Abstract
The type VI protein secretion system (T6SS) is a powerful needle-like machinery found in Gram-negative bacteria that can penetrate the cytosol of receiving cells in milliseconds by physical ...force. Anchored by its membrane-spanning complex (MC) and a baseplate (BP), the T6SS sheath-tube is assembled in a stepwise process primed by TssA and terminated by TagA. However, the molecular details of its assembly remain elusive. Here, we systematically examined the initiation and termination of contractile and non-contractile T6SS sheaths in MC-BP,
tssA
and
tagA
mutants by fluorescence microscopy. We observe long pole-to-pole sheath-tube structures in the non-contractile MC-BP defective mutants but not in the Hcp tube or VgrG spike mutants. Combining overexpression and genetic mutation data, we demonstrate complex effects of TssM, TssA and TagA interactions on T6SS sheath-tube dynamics. We also report promiscuous interactions of TagA with multiple T6SS components, similar to TssA. Our results demonstrate that priming of the T6SS sheath-tube assembly is not dependent on TssA, nor is the assembly termination dependent on the distal end TssA–TagA interaction, and highlight the tripartite control of TssA–TssM–TagA on sheath-tube initiation and termination.
Abstract
Epigenetic reprogramming occurs during reproduction to reset the genome for early development. In flowering plants, mechanistic details of parental methylation remodeling in zygote remain ...elusive. Here we analyze allele-specific DNA methylation in rice hybrid zygotes and during early embryo development and show that paternal DNA methylation is predominantly remodeled to match maternal allelic levels upon fertilization, which persists after the first zygotic division. The DNA methylation remodeling pattern supports the predominantly maternal-biased gene expression during zygotic genome activation (ZGA) in rice. However, parental allelic-specific methylations are reestablished at the globular embryo stage and associate with allelic-specific histone modification patterns in hybrids. These results reveal that paternal DNA methylation is remodeled to match the maternal pattern during zygotic genome reprogramming and suggest existence of a chromatin memory allowing parental allelic-specific methylation to be maintained in the hybrid.
Gesture interaction via surface electromyography (sEMG) signal is a promising approach for advanced human-computer interaction systems. However, improving the performance of the myoelectric interface ...is challenging due to the domain shift caused by the signal's inherent variability. To enhance the interface's robustness, we propose a novel adaptive information fusion neural network (AIFNN) framework, which could effectively reduce the effects of multiple scenarios. Specifically, domain adversarial training is established to inhibit the shared network's weights from exploiting domain-specific representation, thus allowing for the extraction of domain-invariant features. Effectively, classification loss, domain diversence loss and domain discrimination loss are employed, which improve classification performance while reduce distribution mismatches between the two domains. To simulate the application of myoelectric interface, experiments were carried out involving three scenarios (intra-session, inter-session and inter-subject scenarios). Ten non-disabled subjects were recruited to perform sixteen gestures for ten consecutive days. The experimental results indicated that the performance of AIFNN was better than two other state-of-the-art transfer learning approaches, namely fine-tuning (FT) and domain adversarial network (DANN). This study demonstrates the capability of AIFNN to maintain robustness over time and generalize across users in practical myoelectric interface implementations. These findings could serve as a foundation for future deployments.
