connection between HLH-30-mediated autophagy and epithelium intrinsic cellular defense against the single most common mode of bacterial attack in vivo.
Clostridioides difficile is a Gram-positive, anaerobic, and spore-forming bacterial member of the human gut microbiome. The primary virulence factors of C. difficile are toxin A and toxin B. These ...toxins damage the cell cytoskeleton and cause various diseases, from diarrhea to severe pseudomembranous colitis. Evidence suggests that bacteriophages can regulate the expression of the pathogenicity locus (PaLoc) genes of C. difficile. We previously demonstrated that the genome of the C. difficile RT027 strain NCKUH-21 contains a prophage-like DNA sequence, which was found to be markedly similar to that of the φCD38-2 phage. In the present study, we investigated the mechanisms underlying the φNCKUH-21-mediated regulation of the pathogenicity and the PaLoc genes expression in the lysogenized C. difficile strain R20291. The carriage of φNCKUH-21 in R20291 cells substantially enhanced toxin production, bacterial motility, biofilm formation, and spore germination in vitro. Subsequent mouse studies revealed that the lysogenized R20291 strain caused a more severe infection than the wild-type strain. We screened three φNCKUH-21 genes encoding DNA-binding proteins to check their effects on PaLoc genes expression. The overexpression of NCKUH-21_03890, annotated as a transcriptional regulator (phage transcriptional regulator X, PtrX), considerably enhanced toxin production, biofilm formation, and bacterial motility of R20291. Transcriptome analysis further confirmed that the overexpression of ptrX led to the upregulation of the expression of toxin genes, flagellar genes, and csrA. In the ptrX-overexpressing R20291 strain, PtrX influenced the expression of flagellar genes and the sigma factor gene sigD, possibly through an increased flagellar phase ON configuration ratio.
The enteric pathogen enterohemorrhagic Escherichia coli (EHEC) is responsible for outbreaks of bloody diarrhea and hemolytic uremic syndrome (HUS) worldwide. Several molecular mechanisms have been ...described for the pathogenicity of EHEC; however, the role of bacterial metabolism in the virulence of EHEC during infection in vivo remains unclear. Here we show that aerobic metabolism plays an important role in the regulation of EHEC virulence in Caenorhabditis elegans. Our functional genomic analyses showed that disruption of the genes encoding the succinate dehydrogenase complex (Sdh) of EHEC, including the sdhA gene, attenuated its toxicity toward C. elegans animals. Sdh converts succinate to fumarate and links the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC) simultaneously. Succinate accumulation and fumarate depletion in the EHEC sdhA mutant cells were also demonstrated to be concomitant by metabolomic analyses. Moreover, fumarate replenishment to the sdhA mutant significantly increased its virulence toward C. elegans. These results suggest that the TCA cycle, ETC, and alteration in metabolome all account for the attenuated toxicity of the sdhA mutant, and Sdh catabolite fumarate in particular plays a critical role in the regulation of EHEC virulence. In addition, we identified the tryptophanase (TnaA) as a downstream virulence determinant of SdhA using a label-free proteomic method. We demonstrated that expression of tnaA is regulated by fumarate in EHEC. Taken together, our multi-omic analyses demonstrate that sdhA is required for the virulence of EHEC, and aerobic metabolism plays important roles in the pathogenicity of EHEC infection in C. elegans. Moreover, our study highlights the potential targeting of SdhA, if druggable, as alternative preventive or therapeutic strategies by which to combat EHEC infection.
To improve the delivery efficiency of chemotherapeutic agents, selective drug carriers have been developed to encapsulate chemotherapeutic drugs. Green biomaterials, highly biocompatible with and ...non-toxic to organisms, have been attracting attention in the biomedical field. Kiwifruit-derived nucleic acids were treated with HCl to expose the aldehyde groups in their deoxyriboses. The product, DNA-HCl, was then crosslinked with two disulfides, cystamine (CTM) or cystine (CYS) under an emulsification process. As the aldehyde groups react with the primary amine in the disulfides, stable imine bonds form. When DNA-HCl-CTM and DNA-HCl-CYS enter cancerous microenvironments, the disulfide bonds will be catalyzed by overexpressed GSH and release the chemotherapeutic agent, DOX. We also found that when both solutions contain GSH, the above NGs release more DOX in the one with weak acidity than the one with a neutral pH. Therefore, when compared to cancer cells treated with free DOX and DOX/DNA-HCl NGs, those dosed with DOX/DNA-HCl-CTM and DOX/DNA-HCl-CYS NGs showed a higher uptake. The enhanced uptake of DOX induced apoptosis in cancer cells and cancer organoids, evidenced by DAPI-stained condensed DNA as well as caspase-3 and PARP expression. The results of this study verify a new approach to encapsulating chemotherapeutic drugs with modified nucleic acid while selectively triggering the cytotoxic effects in cancer cells.
The kiwifruit-derived DNA was modified with HCl to expose aldehyde groups, and then underwent an emulsification process to be crosslinked with cystamine (CTM) or cystine (CYS) through imine bonds formed between the said aldehyde groups and the primary amine groups in the disulfides. The products are the spherical structures that we call DNA-HCl-CTM and DNA-HCl-CYS NGs. DOX were then loaded into these nanogels to obtain DOX/DNA-HCl-CTM and DOX/DNA-HCl-CYS NGs, which were evaluated for their anticancer effects. In vitro results show that the DOX/DNA-HCl-CTM and DOX/DNA-HCl-CYS NGs release more DOX in cancer cells and cancer organoids than free DOX and DOX/DNA-HCl NGs, inducing apoptotic signaling shown as the expression of caspase-3 and PARP. These DNA-HCl-CTM and DNA-HCl-CYS NGs can potentially be used as a new drug carrier for cancer treatment. Display omitted
•DNA-HCl and CTM or CYS are crosslinked under emulsification to produce DOX-loaded disulfide NGs.•DOX-loaded disulfide NGs release more DOX in a GSH solution with weak acidity than that with a neutral pH.•DOX-loaded disulfide NGs induced significant DNA condensation in cancer cells and organoids.•DOX-loaded disulfide NGs triggered cancer organoids to express active caspase-3 and PARP significantly.
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