Spoofing interference is one of the most emerging threats to the Global Navigation Satellite System (GNSS); therefore, the research on anti-spoofing technology is of great significance to improving ...the security of GNSS. For single spoofing source interference, all the spoofing signals are broadcast from the same antenna. When the receiver is in motion, the pseudo-range of spoofing signals changes nonlinearly, while the difference between any two pseudo-ranges changes linearly. Authentic signals do not have this characteristic. On this basis, an anti-spoofing method is proposed by jointly monitoring the linearity of the pseudo-range difference (PRD) sequence and pseudo-range sum (PRS) sequence, which transforms the spoofing detection problem into the sequence linearity detection problem. In this paper, the model of PRD and PRS is derived, the hypothesis based on the linearity of PRD sequence and PRS sequence is given, and the detection performance of the method is evaluated. This method uses the sum of squares of errors (SSE) of linear fitting of the PRD sequence and PRS sequence to construct detection statistics, and has low computational complexity. Simulation results show that this method can effectively detect spoofing interference and distinguish spoofing signals from authentic signals.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Augmented reality (AR) surgical navigation systems based on image overlay have been used in minimally invasive surgery. However, conventional systems still suffer from a limited viewing zone, a ...shortage of intuitive three-dimensional (3D) image guidance and cannot be moved freely. To fuse the 3-D overlay image with the patient in situ, it is essential to track the overlay device while it is moving. A direct line-of-sight should be maintained between the optical markers and the tracker camera. In this study, we propose a moving-tolerant AR surgical navigation system using autostereoscopic image overlay, which can avoid the use of the optical tracking system during the intraoperative period. The system captures binocular image sequences of environmental change in the operation room to locate the overlay device, rather than tracking the device directly. Therefore, it is no longer required to maintain a direct line-of-sight between the tracker and the tracked devices. The movable range of the system is also not limited by the scope of the tracker camera. Computer simulation experiments demonstrate the reliability of the proposed moving-tolerant AR surgical navigation system. We also fabricate a computer-generated integral photography-based 3-D overlay AR system to validate the feasibility of the proposed moving-tolerant approach. Qualitative and quantitative experiments demonstrate that the proposed system can always fuse the 3-D image with the patient, thus, increasing the feasibility and reliability of traditional 3-D overlay image AR surgical navigation systems.
We report a comparative study of the binding of I2 (iodine) in a pair of redox-active metal–organic framework (MOF) materials, MFM-300(VIII) and its oxidized, deprotonated analogue, MFM-300(VIV). ...Adsorption of I2 in MFM-300(VIII) triggers a host-to-guest charge-transfer, accompanied by a partial (∼30%) oxidation of the VIII centers in the host framework and formation of I3 – species residing in the MOF channels. Importantly, this charge-transfer induces a significant enhancement in the electrical conductivity (Δσ = 700000) of I2@MFM-300(VIII/IV) in comparison to MFM-300(VIII). In contrast, no host–guest charge-transfer or apparent change in the conductivity was observed upon adsorption of I2 in MFM-300(VIV). High-resolution synchrotron X-ray diffraction of I2@MFM-300(VIII/IV) confirms the first example of self-aggregation of adsorbed iodine species (I2 and I3 –) into infinite helical chains within a MOF.
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IJS, KILJ, NUK, PNG, UL, UM
In female mammals, the majority of primordial follicles (PFs) are physiologically quiescent, and only a few of them are activated and enter the growing follicle pool. Specific molecules, such as ...mammalian target of rapamycin (mTOR) and the serine/threonine kinase Akt (AKT), have been proven to be important for PF activation. However, how the transcription of these genes is regulated is not clear. Although activators of mTOR or AKT have been successfully used to rescue the fertility of patients with premature ovarian insufficiency, the low efficacy and unclear safety profile of these drugs hinder their clinical use in the in vitro activation (IVA) of PFs. Here, sirtuin 1 (SIRT1), an NAD‐dependent deacetylase, was demonstrated to activate mouse PFs independent of its deacetylase activity. SIRT1 was prominently expressed in pregranulosa cells (pGCs) and oocytes, and its expression was increased during PF activation. PF activation was achieved by either up‐regulating SIRT1 with a specific activator or overexpressing SIRT1. Moreover, SIRT1 knockdown in oocytes or pGCs could significantly suppress PF activation. Further studies demonstrated that SIRT1 enhanced both Akt1 and mTOR expression by acting more as a transcription cofactor, directly binding to the respective gene promoters, than as a deacetylase. Importantly, we explored the potential clinical applications of targeting SIRT1 in IVA via short‐term treatment of cultured ovaries from mice and human ovarian tissues to activate PFs by applying the SIRT1 activator resveratrol. RSV‐induced IVA could be a candidate strategy to develop more efficient procedures for future clinical treatment of infertility.—Zhang, T., Du, X., Zhao, L., He, M., Lin, L., Guo, C., Zhang, X., Han, J., Yan, H., Huang, K., Sun, G., Yan, L., Zhou, B., Xia, G., Qin, Y., Wang, C. SIRT1 facilitates primordial follicle recruitment independent of deacetylase activity through directly modulating Akt1 and mTOR transcription. FASEB J. 33, 14703‐14716 (2019). www.fasebj.org
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objective
To investigate the anti-cancer effects and potential mechanisms of eupalinilide B in laryngeal cancer cells.
Methods
Laryngeal cancer cell lines were selected to study the anti-tumor ...effects of eupalinilide B in vitro and in vivo. Lysine-specific demethylase 1 (LSD1) activity was assessed in vitro and dialysis experiments were performed to identify the anti-tumor target of the drug.
Results
Eupalinilide B concentration-dependently inhibited the proliferation of laryngeal cancer cells, exhibiting potent inhibitory activity against TU686 (IC50 = 6.73 µM), TU212 (IC50 = 1.03 µM), M4e (IC50 = 3.12 µM), AMC-HN-8 (IC50 = 2.13 µM), Hep-2 (IC50 = 9.07 µM), and LCC cells (IC50 = 4.20 µM). Subsequent target verification experiments demonstrated that eupalinilide B selectively and reversibly inhibited LSD1. Furthermore, eupalinilide B, as a natural product, suppressed epithelial–mesenchymal transition in TU212 cells. An in vivo experiment further indicated that eupalinilide B could significantly reduce the growth of tumors in TU212 xenograft mouse models.
Conclusions
Eupalinilide B might be a novel LSD1 inhibitor for treating laryngeal cancer.
The demand for xylenes is projected to increase over the coming decades. The separation of xylene isomers, particularly p- and m-xylenes, is vital for the production of numerous polymers and ...materials. However, current state-of-the-art separation is based upon fractional crystallisation at 220 K which is highly energy intensive. Here, we report the discrimination of xylene isomers via refinement of the pore size in a series of porous metal-organic frameworks, MFM-300, at sub-angstrom precision leading to the optimal kinetic separation of all three xylene isomers at room temperature. The exceptional performance of MFM-300 for xylene separation is confirmed by dynamic ternary breakthrough experiments. In-depth structural and vibrational investigations using synchrotron X-ray diffraction and terahertz spectroscopy define the underlying host-guest interactions that give rise to the observed selectivity (p-xylene < o-xylene < m-xylene) and separation factors of 4.6-18 for p- and m-xylenes.
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•A 3D electrode was fabricated via the PEDOT in-situ synthesized on HFMs framework.•HFMs facilitate high loading and entrapment of enzyme loaded nanoparticles in confined ...micro-space.•The spatial location of enzymes in PEDOT-HFMs can be modulated through controllable physical entrapment patterns.•The porous 3D electrode ensures the integration of separation and detection synchronously.•The electrochemical sensor shows fast current response (~3 s), wide linear range, and low detection limit.
We have developed a three-dimensional (3D) enzyme loading strategy by modular assembly of enzyme loaded nanoparticles with porous conductive membranes. A 3D conductive structure was fabricated as electrode via the poly-(3,4-ethylenedioxythiophene) (PEDOT) in-situ synthesized on hollow fiber membranes (HFMs) framework, retaining the original gradient porous structures and capillary effect. Using physical entrapment pattern, enzyme-carrying nanoparticles were modularly assembled in the 3D conductive support and their spatial distribution can be regulated by particle size-tuning. The obtained enzyme entrapped 3D composites can be applied as a promising electrode in electrochemical sensing and catalysis. HFMs provide large surface area and gradient porous structure for entrapping the enzyme-carrying nanoparticles in the confined micro-space. The physical entrapment improves the enzymatic stability and promotes full contact between the enzymes and the conductive/catalytic substrates. The conductive support creates an interconnected network to increase the electrode area and the response current, thus enhancing the sensitivity of biosensors. It shows fast current response (~3 s), wide linear range (glucose, 2–24 mM; lactic acid, 0.1–6 mM), high sensitivity, and low detection limit (glucose, 100 µM; lactic acid, 10 µM) towards cancer cell metabolism monitoring. This electrode structure can be further applied in multi-target array detection towards metabolic markers by modulating different enzymes on the conductive HFMs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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